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Sample records for neurodegenerative movement disorder

  1. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease.

    Science.gov (United States)

    Howell, Michael Joseph; Schenck, Carlos Hugh

    2015-06-01

    The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies. To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder. Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014. Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime. Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease

  2. [Sleep in neurodegenerative disorders].

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    Happe, S; Mayer, G

    2006-10-01

    Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.

  3. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

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    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  4. Sleep disorders in neurodegenerative diseases.

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    Raggi, A; Ferri, R

    2010-11-01

    The aim of this review is to provide data on sleep disturbances in three categories of neurodegenerative disorders: synucleinopathies, tauopathies, and other diseases (this heterogeneous group includes also spinocerebellar degeneration and amyotrophic lateral sclerosis). Analysing and knowing sleep disorders in neurodegenerative diseases may offer important insights into the pathomechanism of some of these diseases and calls attention to the still insufficiently known 'sleep neurology'. The identification of sleep disorders in some neurodegenerative conditions may make their diagnosis easier and earlier; for example, rapid eye movements sleep behaviour disorder may precede any other clinical manifestation of synucleinopathies by more than 10 years. © 2010 The Author(s). Journal compilation © 2010 EFNS.

  5. High-speed video gait analysis reveals early and characteristic locomotor phenotypes in mouse models of neurodegenerative movement disorders.

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    Preisig, Daniel F; Kulic, Luka; Krüger, Maik; Wirth, Fabian; McAfoose, Jordan; Späni, Claudia; Gantenbein, Pascal; Derungs, Rebecca; Nitsch, Roger M; Welt, Tobias

    2016-09-15

    Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. REM behaviour disorder and neurodegenerative diseases.

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    Zanigni, Stefano; Calandra-Buonaura, Giovanna; Grimaldi, Daniela; Cortelli, Pietro

    2011-12-01

    Rapid-eye movement (REM) sleep behaviour disorder (RBD) is an REM sleep parasomnia characterized by enactment of dream content during REM sleep associated with loss of muscle atonia. RBD can be either idiopathic or secondary to drugs or other diseases. The best recognized association is with neurodegenerative diseases, namely alpha-synucleinopathies. RBD may represent the first feature of neurodegeneration and can be considered an early marker of these disorders. This review describes the main clinical, pathogenetic, and therapeutic features of RBD, pointing to its association with neurodegenerative diseases and emphasizing the clinical and prognostic implications. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Molecular diagnostics of neurodegenerative disorders

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    Megha eAgrawal

    2015-09-01

    Full Text Available Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  8. Endocannabinoid system in neurodegenerative disorders.

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    Basavarajappa, Balapal S; Shivakumar, Madhu; Joshi, Vikram; Subbanna, Shivakumar

    2017-09-01

    Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs. © 2017 International Society for Neurochemistry.

  9. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study.

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    Iranzo, Alex; Tolosa, Eduard; Gelpi, Ellen; Molinuevo, José Luis; Valldeoriola, Francesc; Serradell, Mónica; Sanchez-Valle, Raquel; Vilaseca, Isabel; Lomeña, Francisco; Vilas, Dolores; Lladó, Albert; Gaig, Carles; Santamaria, Joan

    2013-05-01

    We postulated that idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) represents the prodromal phase of a Lewy body disorder and that, with sufficient follow-up, most cases would eventually be diagnosed with a clinical defined Lewy body disorder, such as Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Patients from an IRBD cohort recruited between 1991 and 2003, and previously assessed in 2005, were followed up during an additional period of 7 years. In this original cohort, we sought to identify the nature and frequency of emerging defined neurodegenerative syndromes diagnosed by standard clinical criteria. We estimated rates of survival free from defined neurodegenerative disease by means of the Kaplan-Meier method. We further characterised individuals who remained diagnosed as having only IRBD, through dopamine transporter (DAT) imaging, transcranial sonography (TCS), and olfactory testing. We did a neuropathological assessment in three patients who died during follow-up and who had the antemortem diagnosis of PD or DLB. Of the 44 participants from the original cohort, 36 (82%) had developed a defined neurodegenerative syndrome by the 2012 assessment (16 patients were diagnosed with PD, 14 with DLB, one with multiple system atrophy, and five with mild cognitive impairment). The rates of neurological-disease-free survival from time of IRBD diagnosis were 65·2% (95% CI 50·9 to 79·5) at 5 years, 26·6% (12·7 to 40·5) at 10 years, and 7·5% (-1·9 to 16·9) at 14 years. Of the four remaining neurological-disease-free individuals who underwent neuroimaging and olfactory tests, all four had decreased striatal DAT uptake, one had substantia nigra hyperechogenicity on TCS, and two had impaired olfaction. In three patients, the antemortem diagnoses of PD and DLB were confirmed by neuropathological examination showing widespread Lewy bodies in the brain, and α-synuclein aggregates in the peripheral autonomic nervous system in one case

  10. Sleep in Neurodevelopmental and Neurodegenerative Disorders.

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    Kotagal, Suresh

    2015-06-01

    There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Neurobiology of sleep disturbances in neurodegenerative disorders.

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    Gagnon, J-F; Petit, D; Latreille, V; Montplaisir, J

    2008-01-01

    This review presents sleep disturbances and their underlying pathophysiology in three categories of neurodegenerative disorders namely tauopathies, synucleinopathies, and Huntington's disease (HD) and prion-related diseases. Sleep abnormalities are a major and early feature of neurodegenerative disorders, especially for synucleinopathies, HD and prion-related diseases, in which the sleep-related brainstem regions are severely altered and impaired sooner than in most of the tauopathies. In synucleinopathies, HD and prion-related diseases, specific sleep disturbances, different from those observed in tauopathies, are considered as core manifestations of the disease and in some cases, as preclinical signs. For this reason, the evaluation of sleep components in these neurodegenerative disorders may be useful to make a diagnosis and to assess the efficacy of pharmacotherapy. Since sleep disruption may occur early in the course of neurodegeneration, sleep disturbance may serve as groundwork to study the efficacy of neuroprotective agents to prevent or delay the development of a full-blown neurodegenerative disorder. The cause of sleep disturbances in neurodegenerative disorders may be attributed to several factors, including age-related modifications, symptoms of the disease, comorbid conditions and the neurodegenerative process itself.

  12. Genetically modified pig models for neurodegenerative disorders.

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    Holm, Ida E; Alstrup, Aage Kristian Olsen; Luo, Yonglun

    2016-01-01

    Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia-telangiectasia. We also highlight how non-invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground-breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease-causing mutations and recapitulate pathological features of human conditions. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Movement disorders.

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    Stoessl, A Jon; Mckeown, Martin J

    2016-01-01

    Movement disorders can be hypokinetic (e.g., parkinsonism), hyperkinetic, or dystonic in nature and commonly arise from altered function in nuclei of the basal ganglia or their connections. As obvious structural changes are often limited, standard imaging plays less of a role than in other neurologic disorders. However, structural imaging is indicated where clinical presentation is atypical, particularly if the disorder is abrupt in onset or remains strictly unilateral. More recent advances in magnetic resonance imaging (MRI) may allow for differentiation between Parkinson's disease and atypical forms of parkinsonism. Functional imaging can assess regional cerebral blood flow (functional MRI (fMRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT)), cerebral glucose metabolism (PET), neurochemical and neuroreceptor status (PET and SPECT), and pathologic processes such as inflammation or abnormal protein deposition (PET) (Table 49.1). Cerebral blood flow can be assessed at rest, during the performance of motor or cognitive tasks, or in response to a variety of stimuli. In appropriate situations, the correct imaging modality and/or combination of modalities can be used to detect early disease or even preclinical disease, and to monitor disease progression and the effects of disease-modifying interventions. Various approaches are reviewed here. © 2016 Elsevier B.V. All rights reserved.

  14. Mood, memory and movement: an age-related neurodegenerative complex?

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    Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E

    2008-07-01

    The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled "Thinking, moving and feeling: Common underlying mechanisms? 4(th) Annual Bedside-to-Bench Conference" and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve "successful aging"? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized.

  15. Evidence-based therapy for sleep disorders in neurodegenerative diseases

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    LIU Ling

    2013-08-01

    Full Text Available Objective To evaluate the effectiveness of the treatments for sleep disorders in neurodegenerative diseases so as to provide the best therapeutic regimens for the evidence-based treatment. Methods Search PubMed, MEDLINE, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases with "sleep disorder or sleep disturbance", "neurodegenerative diseases", "Parkinson's disease or PD", "Alzheimer's disease or AD", "multiple system atrophy or MSA" as retrieval words. The quality of the articles were evaluated with Jadad Scale. Results A total of 35 articles, including 2 systematic reviews, 5 randomized controlled trials, 13 clinical controlled trials, 13 case series and 2 epidemiological investigation studies were included for evaluation, 13 of which were high grade and 22 were low grade articles. Clinical evidences showed that: 1 advice on sleep hygiene, careful use of dopaminergic drugs and hypnotic sedative agents should be considered for PD. Bright light therapy (BLT may improve circadian rhythm sleep disorders and clonazepam may be effective for rapid eye movement sleep behavior disorder (RBD. However, to date, very few controlled studies are available to make a recommendation for the management of sleep disorders in PD; 2 treatments for sleep disorders in AD include drug therapy (e.g. melatonin, acetylcholinesterase inhibitors, antipsychotic drugs, antidepressants and non-drug therapy (e.g. BLT, behavior therapy, but very limited evidence shows the effectiveness of these treatments; 3 the first line treatment for sleep-related breathing disorder in MSA is nasal continuous positive airway pressure (nCPAP, and clonazepam is effective for RBD in MSA; 4 there is rare evidence related to the treatment of sleep disorders in dementia with Lewy body (DLB and amyotrophic lateral sclerosis (ALS. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment in neurodegenerative

  16. Supranuclear eye movement disorders.

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    Lemos, João; Eggenberger, Eric

    2014-11-01

    This work reviews supranuclear ocular motor disorders, highlighting new data published during the past year. Perceptional adaptative mechanisms may explain recent research concerning the discrepancy between objective measurement of saccade abnormalities and their putative functional visual impairment. Eye movement classes seem to be selectively disrupted by different neurodegenerative disorders. Deep brain stimulation in Parkinson's disease patients may improve pursuit deficits, highlighting the role of basal ganglia in the control of smooth pursuit. Subcortical optokinetic pathways seem to play an important role in maintaining the monocular nasotemporal optokinetic asymmetry seen in patients with infantile esotropia. Vergence-vestibular interaction has been further delineated in patients with idiopathic bilateral vestibular failure. Pharmacological treatment of central vestibular disorders with 4-aminopyridine has been extended to patients with ataxia-telangiectasia in whom it seems to reduce slow-phase velocity of nystagmus. Recent data derived from anatomic and functional imaging studies are providing new insights into supranuclear ocular motor circuitry. Novel pharmacological and surgical therapies may have future implications in visual and vestibular rehabilitation of patients with supranuclear eye movement disorders.

  17. Sleep-disordered breathing in neurodegenerative diseases.

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    Gaig, Carles; Iranzo, Alex

    2012-04-01

    Sleep disorders are common in neurodegenerative diseases such as Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), hereditary ataxias, and Alzheimer's disease (AD). Type, frequency, and severity of sleep disturbances vary depending on each of these diseases. Cell loss of the brainstem nuclei that modulates respiration, and dysfunction of bulbar and diaphragmatic muscles increase the risk for sleep-disordered breathing (SDB) in MSA and ALS. The most relevant SDB in MSA is stridor, whereas in ALS nocturnal hypoventilation due to diaphragmatic weakness is the most common sleep breathing abnormality. Stridor and nocturnal hypoventilation are associated with reduced survival in MSA and ALS. In contrast, sleep apnea seems not to be more prevalent in PD than in the general population. In some PD patients, however, coincidental obstructive sleep apnea (OSA) can be the cause of excessive daytime sleepiness (EDS). SDB can also occur in some hereditary ataxias, such as stridor in spinocerebellar ataxia type 3 (Machado-Joseph disease). The presence of concomitant OSA in patients with AD can have deleterious effects on nocturnal sleep, may result in EDS, and might aggravate the cognitive deficits inherent to the disease. However, whether OSA is more frequent in patients with AD than in the general population is uncertain. Recognition of SDB in neurodegenerative disease is important because they are associated with significant morbidity and potential effective treatments are available.

  18. Ghrelin and Neurodegenerative Disorders-a Review.

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    Shi, Limin; Du, Xixun; Jiang, Hong; Xie, Junxia

    2017-03-01

    Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

  19. Eye Movement Disorders

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    ... t work properly. There are many kinds of eye movement disorders. Two common ones are Strabismus - a disorder ... of the eyes, sometimes called "dancing eyes" Some eye movement disorders are present at birth. Others develop over ...

  20. Connected Speech in Neurodegenerative Language Disorders: A Review.

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    Boschi, Veronica; Catricalà, Eleonora; Consonni, Monica; Chesi, Cristiano; Moro, Andrea; Cappa, Stefano F

    2017-01-01

    Language assessment has a crucial role in the clinical diagnosis of several neurodegenerative diseases. The analysis of extended speech production is a precious source of information encompassing the phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic levels of language organization. The knowledge about the distinctive linguistic variables identifying language deficits associated to different neurodegenerative diseases has progressively improved in the last years. However, the heterogeneity of such variables and of the way they are measured and classified limits any generalization and makes the comparison among studies difficult. Here we present an exhaustive review of the studies focusing on the linguistic variables derived from the analysis of connected speech samples, with the aim of characterizing the language disorders of the most prevalent neurodegenerative diseases, including primary progressive aphasia, Alzheimer's disease, movement disorders, and amyotrophic lateral sclerosis. A total of 61 studies have been included, considering only those reporting group analysis and comparisons with a group of healthy persons. This review first analyzes the differences in the tasks used to elicit connected speech, namely picture description, story narration, and interview, considering the possible different contributions to the assessment of different linguistic domains. This is followed by an analysis of the terminologies and of the methods of measurements of the variables, indicating the need for harmonization and standardization. The final section reviews the linguistic domains affected by each different neurodegenerative disease, indicating the variables most consistently impaired at each level and suggesting the key variables helping in the differential diagnosis among diseases. While a large amount of valuable information is already available, the review highlights the need of further work, including the development of automated methods, to

  1. Stereotypic movement disorder

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    ... this page: //medlineplus.gov/ency/article/001548.htm Stereotypic movement disorder To use the sharing features on this page, please enable JavaScript. Stereotypic movement disorder is a condition in which a person makes ...

  2. Comparative Incidence of Conformational, Neurodegenerative Disorders.

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    Jesús de Pedro-Cuesta

    Full Text Available The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs.We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD. We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD forms, amyotrophic lateral sclerosis (ALS, and sporadic rapidly progressing neurodegenerative dementia (sRPNDd. For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD, to 1589 and 2589 for AMD and Alzheimer's disease (AD respectively. Age-specific profiles varied from (a symmetrical, inverted V-shaped curves for low incidences to (b those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might

  3. Psychogenic Movement Disorders

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    Chakravarty Ambar

    2004-01-01

    Full Text Available Psychogenic movement Disorders (PMD may result from somatoform disorders, factitious disorders, malingering, depression anxiety disorders and less frequently, histrionic personality disorders. First recognized by Henry Head in early twentieth century, PMD s commonly encountered and clues to their differentiation from organic disease. A generally accepted management protocol has been outlined.

  4. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus

    2016-01-01

    : Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether...... excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. RESULTS: Among included patients, 2.......9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy...

  5. Recent Patent Advances For Neurodegenerative Disorders And Its Treatment.

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    Kumar, Bhavna; Sharma, Deepika

    2017-10-10

    Neurodegenerative disorders are one of the common diseases that affect our society with tremendous medical and financial burdens. As a whole, neurodegeneration affects individuals of all ages, but becomes increasingly frequent with age, coming to affect a very large share of our elderly population which is severely affecting the patient, caregivers, and enormously increasing the financial burden of the nation. These diseases share a very complex nature, which often result from combined genetic, environment and pathogenic factors. Various challenges are faced by the scientific community that researches on the pathogenesis and the therapy of neurodegenerative disorder. The review has been analysed for recent patent documents and treatment approaches for neurodegenerative disorders. The study design is based on updating the international and national literatures and an exhaustive patent search and compiling of various patented documents for the treatment of neurodegenerative disorders (EP2282779 A1, US20110229555 A1) to provide information in the state of technological innovation in terms of research and development. In the present review, the authors described various neurodegenerative diseases, there treatment strategies and emphasized on various patented approaches for age-related neurodegenerative disorders such as New therapeutic approaches for treating Alzheimer disease and related disorders through a modulation of cell stress response EP2282779 A1, through combined therapies that modulate angiogenesis US20120058992 A1. The review will attract the interest of academics, researchers, students and pharmaceutical companies in the recent on-going activities in neurodegenerative disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

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    Kurt A. Jellinger

    2011-01-01

    Full Text Available Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

  7. Ghrelin: a link between ageing, metabolism and neurodegenerative disorders

    NARCIS (Netherlands)

    Stoyanova, Irina

    2014-01-01

    Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics:

  8. Cognitive performance in REM sleep behaviour disorder: a possible early marker of neurodegenerative disease?

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    Terzaghi, Michele; Sinforiani, Elena; Zucchella, Chiara; Zambrelli, Elena; Pasotti, Chiara; Rustioni, Valter; Manni, Raffaele

    2008-05-01

    Rapid eye movement [REM] sleep behaviour disorder (RBD) may herald neurodegenerative diseases. Neurobiological deficits similar to those identified in neurodegenerative diseases have been reported in idiopathic RBD. Researchers are looking for early markers supporting a possible role of RBD as a harbinger of impending neurodegenerative disease. To examine the neuropsychological functions in idiopathic RBD subjects. Should they be found to present a neuropsychological dysfunction that overlaps that reported in neurodegenerative diseases, it would be possible to consider cognitive deficits as possible early markers of an underlying degenerative process. Twenty-three subjects with idiopathic RBD (21 males, mean age 67.0+/-7.0 years) and a group of healthy controls matched for sex, age and education underwent a neuropsychological battery evaluating different cognitive domains. Considering mean values, poorer performances were observed in the Word Span (pneurodegenerative disease, but until more prolonged long-term follow-up data are available, the true neurobiological significance of cognitive deficits in RBD will remain unknown.

  9. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

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    Yajin Liao

    2017-02-01

    Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

  10. [Sleep related movement disorders].

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    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2015-06-01

    Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD.

  11. Global warming and neurodegenerative disorders: speculations on their linkage.

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  12. Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Trotti, Lynn Marie; Karroum, Elias G

    2016-07-01

    In patients with neurodegenerative diseases, sleep disorders are common; they impair the quality of life for patients and caregivers and are associated with poorer clinical outcomes. Melatonin has circadian, hypnotic, and free radical-scavenging effects, and preclinical data suggest benefits of melatonin on neurodegeneration. However, randomized, controlled trials of melatonin in patients with neurodegenerative diseases have not shown strong effects. Trials in Alzheimer's patients demonstrate a lack of benefit on sleep quantity. Subjective measures of sleep quality are mixed, with possible symptomatic improvements seen only on some measures or at some time points. Benefits on cognition have not been observed across several studies. In Parkinson's patients, there may be minimal benefit on objective sleep measures, but a suggestion of subjective benefit in few, small studies. Effective treatments for the sleep disorders associated with neurodegenerative diseases are urgently needed, but current data are insufficient to establish melatonin as such a treatment.

  13. DNA triplex structures in neurodegenerative disorder, Friedreich's ...

    Indian Academy of Sciences (India)

    2012-06-25

    Jun 25, 2012 ... 3. DNA triplet repeat expansions in human genome. In the beginning of the last decade, expanded DNA-trinucleotide repeats in genes were identified as unstable and responsible for a large number of neurological disorders like FRDA, fragile X syndrome, spinocerebellar ataxia and muscular dystrophy.

  14. Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction

    Science.gov (United States)

    2007-09-01

    TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Table of Contents 1 Narrative...neurodegenerative disorders including Wernicke -Korsakoff syndrome (reviewed in Martin et al., 2005). 2. Results At E15.5, Ts16 brains are slightly

  15. Predictive gene testing for Huntington disease and other neurodegenerative disorders.

    Science.gov (United States)

    Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

    2013-12-01

    Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  16. Nanomedicine and neurodegenerative disorders: so close yet so far.

    Science.gov (United States)

    Tosi, Giovanni; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara

    2015-07-01

    This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

  17. Psychostimulants and movement disorders.

    Directory of Open Access Journals (Sweden)

    Andres eAsser

    2015-04-01

    Full Text Available Psychostimulants are a diverse group of substances with their main psychomotor effects resembling those of amphetamine, methamphetamine, cocaine or cathinone. Due to their potential as drugs of abuse, recreational use of most of these substances is illegal since the 1971 Convention on Psychotropic Substances. In recent years, new psychoactive substances have emerged mainly as synthetic cathinones with new molecules frequently complementing the list.Psychostimulant related movement disorders are a known entity often seen in emergency rooms around the world. These admissions are becoming more frequent as are fatalities associated with drug abuse. Still the legal constraints of the novel synthetic molecules are bypassed. At the same time chronic and permanent movement disorders are much less frequently encountered. These disorders frequently manifest as a combination of movement disorders. The more common symptoms include agitation, tremor, hyperkinetic and stereotypical movements, cognitive impairment, and also hyperthermia and cardiovascular dysfunction.The pathophysiological mechanisms behind the clinical manifestations have been researched for decades. The common denominator is the monoaminergic signaling. Dopamine has received the most attention but further research has demonstrated involvement of other pathways. Common mechanisms linking psychostimulant use and several movement disorders exist.

  18. Psychostimulants and Movement Disorders

    Science.gov (United States)

    Asser, Andres; Taba, Pille

    2015-01-01

    Psychostimulants are a diverse group of substances with their main psychomotor effects resembling those of amphetamine, methamphetamine, cocaine, or cathinone. Due to their potential as drugs of abuse, recreational use of most of these substances is illegal since 1971 Convention on Psychotropic Substances. In recent years, new psychoactive substances have emerged mainly as synthetic cathinones with new molecules frequently complementing the list. Psychostimulant related movement disorders are a known entity often seen in emergency rooms around the world. These admissions are becoming more frequent as are fatalities associated with drug abuse. Still the legal constraints of the novel synthetic molecules are bypassed. At the same time, chronic and permanent movement disorders are much less frequently encountered. These disorders frequently manifest as a combination of movement disorders. The more common symptoms include agitation, tremor, hyperkinetic and stereotypical movements, cognitive impairment, and also hyperthermia and cardiovascular dysfunction. The pathophysiological mechanisms behind the clinical manifestations have been researched for decades. The common denominator is the monoaminergic signaling. Dopamine has received the most attention but further research has demonstrated involvement of other pathways. Common mechanisms linking psychostimulant use and several movement disorders exist. PMID:25941511

  19. Metals and movement disorders.

    Science.gov (United States)

    Taba, Pille

    2013-08-01

    Recent advances in genetics, diagnosis, and management of disorders associated with brain manganese, copper, and iron brain accumulation are reviewed. A genetic disorder leading to manganese accumulation in children and young adults has recently been identified and may be treated successfully with chelation. Neurodegeneration of the basal ganglia in chronic acquired hepatocerebral syndrome and ephedrone toxicity has been linked with acquired manganism. New mutations in genes linked with accumulation of iron and copper in the brain have also been identified. Recent genetic findings have shed light on the role of iron, manganese, and copper in neurodegenerative disease. MRI is a helpful diagnostic tool in the investigation of basal ganglia disease when iron accumulation is suspected. Chelation therapy is effective for Wilson's disease and hereditary hypermanganesemia, but there is no proven effective treatment for toxic manganese exposure.

  20. REM Sleep Behavior Disorder (RBD) as a marker of neurodegenerative disorders.

    Science.gov (United States)

    Ferini-Strambi, L; Marelli, S; Galbiati, A; Rinaldi, F; Giora, E

    2014-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) can occur in the absence of any other obvious associated neurologic disorder or in association with a neurodegenerative disease, in which case it is considered as symptomatic RBD. RBD is frequently associated with Parkinson's disease (PD), Lewy body dementia or multiple system atrophy (MSA), and in several cases may even antedate the occurrence of motor symptoms by decades. When no neurologic disorder is obvious, RBD can be considered as idiopathic (iRBD). Several studies have looked at neurophysiologic and neuropsychological functions in iRBD and have found evidence of CNS dysfunction during both wakefulness and sleep in a variable proportion of these patients, challenging the concept of iRBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial in order to develop early intervention strategies. Some prospective results in iRBD showed that potential markers of neurodegeneration are the following: 1) marked EEG slowing on spectral analysis; 2) decreased striatal 123I-FPCIT; 3) impaired color vision.

  1. Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Zhang, Wei; Chen, Xue-yan; Su, Su-wen; Jia, Qing-zhong; Ding, Tao; Zhu, Zhong-ning; Zhang, Tong

    2016-01-01

    The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.

  2. Yeast buddies helping to unravel the complexity of neurodegenerative disorders.

    Science.gov (United States)

    Fruhmann, Gernot; Seynnaeve, David; Zheng, Ju; Ven, Karen; Molenberghs, Sofie; Wilms, Tobias; Liu, Beidong; Winderickx, Joris; Franssens, Vanessa

    2017-01-01

    Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furthermore, by using so-called humanized yeast systems, the findings in yeast can be interpolated to humans. In this review, we will give an overview of the current body of knowledge on the use of yeast models with regard to Huntington's, Parkinson's and Alzheimer's disease. In addition to the results, obtained with the baker's yeast Saccharomyces cerevisiae, we also consider the existing literature on the less common but promising fission yeast Schizosaccharomyces pombe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Localization of Axonal Motor Molecules Machinery in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Fulvio Florenzano

    2012-04-01

    Full Text Available Axonal transport and neuronal survival depend critically on active transport and axon integrity both for supplying materials and communication to different domains of the cell body. All these actions are executed through cytoskeleton, transport and regulatory elements that appear to be disrupted in neurodegenerative diseases. Motor-driven transport both supplies and clears distal cellular portions with proteins and organelles. This transport is especially relevant in projection and motor neurons, which have long axons to reach the farthest nerve endings. Thus, any disturbance of axonal transport may have severe consequences for neuronal function and survival. A growing body of literature indicates the presence of alterations to the motor molecules machinery, not only in expression levels and phosphorylation, but also in their subcellular distribution within populations of neurons, which are selectively affected in the course of neurodegenerative diseases. The implications of this altered subcellular localization and how this affects axon survival and neuronal death still remain poorly understood, although several hypotheses have been suggested. Furthermore, cytoskeleton and transport element localization can be selectively disrupted in some disorders suggesting that specific loss of the axonal functionality could be a primary hallmark of the disorder. This can lead to axon degeneration and neuronal death either directly, through the functional absence of essential axonal proteins, or indirectly, through failures in communication among different cellular domains. This review compares the localization of cytoskeleton and transport elements in some neurodegenerative disorders to ask what aspects may be essential for axon survival and neuronal death.

  4. [Neuropsychiatry Of Movement Disorders].

    Science.gov (United States)

    Orjuela-Rojas, Juan Manuel; Barrios Vincos, Gustavo Adolfo; Martínez Gallego, Melisa Alejandra

    2017-10-01

    Movement disorders can be defined as neurological syndromes presenting with excessive or diminished automatic or voluntary movements not related to weakness or spasticity. Both Parkinson's disease (PD) and Huntington's disease (HD) are well-known examples of these syndromes. The high prevalence of comorbid psychiatric symptoms like depression, anxiety, obsessive-compulsive symptoms, hallucinations, delusions, impulsivity, sleep disorders, apathy and cognitive impairment mean that these conditions must be regarded as neuropsychiatric diseases. In this article, we review neuroanatomical (structural and functional), psychopathological and neuropsychological aspects of PD and HD. The role of fronto-subcortical loops in non-motor functions is particularly emphasised in order to understand the clinical spectrum of both diseases, together with the influence of genetic, psychological and psychosocial aspects. A brief description of the main psychopharmacological approaches for both diseases is also included. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  5. Stereotypic movement disorders.

    Science.gov (United States)

    Singer, Harvey S

    2011-01-01

    Stereotypic movements are repetitive, rhythmic, fixed, patterned in form, amplitude, and localization, but purposeless (e.g., hand shaking, waving, body rocking, head nodding). They are commonly seen in children; both in normal children (primary stereotypy) and in individuals with additional behavioral or neurological signs and symptoms (secondary stereotypy). They should be differentiated from compulsions (OCD), tics (tic disorders), trichotillomania, skin picking disorder, or the direct physiological effect of a substance. There is increasing evidence to support a neurobiological mechanism. Response to behavioral and pharmacological therapies is variable. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Chronic Traumatic Encephalopathy and Movement Disorders: Update.

    Science.gov (United States)

    Tarazi, Apameh; Tator, Charles H; Tartaglia, Maria Carmela

    2016-05-01

    Association of repetitive brain trauma with progressive neurological deterioration has been described since the 1920s. Punch drunk syndrome and dementia pugilistica (DP) were introduced first to explain symptoms in boxers, and more recently, chronic traumatic encephalopathy (CTE) has been used to describe a neurodegenerative disease in athletes and military personal with a history of multiple concussions. Although there are many similarities between DP and CTE, a number of key differences are apparent especially when comparing movement impairments. The aim of this review is to compare clinical and pathological aspects of DP and CTE with a focus on disorders of movement.

  7. Transposable elements in TDP-43-mediated neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Wanhe Li

    Full Text Available Elevated expression of specific transposable elements (TEs has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

  8. Need to improve clinical trials in rare neurodegenerative disorders.

    Science.gov (United States)

    Puopolo, Maria; Pocchiari, Maurizio

    2011-01-01

    Rare neurodegenerative diseases are fatal and no therapy is available to cure or slow down the progression of disease. We report possibly weaknesses in the management of clinical studies in these diseases, ranging from poor preclinical studies, difficulties in the recruitment of patients, delay in the onset of treatment because of lack in early disease-specific biomarkers, and suboptimal design of Phase II clinical trials. The adoption of innovative statistical approaches in early Phase II trials might improve the screening of drugs in rare neurodegenerative disorders, but this implicates efforts from clinical researchers, statisticians, and regulatory people to the development of new strategies that should maintain rigorous scientific integrity together with a more ethical approach to human experimentations.

  9. Need to improve clinical trials in rare neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Maria Puopolo

    2011-01-01

    Full Text Available Rare neurodegenerative diseases are fatal and no therapy is available to cure or slow down the progression of disease. We report possibly weaknesses in the management of clinical studies in these diseases, ranging from poor preclinical studies, difficulties in the recruitment of patients, delay in the onset of treatment because of lack in early disease-specific biomarkers, and suboptimal design of Phase II clinical trials. The adoption of innovative statistical approaches in early Phase II trials might improve the screening of drugs in rare neurodegenerative disorders, but this implicates efforts from clinical researchers, statisticians, and regulatory people to the development of new strategies that should maintain rigorous scientific integrity together with a more ethical approach to human experimentations.

  10. Potential future neuroprotective therapies for neurodegenerative disorders and stroke.

    Science.gov (United States)

    Tarawneh, Rawan; Galvin, James E

    2010-02-01

    The cellular mechanisms underlying neuronal loss and neurodegeneration have been an area of interest in the last decade. Although neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease each have distinct clinical symptoms and pathologies, they all share common mechanisms such as protein aggregation, oxidative injury, inflammation, apoptosis, and mitochondrial injury that contribute to neuronal loss. Although cerebrovascular disease has different causes from the neurodegenerative disorders, many of the same common disease mechanisms come into play following a stroke. Novel therapies that target each of these mechanisms may be effective in decreasing the risk of disease, abating symptoms, or slowing down their progression. Although most of these therapies are experimental, and require further investigation, a few seem to offer promise.

  11. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases.

    Science.gov (United States)

    Iranzo, Alex; Santamaria, Joan; Tolosa, Eduard

    2009-12-01

    REM sleep behavior disorder (RBD) is characterized by vigorous movements associated with unpleasant dreams and increased electromyographic activity during REM sleep. Polysomnography with audiovisual recording is needed to confirm the diagnosis of RBD and to exclude other sleep disorders that can mimic its symptoms including obstructive sleep apnea, nocturnal hallucinations and confusional awakenings. RBD may be idiopathic or related to neurodegenerative diseases, particularly multiple system atrophy, Parkinson's disease and dementia with Lewy bodies. RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years. RBD should thus be considered an integral part of the disease process. When effective, neuroprotective strategies should be considered in subjects with idiopathic RBD. Patients with other neurodegenerative diseases, though, such as spinocerebellar ataxias, may also present with RBD. When clinically required, clonazepam at bedtime is effective in decreasing the intensity of dream-enacting behaviors and unpleasant dreams in both the idiopathic and secondary forms. When part of a neurodegenerative disorder the development of RBD is thought to reflect the location and extent of the underlying lesions involving the REM sleep centers of the brain (e.g., locus subceruleus, amygdala, etc.), leading to a complex multiple neurotransmitter dysfunction that involves GABAergic, glutamatergic and monoaminergic systems. RBD is mediated neither by direct abnormal alpha-synuclein inclusions nor by striatonigral dopaminergic deficiency alone.

  12. Vestibular Deficits in Neurodegenerative Disorders: Balance, Dizziness, and Spatial Disorientation.

    Science.gov (United States)

    Cronin, Thomas; Arshad, Qadeer; Seemungal, Barry M

    2017-01-01

    The vestibular system consists of the peripheral vestibular organs in the inner ear and the associated extensive central nervous system projections-from the cerebellum and brainstem to the thalamic relays to cortical projections. This system is important for spatial orientation and balance, both of critical ecological importance, particularly for successful navigation in our environment. Balance disorders and spatial disorientation are common presenting features of neurodegenerative diseases; however, little is known regarding central vestibular processing in these diseases. A ubiquitous aspect of central vestibular processing is its promiscuity given that vestibular signals are commonly found in combination with other sensory signals. This review discusses how impaired central processing of vestibular signals-typically in combination with other sensory and motor systems-may account for the impaired balance and spatial disorientation in common neurodegenerative conditions. Such an understanding may provide for new diagnostic tests, potentially useful in detecting early disease while a mechanistic understanding of imbalance and spatial disorientation in these patients may enable a vestibular-targeted therapy for such problems in neurodegenerative diseases. Studies with state of the art central vestibular testing are now much needed to tackle this important topic.

  13. Vestibular Deficits in Neurodegenerative Disorders: Balance, Dizziness, and Spatial Disorientation

    Directory of Open Access Journals (Sweden)

    Thomas Cronin

    2017-10-01

    Full Text Available The vestibular system consists of the peripheral vestibular organs in the inner ear and the associated extensive central nervous system projections—from the cerebellum and brainstem to the thalamic relays to cortical projections. This system is important for spatial orientation and balance, both of critical ecological importance, particularly for successful navigation in our environment. Balance disorders and spatial disorientation are common presenting features of neurodegenerative diseases; however, little is known regarding central vestibular processing in these diseases. A ubiquitous aspect of central vestibular processing is its promiscuity given that vestibular signals are commonly found in combination with other sensory signals. This review discusses how impaired central processing of vestibular signals—typically in combination with other sensory and motor systems—may account for the impaired balance and spatial disorientation in common neurodegenerative conditions. Such an understanding may provide for new diagnostic tests, potentially useful in detecting early disease while a mechanistic understanding of imbalance and spatial disorientation in these patients may enable a vestibular-targeted therapy for such problems in neurodegenerative diseases. Studies with state of the art central vestibular testing are now much needed to tackle this important topic.

  14. Movement Disorders and Neuromodulation

    Directory of Open Access Journals (Sweden)

    Edward A. Shipton

    2012-01-01

    Full Text Available Movement disorders are neurological conditions affecting speed, fluency, quality, and ease of movement. Deep brain stimulation (DBS is used to treat advanced Parkinson’s disease, essential tremor, and dystonia. Possible target sites for DBS include the ventral intermediate nucleus of the thalamus, the globus pallidus internus, and the subthalamic nucleus. High-frequency DBS leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity. This has a profound effect on the efficiency of movement. Indications for the use of DBS include the need to improve function, reduce medication dependency, and avoid ablative neurosurgery. Appropriate patient selection is critical for success. The implantation technique is briefly described. Programming stimulation parameters are performed via telemetry. The adverse effects of DBS are discussed. The future should see the development of “closed-loop” systems. Its use has promoted interdisciplinary team work and provided an improved understanding of the complex neurocircuitry associated with these disorders. DBS is a highly effective, safe, and reversible surgical treatment for advanced Parkinson’s disease, tremor, and dystonia. It is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms, functional status, and quality of life.

  15. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

    Science.gov (United States)

    Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W

    2015-12-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future

  16. Ghrelin: a link between ageing, metabolism and neurodegenerative disorders.

    Science.gov (United States)

    Stoyanova, I I

    2014-12-01

    Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics: 1) neuronal loss in motor, sensory or cognitive systems, leading to cognitive and motor decline; and 2) a strong correlation between metabolic changes and neurodegeneration. In order to treat them, a better understanding of their complexity is required: it is necessary to interpret the neuronal damage in light of the metabolic changes, and to find the disrupted link between the peripheral organs governing energy metabolism and the CNS. This review is an attempt to present ghrelin as part of molecular regulatory interface between energy metabolism, neuroendocrine and neurodegenerative processes. Ghrelin takes part in lipid and glucose metabolism, in higher brain functions such as sleep-wake state, learning and memory consolidation; it influences mitochondrial respiration and shows neuroprotective effect. All these make ghrelin an attractive target for development of biomarkers or therapeutics for prevention or treatment of disorders, in which cell protection and recruitment of new neurons or synapses are needed. Copyright © 2014. Published by Elsevier Inc.

  17. REM behaviour disorder detection associated with neurodegenerative diseases

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle

    2010-01-01

    Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection......, a computerized algorithm has been attempted implemented. By analysing the REM and non-REM EMG activity, using advanced signal processing tools combined with a statistical classifier, it is possible to discriminate normal and abnormal EMG activity. Due to the small number of patients, the overall performance...

  18. Context-dependent neural activation: internally and externally guided rhythmic lower limb movement in individuals with and without neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Madeleine Eve Hackney

    2015-12-01

    Full Text Available Parkinson’s Disease (PD is a neurodegenerative disorder that has received considerable attention in allopathic medicine over the past decades. However, it is clear that, to date, pharmacological and surgical interventions do not fully address symptoms of PD and patients’ quality of life. As both an alternative therapy and as an adjuvant to conventional approaches, several types of rhythmic movement (e.g., movement strategies, dance, tandem biking, tai chi have shown improvements to motor symptoms, lower limb control and postural stability in people with PD (Amano, Nocera, Vallabhajosula, Juncos, Gregor, Waddell et al., 2013; Earhart, 2009; M. E. Hackney & Earhart, 2008; Kadivar, Corcos, Foto, & Hondzinski, 2011; Morris, Iansek, & Kirkwood, 2009; Ridgel, Vitek, & Alberts, 2009. However, while these programs are increasing in number, still little is known about the neural mechanisms underlying motor improvements attained with such interventions. Studying limb motor control under task specific contexts can help determine the mechanisms of rehabilitation effectiveness. Both internally guided (IG and externally guided (EG movement strategies have evidence to support their use in rehabilitative programs. However, there appears to be a degree of differentiation in the neural substrates involved in IG versus EG designs. Because of the potential task specific benefits of rhythmic training within a rehabilitative context, this report will consider the use of IG and EG movement strategies, and observations produced by functional magnetic resonance imaging (fMRI and other imaging techniques. This review will present findings from lower limb imaging studies, under IG and EG conditions for populations with and without movement disorders. We will discuss how these studies might inform movement disorders rehabilitation (in the form of rhythmic, music-based movement training and highlight research gaps. We believe better understanding of lower limb neural

  19. Support system and method for detecting neurodegenerative disorder

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a system and a method for detection of abnormal motor activity during REM sleep, and further to systems and method for assisting in detecting neurodegenerative disorders such as Parkinson's. One embodiment relates to a method for detection of abnormal motor activity...... during REM sleep comprising the steps of: performing polysomnographic recordings of a sleeping subject, thereby obtaining one or more electromyography (EMG) derivations, preferably surface EMG recordings, and one or more EEG derivations, and/or one or more electrooculargraphy (EOG) derivations, detecting...... one or more REM sleep stages, preferably based on the one or more EEG and/or EOG derivations, determining the level of muscle activity during the one or more REM sleep stages based on the one or more EMG derivations, wherein a subject having an increased level of muscle activity during REM sleep...

  20. Melatonin in Alzheimer's disease and other neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Poeggeler B

    2006-05-01

    Full Text Available Abstract Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD, Parkinson's disease (PD and Huntington's disease (HD. As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-β toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin

  1. Few patients with neurodegenerative disorders require spinal surgery

    Science.gov (United States)

    Epstein, Nancy E.; Gottesman, Malcolm

    2014-01-01

    Background: Few patients with neurodegenerative disorders (ND) (e.g., Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Postpolio Syndrome (PPS)) require spinal surgery. Typically, their neurological symptoms and signs reflect their underlying neurologic disorders rather than structural spinal pathology reported on magnetic resonance images (MR) or computed tomographic scans (CT). Methods: The first author, a neurosurgeon, reviewed 437 spinal consultations performed over a 20-month period. Of 254 patients seen in first opinion (e.g., had not been seen by a spinal surgeon), 9 had MS, while 2 had ALS. Of 183 patients seen in second opinion (e.g., prior spinal surgeons recommended surgery), 4 had MS, 2 had ALS, and 1 had PPS. We performed this study to establish how often patients with ND, seen in first or second opinion, require spinal surgery. We focused on whether second opinions from spinal surgeons would limit the number of operations offered to these patients. Results: Two of 11 patients with ND seen in first opinion required surgery. The first patient required a C5-7 laminectomy/C2-T2 fusion, followed by a L2-S1 laminectomy/L5S1 fusion. The second patient required a L2-L3 laminectomy/diskectomy/fusion. However, none of the seven patients seen in second opinion, who were previously told by outside surgeons they needed spinal surgery, required operations. Conclusions: Few patients with neurodegenerative syndromes (MS, ALS, PPS) and reported “significant” spondyloitic spinal disease interpreted on MR/CT studies required surgery. Great caution should be exercised in offering patients with ND spinal surgery, and second opinions should be encouraged to limit “unnecessary” procedures. PMID:24843817

  2. The role of a movement disorders clinic.

    LENUS (Irish Health Repository)

    Yssel, J

    2012-02-01

    Ireland\\'s ageing population will result in a substantial increase in neurodegenerative disease with a projected increase in prevalence of Idiopathic Parkinson\\'s disease (IPD) to 9,000 by 2021. There are few published audits of neurology services to assist care planning. As a first step towards evaluating future service needs for this group of patients, we audited a single tertiary referral IPD and Other Movement Disorders clinic for 2006. A total of 497 patients from all counties in Ireland were seen; 225 (59%) of patients had IPD, 32 (8.2%) had atypical parkinsonism, and 22 (5.8%) dystonia. In a subset of 275 patients, 151 (55%) were referred by GPs, 74 (27%) by other consultants, and 49 (18%) by other consultant neurologists. Diagnosis was changed in 22 (38%) and medication was adjusted in 203 (74%). A telephone survey of 50 patients demonstrated 100% satisfaction with the improved access to the clinical nurse specialist, telephone support and improved continuity of care. The IPD and Other Movement Disorders clinic provides an important local, regional, and national diagnostic and therapeutic service for complex movement disorders. It is proposed that a national registry of IPD and audit of the delivery of care to patients with movement disorders is needed.

  3. Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases.

    Science.gov (United States)

    Irwin, Michael H; Moos, Walter H; Faller, Douglas V; Steliou, Kosta; Pinkert, Carl A

    2016-05-01

    Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Movement disorders in spinocerebellar ataxias

    NARCIS (Netherlands)

    Gaalen, J. van; Giunti, P.; Warrenburg, B.P.C. van de

    2011-01-01

    Autosomal dominant spinocerebellar ataxias (SCAs) can present with a large variety of noncerebellar symptoms, including movement disorders. In fact, movement disorders are frequent in many of the various SCA subtypes, and they can be the presenting, dominant, or even isolated disease feature. When

  5. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

    Science.gov (United States)

    Kocot, Joanna; Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

    2017-06-27

    Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders.

  6. Idiopathic REM sleep behavior disorder as a long-term predictor of neurodegenerative disorders.

    Science.gov (United States)

    Fulda, Stephany

    2011-12-01

    REM sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behavior and loss of muscle atonia during REM sleep. Idiopathic RBD occurs in the absence of any neurological disease or other possible cause, is male-predominant and its clinical course is generally chronic progressive. Secondary RBD may be related to neurodegenerative disorders such as multiple system atrophy, Parkinson's disease and Lewy body dementia. Recent long-term prospective studies have shown that 30% to 65% of patients with idiopathic RBD will eventually develop a neurodegenerative disorder with the rate of emergence depending on the length of the follow-up period. RBD may therefore be one of the earliest signs of and/or a long-term predictor for neurodegenerative disorders. Because RBD antecedes the development of these disorders by several years or decades, its recognition may enable the delay or prevention of neurodegenerative disorders through the early application of neuroprotective or disease-modifying therapies in the future.

  7. Movement disorders in mitochondrial disease.

    Science.gov (United States)

    Ghaoui, Roula; Sue, Carolyn M

    2018-01-06

    Mitochondrial disease presents with a wide spectrum of clinical manifestations that may appear at any age and cause multisystem dysfunction. A broad spectrum of movement disorders can manifest in mitochondrial diseases including ataxia, Parkinsonism, myoclonus, dystonia, choreoathetosis, spasticity, tremor, tic disorders and restless legs syndrome. There is marked heterogeneity of movement disorder phenotypes, even in patients with the same genetic mutation. Moreover, the advent of new technologies, such as next-generation sequencing, is likely to identify novel causative genes, expand the phenotype of known disease genes and improve the genetic diagnosis in these patients. Identification of the underlying genetic basis of the movement disorder is also a crucial step to allow for targeted therapies to be implemented as well as provide the basis for a better understanding of the molecular pathophysiology of the disease process. The aim of this review is to discuss the spectrum of movement disorders associated with mitochondrial disease.

  8. [Stereotactic radiosurgery for movement disorders].

    Science.gov (United States)

    Sobstyl, Michał; Ząbek, Mirosław

    2012-01-01

    Nowadays, functional neurosurgery is an established treatment for movement disorders such as Parkinson's disease, essential tremor, and dystonia. The effectiveness and safety of neuromodulation procedures (deep brain stimulation) replaced in the last years ablative irreversible stereotactic lesions for movement disorders. Stereotactic radiosurgery with gamma knife is a non-invasive form of treatment for movement disorders. The main limitation of stereotactic radiosurgery is the impossibility of electrophysiological confirmation of the target structure. Nevertheless, patients with advanced age and significant medical conditions that preclude classic open stereotactic procedures or patients who must receive anticoagulation therapy may gain great functional benefit using gamma knife stereotactic radiosurgery.

  9. Therapeutic potential of cannabinoids in neurodegenerative disorders: a selective review.

    Science.gov (United States)

    Velayudhan, Latha; Van Diepen, Erik; Marudkar, Mangesh; Hands, Oliver; Suribhatla, Srinivas; Prettyman, Richard; Murray, Jonathan; Baillon, Sarah; Bhattacharyya, Sagnik

    2014-01-01

    The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS). Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some diseases. Although still preliminary, recent reports suggest that modulation of the ECS may constitute a novel approach for the treatment of AD. There are windows of opportunity in conditions caused by acute events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD. The ECS changes in Parkinson's disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical studies are still in the preliminary stage. There is not enough evidence to support use of cannabinoids in treating Huntington's disease, tics and obsessive compulsive behaviour in Tourette's syndrome. Evidence on therapeutic use of cannabinoids in multiple sclerosis and ALS is currently limited. A major challenge for future research is the development of novel compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.

  10. Environmental Pollutants as Risk Factors for Neurodegenerative Disorders

    OpenAIRE

    Miguel eChin-Chan; Juliana eNavarro-Yepes; Betzabet eQuintanilla-Vega

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment, from diet to the new nanomaterials as putative risk factors has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metal...

  11. [Scenes in movement. Movement disorders on film].

    Science.gov (United States)

    Olivares Romero, J

    2010-03-01

    There are publications in which various neurological diseases are analysed on film. However, no references have been found on movement disorders in this medium. A total of 104 documents were collected and reviewed using the internet movie data base (IMDb). The majority were associated with dystonia, Parkinson's and tics, were American commercial productions, and the most common genre was drama. The cinema usually depicts old men with developed Parkinson's disease. However, motor complications only appear in 19% and non-motor symptoms in 14%. The image of dystonia is generally that of a young man, with disabling dystonia secondary to childhood cerebral palsy. Tics appear associated with Tourette's syndrome, with the excessive use of obscene expressions and with very few references to other important aspects of this syndrome, such as mood and behavioural changes. The majority of tremors portrayed on film are associated with Parkinsonism and are not pathological. Myoclonus appears anecdotically and is normally symptomatic. Parkinson's disease is the type of movement disorder that the cinema portrays with greater neurological honesty and in a more dignified manner.

  12. What’s on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths

    Directory of Open Access Journals (Sweden)

    David Paul Crabb

    2014-11-01

    Full Text Available Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie. Methods: Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64 to 75 yrs and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63 to 77 yrs had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD. All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada. Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA. Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI of classification sensitivity and specificity. Results: Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was -7 [-13 to -5] dB and -9 [-15 to -4] dB respectively. Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58 to 86%. The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82 to 0.87. Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement

  13. What's on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths.

    Science.gov (United States)

    Crabb, David P; Smith, Nicholas D; Zhu, Haogang

    2014-01-01

    We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie. Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64-75 years) and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63-77 years) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD). All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada). Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA). Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI) of classification sensitivity and specificity. Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was -7 [-13 to -5] dB and -9 [-15 to -4] dB, respectively). Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58-86%). The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82-0.87). Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement signatures alone.

  14. Cranial functional (psychogenic) movement disorders.

    Science.gov (United States)

    Kaski, Diego; Bronstein, Adolfo M; Edwards, Mark J; Stone, Jon

    2015-12-01

    Functional (psychogenic) neurological symptoms are frequently encountered in neurological practice. Cranial movement disorders--affecting the eyes, face, jaw, tongue, or palate--are an under-recognised feature of patients with functional symptoms. They can present in isolation or in the context of other functional symptoms; in particular, for functional eye movements, positive clinical signs such as convergence spasms can be triggered by the clinical examination. Although the specialty of functional neurological disorders has expanded, appreciation of cranial functional movement disorders is still insufficient. Identification of the positive features of cranial functional movement disorders such as convergence and unilateral platysmal spasm might lend diagnostic weight to a suspected functional neurological disorder. Understanding of the differential diagnosis, which is broad and includes many organic causes (eg, stroke), is essential to make an early and accurate diagnosis to prevent complications and initiate appropriate management. Increased understanding of these disorders is also crucial to drive clinical trials and studies of individually tailored therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Gene Therapy-Based Modeling of Neurodegenerative Disorders: Huntington's Disease.

    Science.gov (United States)

    Young, Deborah

    2016-01-01

    Huntington's disease is a fatal neurodegenerative disease characterized by impairments in motor control, and cognitive and psychiatric disturbances. In this chapter, viral vector-mediated approaches used in modeling the key neuropathological features of the disease including the production of abnormal intracellular protein aggregates, neuronal dysfunction and degeneration and motor impairments in rodents are described.

  16. Sensory aspects of movement disorders

    Science.gov (United States)

    Patel, Neepa; Jankovic, Joseph; Hallett, Mark

    2016-01-01

    Movement disorders, which include disorders such as Parkinson’s disease, dystonia, Tourette’s syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed. PMID:24331796

  17. Surgical management of movement disorders

    African Journals Online (AJOL)

    Disability from movement disorders is often seen as par for the course in the ageing process. It is the price paid by those who are lucky enough to grow old. There are, however, also young patients who develop. Parkinson's disease (PD) and dystonia and have to discontinue their profession owing to a severely disabling ...

  18. Ketotic hyperglycemia with movement disorder

    Directory of Open Access Journals (Sweden)

    Disha Awasthi

    2012-01-01

    Full Text Available Chorea, hemichorea-hemiballismus and severe partial seizures may be the presenting features of nonketotic hyperglycemia in older adults with type 2 diabetes, but cases in young adults with type 1 diabetes are rare. We hereby report a very rare case of diabetic ketosis with movement disorder in a young patient.

  19. RBD and Neurodegenerative Diseases.

    Science.gov (United States)

    Jiang, Haiyang; Huang, Jinsha; Shen, Yan; Guo, Shiyi; Wang, Luxi; Han, Chao; Liu, Ling; Ma, Kai; Xia, Yun; Li, Jie; Xu, Xiaoyun; Xiong, Nian; Wang, Tao

    2017-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by enacting one's dreams during the REM sleep, with most of the dreams being violent or aggressive, so that patients often come to see the doctor complaining hurting themselves or bed partners during sleep. Prevalence of RBD, based on population, is 0.38-2.01 %, but much higher in patients with neurodegenerative diseases, especially synucleinopathies. RBD may herald the emergence of synucleinopathies by decades, such that it may be used as an effective early marker of neurodegenerative diseases. Pharmaceutical treatment of RBD includes clonazepam, melatonin, pramipexole, and some newly reported medications. In this review, we summarized the clinical and PSG features of RBD, the pathophysiology and the therapy of it, focusing on the correlation between neurodegenerative diseases and RBD, in order to emphasize the significance of RBD as an early marker of neurodegenerative diseases.

  20. Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

    Science.gov (United States)

    Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-Young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin

    2016-04-05

    Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

  1. Morbidities in rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Jennum, Poul; Mayer, Geert; Ju, Yo-El

    2013-01-01

    Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, RBD without any obvious comorbid major neurological disease), is strongly associated with numerous comorbid conditions. The most prominent is that with neurodegenerative disorders, especially synuclein-mediated disorders, above all...... of dementia with Lewy bodies. These findings underline the progressive disease process, suggesting involvement of more brain regions in patients with a more advanced disease stage. RBD is also associated with narcolepsy, and it is likely that RBD associated with narcolepsy is a distinct subtype associated...

  2. Disorders of vergence eye movements.

    Science.gov (United States)

    Serra, Alessandro; Chen, Athena L; Leigh, R John

    2011-02-01

    The aim is to re-interpret disorders of vergence in the light of recent studies that view disjunctive eye movements as but one component of three-dimensional gaze control. Most natural eye movements combine vergence with saccades, pursuit and vestibular eye movements. Electrophysiological studies in epileptic patients, as well as evidence from monkeys, indicate that frontal and parietal cortex govern vergence as a component of three-dimensional gaze. Clinicians apply Hering's law of equal innervation to interpret disjunctive movements as the superposition of conjugate and vergence commands. However, electrophysiological studies indicate that disjunctive saccades are achieved by programming each eye's movement independently. Patients with internuclear ophthalmoplegia (INO) may have preserved vergence, which can be recruited to compensate for loss of conjugacy. Vergence may also enable gaze shifts in saccadic palsy. Some forms of nystagmus suppress or change with convergence; co-contraction of the horizontal rectus muscles does not appear to be the explanation. Rather, effects of near viewing on central vestibular mechanisms or differential activation of specific types of extra-ocular muscle fiber may be responsible. Interpretation of disorders of vergence is aided by applying a scheme in which their contributions to three-dimensional gaze control is considered.

  3. Sensorimotor integration in movement disorders.

    Science.gov (United States)

    Abbruzzese, Giovanni; Berardelli, Alfredo

    2003-03-01

    Although current knowledge attributes movement disorders to a dysfunction of the basal ganglia-motor cortex circuits, abnormalities in the peripheral afferent inputs or in their central processing may interfere with motor program execution. We review the abnormalities of sensorimotor integration described in the various types of movement disorders. Several observations, including those of parkinsonian patients' excessive reliance on ongoing visual information during movement tasks, suggest that proprioception is defective in Parkinson's disease (PD). The disturbance of proprioceptive regulation, possibly related to the occurrence of abnormal muscle-stretch reflexes, might be important for generating hypometric or bradykinetic movements. Studies with somatosensory evoked potentials (SEPs), prepulse inhibition, and event-related potentials support the hypothesis of central abnormalities of sensorimotor integration in PD. In Huntington's disease (HD), changes in SEPs and long-latency stretch reflexes suggest that a defective gating of peripheral afferent input to the brain might impair sensorimotor integration in cortical motor areas, thus interfering with the processing of motor programs. Defective motor programming might contribute to some features of motor impairment in HD. Sensory symptoms are frequent in focal dystonia and sensory manipulation can modify the dystonic movements. In addition, specific sensory functions (kinaesthesia, spatial-temporal discrimination) can be impaired in patients with focal hand dystonia, thus leading to a "sensory overflow." Sensory input may be abnormal and trigger focal dystonia, or defective "gating" may cause an input-output mismatch in specific motor programs. Altogether, several observations strongly support the idea that sensorimotor integration is impaired in focal dystonia. Although elemental sensation is normal in patients with tics, tics can be associated with sensory phenomena. Some neurophysiological studies suggest that

  4. Environmental Pollutants as Risk Factors for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Miguel eChin-Chan

    2015-04-01

    Full Text Available Neurodegenerative diseases including Alzheimer (AD and Parkinson (PD have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment, from diet to the new nanomaterials as putative risk factors has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ peptide and the phosphorylation of Tau protein (P-Tau, causing senile/amyloid plaques and neurofibrillary tangles characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn, which is a key constituent of Lewy bodies, a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzymes such as neprilysin or insulin degrading enzyme. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

  5. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without......Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...

  6. Perspectives on functional and hyperkinetic movement disorders : Phenomenology & pathophysiology

    NARCIS (Netherlands)

    van der Salm, S.M.A.

    2017-01-01

    Functional movement disorders (FMD), previously known as conversion disorders or psychogenic movement disorders, are abnormal movements which cannot be attributed to other neurological disorders. FMD are frequently encountered in movement disorder outpatient clinics. Yet, most neurologists consider

  7. Stereotactic radiosurgery for movement disorders

    Science.gov (United States)

    Frighetto, Leonardo; Bizzi, Jorge; Annes, Rafael D’Agostini; Silva, Rodrigo dos Santos; Oppitz, Paulo

    2012-01-01

    Initially designed for the treatment of functional brain targets, stereotactic radiosurgery (SRS) has achieved an important role in the management of a wide range of neurosurgical pathologies. The interest in the application of the technique for the treatment of pain, and psychiatric and movement disorders has returned in the beginning of the 1990s, stimulated by the advances in neuroimaging, computerized dosimetry, treatment planning software systems, and the outstanding results of radiosurgery in other brain diseases. Since SRS is a neuroimaging-guided procedure, without the possibility of neurophysiological confirmation of the target, deep brain stimulation (DBS) and radiofrequency procedures are considered the best treatment options for movement-related disorders. Therefore, SRS is an option for patients who are not suitable for an open neurosurgical procedure. SRS thalamotomy provided results in tremor control, comparable to radiofrequency and DBS. The occurrence of unpredictable larger lesions than expected with permanent neurological deficits is a limitation of the procedure. Improvements in SRS technique with dose reduction, use of a single isocenter, and smaller collimators were made to reduce the incidence of this serious complication. Pallidotomies performed with radiosurgery did not achieve the same good results. Even though the development of DBS has supplanted lesioning as the first alternative in movement disorder surgery; SRS might still be the only treatment option for selected patients. PMID:22826805

  8. Eye movements in vestibular disorders.

    Science.gov (United States)

    Kheradmand, A; Colpak, A I; Zee, D S

    2016-01-01

    The differential diagnosis of patients with vestibular symptoms usually begins with the question: is the lesion central or is it peripheral? The answer commonly emerges from a careful examination of eye movements, especially when the lesion is located in otherwise clinically silent areas of the brain such as the vestibular portions of the cerebellum (flocculus, paraflocculus which is called the tonsils in humans, nodulus, and uvula) and the vestibular nuclei as well as immediately adjacent areas (the perihypoglossal nuclei and the paramedian nuclei and tracts). The neural circuitry that controls vestibular eye movements is intertwined with a larger network within the brainstem and cerebellum that also controls other types of conjugate eye movements. These include saccades and pursuit as well as the mechanisms that enable steady fixation, both straight ahead and in eccentric gaze positions. Navigating through this complex network requires a thorough knowledge about all classes of eye movements to help localize lesions causing a vestibular disorder. Here we review the different classes of eye movements and how to examine them, and then describe common ocular motor findings associated with central vestibular lesions from both a topographic and functional perspective. © 2016 Elsevier B.V. All rights reserved.

  9. Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

    Science.gov (United States)

    Beach, Thomas G; Adler, Charles H; Sue, Lucia I; Serrano, Geidy; Shill, Holly A; Walker, Douglas G; Lue, LihFen; Roher, Alex E; Dugger, Brittany N; Maarouf, Chera; Birdsill, Alex C; Intorcia, Anthony; Saxon-Labelle, Megan; Pullen, Joel; Scroggins, Alexander; Filon, Jessica; Scott, Sarah; Hoffman, Brittany; Garcia, Angelica; Caviness, John N; Hentz, Joseph G; Driver-Dunckley, Erika; Jacobson, Sandra A; Davis, Kathryn J; Belden, Christine M; Long, Kathy E; Malek-Ahmadi, Michael; Powell, Jessica J; Gale, Lisa D; Nicholson, Lisa R; Caselli, Richard J; Woodruff, Bryan K; Rapscak, Steven Z; Ahern, Geoffrey L; Shi, Jiong; Burke, Anna D; Reiman, Eric M; Sabbagh, Marwan N

    2015-08-01

    The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200

  10. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder.

    Science.gov (United States)

    Postuma, R B; Gagnon, J F; Vendette, M; Fantini, M L; Massicotte-Marquez, J; Montplaisir, J

    2009-04-14

    Idiopathic REM sleep behavior disorder (RBD) is a potential preclinical marker for the development of neurodegenerative diseases, particularly Parkinson disease (PD) and Lewy body dementia. However, the long-term risk of developing neurodegeneration in patients with idiopathic RBD has not been established. Obtaining an accurate picture of this risk is essential for counseling patients and for development of potential neuroprotective therapies. We conducted a follow-up study of all patients seen at the sleep disorders laboratory at the Hôpital du Sacré Coeur with a diagnosis of idiopathic RBD. Diagnoses of parkinsonism and dementia were defined according to standard criteria. Survival curves were constructed to estimate the 5-, 10-, and 12-year risk of developing neurodegenerative disease. Of 113 patients, 93 (82%) met inclusion criteria. The mean age of participants was 65.4 years and 75 patients (80.4%) were men. Over the follow-up period, 26/93 patients developed a neurodegenerative disorder. A total of 14 patients developed PD, 7 developed Lewy body dementia, 4 developed dementia that met clinical criteria for AD, and 1 developed multiple system atrophy. The estimated 5-year risk of neurodegenerative disease was 17.7%, the 10-year risk was 40.6%, and the 12-year risk was 52.4%. Although we have found a slightly lower risk than other reports, the risk of developing neurodegenerative disease in idiopathic REM sleep behavior disorder is substantial, with the majority of patients developing Parkinson disease and Lewy body dementia.

  11. Stereotypic movement disorder: easily missed.

    Science.gov (United States)

    Freeman, Roger D; Soltanifar, Atefeh; Baer, Susan

    2010-08-01

    To expand the understanding of stereotypic movement disorder (SMD) and its differentiation from tics and autistic stereotypies. Forty-two children (31 males, mean age 6y 3mo, SD 2y 8mo; 11 females, mean age 6y 7mo, SD 1y 9mo) consecutively diagnosed with SMD, without-self-injurious behavior, intellectual disability, sensory impairment, or an autistic spectrum disorder (ASD), were assessed in a neuropsychiatry clinic. A list of probe questions on the nature of the stereotypy was administered to parents (and to children if developmentally ready). Questionnaires administered included the Stereotypy Severity Scale, Short Sensory Profile, Strengths and Difficulties Questionnaire, Repetitive Behavior Scale--Revised, and the Developmental Coordination Disorder Questionnaire. The stereotyped movement patterns were directly observed and in some cases further documented by video recordings made by parents. The probe questions were used again on follow-up at a mean age of 10 years 7 months (SD 4y 4mo). Mean age at onset was 17 months. Males exceeded females by 3:1. Family history of a pattern of SMD was reported in 13 and neuropsychiatric comorbidity in 30 (attention-deficit-hyperactivity disorder in 16, tics in 18, and developmental coordination disorder in 16). Obsessive-compulsive disorder occurred in only two. The Short Sensory Profile correlated with comorbidity (p<0.001), the Stereotypy Severity Scale (p=0.009), and the Repetitive Behavior Scale (p<0.001); the last correlated with the Stereotypy Severity Scale (p=0.001). Children (but not their parents) liked their movements, which were usually associated with excitement or imaginative play. Mean length of follow-up was 4 years 8 months (SD 2y 10mo). Of the 39 children followed for longer than 6 months, the behavior stopped or was gradually shaped so as to occur primarily privately in 25. Misdiagnosis was common: 26 were initially referred as tics, 10 as ASD, five as compulsions, and one as epilepsy. Co-occurring facial

  12. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

    Science.gov (United States)

    Iranzo, Alex; Fernández-Arcos, Ana; Tolosa, Eduard; Serradell, Mónica; Molinuevo, José Luis; Valldeoriola, Francesc; Gelpi, Ellen; Vilaseca, Isabel; Sánchez-Valle, Raquel; Lladó, Albert; Gaig, Carles; Santamaría, Joan

    2014-01-01

    To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up. Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.

  13. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

    Directory of Open Access Journals (Sweden)

    Alex Iranzo

    Full Text Available OBJECTIVE: To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD patients with long follow-up. METHODS: Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. RESULTS: The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4% were dementia with Lewy bodies (DLB in 29 subjects, Parkinson disease (PD in 22, multiple system atrophy (MSA in two, and mild cognitive impairment (MCI in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. CONCLUSIONS: In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.

  14. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

    DEFF Research Database (Denmark)

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-01-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized...... by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however......, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients...

  15. Disease modeling in functional movement disorders.

    Science.gov (United States)

    Pellicciari, Roberta; Superbo, Maria; Gigante, Angelo Fabio; Livrea, Paolo; Defazio, Giovanni

    2014-11-01

    The mechanisms underlying functional movement disorders are poorly known. We examined whether experience of a movement disorder model in the family and/or the friendships contributes to functional movement disorders. The hypothesis was tested in a case-control study including 33 patients with functional movement disorders and 66 age- and sex-matched patients with organic movement disorders and using a conditional logistic multivariable analysis (adjusted by age, education, disease duration, chronic medical illnesses and clinical phenotype). Case-control comparison yielded a significant association between functional movement disorders and exposure to phenotypically congruent movement disorder models (Odds ratio, 3.9, p = 0.01), mainly when disease model came from friendships (Odds ratio, 5.9, p = 0.04). By contrast no association was found between functional movement disorders and phenotypically different neurological or non neurological disease models. A significant inverse relationship between exposure to a phenotypically concordant movement disorder model and age of disease onset was also observed. These findings support disease modeling as a factor contributing to the phenomenology of functional movement disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. [Sleep disorder, a potential early diagnostic marker for psychiatric and neurodegenerative diseases].

    Science.gov (United States)

    Chen, Yan-Mei; Qin, Dong-Dong; Jiang, Hui-Hui; Hu, Xin-Tian; Ma, Yuan-Ye

    2011-02-01

    Sleep/circadian timing depends on several neurotransmitter systems, including 5-HT, NE, DA, Ach, GABA, etc. These neurotransmitter systems play critical roles in mental, emotional and cognitive functions in the brain. Dysfunctions of these systems not only result in sleep disorder, but are also related to many psychiatric and neurodegenerative diseases. Sleep disruption is tightly associated with an increased susceptibility to a broad range of psychiatric and neurodegenerative diseases, such as depression and Parkinson diseases. Non-human primates, especially the rhesus monkey is an excellent biomedical model for human sleep and CNS diseases. Establishing nonhuman primates' model of mental disorders and monitoring the sleep changes during the development of the model will help us to know more about the relationships between sleep disorder and psychiatric and neurodegenerative diseases. Sleep disorder as an early marker for psychiatric and neurodegenerative diseases would permit early intervention of these diseases and draw attention to the potential therapeutic benefits of normalizing sleep rhythms in individuals with brain pathologies.

  17. DNA methylation in neurodegenerative disorders: a missing link between genome and environment?

    Science.gov (United States)

    Iraola-Guzmán, S; Estivill, X; Rabionet, R

    2011-07-01

    The risk of developing neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease is influenced by genetic and environmental factors. Environmental events occurring during development or later in life can be related to disease susceptibility. One way by which the environment may exert its effect is through epigenetic modifications, which might affect the functioning of genes. These include nucleosome positioning, post-translational histone modifications, and DNA methylation. In this review we will focus in the potential role of DNA methylation in neurodegenerative disorders and in the approaches to explore such epigenetic changes. Advances in deciphering the role of epigenetic modifications in phenotype are being uncovered for a variety of diseases, including cancer, autoimmune, neurodevelopmental and cognitive disorders. Epigenetic modifications are now being also associated with cardiovascular and metabolic traits, and they are expected to be especially involved in learning and memory processes, as well as in neurodegenerative disease. The study of the role of methylation and other epigenetic modifications in disease development will provide new insights in the etiopathogenesis of neurodegenerative disorders, and should hopefully shape new avenues in the development of therapeutic strategies. © 2011 John Wiley & Sons A/S.

  18. Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes

    NARCIS (Netherlands)

    Franceschi, L. De; Bosman, G.J.C.G.M.; Mohandas, N.

    2014-01-01

    PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod

  19. Functional jerks, tics, and paroxysmal movement disorders

    NARCIS (Netherlands)

    Dreissen, Y. E. M.; Cath, D C; Tijssen, M A J; Hallet, Mark; Stone, Jon; Carson, Alan

    2017-01-01

    Functional jerks are among the most common functional movement disorders. The diagnosis of functional jerks is mainly based on neurologic examination revealing specific positive clinical signs. Differentiation from other jerky movements, such as tics, organic myoclonus, and primary paroxysmal

  20. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions.

    Science.gov (United States)

    Boeve, Bradley F

    2010-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straightforward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail.

  1. Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through "Functional" (Neuro)Psychiatric Disorders.

    Science.gov (United States)

    Peralta, Victor; Cuesta, Manuel J

    2017-09-01

    Motor abnormalities (MAs) of severe mental disorders have been traditionally neglected both in clinical practice and research, although they are an increasing focus of attention because of their clinical and neurobiological relevance. For historical reasons, most of the literature on MAs has been focused to a great extent on schizophrenia, and as a consequence their prevalence and featural properties in other psychiatric or neuropsychiatric disorders are poorly known. In this article, we evaluated the extent to which catatonic, extrapyramidal and neurological soft signs, and their associated clinical features, are present transdiagnostically. We examined motor-related features in neurodevelopmental (schizophrenia, obsessive compulsive disorder, autism spectrum disorders), "functional" (nonschizophrenic nonaffective psychoses, mood disorders) and neurodegenerative (Alzheimer's disease) disorders. Examination of the literature revealed that there have been very few comparisons of motor-related features across diagnoses and we had to rely mainly in disorder-specific studies to compare it transdiagnostically. One or more motor domains had a substantial prevalence in all the diagnoses examined. In "functional" disorders, MAs, and particularly catatonic signs, appear to be markers of episode severity; in chronic disorders, although with different degree of strength or evidence, all motor domains are indicators of both disorder severity and poor outcome; lastly, in Alzheimer's disease they are also indicators of disorder progression. MAs appear to represent a true transdiagnostic domain putatively sharing neurobiological mechanisms of neurodevelopmental, functional or neurodegenerative origin.

  2. Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?

    Directory of Open Access Journals (Sweden)

    Rosanna Parlato

    2015-05-01

    Full Text Available Within the cell nucleus the nucleolus is the site of rRNA transcription and ribosome biogenesis and its activity is clearly essential for a correct cell function, however its specific role in neuronal homeostasis remains mainly unknown. Here we review recent evidence that impaired nucleolar activity is a common mechanism in different neurodegenerative disorders. We focus on the specific causes and consequences of impaired nucleolar activity to better understand the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD, Parkinson's disease (PD, Huntington's disease (HD and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD. In particular, we discuss the genetic and epigenetic factors that might regulate nucleolar function in these diseases. In addition, we describe novel animal models enabling the dissection of the context-specific series of events triggered by nucleolar disruption, also known as nucleolar stress. Finally, we suggest how this novel mechanism could help to identify strategies to treat these still incurable disorders.

  3. Sleep in Neurodegenerative Diseases.

    Science.gov (United States)

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

    Science.gov (United States)

    Postuma, Ronald B; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y

    2013-11-01

    Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Prospective cohort study. Tertiary sleep disorders center. 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

  5. Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

    Science.gov (United States)

    Perluigi, Marzia; Reed, Tanea; Muharib, Tasneem; Hughes, Christopher P.; Robinson, Renã A.S.; Sultana, Rukhsana

    2012-01-01

    Abstract Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidative-stress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610–1655. PMID:22115501

  6. Eye Movement Disorders in Dyslexia. Final Report.

    Science.gov (United States)

    Festinger, Leon; And Others

    Eye movements of 18 male and seven female dyslexic children and 10 normal children were evaluated to determine if eye movement disorders may be the cause of some of the symptoms associated with dyslexia. Data on eye movements were collected while Ss moved their eyes from one fixation point to another in a nonreading situation. Errors in vertical…

  7. Surgical management of movement disorders | Enslin | South ...

    African Journals Online (AJOL)

    Movement disorders are usually treated by neurologists, and appropriately so. The first-line management of all conditions that are grouped together as movement disorders (e.g. Parkinson's disease, dystonia, essential tremor) is with medication and, in some, with rehabilitative strategies, such as occupational therapy, ...

  8. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Schenck, C H; Montplaisir, J Y; Frauscher, B

    2013-01-01

    We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD...

  9. Hydrogel-Based Nanocomposites and Mesenchymal Stem Cells: A Promising Synergistic Strategy for Neurodegenerative Disorders Therapy

    Directory of Open Access Journals (Sweden)

    Diego Albani

    2013-01-01

    Full Text Available Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs, to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed.

  10. Endocannabinoids and Neurodegenerative Disorders: Parkinson's Disease, Huntington's Chorea, Alzheimer's Disease, and Others.

    Science.gov (United States)

    Fernández-Ruiz, Javier; Romero, Julián; Ramos, José A

    2015-01-01

    This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders. First, we will describe the cellular and molecular mechanisms, and the signaling pathways, underlying these neuroprotective properties, including the control of glutamate homeostasis, calcium influx, the toxicity of reactive oxygen species, glial activation and other inflammatory events; and the induction of autophagy. We will then concentrate on the preclinical studies and the few clinical trials that have been carried out targeting endocannabinoid signaling in three important chronic progressive neurodegenerative disorders (Parkinson's disease, Huntington's chorea, and Alzheimer's disease), as well as in other less well-studied disorders. We will end by offering some ideas and proposals for future research that should be carried out to optimize endocannabinoid-based treatments for these disorders. Such studies will strengthen the possibility that these therapies will be investigated in the clinical scenario and licensed for their use in specific disorders.

  11. Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds

    Directory of Open Access Journals (Sweden)

    Mahmood Rasool

    2014-01-01

    Full Text Available Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS. Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer’s disease, Parkinson’s disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

  12. The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.

    Science.gov (United States)

    Eira, Jessica; Silva, Catarina Santos; Sousa, Mónica Mendes; Liz, Márcia Almeida

    2016-06-01

    Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Glucose 6 phosphatase dehydrogenase (G6PD and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-12-01

    Full Text Available Glucose 6 phosphate dehydrogenase (G6PD is a key and rate limiting enzyme in the pentose phosphate pathway (PPP. The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH. There are preponderance research findings that demonstrate the enzyme (G6PD role in the energy balance, and it is associated with blood-related diseases and disorders, primarily the anemia resulted from G6PD deficiency. The X-linked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe. Recent advancement in biology, more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders. The neuroprotective role of the enzyme (G6PD has also been established, as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species (ROS produced in cerebral ischemia. Though G6PD deficiency remains a global health issue, however, a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics. Here, in this study, more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia, thus providing diagnostic and therapeutic opportunities.

  14. Cognition in rapid eye movement sleep behavior disorder

    Directory of Open Access Journals (Sweden)

    Jean-François eGagnon

    2012-05-01

    Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is a parasomnia characterized by excessive muscle activity and undesirable motor events during REM sleep. RBD occurs in approximately 0.5% of the general population, with a higher prevalence in older men. RBD is a frequent feature of dementia with Lewy bodies (DLB, but is only rarely reported in Alzheimer’s disease. RBD is also a risk factor for α-synuclein-related diseases, such as DLB, Parkinson’s disease (PD, and multiple system atrophy. Therefore, RBD has major implications for the diagnosis and treatment of neurodegenerative disorders and for understanding neurodegeneration mechanisms. Several markers of neurodegeneration have been identified in RBD, including cognitive impairments such as deficits in attention, executive functions, learning capacities, and visuospatial abilities. Approximately 50% of RBD patients present mild cognitive impairment (MCI. Moreover, RBD is also associated with cognitive decline in PD.

  15. Fundamental Movement Skills and Autism Spectrum Disorders

    Science.gov (United States)

    Staples, Kerri L.; Reid, Greg

    2010-01-01

    Delays and deficits may both contribute to atypical development of movement skills by children with ASD. Fundamental movement skills of 25 children with autism spectrum disorders (ASD) (ages 9-12 years) were compared to three typically developing groups using the "Test of Gross Motor Development" ("TGMD-2"). The group matched on chronological age…

  16. Stereotyped movement disorder in ICD-11.

    Science.gov (United States)

    Stein, Dan J; Woods, Douglas W

    2014-01-01

    According to current proposals for ICD-11, stereotyped movement disorder will be classified in the grouping of neurodevelopmental disorders, with a qualifier to indicate whether self-injury is present, similar to the classification of stereotypic movement disorder in DSM-5. At the same time, the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders has proposed a grouping of body-focused repetitive behavior disorders within the obsessive-compulsive and related disorders (OCRD) cluster to include trichotillomania and skin-picking disorder. DSM-5 has taken a slightly different approach: trichotillomania and excoriation (skin picking) disorder are included in the OCRD grouping, while body-focused repetitive behavior disorder is listed under other specified forms of OCRD. DSM-5 also includes a separate category of nonsuicidal self-injury in the section on "conditions for further study." There are a number of unresolved nosological questions regarding the relationships among stereotyped movement disorder, body-focused repetitive behavior disorders, and nonsuicidal self-injury. In this article, we attempt to provide preliminary answers to some of these questions as they relate to the ICD-11 classification of mental and behavioral disorders.

  17. Video recording in movement disorders: practical issues.

    Science.gov (United States)

    Duker, Andrew P

    2013-10-01

    Video recording can provide a valuable and unique record of the physical examinations of patients with a movement disorder, capturing nuances of movement and supplementing the written medical record. In addition, video is an indispensable tool for education and research in movement disorders. Digital file recording and storage has largely replaced analog tape recording, increasing the ease of editing and storing video records. Practical issues to consider include hardware and software configurations, video format, the security and longevity of file storage, patient consent, and video protocols.

  18. Importance of Rapid Eye Movement Sleep Behavior Disorder to the Primary Care Physician.

    Science.gov (United States)

    McCarter, Stuart J; Howell, Michael J

    2016-10-01

    Sleep disorders and neurodegenerative diseases are commonly encountered in primary care. A common, but underdiagnosed sleep disorder, rapid eye movement sleep behavior disorder (RBD), is highly associated with Parkinson disease and related disorders. Rapid eye movement sleep behavior disorder is common. It is estimated to affect 0.5% of the general population and more than 7% of individuals older than 60 years; however, most cases go unrecognized. Rapid eye movement sleep behavior disorder presents as dream enactment, often with patients thrashing, punching, and kicking while they are sleeping. Physicians can quickly assess for the presence of RBD with high sensitivity and specificity by asking patients the question "Have you ever been told that you act out your dreams, for example by punching or flailing your arms in the air or screaming and shouting in your sleep?" Patients with RBD exhibit subtle signs of neurodegenerative disease, such as mild motor slowing, constipation, or changes in sense of smell. These signs and symptoms may predict development of a neurodegenerative disease within 3 years. Ultimately, most patients with RBD develop a neurodegenerative disease, highlighting the importance of serial neurological examinations to assess for the presence of parkinsonism and/or cognitive impairment and prognostic counseling for these patients. Rapid eye movement sleep behavior disorder is treatable with melatonin (3-6 mg before bed) or clonazepam (0.5-1 mg before bed) and may be the most common, reversible cause of sleep-related injury. Thus, it is important to identify patients at risk of RBD in a primary care setting so that bedroom safety can be addressed and treatment may be initiated. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  19. Ictal SPECT in patients with rapid eye movement sleep behaviour disorder.

    Science.gov (United States)

    Mayer, Geert; Bitterlich, Marion; Kuwert, Torsten; Ritt, Philipp; Stefan, Hermann

    2015-05-01

    Rapid eye movement sleep behaviour disorder is a rapid eye movement parasomnia clinically characterized by acting out dreams due to disinhibition of muscle tone in rapid eye movement sleep. Up to 80-90% of the patients with rapid eye movement sleep behaviour disorder develop neurodegenerative disorders within 10-15 years after symptom onset. The disorder is reported in 45-60% of all narcoleptic patients. Whether rapid eye movement sleep behaviour disorder is also a predictor for neurodegeneration in narcolepsy is not known. Although the pathophysiology causing the disinhibition of muscle tone in rapid eye movement sleep behaviour disorder has been studied extensively in animals, little is known about the mechanisms in humans. Most of the human data are from imaging or post-mortem studies. Recent studies show altered functional connectivity between substantia nigra and striatum in patients with rapid eye movement sleep behaviour disorder. We were interested to study which regions are activated in rapid eye movement sleep behaviour disorder during actual episodes by performing ictal single photon emission tomography. We studied one patient with idiopathic rapid eye movement sleep behaviour disorder, one with Parkinson's disease and rapid eye movement sleep behaviour disorder, and two patients with narcolepsy and rapid eye movement sleep behaviour disorder. All patients underwent extended video polysomnography. The tracer was injected after at least 10 s of consecutive rapid eye movement sleep and 10 s of disinhibited muscle tone accompanied by movements registered by an experienced sleep technician. Ictal single photon emission tomography displayed the same activation in the bilateral premotor areas, the interhemispheric cleft, the periaqueductal area, the dorsal and ventral pons and the anterior lobe of the cerebellum in all patients. Our study shows that in patients with Parkinson's disease and rapid eye movement sleep behaviour disorder-in contrast to wakefulness

  20. Potential for targeting dopamine/DARPP-32 signaling in neuropsychiatric and neurodegenerative disorders.

    Science.gov (United States)

    Nishi, Akinori; Shuto, Takahide

    2017-03-01

    Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease. In general, under physiological and pathophysiological conditions, DARPP-32 in D1 receptor expressing (D1R) -medium spiny neurons (MSNs) promotes dopamine/D1 receptor/PKA signaling, whereas DARPP-32 in D2 receptor expressing (D2R)-MSNs counteracts dopamine/D2 receptor signaling. However, the function of DARPP-32 is differentially regulated in acute and chronic phases of drug addiction; DARPP-32 enhances D1 receptor/PKA signaling in the acute phase, whereas DARPP-32 suppresses D1 receptor/PKA signaling in the chronic phase through homeostatic mechanisms. Therefore, DARPP-32 plays a bidirectional role in dopamine neurotransmission, depending on the cell type and experimental conditions, and is involved in dopamine-related behavioral abnormalities. Expert opinion: DARPP-32 differentially regulates dopamine signaling in D1R- and D2R-MSNs, and a shift of balance between D1R- and D2R-MSN function is associated with behavioral abnormalities. An adjustment of this imbalance is achieved by therapeutic approaches targeting DARPP-32-related signaling molecules.

  1. Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders?

    Science.gov (United States)

    Jodeiri Farshbaf, Mohammad; Ghaedi, Kamran

    2017-02-01

    The prevalence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease are increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the research to establish novel therapeutic strategies. Iron as the one of most important cation not only play important role in the structure of electron transport chain proteins but also has pivotal duties in cellular activities. But disruption in iron hemostasis can make it toxin to neurons which causes lipid peroxidation, DNA damage and etc. In patients with Alzheimer and Parkinson misbalancing in iron homeostasis accelerate neurodegeneration and cause neuroinflmmation. mTOR as the common signaling pathway between cancer and neurodegenerative disorders controls iron uptake and it is in active form in both diseases. Anti-cancer drugs which target mTOR causes iron deficiency and dual effects of mTOR inhibitors can candidate them as a therapeutic strategy to alleviate neurodegeneration/inflammation because of iron overloading.

  2. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Chanshuai Han

    2018-02-01

    Full Text Available Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  3. Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

    Science.gov (United States)

    Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

    2014-01-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

  4. Lower urinary tract dysfunction in patients with parkinsonism and other neurodegenerative disorders

    DEFF Research Database (Denmark)

    Winge, Kristian

    2015-01-01

    be present, most commonly in disorders with spinal cord involvement. The systematic and careful tracking of symptoms, evaluation using non-invasive techniques, and conservative management including pharmacologic treatments can often markedly improve the lives of patients and their caregivers....... of dopaminergic neurons in the substantia nigra and possibly also in the ventral tegmental area induces loss of neurogenic bladder control through dysfunction of a complex network in which selective disinhibition of bladder reflexes is lost. In PD, more than 60% of patients have troublesome bladder symptoms...... of incontinence in Alzheimer's disease, but higher cognitive function including attention and self-management may play a role. Incontinence is a major risk factor for loss of independence. The complex pathophysiologic mechanisms of neurodegenerative disorders and hence complex symptoms play important roles...

  5. Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Douglas eGray

    2013-08-01

    Full Text Available Whereas many cases of neurodegenerative disease feature the abnormal accumulationof protein, an abundance of recent literature highlights loss of RNA homeostasis as aubiquitous and central feature of pathological states. In some diseases expandedrepeats have been identified in non-coding regions of disease-associated transcripts,calling into question the relevance of protein in the disease mechanism. We review theliterature in support of a hypothesis that intrinsically disordered proteins (proteins thatlack a stable three dimensional conformation are particularly sensitive to an age-relateddecline in maintenance of protein homeostasis. The potential consequences forstructurally disordered RNA binding proteins are explored, including their aggregationinto complexes that could be transmitted through a prion-like mechanism. We proposethat the spread of ribonucleoprotein complexes through the nervous system couldpropagate a neuronal error catastrophe at the level of RNA metabolism.

  6. Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders.

    Science.gov (United States)

    Sukoff Rizzo, Stacey J; Crawley, Jacqueline N

    2017-02-08

    Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.

  7. Application of monoterpenoids and their derivatives for treatment of neurodegenerative disorders.

    Science.gov (United States)

    Volcho, Konstantin P; Laev, Sergey S; Ashraf, Ghulam Md; Aliev, Gjumrakch; Salakhutdinov, Nariman F

    2017-01-11

    Neurodegenerative disorders (NDDs) like Alzheimer disease, Parkinson's disease and Huntington's disease are a heterogeneous group of disorders with the progressive and severe loss of neurons. There are no full proof cures for these diseases, and only medicines are available that can alleviate some of the symptoms. Developing effective treatments for the NDDs is a difficult but necessary task. Hence, the investigation of monoterpenoids which modulate targets applicable to many NDDs is highly relevant. Many monoterpenoids have demonstrated promising neuroprotective activity mediated by various systems. It can form the basis for elaboration of agents which will be useful both for the alleviation of symptoms of NDDs and for the treatment of diseases progression and also for prevention of neurodegeneration. The further developments including detections of monoterpenoids and their derivatives with high neuroprotective or neurotrophic activity as well as the results of qualified clinical trials are needed to draw solid conclusions regarding the efficacy of these agents.

  8. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8

    Directory of Open Access Journals (Sweden)

    Sehgal SA

    2016-05-01

    Full Text Available Sheikh Arslan Sehgal,1–4 Shazia Mannan,1 Sannia Ali1 1Department of Bioscience, COMSATS Institute of Information Technology, Sahiwal, Pakistan; 2State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan Abstract: Charcot–Marie–Tooth (CMT disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand–receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. Keywords: bioinformatics, computer

  9. Targeting innate immunity for neurodegenerative disorders of the central nervous system.

    Science.gov (United States)

    Andreasson, Katrin I; Bachstetter, Adam D; Colonna, Marco; Ginhoux, Florent; Holmes, Clive; Lamb, Bruce; Landreth, Gary; Lee, Daniel C; Low, Donovan; Lynch, Marina A; Monsonego, Alon; O'Banion, M Kerry; Pekny, Milos; Puschmann, Till; Russek-Blum, Niva; Sandusky, Leslie A; Selenica, Maj-Linda B; Takata, Kazuyuki; Teeling, Jessica; Town, Terrence; Van Eldik, Linda J

    2016-09-01

    Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of

  10. Rapid Eye Movement Sleep Behavior Disorder: A Review of the Literature and Update on Current Concepts.

    Science.gov (United States)

    Rodriguez, Carlos L; Jaimchariyatam, Nattapong; Budur, Kumar

    2017-09-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormal behaviors emerging during REM sleep that may cause injury or sleep disruption. The diagnosis requires polysomnography (PSG) demonstrating a loss of normal skeletal muscle atonia during REM sleep. RBD results from dysfunction of the brain stem circuits responsible for maintaining normal REM sleep atonia and suppressing behaviors during REM sleep. The diagnosis of idiopathic RBD (IRBD), that is, RBD without an identifiable cause, is frequently followed years later by the development of a neurodegenerative disorder, most commonly one of the synucleinopathies. As such, RBD is often a step in the progression of a neurodegenerative disorder. In this circumstance, it is a manifestation of neurodegeneration occurring in the brain stem before spreading to adjacent and other CNS regions, resulting in the development of symptoms and signs that permit recognition of a specific neurodegenerative disorder. RBD has been linked with narcolepsy and has been associated with a variety of other disorders. The management of RBD focuses on preventive/safety measures, counseling, monitoring for the development of a neurodegenerative disorder, and pharmacotherapy, which is typically effective but not well understood. The purpose of this article is to review and update our current understanding of the clinical features, epidemiology, demographics, pathophysiology, evaluation, diagnosis, differential diagnosis, causes, associations, and the clinical management of RBD. Copyright © 2017. Published by Elsevier Inc.

  11. Advances in clinical trials for movement disorders.

    Science.gov (United States)

    Kieburtz, Karl; Olanow, C Warren

    2015-09-15

    In the past several years, there have been several innovations in the design of clinical trials assessing new therapies for patients with movement disorders. These include attempts to address difficulties in conducting clinical trials in treated patients in the advanced stages of their illness, demonstrating disease-modifying effects or a reduction in the development of cumulative disability, and assessing the effects of interventions in patients in the premanifest state of their disease. In addition, there have been advances in clinical trial methodologies and changes in regulatory guidelines that permit the performance of more efficient studies, with a reduction in the cost and duration of the development period. These will be reviewed in the present article. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

  12. Movement disorder symptoms associated with Unified ...

    Science.gov (United States)

    Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UPDRS: Activities of Daily Living (ADL) and Motor abnormalities; and 2) which symptoms were most related to increased abnormalities on these UPDRS subscales. Participants & Methods: Correlations between self-reported movement disorder symptoms from a health questionnaire and scores obtained on UPDRS: ADL and Motor subscales, and the Bradykinesia domain of the Motor subscale, were assessed during a medical examination among 185 Mn-exposed participants from two Ohio towns. Partial correlations were used for statistical analyses, controlling for age, sex, education and a history of musculoskeletal disease.Results: The presence of movement disorder symptoms was positively associated with ADL (pr =0.647, p = disorder symptoms most strongly associated with increased ADL and Motor scores included having difficulty getting out of chairs (pr =0.458, p = <0.001), writing (pr =0.481, p = <0.001), skilled movements (pr =0.478, p = <0.001), loss of coordination/balance (pr =0.457, p = <0.001), changes in walking (pr =0.412, p = <0.001) and slowness of movement (pr =0.539, p = <0.0

  13. Saccadic eye movement applications for psychiatric disorders

    Science.gov (United States)

    Bittencourt, Juliana; Velasques, Bruna; Teixeira, Silmar; Basile, Luis F; Salles, José Inácio; Nardi, Antonio Egídio; Budde, Henning; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2013-01-01

    Objective The study presented here analyzed the patterns of relationship between oculomotor performance and psychopathology, focusing on depression, bipolar disorder, schizophrenia, attention-deficit hyperactivity disorder, and anxiety disorder. Methods Scientific articles published from 1967 to 2013 in the PubMed/Medline, ISI Web of Knowledge, Cochrane, and SciELO databases were reviewed. Results Saccadic eye movement appears to be heavily involved in psychiatric diseases covered in this review via a direct mechanism. The changes seen in the execution of eye movement tasks in patients with psychopathologies of various studies confirm that eye movement is associated with the cognitive and motor system. Conclusion Saccadic eye movement changes appear to be heavily involved in the psychiatric disorders covered in this review and may be considered a possible marker of some disorders. The few existing studies that approach the topic demonstrate a need to improve the experimental paradigms, as well as the methods of analysis. Most of them report behavioral variables (latency/reaction time), though electrophysiological measures are absent. PMID:24072973

  14. Electrophysiologic Evaluation of Psychogenic Movement Disorders

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Pal

    2011-05-01

    Full Text Available Psychogenic movement disorders (PMD are a group of disorders which are in the border zone between neurology and psychiatry. All necessary laboratory investigations should be done to rule out an underlying organic disorder. While clinical acumen of a trained movement disorder specialist may be sufficient to diagnose most PMD, there are clinical situations where electrophysiological tests are required either to rule out an organic movement disorder or even diagnose a PMD. Current electrophysiological test are most useful for tremor, followed by jerks and least for spasms or dystonia. Commonly used electrophysiologic tests include multichannel surface electromyography (EMG, accelerometry, electroencephalography time locked with EMG, premovement potential (Bereitschaftspotential, and somatosensory evoked potentials. Psychogenic tremor is a low frequency tremor with variable frequency and duration of EMG bursts, entrainable, has a high coherence with voluntary movements, and presence of coactivation sign. Patients with psychogenic jerks have well organized triphasic pattern of activation of agonist and antagonist muscles. The jerks are associated with EMG bursts of long duration (usually > 70 ms, long and variable latencies in stimulus induced jerks, absence of craniocaudal pattern of muscle recruitment in apparent startle response, and often a Breitschaftspotential (premovement potential precedes the jerk. Electrophysiological characterization of psychogenic dystonia is difficult and the tests are usually performed to rule out organic dystonia with characteristic findings. Finally, caution should be exerted in interpreting the electrophysiological tests as both false positive and false negative diagnosis of PMD may still occur.

  15. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders -- therapeutic potential or a mirage?

    Science.gov (United States)

    Gladkevich, A; Bosker, F; Korf, J; Yenkoyan, K; Vahradyan, H; Aghajanov, M

    2007-10-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experimental data have shown that proline-rich polypeptides isolated from bovine neurohypophisis possess neuroprotective and neuromodulatory properties in mice with aluminum neurotoxicosis or neuronal damage caused by venoms and toxins. Proline-rich polypeptides from ovine colostrums, so called Colostrinin, have been shown to produce cognitive improvement in an experimental model and in patients with Alzheimer disease. However, the precise mechanism underlying the neuroprotective action of proline-rich polypeptides is not very well established. Moreover, studies pointing at a neuroprotective effect of proline-rich polypeptides from bovine neurohypophisis in humans have not been reported thus far. The authors conclude that more detailed information on the mode of action of proline-rich polypeptides is needed as well as confirmation of their efficacy in broad clinical trials before this approach can really show its potential in the treatment of neurodegenerative disorders.

  16. Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review of Brief Neuropsychological Tools

    Directory of Open Access Journals (Sweden)

    Helena S. Moreira

    2017-11-01

    Full Text Available Executive function (EF has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25, Frontal Assessment Battery (FAB, INECO Frontal Screening (IFS, and FRONTIER Executive Screen (FES. We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.

  17. Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review of Brief Neuropsychological Tools.

    Science.gov (United States)

    Moreira, Helena S; Costa, Ana S; Castro, São L; Lima, César F; Vicente, Selene G

    2017-01-01

    Executive function (EF) has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25), Frontal Assessment Battery (FAB), INECO Frontal Screening (IFS), and FRONTIER Executive Screen (FES). We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.

  18. Epigenetic Research of Neurodegenerative Disorders Using Patient iPSC-Based Models

    Science.gov (United States)

    2016-01-01

    Epigenetic mechanisms play a role in human disease but their involvement in pathologies from the central nervous system has been hampered by the complexity of the brain together with its unique cellular architecture and diversity. Until recently, disease targeted neural types were only available as postmortem materials after many years of disease evolution. Current in vitro systems of induced pluripotent stem cells (iPSCs) generated by cell reprogramming of somatic cells from patients have provided valuable disease models recapitulating key pathological molecular events. Yet whether cell reprogramming on itself implies a truly epigenetic reprogramming, the epigenetic mechanisms governing this process are only partially understood. Moreover, elucidating epigenetic regulation using patient-specific iPSC-derived neural models is expected to have a great impact to unravel the pathophysiology of neurodegenerative diseases and to hopefully expand future therapeutic possibilities. Here we will critically review current knowledge of epigenetic involvement in neurodegenerative disorders focusing on the potential of iPSCs as a promising tool for epigenetic research of these diseases. PMID:26697081

  19. Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders.

    Science.gov (United States)

    Su, Kuo-Hui; Dai, Chengkai

    2016-11-01

    Proteome homeostasis, or proteostasis, is essential to maintain cellular fitness and its disturbance is associated with a broad range of human health conditions and diseases. Cells are constantly challenged by various extrinsic and intrinsic insults, which perturb cellular proteostasis and provoke proteotoxic stress. To counter proteomic perturbations and preserve proteostasis, cells mobilize the proteotoxic stress response (PSR), an evolutionarily conserved transcriptional program mediated by heat shock factor 1 (HSF1). The HSF1-mediated PSR guards the proteome against misfolding and aggregation. In addition to proteotoxic stress, emerging studies reveal that this proteostatic mechanism also responds to cellular energy state. This regulation is mediated by the key cellular metabolic sensor AMP-activated protein kinase (AMPK). In this review, we present an overview of the maintenance of proteostasis by HSF1, the metabolic regulation of the PSR, particularly focusing on AMPK, and their implications in the two major age-related diseases-diabetes mellitus and neurodegenerative disorders.

  20. Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Michael Zech

    Full Text Available Niemann-Pick type C (NPC disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95% or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD, frontotemporal lobar degeneration (FTLD and progressive supranuclear palsy (PSP, and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563, FTLD (n = 133 and PSP (n = 94, and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1% and seven control subjects (0.8%, but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted.

  1. Movement disorders and inactivity in dementia

    NARCIS (Netherlands)

    dr. Hans Hobbelen

    2014-01-01

    Movement disorders in dementia An interesting article by Ramakers et al in 2007 showed that 5 years prior to the diagnosis of dementia these people significantly more often visited their home physician in contrast with cognitive healthy age matched controls. 5 year prior to the diagnosis of dementia

  2. The bereitschaftspotential in jerky movement disorders

    NARCIS (Netherlands)

    van der Salm, Sandra M. A.; Tijssen, Marina A. J.; Koelman, Johannes H. T. M.; van Rootselaar, Anne-Fleur

    2012-01-01

    Objective To assess the diagnostic value of the bereitschaftspotential (BP) in jerky movement disorders. Methods A cross-sectional case series of 48 patients with psychogenic jerks, Gilles de la Tourette syndrome (GTS) or myoclonus was investigated. We measured the BP prior to the spontaneous jerk

  3. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease.

    Science.gov (United States)

    Boeve, B F; Silber, M H; Saper, C B; Ferman, T J; Dickson, D W; Parisi, J E; Benarroch, E E; Ahlskog, J E; Smith, G E; Caselli, R C; Tippman-Peikert, M; Olson, E J; Lin, S-C; Young, T; Wszolek, Z; Schenck, C H; Mahowald, M W; Castillo, P R; Del Tredici, K; Braak, H

    2007-11-01

    REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in

  4. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases.

    Science.gov (United States)

    Shan, Ling; Hofman, Michel A; van Wamelen, Daniel J; Van Someren, Eus J W; Bao, Ai-Min; Swaab Dick, F

    2012-05-01

    Neuronal histamine shows diurnal rhythms in rodents and plays a major role in the maintenance of vigilance. No data are available on its diurnal fluctuation in humans, either in health or in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD), or Huntington disease (HD), all of which are characterized by sleep-wake disturbances. Quantitative in situ hybridization was used to study the mRNA expression of histidine decarboxylase (HDC), the key enzyme of histamine production in the tuberomammillary nucleus (TMN) in postmortem human hypothalamic tissue, obtained from 33 controls and 31 patients with a neurodegenerative disease-PD (n = 15), AD (n = 9), and HD (n = 8)-and covering the full 24-h cycle with respect to clock time of death. HDC-mRNA levels in controls were found to be significantly higher during the daytime than at night (e.g., 08:01-20:00 versus 20:01-08:00, P = 0.004). This day-night fluctuation was markedly different in patients with neurodegenerative diseases. The diurnal fluctuation of HDC-mRNA expression in human TMN supports a role for neuronal histamine in regulating day-night rhythms. Future studies should investigate histamine rhythm abnormalities in neurodegenerative disorders. Shan L; Hofman MA; van Wamelen DJ; Van Someren EJW; Bao AM; Swaab DF. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases.

  5. Molecular underpinnings of neurodegenerative disorders: striatal-enriched protein tyrosine phosphatase signaling and synaptic plasticity.

    Science.gov (United States)

    Lombroso, Paul J; Ogren, Marilee; Kurup, Pradeep; Nairn, Angus C

    2016-01-01

    This commentary focuses on potential molecular mechanisms related to the dysfunctional synaptic plasticity that is associated with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Specifically, we focus on the role of striatal-enriched protein tyrosine phosphatase (STEP) in modulating synaptic function in these illnesses. STEP affects neuronal communication by opposing synaptic strengthening and does so by dephosphorylating several key substrates known to control synaptic signaling and plasticity. STEP levels are elevated in brains from patients with Alzheimer's and Parkinson's disease. Studies in model systems have found that high levels of STEP result in internalization of glutamate receptors as well as inactivation of ERK1/2, Fyn, Pyk2, and other STEP substrates necessary for the development of synaptic strengthening. We discuss the search for inhibitors of STEP activity that may offer potential treatments for neurocognitive disorders that are characterized by increased STEP activity. Future studies are needed to examine the mechanisms of differential and region-specific changes in STEP expression pattern, as such knowledge could lead to targeted therapies for disorders involving disrupted STEP activity.

  6. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders.

    Science.gov (United States)

    Sas, Katalin; Robotka, Hermina; Toldi, József; Vécsei, László

    2007-06-15

    The mitochondria have several important functions in the cell. A mitochondrial dysfunction causes an abatement in ATP production, oxidative damage and the induction of apoptosis, all of which are involved in the pathogenesis of numerous disorders. This review focuses on mitochondrial dysfunctions and discusses their consequences and potential roles in the pathomechanism of neurodegenerative disorders. Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain neurodegenerative diseases. During energy production, most of the O(2) consumed by the mitochondria is reduced fully to water, but 1-2% of the O(2) is reduced incompletely to give the superoxide anion (O(2)(-)). If the function of one or more respiratory chain complexes is impaired for any reason, the enhanced production of free radicals further worsens the mitochondrial function by causing oxidative damage to macromolecules, and by opening the mitochondrial permeability transition pores thereby inducing apoptosis. These high-conductance pores offer a pathway which can open in response to certain stimuli, leading to the induction of the cells' own suicide program. This program plays an essential role in regulating growth and development, in the differentiation of immune cells, and in the elimination of abnormal cells from the organism. Both failure and exaggeration of apoptosis in a human body can lead to disease. The increasing amount of superoxide anions can react with nitric oxide to yield the highly toxic peroxynitrite anion, which can destroy cellular macromolecules. The roles of oxidative, nitrative and nitrosative damage are discussed. Senescence is accompanied by a higher degree of reactive oxygen species production, and by diminished functions of the endoplasmic reticulum and the proteasome system, which are responsible for maintenance of the

  7. Non-opioid nociceptive activity of human dynorphin mutants that cause neurodegenerative disorder spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Watanabe, Hiroyuki; Mizoguchi, Hirokazu; Verbeek, Dineke S.; Kuzmin, Alexander; Nyberg, Fred; Krishtal, Oleg; Sakurada, Shinobu; Bakalkin, Georgy

    We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23). Three mutations substitute Leu(5), Arg(6), and Arg(9) to Ser (L5S), Trp (R6W) and Cys (R9C) in dynorphin A(1-17) (Dyn A), a peptide with both

  8. Laryngeal electromyography in movement disorders: preliminary data

    Directory of Open Access Journals (Sweden)

    Kimaid Paulo A.T.

    2004-01-01

    Full Text Available This study describes preliminary laryngeal electromyography (LEMG data and botulinum toxin treatment in patients with dysphonia due to movement disorders. Twenty-five patients who had been clinically selected for botulinum toxin administration were examined, 19 with suspected laryngeal dystonia or spasmodic dysphonia (SD, 5 with vocal tremor, and 1 with Gilles de la Tourette syndrome (GTS. LEMG evaluations were performed before botulinum toxin administration using monopolar electrodes. Electromyography was consistent with dystonia in 14 patients and normal in 5, and differences in frequency suggesting essential tremor in 3 and Parkinson tremors in 2. The different LEMG patterns and significant improvement in our patients from botulinum toxin therapy has led us to perform laryngeal electromyography as a routine in UNICAMP movement disorders ambulatory.

  9. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul

    2009-01-01

    and neurological disease. RBD is related to brainstem pathology. Furthermore, it is increasingly recognized that RBD is frequently related to Parkinsonian disorders and narcolepsy. This article reviews recent knowledge about RBD with focus on the diagnostic process and management. Udgivelsesdato: 2009-May......Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...

  10. Neurobiology of functional (psychogenic) movement disorders.

    Science.gov (United States)

    Edwards, Mark J; Fotopoulou, Aikaterini; Pareés, Isabel

    2013-08-01

    This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms. Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement. New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health.

  11. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy.

    Science.gov (United States)

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-08-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. The neurophysiology of paediatric movement disorders.

    Science.gov (United States)

    McClelland, Verity M

    2017-12-01

    To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain. Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements. Analyses of evoked potentials and event-related changes in the electroencephalogaphy spectral activity provide growing evidence for the important role of aberrant sensory processing in the pathophysiology of many different movement disorders. Neurophysiological findings demonstrate that children with clinically similar phenotypes may have differing underlying pathophysiology, which in turn may explain differential response to therapy. Neurophysiological parameters can act as biomarkers, providing a means to stratify individuals, and are well suited to provide biofeedback. They therefore have enormous potential to facilitate improvements to therapy. Although currently a small field, the role of neurophysiology in paediatric movement disorders is poised to expand, both fuelled by and contributing to the rapidly growing fields of neuro-rehabilitation and neuromodulation and the move towards a more individualized therapeutic approach.

  13. [Electromyography Analysis of Rapid Eye Movement Sleep Behavior Disorder].

    Science.gov (United States)

    Nakano, Natsuko; Kinoshita, Fumiya; Takada, Hiroki; Nakayama, Meiho

    2018-01-01

    Polysomnography (PSG), which records physiological phenomena including brain waves, breathing status, and muscle tonus, is useful for the diagnosis of sleep disorders as a gold standard. However, measurement and analysis are complex for several specific sleep disorders, such as rapid eye movement (REM) sleep behavior disorder (RBD). Usually, brain waves during REM sleep indicate an awakening pattern under relaxed conditions of skeletal and antigravity muscles. However, these muscles are activated during REM sleep when patients suffer from RBD. These activated muscle movements during REM, so-called REM without atonia (RWA) recorded by PSG, may be related to a neurodegenerative disease such as Parkinson's disease. Thus, careful analysis of RWA is significant not only physically, but also clinically. Commonly, manual viewing measurement analysis of RWA is time-consuming. Therefore, quantitative studies on RWA are rarely reported. A software program, developed from Microsoft Office Excel ® , was used to semiautomatically analyze the RWA ratio extracted from PSG to compare with manual viewing measurement analysis. In addition, a quantitative muscle tonus study was carried out to evaluate the effect of medication on RBD patients. Using this new software program, we were able to analyze RWA on the same cases in approximately 15 min as compared with 60 min in the manual viewing measurement analysis. This software program can not only quantify RWA easily but also identify RWA waves for either phasic or tonic bursts. We consider that this software program will support physicians and scientists in their future research on RBD. We are planning to offer this software program for free to physicians and scientists.

  14. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

    Science.gov (United States)

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-01-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

  15. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders

    NARCIS (Netherlands)

    Kos, Claire; van Tol, Marie-Jose; Marsman, Jan-Bernard C.; Knegtering, Henderikus; Aleman, Andre

    2016-01-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar

  16. Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel

    Directory of Open Access Journals (Sweden)

    Valeria Manera

    2017-07-01

    Full Text Available The use of Serious Games (SG in the health domain is expanding. In the field of neurodegenerative disorders (ND such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014. The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI. SG are more adapted for use with trained caregivers (both at home and in clinical settings, with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game, and should be personalized with the help of a clinician.

  17. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Adriana Covarrubias-Pinto

    2015-11-01

    Full Text Available Ascorbic acid is a key antioxidant of the Central Nervous System (CNS. Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  18. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders.

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-11-27

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  19. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-01-01

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders. PMID:26633354

  20. The link between Parkinson's disease and rapid eye movement sleep behavior disorder with dream enactment: Possible implications for early rehabilitation.

    Science.gov (United States)

    Johnson, Brian P; Westlake, Kelly P

    2017-09-07

    The purpose of this paper is twofold. First, to inform readers of the link between the loss of motor inhibition during rapid eye movement (REM) sleep dreaming, diagnosed as REM sleep behavior disorder (RBD), and the future onset of neurodegenerative disorders, such as Parkinson's Disease and dementia with lewy bodies. It has been reported that motor disinhibition during rapid eye movement sleep often precedes onset of these disorders by years or even decades. Second, to consider that identification of RBD and the early involvement of rehabilitation and/or development of home exercise plans may aid in prolonging and even increasing function, independence, and quality of life should such neurodegenerative disorders develop later in life. Copyright © 2017. Published by Elsevier Inc.

  1. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

    Science.gov (United States)

    Fernández-Ruiz, Javier; Sagredo, Onintza; Pazos, M Ruth; García, Concepción; Pertwee, Roger; Mechoulam, Raphael; Martínez-Orgado, José

    2013-01-01

    Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. PMID:22625422

  2. Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice.

    Science.gov (United States)

    Atri, Alireza

    2016-01-01

    This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as

  3. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

    Science.gov (United States)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-10-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

  4. Dopamine transporter imaging in rapid eye movement sleep behavior disorder

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Yoon, In Young; Kim, Jong Min; Jeong, Seok Hoon; Kim, Ji Sun; Lee, Byung Chul; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is still unknown. However, involvement of dopaminergic system in RBD has been hypothesized because of frequent association with degenerative movement disorders such as Parkinson's disease. The purpose of this study was to examine the extent and pattern of loss of dopamine transporter in RBD using FP-CIT SPECT. Fourteen patient with idiopathic RBD (mean age:665 yrs, M:F=10:3) participated in this study. Polysonmography confirmed loss of REM atonia and determined RBD severities by amount of tonic/phasic muscle activity during REM sleep in all cases. To compare with RBD, 14 early idiopathic Parkinson's disease rated as Hoehn and Yahr stage 1 (IPD) and 12 healthy controls were also selected. All participants performed single-photon emission computed tomography (SPECT) imaging 3 hours after injection of [123I]FP-CIT. Regions of interest were drawn on bilateral caudate and putamen, whole striatum and occipital cortex. Specific binding for dopamine transporters (DAT) were calculated using region to occipital uptake ratio based on the transient equilibrium method. Overall mean of DAT density in the striatum was lower in RBD group than controls, and higher than IPD group, However, DAT density in most individual RBD was still within normal range, and total striatal DAT density was not correlated with severity of RBD. Meanwhile, the caudate to putamen uptake ratio (C/P ratio) in RBD group was insignificantly higher than those in healthy controls. Nevertheless, C/P ratio within RBD group was reversely correlated with the RBD severity. Our study suggested that nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. Further longitudinal evaluation of presynaptic dopaminergic system in idiopathic RBD may guarantee the more understanding for RBD and associated neurodegenerative disease.

  5. Seventy years of pallidotomy for movement disorders.

    Science.gov (United States)

    Cif, Laura; Hariz, Marwan

    2017-07-01

    The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid-1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa-induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  6. Cannabinoids and value-based decision making: Implications for neurodegenerative disorders

    NARCIS (Netherlands)

    Lee, AM; Oleson, E.B.; Diergaarde, L.; Cheer, J.F.; Pattij, T.

    2012-01-01

    In recent years, disturbances in cognitive function have been increasingly recognized as important symptomatic phenomena in neurodegenerative diseases, including Parkinson's disease (PD). Value-based decision making in particular is an important executive cognitive function that is not only impaired

  7. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

    OpenAIRE

    Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, ...

  8. Saccadic eye movement applications for psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Bittencourt J

    2013-09-01

    Med/Medline, ISI Web of Knowledge, Cochrane, and SciELO databases were reviewed. Results: Saccadic eye movement appears to be heavily involved in psychiatric diseases covered in this review via a direct mechanism. The changes seen in the execution of eye movement tasks in patients with psychopathologies of various studies confirm that eye movement is associated with the cognitive and motor system. Conclusion: Saccadic eye movement changes appear to be heavily involved in the psychiatric disorders covered in this review and may be considered a possible marker of some disorders. The few existing studies that approach the topic demonstrate a need to improve the experimental paradigms, as well as the methods of analysis. Most of them report behavioral variables (latency/reaction time, though electrophysiological measures are absent. Keywords: depression, bipolar disorder, attention-deficit hyperactivity disorder, schizophrenia, anxiety disorder

  9. Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders.

    Science.gov (United States)

    Tse, Joyce K Y

    2017-07-19

    Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g., superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation. NO also instigates a down-regulated secretion of brain-derived neurotrophic factor, which is essential for neuronal survival, development and differentiation, synaptogenesis, and learning and memory. The gut-brain axis denotes communication between the enteric nervous system (ENS) of the GI tract and the central nervous system (CNS) of the brain, and the modes of communication include the vagus nerve, passive diffusion and carrier by oxyhemoglobin. Amyloid precursor protein that forms amyloid beta plaques in AD is normally expressed in the ENS by gut bacteria, but when amyloid beta accumulates, it compromises CNS functions. Escherichia coli and Salmonella enterica are among the many bacterial strains that express and secrete amyloid proteins and contribute to AD pathogenesis. Gut microbiota is essential for regulating microglia maturation and activation, and activated microglia secrete significant amounts of iNOS. Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.

  10. Acupuncture for psychogenic movement disorders: Treatment or diagnostic tool?

    NARCIS (Netherlands)

    Nuenen, B.F.L. van; Wohlgemuth, M.; Wong-Chung, R.E.; Abdo, W.; Bloem, B.R.

    2007-01-01

    Psychogenic movement disorders are common in everyday neurological practice, comprising up to 25% of the patient population in movement disorders clinics. The diagnosis is often difficult, as is illustrated by the high proportion of patients with an organic neurological disease whose movement

  11. The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review.

    Science.gov (United States)

    Pang, Shirley Yin-Yu; Teo, Kay-Cheong; Hsu, Jacob Shujui; Chang, Richard Shek-Kwan; Li, Miaoxin; Sham, Pak-Chung; Ho, Shu-Leong

    2017-01-01

    The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The observation of pleiotropy has emerged, with mutations in the same gene giving rise to diverse phenotypes, which further increases the complexity of phenotype-genotype correlation. Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene, presence of modifier genes, and oligogenic inheritance. Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms, translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately finding disease-modifying therapies for neurodegenerative disorders.

  12. Movement disorders due to bilirubin toxicity

    Science.gov (United States)

    Rose, Jessica; Vassar, Rachel

    2015-01-01

    Summary Advances in the care of neonatal hyperbilirubinemia have decreased the incidence of kernicterus. However, neonatal exposure to high levels of bilirubin continues to cause severe motor symptoms and cerebral palsy (CP). Exposure to moderate levels of unconjugated bilirubin may also cause damage to the developing central nervous system, specifically the basal ganglia and cerebellum. Brain lesions identified using magnetic resonance imaging following extreme hyperbilirubinemia have been linked to dyskinetic CP. Newer imaging techniques, such as diffusion tensor imaging or single-photon emission computed tomography, allow quantification of more subtle white matter injury following presumed exposure to unbound bilirubin, and may explain more subtle movement disorders. New categories of bilirubin-induced neurologic dysfunction, either independently or characterized by subtle bilirubin encephalopathy, following moderate hyperbilirubinemia have been implicated in long-term motor function. Further research is needed to identify subtle impairments resulting from moderate to severe neonatal hyperbilirubinemia, understand the influence of perinatal risk factors on bilirubin toxicity, and develop neuroprotective treatment strategies to prevent movement disorders due to bilirubin toxicity. PMID:25524299

  13. Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder.

    Science.gov (United States)

    Barber, Thomas R; Lawton, Michael; Rolinski, Michal; Evetts, Samuel; Baig, Fahd; Ruffmann, Claudio; Gornall, Aimie; Klein, Johannes C; Lo, Christine; Dennis, Gary; Bandmann, Oliver; Quinnell, Timothy; Zaiwalla, Zenobia; Ben-Shlomo, Yoav; Hu, Michele T M

    2017-08-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson's (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations. Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson's Disease Rating Scale (UPDRS)-III, timed "get-up-and-go", Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson's compared to 0.3% (95% CI 0.009%, 2%) of controls. RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions.

  14. Pathophysiology of movement disorders studied using PET

    NARCIS (Netherlands)

    Leenders, KL

    1997-01-01

    PET radiotracer methods can measure various biochemical features of brain tissue in the living human brain. Here, local brain energy consumption and striatal dopaminergic function will be discussed in the light of the . neurodegenerative processes underlying Parkinson's disease. Particularly,

  15. Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Rockenstein Edward

    2011-09-01

    Full Text Available Abstract Background Recent studies suggest that the pathogenic process in neurodegenerative disorders may disrupt mature neuronal circuitries and neurogenesis in the adult brain. Abnormal activation of CDK5 is associated with neurodegenerative disorders, and recently a critical role for CDK5 in adult neurogenesis has been identified. We have developed an in vitro model of abnormal CDK5 activation during adult hippocampal neurogenesis, and here we used this model to investigate aberrantly phosphorylated downstream targets of CDK5. Results Abnormal CDK5 activation in an in vitro model of adult neurogenesis results in hyperphosphorylation of collapsin-response mediator protein-2 (CRMP2 and impaired neurite outgrowth. Inhibition of CDK5, or expression of a non-phosphorylatable (S522A CRMP2 construct reduced CRMP2 hyperphosphorylation, and reversed neurite outgrowth deficits. CRMP2 plays a role in microtubule dynamics; therefore we examined the integrity of microtubules in this model using biochemical and electron microscopy techniques. We found that microtubule organization was disrupted under conditions of CDK5 activation. Finally, to study the relevance of these findings to neurogenesis in neurodegenerative conditions associated with HIV infection, we performed immunochemical analyses of the brains of patients with HIV and transgenic mice expressing HIV-gp120 protein. CDK5-mediated CRMP2 phosphorylation was significantly increased in the hippocampus of patients with HIV encephalitis and in gp120 transgenic mice, and this effect was rescued by genetic down-modulation of CDK5 in the mouse model. Conclusions These results reveal a functional mechanism involving microtubule destabilization through which abnormal CDK5 activation and CRMP2 hyperphosphorylation might contribute to defective neurogenesis in neurodegenerative disorders such as HIV encephalitis.

  16. REM Sleep Behavior Disorder: Updated Review of the Core Features, the RBD-Neurodegenerative Disease Association, Evolving Concepts, Controversies, and Future Directions

    Science.gov (United States)

    Boeve, Bradley F.

    2010-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to “act out their dreams,” in which the exhibited behaviors mirror the content of the dreams, and the dream content often involves a chasing or attacking theme. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straight-forward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail. PMID:20146689

  17. Increased sexual arousal in patients with movement disorders

    OpenAIRE

    Teive, Hélio A. G.; Moro, Adriana; Moscovich, Mariana; Munhoz, Renato P.

    2016-01-01

    ABSTRACT Increased of sexual arousal (ISA) has been described in different neurological diseases. The purpose of this study was present a case series of ISA in patients with movement disorders. Method Fifteen patients with different forms of movement disorders (Parkinson’s disease, Huntington’s disease, Tourette´s syndrome, spinocerebellar ataxia type 3), were evaluated in the Movement Disorders Unit of the Federal University of Paraná. Results Among Parkinson’s disease patients there were ...

  18. Combination Comprising Parthenolide For Use In The Treatment Of Alzheimer's Disease And Other Neurodegenerative Disorders

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-18

    The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer\\'s Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent, including an inhibitor of TLR4/MD-2/CD14, nAChR agonist, Resatorvid, Curcumin, Tilorone or a Tilorone analog, or a combination thereof.

  19. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - Therapeutic potential or a mirage?

    NARCIS (Netherlands)

    Gladkevich, A.; Bosker, F.; Korf, J.; Yenkoyan, K.; Vahradyan, H.; Aghajanov, M.

    2007-01-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease.

  20. Visual Hallucinations in the Psychosis Spectrum and Comparative Information From Neurodegenerative Disorders and Eye Disease

    NARCIS (Netherlands)

    Waters, Flavie; Collerton, Daniel; Ffytche, Dominic H.; Jardri, Renaud; Pins, Delphine; Dudley, Robert; Blom, Jan Dirk; Mosimann, Urs Peter; Eperjesi, Frank; Ford, Stephen; Laroi, Frank

    Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding

  1. PET Imaging of the Peripheral Benzodiazepine Receptor : Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders

    NARCIS (Netherlands)

    Doorduin, Janine; de Vries, Erik F. J.; Dierckx, Rudi A.; Klein, Hans C.

    2008-01-01

    It is important to gain more insight into neurodegenerative diseases, because these debilitating diseases can not be cured. A common characteristic of many neurological diseases is neuroinflammation, which is accompanied by the presence of activated microglia cells. In activated microglia cells, an

  2. Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies

    Czech Academy of Sciences Publication Activity Database

    Doležalová, D.; Hruška-Plocháň, M.; Bjarkam, C. R.; Sorensen, J. C. H.; Cunningham, M.; Weingarten, D.; Ciacci, J. D.; Juhás, Štefan; Juhásová, Jana; Motlík, Jan; Hefferan, M. P.; Hazel, T.; Johe, K.; Carromeu, C.; Muotri, A.; Bui, J. D.; Strnádel, J.; Marsala, M.

    2014-01-01

    Roč. 522, č. 12 (2014), s. 2784-2801 ISSN 0021-9967 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : pig * neurodegenerative models * stem cells Subject RIV: FH - Neurology Impact factor: 3.225, year: 2014

  3. Paroxysmal movement disorders and episodic ataxias.

    Science.gov (United States)

    Fernández-Alvarez, Emilio; Perez-Dueñas, Belén

    2013-01-01

    This chapter summarizes clinical symptoms of some paroxysmal dyskinesias (PDs) of infancy and childhood, as well as episodic ataxias. PDs refer to a complex group of disorders whose main feature is the occurrence of sudden, intermittent attacks of abnormal postures and involuntary movements. PDs can sometimes be symptomatic (secondary PDs), but usually an underlying cerebral lesion is not present (primary PDs). Some of the primary PDs are transient, such as benign paroxysmal torticollis of infancy. Chronic PDs are subdivided into nonkinesigenic (Mount and Reback type), kinesigenic (Kertesz type), and exercise-induced (Lance type) but cases that overlap with these types are on record. They are autosomal dominant inherited conditions. The myofibrillogenesis regulator-1 gene is responsible for nonkinesigenic PDs. To date, the genetic basis of kinesigenic PDs remains unknown. Several clinical entities associated epilepsy with PDs, such as infantile convulsions and choreoathetosis (ICCA). Exercise-induced PD type can be produced by mutations in the SLC2A1 gene that encodes Glut1 (glucose transporter type1). Episodic ataxias are inherited disorders of intermittent ataxia. The attacks are brief and triggered by abrupt exercise and emotional stimulus. Between attacks, palpebral and hand muscle myokymia is often seen in episodic ataxia type 1 (EA1). In episodic ataxia type 2 (EA2) interictal nystagmus is usually present. Some of these latter patients develop progressive ataxia with vermian atrophy. This disorder is associated with mutations in the human Ca channel alfa 1 subunit CACN1A4 gene. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

    Science.gov (United States)

    Fagherazzi, Elen V; Garcia, Vanessa A; Maurmann, Natasha; Bervanger, Thielly; Halmenschlager, Luis H; Busato, Stefano B; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Schröder, Nadja

    2012-02-01

    Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

  5. Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several neurodegenerative disorders.

    Science.gov (United States)

    Cassiano, Chiara; Esposito, Roberta; Tosco, Alessandra; Zampella, Angela; D'Auria, Maria Valeria; Riccio, Raffaele; Casapullo, Agostino; Monti, Maria Chiara

    2014-01-14

    Trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in several neurodegenerative conditions, was discovered as a novel target of heteronemin by chemical proteomics. Combining bio-physical orthogonal approaches with biological analysis, heteronemin was found to influence the binding of TDP-43-cognate nucleic acids and to modulate the TDP-43 aggregation state and its cellular localization.

  6. Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Martin Hofmann-Apitius

    2015-12-01

    Full Text Available Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies—data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI; which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations

  7. ECEM (Eye Closure, Eye Movements): application to depersonalization disorder.

    Science.gov (United States)

    Harriet, E Hollander

    2009-10-01

    Eye Closure, Eye Movements (ECEM) is a hypnotically-based approach to treatment that incorporates eye movements adapted from the Eye Movement Desensitization and Reprocessing (EMDR) protocol in conjunction with hypnosis for the treatment of depersonalization disorder. Depersonalization Disorder has been differentiated from post-traumatic stress disorders and has recently been conceptualized as a subtype of panic disorder (Baker et al., 2003; David, Phillips, Medford, & Sierra, 2004; Segui et. al., 2000). During ECEM, while remaining in a hypnotic state, clients self-generated six to seven trials of eye movements to reduce anticipatory anxiety associated with depersonalization disorder. Eye movements were also used to process triggers that elicited breath holding, often followed by episodes of depersonalization. Hypnotic suggestions were used to reverse core symptoms of depersonalization, subjectively described as "feeling unreal" (Simeon et al., 1997).

  8. Speech and voice disorders in patients with psychogenic movement disorders.

    Science.gov (United States)

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2015-11-01

    Psychogenic speech and voice disorders (PSVDs) may occur in isolation but more typically are encountered in the setting of other psychogenic disorders. We aimed to characterize the phenomenology, frequency, and correlates of PSVDs in a cohort of patients with psychogenic movement disorders (PMDs). We studied 182 consecutive patients with PMDs, 30 of whom (16.5 %) also exhibited PSVD. Stuttering was the most common speech abnormality (n = 16, 53.3 %), followed by speech arrests (n = 4, 13.3 %), foreign accent syndrome (n = 2, 6.6 %), hypophonia (n = 2, 6.6 %), and dysphonia (n = 2, 6.6 %). Four patients (13.2 %) had more complex presentations with different combinations of these patterns. No differences in gender, age at onset, and distribution of PMDs were observed between patients with and without PSVD. PSVDs are relatively frequent in patients with PMDs and are manifested by a wide variety of abnormal speech and voice phenomena, with stuttering being the most common presentation. Speech therapy and insight-oriented counseling may be helpful to some patients.

  9. The interplay between iron accumulation, mitochondrial dysfunction and inflammation during the execution step of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Pamela J. Urrutia

    2014-03-01

    Full Text Available A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich’s ataxia and Parkinson’s disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson’s disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.

  10. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

    Science.gov (United States)

    Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

  11. Eyelid Dysfunction in Neurodegenerative, Neurogenetic, and Neurometabolic Disease

    Directory of Open Access Journals (Sweden)

    Ali G. Hamedani

    2017-07-01

    Full Text Available Eye movement abnormalities are among the earliest clinical manifestations of inherited and acquired neurodegenerative diseases and play an integral role in their diagnosis. Eyelid movement is neuroanatomically linked to eye movement, and thus eyelid dysfunction can also be a distinguishing feature of neurodegenerative disease and complements eye movement abnormalities in helping us to understand their pathophysiology. In this review, we summarize the various eyelid abnormalities that can occur in neurodegenerative, neurogenetic, and neurometabolic diseases. We discuss eyelid disorders, such as ptosis, eyelid retraction, abnormal spontaneous and reflexive blinking, blepharospasm, and eyelid apraxia in the context of the neuroanatomic pathways that are affected. We also review the literature regarding the prevalence of eyelid abnormalities in different neurologic diseases as well as treatment strategies (Table 1.

  12. FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders.

    Science.gov (United States)

    Fanjul-Vélez, Félix; Salas-García, Irene; Ortega-Quijano, Noé; Arce-Diego, José Luis

    2015-01-01

    Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Movement disorders associated with complex regional pain syndrome in children.

    Science.gov (United States)

    Agrawal, Shakti K; Rittey, Christopher D; Harrower, Neil A; Goddard, John M; Mordekar, Santosh R

    2009-07-01

    The aim of the present study was to review the history, clinical course, treatment, and outcome of movement disorders in children and young people with complex regional pain syndrome (CRPS). Case notes were reviewed retrospectively of children and young people who presented with movement disorders in CRPS to our tertiary paediatric pain service over a period of 13 years. Ten children with CRPS presented with movement disorders (eight females, two males). The age at first presentation with symptoms of CRPS ranged from 8 to 15 years (mean 11 y 2 mo, median 13 y). The most common movement disorder was dystonia (n=8), followed by tremors (n=3) and myoclonus (n=3); two patients had all three movement disorders. The movement disorder affected mainly the lower limb (n=9) with a predilection for the foot (n=7) and was frequently initiated by minor trauma (n=7). Follow-up ranged from 6 months to 14 years. The outcome was variable, with good prognosis in nearly half of the cases: four children experienced complete resolution of symptoms. Two children showed a slight improvement. Four children showed no improvement. Movement disorders in CRPS are under-recognized in children. The management has to be multidisciplinary with an expertise in paediatric pain.

  14. Mixed movements disorders as an initial feature of pediatric lupus.

    Science.gov (United States)

    Mrabet, Saloua; Benrhouma, Hanene; Kraoua, Ichraf; Naas, Amira; Achour, Nedia Ben; Klaa, Hedia; Turki, Ilhem

    2015-10-01

    Systemic lupus erythematosus (SLE) is an immunologic disease of the early adulthood. In children, SLE is rare and neurological onset is uncommon. We report on an observation of pediatric lupus in heterozygous twins revealed by mixed movement disorders. An 8-year-old boy, born to non consanguineous parents, with a family history of depression and a personal history of macular eruption, inflammatory polyarthralgias and a recurrent angina presented with acute movement and mood disorders. Neurological exam showed mild generalized choreic movements with motor and vocal tics. Antinuclear antibodies were positive. Brain MRI was normal. One year after, his twin brother presented with the same features. Movement disorders are described in pediatric lupus but are unusual as inaugural features of the disease. In SLE, movement disorders such as chorea are usually reported. However, Tics seem to be exceptional. Pathophysiology remains unclear. Early onset and familial form support genetic implication in the pathogenesis of lupus. Immune-mediated movement disorders such as in SLE are an established cause of acute movement disorders in child. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Progressive and self-limiting neurodegenerative disorders in Africa: a new prominent field of research led by South Africa but without strong health policy.

    Science.gov (United States)

    Poreau, Brice

    2016-01-01

    Neurodegenerative disorders are involved in mortality and morbidity of every country. A high prevalence is estimated in Africa. Neurodegenerative disorders are defined by a progressive or self-limiting alteration of neurons implied in specific functional and anatomical functions. It encompasses a various range of clinical disorders from self-limiting to progressive. Focus on public health policies and scientific research is needed to understand the mechanisms to reduce this high prevalence. We use bibliometrics and mapping tools to explore the area studies and countries involved in scientific research on neurodegenerative disorders in Africa. We used two databases: Web of Science and Pubmed. We analyzed the journals, most cited articles, authors, publication years, organizations, funding agencies, countries and keywords in Web of Science Core collection database and publication years and Medical Subject Headings in Pubmed database. We mapped the data using VOSviewer. We accessed 44 articles published between 1975 and 2014 in Web of Science Core collection Database and 669 from Pubmed database. The majority of which were after 2006. The main countries involved in research on neurodegenerative disorders in Africa the USA, the United Kingdom, France and South Africa representing the main network collaboration. Clinical neurology and Genetics hereditary are the main Web of Science categories whereas Neurosciences and Biochemistry and Molecular Biology are the main Web of Science categories for the general search "neurodegenerative disorders" not restrained to Africa. This is confirmed by Medical Subject Headings analysis from Pubmed with one more area study: Treatment. Neurodegenerative disorders research is leaded by South Africa with a network involving the USA, the UK, as well as African countries such Zambia. The chief field that emerged was on patient and hereditary as well as treatment. Public health policies were lacking fields in research whereas prevalence is

  16. Characteristic Eye Movements in Ataxia-Telangiectasia-Like Disorder: An Explanatory Hypothesis

    Directory of Open Access Journals (Sweden)

    Pamela Federighi

    2017-11-01

    Full Text Available ObjectiveTo investigate cerebellar dysfunctions and quantitatively characterize specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD, a rare autosomal recessive disease caused by mutations in the MRE11 gene. Additionally, to further elucidate the pathophysiology of cerebellar damage in the ataxia-telangiectasia (AT spectrum disorders.MethodsSaccade dynamics, metrics, and visual fixation deficits were investigated in two Italian adult siblings with genetically confirmed ATLD. Visually guided saccades were compared with those of 40 healthy subjects. Steady fixation was tested in primary and eccentric positions. Quantitative characterization of saccade parameters, saccadic intrusions (SI, and nystagmus was performed.ResultsPatients showed abnormally hypermetric and fast horizontal saccades to the left and greater inaccuracy than healthy subjects in all saccadic eye movements. Eye movement abnormalities included slow eye movements that preceded the initial saccade. Horizontal and vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic oscillations.ConclusionSlow eye movements accompanying saccades, SI, and cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD patients showed the presence of fast and hypermetric saccades suggesting damage of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative changes is hypothesized to explain the peculiar phenotype of this disease.

  17. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding.

    Science.gov (United States)

    Nakamura, T; Lipton, S A

    2007-07-01

    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity.

  18. Acute movement disorders in children: experience from a developing country.

    Science.gov (United States)

    Goraya, Jatinder Singh

    2015-03-01

    We describe acute movement disorders in 92 children, aged 5 days to 15 years, from an Indian tertiary hospital. Eighty-nine children had hyperkinetic movement disorders, with myoclonus in 25, dystonia in 21, choreoathetosis in 19, tremors in 15, and tics in 2. Tetany and tetanus were seen in 5 and 2 children, respectively. Hypokinetic movement disorders included acute parkinsonism in 3 children. Noninflammatory and inflammatory etiology were present in 60 and 32 children, respectively. Benign neonatal sleep myoclonus in 16 and opsoclonus myoclonus syndrome in 7 accounted for the majority of myoclonus cases. Vitamin B12 deficiency in 13 infants was the most common cause of tremors. Rheumatic fever and encephalitis were the most common causes of acute choreoathetosis. Acute dystonia had metabolic etiology in 6 and encephalitis and drugs in 3 each. Psychogenic movement disorders were seen in 4 cases only, although these patients may be underreported. © The Author(s) 2014.

  19. Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS)

    Science.gov (United States)

    ... the syndrome. Risk factors include the following: A sedentary lifestyle Smoking Obesity Many people with narcolepsy or rapid eye movement (REM) behavior disorder move their legs periodically during sleep. Both ...

  20. Trichotillomania (hair pulling disorder), skin picking disorder, and stereotypic movement disorder: toward DSM-V.

    Science.gov (United States)

    Stein, Dan J; Grant, Jon E; Franklin, Martin E; Keuthen, Nancy; Lochner, Christine; Singer, Harvey S; Woods, Douglas W

    2010-06-01

    In DSM-IV-TR, trichotillomania (TTM) is classified as an impulse control disorder (not classified elsewhere), skin picking lacks its own diagnostic category (but might be diagnosed as an impulse control disorder not otherwise specified), and stereotypic movement disorder is classified as a disorder usually first diagnosed in infancy, childhood, or adolescence. ICD-10 classifies TTM as a habit and impulse disorder, and includes stereotyped movement disorders in a section on other behavioral and emotional disorders with onset usually occurring in childhood and adolescence. This article provides a focused review of nosological issues relevant to DSM-V, given recent empirical findings. This review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Although TTM fits optimally into a category of body-focused repetitive behavioral disorders, in a nosology comprised of relatively few major categories it fits best within a category of motoric obsessive-compulsive spectrum disorders, (2) available evidence does not support continuing to include (current) diagnostic criteria B and C for TTM in DSM-V, (3) the text for TTM should be updated to describe subtypes and forms of hair pulling, (4) there are persuasive reasons for referring to TTM as "hair pulling disorder (trichotillomania)," (5) diagnostic criteria for skin picking disorder should be included in DSM-V or in DSM-Vs Appendix of Criteria Sets Provided for Further Study, and (6) the diagnostic criteria for stereotypic movement disorder should be clarified and simplified, bringing them in line with those for hair pulling and skin picking disorder. (c) 2010 Wiley-Liss, Inc.

  1. Identifying the genetic components underlying the pathophysiology of movement disorders

    Directory of Open Access Journals (Sweden)

    Ezquerra M

    2011-06-01

    Full Text Available Mario Ezquerra, Yaroslau Compta, Maria J MartiParkinson’s Disease and Movement Disorders Unit, Service of Neurology, Institute of Clinical Neurosciences, Hospital Clinic of Barcelona, IDIBAPS, CIBERNED, SpainAbstract: Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntington’s chorea, for instance. Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia. In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinson’s disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.Keywords: genetics, movement disorders, Parkinson’s disease, parkinsonism, dystonia

  2. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  3. Application of PIXE in medical study. Environmental minerals and neurodegenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, S. [Department of Neurology, Wakayama Medical College, Wakayama (Japan)

    1999-07-01

    Comparative study on amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PDC) in the Kii Peninsula of Japan and Guam was conducted to evaluate the participatory role of environmental minerals in the pathogenesis of the above neurodegenerative diseases, using particle-induced x-ray emission (PIXE) spectrometry and morphometric-statistical analysis. A significantly high content of Al in the hippocampus and spinal cord or Kii and Guamanian ALS/PD cases was found with a positive correlation for Fe and Cu, and a negative correlation for Zn. The numbers of hippocampal neurons in Guamanian PDC, Alzheimer's disease, and Parkinson's disease were significantly decreased with a high Al content. Al content significantly and positively correlated with the number of Alzheimer's neurofibrillary tangles (NFTs) in the hippocampus of ALS cases and controls in both foci, especially in Guamanian cases. The slope of best linear regression of Guamanian cases was markedly steeper than that of Japanese cases (p < 0,001), Morin staining for Al showed green fluorescence on the nucleolus, cytoplasm, and NFT in the hippocampus of Kii ALS cases. These findings suggest that Guamanian and Kii people have a predisposition to develop ALS/PDC precipitated by their geological/geochemical environmental status, i.e., a prolonged low intake or Ca and Mg together with excess exposure to Al and other environmental minerals. (author)

  4. In search of innovative therapeutics for neuropsychiatric disorders: the case of neurodegenerative diseases.

    Science.gov (United States)

    Féger, J; Hirsch, E C

    2015-01-01

    The recent medical literature highlights the lack of new drugs able to prevent or treat neurodegenerative diseases such as Alzheimer disease or Parkinson disease. Yet, the prevalence of these diseases is growing, related to increasing life expectancy, and is leading to a rise in their economic and social cost. At the same time, pharmaceutical companies are reducing or halting their investment in neuropharmacological research. Why have advances in basic neuroscience and our understanding of these diseases not allowed innovative discoveries in drug research? This review will try to explain this failure and suggest possible solutions: develop basic and clinical research but with the emphasis on translational and truly collaborative research; improve preclinical studies by developing more appropriate animal models, using new biomarkers and methodologies such as imaging suitable for clinical trials, providing worthwhile information on the ability of the drug to reach its intended target and induce significant pharmacological changes; build a new system of research management, based on stronger interdisciplinary relations between preclinical and clinical research and including the introduction of international precompetitive research between academic teams, start-up companies and pharmaceutical laboratories; hold early discussions with the regulatory authorities during preclinical studies and at the beginning of clinical trials in order to validate the methodological approaches; involve patients' associations in this new organization of research. These changes should help to ensure the discovery of effective treatments for these pathologies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA.

    Science.gov (United States)

    King, Barbara; Hassiotis, Sofia; Rozaklis, Tina; Beard, Helen; Trim, Paul J; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-05-01

    Repeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained-release (osmotic pump-delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six-week-old MPS IIIA and unaffected mice were implanted with subcutaneous mini-osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part-way through the experimental period. We observed near-normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM 3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump-like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain. Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre-clinical study, we examined an alternative approach - slow, continual infusion

  6. Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Stella, Anna Maria Giuffrida; Calabrese, Edward J

    2010-12-01

    The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre

  7. Hypnosis and movement disorders: State of the art and perspectives.

    Science.gov (United States)

    Flamand-Roze, C; Célestin-Lhopiteau, I; Roze, E

    Hypnosis might represent an interesting complementary therapeutic approach to movement disorders, as it takes into account not only symptoms, but also well-being, and empowers patients to take a more active role in their treatment. Our review of the literature on the use of hypnosis to treat movement disorders was done by systematically searching the PubMed database for reports published between 1984 and November 2015. The following variables were extracted from each selected paper: study design; sample size; type of movement disorder; hypnotic procedure; treatment duration; and efficacy. Thirteen papers were selected for detailed analysis. Most concerned tremor in Parkinson's disease and tics in Gilles de la Tourette syndrome. Although promising, the data were insufficient to allow conclusions to be drawn on the efficacy of hypnosis in movement disorders or to recommend its use in this setting. Well-designed studies taking into account some specific methodological challenges are needed to determine the possible therapeutic utility of hypnosis in movement disorders. In addition to the potential benefits for such patients, hypnosis might also be useful for studying the neuroanatomical and functional underpinnings of normal and abnormal movements. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Kinematic and electromyographic tools for characterizing movement disorders in mice.

    Science.gov (United States)

    Scholle, Hans C; Jinnah, H A; Arnold, Dirk; Biedermann, Frank H W; Faenger, Bernd; Grassme, Roland; Hess, Ellen J; Schumann, Nikolaus P

    2010-02-15

    Increasing interest in rodent models for movement disorders has led to an increasing need for more accurate and precise methods for both delineating the nature of abnormal movements and measuring their severity. These studies describe application of simultaneous high-speed video kinematics with multichannel electromyography (EMG) to characterize the movement disorder exhibited by tottering mutant mice. These mice provide a uniquely valuable model, because they exhibit paroxysmal dystonia superimposed on mild baseline ataxia, permitting the examination of these two different problems within the same animals. At baseline with mild ataxia, the mutants exhibited poorly coordinated movements with increased variation of stance and swing times, and slower spontaneous walking velocities. The corresponding EMG showed reduced mean amplitudes of biceps femoris and vastus lateralis, and poorly modulated EMG activities during the step cycle. Attacks of paroxysmal dystonia were preceded by trains of EMG bursts with doublets and triplets simultaneously in the biceps femoris and vastus lateralis followed by more sustained coactivation. These EMG characteristics are consistent with the clinical phenomenology of the motor phenotype of tottering mice as a baseline of mild ataxia with intermittent attacks of paroxysmal dystonia. The EMG characteristics of ataxia and dystonia in the tottering mice also are consistent with EMG studies of other ataxic or dystonic animals and humans. These studies provide insights into how these methods can be used for delineating movement disorders in mice and for how they may be compared with similar disorders of humans. (c) 2010 Movement Disorder Society.

  9. Characteristics of rapid eye movement sleep behavior disorder in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Frandsen, Rune Asger Vestergaard; Knudsen, Stine

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients with narcol...

  10. Clinical decision-making in functional and hyperkinetic movement disorders

    NARCIS (Netherlands)

    van der Salm, Sandra M. A.; van Rootselaar, Anne-Fleur; Cath, Danielle C.; de Haan, Rob J.; Koelman, Johannes H. T. M.; Tijssen, Marina A. J.

    2017-01-01

    Objective: Functional or psychogenic movement disorders (FMD) present a diagnostic challenge. To diagnose FMD, clinicians must have experience with signs typical of FMD and distinguishing features from other hyperkinetic disorders. The aim of this study was to clarify the decision-making process of

  11. Eye Movement Indices in the Study of Depressive Disorder.

    Science.gov (United States)

    Li, Yu; Xu, Yangyang; Xia, Mengqing; Zhang, Tianhong; Wang, Junjie; Liu, Xu; He, Yongguang; Wang, Jijun

    2016-12-25

    Impaired cognition is one of the most common core symptoms of depressive disorder. Eye movement testing mainly reflects patients' cognitive functions, such as cognition, memory, attention, recognition, and recall. This type of testing has great potential to improve theories related to cognitive functioning in depressive episodes as well as potential in its clinical application. This study investigated whether eye movement indices of patients with unmedicated depressive disorder were abnormal or not, as well as the relationship between these indices and mental symptoms. Sixty patients with depressive disorder and sixty healthy controls (who were matched by gender, age and years of education) were recruited, and completed eye movement tests including three tasks: fixation task, saccade task and free-view task. The EyeLink desktop eye tracking system was employed to collect eye movement information, and analyze the eye movement indices of the three tasks between the two groups. (1) In the fixation task, compared to healthy controls, patients with depressive disorder showed more fixations, shorter fixation durations, more saccades and longer saccadic lengths; (2) In the saccade task, patients with depressive disorder showed longer anti-saccade latencies and smaller anti-saccade peak velocities; (3) In the free-view task, patients with depressive disorder showed fewer saccades and longer mean fixation durations; (4) Correlation analysis showed that there was a negative correlation between the pro-saccade amplitude and anxiety symptoms, and a positive correlation between the anti-saccade latency and anxiety symptoms. The depression symptoms were negatively correlated with fixation times, saccades, and saccadic paths respectively in the free-view task; while the mean fixation duration and depression symptoms showed a positive correlation. Compared to healthy controls, patients with depressive disorder showed significantly abnormal eye movement indices. In addition

  12. Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?

    Directory of Open Access Journals (Sweden)

    Alessandro Castorina

    2015-01-01

    Full Text Available Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration.Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

  13. Verb naming fluency in hypokinetic and hyperkinetic movement disorders.

    Science.gov (United States)

    Bayram, Ece; Akbostanci, Muhittin C

    2017-07-01

    Cortical motor regions are considered to play a role in action related language. These regions are affected differently in different types of movement disorders. Parkinson's disease, a hypokinetic movement disorder, has been shown to cause action language disruptions alongside movement deficits. Action language, however, has not been investigated in primary cervical dystonia, a hyperkinetic movement disorder. The aim of this study is to investigate whether action language is affected differently in hypokinetic and hyperkinetic movement disorders which have different effects on movements. Thirty patients with Parkinson's disease, thirty primary cervical dystonia patients and thirty healthy controls were included in the study. Participants performed phonemic, semantic and action fluency tasks. Verbs produced during action fluency were grouped as action and non-action verbs and group differences were investigated. Our results showed that all participants performed similarly in all of the fluency tasks. Mean action content of the verbs produced in action fluency did not differ between groups. During action fluency, however, whereas healthy controls produced more action verbs than non-action verbs, both patient groups did not have this difference between verb groups. Primary cervical dystonia patients produced less action verbs compared to healthy controls. The lack of action language deficits in Parkinson's disease and only an action verb deficit in primary cervical dystonia without any other action language deficits reject strong embodiment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Sleep and circadian dysfunction in neurodegenerative disorders: insights from a mouse model of Huntington's disease.

    Science.gov (United States)

    Kuljis, Dika; Schroeder, Analyne M; Kudo, Takashi; Loh, Dawn H; Willison, David L; Colwell, Christopher S

    2012-09-01

    Sleep disorders are common in patients with neurogenerative diseases and manifest early in the disease process. Among a number of possible mechanisms underlying the sleep disturbances, there is evidence that dysfunction in the circadian system is a contributing factor. Focusing on a mouse model of Huntington's disease has enabled us to determine that at the onset of symptoms, spontaneous electrical activity of neurons within the central clock is disrupted even though the molecular clockwork is still functional. These findings suggest that the fundamental deficit contributing to disordered sleep is reduced SCN output. The mechanism underlying this deficit is not yet known, but mitochondrial dysfunction and oxidative stress are likely involved. Disruption of circadian output from the SCN would be expected to have wide ranging impact on the body including SCN regulated brain regions and the heart. In fact, there is a great deal of overlap in the non-motor symptoms experienced by HD patients and the consequences of circadian disruption. This raises the possibility that the disordered sleep and circadian function experienced by HD patients may be an integral part of the disease. Furthermore, we speculate that circadian dysfunction may accelerate the pathology underlying HD. If these hypotheses are correct, we should focus on treating circadian misalignment and sleep disruptions early in disease progression.

  15. Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging

    Directory of Open Access Journals (Sweden)

    Bryan Holvoet

    2016-01-01

    Full Text Available Numerous neurodegenerative and neuromuscular disorders are associated with cell-specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in their in vivo behavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling their in vivo behavior further improvement in stem cell transplantations will be achieved.

  16. 123-I ioflupane (Datscan® presynaptic nigrostriatal imaging in patients with movement disorders

    Directory of Open Access Journals (Sweden)

    Angel Soriano Castrejón

    2005-10-01

    Full Text Available 123-I Ioflupane (Datscan® presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between Parkinson’s disease (PD and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disorders involving the substantia nigra.A imagem pré-sináptica através de 123-I Ioflupane (Datscan® tem mostrado um papel significante na avaliação de pacientes com distúrbios do movimento. 123-I Ioflupane SPECT é capaz de distinguir entre Mal de Parkinson (MP e outras formas de parkinsonismo sem degenerações da via nigroestriatal incluindo um distúrbio comum de movimento parecido com o tremor essencial e para medir a evolução da doença no Mal de Parkinson e outros distúrbios neurodegenerativos envolvendo a substantia nigra.

  17. What Have We Learned About Movement Disorders from Functional Neurosurgery?

    Science.gov (United States)

    Lozano, Andres M; Hutchison, William D; Kalia, Suneil K

    2017-07-25

    Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically.

  18. Mortality and Its Risk Factors in Patients with Rapid Eye Movement Sleep Behavior Disorder.

    Science.gov (United States)

    Zhou, Junying; Zhang, Jihui; Lam, Siu Ping; Mok, Vincent; Chan, Anne; Li, Shirley Xin; Liu, Yaping; Tang, Xiangdong; Yung, Wing Ho; Wing, Yun Kwok

    2016-08-01

    To determine the mortality and its risk factors in patients with rapid eye movement (REM) sleep behavior disorder (RBD). A total of 205 consecutive patients with video-polysomnography confirmed RBD (mean age = 66.4 ± 10.0 y, 78.5% males) were recruited. Medical records and death status were systematically reviewed in the computerized records of the health care system. Standardized mortality ratio (SMR) was used to calculate the risk ratio of mortality in RBD with reference to the general population. Forty-three patients (21.0%) died over a mean follow-up period of 7.1 ± 4.5 y. The SMR was not increased in the overall sample, SMR (95% confidence interval [CI]) = 1.00 (0.73-1.33). However, SMR (95% CI) increased to 1.80 (1.21-2.58) and 1.75 (1.11-2.63) for RBD patients in whom neurodegenerative diseases and dementia, respectively, eventually developed. In the Cox regression model, mortality risk was significantly associated with age (hazard ratio [HR] = 1.05; 95% CI, 1.01-1.10), living alone (HR = 2.04; 95% CI, 1.39-2.99), chronic obstructive pulmonary disease (HR = 3.38; 95% CI, 1.21-9.46), cancer (HR = 10.09; 95% CI, 2.65-38.42), periodic limb movements during sleep (HR = 3.06; 95% CI, 1.50-6.24), and development of neurodegenerative diseases (HR = 2.84; 95% CI, 1.47-5.45) and dementia (HR = 2.66; 95% CI, 1.39-5.08). Patients with RBD have a higher mortality rate than the general population only if neurodegenerative diseases develop. Several risk factors on clinical and sleep aspects are associated with mortality in RBD patients. Our findings underscore the necessity of timely neuroprotective interventions in the early phase of RBD before the development of neurodegenerative diseases. © 2016 Associated Professional Sleep Societies, LLC.

  19. Binocular vision and eye movement disorders in older adults.

    Science.gov (United States)

    Leat, Susan J; Chan, Lisa Li-Li; Maharaj, Priya-Devi; Hrynchak, Patricia K; Mittelstaedt, Andrea; Machan, Carolyn M; Irving, Elizabeth L

    2013-05-31

    To determine the prevalence of binocular vision (BV) and eye movement disorders in a clinic population of older adults. Retrospective clinic data were abstracted from files of 500 older patients seen at the University of Waterloo Optometry Clinic over a 1-year period. Stratified sampling gave equal numbers of patients in the 60 to 69, 70 to 79, and 80+ age groups. Data included age, general and ocular history and symptoms, use of antidepressants, a habit of smoking, refraction, visual acuity, BV and eye movement status for the most recent full oculo-visual assessment, and an assessment 10 years prior. The prevalence of any BV or eye movement abnormal test (AT) result, defined as a test result outside the normal range, was determined. This included strabismus (any) or phoria; incomitancy; poor pursuits; and remote near point of convergence (NPC). The prevalence of significant BV disorders (diagnostic entities, i.e., a clinical condition that may need treatment and may have functional implications) was also determined. The prevalence of any BV or eye movement at was 41%, 44%, and 51% in the 60 to 69, 70 to 79, and 80+ age groups, respectively. These figures were lower for 10 years earlier: 31%, 36%, and 40% for ages 50 to 59, 60 to 69, and 70+, respectively. The prevalence of any BV or eye movement disorder was 27%, 30%, and 38% for the three age groups and 17%, 19%, and 24% for 10 years prior. Age and use of antidepressants most commonly predicted BV or eye movement AT or disorder. BV disorders are common among older adults.

  20. Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders

    Science.gov (United States)

    Brzdak, Patrycja; Nowak, Daria; Wiera, Grzegorz; Mozrzymas, Jerzy W.

    2017-01-01

    The extracellular matrix (ECM) and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs) and astacins in physiological and pathological processes in the central nervous system (CNS). The expression and activity of metzincins are strictly controlled at different levels (e.g., through the regulation of translation, limited activation in the extracellular space, the binding of endogenous inhibitors and interactions with other proteins). Thus, unsurprising is that the dysregulation of proteolytic activity, especially the greater expression and activation of metzincins, is associated with neurodegenerative disorders that are considered synaptopathies, especially Alzheimer’s disease (AD). We review current knowledge of the functions of metzincins in the development of AD, mainly the proteolytic processing of amyloid precursor protein, the degradation of amyloid β (Aβ) peptide and several pathways for Aβ clearance across brain barriers (i.e., blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB)) that contain specific receptors that mediate the uptake of Aβ peptide. Controlling the proteolytic activity of metzincins in Aβ-induced pathological changes in AD patients’ brains may be a promising therapeutic strategy. PMID:28713245

  1. Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Patrycja Brzdak

    2017-06-01

    Full Text Available The extracellular matrix (ECM and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs, A Disintegrin and Metalloproteinases (ADAMs, A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs and astacins in physiological and pathological processes in the central nervous system (CNS. The expression and activity of metzincins are strictly controlled at different levels (e.g., through the regulation of translation, limited activation in the extracellular space, the binding of endogenous inhibitors and interactions with other proteins. Thus, unsurprising is that the dysregulation of proteolytic activity, especially the greater expression and activation of metzincins, is associated with neurodegenerative disorders that are considered synaptopathies, especially Alzheimer’s disease (AD. We review current knowledge of the functions of metzincins in the development of AD, mainly the proteolytic processing of amyloid precursor protein, the degradation of amyloid β (Aβ peptide and several pathways for Aβ clearance across brain barriers (i.e., blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB that contain specific receptors that mediate the uptake of Aβ peptide. Controlling the proteolytic activity of metzincins in Aβ-induced pathological changes in AD patients’ brains may be a promising therapeutic strategy.

  2. Relevance of the chronobiological and non-chronobiological actions of melatonin for enhancing therapeutic efficacy in neurodegenerative disorders.

    Science.gov (United States)

    Cecon, Erika; Markus, Regina P

    2011-05-01

    Melatonin is an indolamine with a large spectrum of functions that can be divided into chronobiotic and nonchronobiotic. Chronobiotic effects are mediated by the daily rhythm of melatonin in the plasma due to nocturnal pineal synthesis, whereas the melatonin produced by other cells, such as gastrointestinal and immune competent cells, is independent of the light/dark cycle and exert non-chronobiotic effects. The concentrations achieved by the two sources are significantly different, varying in the pM-nM range in the plasma, and may achieve concentrations in the mM range when released locally by activated immune-competent cells. Consequently, the effects of the melatonin produced in these two situations are distinct. Much has been reported about the beneficial response to exogenous melatonin administration in several pathological conditions. However, the relationship between the establishment of a disease and the state of the physiological activity of the pineal gland is still poorly understood. Here, we review the state of art in the modulation of pineal melatonin synthesis, relevant patents, and discuss its relationship with neurodegenerative disorders that involve a central inflammatory response, such as Alzheimer's disease, to suggest the putative relevance of new therapeutic protocols that replace this pineal hormone.

  3. Synopsis on Managment Strategies for Neurodegenerative Disorders: Challenges from Bench to Bedside in Successful Drug Discovery and Development.

    Science.gov (United States)

    Bhat, Sheraz Ahmad; Kamal, Mohammad Amjad; Yarla, Nagendra Sastry; Ashraf, Ghulam Md

    2017-01-01

    The maintenance of health requires successful cell functioning, which in turn depends upon the proper and active conformation of proteins besides other biomolecules. However, occasionally these proteins may misfold and lead to the appearance and progression of protein conformational diseases. These diseases apart from others include several neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other lesser known diseases. Although much knowledge has been gained, these NDDs still warrant advance research in the elucidation of their mechanisms as well as effective therapeutic interventions and proper management. There is an ever-growing and urgent need to improve the diagnosis and management of NDDs due to their devastating nature, serious social impact and neuropsychiatric symptoms. It is also envisioned that we may be able to encourage, develop, and strengthen the cell defenses against amyloid toxicity and prevent neuronal destruction and consequently neurodegeneration. In this review, the implications of protein misfolding and aggregation in NDDs are discussed along with some of the most recent findings on the curative and beneficial effects of natural molecules such as polyphenols. This paper also reviews the anti-aggregation and protective effects of some organic and peptidic compounds duly supported experimentally, as prospective future therapeutics for NDDs. The synopses presented in this review shall prove helpful in further understanding of the causes, cures and management of lethal NDDs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

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    Aasef G Shaikh

    Full Text Available Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task, while arms were outstretched (postural task, and at rest. Almost all ataxia-telangiectasia subjects (79/80 had abnormal involuntary movements, such as rhythmic oscillations (tremor, slow drifts (dystonia or athetosis, and isolated rapid movements (dystonic jerks or myoclonus. All patients with involuntary movements had both kinetic and postural tremor, while 48 (61% also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

  5. Potential contribution of the neurodegenerative disorders risk loci to cognitive performance in an elderly male gout population.

    Science.gov (United States)

    Han, Lin; Jia, Zhaotong; Cao, Chunwei; Liu, Zhen; Liu, Fuqiang; Wang, Lin; Ren, Wei; Sun, Mingxia; Wang, Baoping; Li, Changgui; Chen, Li

    2017-09-01

    Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function.This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls.Compared with controls, gout patients had significantly lower MoCA scores [22.78 ± 3.01 vs 23.42 ± 2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P gout in further analysis (all P > .05).Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our Chinese elderly male gout population. Larger prospective studies of the cognitive performance and genetic analysis in gout subjects are recommended.

  6. Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports.

    Science.gov (United States)

    Dastsooz, Hassan; Nemati, Hamid; Fard, Mohammad Ali Farazi; Fardaei, Majid; Faghihi, Mohammad Ali

    2017-08-18

    Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17. The purpose of this study was to investigate disease-causing mutations in two patients with distinct NBIA disorders. Whole Exome sequencing using Next Generation Illumina Sequencing was used to enrich all exons of protein-coding genes as well as some other important genomic regions in these two affected patients. A deleterious homozygous four-nucleotide deletion causing frameshift deletion in PANK2 gene (c.1426_1429delATGA, p.M476 fs) was identified in an 8 years old girl with dystonia, bone fracture, muscle rigidity, abnormal movement, lack of coordination and chorea. In addition, our study revealed a novel missense mutation in PLA2G6 gene (c.3G > T:p.M1I) in one and half-year-old boy with muscle weakness and neurodevelopmental regression (speech, motor and cognition). The novel mutations were also confirmed by Sanger sequencing in the proband and their parents. Current study uncovered two rare novel mutations in PANK2 and PLA2G6 genes in patients with NBIA disorder and such studies may help to conduct genetic counseling and prenatal diagnosis more accurately for individuals at the high risk of these types of disorders.

  7. Quantification of symptoms of movement disorders employing motion sensors

    NARCIS (Netherlands)

    Martinez Manzanera, Octavio

    2017-01-01

    Clinical evaluation plays a fundamental role in the diagnosis and evaluation of a movement disorder. This evaluation depends, at least to some extent, on a human decision process. To homogenize and improve the reliability of the evaluation rating scales have been developed through the years. In

  8. Impaired Awareness of Movement Disorders in Parkinson's Disease

    Science.gov (United States)

    Amanzio, Martina; Monteverdi, Silvia; Giordano, Alessandra; Soliveri, Paola; Filippi, Paola; Geminiani, Giuliano

    2010-01-01

    Background: This study analyzed the presence of awareness of movement disorders (dyskinesias and hypokinesias) in 25 patients with Parkinson's disease (PD) and motor fluctuations (dyskinesias, wearing off, on-off fluctuations). Of the few studies that have dealt with this topic, none have analyzed the differences in the awareness of motor deficits…

  9. Neurophysiological basis of rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Jennum, Poul; Christensen, Julie Anja Engelhard; Zoetmulder, Marielle

    2016-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities ha...

  10. Treatment of Movement Disorders With Focused Ultrasound

    Directory of Open Access Journals (Sweden)

    Paul S Fishman

    2017-05-01

    Full Text Available Although the use of ultrasound as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists or neurologists are familiar with this technology. Stereotactic brain lesioning had been widely used as a treatment for medically refractory patients with essential tremor (ET, Parkinson disease (PD, and dystonia but has been largely replaced by deep brain stimulation (DBS surgery, with advantages both in safety and efficacy. However, DBS is associated with complications including intracerebral hemorrhage, infection, and hardware malfunction. The occurrence of these complications has spurred interest in less invasive stereotactic brain lesioning methods including magnetic resonance imaging–guided high intensity–focused ultrasound (FUS surgery. Engineering advances now allow sound waves to be targeted noninvasively through the skull to a brain target. High intensities of sonic energy can create a coagulation lesion similar to that of older radiofrequency stereotactic methods, but without opening the skull, recent Food and Drug Administration approval of unilateral thalamotomy for treatment of ET. Clinical studies of stereotactic FUS for aspects of PD are underway. Moderate intensity, pulsed FUS has also demonstrated the potential to safely open the blood-brain barrier for localized delivery of therapeutics including proteins, genes, and cell-based therapy for PD and related disorders. The goal of this review is to provide basic and clinical neuroscientists with a level of understanding to interact with medical physicists, biomedical engineers, and radiologists to accelerate the application of this powerful technology to brain disease

  11. Sleep disturbance in mental health problems and neurodegenerative disease

    National Research Council Canada - National Science Library

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    ... and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative...

  12. Using the WHOQOL-DIS to measure quality of life in persons with physical disabilities caused by neurodegenerative disorders.

    Science.gov (United States)

    Lucas-Carrasco, Ramona; Pascual-Sedano, Berta; Galán, Ingrid; Kulisevsky, Jaime; Sastre-Garriga, Jaume; Gómez-Benito, Juana

    2011-01-01

    Neurodegenerative disorders (ND) have a major impact on quality of life (QoL) and place a substantial burden on patients, their families and carers; they are the second leading cause of disability. The objective of this study was to examine QoL in persons with ND. A battery of subjective assessments was used, including the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the World Health Organization Quality of Life - Disability (WHOQOL-DIS). Psychometric properties of the WHOQOL-BREF and WHOQOL-DIS were investigated using classical psychometric methods. Participants (n = 149) were recruited and interviewed at two specialized centers to obtain information on health and disability perceptions, depressive symptoms (Hospital Anxiety and Depression Scale - Depression, HADS-D), Fatigue Assessment Scale (FAS), Satisfaction with Life (SWL), generic QoL (WHOQOL-BREF, WHOQOL-DIS), specific QoL (Multiple Sclerosis Impact Scale, MSIS-29; Parkinson's Disease Questionnaire, PDQ-39) and sociodemographics. Internal consistency was acceptable, except for the WHOQOL-BREF social (0.67). Associations, using Pearson's and Spearman's rho correlations, were confirmed between WHOQOL-BREF and WHOQOL-DIS with MSIS-29, PDQ-39, HADS-D, FAS and SWL. Regarding 'known group' differences, Student's t tests showed that WHOQOL-BREF and WHOQOL-DIS scores significantly discriminated between depressed and nondepressed and those perceiving a more severe impact of the disability on their lives. This study is the first to report on use of the WHOQOL-BREF and WHOQOL-DIS in Spanish persons with ND; they are promising useful tools in assessing persons with ND through the continuum of care, as they include important dimensions commonly omitted from other QoL measures. Copyright © 2010 S. Karger AG, Basel.

  13. Genomic Characteristics of Genetic Creutzfeldt-Jakob Disease Patients with V180I Mutation and Associations with Other Neurodegenerative Disorders.

    Science.gov (United States)

    Lee, Sol Moe; Chung, Myungguen; Hyeon, Jae Wook; Jeong, Seok Won; Ju, Young Ran; Kim, Heebal; Lee, Jeongmin; Kim, SangYun; An, Seong Soo A; Cho, Sung Beom; Lee, Yeong Seon; Kim, Su Yeon

    2016-01-01

    Inherited prion diseases (IPDs), including genetic Creutzfeldt-Jakob disease (gCJD), account for 10-15% of cases of prion diseases and are associated with several pathogenic mutations, including P102L, V180I, and E200K, in the prion protein gene (PRNP). The valine to isoleucine substitution at codon 180 (V180I) of PRNP is the most common pathogenic mutation causing gCJD in East Asian patients. In this study, we conducted follow-up analyses to identify candidate factors and their associations with disease onset. Whole-genome sequencing (WGS) data of five gCJD patients with V180I mutation and 145 healthy individuals were used to identify genomic differences. A total of 18,648,850 candidate variants were observed in only the patient group, 29 of them were validated as variants. Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20. More than half of validated variants were categorized in Gene Ontology (GO) terms of binding and/or catalytic activity. Moreover, we found differential genome variants in gCJD patients with V180I mutation, including one uniquely surviving 10 years after diagnosis of the disease. Elucidation of the relationships between gCJD and Alzheimer's disease or Parkinson's disease at the genomic level will facilitate further advances in our understanding of the specific mechanisms mediating the pathogenesis of NDs and gold standard therapies for NDs.

  14. Diagnosis and treatment of impulse control disorders in patients with movement disorders

    OpenAIRE

    Mestre, Tiago A.; Antonio P Strafella; Thomsen, Teri; Voon, Valerie; Miyasaki, Janis

    2013-01-01

    Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson’s disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age,...

  15. ANALYSIS OF DYSLEXIC STUDENTS READING DISORDER WITH EYE MOVEMENT TRACKING

    Directory of Open Access Journals (Sweden)

    Servet Bayram,

    2012-04-01

    Full Text Available In the study, we examine and compare dyslexic and normal readers, reading habits and eye movements during reading passages and pseudowords. Participants were 15 Turkish dyslexic students, suffering mainly from reading disorder. In addition there were 15 Turkish students who were regular readers and who did not have problems with reading. During reading passages and pseudowords, the eye movements of participants were recorded. For both text and pseudoword reading, the dyslexic readers exhibited more and much longer fixations, but relatively few regressions. An increased length of words and pseudowords led to a greater increase in the number of fixations for dyslexics rather than normal readers.

  16. Increased sexual arousal in patients with movement disorders

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    Hélio A. G. Teive

    2016-04-01

    Full Text Available ABSTRACT Increased of sexual arousal (ISA has been described in different neurological diseases. The purpose of this study was present a case series of ISA in patients with movement disorders. Method Fifteen patients with different forms of movement disorders (Parkinson’s disease, Huntington’s disease, Tourette´s syndrome, spinocerebellar ataxia type 3, were evaluated in the Movement Disorders Unit of the Federal University of Paraná. Results Among Parkinson’s disease patients there were seven cases with different forms of ISA due to dopaminergic agonist use, levodopa abuse, and deep brain stimulation (DBS. In the group with hyperkinetic disorders, two patients with Huntington’s disease, two with Tourette’s syndrome, and four with spinocerebellar ataxia type 3 presented with ISA. Conclusions ISA in this group of patients had different etiologies, predominantly related to dopaminergic treatment or DBS in Parkinson’s disease, part of the background clinical picture in Huntington’s disease and Tourette’s syndrome, and probably associated with cultural aspects in patients with spinocerebellar ataxia type 3.

  17. Current applications and limitations of surgical treatments for movement disorders.

    Science.gov (United States)

    Krack, Paul; Martinez-Fernandez, Raul; Del Alamo, Marta; Obeso, Jose A

    2017-01-01

    Functional neurosurgery for the treatment of both psychiatric and neurological disorders has been performed regularly since the 1940s. However, misuse in the early days and the appearance of effective medical treatments, such as levodopa and neuroleptic drugs, greatly reduced surgical approaches over several decades. The development of a comprehensive model of basal ganglia pathophysiology in the 1990s facilitated the resurgence of functional neurosurgery, mainly for the treatment of levodopa-related motor complications in Parkinson's disease. This led first to the re-emergence of posteroventral pallidotomy and subsequently to deep brain stimulation. Thirty years on from this turning point, we find ourselves looking at a new scenario. Although deep brain stimulation is accepted worldwide and technical advances continue to improve this therapy, new questions and challenges such as long-term benefits and optimal targeting have emerged. In addition, new nonincisional tools used to perform ablative treatments, such as high-intensity focused ultrasound and gamma-knife, are challenging classical reluctance to therapeutic lesioning, and it remains to be determined how these approaches will fit into the array of movement disorder treatments. This review discusses the current clinical state of the art of functional neurosurgery in the treatment of Parkinson's disease, tremor, and dystonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  18. Cheek-biting disorder: another stereotypic movement disorder?

    Science.gov (United States)

    Sarkhel, Sujit; Praharaj, Samir Kumar; Akhtar, Sayeed

    2011-12-01

    Recurrent cheek biting, a form of self-injurious behavior is a rare entity which presents mostly to dentists and dermatologists. We report a case of recurrent severe cheek biting in an adult male leading to mucosal ulceration. The stereotypic pattern of cheek biting and associated behavior bears striking resemblance to other impulse control disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Fetal programming of the human brain: is there a link with insurgence of neurodegenerative disorders in adulthood?

    Science.gov (United States)

    Faa, G; Marcialis, M A; Ravarino, A; Piras, M; Pintus, M C; Fanos, V

    2014-01-01

    In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to

  20. Movement Disorders Syndromes Associated With Lacunar Infarcts, Clinical Case Series

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    A Chitsaz

    2017-02-01

    Full Text Available Lacunar infarcts are small (<15 mm diameter subcortical infarcts that results from occlusion of a single penetrating artery. Lacunar infarcts are associated with clinical lacunar syndromes, one of lacunar syndromes is movement disorders syndrome such as chore, dystonia, hemibolismus and asterixis. Several types of movement disorders have been described with small, deep infarct, majority of these syndrome is caused by penetrating small- artery disease. The movement disorder may appear as the only sign of the infarct or may develop later, after an initial syndrome, different in character, has resolved. Hemichorea – hemiballismus is the most common of movement disorder due to lacunar infarcts. The lacunar size infarcts found in different parts of the striatum including in head of the caudate nucleus and adjacent corona radiate, the subthalamic  and the thalamus. The onset is typically abrupt and is usually- unaccompanied by other complaints. The chorea usually involves the forearm, hand, and fingers. In some cases, chorea has been delayed by some weeks or months after the initial occurrence of hemiparesis.  Dystonia: Two types of dystonia have been described in cases of lacunes, action- induced and focal dystonia. Case I-  in a 63 year old woman with lacunar stroke, with abrupt onset of chorea, chorea involves the foream, hand, and fingers, it was  accompanied by hemiparesis that faded within 3 months even though the chorea persisted unchanged. Case II-  In a 75 years old man chorea was delayed by some weeks after initial occurrence of hemiparesis due to lacunar infarct. Case III-  in a 81 years old woman lacunar infarct, whose putaminal lesions was documented by CT scan, suffer choreic movements of the distal parts of the arm and leg that interfered with normal activity and prevented easy walking for more than a weeks, the examination revealed normal strength, sensation and reflexes. Case IV-  A 69 years old man , with lacunar infarct in

  1. Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

    Science.gov (United States)

    Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

    2008-04-18

    Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

  2. Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

    Directory of Open Access Journals (Sweden)

    Tuisku Katinka

    2008-04-01

    Full Text Available Abstract Background Neuroleptic-induced movement disorders (NIMDs have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV. Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA and pseudoakathisia (PsA were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

  3. Major depressive disorder alters perception of emotional body movements.

    Science.gov (United States)

    Kaletsch, Morten; Pilgramm, Sebastian; Bischoff, Matthias; Kindermann, Stefan; Sauerbier, Isabell; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Sammer, Gebhard; Zentgraf, Karen; Munzert, Jörn; Lorey, Britta

    2014-01-01

    Much recent research has shown an association between mood disorders and an altered emotion perception. However, these studies were conducted mainly with stimuli such as faces. This is the first study to examine possible differences in how people with major depressive disorder (MDD) and healthy controls perceive emotions expressed via body movements. Thirty patients with MDD and thirty healthy controls observed the video scenes of human interactions conveyed by point-light displays (PLDs). They rated the depicted emotions and judged their confidence in their rating. Results showed that patients with MDD rated the depicted interactions more negatively than healthy controls. They also rated interactions with negative emotionality as being more intense and were more confident in their ratings. It is concluded that patients with MDD exhibit an altered emotion perception compared to healthy controls when rating emotions expressed via body movements depicted in PLDs.

  4. Major depressive disorder alters perception of emotional body movements

    Directory of Open Access Journals (Sweden)

    Morten eKaletsch

    2014-01-01

    Full Text Available Much recent research has shown an association between mood disorders and an altered emotion perception. However, these studies were conducted mainly with stimuli such as faces. This is the first study to examine possible differences in how people with major depressive disorder (MDD and healthy controls perceive emotions expressed via body movements. 30 patients with MDD and 30 healthy controls observed video scenes of human interactions conveyed by point–light displays (PLDs. They rated the depicted emotions and judged their confidence in their rating. Results showed that patients with MDD rated the depicted interactions more negatively than healthy controls. They also rated interactions with negative emotionality as being more intense and were more confident in their ratings. It is concluded that patients with MDD exhibit an altered emotion perception compared to healthy controls when rating emotions expressed via body movements depicted in PLDs.

  5. Chronic sleep disturbance and neural injury: links to neurodegenerative disease.

    Science.gov (United States)

    Abbott, Sabra M; Videnovic, Aleksandar

    2016-01-01

    Sleep-wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep-wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep-wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer's disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson's disease, and the insomnia and circadian dysregulation associated with Huntington's disease.

  6. Chronic sleep disturbance and neural injury: links to neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Abbott SM

    2016-01-01

    Full Text Available Sabra M Abbott,1 Aleksandar Videnovic21Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, IL, USA; 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: Sleep–wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep–wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep–wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer’s disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson’s disease, and the insomnia and circadian dysregulation associated with Huntington’s disease. Keywords: sleep, neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease

  7. The representation of movement disorders in fictional literature.

    Science.gov (United States)

    Voss, Hendrik

    2012-10-01

    This review considers novels, plays and poems dealing with movement disorders in order to show the relevance in the literary context. The motifs are arranged and compared following a modern neurological nosology according to Parkinson syndromes, dystonia, myoclonus, tics, hemifacial spasm, Tourette syndrome, Huntington's disease and hyperekplexia. There is considerable variety in how movement disorders are depicted and how much influence they have on the plot structures. Their usage ranges from a brief reference in order to accentuate aspects of a character's personality or social position, such as in Shakespeare, Dickens, Tolstoy or Galdós; to truly constituting one of the plot's main themes as, for example, with the representation of Lewy body disease in Franzen's The Corrections and Huntington's disease in Vonnegut's Galápagos, Sawyer's Frameshift or McEwan's Saturday. The symbolic connotation of the disease is of major importance, as is its social and psychological impact. Some 20th century authors transfer rhythm patterns of specific movement disorders into the textual structure, including, among others, Beckett.

  8. The Therapeutic Potential of Cannabinoids for Movement Disorders

    Science.gov (United States)

    Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

    2014-01-01

    Background There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and particularly for neurologic conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science, preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. Results The pharmacology of cannabis is complex with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits but more consistently suggest potential neuroprotective effects in several animal models of Parkinson’s (PD) and Huntington’s disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia or ataxia and nonexistent for myoclonus or restless legs syndrome. Conclusions Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders. PMID:25649017

  9. Cognitive and Psychiatric Phenotypes of Movement Disorders in Children: A Systematic Review

    Science.gov (United States)

    Ben-Pazi, Hilla; Jaworowski, Solomon; Shalev, Ruth S

    2011-01-01

    Aim: The cognitive and psychiatric aspects of adult movement disorders are well established, but specific behavioural profiles for paediatric movement disorders have not been delineated. Knowledge of non-motor phenotypes may guide treatment and determine which symptoms are suggestive of a specific movement disorder and which indicate medication…

  10. A boy infant with sleep related rhythmic movement disorder showing arm banging

    Directory of Open Access Journals (Sweden)

    Jun Kohyama

    2014-09-01

    Discussion: We diagnosed him as having arm banging type of sleep related rhythmic movement disorder. To our knowledge, no precise description on this type of sleep related rhythmic movement disorder has been found. In addition, this patient seemed to be the youngest case of sleep related rhythmic movement disorder showing arm banging.

  11. Quantitative assessment of motor speech abnormalities in idiopathic rapid eye movement sleep behaviour disorder.

    Science.gov (United States)

    Rusz, Jan; Hlavnička, Jan; Tykalová, Tereza; Bušková, Jitka; Ulmanová, Olga; Růžička, Evžen; Šonka, Karel

    2016-03-01

    Patients with idiopathic rapid eye movement sleep behaviour disorder (RBD) are at substantial risk for developing Parkinson's disease (PD) or related neurodegenerative disorders. Speech is an important indicator of motor function and movement coordination, and therefore may be an extremely sensitive early marker of changes due to prodromal neurodegeneration. Speech data were acquired from 16 RBD subjects and 16 age- and sex-matched healthy control subjects. Objective acoustic assessment of 15 speech dimensions representing various phonatory, articulatory, and prosodic deviations was performed. Statistical models were applied to characterise speech disorders in RBD and to estimate sensitivity and specificity in differentiating between RBD and control subjects. Some form of speech impairment was revealed in 88% of RBD subjects. Articulatory deficits were the most prominent findings in RBD. In comparison to controls, the RBD group showed significant alterations in irregular alternating motion rates (p = 0.009) and articulatory decay (p = 0.01). The combination of four distinctive speech dimensions, including aperiodicity, irregular alternating motion rates, articulatory decay, and dysfluency, led to 96% sensitivity and 79% specificity in discriminating between RBD and control subjects. Speech impairment was significantly more pronounced in RBD subjects with the motor score of the Unified Parkinson's Disease Rating Scale greater than 4 points when compared to other RBD individuals. Simple quantitative speech motor measures may be suitable for the reliable detection of prodromal neurodegeneration in subjects with RBD, and therefore may provide important outcomes for future therapy trials. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Dissociating oral motor capabilities: Evidence from patients with movement disorders.

    Science.gov (United States)

    Staiger, Anja; Schölderle, Theresa; Brendel, Bettina; Ziegler, Wolfram

    2017-01-27

    Abnormal articulation rate is a frequent symptom in neurogenic speech disorders. Performance rates in speech-like or nonspeech tasks involving the vocal motor apparatus are commonly accepted predictors of speech motor function in general and of articulation rate in particular. However, theoretical arguments and behavioral observations in populations with disordered speech indicate that different oral motor behaviors may be governed by distinct mechanisms. The objective of the present study was to expand our knowledge of the relationship between speech movements, on the one hand, and speech-like and nonspeech oral motor behaviors, on the other, by using a rate paradigm. 130 patients with neurological movement disorders of different origins and 130 neurologically healthy subjects participated in the study. Rate data was collected in a speech task (oral reading/repetition), in speech-like tasks (rapid syllable repetitions), and in nonspeech tasks (rapid single articulator movements of the tongue/lips). The main analyses involved a multiple single-case method, by which we tested for differences among each patient's performance rates on the three task types. The results disclosed statistically significant (classical and strong) dissociations between movement rates obtained from the speech task and those obtained from speech-like and nonspeech oral motor tasks in a number of patients. The findings can be interpreted as reflecting major differences in task demands and underlying control mechanisms. The validity of diagnostic indices for speech obtained from speech-like or nonspeech tasks must thus be called into question. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease.

    Science.gov (United States)

    Wang, Pan; Wing, Yun Kwok; Xing, Jianli; Liu, Yong; Zhou, Bo; Zhang, Zengqiang; Yao, Hongxiang; Guo, Yan'e; Shang, Yanchang; Zhang, Xi

    2016-10-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by α-synuclein deposition, including Parkinson's disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer's disease (AD), a non-synucleinopathy. We recruited 105 clinically probable AD patients. Fifteen clinically probable AD patients with suspected RBD underwent a video-polysomnography (vPSG) examination. Five patients with probable AD exhibited RBD. One of the patients performed repeated touching of the head and the face with his hands and flailed his arms. Three patients exhibited hand twisting, exploring, prominent limb kicking, and jerking. The fifth patient exhibited all of the characteristics of RBD (he recalled a dream about fighting animals), and his wife was awakened by his screaming. Of these five patients, one patient took the acetylcholinesterase inhibitor drug donepezil. The patients with AD + RBD demonstrated increases in both tonic and phasic electromyography activity during REM sleep, but sleep architecture did not differ between the AD + RBD and AD-alone groups. RBD can occur in patients with AD. The occurrence of RBD does not change the sleep architecture of AD patients.

  14. The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy.

    Science.gov (United States)

    De Cock, Valérie Cochen; Debs, Rachel; Oudiette, Delphine; Leu, Smaranda; Radji, Fatai; Tiberge, Michel; Yu, Huan; Bayard, Sophie; Roze, Emmanuel; Vidailhet, Marie; Dauvilliers, Yves; Rascol, Olivier; Arnulf, Isabelle

    2011-03-01

    Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system

  15. Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha.

    Science.gov (United States)

    Ven Murthy, M R; Ranjekar, Prabhakar K; Ramassamy, Charles; Deshpande, Manasi

    2010-09-01

    nontoxic medication that normalizes physiological functions, disturbed by chronic stress, through correction of imbalances in the neuroendocrine and immune systems [9, 10]. The scientific research that has been carried out on Ashwagandha and other ayurvedic herbal medicines may be classified into three major categories, taking into consideration the endogenous or exogenous phenomena that are known to cause physiological disequilibrium leading to the pathological state; (A) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on specific non-neurological diseases; (B) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on neurodegenerative disorders; and (C) biochemical, physiological and genetic studies on the herbal plants themselves, in order to distinguish between those originating from different habitats, or to improve the known medicinal quality of the indigenous plant. Some of the major points on its use in the treatment of neurodegenerative disorders are described below.

  16. Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study.

    Science.gov (United States)

    Stefani, Ambra; Gabelia, David; Högl, Birgit; Mitterling, Thomas; Mahlknecht, Philipp; Stockner, Heike; Poewe, Werner; Frauscher, Birgit

    2015-11-15

    Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a harbinger of synuclein-mediated neurodegenerative diseases. It is unknown if this also applies to isolated REM sleep without atonia (RWA). We performed a long-term follow-up investigation of subjects with isolated RWA. Participants were recruited from 50 subjects with isolated RWA who were identified at the sleep laboratory of the Department of Neurology at the Medical University of Innsbruck between 2003 and 2005. Eligible subjects underwent follow-up clinical examination, polysomnography, and assessment of neurodegenerative biomarkers (cognitive impairment, finger speed deficit, impaired color vision, olfactory dysfunction, orthostatic hypotension, and substantia nigra hyperechogenicity). After a mean of 8.6 ± 0.9 y, 1 of 14 participating subjects (7.3%) progressed to RBD. Ten of 14 RWA subjects (71.4%) were positive for at least one neurodegenerative biomarker. Substantia nigra hyperechogenicity and presence of mild cognitive impairment were both present in 4 of 14 subjects with isolated RWA. Electromyographic activity measures increased significantly from baseline to follow-up polysomnography ("any" mentalis and both anterior tibialis muscles: 32.5 ± 9.4 versus 52.2 ± 16.6%; p = 0.004). This study provides first evidence that isolated RWA is an early biomarker of synuclein-mediated neurodegeneration. These results will have to be replicated in larger studies with longer observational periods. If confirmed, these disease findings have implications for defining at-risk cohorts for Parkinson disease. © 2015 American Academy of Sleep Medicine.

  17. Abnormal beta power is a hallmark of explicit movement control in functional movement disorders.

    Science.gov (United States)

    Teodoro, Tiago; Meppelink, Anne Marthe; Little, Simon; Grant, Robert; Nielsen, Glenn; Macerollo, Antonella; Pareés, Isabel; Edwards, Mark J

    2018-01-16

    To determine whether sensorimotor beta-frequency oscillatory power is raised during motor preparation in patients with functional movement disorders (FMD) and could therefore be a marker of abnormal "body-focused" attention. We analyzed motor performance and beta-frequency cortical oscillations during a precued choice reaction time (RT) task with varying cue validity (50% or 95% congruence between preparation and go cues). We compared 21 patients with FMD with 13 healthy controls (HCs). In HCs, highly predictive cues were associated with faster RT and beta desynchronization in the contralateral hemisphere (contralateral slope -0.045 [95% confidence interval (CI) -0.057 to -0.033] vs ipsilateral -0.033 [95% CI -0.046 to -0.021], p < 0.001) and with a tendency for reaching lower contralateral end-of-preparation beta power (contralateral -0.482 [95% CI -0.827 to -0.137] vs ipsilateral -0.328 [95% CI -0.673 to 0.016], p = 0.069). In contrast, patients with FMD had no improvement in RTs with highly predictive cues and showed an impairment of beta desynchronization and lateralization before movement. Persistent beta synchronization during motor preparation could reflect abnormal explicit control of movement in FMD. Excessive attention to movement itself rather than the goal might maintain beta synchronization and impair performance. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  18. Idiopathic REM sleep behavior disorder and neurodegenerative risk: To tell or not to tell to the patient? How to minimize the risk?

    Science.gov (United States)

    Arnaldi, Dario; Antelmi, Elena; St Louis, Erik K; Postuma, Ronald B; Arnulf, Isabelle

    2016-11-10

    Most people with idiopathic REM sleep behavior disorder (iRBD) have an underlying synucleinopathy, mainly Parkinson's disease (PD) or dementia with Lewy bodies, with median conversion time of 4-9 y from iRBD diagnosis and of 11-16 y from symptom onset. Subtle signs and imaging tests indicate concomitant neurodegeneration in widespread brain areas. Risk factor studies suggest that iRBD patients may have prior head injury, occupational farming, pesticide exposure, low education level and possibly more frequent family history of dream-enactment behavior (but not of PD), plus unexpected risk factors (smoking, ischemic heart disease and inhaled corticosteroid use). Unlike PD, caffeine and smoking appear not to have a protective role. Prior depression and antidepressant use may be early neurodegenerative signs rather than exclusively causative factors. Age, hyposmia, impaired color vision, abnormal dopaminergic imaging, mild cognitive impairment and possibly sleepiness, may identify patients at greater risk of more rapid conversion. The consensus is to generally disclose the neurodegenerative risk to patients (with the caveat that phenoconversion and its temporal course remain uncertain in individuals without "soft neurodegenerative signs" and those under 50 y of age), to suggest a healthy lifestyle and to take part in prospective cohort studies in anticipation of eventual neuroprotective trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.

    Science.gov (United States)

    Forrester, Joseph D; Kugeler, Kiersten J; Perea, Anna E; Pastula, Daniel M; Mead, Paul S

    2015-11-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.

  20. Milestones in movement disorders clinical trials: advances and landmark studies.

    Science.gov (United States)

    Olanow, C Warren; Wunderle, Kathryn B; Kieburtz, Karl

    2011-05-01

    Over the past 25 years clinical trials testing in movement disorders has evolved in order to more effectively and efficiently analyze the safety and efficacy of new interventions. Studies today regularly incorporate methods to decrease placebo and bias effects and to ensure more rigorous statistical analyses. Newer, standardized, and validated rating scales such as the Unified Parkinson's Disease Rating Scale and the Unified Huntington's Disease Rating Scale are routinely employed in an effort to produce results that are comparable across different sites and studies. Several landmark studies in movement disorder research highlight these and other prominent procedural advances. The Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial pioneered the use of functional clinical end points, utilized a 2 × 2 factorial design to more efficiently analyze multiple interventions, and employed a washout design to assist in sorting putative neuroprotective from symptomatic effects. PRECEPT included neuroimaging as an outcome measure and highlighted the importance of futility studies in more efficiently directing resources. TEMPO and ADAGIO introduced the use of delayed-start (or 2-period) trials to try to identify disease-modifying interventions. NET-PD used futility studies to streamline the evaluation of potentially valuable treatments, followed by a large, long-term simple study design to assess the clinical significance of a new intervention. There have also been advances in clinical trials testing new surgical interventions, with the introduction of blinded outcome assessments and sham-surgery control groups. Collectively, methodological advances in clinical trials have permitted the safety and efficacy of new interventions to be tested more efficiently and economically and with a higher level of certainty that the potential benefits and adverse effects of interventions recommended for general use are well understood. Copyright © 2011 Movement Disorder

  1. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001?2010

    OpenAIRE

    Forrester, Joseph D; Kugeler, Kiersten J.; Perea, Anna E.; Pastula, Daniel M.; Mead, Paul S.

    2015-01-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were i...

  2. [Neurosurgical treatment of Parkinson disease and other movement disorders].

    Science.gov (United States)

    Krauss, J K

    1997-10-04

    The surgical treatment of movement disorders has attracted widespread attention in the past few years. Better understanding of pathophysiological mechanisms, and also the refinement of neurosurgical, neuroradiological and neurophysiological methods and techniques have contributed to the redefinition of surgical treatment. With appropriate selection criteria, symptomatic and functional benefit can be achieved in the majority of patients. Functional neurosurgical procedures nowadays are performed most frequently in patients with Parkinson's disease or cervical dystonia. Functional neurosurgery today has the choice of a variety of different surgical options. The most appropriate operative technique is chosen with regard of the clinical presentation of the individual patient. The different operative procedures and the postoperative results are briefly described.

  3. Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

    Science.gov (United States)

    Yang, Zi-Jiao; Wei, Jing; Mao, Cheng-Jie; Zhang, Jin-Ru; Chen, Jing; Ji, Xiao-Yan; Liu, Jun-Yi; Shen, Yun; Xiong, Kang-Ping; Huang, Jun-Ying; Yang, Ya-Ping; Liu, Chun-Feng

    2016-12-01

    Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

  4. Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

    Science.gov (United States)

    Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

    2016-06-01

    Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

  5. Improving MRT image quality in patients with movement disorders.

    Science.gov (United States)

    Schültke, Elisabeth; Nanko, Norbert; Pinsker, Marcus; Katzev, Michael; Sebastian, Alexandra; Feige, Bernd; Nikkhah, Guido

    2013-01-01

    In order to improve image quality in a simultaneous fMRI-EEG study with patients suffering from the involuntary movements typical for Huntington's disease, the aim was to develop a technique for immobilizing the heads of our patients inside an MRI head coil. We modified a mask technique previously used for reliable repositioning in temporally fractionated radiotherapy. The mask was tested in three patients with Huntington's disease, acquiring structural and functional MR images with simultaneous EEG with and without the mask. Image as well as EEG signal quality were significantly improved in patients wearing the mask. However, the image quality with mask was comparable to acquisitions from patients without movement disorders only in patients with light to moderate dyskinesia. Although image quality was also significantly improved in a patient suffering from severe dyskinesia with quasi-continuous involuntary movements, the quality of both the MR images as well as the EEG signal was lower than what would be expected in a healthy control person. We have succeeded in developing a mask that fits into the MRI head coil, does not disturb the MRI signal, and significantly improves both fMRI and EEG signal quality.

  6. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  7. Design of a Magnetic Resonance-Safe Haptic Wrist Manipulator for Movement Disorder Diagnostics

    NARCIS (Netherlands)

    Bode, Dyon; Mugge, Winfred; Schouten, Alfred C.; van Rootselaar, Anne-Fleur; Bour, Lo J.; van der Helm, Frans C. T.; Lammertse, Piet

    2017-01-01

    Tremor, characterized by involuntary and rhythmical movements, is the most common movement disorder. Tremor can have peripheral and central oscillatory components which properly assessed may improve diagnostics. A magnetic resonance (MR)-safe haptic wrist manipulator enables simultaneous measurement

  8. [Parkinson Disease With Rapid Eye Movement Sleep Behavior Disorder].

    Science.gov (United States)

    Hu, Yang; Zhang, Wei

    2015-06-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by lack of muscle atonia during REM sleep and enactment of dream content. RBD is associated with Parkinson disease (PD) and has high incidence in PD patients. PD patient with RBD mainly presents rigid type, has longer disease duration, more severe motor and non-motor symptoms and poorer activity of daily living and life quality. The pathophysiological mechanisms of RBD may be related to dysfunctions of pontine tegmentum, locus coeruleus/sub-locus coeruleus complex and related projections. The diagnosis of RBD depends on clinical histories and video-polysomnography (v-PSG). Besides treatment for PD, protective measures have to be taken for patients and their sleep partners. If abnormal behaviors during sleep cause distress and danger,patients should be given drug therapy.

  9. Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of alzheimer disease and other selected age-related neurodegenerative disorders.

    Science.gov (United States)

    Di Domenico, Fabio; Tramutola, Antonella; Butterfield, D Allan

    2017-10-01

    Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products. One of the most abundant and cytotoxic lipid -derived aldehydes is 4-hydroxy 2-nonenal (HNE). HNE toxicity is mainly due to the alterations of cell functions by the formation of covalent adducts of HNE with proteins. A key marker of lipid peroxidation, HNE-protein adducts, were found to be elevated in brain tissues and body fluids of Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis subjects and/or models of the respective age-related neurodegenerative diseases. Although only a few proteins were identified as common targets of HNE modification across all these listed disorders, a high overlap of these proteins occurs concerning the alteration of common pathways, such as glucose metabolism or mitochondrial function that are known to contribute to cognitive decline. Within this context, despite the different etiological and pathological mechanisms that lead to the onset of different neurodegenerative diseases, the formation of HNE-protein adducts might represent the shared leit-motif, which aggravates brain damage contributing to disease specific clinical presentation and decline in cognitive performance observed in each case. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    Science.gov (United States)

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. © 2014 New York Academy of Sciences.

  11. New strategies for the treatment of Parkinson's disease hold considerable promise for future management of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Bjarkam, Carsten Reidies; Sørensen, Jens Christian; Sunde, Niels Å

    2001-01-01

    or more. Parkinson's disease ischaracterized by a massive loss of dopaminergicneurons in the substantia nigra, leading tosevere functional disturbance of the neuronalcircuitry in the basal ganglia. A thoroughdescription of basal ganglia circuitry inhealth and disease is presented. We describehow...... the functional disturbances seen inParkinson's disease may be corrected atspecific sites in this circuitry by medicaltreatment or, in advanced stages of Parkinson'sdisease, by neurosurgical methods. The latterinclude lesional surgery, neuraltransplantation and deep brain stimulation,together with future......Neurodegenerative diseases are often consideredincurable with no efficient therapies to modifyor halt the progress of disease, and ultimatelylead to reduced quality of life and to death.Our knowledge of the nervous system in healthand disease has, however, increasedconsiderably during the last...

  12. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders.

    Science.gov (United States)

    Romanucci, Mariarita; Della Salda, Leonardo

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  13. Periodic Limb Movements During Sleep Mimicking REM Sleep Behavior Disorder: A New Form of Periodic Limb Movement Disorder.

    Science.gov (United States)

    Gaig, Carles; Iranzo, Alex; Pujol, Montserrat; Perez, Hernando; Santamaria, Joan

    2017-03-01

    To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and

  14. Puckering and Blowing Facial Expressions in People With Facial Movement Disorders

    Science.gov (United States)

    Denlinger, Rachel L; VanSwearingen, Jessie M; Cohn, Jeffrey F; Schmidt, Karen L

    2008-01-01

    Background and Purpose: People with facial movement disorders are instructed to perform various facial movements as part of their physical therapy rehabilitation. A difference in the movement of the orbicularis oris muscle has been demonstrated among people without facial nerve impairments when instructed to “pucker your lips” and to “blow, as if blowing out a candle.” The objective of this study was to determine whether the within-subject difference between “pucker your lips” and “blow, as if blowing out a candle” found in people without facial nerve impairments is present in people with facial movement disorders. Subjects and Methods: People (N=68) with unilateral facial movement disorders were observed as they produced puckering and blowing movements. Automated facial image analysis of both puckering and blowing was used to determine the difference between facial actions for the following movement variables: maximum speed, amplitude, duration, and corresponding asymmetry. Results: There was a difference between the amplitudes of movement for puckering and blowing. “Blow, as if blowing out a candle” produced a larger amplitude of movement. Discussion and Conclusion: The findings demonstrate that puckering and blowing movements in people with facial movement disorders differ in a manner that is consistent with differences found in people who are healthy. This information may be useful in the assessment of and intervention for facial movement disorders affecting the lower face. PMID:18617578

  15. Rapid eye movement sleep behavior disorder in Parkinson's disease: magnetic resonance imaging study.

    Science.gov (United States)

    Ford, Andrew H; Duncan, Gordon W; Firbank, Michael J; Yarnall, Alison J; Khoo, Tien K; Burn, David J; O'Brien, John T

    2013-06-01

    Rapid eye movement sleep behavior disorder has poor prognostic implications for Parkinson's disease. The authors recruited 124 patients with early Parkinson's disease to compare clinical and neuroimaging findings based on the presence of this sleep disorder. The presence of rapid eye movement sleep behavior disorder was assessed with the Mayo Sleep Questionnaire. Magnetic resonance imaging sequences were obtained for voxel-based morphometry and diffusion tensor imaging. Patients with sleep disorder had more advanced disease, but groups had similar clinical characteristics and cognitive performance. Those with sleep disorder had areas of reduced cortical grey matter volume and white matter changes compared with those who did not have sleep disorder. However, differences were slight and were not significant when the analyses were adjusted for multiple comparisons. Rapid eye movement sleep behavior disorder was associated with subtle changes in white matter integrity and grey matter volume in patients with early Parkinson's disease. Copyright © 2013 Movement Disorder Society.

  16. Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model.

    Science.gov (United States)

    Leclair-Visonneau, Laurène; Oudiette, Delphine; Gaymard, Bertrand; Leu-Semenescu, Smaranda; Arnulf, Isabelle

    2010-06-01

    Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38-42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended

  17. Diagnosis and treatment of impulse control disorders in patients with movement disorders

    Science.gov (United States)

    Mestre, Tiago A.; Strafella, Antonio P.; Thomsen, Teri; Voon, Valerie

    2013-01-01

    Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson’s disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson’s disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease has been developed specifically for Parkinson’s disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine. PMID:23634190

  18. Diagnosis and treatment of impulse control disorders in patients with movement disorders.

    Science.gov (United States)

    Mestre, Tiago A; Strafella, Antonio P; Thomsen, Teri; Voon, Valerie; Miyasaki, Janis

    2013-05-01

    Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.

  19. Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting with a Rapid Eye Movement Sleep Behavior Disorder.

    Science.gov (United States)

    Barker, E N; Dawson, L J; Rose, J H; Van Meervenne, S; Frykman, O; Rohdin, C; Leijon, A; Soerensen, K E; Järnegren, J; Johnson, G C; O'Brien, D P; Granger, N

    2016-09-01

    Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation. To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder. Case series review. Clinical signs of neurological dysfunction began between 2 months and 5 years of age and were progressive in nature. They were characterized by episodes of marked movements during sleep, increased anxiety, noise phobia, and gait abnormalities. Magnetic resonance imaging documented symmetrical, progressively increasing, T2-weighted image intensity, predominantly within the caudate nuclei, consistent with necrosis secondary to gray matter degeneration. Abnormalities were not detected on clinicopathological analysis of blood and cerebrospinal fluid, infectious disease screening or urine metabolite screening in most cases. Postmortem examination of brain tissue identified symmetrical malacia of the caudate nuclei and axonal dystrophy within the brainstem and spinal cord. Genealogical analysis supports an autosomal recessive mode of inheritance. A degenerative encephalopathy was identified in young adult NSDTRs consistent with a hereditary disease. The prognosis is guarded due to the progressive nature of the disease, which is minimally responsive to empirical treatment. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder

    National Research Council Canada - National Science Library

    Frauscher, Birgit; Iranzo, Alex; Gaig, Carles; Gschliesser, Viola; Guaita, Marc; Raffelseder, Verena; Ehrmann, Laura; Sola, Nuria; Salamero, Manel; Tolosa, Eduardo; Poewe, Werner; Santamaria, Joan; Högl, Birgit

    2012-01-01

    Correct diagnosis of rapid eye movement sleep behavior disorder (RBD) is important because it can be the first manifestation of a neurodegenerative disease, it may lead to serious injury, and it is a well-treatable disorder...

  1. Cerebral blood flow and Aβ-amyloid estimates by WARM analysis of [11C]PiB uptake distinguish among and between neurodegenerative disorders and aging

    DEFF Research Database (Denmark)

    Rodell, Anders B.; O'Keefe, Graeme; Rowe, Christopher C.

    2017-01-01

    Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [11C]Pittsburgh Compound B ([11C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including...... metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer's disease. Methods: Previously reported images of [11C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer's Disease (AD), eight subjects with dementia......) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [11C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [11C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among...

  2. Pain in Neurodegenerative Disease : Current Knowledge and Future Perspectives

    NARCIS (Netherlands)

    de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

    2016-01-01

    Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD),

  3. [Neuropathological diagnosis of neurodegenerative and dementia diseases].

    Science.gov (United States)

    Kretzschmar, H A; Neumann, M

    2000-09-01

    Neurodegenerative and dementing disorders such as Parkinson disease and Alzheimer disease are among the most common diseases of advanced age. Despite progress in the clinical diagnosis of neurodegenerative disorders, definite diagnosis for most of these disorders is still possible only by neuropathological examination of the brain. The neuropathological diagnosis and classification of neurodegenerative disorders has made clear advances in recent years, particularly due to the results of genetic and biochemical studies, resulting in the development of new disease-specific antibodies. Internationally recognized consensus criteria for most neurodegenerative disorders allow a definite and standardized diagnosis to be made. To obtain further knowledge about the etiopathogenesis, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are needed. The project "Brain-Net" has therefore been established with the aim of setting up a German Brain and Tissue Bank for Diseases of the Central Nervous System. The project is funded by the Federal Ministry of Education and Research.

  4. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet

    NARCIS (Netherlands)

    Leen, W.G.; Mewasingh, L.; Verbeek, M.M.; Kamsteeg, E.J.; Warrenburg, B.P.C. van de; Willemsen, M.A.A.P.

    2013-01-01

    BACKGROUND: Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in

  5. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism.

    NARCIS (Netherlands)

    Steinfeld, R.; Grapp, M.; Kraetzner, R.; Dreha-Kulaczewski, S.; Helms, G.; Dechent, P.; Wevers, R.A.; Grosso, S.; Gartner, J.

    2009-01-01

    Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited

  6. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Heintz-Buschart, Anna; Pandey, Urvashi; Wicke, Tamara; Sixel-Döring, Friederike; Janzen, Annette; Sittig-Wiegand, Elisabeth; Trenkwalder, Claudia; Oertel, Wolfgang H; Mollenhauer, Brit; Wilmes, Paul

    2017-08-26

    Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement

  7. Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease.

    Science.gov (United States)

    Bayard, Sophie; Dauvilliers, Yves; Yu, Huan; Croisier-Langenier, Muriel; Rossignol, Alexia; Charif, Mahmoud; Geny, Christian; Carlander, Bertrand; Cochen De Cock, Valérie

    2014-12-01

    The relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease. Ninety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview. Half of the patients (n = 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n = 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR = 0.34, 95% CI = 0.07-1.48, P = 0.15) and polysomnographic confirmed RBD diagnoses (OR = 0.1.28, 95% CI = 0.31-5.33, P = 0.34) were not associated with impulse control disorder. In Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Depressive symptoms in neurodegenerative diseases

    Science.gov (United States)

    Baquero, Miquel; Martín, Nuria

    2015-01-01

    Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

  9. Movement disorders in adult patients with classical galactosemia.

    Science.gov (United States)

    Rubio-Agusti, Ignacio; Carecchio, Miryam; Bhatia, Kailash P; Kojovic, Maja; Parees, Isabel; Chandrashekar, Hoskote S; Footitt, Emma J; Burke, Derek; Edwards, Mark J; Lachmann, Robin H L; Murphy, Elaine

    2013-06-01

    Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long-term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross-sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty-seven patients were included. Thirty-one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients. Copyright © 2013 Movement Disorder Society.

  10. Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum.

    Science.gov (United States)

    Schreglmann, Sebastian R; Riederer, Franz; Galovic, Marian; Ganos, Christos; Kägi, Georg; Waldvogel, Daniel; Jaunmuktane, Zane; Schaller, Andre; Hidding, Ute; Krasemann, Ernst; Michels, Lars; Baumann, Christian R; Bhatia, Kailash; Jung, Hans H

    2018-01-01

    Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  11. Chronic Temporomandibular Disorders: disability, pain intensity and fear of movement.

    Science.gov (United States)

    Gil-Martínez, Alfonso; Grande-Alonso, Mónica; López-de-Uralde-Villanueva, Ibai; López-López, Almudena; Fernández-Carnero, Josué; La Touche, Roy

    2016-12-01

    The objective was to compare and correlate disability, pain intensity, the impact of headache on daily life and the fear of movement between subgroups of patients with chronic temporomandibular disorder (TMD). A cross-sectional study was conducted in patients diagnosed with chronic painful TMD. Patients were divided into: 1) joint pain (JP); 2) muscle pain (MP); and 3) mixed pain. The following measures were included: Craniomandibular pain and disability (Craniofacial pain and disability inventory), neck disability (Neck Dsiability Index), pain intensity (Visual Analogue Scale), impact of headache (Headache Impact Test 6) and kinesiophobia (Tampa Scale of Kinesiophobia-11). A total of 154 patients were recruited. The mixed pain group showed significant differences compared with the JP group or MP group in neck disability (p pain and disability (p pain and disability for the MP group (β = 0.62; p pain group, neck disability (β = 0.40; p pain and disability. Mixed chronic pain patients show greater craniomandibular and neck disability than patients diagnosed with chronic JP or MP. Neck disability predicted the variance of craniofacial pain and disability for patients with MP. Neck disability and kinesiophobia predicted the variance of craniofacial pain and disability for those with chronic mixed pain.

  12. Weight change following deep brain stimulation for movement disorders.

    Science.gov (United States)

    Strowd, Roy E; Cartwright, Michael S; Passmore, Leah V; Ellis, Thomas L; Tatter, Stephen B; Siddiqui, Mustafa S

    2010-08-01

    Patients with Parkinson's disease (PD) and essential tremor (ET) tend to lose weight progressively over years. Weight gain following deep brain stimulation (DBS) of the subthalamic nucleus (STN) for treatment of PD has been documented in several studies that were limited by small sample size and exclusive focus on PD patients with STN stimulation. The current study was undertaken to examine weight change in a large sample of movement disorder patients following DBS. A retrospective review was undertaken of 182 patient charts following DBS of the STN, ventralis intermedius nucleus of the thalamus (VIM), and globus pallidus internus (GPi). Weight was collected preoperatively and postoperatively up to 24 months following surgery. Data were adjusted for baseline weight and multivariate linear regression was performed with repeated measures to assess weight change. Statistically significant mean weight gain of 1.8 kg (2.8% increase from baseline, p = 0.0113) was observed at a rate of approximately 1 kg per year up to 24 months following surgery. This gain was not predicted by age, gender, diagnosis, or stimulation target in a multivariate model. Significant mean weight gain of 2.3 kg (p = 0.0124) or 4.2% was observed in our PD patients. Most patients with PD and ET gain weight following DBS, and this gain is not predicted by age, gender, diagnosis, or stimulation target.

  13. Relationship between movement disorders and obsessive-compulsive disorder : beyond the obsessive-compulsive-tic phenotype. A systematic review

    NARCIS (Netherlands)

    Fibbe, Lieneke A.; Cath, Danielle C.; van den Heuvel, Odile A.; Veltman, Dick J.; Tijssen, Marina A. J.; Van Balkom, Anton J. L. M.

    Background Obsessive-compulsive disorder (OCD) and symptoms (OC symptoms) are associated with tic disorders and share an aetiological relationship. The extent to which OCD/OC symptoms are correlated with other hyperkinetic movement disorders is unclear. The aim of this review was to investigate this

  14. Periodic Limb Movements during Sleep Mimicking REM Sleep Behavior Disorder.

    Science.gov (United States)

    Gaig, Carles; Iranzo, Alex; Pujo, Montserrat; Perez, Hernando; Santamaria, Joan

    2016-11-28

    prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors.

  15. The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

    Science.gov (United States)

    Lam, Virginie; Takechi, Ryusuke; Pallabage-Gamarallage, Menuka; Giles, Corey; Mamo, John C L

    2015-01-01

    Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular

  16. The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Virginie Lam

    Full Text Available Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX, or exogenous infusion of parathyroid hormone (PTH on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX and hippocampal formation (HPF. Vitamin D was also associated with increased plasma ionised calcium (iCa and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP, a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of

  17. Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders.

    Science.gov (United States)

    Wrasidlo, Wolf; Crews, Leslie A; Tsigelny, Igor F; Stocking, Emily; Kouznetsova, Valentina L; Price, Diana; Paulino, Amy; Gonzales, Tania; Overk, Cassia R; Patrick, Christina; Rockenstein, Edward; Masliah, Eliezer

    2014-12-01

    Anti-retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood-brain barrier. We screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV-gp120 neurotoxicity. Among 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 μM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology. Compounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders. © 2014 The British Pharmacological Society.

  18. Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation

    DEFF Research Database (Denmark)

    Thrane, Jens F; Sunde, Niels A; Bergholt, Bo

    2014-01-01

    Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation......Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation...

  19. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet.

    Science.gov (United States)

    Leen, Wilhelmina G; Mewasingh, Leena; Verbeek, Marcel M; Kamsteeg, Erik-Jan; van de Warrenburg, Bart P; Willemsen, Michel A

    2013-09-01

    Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in GLUT1DS. Four patients with GLUT1DS ages 15 to 30 years who had movement disorders as the most prominent feature were prospectively evaluated after initiation of the modified Atkins diet. Movement disorders included dystonia, ataxia, myoclonus, and spasticity, either continuous or paroxysmal, triggered by action or exercise. Duration of treatment ranged from 3 months to 16 months. All patients reached mild to moderate ketosis and experienced remarkable improvement in the frequency and severity of paroxysmal movement disorders. Cognitive function also improved subjectively. The modified Atkins diet is an effective and feasible alternative to the ketogenic diet for the treatment of GLUT1DS-related paroxysmal movement disorders in adolescence and adulthood. © 2013 International Parkinson and Movement Disorder Society.

  20. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2011-08-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  1. Characteristics of early- and late-onset rapid eye movement sleep behavior disorder in China: a case-control study.

    Science.gov (United States)

    Zhou, Junying; Zhang, Jihui; Du, Lina; Li, Zhe; Li, Yun; Lei, Fei; Wing, Yun-Kwok; Kushida, Clete A; Zhou, Dong; Tang, Xiangdong

    2014-06-01

    To investigate demography and clinic and polysomnographic characteristics in Chinese rapid eye movement (REM) sleep behavior disorder (RBD) patients across onset ages. Ninety consecutive patients fulfilling the criteria for RBD were recruited for study in our sleep center. Patients were separated into early- and late-onset groups according to age when symptoms began (50 years, respectively). Ninety age- and gender-matched healthy subjects served as controls. All subjects were interviewed for their clinical history, completed an RBD questionnaire, and underwent an overnight video polysomnography assessment. Demographics, comorbidities, scores on the RBD questionnaire, sleep architecture, and EMG activity were compared between the patients and controls and between the early- and late-onset groups. Of all RBD patients, 63 were male, and mean age of RBD onset was 54.3±15.7 years. In 25 patients (28%), RBD was secondary and associated with neurodegenerative disease, narcolepsy or antidepressant use. Twenty-three patients (26%) had early-onset RBD and 67 (74%) were in the late-onset group. RBD patients had significantly more comorbidities, dreams and dream-enacting behaviors, and poorer sleep quality than did controls. The early-onset group had a high proportion of females (48%) and an increased proportion of cases associated with narcolepsy. The early-onset group also had fewer movements, lower EMG activity during REM sleep, and better sleep quality when compared to the late-onset group. EMG activity was positively correlated with age of onset. The mean follow-up time was 1.57±0.82 years, and four patients in the late-onset group were subsequently diagnosed with neurodegenerative diseases. Stratifying patients into early and late-onset RBD revealed different characteristics from those previously described as typical for RBD. EMG activity during REM sleep was positively correlated with age of onset. We suggest that it will be valuable to explore the relationship

  2. Are smooth pursuit eye movements altered in chronic whiplash-associated disorders? A cross-sectional study

    DEFF Research Database (Denmark)

    Kongsted, Alice; Jørgensen, L V; Bendix, T

    2007-01-01

    To evaluate whether smooth pursuit eye movements differed between patients with long-lasting whiplash-associated disorders and controls when using a purely computerized method for the eye movement analysis.......To evaluate whether smooth pursuit eye movements differed between patients with long-lasting whiplash-associated disorders and controls when using a purely computerized method for the eye movement analysis....

  3. Technological Advances In The Surgical Treatment Of Movement Disorders

    Science.gov (United States)

    Gross, Robert E.; McDougal, Margaret E.

    2013-01-01

    Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in getting neuromodulation modalities, including DBS, to the target; and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength MRI and other innovations such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable CT scanners also are facilitating lead implantation without monitoring as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue, and in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system reflected in Œbiomarkers1 continuously recorded by the devices. Finer grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via Œcurrent steering1 algorithms. Finally, even thermocoagulation - essentially replaced by DBS - is being advanced by new Œminimally-invasive1 approaches that may improve this therapy for selected patients in whom it may be preferred. Functional neurosurgery has a history of

  4. Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders

    Directory of Open Access Journals (Sweden)

    Kara M. Smith

    2015-02-01

    Full Text Available Background: In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.Methods: A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus. Results: We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies.Discussion: Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.

  5. Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders

    Science.gov (United States)

    Smith, Kara M.; Spindler, Meredith A.

    2015-01-01

    Background In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study. Methods A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus. Results We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies. Discussion Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study. PMID:25713746

  6. Technological advances in the surgical treatment of movement disorders.

    Science.gov (United States)

    Gross, Robert E; McDougal, Margaret E

    2013-08-01

    Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional

  7. Automatic sleep scoring in normals and in individuals with neurodegenerative disorders according to new international sleep scoring criteria

    DEFF Research Database (Denmark)

    Jensen, Peter S.; Sørensen, Helge Bjarup Dissing; Jennum, P. J.

    2010-01-01

    Introduction: Reliable polysomnographic classification is the basis for evaluation of sleep disorders in neurological diseases. Aim: To develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep...... Medicine (AASM). Methods: A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic (PSG) recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance...... of the algorithm was tested using 28 manually classified day-night PSGs from 18 normal subjects and 10 patients with Parkinson's disease (PD) or multiple system atrophy (MSA). This led to quantification of automaticversus- manual epoch-by-epoch agreement rates for both normal and abnormal recordings. Results...

  8. Meditation and neurodegenerative diseases

    National Research Council Canada - National Science Library

    Newberg, Andrew B; Serruya, Mijail; Wintering, Nancy; Moss, Aleezé Sattar; Reibel, Diane; Monti, Daniel A

    2014-01-01

    .... Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive, and easy to teach and perform...

  9. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder

    NARCIS (Netherlands)

    Wortmann, S.B.; Zietkiewicz, S.; Kousi, M.; Szklarczyk, R.J.; Haack, T.B.; Gersting, S.W.; Muntau, A.C.; Rakovic, A.; Renkema, G.H.; Rodenburg, R.J.; Strom, T.M.; Meitinger, T.; Rubio-Gozalbo, M.E.; Chrusciel, E.; Distelmaier, F.; Golzio, C.; Jansen, J.H.; Karnebeek, C. van; Lillquist, Y.; Lucke, T.; Ounap, K.; Zordania, R.; Yaplito-Lee, J.; Bokhoven, H. van; Spelbrink, J.N.; Vaz, F.M.; Pras-Raves, M.; Ploski, R.; Pronicka, E.; Klein, C.; Willemsen, M.A.A.P.; Brouwer, A.P.M. de; Prokisch, H.; Katsanis, N.; Wevers, R.A.

    2015-01-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder,

  10. BRAIN PLASTICITY INVESTIGATED WITH TRANSCRANIAL MAGNETIC STIMULATION IN HEALTHY HUMANS AND IN PATIENTS WITH MOVEMENT DISORDERS

    OpenAIRE

    Suppa, Antonio

    2011-01-01

    Investigating mechanisms of short-term and long-term synaptic plasticity in primary motor cortex with the transcranial magnetic stimulation (TMS) technique in healthy subjects and in patients with different types of movement disorders.

  11. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile

    Directory of Open Access Journals (Sweden)

    Di Benedetto Giulia

    2008-09-01

    Full Text Available Abstract This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.

  12. A review of the potential role of nano-enabled drug delivery technologies in amyotrophic lateral sclerosis: lessons learned from other neurodegenerative disorders.

    Science.gov (United States)

    Mazibuko, Zamanzima; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

    2015-04-01

    Amyotrophic lateral sclerosis (ALS) has a multitude of factors implicated in its etiology. The complex neuro-etiology and the restrictive nature of the blood-brain barrier (BBB) have significantly hindered the drug therapy of ALS. Riluzole, a moderately performing drug, is the only agent approved for treating ALS. However, several promising nanocarrier approaches are surfacing that can provide more efficient drug delivery. In addition, biologicals such as stem cells are able to carry neurotrophic factors to their target site, providing motor neurons with the benefits of both, stem cells and neurotrophic factors. This review examines the current drug delivery strategies investigated for optimally treating ALS and related neurodegenerative disorders. Examples include cerium oxide nanoparticles in Alzheimer's disease, odorranalectin, and lactoferrin-coupled PEG-PLGA nanoparticles for urocortin transportation in Parkinson's disease that can also be employed in ALS to bypass the BBB and increase drug bioavailability. A concise incursion into the progress (and lack thereof) made in ALS clinical trials is also discussed. Nanocarriers can potentially eliminate the challenges of poor drug bioavailability in ALS as they have been proven to cross the BBB and reach target sites while minimizing systemic side-effects. Nanocarrier-based delivery of ALS drugs is an area that requires much needed investigation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. When Cytokinin, a Plant Hormone, Meets the Adenosine A2A Receptor: A Novel Neuroprotectant and Lead for Treating Neurodegenerative Disorders?

    Science.gov (United States)

    Huang, Chuen-Lin; Kuo, Tsun-Yung; Lin, Jung-Hsin; Yang, De-Ming; Huang, Nai-Kuei

    2012-01-01

    It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12) cells from serum deprivation-induced apoptosis by acting on the adenosine A2A receptor (A2A-R), which was blocked by an A2A-R antagonist and a protein kinase A (PKA) inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A2A-R signaling event. Since the A2A-R was implicated as a therapeutic target in treating Huntington’s disease (HD), a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt)-induced protein aggregations and proteasome deactivation through A2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders. PMID:22719969

  14. General movements : A window for early identification of children at high risk for developmental disorders

    NARCIS (Netherlands)

    Hadders-Algra, M

    Detection of children with a developmental disorder, such as cerebral palsy, at an early age is notoriously difficult. Recently, a new form of neuromotor assessment of young infants was developed, based on the assessment of the quality of general movements (GMs). GMs are movements of the fetus and

  15. Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Boot, Erik; Butcher, Nancy J.; van Amelsvoort, Thérèse A. M. J.; Lang, Anthony E.; Marras, Connie; Pondal, Margarita; Andrade, Danielle M.; Fung, Wai Lun Alan; Bassett, Anne S.

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In

  16. Construction of standardized Arabic questionnaires for screening neurological disorders (dementia, stroke, epilepsy, movement disorders, muscle and neuromuscular junction disorders

    Directory of Open Access Journals (Sweden)

    El Tallawy HN

    2016-08-01

    Full Text Available Hamdy N El Tallawy,1 Wafaa MA Farghaly,1 Tarek A Rageh,1 Ahmed O Saleh,2 Taha AH Mestekawy,3 Manal MM Darwish,4 Mohamed A Abd El Hamed,1 Anwar M Ali,1 Doaa M Mahmoud1 1Department of Neurology and Psychiatry, Faculty of Medicine, 2Psychology Department, Faculty of Education, 3Psychology Department, Faculty of Arts, 4Public Health Department, Faculty of Medicine, Assiut University, Assiut, Egypt Abstract: A screening questionnaire is an important tool for early diagnosis of neurological disorders, and for epidemiological research. This screening instrument must be both feasible and valid. It must be accepted by the community and must be sensitive enough. So, the aim of this study was to prepare different Arabic screening questionnaires for screening different neurological disorders. This study was carried out in three stages. During the first stage, construction of separate questionnaires designed for screening the five major neurological disorders: cerebrovascular stroke, dementias, epilepsy, movement disorders, and muscle and neuromuscular disorders were done. Validation of the screening questionnaires was carried out in the second stage. Finally, questionnaire preparation was done in the third stage. Questions with the accepted sensitivity and specificity in each questionnaire formed the refined separate questionnaires. Keywords: screening questionnaires, neurological disorders

  17. Mitchell's case of "pendulum spasms": psychogenic movement disorder considered as male hysteria.

    Science.gov (United States)

    Lanska, Douglas J

    2015-01-27

    In the late 19th century, a man with a psychogenic movement disorder was evaluated by many of the Philadelphia neurologists associated with Silas Weir Mitchell. In 1885, prior to the development of movie cameras or projectors, the patient was photographed by pioneering photographer Eadweard Muybridge, in collaboration with neurologist Francis Dercum, using arrays of sequentially triggered single-image cameras. The photographic sequences are among the first motion picture sequences of patients with neurologic disorders. Examination of extant primary source documents concerning this patient, including published writings and photographic sequences by Muybridge and Dercum, the original clinical descriptions, Mitchell's documentation of the patient's later clinical course, and results of the autopsy. Mitchell and his colleagues concluded that this was a "case of undoubted hysteria" in a man. Support for this contention includes the following: protracted course, spanning decades with temporary remissions; inconsistent character of the movement and features incongruous with typical "organic" tremors; complex, bizarre movements that are difficult to classify; increase in movements with attention; alteration in frequency of the movements with movement of the opposite arm; ability to trigger or temporarily stop the movements with unusual or nonphysiologic interventions; involvement of the opposite arm in a synchronous abnormal movement later in the course; remission with hypnotic suggestion; absence of other neurologic signs; and normal brain autopsy. The clinical history, serial examinations, photographic documentation, and autopsy results support Mitchell's contention that this was a case of male hysteria, or, in modern terminology, a psychogenic movement disorder. © 2015 American Academy of Neurology.

  18. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson's disease.

    Science.gov (United States)

    Wang, Yan-Hong; Samoylenko, Volodymyr; Tekwani, Babu L; Khan, Ikhlas A; Miller, Loren S; Chaurasiya, Narayan D; Rahman, Md Mostafizur; Tripathi, Lalit M; Khan, Shabana I; Joshi, Vaishali C; Wigger, Frank T; Muhammad, Ilias

    2010-04-21

    Banisteriopsis caapi, a woody vine from the Amazonian basin, is popularly known as an ingredient of a sacred drink ayahuasca, widely used throughout the Amazon as a medicinal tea for healing and spiritual exploration. The usefulness of Banisteriopsis caapi has been established for alleviating symptoms of neurological disorders including Parkinson's disease. Primary objective of this study was to develop the process for preparing standardized extracts of Banisteriopsis caapi to achieve high potency for inhibition of human monoamine oxidases (MAO) and antioxidant properties. The aqueous extracts prepared from different parts of the plant collected from different geographical locations and seasons were analyzed by HPLC for principal bioactive markers. The extracts were simultaneously tested in vitro for inhibition of human MAOs and antioxidant activity for analysis of correlation between phytochemical composition of the extracts and bioactivities. Reversed-phase HPLC with photodiode array detection was employed to profile the alkaloidal and non-alkaloidal components of the aqueous extract of Banisteriopsis caapi. The Banisteriopsis caapi extracts and standardized compositions were tested in vitro for inhibition of recombinant preparations of human MAO-A and MAO-B. In vitro cell-based assays were employed for evaluation of antioxidant property and mammalian cell cytotoxicity of these preparations. Among the different aerial parts, leaves, stems/large branches and stem bark of Banisteriopsis caapi, HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7-9) were present in high concentrations in dried bark of large branch. A library of HPLC chromatograms has also been generated as a tool for fingerprinting and authentication of the studied Banisteriopsis caapi species. The correlation between potency of MAO inhibition and antioxidant activity with the content of the main active constituents of the aqueous Banisteriopsis caapi extracts

  19. Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.

    Science.gov (United States)

    Janno, Sven; Holi, Matti; Tuisku, Katinka; Wahlbeck, Kristian

    2004-01-01

    Since most of the world's schizophrenia patients are treated with conventional antipsychotics, the authors evaluated various methods for establishing the prevalence of neuroleptic-induced movement disorders in these patients. DSM-IV criteria and established score thresholds on a movement disorder rating scale were used to identify cases of neuroleptic-induced movement disorder in a representative Estonian patient sample of 99 chronic institutionalized schizophrenia patients, 18-65 years old, treated with conventional neuroleptics (79.8%) or clozapine (20.2%). Neuroleptic-induced movement disorders according to DSM-IV criteria were found in 61.6% of the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence rates for akathisia and tardive dyskinesia were similar when either DSM-IV criteria or rating scale scores were used, but the prevalence rate for parkinsonism was much lower per DSM-IV criteria than according to rating scale score. Nearly two-thirds of chronic schizophrenia patients suffered from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse effects still impose a huge burden on the majority of neuroleptic-treated individuals with schizophrenia. The discrepancy between the standard identification methods for neuroleptic-induced movement disorder indicate the need for further research.

  20. Recent data on rapid eye movement sleep behavior disorder in patients with Parkinson disease: analysis of behaviors, movements, and periodic limb movements.

    Science.gov (United States)

    Cochen De Cock, Valérie

    2013-08-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a fascinating parasomnia in which patients are able to enact their dreams because of a lack of muscle atonia during REM sleep. RBD represents a unique window into the dream world. Frequently associated with Parkinson's disease (PD), RBD raises various issues about dream modifications in this pathology and about aggressiveness during RBD episodes in placid patients during wakefulness. Studies on these behaviors have underlined their non-stereotyped, action-filled and violent characteristics but also their isomorphism with dream content. Complex, learnt behaviors may reflect the cortical involvement in this parasomnia but the more frequent elementary movements and the associated periodic limb movements during sleep also implicate the brainstem. Surprisingly, patients with PD have an improvement of their movements during their RBD as if they were disease-free. Also not yet understood, this improvement of movement during REM sleep raises issues about the pathways involved in RBD and about the possibility of using this pathway to improve movement in PD during the day. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

  2. Proprioceptive rehabilitation of upper limb dysfunction in movement disorders: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Giovanni eAbbruzzese

    2014-11-01

    Full Text Available Movement disorders are frequently associated with sensory abnormalities. In particular, proprioceptive deficits have been largely documented in both hypokinetic (Parkinson’s disease and hyperkinetic conditions (dystonia suggesting a possible role in their pathophysiology. Proprioceptive feedback is a fundamental component of sensorimotor integration allowing effective planning and execution of voluntary movements. Rehabilitation has become an essential element in the management of patients with movement disorders and there is a strong rationale to include proprioceptive training in rehabilitation protocols focused on mobility problems of the upper limbs. Proprioceptive training is aimed at improving the integration of proprioceptive signals using task intrinsic or augmented feedback. This perspective article reviews the available evidences on the effects of proprioceptive stimulation in improving upper limb mobility in patients with movement disorders and highlights the emerging innovative approaches targeted to maximizing the benefits of exercise by means of enhanced proprioception.

  3. The diagnostic value of saccades in movement disorder patients: a practical guide and review.

    Science.gov (United States)

    Termsarasab, Pichet; Thammongkolchai, Thananan; Rucker, Janet C; Frucht, Steven J

    2015-01-01

    Saccades are rapid eye movements designed to shift the fovea to objects of visual interest. Abnormalities of saccades offer important clues in the diagnosis of a number of movement disorders. In this review, we explore the anatomy of horizontal and vertical saccades, discuss practical aspects of their examination, and review how saccadic abnormalities in hyperkinetic and hypokinetic movement disorders aid in diagnosis, with video demonstration of classic examples. Documentation of the ease of saccade initiation, range of motion and conjugacy of saccades, speed and accuracy of saccades, dynamic saccadic trajectory, and the presence or absence of saccadic intrusions and oscillations are important components of this exam. We also provide a practical algorithm to demonstrate the value of saccades in the differential diagnosis of the movement disorders patient.

  4. Shell Shock: Psychogenic Gait and Other Movement Disorders - A Film Review

    Directory of Open Access Journals (Sweden)

    Mariana Moscovich

    2013-04-01

    Full Text Available Background: The psychological pressure on soldiers during World War I (WWI and other military conflicts has resulted in many reported cases of psychogenic gait as well as other movement disorders. In this paper, psychogenic movement disorders captured in the WWI film footage "War Neuroses" is reanalyzed. Methods: Two movement disorders specialists re-examined film images of 21 WWI patients with various and presumed psychogenic manifestations, pre- and post treatment. The film was recorded by Arthur Hurst, a general physician with an interest in neurology. Results: All 21 subjects were males, and all presented with symptoms relating to war trauma or a psychological stressor (e.g., being buried, shrapnel wounds, concussion, or trench fever. The most common presenting feature was a gait disorder, either pure or mixed with another movement disorder (15, followed by retrograde amnesia (2, abnormal postures (pure dystonia (1, facial spasm (1, head tremor (1, "hyperthyroidism-hyperadrenalism" (1. Nineteen patients received treatment, and the treatment was identified in nine cases. In most cases, treatment was short and patients improved almost immediately. Occupational therapy was the most common treatment. Other effective methods were hypnosis (1, relaxation (1, passive movements (2, and probable "persuasion and re-education" (6. Discussion: The high success rate in treating psychogenic disorders in Hurst's film would be considered impressive by modern standards, and has raised doubt in recent years as to whether parts of the film were staged and/or acted.

  5. Fixing the Mirrors: A Feasibility Study of the Effects of Dance Movement Therapy on Young Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Koch, Sabine C.; Mehl, Laura; Sobanski, Esther; Sieber, Maik; Fuchs, Thomas

    2015-01-01

    From the 1970s on, case studies reported the effectiveness of therapeutic mirroring in movement with children with autism spectrum disorder. In this feasibility study, we tested a dance movement therapy intervention based on mirroring in movement in a population of 31 young adults with autism spectrum disorder (mainly high-functioning and…

  6. Subjective sleep quality and suggested immobilization test in restless leg syndrome and periodic limb movement disorder.

    Science.gov (United States)

    Inoue, Yuichi; Nanba, Kazuyoshi; Honda, Yutaka; Takahashi, Yasuro; Arai, Heii

    2002-06-01

    The severity of restless leg syndrome (RLS) and/or periodic limb movement disorder (PLMD) was investigated by using a suggested immobilization test (SIT) and by measuring the influence of these disorders on the subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and those with both RLS and PLMD showed remarkably high values for PSQI and SIT, whereas patients with PLMD only showed normal values for PSQI. These findings suggest that there is only a small pathological significance for periodic limb movements, and demonstrate the efficacy of SIT and PSQI for evaluating the severity of these disorders.

  7. Longitudinal Study of Neurodegenerative Disorders

    Science.gov (United States)

    2018-01-31

    MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

  8. Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

    Science.gov (United States)

    Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Guaita, Marc; Salamero, Manel; Santamaria, Joan

    2017-04-01

    To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs.

  9. Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

    Science.gov (United States)

    Zueva, Marina V.

    2015-01-01

    The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

  10. Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation

    OpenAIRE

    Christianne Martins Corrêa da Silva Bahia; João Santos Pereira

    2015-01-01

    Sleep disorders are common during the clinical course of the main neurodegenerative diseases. Among these disorders, obstructive sleep apnea has been extensively studied in the last decade and recent knowledge regarding its relationship with the neurodegenerative process points a bidirectional relationship. Neurodegenerative diseases can lead to functional changes in the respiratory system that facilitate the emergence of apnea. On the other hand, obstructive sleep apnea itself can lead to ac...

  11. Quality of life in patients with an idiopathic rapid eye movement sleep behaviour disorder in Korea.

    Science.gov (United States)

    Kim, Keun Tae; Motamedi, Gholam K; Cho, Yong Won

    2017-08-01

    There have been few quality of life studies in patients with idiopathic rapid eye movement sleep behaviour disorder. We compared the quality of life in idiopathic rapid eye movement sleep behaviour disorder patients to healthy controls, patients with hypertension, type 2 diabetes mellitus without complication and idiopathic restless legs syndrome. Sixty patients with idiopathic rapid eye movement sleep behaviour disorder (24 female; mean age: 61.43 ± 8.99) were enrolled retrospectively. The diagnosis was established based on sleep history, overnight polysomnography, neurological examination and Mini-Mental State Examination to exclude secondary rapid eye movement sleep behavior disorder. All subjects completed questionnaires, including the Short Form 36-item Health Survey for quality of life. The total quality of life score in idiopathic rapid eye movement sleep behaviour disorder (70.63 ± 20.83) was lower than in the healthy control group (83.38 ± 7.96) but higher than in the hypertension (60.55 ± 24.82), diabetes mellitus (62.42 ± 19.37) and restless legs syndrome (61.77 ± 19.25) groups. The total score of idiopathic rapid eye movement sleep behaviour disorder patients had a negative correlation with the Pittsburg Sleep Quality Index (r = -0.498, P Health Survey score and the Insomnia Severity Index (β = -1.100, P = 0.001) and Beck Depression Inventory-2 (β = -1.038, P sleep behaviour disorder had a significant negative impact on quality of life, although this effect was less than that of other chronic disorders. This negative effect might be related to a depressive mood associated with the disease. © 2016 European Sleep Research Society.

  12. Eye movement in unipolar depression and bipolar disorders: A systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Nicolas eCarvalho

    2015-12-01

    Full Text Available Background:The analysis of eye movements (EM by eye-tracking has been carried out for several decades to investigate mood regulation, emotional information processing, and psychomotor disturbances in depressive disorders. Method:A systematic review of all English language PubMed articles using the terms saccadic eye movements OR eye-tracking AND depression OR bipolar disorders was conducted using PRISMA guidelines. The aim of this review was to identify the specific alterations of EM in unipolar and bipolar disorders. Results:Unipolar depression has been characterized by an increase in reaction time in prosaccade and antisaccade tasks, and a specific attraction for negative pictures. Bipolar disorders have been associated with an increase in reaction time in prosaccade and antisaccade tasks, and an attraction for threatening images. Methodological limitations include mixed samples sometimes undifferentiating unipolar and bipolar patients, or an absence of specification regarding the polarity of the episode in bipolar disorders. Moreover, we found no study explicitly comparing EM in both unipolar depression and bipolar disorders.Conclusion: Unipolar depression and bipolar disorders can be characterized by different psychomotor alterations and affective regulation strategies. Eye movement analysis could be a useful tool as a potential biomarker to distinguish between the two diseases. However, further research is needed to directly and systematically compare eye movement data in both diseases under strictly identical experimental conditions.

  13. The Neuropsychiatry of Hyperkinetic Movement Disorders: Insights from Neuroimaging into the Neural Circuit Bases of Dysfunction

    Directory of Open Access Journals (Sweden)

    Bradleigh D. Hayhow

    2013-09-01

    Full Text Available Background: Movement disorders, particularly those associated with basal ganglia disease, have a high rate of comorbid neuropsychiatric illness.Methods: We consider the pathophysiological basis of the comorbidity between movement disorders and neuropsychiatric illness by 1 reviewing the epidemiology of neuropsychiatric illness in a range of hyperkinetic movement disorders, and 2 correlating findings to evidence from studies that have utilized modern neuroimaging techniques to investigate these disorders. In addition to diseases classically associated with basal ganglia pathology, such as Huntington disease, Wilson disease, the neuroacanthocytoses, and diseases of brain iron accumulation, we include diseases associated with pathology of subcortical white matter tracts, brain stem nuclei, and the cerebellum, such as metachromatic leukodystrophy, dentatorubropallidoluysian atrophy, and the spinocerebellar ataxias.Conclusions: Neuropsychiatric symptoms are integral to a thorough phenomenological account of hyperkinetic movement disorders. Drawing on modern theories of cortico-subcortical circuits, we argue that these disorders can be conceptualized as disorders of complex subcortical networks with distinct functional architectures. Damage to any component of these complex information-processing networks can have variable and often profound consequences for the function of more remote neural structures, creating a diverse but nonetheless rational pattern of clinical symptomatology.

  14. Use of Botulinum Neurotoxin for the Treatment of Movement Disorders

    Science.gov (United States)

    ... this disorder. Will BoNT help my facial spasms (hemifacial spasms)? There is good evidence that BoNT injection is useful in treating hemifacial spasms. People with hemifacial spasms who have had BoNT ...

  15. The parasomnias and other sleep-related movement disorders

    National Research Council Canada - National Science Library

    Thorpy, Michael J; Plazzi, Giuseppe

    2010-01-01

    .... With increasing awareness of abnormal behaviors in sleep, the book fulfils the need for in-depth descriptions of clinical and research aspects of these disorders, including differential diagnosis...

  16. Impaired sense of agency in functional movement disorders: An fMRI study.

    Directory of Open Access Journals (Sweden)

    Fatta B Nahab

    Full Text Available The sense of agency (SA is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders.

  17. More Than Ataxia: Hyperkinetic Movement Disorders in Childhood Autosomal Recessive Ataxia Syndromes

    Science.gov (United States)

    Pearson, Toni S.

    2016-01-01

    Background The autosomal recessive ataxias are a heterogeneous group of disorders that are characterized by complex neurological features in addition to progressive ataxia. Hyperkinetic movement disorders occur in a significant proportion of patients, and may sometimes be the presenting motor symptom. Presentations with involuntary movements rather than ataxia are diagnostically challenging, and are likely under-recognized. Methods A PubMed literature search was performed in October 2015 utilizing pairwise combinations of disease-related terms (autosomal recessive ataxia, ataxia–telangiectasia, ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia type 2 (AOA2), Friedreich ataxia, ataxia with vitamin E deficiency), and symptom-related terms (movement disorder, dystonia, chorea, choreoathetosis, myoclonus). Results Involuntary movements occur in the majority of patients with ataxia–telangiectasia and AOA1, and less frequently in patients with AOA2, Friedreich ataxia, and ataxia with vitamin E deficiency. Clinical presentations with an isolated hyperkinetic movement disorder in the absence of ataxia include dystonia or dystonia with myoclonus with predominant upper limb and cervical involvement (ataxia–telangiectasia, ataxia with vitamin E deficiency), and generalized chorea (ataxia with oculomotor apraxia type 1, ataxia-telangiectasia). Discussion An awareness of atypical presentations facilitates early and accurate diagnosis in these challenging cases. Recognition of involuntary movements is important not only for diagnosis, but also because of the potential for effective targeted symptomatic treatment. PMID:27536460

  18. Determination of range of mandibular movements in children without temporomandibular disorders.

    Science.gov (United States)

    Cortese, Silvina G; Oliver, Liliana M; Biondi, Ana María

    2007-07-01

    Mandibular movement values are an important parameter within the clinical evaluation of the temporomandibular joint. Limited or increased movement is a sign of dysfunction. Normal values used as reference correspond to adult populations, and information on child populations is scant. The aim of this study was to establish reference measurements of children with primary (Group A) and mixed dentition (Group B) without signs of temporomandibular disorders. The study population comprised 212 boys and girls, aged 3 to 11 years, attending a state school in the San Martin district in the province of Buenos Aires, who presented no joint sounds, clicking or pain. A calibrated operator determined maximal opening, protrusion, and lateral movements. Group A (n=105): mean age 4.61+/-0.9; maximal opening 38.59 mm +/- 4.03; protrusion 3.71 mm+/-1.79; right lateral movement 5.43 mm+/-1.83 and left lateral movement 5.52 mm +/- 1.73. Group B (n= 107): mean age 6.9+/-1.65; maximal opening 41.97 mm +/- 5.27; protrusion 3.96 mm+/-1.92; right lateral movement 6.05 mm+/-1.99 and left lateral movement 6.13 mm+/-2.21. Opening and lateral movements were found to increase with age. Comparison between groups using Welch t Test showed significant differences in maximal opening (pmovement. Mandibular movements are associated with growth. Mandibular movements of pediatric patients must be assessed in relation to age and type of dentition.

  19. Acute Movement Disorder as a Presenting Feature of Hyperglycemia

    African Journals Online (AJOL)

    The female patients had blood sugar levels of 8.1mmol/L, 8.9mm 13.5 mmol/L, and 16.3 mmol/L, respectively. The males had blood sugar levels of 11.5 and 14 mmol/L, respectively. Four (4) of the patients recovered completely from involuntary movements following good glycaemic control and use of haloperidol or ...

  20. Disrupted rapid eye movement sleep predicts poor declarative memory performance in post-traumatic stress disorder.

    Science.gov (United States)

    Lipinska, Malgorzata; Timol, Ridwana; Kaminer, Debra; Thomas, Kevin G F

    2014-06-01

    Successful memory consolidation during sleep depends on healthy slow-wave and rapid eye movement sleep, and on successful transition across sleep stages. In post-traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post-traumatic stress disorder. We recruited three matched groups of participants: post-traumatic stress disorder (n = 16); trauma-exposed non-post-traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep-adapted electroencephalography. Post-traumatic stress disorder-diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post-traumatic stress disorder-diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post-traumatic stress disorder-diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post-traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post-traumatic stress disorder. © 2014 European Sleep Research Society.

  1. Neuropsychological profile of psychogenic jerky movement disorders : Importance of evaluating non-credible cognitive performance and psychopathology

    NARCIS (Netherlands)

    Heintz, Carolien E. J.; van Tricht, Mirjam J.; van der Salm, Sandra M. A.; van Rootselaar, A. F.; Cath, Danielle; Schmand, Ben; Tijssen, Marina A. J.

    2013-01-01

    Background Psychogenic movement disorders are disorders of movements that cannot be explained by a known neurological disorder and are assumed to be associated with psychiatric symptoms such as depression and anxiety. Objective To examine the neuropsychological profile of patients with psychogenic

  2. Coenzyme Q10 effects in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Meredith Spindler

    2009-11-01

    Full Text Available Meredith Spindler1, M Flint Beal1,2, Claire Henchcliffe1,21Department of Neurology, 2Department of Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Coenzyme Q10 (CoQ10 is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.Keywords: coenzyme Q10, neurodegenerative disease, Parkinson’s disease, Huntington’s disease, mitochondrial dysfunction

  3. Impaired visual perception in rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Plomhause, Lucie; Dujardin, Kathy; Boucart, Muriel; Herlin, Virginie; Defebvre, Luc; Derambure, Philippe; Monaca Charley, Christelle

    2014-05-01

    Patients with idiopathic REM sleep behavior disorder (iRBD) often develop synucleinopathies (Parkinson's disease [PD], in particular). Cognitive disorders affecting different domains have been reported in patients with iRBD. Dysexecutive disorders seem to predominate, but there is no consensus on the nature of visuospatial disorders in iRBD. The objective is to identify and characterize visuospatial disorders in patients with REM sleep behavior disorder (RBD - either idiopathic or associated with PD). Fifteen patients with iRBD, 30 patients with PD (15 of whom had RBD), and 20 healthy control subjects underwent an extensive assessment of visuospatial functions. Two computerized tasks were used: a Biederman task (to assess the 3 levels of visuoperceptive processing) and a Posner paradigm (to assess visual attention). The visual priming effects classically described for the Biederman task in healthy controls were not found in iRBD patients. Patients with iRBD were no quicker in naming objects with the same general structure as previously presented objects but did have a normal priming effect for strictly identical objects. Parkinson's disease patients with RBD had poorer visuoperceptive performance levels than PD patients without RBD. There were no significant differences between the 4 groups in the Posner attentional task. First, this study confirms the presence of visuoperceptive dysfunction in iRBD patients and revealed a selective defect in intermediate visuoperceptive processing (i.e., general object representation). Second, RBD in PD appeared to be associated with poorer visuoperceptive abilities. Third, this visuoperceptive dysfunction in RBD patients was not associated with impaired attention.

  4. Lysosomal dysfunction in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Klaudia Tomala

    2017-05-01

    Full Text Available Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

  5. Deep Learning for Automatic Stereotypical Motor Movement Detection using Wearable Sensors in Autism Spectrum Disorders

    OpenAIRE

    Rad, Nastaran Mohammadian; Kia, Seyed Mostafa; Zarbo, Calogero; van Laarhoven, Twan; Jurman, Giuseppe; Venuti, Paola; Marchiori, Elena; Furlanello, Cesare

    2017-01-01

    Autism Spectrum Disorders are associated with atypical movements, of which stereotypical motor movements (SMMs) interfere with learning and social interaction. The automatic SMM detection using inertial measurement units (IMU) remains complex due to the strong intra and inter-subject variability, especially when handcrafted features are extracted from the signal. We propose a new application of the deep learning to facilitate automatic SMM detection using multi-axis IMUs. We use a convolution...

  6. Kalman Smoothing and Wavelet Analysis for Inertial Data of Human Movement Disorder Motion

    Directory of Open Access Journals (Sweden)

    Wesley TESKEY

    2010-05-01

    Full Text Available Human movement disorders examined include essential tremor and Parkinson’s disease; both disorders feature possible uncontrollable tremor. In most literature, limited numbers of inertial sensors (accelerometers and gyroscopes are used when examining movement disorder subjects for purposes of diagnosis and attenuation (active mitigation and consequently a full rendering of motion (and tremor for subjects is not possible. The examination carried out for this work utilizes six inertial sensors capable of rendering all six degrees-of-freedom of motion with the assistance of Kalman smoothing. Because of this full rendering of motion, movement patterns largely unexamined by other researchers are visible. Key findings are that the measured frequency content of motion (displayed using wavelets is largely unaffected by the axis of measurement or by whether lateral or rotational motion is being measured, as well, accelerometers are largely unaffected by rotational tremor even though some measured frequency content would be expected due to gravity’s influence.

  7. Complex regional pain syndrome in children: a systematic review of clinical features and movement disorders.

    Science.gov (United States)

    Abu-Arafeh, Hashem; Abu-Arafeh, Ishaq

    2017-03-01

    To ascertain clinical features of complex regional pain syndrome (CRPS) in children with a focus on movement disorders. all publications with original data on children with CRPS were assessed. Data were tabulated and descriptive statistics were applied. One population-based study and nine clinic-based studies provided data on demographic and clinical characteristics of childhood CRPS. Mean age of onset was 12.5 years and 85% of patients were females (risk ratio: 1.70; 95% CI: 1.54-1.88). History of trauma in 71% and the lower limbs were affected in 75% of patients. A secondary site involvement was present in 15%. Movement disorders and dystonia were reported in 30% of children. Majority of cases of CRPS in children are females with mean age of 12.5 years. Movement disorders (mainly dystonia) affect at least one in three children with CRPS.

  8. Effectiveness of an Inpatient Movement Disorders Program for Patients with Atypical Parkinsonism

    Directory of Open Access Journals (Sweden)

    Anna D. Hohler

    2012-01-01

    Full Text Available This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM, timed up and go test (TUG, two-minute walk test (TMW, Berg balance scale (BBS and finger tapping test (FT, and all showed significant improvement on discharge (>.001. Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status.

  9. Pial Synangiosis Ameliorates Movement Disorders in the Absence of Prior Stroke in Moyamoya Disease.

    Science.gov (United States)

    Greene, Stephanie; Bansal, Lalit; Coffman, Keith A; Nardone, Raffaele; Zuccoli, Giulio

    2016-04-01

    Moyamoya disease is a rare cerebrovascular disease characterized by progressive stenosis of the bilateral distal internal carotid arteries and their proximal branches. Both chorea and dystonia have been reported as the initial presentation of moyamoya disease. The objective was to define the clinical presentation and describe the disease course following pial synangiosis of 3 patients with dyskinesias. A retrospective chart review of 3 cases of patients presenting with movement disorders and ultimately diagnosed with moyamoya disease was performed. The authors present a case series of 1 patient with dystonia and 2 patients with chorea, all diagnosed with moyamoya disease. All patients experienced resolution of their movement disorders following pial synangiosis. Magnetic resonance imaging disclosed moyamoya disease-related basal ganglia anomalies in all patients. Moyamoya disease is an important and surgically treatable cause of movement disorders. © The Author(s) 2015.

  10. A boy infant with sleep related rhythmic movement disorder showing arm banging.

    Science.gov (United States)

    Kohyama, Jun; Takano, Tomoyuki

    2014-09-01

    To present a male patient who performed arm banging on his face during sleep every night since 7 months of age. Clinical course of this patient with electroencephalographic recording with video recording at 23 months of age was shown. His arm banging began at the age of 7 months and showed no complete remission at the age of 57 months of age, although clonazepam revealed mild effects on its intensity and frequency. We diagnosed him as having arm banging type of sleep related rhythmic movement disorder. To our knowledge, no precise description on this type of sleep related rhythmic movement disorder has been found. In addition, this patient seemed to be the youngest case of sleep related rhythmic movement disorder showing arm banging.

  11. Coping Strategies and IQ in Psychogenic Movement Disorders and Paralysis

    NARCIS (Netherlands)

    van Beilen, M.; Griffioen, Brecht T.; Leenders, Klaus L.

    2009-01-01

    Inadequate coping strategies may cause some patients to develop psychogenic symptoms in periods of stress. This may be more prominent in patients with lower intelligence levels. Twenty-six patients with psychogenic neurological disorders (PND) were tested for coping abilities and intelligence and

  12. Eye movement abnormalities in AQP4-IgG positive neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Sun, Houliang; Cui, Shilei; Gao, Fei; You, Qisheng; Li, Yong; Wang, Jiawei; Zhang, Xiaojun

    2018-01-15

    Neuromyelitis optica spectrum disorder (NMOSD) has been recognized as a disease characterized by severe visual afferent impairment. Abnormal eye movements, as the other important neuro-ophthalmic manifestation of NMOSD, were commonly overlooked. The aim of our study was to describe the ocular motor manifestations of AQP4-IgG positive NMOSD patients, and explore the value of eye movement abnormalities in the evaluation of the disabled disease. Systemic clinical bedside ocular motor examinations and quantitative horizontal saccadic eye movement assessments were performed in 90 patients with AQP4-IgG positive NMOSD. General disability was evaluated by expanded disability status scale (EDSS). Vision-specific functional status was evaluated by the National Eye Institute-Visual Function Questionnaire (NEI-VFQ 25) and the 10-item neuro-ophthalmic supplement. Brain magnetic resonance imaging (MRI) was acquired in all patients. In clinical examination, eye movement abnormalities were found in 38% of NMOSD patients. Abnormalities in the quantitative saccadic test were found in 67% of NMOSD patients, including 48% of patients with clinically normal eye movements. EDSS scores in patients with clinical eye movement abnormality were significantly higher (Peye movement abnormalities (P=0.031). Eye movement abnormalities were common in AQP4-IgG positive NMOSD patients, and were associated with general disability and specific visual handicap. The systemic clinical eye movement examination combined with the quantitative saccade test was easy to perform, and could provide additional useful information in evaluating NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. "We Dance and Find Each Other"1: Effects of Dance/Movement Therapy on Negative Symptoms in Autism Spectrum Disorder

    National Research Council Canada - National Science Library

    Malin K Hildebrandt; Sabine C Koch; Thomas Fuchs

    2016-01-01

    .... The randomized controlled trial at hand investigated the effects of a 10-week manualized dance and movement therapy intervention on negative symptoms in participants with autism spectrum disorder...

  14. Compounded analgesic therapy for disorders of movement: arthritis, neuropathic pain, and postpolio syndrome.

    Science.gov (United States)

    Brown, Scott; Erickson, Brian; Muller, George; Bryant-Snure, Susan J; Mestayer, Richard F

    2010-01-01

    Pain caused by disorders of movement is often chronic and severe and may not be alleviated by commercially available medications. In such cases, the use of a compounded formulation can provide relief, either as sole therapy or as part of a combination treatment regimen. In this report, we review the effects of compounded analgesic preparations on chronic severe pain like that produced by arthritis, neuropathy, or postpolio syndrome. Case reports are included, formulations are presented, and two patients (one of whom, RFM III, is a coauthor of this paper) with a painful movement disorder describe their response to custom compounded therapy.

  15. Evolution of Movement Disorders Surgery Leading to Contemporary Focused Ultrasound Therapy for Tremor.

    Science.gov (United States)

    Ahmed, Hena; Field, Wesley; Hayes, Michael T; Lopez, William Omar Contreras; McDannold, Nathan; Mukundan, Srinivasan; Tierney, Travis S

    2015-11-01

    Progressively less invasive neurosurgical approaches for the treatment of movement disorders have evolved, beginning with open craniotomy for placement of lesions within pyramidal structures followed by refined stereotactic ablation of extrapyramidal targets that encouraged nondestructive electrode stimulation of deep brain structures. A noninvasive approach using transcranial high-energy focused ultrasound has emerged for the treatment of intractable tremor. The ability to target discreet intracranial sites millimeters in size through the intact skull using focused acoustic energy marks an important milestone in movement disorders surgery. This article describes the evolution of magnetic resonance-guided focused ultrasound for ventrolateral thalamotomy for tremor. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation

    Directory of Open Access Journals (Sweden)

    Christianne Martins Corrêa da Silva Bahia

    Full Text Available Sleep disorders are common during the clinical course of the main neurodegenerative diseases. Among these disorders, obstructive sleep apnea has been extensively studied in the last decade and recent knowledge regarding its relationship with the neurodegenerative process points a bidirectional relationship. Neurodegenerative diseases can lead to functional changes in the respiratory system that facilitate the emergence of apnea. On the other hand, obstructive sleep apnea itself can lead to acceleration of neuronal death due to intermittent hypoxia. Considering that obstructive sleep apnea is a potentially treatable condition, its early identification and intervention could have a positive impact on the management of patients with neurodegenerative diseases.

  17. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Edyta Paczkowska

    that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

  18. Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

  19. Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire.

    Science.gov (United States)

    Bolitho, Samuel J; Naismith, Sharon L; Terpening, Zoe; Grunstein, Ron R; Melehan, Kerri; Yee, Brendon J; Coeytaux, Alessandra; Gilat, Moran; Lewis, Simon J G

    2014-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty-six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self-report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society.

  20. Sleep and neurodegenerative diseases.

    Science.gov (United States)

    Chokroverty, Sudhansu

    2009-09-01

    Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can result in fatigue, irritability, morning headaches, impaired motor and cognitive skills, depression, and daytime somnolence. The major sleep complaints include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic mechanisms of sleep disturbances may be secondary to direct structural alteration of the sleep-wake generating neurons or from several other indirect mechanisms. At the biochemical level, neurodegenerative diseases may be largely classified as tauopathies, alpha-synucleinopathies, and other diseases. Overnight polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and actigraphy are some important diagnostic laboratory tests in the evaluation of sleep disturbances. Management of sleep disturbances is complex and is based primarily on the nature of the sleep disturbance. The clinical profiles, pathogenetic mechanisms, PSG findings, and management issues are discussed here with reference to some common neurodegenerative diseases. Thieme Medical Publishers.

  1. Review and update of involuntary facial movement disorders presenting in the ophthalmological setting.

    Science.gov (United States)

    Ross, Adam H; Elston, John S; Marion, Marie-Helene; Malhotra, Raman

    2011-01-01

    We review the existing literature on the involuntary facial movement disorders-benign essential blepharospasm, apraxia of eyelid opening, hemifacial spasm, and aberrant facial nerve regeneration. The etiology of idiopathic blepharospasm, a disorder of the central nervous system, and hemifacial spasm, a condition involving the facial nerve of the peripheral nervous system, is markedly different. We discuss established methods of managing patients and highlight new approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Post-traumatic stress disorder: neurobiology and effects of eye movement desensitization and reprocessing

    OpenAIRE

    Högberg, Göran

    2008-01-01

    The aim of this study was to evaluate a new psychotherapy method, eye movement desensitization and reprocessing (EMDR) in the treatment of post-traumatic stress disorder (PTSD) and to study the biological reactions in PTSD during a script-driven symptom provocation. PTSD is a disorder that may occur after a major psychological trauma. It is characterised by the phenomenon of reliving, bringing the person back to the sensations and reactions that prevailed during the traumat...

  3. [Functional models of movement disorders of basal ganglia origin and effects of functional neurosurgery].

    Science.gov (United States)

    Hashimoto, Takao

    2007-01-01

    The rate model regarding the development of movement disorders of basal ganglia origin suggests that hyperkinetic and hypokinetic disorders occur as a result of changes in the firing rates in the GPi and SNr, which in turn suppress thalamocortical output. Dopamine depletion in Parkinson's disease increases basal ganglia output, then decreases thalamocortical output, leading to bradykinesia. This model, however, cannot explain a lack of deterioration of parkinsonian signs following thalamic coagulation surgery. Instead of the rate model, the beta oscillation hypothesis has been proposed, explaining that synchronized oscillation in the beta frequency in the basal ganglia disturbs initiation of voluntary movement. We observed that effective high-frequency STN stimulation in parkinsonian monkeys was associated with increase in the firing rate and the pattern shift from irregular burst firing to regular high-frequency firing in the projecting sites. High-frequency neural activation by deep brain stimulation is supposed to cancel lower frequency oscillation including beta oscillation, leading to improvement of bradykinesia. Our observation supports the significance of the neural activity pattern, rather than the tonic activity level, in the development of movement disorders. The rate model cannot explain the improvement of ballismus and chorea by pallidotomy because pallidotomy increases the disinhibition of the thalamocortical projection, which should increase the movements. We observed repetitive bursts or pauses of neuronal firing of the globus pallidus synchronized to ballistic movements in patients with hemiballism or chorea, suggesting that phasic neuronal driving in the basal ganglia is important as their pathophysiology.

  4. Expression of prion protein in the cerebrospinal fluid of patients with Parkinson's disease complicated with rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Zhang, W J; Shang, X L; Peng, J; Zhou, M H; Sun, W J

    2017-01-23

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases and mainly manifests with decreasing numbers of dopaminergic neurons. Rapid eye movement (REM) sleep behavior disorder (RBD) has an incidence of 15-47% in all PD patients. Prion proteins (PrPs), which are expressed in both neurons and glial cells of the brain, are believed to be correlated with abnormal neurological functions, although their role in PD-related sleeping disorders remains unclear. We therefore investigated the expressional profiles of PrP in PD patients with RBD. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein levels of PrP, respectively, in the cerebrospinal fluid (CSF) of PD patients with RBD, PD patients without sleeping disorder, and healthy people (N = 23 each). We investigated the correlation between the CSF PrP level and sleeping behavior in PD patients. Patients with PD complicated with RBD had significantly elevated CSF PrP expression levels (both mRNA and protein) compared with either PD patients without sleeping disorder or healthy individuals (P < 0.05 in both cases). There is elevated expression of PrP in the CSF of PD patients with RBD. This may benefit the diagnosis of PD-related RBD.

  5. MicroRNAs in Experimental Models of Movement Disorders

    Directory of Open Access Journals (Sweden)

    Soon-Tae Lee

    2011-10-01

    Full Text Available MicroRNAs (miRNAs are small RNAs comprised of 20–25 nucleotides that regulates gene expression by inducing translational repression or degradation of target mRNA. The importance of miRNAs as a mediator of disease pathogenesis and therapeutic targets is rapidly emerging in neuroscience, as well as oncology, immunology, and cardiovascular diseases. In Parkinson’s disease and related disorders, multiple studies have identified the implications of specific miRNAs and the polymorphisms of miRNA target genes during the disease pathogenesis. With a focus on Parkinson’s disease, spinocerebellar ataxia, hereditary spastic paraplegia, and Huntington’s disease, this review summarizes and interprets the observations, and proposes future research topics in this field.

  6. Rapid eye movement sleep behavior disorder--diagnostik, årsager og behandling

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul Jørgen

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...

  7. An Eye-Movement Study of Relational Memory in Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Ring, Melanie; Bowler, Dermot M.; Gaigg, Sebastian B.

    2017-01-01

    Persons with Autism Spectrum Disorder (ASD) demonstrate good memory for single items but difficulties remembering contextual information related to these items. Recently, we found compromised explicit but intact implicit retrieval of object-location information in ASD (Ring et al. "Autism Res" 8(5):609-619, 2015). Eye-movement data…

  8. Acute movement disorder with bilateral basal ganglia lesions in diabetic uremia

    Directory of Open Access Journals (Sweden)

    Gurusidheshwar M Wali

    2011-01-01

    Full Text Available Acute movement disorder associated with symmetrical basal ganglia lesions occurring in the background of diabetic end stage renal disease is a recently described condition. It has distinct clinico-radiological features and is commonly described in Asian patients. We report the first Indian case report of this potentially reversible condition and discuss its various clinico-radiological aspects.

  9. Complex regional pain syndrome related movement disorders : studies on pathophysiology and therapy.

    NARCIS (Netherlands)

    Munts, Alexander Gerard

    2011-01-01

    Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterised by pain and disturbed blood flow, temperature regulation and motor control. Knowledge on CRPS and its movement disorders is scarce. Dysfunction in small nerve fiber processing was found in CRPS

  10. Stability and Composition of Functional Synergies for Speech Movements in Children with Developmental Speech Disorders

    Science.gov (United States)

    Terband, H.; Maassen, B.; van Lieshout, P.; Nijland, L.

    2011-01-01

    The aim of this study was to investigate the consistency and composition of functional synergies for speech movements in children with developmental speech disorders. Kinematic data were collected on the reiterated productions of syllables spa(/spa[image omitted]/) and paas(/pa[image omitted]s/) by 10 6- to 9-year-olds with developmental speech…

  11. The Use of Video Clips in Teleconsultation for Preschool Children With Movement Disorders

    NARCIS (Netherlands)

    Gorter, Hetty; Lucas, Cees; Groothuis-Oudshoorn, Catharina Gerarda Maria; Maathuis, Carel; van Wijlen-Hempel, Rietje; Elvers, Hans

    2013-01-01

    Purpose: To investigate the reliability and validity of video clips in assessing movement disorders in preschool children. Methods: The study group included 27 children with neuromotor concerns. The explorative validity group included children with motor problems (n = 21) or with typical development

  12. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin...

  13. Stability and composition of functional synergies for speech movements in children with developmental speech disorders

    NARCIS (Netherlands)

    Terband, H.; Maassen, B.; van Lieshout, P.; Nijland, L.

    2011-01-01

    The aim of this study was to investigate the consistency and composition of functional synergies for speech movements in children with developmental speech disorders. Kinematic data were collected on the reiterated productions of syllables spa (/spa:/) and paas (/pa:s/) by 10 6- to 9-year-olds with

  14. Stability and composition of functional synergies for speech movements in children with developmental speech disorders

    NARCIS (Netherlands)

    Terband, H.R.; Maassen, B.A.M.; Lieshout, P. van; Nijland, L.

    2011-01-01

    The aim of this study was to investigate the consistency and composition of functional synergies for speech movements in children with developmental speech disorders. Kinematic data were collected on the reiterated productions of syllables spa(/spa/) and paas(/pas/) by 10 6- to 9-year-olds with

  15. Using Constraints to Design Developmentally Appropriate Movement Activities for Children with Autism Spectrum Disorders

    Science.gov (United States)

    Pope, Michelle; Breslin, Casey M.; Getchell, Nancy; Liu, Ting

    2012-01-01

    Some of the characteristics and behaviors of children with autism spectrum disorder (ASD), such as difficulty with social interactions and sensory integration, make physical education instruction difficult. Children with ASD also encounter movement difficulties, such as motor-planning and anticipatory deficits. One way to enhance the ability of…

  16. Arm and Hand Movement in Children Suspected of Having Autism Spectrum Disorder

    Science.gov (United States)

    Braddock, Barbara A.; Hilton, Jane C.

    2016-01-01

    The aim of this study was to describe arm and hand movement in children suspected of having autism spectrum disorder (ASD; age range 29-43 months). A videotaped retrospective review of five children with symptoms of ASD during "Communication Temptation Tasks" was completed at two time points (pre-testing and 6 weeks later). Categories of…

  17. Rapid eye movement sleep behavior disorder--diagnostik, årsager og behandling

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul Jørgen

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical and neu...

  18. A Case of KCNQ2-Associated Movement Disorder Triggered by Fever.

    Science.gov (United States)

    Dhamija, Radhika; Goodkin, Howard P; Bailey, Russell; Chambers, Chelsea; Brenton, J Nicholas

    2017-12-01

    The differential diagnosis of fever-induced movement disorders in childhood is broad. Whole exome sequencing has yielded new insights into those cases with a suspected genetic basis. We report the case of an 8-year-old boy with a history of neonatal seizures who presented with near-continuous hyperkinetic movements of his limbs during a febrile illness. Initial diagnostic testing did not explain his abnormalities; however, given the suspicion for a channelopathy, whole exome sequencing was performed and it demonstrated a de novo pathogenic heterozygous variant in KCNQ2. There is an expanding phenotypic spectrum of heterozygous alterations in KCNQ2; however, this report provides the first description of a pathogenic KCNQ2 variant fever-induced hyperkinetic movement disorder in childhood. We also review the literature of cases previously published with the same pathogenic variant.

  19. Meta Review of Systematic and Meta Analytic Reviews on Movement Differences, Effect of Movement Based Interventions, and the Underlying Neural Mechanisms in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Motohide eMiyahara

    2013-03-01

    Full Text Available Purposes: The aims of this paper are three-folds: first, to identify and appraise evidence from published systematic and meta-analytic reviews on 1 movement characteristics of individuals with autism spectrum disorders (ASD; 2 the effects of movement based interventions for ASD; 3 hypothesized underlying neural mechanisms for the movement characteristics. Methods: A meta review of published systematic and meta-analytic reviews on movement characteristics, structural and functional brain anomalies in ASD and the effects of movement based interventions for individuals with ASD between 1806 and October 2012. The methodological quality of the identified systematic and meta-analytic reviews was independently assessed by two assessors with the assessment of multiple systematic reviews (AMSTAR.Results: The search yielded a total of twelve reviews on the movement differences or the movement based interventions. The methodological quality of the reviews varied, but the review conclusions were similar. Although individuals with ASD generally perform less well than age-matched controls in developmental movement tasks, there are few exceptions whose movement abilities are intact. Most movement based interventions report their efficacies. However, all existing studies employ the research design that is inherently incapable of providing strong evidence, and they often fail to report the extent of psychosocial interactions within the movement interventions. The hypothesized neural mechanisms are still under development and speculative in nature.Conclusions: It is premature to designate movement disturbance as a core symptom of ASD. The effects of movement based interventions on ASD core symptoms need to be further validated by stronger evidence based on verified theoretical mechanisms linking ASD with movement disorders.

  20. The Clinical Phenotype of Idiopathic Rapid Eye Movement Sleep Behavior Disorder at Presentation: A Study in 203 Consecutive Patients.

    Science.gov (United States)

    Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Santamaria, Joan

    2016-01-01

    To describe the clinical phenotype of idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) at presentation in a sleep center. Clinical history review of 203 consecutive patients with IRBD identified between 1990 and 2014. IRBD was diagnosed by clinical history plus video-polysomnographic demonstration of REM sleep with increased electromyographic activity linked to abnormal behaviors. Patients were 80% men with median age at IRBD diagnosis of 68 y (range, 50-85 y). In addition to the already known clinical picture of IRBD, other important features were apparent: 44% of the patients were not aware of their dream-enactment behaviors and 70% reported good sleep quality. In most of these cases bed partners were essential to convince patients to seek medical help. In 11% IRBD was elicited only after specific questioning when patients consulted for other reasons. Seven percent did not recall unpleasant dreams. Leaving the bed occurred occasionally in 24% of subjects in whom dementia with Lewy bodies often developed eventually. For the correct diagnosis of IRBD, video-polysomnography had to be repeated in 16% because of insufficient REM sleep or electromyographic artifacts from coexistent apneas. Some subjects with comorbid obstructive sleep apnea reported partial improvement of RBD symptoms following continuous positive airway pressure therapy. Lack of therapy with clonazepam resulted in an increased risk of sleep related injuries. Synucleinopathy was frequently diagnosed, even in patients with mild severity or uncommon IRBD presentations (e.g., patients who reported sleeping well, onset triggered by a life event, nocturnal ambulation) indicating that the development of a neurodegenerative disease is independent of the clinical presentation of IRBD. We report the largest IRBD cohort observed in a single center to date and highlight frequent features that were not reported or not sufficiently emphasized in previous publications. Physicians should be aware of

  1. Detecting Disordered Breathing and Limb Movement Using In-Bed Force Sensors.

    Science.gov (United States)

    Waltisberg, Daniel; Amft, Oliver; Brunner, Daniel P; Troster, Gerhard

    2017-07-01

    We present and evaluate measurement fusion and decision fusion for recognizing apnea and periodic limb movement in sleep episodes. We used an in-bed sensor system composed of an array of strain gauges to detect pressure changes corresponding to respiration and body movement. The sensor system was placed under the bed mattress during sleep and continuously recorded pressure changes. We evaluated both fusion frameworks in a study with nine adult participants that had mixed occurrences of normal sleep, apnea, and periodic limb movement. Both frameworks yielded similar recognition accuracies of 72.1 ± ∼  12% compared to 63.7 ± 17.4% for a rule-based detection reported in the literature. We concluded that the pattern recognition methods can outperform previous rule-based detection methods for classifying disordered breathing and period limb movements simultaneously.

  2. Eye movements in patients with Whiplash Associated Disorders: a systematic review.

    Science.gov (United States)

    Ischebeck, Britta Kristina; de Vries, Jurryt; Van der Geest, Jos N; Janssen, Malou; Van Wingerden, Jan Paul; Kleinrensink, Gert Jan; Frens, Maarten A

    2016-10-21

    Many people with Whiplash Associated Disorders (WAD) report problems with vision, some of which may be due to impaired eye movements. Better understanding of such impaired eye movements could improve diagnostics and treatment strategies. This systematic review surveys the current evidence on changes in eye movements of patients with WAD and explains how the oculomotor system is tested. Nine electronic data bases were searched for relevant articles from inception until September 2015. All studies which investigated eye movements in patients with WAD and included a healthy control group were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the Methodology Checklists provided by the Scottish Intercollegiate Guidelines Network. Fourteen studies out of 833 unique hits were included. Ten studies reported impaired eye movements in patients with WAD and in four studies no differences compared to healthy controls were found. Different methods of eye movement examination were used in the ten studies: in five studies, the smooth pursuit neck torsion test was positive, in two more the velocity and stability of head movements during eye-coordination tasks were decreased, and in another three studies the cervico-ocular reflex was elevated. Overall the reviewed studies show deficits in eye movement in patients with WAD, but studies and results are varied. When comparing the results of the 14 relevant publications, one should realise that there are significant differences in test set-up and patient population. In the majority of studies patients show altered compensatory eye movements and smooth pursuit movements which may impair the coordination of head and eyes.

  3. Study on the relation of brain functional connectivity to movement disorders and cognitive impairment in patients with rapid eye movement sleep behavior disorder

    Directory of Open Access Journals (Sweden)

    Hong-ju ZHANG

    2017-09-01

    Full Text Available Objective To explore the relation between abnormal functional connectivity of substantia nigra and impairment of movement and cognition in patients with rapid eye movement sleep behavior disorder (RBD. Methods A total of 22 subjects, including 14 patients with RBD and 8 sex, age, education-matched healthy controls, were enrolled in this study according to international diagnostic criteria. Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ and Hoehn-Yahr Stage were used to evaluate motor function. Digit Ordering Test - Attention (DOT - A, Symbol Digit Modalities Test (SDMT, Stroop Color-Word Test (SCWT, Trail Making Test (TMT, Rey-Osterrieth Complex Figure Test (ROCFT, Clock Drawing Test (CDT, Boston Naming Test (BNT and Auditory Verbal Learning Test (AVLT were used to evaluate cognitive function. The functional connectivity from left and right substantia nigra to brain region were examined. Results There were no statistical differences of UPDRSⅢ and Hoehn?Yahr Stage between 2 groups (P > 0.05, for all. In comparison with control group, SDMT (P = 0.001, ROCFT-copy (P = 0.013 and AVLT-N2 (P = 0.032 were significantly lower, while TMT-B test was significantly higher (P =0.005 in RBD group. Compared with control group, the functional connectivity of right substantia nigra to left precentral gyrus (P < 0.005 and right angular gyrus (P < 0.005 were all decreased in RBD group. Conclusions The results suggest that cognitive impairment occurs earlier than movement disorders in RBD, and there are abnormal functional connectivity from right substantia nigra to left precentral gyrus and right angular gyrus, proving that abnormal functional connectivity is the base of behavior disorders in RBD. DOI: 10.3969/j.issn.1672-6731.2017.09.005

  4. A single-question screen for rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Postuma, Ronald B; Arnulf, Isabelle; Hogl, Birgit

    2012-01-01

    Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinson's disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epi......Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinson's disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large......-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response....

  5. Automated quantitative gait analysis in animal models of movement disorders

    Directory of Open Access Journals (Sweden)

    Vandeputte Caroline

    2010-08-01

    Full Text Available Abstract Background Accurate and reproducible behavioral tests in animal models are of major importance in the development and evaluation of new therapies for central nervous system disease. In this study we investigated for the first time gait parameters of rat models for Parkinson's disease (PD, Huntington's disease (HD and stroke using the Catwalk method, a novel automated gait analysis test. Static and dynamic gait parameters were measured in all animal models, and these data were compared to readouts of established behavioral tests, such as the cylinder test in the PD and stroke rats and the rotarod tests for the HD group. Results Hemiparkinsonian rats were generated by unilateral injection of the neurotoxin 6-hydroxydopamine in the striatum or in the medial forebrain bundle. For Huntington's disease, a transgenic rat model expressing a truncated huntingtin fragment with multiple CAG repeats was used. Thirdly, a stroke model was generated by a photothrombotic induced infarct in the right sensorimotor cortex. We found that multiple gait parameters were significantly altered in all three disease models compared to their respective controls. Behavioural deficits could be efficiently measured using the cylinder test in the PD and stroke animals, and in the case of the PD model, the deficits in gait essentially confirmed results obtained by the cylinder test. However, in the HD model and the stroke model the Catwalk analysis proved more sensitive than the rotarod test and also added new and more detailed information on specific gait parameters. Conclusion The automated quantitative gait analysis test may be a useful tool to study both motor impairment and recovery associated with various neurological motor disorders.

  6. Mandibular movement patterns during speech in subjects with temporomandibular disorders and in asymptomatic individuals.

    Science.gov (United States)

    Bianchini, Esther M G; Paiva, Guiovaldo; de Andrade, Cláudia R F

    2008-01-01

    The mandibular movements used during speech modify space to allow different articulation postures proper for each sound. Temporomandibular disorders (TMD) may cause modifications in these movements due to joint and muscular conditions. The aim of this study was to verify the amplitude and the characterization of the mandibular movements during speech, using computerized electrognathography, in individuals with TMD and in asymptomatic individuals, analyzing possible interferences of these dysfunctions. One hundred thirty-five (135) adult subjects were divided into two groups: GI with 90 participants diagnosed with TMD and GIII with 45 asymptomatic participants. Their mandibular movements were observed during the sequential naming of pictures containing all of the word sounds, which occur in the Brazilian Portuguese language. The records were obtained with computerized electrognathography (BioEGN-BioPak system, BioResearch Associates, Inc., Milwaukee, WI). Mean values of the amplitude were described for the two groups. The analysis of such results showed statistically significant differences between the means of the values, obtained for the two groups in the opening and retrusion ranges. Statistically significant differences were not established for the presence and the range of the deviations in laterality, during speech. Prevalence of bilateral deviations was verified in GIII and unilateral deviations in GI. This study describes the 3-dimensional thresholds of mandibular movements in speech for Brazilian Portuguese, for the investigated individuals of both groups. The presence of TMD shows reduction in mandibular opening and retrusion ranges and prevalence of unilateral deviation movements during speech.

  7. The impact of obesity on neurodegenerative diseases.

    Science.gov (United States)

    Mazon, Janaína Niero; de Mello, Aline Haas; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza

    2017-08-01

    Neurodegenerative diseases are a growing health concern. The increasing incidences of these disorders have a great impact on the patients' quality of life. Although the mechanisms of neurodegenerative diseases are still far from being clarified, several studies look for new discoveries about their pathophysiology and prevention. Furthermore, evidence has shown a strong correlation between obesity and the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Metabolic changes caused by overweight are related to damage to the central nervous system (CNS), which can lead to neural death, either by apoptosis or cell necrosis, as well as alter the synaptic plasticity of the neuron. This review aims to show the association between neurodegenerative diseases, focusing on AD and PD, and metabolic alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Rapid eye movement sleep behavior disorder as an outlier detection problem

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sørensen, Gertrud Laura; Nikolic, M.

    2014-01-01

    OBJECTIVE: Idiopathic rapid eye movement (REM) sleep behavior disorder is a strong early marker of Parkinson's disease and is characterized by REM sleep without atonia and/or dream enactment. Because these measures are subject to individual interpretation, there is consequently need...... for quantitative methods to establish objective criteria. This study proposes a semiautomatic algorithm for the early detection of Parkinson's disease. This is achieved by distinguishing between normal REM sleep and REM sleep without atonia by considering muscle activity as an outlier detection problem. METHODS...... limb movements did only have a minor influence on the quantification of the muscle activity. Analysis of muscle activity during nonrapid eye movement sleep may improve the separation even further. Copyright © 2014 by the American Clinical Neurophysiology Society....

  9. Eye movement desensitization and reprocessing therapy for personality disorders in older adults?

    Science.gov (United States)

    Gielkens, E M J; Sobczak, S; Van Alphen, S P J

    2016-10-01

    Eye Movement Desensitization and Reprocessing (EMDR) is a kind of psychotherapy, which is growing in popularity, particularly for treatment of post-traumatic stress disorder (PTSD). When Shapiro first introduced EMDR in 1989, it was approached as a controversial treatment because of lack of evidence. However, nowadays there is growing evidence for EMDR efficacy in PTSD (Mc Guire et al., 2014) and EMDR is recommended by international and national treatment guidelines for PTSD. Moreover, EMDR is also used for the treatment of other anxiety disorders, such as panic disorders (De Jongh et al., 2002). Furthermore, research continues on effects of EMDR in addiction, somatoform disorders and psychosis. So far, there is no empirical research on the efficacy of EMDR treatment in older adults.

  10. Borderline personality disorder is associated with lower confidence in perception of emotional body movements.

    Science.gov (United States)

    Kaletsch, Morten; Krüger, Britta; Pilgramm, Sebastian; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Zentgraf, Karen; Munzert, Jörn; Sammer, Gebhard

    2014-01-01

    Much recent research has shown that personality disorders are associated with an altered emotion perception. Whereas most of this research was conducted with stimuli such as faces, the present study examined possible differences in the perception of emotions expressed via body language and body movements. 30 patients with borderline personality disorder (BPD) and 30 non-patients observed video scenes of emotional human interactions conveyed by point-light displays, rated the depicted valence, and judged their confidence in this rating. Patients with BPD showed no altered emotion perception (i.e., no biased perception in either a negative or a positive direction). They did not perceive and evaluate depicted emotions as being more extreme than healthy controls. However, patients with BPD showed less confidence in their perception of depicted emotions, especially when these were difficult to identify. The findings extend insights on altered emotion perception in persons with BPD to include the field of body movements.

  11. Nursing time to program and assess deep brain stimulators in movement disorder patients.

    Science.gov (United States)

    Hunka, Karen; Suchowersky, Oksana; Wood, Susan; Derwent, Lorelei; Kiss, Zelma H T

    2005-08-01

    The use of deep brain stimulation (DBS) to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia is increasing. Although some published literature describes the methods for DBS programming, the time and nursing requirements to run a DBS surgical program have not been examined previously. For this study, we prospectively recorded the time required for both assessments and programming of the DBS from the preoperative period to 1 year after surgery in a variety of patients. Results showed that the mean total time spent programming the stimulator and assessing these patients ranged from 18.0-36.2 hours per patient. It took twice as long to program the stimulator in patients with Parkinson's disease as it did in patients with essential tremor or dystonia. When setting up a program for movement disorders surgery, nursing time spent on patient assessment and programming should be considered in the workload.

  12. Rapid eye movement sleep behavior disorder--diagnostik, årsager og behandling

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul Jørgen

    2009-01-01

    and neurological disease. RBD is related to brainstem pathology. Furthermore, it is increasingly recognized that RBD is frequently related to Parkinsonian disorders and narcolepsy. This article reviews recent knowledge about RBD with focus on the diagnostic process and management.......Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...

  13. Rapid eye movement sleep behavior disorder--diagnostik, årsager og behandling

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul Jørgen

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...... and neurological disease. RBD is related to brainstem pathology. Furthermore, it is increasingly recognized that RBD is frequently related to Parkinsonian disorders and narcolepsy. This article reviews recent knowledge about RBD with focus on the diagnostic process and management....

  14. Rapid eye movement sleep behavior disorder--diagnostik, årsager og behandling

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul Jørgen

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical and neu...... and neurological disease. RBD is related to brainstem pathology. Furthermore, it is increasingly recognized that RBD is frequently related to Parkinsonian disorders and narcolepsy. This article reviews recent knowledge about RBD with focus on the diagnostic process and management....

  15. Borderline Personality Disorder is Associated with Lower Confidence in Perception of Emotional Body Movements

    Directory of Open Access Journals (Sweden)

    Morten eKaletsch

    2014-11-01

    Full Text Available Much recent research has shown that personality disorders are associated with an altered emotion perception. Whereas most of this research was conducted with stimuli such as faces, the present study examined possible differences in the perception of emotions expressed via body language and body movements. 30 patients with borderline personality disorder and 30 non-patients observed video scenes of emotional human interactions conveyed by point–light displays, rated the depicted valence, and judged their confidence in this rating. Patients with borderline personality disorder showed no altered emotion perception (i.e., no biased perception in either a negative or a positive direction. They did not perceive and evaluate depicted emotions as being more extreme than healthy controls. However, patients with borderline personality disorder showed less confidence in their perception of depicted emotions, especially when these were difficult to identify. The findings extend insights on altered emotion perception in persons with borderline personality disorder to include the field of body movements.

  16. Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

    Science.gov (United States)

    Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities. PMID:21930661

  17. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study.

    Science.gov (United States)

    Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc

    2014-06-01

    Autoimmunity might be associated with or implicated in sleep and neurodegenerative disorders. We aimed to describe the features of a novel neurological syndrome associated with prominent sleep dysfunction and antibodies to a neuronal antigen. In this observational study, we used clinical and video polysomnography to identify a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic, University of Barcelona, Spain, for abnormal sleep behaviours and obstructive sleep apnoea. These patients had antibodies against a neuronal surface antigen, which were also present in five additional patients referred to our laboratory for antibody studies. These five patients had been assessed with polysomnography, which was done in our sleep unit in one patient and the recording reviewed in a second patient. Two patients underwent post-mortem brain examination. Immunoprecipitation and mass spectrometry were used to characterise the antigen and develop an assay for antibody testing. Serum or CSF from 298 patients with neurodegenerative, sleep, or autoimmune disorders served as control samples. All eight patients (five women; median age at disease onset 59 years [range 52-76]) had abnormal sleep movements and behaviours and obstructive sleep apnoea, as confirmed by polysomnography. Six patients had chronic progression with a median duration from symptom onset to death or last visit of 5 years (range 2-12); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid progression with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died 2 months and 6 months, respectively, after symptom onset. In five of five patients, video polysomnography showed features of obstructive sleep apnoea, stridor, and abnormal sleep architecture (undifferentiated non-rapid-eye-movement [non-REM] sleep or poorly structured

  18. Clinical implications of local field potentials for understanding and treating movement disorders.

    Science.gov (United States)

    Thompson, John A; Lanctin, David; Ince, Nuri Firat; Abosch, Aviva

    2014-01-01

    Deep brain stimulation (DBS) for the treatment of movement disorders has provided researchers with an opportunity to record electrical oscillatory activity from electrodes implanted in deep brain structures. Extracellular activity recorded from a population of neurons, termed local field potentials (LFPs), has shed light on the pathophysiology of movement disorders and holds the potential to lead to refinement in existing treatments. This paper reviews the clinical significance of LFPs recorded from macroelectrodes implanted in basal ganglia and thalamic targets for the treatment of Parkinson's disease, essential tremor and dystonia. Neural population dynamics and subthreshold events, which are undetectable by single-unit recordings, can be examined with frequency band analysis of LFPs (frequency range: 1-250 Hz). Of clinical relevance, reliable correlations between motor symptoms and components of the LFP power spectrum suggest that LFPs may serve as a biomarker for movement disorders. In particular, Parkinson's rigidity has been shown to correlate with the power of beta oscillations (13-30 Hz), and essential tremor coheres with oscillations of 8-27 Hz. Furthermore, evidence indicates that the optimal contacts for DBS programming can be predicted from the anatomic location of beta and gamma bands (48-200 Hz). LFP analysis has implications for improved electrode targeting and the development of a real-time, individualized, 'closed-loop' stimulation system. 2014 S. Karger AG, Basel.

  19. Detection of mental imagery and attempted movements in patients with disorders of consciousness using EEG

    Directory of Open Access Journals (Sweden)

    Petar eHorki

    2014-12-01

    Full Text Available Further development of an EEG based communication device for patients with disorders of consciousness (DoC could benefit from addressing the following gaps in knowledge – first, an evaluation of different types of motor imagery; second, an evaluation of passive feet movement as a mean of an initial classifier setup; and third, rapid delivery of biased feedback. To that end we investigated whether complex and / or familiar mental imagery, passive, and attempted feet movement can be reliably detected in patients with DoC using EEG recordings, aiming to provide them with a means of communication. Six patients in a minimally conscious state (MCS took part in this study. The patients were verbally instructed to perform different mental imagery tasks (sport, navigation, as well as attempted feet movements, to induce distinctive event-related (desynchronization (ERD/S patterns in the EEG. Offline classification accuracies above chance level were reached in all three tasks (i.e. attempted feet, sport, and navigation, with motor tasks yielding significant (p<0.05 results more often than navigation (sport: 10 out of 18 sessions; attempted feet: 7 out of 14 sessions; navigation: 4 out of 12 sessions. The passive feet movements, evaluated in one patient, yielded mixed results: whereas time-frequency analysis revealed task-related EEG changes over neurophysiological plausible cortical areas, the classification results were not significant enough (p<0.05 to setup an initial classifier for the detection of attempted movements. Concluding, the results presented in this study are consistent with the current state of the art in similar studies, to which we contributed by comparing different types of mental tasks, notably complex motor imagery and attempted feet movements, within patients. Furthermore, we explored new venues, such as an evaluation of passive feet movement as a mean of an initial classifier setup, and rapid delivery of biased feedback.

  20. Dystonia and paroxysmal dyskinesias: under-recognized movement disorders in domestic animals? A comparison with human dystonia/paroxysmal dyskinesias.

    Directory of Open Access Journals (Sweden)

    Angelika eRichter

    2015-11-01

    Full Text Available Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e. dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans, and summarizes similar hereditary movement disorders reported in domestic animals.

  1. [Therapeutic effects of the Feldenkrais method "awareness through movement" in patients with eating disorders].

    Science.gov (United States)

    Laumer, U; Bauer, M; Fichter, M; Milz, H

    1997-05-01

    Based on the movement-pedagogical concept of Feldenkrais and the findings-of disturbed body perception by eating disordered patients this research aimed at studying the therapeutical effects of the Feldenkrais Method "Awareness through Movement" with eating disorder patients, 15 eating disordered patients treated at the Roseneck hospital for behavioural medicine rated-by means of a questionnaire consisting of scales of the Body Cathexis Scale (BCS), the Body Parts Satisfaction Scale (BPSS), the questionnaire for body perception (Fragebogen zum Körpererleben; FKE), the Emotion inventory (Emotionalitätsinventar; EMI-B), the Anorexia-Nervosa-Inventory for Self-rating (ANIS) and the Eating Disorder Inventory-2 (EDI)-various aspects of their eating disorder before and after participating in a nine hour course of the Feldenkrais Method. The data of these patients were compared to those of the members of a control group, also consisting of 15 eating disordered patients who did not participate in a Feldenkrais course. The participants of the Feldenkrais-course showed increasing contentment with regard to problematic zones of their body and their own health as well as concerning acceptance and familiarity with their own body. Other results were a more spontaneous, open and self-confident behaviour, the decrease of feelings of helplessness and decrease of the wish to return to the security of the early childhood, which indicates the development of felt sense of self, self-confidence and a general process of maturation of the whole personality. The outcome points to the therapeutical effectiveness of the Feldenkrais Method with eating-disorder patients within a multimodal treatment program.

  2. Early noninvasive diagnosis of neurodegenerative diseases.

    Science.gov (United States)

    Danev, Stoyan I; St Stoyanov, Drozdstoy

    2010-01-01

    This paper reviews the contemporary trends in the pathobiochemistry of neurodegenerative disorders with respect to their early predictive diagnosis and possible treatment interventions. If we consider the current epidemiological data related to neurodegenerative disorders, medicine is going to face in the near future latent pandemic situations. The introduction puts an emphasis on the emerging importance of one major cluster of neurodegenerative disorders: diseases of the abnormal protein beta-conformation. The cluster includes such significant diseases as Alzheimer, Pick, Huntington, Parkinson disease, as well as the transmissible spongiform encephalopathies (Creuzfeldt-Jakob disease). The pathogenetic mechanisms in the determination of this group of disorders are explored with an emphasis on the impairment of post-synthetic chaperone correction. The central role of a number of such protein products is discussed. In particular the pathobiochemical mechanisms concerning the formation of beta-amyloid, alpha and beta synucleins, scrapie isoform of the prion protein are presented. A new diagnostic principle allowing the early and specific diagnosis of the conformation diseases protein via amplification techniques is presented. These methods compete in sensitivity with the PCR methods and shows promises for effective treatment. In conclusion, beta-pathies are considered a suitable example for the modern concept of cluster and prototype diagnosis in medicine and especially in clinical neurosciences.

  3. Moving forward: advances in the treatment of movement disorders with deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Terry K Schiefer

    2011-11-01

    Full Text Available The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD, tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced Parkinson’s disease can be treated with thalamic, globus pallidus internus (GPi, or subthalamic nucleus (STN DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted.

  4. Cognitive Behavioral Therapy and Eye Movement Desensitization and Reprocessing in Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Filiz Ýzci

    2017-04-01

    Cognitive behavioral therapy (CBT and eye movement desensitization and reprocessing (EMDR are from the most common treatment methods that have begun to be used in trauma patients in recent years. With the increased applicability of these treatment models in Post Traumatic Stress Disorder (PTSD and on other trauma patients success of treatment rate in trauma patients is increasing steadily. In this article, it is tried to review the application forms and effects of EMDR and CBT methods among patients with PTSD which is a commonly seen trauma disorder. It is aimed in this article to emphasize the importance of CBT and a newly treatment EMDR in post-traumatic acute and chronic disorders with multiple psychiatric symptoms. [JCBPR 2017; 6(1.000: 31-38

  5. [Correction of psychophysical development of preschool children 3-4 year old with movement disorders by means of Bobath therapy

    OpenAIRE

    Bukhovets, B.O.

    2016-01-01

    This study deals with the definition of efficiency application means Bobath therapy as main correction psychophysical development method of preschool age 3 -4 years children, who have movement disorders.

  6. Impaired driving simulation in patients with Periodic Limb Movement Disorder and patients with Obstructive Sleep Apnea Syndrome

    NARCIS (Netherlands)

    Gieteling, Esther W.; Bakker, Marije S.; Hoekema, Aarnoud; Maurits, Natasha M.; Brouwer, Wiebo H.; van der Hoeven, Johannes H.

    Background: Excessive daytime sleepiness (EDS) is considered to be responsible for increased collision rate and impaired driving simulator performance in Obstructive Sleep Apnea Syndrome (OSAS) patients. Periodic Limb Movement Disorder (PLMD) patients also frequently report EDS and may also have

  7. The effectiveness of non-invasive brain stimulation in improving clinical signs of hyperkinetic movement disorders

    Directory of Open Access Journals (Sweden)

    Ignacio eObeso

    2016-01-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is a safe and non-invasive method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols.The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson´s disease with levodopa-induced dyskinesias, essential tremor and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to normalize pathologically decreased or increased levels of cortical activity have given moderate progress in patient´s quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.

  8. Eye Movement Sequences during Simple versus Complex Information Processing of Scenes in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Sheena K. Au-Yeung

    2011-01-01

    Full Text Available Minshew and Goldstein (1998 postulated that autism spectrum disorder (ASD is a disorder of complex information processing. The current study was designed to investigate this hypothesis. Participants with and without ASD completed two scene perception tasks: a simple “spot the difference” task, where they had to say which one of a pair of pictures had a detail missing, and a complex “which one's weird” task, where they had to decide which one of a pair of pictures looks “weird”. Participants with ASD did not differ from TD participants in their ability to accurately identify the target picture in both tasks. However, analysis of the eye movement sequences showed that participants with ASD viewed scenes differently from normal controls exclusively for the complex task. This difference in eye movement patterns, and the method used to examine different patterns, adds to the knowledge base regarding eye movements and ASD. Our results are in accordance with Minshew and Goldstein's theory that complex, but not simple, information processing is impaired in ASD.

  9. Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

    2015-03-01

    ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

  10. A rare case of sleep - related rhythmic movement disorder in adult with literature review

    Directory of Open Access Journals (Sweden)

    Yue HOU

    2017-09-01

    Full Text Available Sleep - related rhythmic movement disorder (RMD is characterized by repetitive,stereotyped and rhythmic motor behaviors (not tremors that occur predominantly during drowsiness or sleep and involve large muscle groups. The onset of RMD is typically in early childhood, rarely continue into adolescence and adulthood. This paper retrospectively analyzed the diagnosis and treatment in a case of adult-onset RMD. A 76 -year-old male mainly presented rhythmic forehead banging during sleep. The number of forehead banging ranged from dozens to tens of seconds, pause seconds after the second attack, lasting 1 to 2 h and can not be recalled after waking up. Polysomnography (PSG showed sleep efficiency decreased, awakening time prolonged, times of wakefulness increased, sleep structure disordered, non-rapid eye movement (NREM 1 and 2 sleep increased, rapid eye movement (REM sleep decreased, sleep latency of REM prolonged. Apnea hypopnea index (AHI was 8.40. Several abnormal behavior attacks were observed, each attack lasting 3 to 18 s, 0.60 to 1.20 Hz, total time lasting 6 min. The diagnosis was RMD, clonazepam 0.50 mg/night and pramipexole 0.0625 mg/night were given and the result of 33 months follow-up showed effective. By literature review, we know the clinical features, diagnosis and treatment of RMD. We also analyze the reasons of misdiagnosis for reducing diagnostic errors and mistreatments. DOI: 10.3969/j.issn.1672-6731.2017.09.008

  11. An Evaluation of Educational Neurological Eye Movement Disorder Videos Posted on Internet Video Sharing Sites.

    Science.gov (United States)

    Hickman, Simon J

    2016-03-01

    Internet video sharing sites allow the free dissemination of educational material. This study investigated the quality and educational content of videos of eye movement disorders posted on such sites. Educational neurological eye movement videos were identified by entering the titles of the eye movement abnormality into the search boxes of the video sharing sites. Also, suggested links were followed from each video. The number of views, likes, and dislikes for each video were recorded. The videos were then rated for their picture and sound quality. Their educational value was assessed according to whether the video included a description of the eye movement abnormality, the anatomical location of the lesion (if appropriate), and the underlying diagnosis. Three hundred fifty-four of these videos were found on YouTube and Vimeo. There was a mean of 6,443 views per video (range, 1-195,957). One hundred nineteen (33.6%) had no form of commentary about the eye movement disorder shown apart from the title. Forty-seven (13.3%) contained errors in the title or in the text. Eighty (22.6%) had excellent educational value by describing the eye movement abnormality, the anatomical location of the lesion, and the underlying diagnosis. Of these, 30 also had good picture and sound quality. The videos with excellent educational value had a mean of 9.84 "likes" per video compared with 2.37 for those videos without a commentary (P educational value with good picture and sound quality had a mean of 10.23 "likes" per video (P = 0.004 vs videos with no commentary). There was no significant difference in the mean number of "dislikes" between those videos that had no commentary or which contained errors and those with excellent educational value. There are a large number of eye movement videos freely available on these sites; however, due to the lack of peer review, a significant number have poor educational value due to having no commentary or containing errors. The number of "likes

  12. Clinical characteristics, management and long-term outcome of suspected rapid eye movement sleep behaviour disorder in 14 dogs.

    Science.gov (United States)

    Schubert, T A; Chidester, R M; Chrisman, C L

    2011-02-01

    To describe the clinical characteristics, management and long-term outcome in dogs with suspected rapid eye movement sleep behaviour disorder. Medical records and video recordings of 14 dogs with suspected rapid eye movement sleep behaviour disorder were reviewed and the owners were contacted via telephone or email for further information. Clinical signs included episodes of violent limb movements, howling, barking, growling, chewing, or biting during sleep. Episodes occurred at night and during daytime naps. The age at onset ranged from 8 weeks to 7·5 years with a median of 6 years but 64% of dogs were one year or less. There was no apparent sex or breed predisposition. Rapid eye movement sleep behaviour disorder events were reduced in severity and frequency in 78% of the dogs treated with 40 mg/kg/day oral potassium bromide. One dog was euthanized within 3 months of the onset of signs because of their severity. The duration of the disorder in the 13 surviving dogs ranged from 1·5 to 9 years. None of the dogs spontaneously recovered. Rapid eye movement sleep behaviour disorder is suspected to occur in dogs, as it does in human beings. It causes concern to the owners and disrupts the home environment. Unlike human beings, rapid eye movement sleep behaviour disorder of dogs often has a juvenile onset. © 2011 British Small Animal Veterinary Association.

  13. Cognitive perspective-taking during scene perception in autism spectrum disorder: evidence from eye movements.

    Science.gov (United States)

    Au-Yeung, Sheena K; Kaakinen, Johanna K; Benson, Valerie

    2014-02-01

    The present study examined how eye movements during scene viewing are modulated by adopting psychological perspectives in both adults with autism spectrum disorders (ASD) and typically developing adults. In the current study, participants viewed house scenes with either non-perspective-taking (look for valuable items/features of the house that need fixing) or perspective-taking instructions (imagine that you are a burglar/repairman) while their eye movements were recorded. The eye movement measures revealed that for the "look for the valuable items" and burglar perspective task, the ASD group showed typical relevance effects (the preference to look at schema-relevant compared with schema-irrelevant targets) in their eye movements. However, we found subtle processing differences between the groups that were related to initial orienting to and processing of schema-relevant items for the "look for the features that need fixing" and the repairman perspective-taking task. There was an absence of a relevance effect for the ASD group for the repairman perspective and its non-perspective-taking equivalent instruction showing that the identification of items relevant to those schemas was more difficult for the ASD group. The present findings suggest that resolving ambiguity may be a defining feature of complex information processing deficits in ASD. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  14. Cognitive Control of Saccadic Eye Movements in Children with Developmental Coordination Disorder.

    Directory of Open Access Journals (Sweden)

    Claudia C Gonzalez

    Full Text Available The ability to use advance information to prepare and execute a movement requires cognitive control of behaviour (e.g., anticipation and inhibition. Our aim was to explore the integrity of saccadic eye movement control in developmental coordination disorder (DCD and typically developing (TD children (8-12 years and assess how these children plan and inhibit saccadic responses, the principal mechanisms within visual attention control. Eye movements and touch responses were measured (separately and concurrently in Cued and Non-Cued conditions. We found that children with DCD had similar saccade kinematics to the TD group during saccade initiation. Advance information decreased hand movement duration in both groups during Cued trials, but decrements in accuracy were significantly worse in the DCD group. In addition, children with DCD exhibited greater inhibitory errors and inaccurate fixation during the Cued trials. Thus, children with DCD were reasonably proficient in executing saccades during reflexive (Non-Cued conditions, but showed deficits in more complex control processes involving prediction and inhibition. These findings have implications for our understanding of motor control in children with DCD.

  15. Engineering enhanced protein disaggregases for neurodegenerative disease

    OpenAIRE

    Jackrel, Meredith E.; Shorter, James

    2015-01-01

    Abstract Protein misfolding and aggregation underpin several fatal neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). There are no treatments that directly antagonize the protein-misfolding events that cause these disorders. Agents that reverse protein misfolding and restore proteins to native form and function could simultaneously eliminate any deleterious loss-of-function or toxic gain-of-function caused by...

  16. Synthetic prions and other human neurodegenerative proteinopathies.

    Science.gov (United States)

    Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

    2015-09-02

    Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson's-like movement disorder.

    Science.gov (United States)

    Lu, Wei; Karuppagounder, Senthilkumar S; Springer, Danielle A; Allen, Michele D; Zheng, Lixin; Chao, Brittany; Zhang, Yan; Dawson, Valina L; Dawson, Ted M; Lenardo, Michael

    2014-09-15

    Mitophagy is a specialized form of autophagy that selectively disposes of dysfunctional mitochondria. Delineating the molecular regulation of mitophagy is of great importance because defects in this process lead to a variety of mitochondrial diseases. Here we report that mice deficient for the mitochondrial protein, phosphoglycerate mutase family member 5 (PGAM5), displayed a Parkinson's-like movement phenotype. We determined biochemically that PGAM5 is required for the stabilization of the mitophagy-inducing protein PINK1 on damaged mitochondria. Loss of PGAM5 disables PINK1-mediated mitophagy in vitro and leads to dopaminergic neurodegeneration and mild dopamine loss in vivo. Our data indicate that PGAM5 is a regulator of mitophagy essential for mitochondrial turnover and serves a cytoprotective function in dopaminergic neurons in vivo. Moreover, PGAM5 may provide a molecular link to study mitochondrial homeostasis and the pathogenesis of a movement disorder similar to Parkinson's disease.

  18. Sleep disturbance in mental health problems and neurodegenerative disease.

    Science.gov (United States)

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep-wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed.

  19. Low-dose, continual enzyme delivery ameliorates some aspects of established brain disease in a mouse model of a childhood-onset neurodegenerative disorder.

    Science.gov (United States)

    King, Barbara; Setford, Meghan L; Hassiotis, Sofia; Trim, Paul J; Duplock, Stephen; Tucker, Justin N; Hattersley, Kathryn; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-04-01

    To determine the capacity of continual low-dose lysosomal enzyme infusion into the cerebrospinal fluid of mucopolysaccharidosis type IIIA (MPS IIIA) mice to reverse established neurodegenerative disease. The rationale behind the study is that there is only limited animal model-derived evidence supporting treatment of symptomatic patients, principally because few studies have been designed to examine disease reversibility. Twelve-week old MPS IIIA mice were implanted with indwelling unilateral intra-ventricular cannulae. These were connected to subcutaneous mini-osmotic pumps infusing recombinant human sulphamidase. Pump replacement was carried out in some mice at 16-weeks of age, enabling treatment to continue for a further month. Control affected/unaffected mice received vehicle via the same method. Behavioural, neuropathological and biochemical parameters of disease were assessed. Improvement in some, but not all, behavioural parameters occurred. Sulphamidase infusion mediated a statistically significant reduction in primary (heparan sulphate) and secondary (gangliosides GM2, GM3) substrate accumulation in the brain, with small reductions in micro- but not astro-gliosis. There was no change in axonal spheroid number. All mice developed a humoural response, however the antibodies were non-neutralising and no adverse clinical effects were observed. Continual infusion of replacement enzyme partially ameliorates clinical, histological and biochemical aspects of MPS IIIA mice, when treatment begins at an early symptomatic stage. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Inertial Sensing to Determine Movement Disorder Motion Present before and after Treatment

    Directory of Open Access Journals (Sweden)

    Naser El-Sheimy

    2012-03-01

    Full Text Available There has been a lot of interest in recent years in using inertial sensors (accelerometers and gyroscopes to monitor movement disorder motion and monitor the efficacy of treatment options. Two of the most prominent movement disorders, which are under evaluation in this research paper, are essential tremor (ET and Parkinson’s disease (PD. These movement disorders are first evaluated to show that ET and PD motion often depict more (tremor motion content in the 3–12 Hz frequency band of interest than control data and that such tremor motion can be characterized using inertial sensors. As well, coherence analysis is used to compare between pairs of many of the six degrees-of-freedom of motions under evaluation, to determine the similarity in tremor motion for the various degrees-of-freedom at different frequency bands of interest. It was quite surprising that this coherence analysis depicts that there is a statistically significant relationship using coherence analysis when differentiating between control and effectively medicated PD motion. The statistical analysis uncovers the novel finding that PD medication induced dyskinesia is depicted within coherence data from inertial signals. Dyskinesia is involuntary motion or the absence of intended motion, and it is a common side effect among medicated PD patients. The results show that inertial sensors can be used to differentiate between effectively medicated PD motion and control motion; such a differentiation can often be difficult to perform with the human eye because effectively medicated PD patients tend to not produce much tremor. As well, the finding that PD motion, when well medicated, does still differ significantly from control motion allows for researchers to quantify potential deficiencies in the use of medication. By using inertial sensors to spot such deficiencies, as outlined in this research paper, it is hoped that medications with even a larger degree of efficacy can be created in

  1. Inertial Sensing to Determine Movement Disorder Motion Present before and after Treatment

    Science.gov (United States)

    Teskey, Wesley J. E.; Elhabiby, Mohamed; El-Sheimy, Naser

    2012-01-01

    There has been a lot of interest in recent years in using inertial sensors (accelerometers and gyroscopes) to monitor movement disorder motion and monitor the efficacy of treatment options. Two of the most prominent movement disorders, which are under evaluation in this research paper, are essential tremor (ET) and Parkinson’s disease (PD). These movement disorders are first evaluated to show that ET and PD motion often depict more (tremor) motion content in the 3–12 Hz frequency band of interest than control data and that such tremor motion can be characterized using inertial sensors. As well, coherence analysis is used to compare between pairs of many of the six degrees-of-freedom of motions under evaluation, to determine the similarity in tremor motion for the various degrees-of-freedom at different frequency bands of interest. It was quite surprising that this coherence analysis depicts that there is a statistically significant relationship using coherence analysis when differentiating between control and effectively medicated PD motion. The statistical analysis uncovers the novel finding that PD medication induced dyskinesia is depicted within coherence data from inertial signals. Dyskinesia is involuntary motion or the absence of intended motion, and it is a common side effect among medicated PD patients. The results show that inertial sensors can be used to differentiate between effectively medicated PD motion and control motion; such a differentiation can often be difficult to perform with the human eye because effectively medicated PD patients tend to not produce much tremor. As well, the finding that PD motion, when well medicated, does still differ significantly from control motion allows for researchers to quantify potential deficiencies in the use of medication. By using inertial sensors to spot such deficiencies, as outlined in this research paper, it is hoped that medications with even a larger degree of efficacy can be created in the future

  2. Treatment of movement disorders using deep brain stimulation – illustrative case reports and technical notes

    Directory of Open Access Journals (Sweden)

    Tadej Strojnik

    2012-05-01

    Full Text Available Operative neuromodulation is the field of electrically or chemically altering the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks to produce therapeutic effects. Deep brain stimulation (DBS is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. This article presents the first DBS cases in Slovenia. In the article the technical features and adjustments of magnetic resonance (MR imaging and development of a new microdrive, which was clinically successfully tested, are described and discussed.

  3. Movement disorders secondary to long-term treatment with cyclosporine A

    OpenAIRE

    Munhoz,Renato P.; Teive,Helio A.G.; Germiniani,Francisco M.B.; Gerytch Jr,Júlio C.; Sá,Daniel S.; Bittencourt,Marco A.; Pasquini,Ricardo; Camargo,Carlos H.F.; Werneck,Lineu César

    2005-01-01

    OBJECTIVE: To analyze the prevalence, severity and functional interference of movement disorders (MD) secondary to chronic use of cyclosporine A (CsA). METHOD: We conducted a cross-sectional study of 60 patients (58.3% male) with mean age 23.1 (3-75) years, followed at the Bone Marrow Transplantation Service of the Hospital de Clínicas of the Federal University of Paraná, Brazil, taking CsA for at least six months. Our protocol included clinical data, assessment of functional interference of ...

  4. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  5. Effect of Aggression Regulation on Eating Disorder Pathology : RCT of a Brief Body and Movement Oriented Intervention

    NARCIS (Netherlands)

    Boerhout, Cees; Swart, Marte; Van Busschbach, Jooske T.; Hoek, Hans W.

    ObjectiveThe objective of the study is to evaluate the effect of a brief body and movement oriented intervention on aggression regulation and eating disorder pathology for individuals with eating disorders. MethodIn a first randomized controlled trial, 40 women were allocated to either the

  6. Inpatient morbidity after spinal deformity surgery in patients with movement disorders.

    Science.gov (United States)

    De la Garza Ramos, Rafael; Goodwin, C Rory; Jain, Amit; Martinez-Ramirez, Daniel; Karikari, Isaac O; Sciubba, Daniel M

    2017-12-01

    To investigate the inpatient perioperative morbidity rate of patients with movement disorders (MD) after spinal deformity surgery. The Nationwide Inpatient Sample database from 2002 to 2011 was queried to identify adult patients with MD who underwent spinal deformity surgery. Complication rates were compared between patients with MD and controls. A multiple logistic regression analysis was conducted to assess the effect of MD on outcome. A total of 365 patients with MD (3.3%) were identified among 11,043 patients undergoing surgery for spinal deformity. Patients with MD were on average 8 years older than the control group (67 vs. 59 years of age, Pspinal deformity surgery may be at risk of higher rate of complications compared to patients without these disorders.

  7. [The role of eye movement desensitization and reprocessing (EMDR) in substance use disorders: A systematic review].

    Science.gov (United States)

    Pilz, René; Hartleb, Riccarda; Konrad, Gabriela; Reininghaus, Eva; Unterrainer, Human Friedrich

    2017-10-01

    Eye Movement Desensitization and Reprocessing (EMDR) is a therapeutic method that has been shown to be especially effective in traumatic disorders. Since the concept of an addiction memory has become widely accepted, the use of EMDR also in substance use disorders (SUD) treatment might count as a separate field. This review summarizes the current state of research on treatment effects EMDR in SUD. The literature search included the databases of PubMed and PsychInfo; four studies met the inclusion criteria. EMDR was found to be related to a decreased amount of craving, fear and depression and to an improvement of emotion regulation and management and self-esteem. Initial findings indicate a high therapeutic potential of EMDR in SUD treatment. Georg Thieme Verlag KG Stuttgart · New York.

  8. The use of video clips in teleconsultation for preschool children with movement disorders.

    Science.gov (United States)

    Gorter, Hetty; Lucas, Cees; Groothuis-Oudshoorn, Karin; Maathuis, Carel; van Wijlen-Hempel, Rietje; Elvers, Hans

    2013-01-01

    To investigate the reliability and validity of video clips in assessing movement disorders in preschool children. The study group included 27 children with neuromotor concerns. The explorative validity group included children with motor problems (n = 21) or with typical development (n = 9). Hempel screening was used for live observation of the child, full recording, and short video clips. The explorative study tested the validity of the clinical classifications "typical" or "suspect." Agreement between live observation and the full recording was almost perfect; Agreement for the clinical classification "typical" or "suspect" was substantial. Agreement between the full recording and short video clips was substantial to moderate. The explorative validity study, based on short video clips and the presence of a neuromotor developmental disorder, showed substantial agreement. Hempel screening enables reliable and valid observation of video clips, but further research is necessary to demonstrate the predictive value.

  9. Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Neutel, Dulce; Tchikviladzé, Maya; Charles, Perrine; Leu-Semenescu, Smaranda; Roze, Emmanuel; Durr, Alexandra; Arnulf, Isabelle

    2015-06-01

    Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown. To evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length. The clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype-phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video. The patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control. The nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Selenium, selenoproteins and neurodegenerative diseases.

    Science.gov (United States)

    Cardoso, Bárbara Rita; Roberts, Blaine R; Bush, Ashley I; Hare, Dominic J

    2015-08-01

    It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

  11. GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

    Science.gov (United States)

    Ohba, Chihiro; Shiina, Masaaki; Tohyama, Jun; Haginoya, Kazuhiro; Lerman-Sagie, Tally; Okamoto, Nobuhiko; Blumkin, Lubov; Lev, Dorit; Mukaida, Souichi; Nozaki, Fumihito; Uematsu, Mitsugu; Onuma, Akira; Kodera, Hirofumi; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Kato, Mitsuhiro; Ogata, Kazuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi

    2015-06-01

    Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations. Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset stereotypic hand movements were observed in two and three patients, respectively. All the four patients exhibited only nonspecific focal and diffuse epileptiform abnormality, and never showed suppression-burst or hypsarrhythmia during infancy. A de novo mosaic mutation (c.1923G>A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor. Clinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  12. Metals and neurodegenerative diseases. A systematic review.

    Science.gov (United States)

    Cicero, Calogero Edoardo; Mostile, Giovanni; Vasta, Rosario; Rapisarda, Venerando; Signorelli, Salvatore Santo; Ferrante, Margherita; Zappia, Mario; Nicoletti, Alessandra

    2017-11-01

    Neurodegenerative processes encompass a large variety of diseases with different pathological patterns and clinical presentation such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD) and Parkinson's disease (PD). Genetic mutations have a known causative role, but the majority of cases are likely to be probably caused by a complex gene-environment interaction. Exposure to metals has been hypothesized to increase oxidative stress in brain cells leading to cell death and neurodegeneration. Neurotoxicity of metals has been demonstrated by several in vitro and in vivo experimental studies and it is likely that each metal could be toxic through specific pathways. The possible pathogenic role of different metals has been supported by some epidemiological evidences coming from occupational and ecological studies. In order to assess the possible association between metals and neurodegenerative disorders, several case-control studies have also been carried out evaluating the metals concentration in different biological specimens such as blood/serum/plasma, cerebrospinal fluid (CSF), nail and hair, often reporting conflicting results. This review provides an overview of our current knowledge on the possible association between metals and ALS, AD and PD as main neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review)

    Science.gov (United States)

    Simpson, D.M.; Blitzer, A.; Brashear, A.; Comella, C.; Dubinsky, R.; Hallett, M.; Jankovic, J.; Karp, B.; Ludlow, C.L.; Miyasaki, J.M.; Naumann, M.; So, Y.

    2017-01-01

    Objective To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of movement disorders. Methods A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and selected movement disorders. Authors reviewed, abstracted, and classified articles based on American Academy of Neurology criteria (Class I–IV). Results The highest quality literature available for the respective indications was as follows: blepharospasm (two Class II studies); hemifacial spasm (one Class II and one Class III study); cervical dystonia (seven Class I studies); focal upper extremity dystonia (one Class I and three Class II studies); focal lower extremity dystonia (one Class II study); laryngeal dystonia (one Class I study); motor tics (one Class II study); and upper extremity essential tremor (two Class II studies). Recommendations Botulinum neurotoxin should be offered as a treatment option for the treatment of cervical dystonia (Level A), may be offered for blepharospasm, focal upper extremity dystonia, adductor laryngeal dystonia, and upper extremity essential tremor (Level B), and may be considered for hemifacial spasm, focal lower limb dystonia, and motor tics (Level C). While clinicians’ practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data. PMID:18458230

  14. Validation of the Turkish Version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire

    Science.gov (United States)

    Tarı Cömert, Itır; Pelin, Zerrin; Arıcak, Tolga; Yapan, Saadet

    2016-01-01

    The aim of this study was to assess the validity and reliability of a Turkish version of the rapid eye movement sleep behavior disorder questionnaire (the RBDSQ-T) for identifying patients with rapid eye movement sleep behavior disorder (RBD) and to ensure that this tool can be applied in Turkish language. Three groups were enrolled to validate the RBDSQ-T: 78 healthy controls, 17 patients previously diagnosed with RBD, and 28 patients with obstructive sleep apnea syndrome (OSAS). Based on a cut-off score of five, the RBDSQ-T was able to discriminate RBD patients from healthy controls with sensitivity of 100% and specificity of 87%. Accordingly, 63% of patients were correctly diagnosed using the RBDSQ-T. Similarly, with a cut-off score of five, the RBDSQ-T was able to discriminate RBD from OSAS with sensitivity of 100% and specificity of 64%. Assessment of test-retest reliability and internal consistency reliability using Kuder-Richardson 20 analysis revealed a test-retest correlation coefficient of 0.95 and a Kuder-Richardson 20 value of 0.82. The findings demonstrate that the RBDSQ-T is a valid and reliable tool. PMID:27340339

  15. Validation of the Turkish Version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire

    Directory of Open Access Journals (Sweden)

    Itır Tarı Cömert

    2016-01-01

    Full Text Available The aim of this study was to assess the validity and reliability of a Turkish version of the rapid eye movement sleep behavior disorder questionnaire (the RBDSQ-T for identifying patients with rapid eye movement sleep behavior disorder (RBD and to ensure that this tool can be applied in Turkish language. Three groups were enrolled to validate the RBDSQ-T: 78 healthy controls, 17 patients previously diagnosed with RBD, and 28 patients with obstructive sleep apnea syndrome (OSAS. Based on a cut-off score of five, the RBDSQ-T was able to discriminate RBD patients from healthy controls with sensitivity of 100% and specificity of 87%. Accordingly, 63% of patients were correctly diagnosed using the RBDSQ-T. Similarly, with a cut-off score of five, the RBDSQ-T was able to discriminate RBD from OSAS with sensitivity of 100% and specificity of 64%. Assessment of test-retest reliability and internal consistency reliability using Kuder-Richardson 20 analysis revealed a test-retest correlation coefficient of 0.95 and a Kuder-Richardson 20 value of 0.82. The findings demonstrate that the RBDSQ-T is a valid and reliable tool.

  16. Autism as a developmental disorder in intentional movement and affective engagement.

    Science.gov (United States)

    Trevarthen, Colwyn; Delafield-Butt, Jonathan T

    2013-01-01

    We review evidence that autistic spectrum disorders have their origin in early prenatal failure of development in systems that program timing, serial coordination and prospective control of movements, and that regulate affective evaluations of experiences. There are effects in early infancy, before medical diagnosis, especially in motor sequencing, selective or exploratory attention, affective expression and intersubjective engagement with parents. These are followed by retardation of cognitive development and language learning in the second or third year, which lead to a diagnosis of ASD. The early signs relate to abnormalities that have been found in brain stem systems and cerebellum in the embryo or early fetal stage, before the cerebral neocortex is functional, and they have clear consequences in infancy when neocortical systems are intensively elaborated. We propose, with evidence of the disturbances of posture, locomotion and prospective motor control in children with autism, as well as of their facial expression of interest and affect, and attention to other persons' expressions, that examination of the psychobiology of motor affective disorders, rather than later developing cognitive or linguistic ones, may facilitate early diagnosis. Research in this area may also explain how intense interaction, imitation or "expressive art" therapies, which respond intimately with motor activities, are effective at later stages. Exceptional talents of some autistic people may be acquired compensations for basic problems with expectant self-regulations of movement, attention and emotion.

  17. Autism as a developmental disorder in intentional movement and affective engagement

    Directory of Open Access Journals (Sweden)

    COLWYN eTREVARTHEN

    2013-07-01

    Full Text Available We review evidence that autistic spectrum disorders have their origin in early, prenatal failure of development in systems that program timing, serial coordination and prospective control of movements and that regulate affective evaluations of experiences. There are effects in early infancy, before medical diagnosis, especially in motor sequencing, selective or exploratory attention, affective expression and intersubjective engagement with parents. These are followed by retardation of cognitive development and language learning in the second or third year, which lead to a diagnosis of ASD. The early signs relate to abnormalities that have been found in brain stem systems and cerebellum in the embryo or early foetal stage, before the cerebral neocortex is functional, and they have clear consequences in infancy when neocortical systems are intensively elaborated. We propose, with evidence of the disturbances of posture, locomotion and prospective motor control in children with autism, as well as facial expression of interest and affect, and attention to other persons’ expressions, that examination of the psychobiology of motor affective disorders, rather than later developing cognitive or linguistic ones, may facilitate early diagnosis. Research in this area may also explain how intense interaction, imitation or ‘expressive art’ therapies, which respond intimately with motor activities, are effective at later stages. Exceptional talents of some autistic people may be acquired compensations for basic problems with expectant self-regulations of movement, attention and emotion.

  18. Impact of Transcranial Magnetic Stimulation on Functional Movement Disorders: Cortical Modulation or a Behavioral Effect?

    Directory of Open Access Journals (Sweden)

    Béatrice Garcin

    2017-07-01

    Full Text Available IntroductionRecent studies suggest that repeated transcranial magnetic stimulation (TMS improves functional movement disorders (FMDs, but the underlying mechanisms are unclear. The objective was to determine whether the beneficial action of TMS in patients with FMDs is due to cortical neuromodulation or rather to a cognitive-behavioral effect.MethodConsecutive patients with FMDs underwent repeated low-frequency (0.25 Hz magnetic stimulation over the cortex contralateral to the symptoms or over the spinal roots [root magnetic stimulation (RMS] homolateral to the symptoms. The patients were randomized into two groups: group 1 received RMS on day 1 and TMS on day 2, while group 2 received the same treatments in reverse order. We blindly assessed the severity of movement disorders before and after each stimulation session.ResultsWe studied 33 patients with FMDs (dystonia, tremor, myoclonus, Parkinsonism, or stereotypies. The median symptom duration was 2.9 years. The magnetic stimulation sessions led to a significant improvement (>50% in 22 patients (66%. We found no difference between TMS and RMS.ConclusionWe suggest that the therapeutic benefit of TMS in patients with FMDs is due more to a cognitive-behavioral effect than to cortical neuromodulation.

  19. Rescue Procedures after Suboptimal Deep Brain Stimulation Outcomes in Common Movement Disorders

    Directory of Open Access Journals (Sweden)

    Adam M. Nagy

    2016-10-01

    Full Text Available Deep brain stimulation (DBS is a unique, functional neurosurgical therapy indicated for medication refractory movement disorders as well as some psychiatric diseases. Multicontact electrodes are placed in “deep” structures within the brain with targets varying depending on the surgical indication. An implanted programmable pulse generator supplies the electrodes with a chronic, high frequency electrical current that clinically mimics the effects of ablative lesioning techniques. DBS’s efficacy has been well established for its movement disorder indications (Parkinson’s disease, essential tremor, and dystonia. However, clinical outcomes are sometimes suboptimal, even in the absence of common, potentially reversible complications such as hardware complications, infection, poor electrode placement, and poor programming parameters. This review highlights some of the rescue procedures that have been explored in suboptimal DBS cases for Parkinson’s disease, essential tremor, and dystonia. To date, the data is limited and difficult to generalize, but a large majority of published reports demonstrate positive results. The decision to proceed with such treatments should be made on a case by case basis. Larger studies are needed to clearly establish the benefit of rescue procedures and to establish for which patient populations they may be most appropriate.

  20. Early Controversies over Athetosis: I. Clinical Features, Differentiation from other Movement Disorders, Associated Conditions, and Pathology.

    Science.gov (United States)

    Lanska, Douglas J

    2013-01-01

    Since the description of athetosis in 1871 by American neurologist William Alexander Hammond (1828-1900) the disorder has been a source of controversy, as were many aspects of Hammond's career. Primary sources have been used to review controversies in the 50-year period since the initial description of athetosis, in particular those concerning clinical features, differentiation from other movement disorders, associated conditions, and pathology. Controversies concerning treatment will be addressed in a subsequent article. Hammond struggled to establish athetosis as a distinct clinical-pathological entity, and had successfully predicted the striatal pathology in his initial case (albeit somewhat serendipitously). Athetosis was, nevertheless, considered by many neurologists to be a form of post-hemiplegic chorea or part of a continuum between chorea and dystonia. European neurologists, and particularly the French, initially ignored or discounted the concept. Additional controversies arose over whether the movements persisted during sleep, whether athetosis was, or could be, associated with imbecility or insanity, and how it should be treated. Some controversies concerning athetosis served to identify areas where knowledge was insufficient to make accurate statements, despite prior self-assured or even dogmatic statements to the contrary. Other controversies illustrated established prejudices, even if these biases were often only apparent with the greater detachment of hindsight.

  1. Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor.

    Science.gov (United States)

    Miller, Kimberly M; Okun, Michael S; Fernandez, Hubert F; Jacobson, Charles E; Rodriguez, Ramon L; Bowers, Dawn

    2007-04-15

    Depression is common in Parkinson's disease (PD) and affects 30 to 50% of all patients. In contrast to the wealth of research on depression in PD, little is known about the occurrence of depression in other movement disorders. The primary objective of the current study was to determine whether the high prevalence of depression symptoms seen in PD is also found in other movement disorders, by directly comparing rates of specific depression symptoms and depression severity across PD, dystonia, and essential tremor (ET). Three hundred and fifty-four patients with PD, 83 patients with dystonia, and 53 patients with ET completed the Beck Depression Inventory (BDI). We found no significant between-groups differences for depression severity, frequency, or endorsement of specific depression symptoms. Forty-eight percent of PD patients, 37.3% of dystonia patients, and 34% of ET patients were found to be at least mildly depressed (BDI score of 10 or higher). The most commonly endorsed symptoms were fatigability, difficulty with work, anhedonia, and sleep disturbance. Clinicians should be aware that depression is a frequent problem in dystonia and ET, in addition to PD, and inquire about depression symptoms in these patients so that they can be appropriately treated.

  2. REM sleep behavior disorder in Parkinson′s disease: A case from India confirmed with polysomnographic data

    Directory of Open Access Journals (Sweden)

    Ravi Gupta

    2013-01-01

    Full Text Available Rapid eye movement (REM sleep behavior disorder is a condition characterized by dream enactment. This condition may accompany neurodegenerative disorders. However, only a few reports from India are available, that too, without any polysomnographic evidence. We are reporting a case of REM sleep behavior disorder with polysomnographic evidence.

  3. Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

    Science.gov (United States)

    Sasai-Sakuma, Taeko; Frauscher, Birgit; Mitterling, Thomas; Ehrmann, Laura; Gabelia, David; Brandauer, Elisabeth; Inoue, Yuichi; Poewe, Werner; Högl, Birgit

    2014-09-01

    Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Age- and sex-dependent laterality of rat hippocampal cholinergic system in relation to animal models of neurodevelopmental and neurodegenerative disorders.

    Science.gov (United States)

    Kristofiková, Zdena; Stástný, Frantisek; Bubeniková, Vera; Druga, Rastislav; Klaschka, Jan; Spaniel, Filip

    2004-04-01

    symmetrical drop in the number of choline carriers of lesioned male rats but a asymmetrical decrease in the activity of remaing carriers, suggesting defects in processes of sexual brain differentiation, leading under normal conditions to the higher activity of carriers in the left hippocampus. The data demonstrate viral infection-mediated alterations in normal patterns of brain asymmetry and are discussed in relation to animal models of neurodevelopmental and neurodegenerative diseases.

  5. Eye movements reveal sexually dimorphic deficits in children with fetal alcohol spectrum disorder

    Directory of Open Access Journals (Sweden)

    Angelina ePaolozza

    2015-03-01

    Full Text Available Background: We examined the accuracy and characteristics of saccadic eye movements in children with fetal alcohol spectrum disorder (FASD compared with typically developing control children. Previous studies have found that children with FASD produce saccades that are quantifiably different from controls. Additionally, animal studies have found sex-based differences for behavioral effects after prenatal alcohol exposure. Therefore, we hypothesized that eye movement measures will show sexually dimorphic results.Methods: Children (aged 5-18 years with FASD (n=71 and typically developing controls (n=113 performed a visually-guided saccade task. Saccade metrics and behavior were analyzed for sex and group differences. Results: Female control participants had greater amplitude saccades than control males or females with FASD. Accuracy was significantly poorer in the FASD group, especially in males, which introduced significantly greater variability in the data. Therefore, we conducted additional analyses including only those trials in which the first saccade successfully reached the target within a ±1˚ window. In this restricted amplitude dataset, the females with FASD made saccades with significantly lower velocity and longer duration, whereas the males with FASD did not differ from the control group. Additionally, the mean and peak deceleration were selectively decreased in the females with FASD. Conclusions: These data support the hypothesis that children with FASD exhibit specific deficits in eye movement control and sensory-motor integration associated with cerebellar and/or brain stem circuits. Moreover, prenatal alcohol exposure may have a sexually dimorphic impact on eye movement metrics, with males and females exhibiting differential patterns of deficit.

  6. Targeting bed nucleus of the stria terminalis for severe obsessive-compulsive disorder: more unexpected lead placement in obsessive-compulsive disorder than in surgery for movement disorders.

    Science.gov (United States)

    Nuttin, Bart; Gielen, Frans; van Kuyck, Kris; Wu, Hemmings; Luyten, Laura; Welkenhuysen, Marleen; Brionne, Thomas C; Gabriëls, Loes

    2013-01-01

    In preparation for a multicenter study, a protocol was written on how to perform surgical targeting of the bed nucleus of the stria terminalis, based on the lead implantation experience in patients with treatment-refractory obsessive-compulsive disorder (OCD) at the Universitaire Ziekenhuizen Leuven (UZ Leuven). When analyzing the postoperative images, we were struck by the fact that the difference between the postoperative position of the leads and the planned position seemed larger than expected. The precision of targeting in four patients with severe OCD who received bilateral model 3391 leads (Medtronic) was compared with the precision of targeting in the last seven patients who underwent surgery at UZ Leuven for movement disorders (four with Parkinson disease and three with essential tremor; all received bilateral leads). Because the leads implanted in six of the seven patients with movement disorders were model 3387 leads (Medtronic), targeting precision was also analyzed in four patients with OCD in whom model 3387 leads were implanted in the same target as the other patients with OCD. In the patients with OCD, every implanted lead deviated at least 1.3 mm from its intended position in at least one of three directions (lateral, anteroposterior, and depth), whereas in the patients with movement disorders, the maximal deviation of any of all implanted leads was 1.3 mm. The deviations in lead placement were comparable in patients with OCD who received a model 3387 implant and patients who received a model 3391 implant. In the patients with OCD, all leads were implanted more posteriorly than planned. The cause of the posterior deviation could not be determined with certainty. The most likely cause was an increased mechanical resistance of the brain tissue along the trajectory when following the targeting protocol compared with the trajectories classically used for subthalamic nucleus or ventral intermediate nucleus of the thalamus stimulation. Copyright © 2013

  7. Electroencephalographic findings related with mild cognitive impairment in idiopathic rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Sasai, Taeko; Matsuura, Masato; Inoue, Yuichi

    2013-12-01

    Mild cognitive impairment (MCI) and electroencephalographic (EEG) slowing have been reported as common findings of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) and α-synucleinopathies. The objective of this study is to clarify the relation between MCI and physiological markers in iRBD. Cross-sectional study. Yoyogi Sleep Disorder Center. Thirty-one patients with iRBD including 17 younger patients with iRBD (younger than 70 y) and 17 control patients for the younger patients with iRBD. N/A. Montreal Cognitive Assessment (MoCA) and n-polysomnogram (PSG) were conducted of all participants. In patients with iRBD, the factors associated with MCI were explored among parameters of REM sleep without atonia (RWA), score of Sniffin' Sticks Test (threshold-discrimination-identification [TDI] score), RBD morbidity, and RBD severity evaluated with the Japanese version of the RBD questionnaire (RBDQ-JP). The younger iRBD group showed significantly lower alpha power during wake and lower MoCA score than the age-matched control group. MCI was detected in 13 of 17 patients (76.5%) on MoCA in this group. Among patients wtih iRBD, the MoCA score negatively correlated with age, proportion of slow wave sleep, TDI score, and EEG spectral power. Multiple regression analysis provided the following equation: MoCA score = 50.871-0.116*age -5.307*log (δ power during REM sleep) + 0.086*TDI score (R² = 0.598, P sleep), and 0.357 for TDI score (F = 9.900, P sleep and olfactory dysfunction, was revealed to be associated with cognitive decline in idiopathic rapid eye movement sleep behavior disorder.

  8. Introduction to the Special Issue on Clinical Neuropsychology of Movement Disorders.

    Science.gov (United States)

    Tröster, Alexander I

    2017-11-01

    The special issue on the clinical neuropsychology of movement disorders provides an overview for the non-subspecialist clinical neuropsychologist and other clinical neuroscientists of the neuropsychological features, assessment and treatment of Parkinson's disease and Lewy body dementias, atypical parkinsonian disorders (corticobasal syndrome, progressive supranuclear palsy, and multiple system atrophy), Huntington's disease, dystonia, and amyotrophic lateral sclerosis. Additionally, articles provide overviews of neuropsychological and ethical issues related to deep brain stimulation and a discussion of non-pharamcologic and non-invasive treatment of cognitive dysfunction in Parkinson's disease. A search of PubMed using neuropsycholog* and parkinson* as search terms indicates that the number of articles dealing with neuropsychology of parkinsonian disorders has more than doubled in each of the past three decades (1990-99:269 entries, 2000-09:575 entries, 2010-17:967 entries). This rapid growth of research makes a special issue on the topic very timely. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

    Science.gov (United States)

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  10. Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients.

    Science.gov (United States)

    Plomhause, Lucie; Dujardin, Kathy; Duhamel, Alain; Delliaux, Marie; Derambure, Philippe; Defebvre, Luc; Monaca Charley, Christelle

    2013-10-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naïve, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups. Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination. Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea-hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs. 18 min, respectively; P=.014). A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Impaired recognition of emotions from body movements is associated with elevated motion coherence thresholds in autism spectrum disorders.

    OpenAIRE

    A. P. Atkinson

    2009-01-01

    Recent research has confirmed that individuals with Autism Spectrum Disorder (ASD) have difficulties in recognizing emotions from body movements. Difficulties in perceiving coherent motion are also common in ASD. Yet it is unknown whether these two impairments are related. Thirteen adults with ASD and 16 age- and IQ-matched typically developing (TD) adults classified basic emotions from point-light and full-light displays of body movements and discriminated the direction of coherent motion in...

  12. The impact of metabotropic glutamate receptors into active neurodegenerative processes: A "dark side" in the development of new symptomatic treatments for neurologic and psychiatric disorders.

    Science.gov (United States)

    Bruno, Valeria; Caraci, Filippo; Copani, Agata; Matrisciano, Francesco; Nicoletti, Ferdinando; Battaglia, Giuseppe

    2017-03-15

    Metabotropic glutamate (mGlu) receptor ligands are under clinical development for the treatment of CNS disorders with high social and economic burden, such as schizophrenia, major depressive disorder (MDD), and Parkinson's disease (PD), and are promising drug candidates for the treatment of Alzheimer's disease (AD). So far, clinical studies have shown symptomatic effects of mGlu receptor ligands, but it is unknown whether these drugs act as disease modifiers or, at the opposite end, they accelerate disease progression by enhancing neurodegeneration. This is a fundamental issue in the treatment of PD and AD, and is also an emerging theme in the treatment of schizophrenia and MDD, in which neurodegeneration is also present and contribute to disease progression. Moving from in vitro data and preclinical studies, we discuss the potential impact of drugs targeting mGlu2, mGlu3, mGlu4 and mGlu5 receptor ligands on active neurodegeneration associated with AD, PD, schizophrenia, and MDD. We wish to highlight that our final comments on the best drug candidates are not influenced by commercial interests or by previous or ongoing collaborations with drug companies. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. “We Dance and Find Each Other”1: Effects of Dance/Movement Therapy on Negative Symptoms in Autism Spectrum Disorder

    National Research Council Canada - National Science Library

    Hildebrandt, Malin; Koch, Sabine; Fuchs, Thomas

    2016-01-01

    .... The randomized controlled trial at hand investigated the effects of a 10-week manualized dance and movement therapy intervention on negative symptoms in participants with autism spectrum disorder...

  14. Rapid Eye Movement Sleep Behavior Disorder: A Window on the Emotional World of Parkinson Disease

    Science.gov (United States)

    Mariotti, Paolo; Quaranta, Davide; Di Giacopo, Raffaella; Bentivoglio, Anna Rita; Mazza, Marianna; Martini, Annalisa; Canestri, Jorge; Della Marca, Giacomo

    2015-01-01

    Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia characterized by motor activity during sleep with dream mentation. Aggressiveness has been considered a peculiar feature of dreams associated with RBD, despite normal score in aggressiveness scales during wakefulness. We aimed to measure daytime aggressiveness and analyze dream contents in a population of patients with Parkinson disease (PD) with and without RBD. Design: This is a single-center prospective observational study; it concerns the description of the clinical features of a medical disorder in a case series. Setting: The study was performed in the Department of Neurosciences of the Catholic University in Rome, Italy. Patients: Three groups of subjects were enrolled: patients with PD plus RBD, patients with PD without RBD, and healthy controls. Interventions: The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. For the evaluation of diurnal aggressiveness, the Buss-Perry Aggression Questionnaire (BPAQ) was used. The content of dreams was evaluated by means of the methods of Hall and Van De Castle. Measurements and Results: Patients with PD without RBD displayed higher levels of anger, and verbal and physical aggressiveness than patients with PD and RBD and controls. Patients with PD and RBD and controls did not differ in hostility. Conclusions: It can be hypothesized that a noradrenergic impairment at the level of the locus coeruleus could, at the same time, explain the presence of REM sleep behavior disorder, as well as the reduction of diurnal aggressiveness. This finding also suggests a role for REM sleep in regulating homeostasis of emotional brain function. Citation: Mariotti P, Quaranta D, Di Giacopo R, Bentivoglio AR, Mazza M, Martini A, Canestri J, Della Marca G. Rapid eye movement sleep behavior disorder: a window on the emotional world of Parkinson disease. SLEEP 2015;38(2):287–294. PMID:25325501

  15. Deficits in facial, body movement and vocal emotional processing in autism spectrum disorders.

    Science.gov (United States)

    Philip, R C M; Whalley, H C; Stanfield, A C; Sprengelmeyer, R; Santos, I M; Young, A W; Atkinson, A P; Calder, A J; Johnstone, E C; Lawrie, S M; Hall, J

    2010-11-01

    Previous behavioural and neuroimaging studies of emotion processing in autistic spectrum disorder (ASD) have focused on the use of facial stimuli. To date, however, no studies have examined emotion processing in autism across a broad range of social signals. This study addressed this issue by investigating emotion processing in a group of 23 adults with ASD and 23 age- and gender-matched controls. Recognition of basic emotions ('happiness', 'sadness', 'anger', disgust' and 'fear') was assessed from facial, body movement and vocal stimuli. The ability to make social judgements (such as approachability) from facial stimuli was also investigated. Significant deficits in emotion recognition were found in the ASD group relative to the control group across all stimulus domains (faces, body movements and voices). These deficits were seen across a range of emotions. The ASD group were also impaired in making social judgements compared to the control group and this correlated with impairments in basic emotion recognition. This study demonstrates that there are significant and broad-ranging deficits in emotion processing in ASD present across a range of stimulus domains and in the auditory and visual modality; they cannot therefore be accounted for simply in terms of impairments in face processing or in the visual modality alone. These results identify a core deficit affecting the processing of a wide range of emotional information in ASD, which contributes to the impairments in social function seen in people with this condition.

  16. Eye-movement patterns are associated with communicative competence in autistic spectrum disorders.

    Science.gov (United States)

    Norbury, Courtenay Frazier; Brock, Jon; Cragg, Lucy; Einav, Shiri; Griffiths, Helen; Nation, Kate

    2009-07-01

    Investigations using eye-tracking have reported reduced fixations to salient social cues such as eyes when participants with autism spectrum disorders (ASD) view social scenes. However, these studies have not distinguished different cognitive phenotypes. The eye-movements of 28 teenagers with ASD and 18 typically developing peers were recorded as they watched videos of peers interacting in familiar situations. Within ASD, we contrasted the viewing patterns of those with and without language impairments. The proportion of time spent viewing eyes, mouths and other scene details was calculated, as was latency of first fixation to eyes. Finally, the association between viewing patterns and social-communicative competence was measured. Individuals with ASD and age-appropriate language abilities spent significantly less time viewing eyes and were slower to fixate the eyes than typically developing peers. In contrast, there were no differences in viewing patterns between those with language impairments and typically developing peers. Eye-movement patterns were not associated with social outcomes for either language phenotype. However, increased fixations to the mouth were associated with greater communicative competence across the autistic spectrum. Attention to both eyes and mouths is important for language development and communicative competence. Differences in fixation time to eyes may not be sufficient to disrupt social competence in daily interactions. A multiple cognitive deficit model of ASD, incorporating different language phenotypes, is advocated.

  17. Hemodynamic responses of eye movement desensitization and reprocessing in posttraumatic stress disorder.

    Science.gov (United States)

    Ohtani, Toshiyuki; Ohta ni, Toshiyuki; Matsuo, Koji; Kasai, Kiyoto; Kato, Tadafumi; Kato, Nobumasa

    2009-12-01

    Eye movement desensitization and reprocessing (EMDR) is an effective psychological intervention for posttraumatic stress disorder (PTSD). Trauma-related recall (Recall) with eye movements (EMs) is thought to reduce distress. However, the neural mechanisms underlying this process remain unknown. Thirteen patients with PTSD received EMDR treatment over the course of 2-10 weeks. We assessed the change in hemoglobin concentration in the lateral prefrontal cortex (PFC) during Recall with and without EM using multi-channel near-infrared spectroscopy (NIRS). Clinical diagnosis and improvement were evaluated using the Clinician-Administered PTSD Scale. Recall with EM was associated with a significant decrease in oxygenated hemoglobin concentration ([oxy-Hb]) in the lateral PFC as compared with Recall without EM. Longitudinally, [oxy-Hb] during Recall significantly decreased and the amount of decrease was significantly correlated with clinical improvement when the post-treatment data was compared with that of the pre-treatment. Our results suggest that performing EM during Recall reduces the over-activity of the lateral PFC, which may be part of the biological basis for the efficacy of EMDR in PTSD. NIRS may be a useful tool for objective assessment of psychological intervention in PTSD.

  18. Processing of Written Irony in Autism Spectrum Disorder: An Eye-Movement Study.

    Science.gov (United States)

    Au-Yeung, Sheena K; Kaakinen, Johanna K; Liversedge, Simon P; Benson, Valerie

    2015-12-01

    Previous research has suggested that individuals with Autism Spectrum Disorders (ASD) have difficulties understanding others communicative intent and with using contextual information to correctly interpret irony. We recorded the eye movements of typically developing (TD) adults ASD adults when they read statements that could either be interpreted as ironic or non-ironic depending on the context of the passage. Participants with ASD performed as well as TD controls in their comprehension accuracy for speaker's statements in both ironic and non-ironic conditions. Eye movement data showed that for both participant groups, total reading times were longer for the critical region containing the speaker's statement and a subsequent sentence restating the context in the ironic condition compared to the non-ironic condition. The results suggest that more effortful processing is required in both ASD and TD participants for ironic compared with literal non-ironic statements, and that individuals with ASD were able to use contextual information to infer a non-literal interpretation of ironic text. Individuals with ASD, however, spent more time overall than TD controls rereading the passages, to a similar degree across both ironic and non-ironic conditions, suggesting that they either take longer to construct a coherent discourse representation of the text, or that they take longer to make the decision that their representation of the text is reasonable based on their knowledge of the world. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  19. Eye movement disorders are an early manifestation of CACNA1A mutations in children.

    Science.gov (United States)

    Tantsis, Esther M; Gill, Deepak; Griffiths, Lyn; Gupta, Sachin; Lawson, John; Maksemous, Neven; Ouvrier, Robert; Riant, Florence; Smith, Robert; Troedson, Christopher; Webster, Richard; Menezes, Manoj P

    2016-06-01

    The alpha-1 isoform of the calcium channel gene is expressed abundantly in neuronal tissue, especially within the cerebellum. Mutations in this gene may manifest with hemiplegic migraine, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) in adults. There are reports of children with CACAN1A mutations presenting with paroxysmal tonic upgaze, abnormal saccades and congenital nystagmus as well as severe forms of hemiplegic migraine. The aim of this study was to review the clinical presentation and subsequent course of all children with a CACNA1A mutation who presented to a tertiary children's hospital. We reviewed retrospectively nine children with a proven CACNA1A mutation who presented to the Children's Hospital at Westmead between 2005-2015. The initial and subsequent clinical presentation, radiological features and molecular genetic profile of each child was reviewed. Nine children presented to out institute over a 10 year period; six were female and three male. The median age of presentation was 1.2 years. Eye movement disorders were the presenting feature in eight children. Three of these children later presented with severe hemiplegic migraine episodes often requiring ICU care. Affected children also had developmental delay and developed classical hemiplegic migraine, episodic ataxia and seizures. Calcium channel blockers were used with some efficacy in preventing severe HM episodes. Eye movement disorders are an early manifestation of CACNA1A mutations in children. Improved recognition of the CACNA1A phenotype in childhood is important for early diagnosis, counselling and appropriate emergency management. There is some early evidence that calcium channel blockers may be an effective prophylactic agent for the severe hemiplegic migraine episodes. © 2016 Mac Keith Press.

  20. [Long-term effects of deep brain stimulation for movement disorders: a literature-based analysis].

    Science.gov (United States)

    Eberhardt, O; Reithmeier, T; Topka, H

    2014-12-01

    Deep brain stimulation has become an established therapy for various movement disorders but questions regarding its long-term effectiveness remain. This study was designed to evaluate the long-term effectiveness of deep brain stimulation for movement disorders refractory to current medical therapy based on published long-term studies. A review was carried out of all available studies with a minimum follow-up of 5 years of patients with deep brain stimulation for Parkinson's disease, essential tremor and dystonia. A total of 23 studies of deep brain stimulation for Parkinson's disease, 7 studies for essential tremor and 14 studies for dystonia were included. After a follow-up of at least 5 years, improvement of current motor scores could be observed in Parkinson's disease (subthalamic stimulation) by approximately 40%, by approximately 50% for essential tremor and by 60% for dystonia (mostly generalized forms). In Parkinson's disease, motor improvements tend to diminish over time due to progression of dysarthria, axial symptoms and other motor features less responsive to deep brain stimulation. Non-dopaminergic symptoms tend to progress and lessen the positive effects on the quality of life. There appears to be a subgroup of patients with essential tremor who show decreasing effectiveness of deep brain stimulation, probably related to disease progression. Currently, no single prognostic marker has been established to identify this subgroup. Most forms of secondary dystonia seem to respond more variably than primary generalized dystonia. Deep brain stimulation remains a relatively safe and effective therapy in carefully selected patients after long-term follow-up according to published data, although disease progression and other disease-specific factors seem to modify its effectiveness over time.

  1. Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

    Science.gov (United States)

    Bhullar, Khushwant S.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders. PMID:23840922

  2. Indian Herbs for the Treatment of Neurodegenerative Disease.

    Science.gov (United States)

    Mannangatti, Padmanabhan; Naidu, Kamalakkannan Narasimha

    2016-01-01

    Ayurveda, an ancient system of medicine that is indigenous to India, is believed to be the world's oldest comprehensive health-care system and is now one of the most recognized and widely practiced disciplines of alternative medicine in the world. Medicinal herbs have been in use for treating diseases since ancient times in India. Ayurvedic therapies with medicinal herbs and herbomineral products generally provide relief without much adverse effects even after prolonged administration. Neurodegenerative disorders are a major cause of mortality and disability, and increasing life spans represent one of the key challenges of medical research. Ayurvedic medicine describes most neurodegenerative diseases and has defined a number of plants with therapeutic benefits for the treatment of neurodegenerative diseases having antioxidant activities. In this chapter, the role of four important Ayurvedic medicinal plants, viz., Withania somnifera (ashwagandha), Bacopa monnieri (brahmi), Centella asiatica (gotu kola), and Mucuna pruriens (velvet bean), on neurodegenerative diseases are discussed.

  3. Longitudinal assessment of probable rapid eye movement sleep behaviour disorder in Parkinson's disease.

    Science.gov (United States)

    Bjørnarå, K A; Dietrichs, E; Toft, M

    2015-08-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is frequently present in patients with Parkinson's disease (PD) and may have prognostic implications. There are few longitudinal studies of RBD in patients with PD. Our aim was to investigate whether RBD was a persistent feature in a follow-up study of 107 patients with PD. After a mean follow-up time of 3 years, 96 patients were available for reassessment. Probable RBD (pRBD) was diagnosed by the REM sleep behaviour disorder screening questionnaire. At follow-up, pRBD was found in 49% of the patients, versus 38% at baseline. The pRBD status remained unchanged in three-quarters of the patients, whilst 17% had new pRBD symptoms. Disease duration was longer in the pRBD group, 9.4 vs. 7.6 years (P = 0.02). Probable RBD is a persistent feature in PD and probably increases over time. © 2015 EAN.

  4. Comparison of eye movement desensitization and reprocessing with citalopram in treatment of obsessive-compulsive disorder.

    Science.gov (United States)

    Nazari, Hedayat; Momeni, Nahid; Jariani, Mojgan; Tarrahi, Mohammad Javad

    2011-11-01

    Obsessive-compulsive disorder (OCD) is one of the chronic anxiety disorders that interfere with routine individual life, occupational and social functions. There is controversy about the first choice of treatment for OCD between medication and psychotherapy. the aim was to investigate the efficacy of eye movement desensitization and reprocessing (EMDR) compared with medication by citalopram in treatment of OCD. This randomized controlled trial was carried out on 90 OCD patients that randomly were assigned into two groups. They either received therapeutic sessions of EMDR or citalopram during 12 weeks. Both groups blindly were evaluated by the Yale-Brown scale before and after the trial period. Pretreatment average Yale-Brown score of citalopram group was about 25.26 as well as 24.83 in EMDR group. The after treatment scores were 19.06 and 13.6, respectively. There was significant difference between the mean Yale-Brown scores of the two groups after treatment and EMDR was more effective than citalopram in improvement of OCD signs. It is concluded that although both therapeutic methods (EMDR and Citalopram) had significant effect in improving obsessive signs but it seems that in short term EMRD has better effect in improvement of final outcome of OCD.

  5. Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder.

    Science.gov (United States)

    Bae, Hwallip; Kim, Daeho; Park, Yong Chon

    2016-01-01

    Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

  6. Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development

    Directory of Open Access Journals (Sweden)

    Jennum P

    2016-04-01

    Full Text Available Poul Jennum, Julie AE Christensen, Marielle Zoetmulder Department of Clinical Neurophysiology, Faculty of Health Sciences, Danish Center for Sleep Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Abstract: Rapid eye movement (REM sleep behavior disorder (RBD is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. Keywords: motor control, brain stem, hypothalamus, hypocretin

  7. Just a scary dream? A brief review of sleep terrors, nightmares, and rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Haupt, Mark; Sheldon, Stephen H; Loghmanee, Darius

    2013-10-01

    The clinical spectrum of sleep disorders in children is broad, ranging from primary snoring and obstructive sleep apnea (OSA) syndrome to complex sleep-related behaviors and movement disorders. Although snoring and OSA typically receive significant attention and discussion, other biologically based sleep disorders are as common, if not more common, in children. A general pediatrician is frequently presented with the complaint of sleep talking, sleep walking, or abnormal movements during sleep. Even more alarming is the presentation of the child suddenly and explosively screaming during sleep. Such complaints fall under the category of parasomnias. Exclusive to sleep and wake-to-sleep transitions, these parasomnias include arousals with abnormal motor, behavioral, autonomic, or sensory symptoms. Parasomnias can be noticeably dissimilar in clinical manifestations, but most share biologic characteristics. Three parasomnias associated with loud vocalizations associated with sleep that can present to general practitioners include sleep terrors, nightmares, and rapid eye movement sleep behavior disorder (RBD). Although usually benign, these sleep disorders can be disruptive and even potentially dangerous to the patient and can often be threatening to quality of life. In this article, we describe the clinical features of some of these disorders and how to differentiate between their alarming presentations. Copyright 2013, SLACK Incorporated.

  8. Rehabilitation of Movement Disorders and Psychomotor Deficiency in Schizophrenia Residual Type

    Directory of Open Access Journals (Sweden)

    Andrej N. Ilanković

    2014-06-01

    Evaluation of efficacy after 6 weeks specific rehabilitation treatment with the Vilan method showed: very satisfactory results in correction of involuntary movements of the torso,   bradykinesia of the hands,  praxia  and the simple simultaneous movements; satisfactory correction of involuntary movements of the extremities, walking  and  the facial gestures. No correction was in: involuntary movement of mouth and face, tremor, ideation, ideo‑motor series and in complex simultaneous movement.

  9. Physical Activity into Socialization: A Movement-Based Social Skills Program for Children with Autism Spectrum Disorder

    Science.gov (United States)

    Lee, Jihyun; Vargo, Kristina K.

    2017-01-01

    Children with autism spectrum disorder (ASD) often exhibit deficits in social-communicative behaviors. Given the increased prevalence of children with ASD, programs designed to teach social-communicative behaviors are necessary. This article introduces a movement-based program that embeds social-skill components to improve the motor skills and…

  10. Movement disorder symptoms associated with Unified Parkinson’s Disease Rating Scale (UPDRS) in two manganese (Mn)-exposed communities

    Science.gov (United States)

    Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UP...

  11. Impaired Recognition of Emotions from Body Movements Is Associated with Elevated Motion Coherence Thresholds in Autism Spectrum Disorders

    Science.gov (United States)

    Atkinson, Anthony P.

    2009-01-01

    Recent research has confirmed that individuals with autism spectrum disorder (ASD) have difficulties in recognizing emotions from body movements. Difficulties in perceiving coherent motion are also common in ASD. Yet it is unknown whether these two impairments are related. Thirteen adults with ASD and 16 age- and IQ-matched typically developing…

  12. Brief eclectic psychotherapy v. eye movement desensitisation and reprocessing therapy for post-traumatic stress disorder: randomised controlled trial

    NARCIS (Netherlands)

    Nijdam, M.J.; Gersons, B.P.R.; Reitsma, J.B.; de Jongh, A.; Ollf, M.

    2012-01-01

    Background Trauma-focused cognitive-behavioural therapy (CBT) and eye movement desensitisation and reprocessing therapy (EMDR) are efficacious treatments for post-traumatic stress disorder (PTSD), but few studies have directly compared them using well-powered designs and few have investigated

  13. Reliability and Responsiveness of the Movement Assessment Battery for Children--Second Edition Test in Children with Developmental Coordination Disorder

    Science.gov (United States)

    Wuang, Yee-Pay; Su, Jui-Hsing; Su, Chwen-Yng

    2012-01-01

    Aim: To examine the internal consistency, test-retest reliability, and responsiveness of the Movement Assessment Battery for Children--Second Edition (MABC-2) Test for children with developmental coordination disorder (DCD). Method: One hundred and forty-four Taiwanese children with DCD aged 6 to 12 years (87 males, 57 females) were tested on…

  14. Neuroprotective Effects of Exercise on Brain Edema and Neurological Movement Disorders Following the Cerebral Ischemia and Reperfusion in Rats.

    Science.gov (United States)

    Shamsaei, Nabi; Erfani, Soheila; Fereidoni, Masoud; Shahbazi, Ali

    2017-01-01

    Cerebral ischemia and reperfusion causes physiological and biochemical changes in the neuronal cells that will eventually lead to cell damage. Evidence indicates that exercise reduces the ischemia and reperfusion-induced brain damages in animal models of stroke. In the present study, the effect of exercise preconditioning on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats was investigated. Twenty-one adult male wistar rats (weighing 260-300 g) were randomly divided into three groups: sham operated, exercise plus ischemia, and ischemia group (7 rats per group). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Transient focal cerebral ischemia and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by reperfusion for 23 hours. After 24 hours ischemia, movement disorders were tested by a special neurological examination. Also, cerebral edema was assessed by determining the brain water content. The results showed that pre-ischemic exercise significantly reduced brain edema (Pexercise preconditioning decreased the neurological movement disorders caused by brain ischemia and reperfusion (Pexercise had neuroprotective effects against brain ischemia and reperfusion-induced edema and movement disorders. Thus, it could be considered as a useful strategy for prevention of ischemic injuries, especially in people at risk.

  15. Composition, Standardization and Chemical Profiling of Banisteriopsis caapi, a Plant for the Treatment of Neurodegenerative Disorders Relevant to Parkinson’s Disease†

    Science.gov (United States)

    Wang, Yan-Hong; Samoylenko, Volodymyr; Tekwani, Babu L.; Khan, Ikhlas A.; Miller, Loren S.; Chaurasiya, Narayan D.; Rahman, Md. Mostafizur; Tripathi, Lalit M.; Khan, Shabana I.; Joshi, Vaishali C.; Wigger, Frank T.; Muhammad, Ilias

    2010-01-01

    Ethnopharmacological relevance Banisteriopsis caapi, a woody vine from the Amazonian basin, is popularly known as an ingredient of a sacred drink ayahuasca, widely used throughout the Amazon as a medicinal tea for healing and spiritual exploration. The usefulness of B. caapi has been established for alleviating symptoms of neurological disorders including Parkinson’s disease. Aim of the study Primary objective of this study was to develop the process for preparing standardized extracts of B. caapi to achieve high potency for inhibition of human monoamine oxidases (MAO) and antioxidant properties. The aqueous extracts prepared from different parts of the plant collected from different geographical locations and seasons were analyzed by HPLC for principal bioactive markers. The extracts were simultaneously tested in vitro for inhibition of human MAOs and antioxidant activity for analysis of correlation between phytochemical composition of the extracts and bioactivities. Materials and methods Reversed-phase HPLC with photodiode array detection was employed to profile the alkaloidal and non-alkaloidal components of the aqueous extract of B. caapi. The B. caapi extracts and standardized compositions were tested in vitro for inhibition of recombinant preparations of human MAO-A and MAO-B. In vitro cell-based assays were employed for evaluation of antioxidant property and mammalian cell cytotoxicity of these preparations. Results Among the different aerial parts, leaves, stems/large branches and stem bark of B. caapi, HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7-9) were present in high concentrations in dried bark of large branch. A library of HPLC chromatograms has also been generated as a tool for fingerprinting and authentication of the studied B. caapi species. The correlation between potency of MAO inhibition and antioxidant activity with the content of the main active constituents of the aqueous B. caapi extracts and

  16. Rare inborn errors of metabolism with movement disorders : a case study to evaluate the impact upon quality of life and adaptive functioning

    NARCIS (Netherlands)

    Eggink, Hendriekje; Kuiper, Anouk; Peall, Kathryn J.; Contarino, Maria Fiorella; Bosch, Annet M.; Post, Bart; Sival, Deborah A.; Tijssen, Marina A. J.; de Koning, Tom J.

    2014-01-01

    Background: Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been

  17. Rare inborn errors of metabolism with movement disorders: a case study to evaluate the impact upon quality of life and adaptive functioning

    NARCIS (Netherlands)

    Eggink, Hendriekje; Kuiper, Anouk; Peall, Kathryn J.; Contarino, Maria Fiorella; Bosch, Annet M.; Post, Bart; Sival, Deborah A.; Tijssen, Marina A. J.; de Koning, Tom J.

    2014-01-01

    Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been investigated.

  18. What is quality of life and how do we measure it? Relevance to Parkinson's disease and movement disorders.

    Science.gov (United States)

    Martinez-Martin, Pablo

    2017-03-01

    Health-related quality of life is a patient-reported outcome that complements clinical evaluation and provides information about disease activity and effects of the treatment. The objective of this review is to present the conceptual framework, the measures, and some of their most relevant applications in the field of Parkinson's disease and movement disorders. Health-related quality of life is a subjective, individual, and multidimensional construct, and its main dimensions are physical, mental, and social, besides global perceptions of health and personal domains. Health-related quality of life measurement is carried out by means of questionnaires or scales, ideally self-applied by patients, and has a diversity of important applications for clinical practice, research, and health policy. Movement disorders and Parkinson's disease are complex conditions impacting all components of patients' health-related quality of life. The use of health-related quality of life tools provides important information on a variety of aspects that are important to patients while complementing clinical evaluations. In particular, studies using this kind of assessment can identify and monitor the most important health-related quality of life determinant factors, allowing tailored assistance and prioritized interventions. In addition, maintaining or improving the patients' health-related quality of life is an objective of care for chronic diseases and, therefore, it has to be monitored over time and as an outcome of clinical trials. Several methods are available for the interpretation of the change in scores of health-related quality of life measures, although a definitive agreement on the most appropriate method is yet to be determined. Presently, health-related quality of life assessment is an important outcome for research and management of chronic conditions such as Parkinson's disease and other movement disorders. © 2016 International Parkinson and Movement Disorder Society.

  19. The impact of robotic rehabilitation in children with acquired or congenital movement disorders.

    Science.gov (United States)

    Frascarelli, F; Masia, L; Di Rosa, G; Cappa, P; Petrarca, M; Castelli, E; Krebs, H I

    2009-03-01

    The aim of this study was to evaluate if the robot-mediated therapy (RMT) can yield positive outcomes in children with acquired or congenital upper extremity movement disorders. This was an uncontrolled pilot study with pre-post treatment outcome comparison carried out by the Pediatric Rehabilitation Department of a Children's Hospital. The study enrolled 12 children, aged 5 to 15 years, suffering from acquired (at least 12 months post-onset) or congenital upper limb motor impairment. 4 stroke, 6 traumatic brain injuries, and 2 hemiplegic cerebral palsy. RMT was provided 3 times a week for an hour during 6 weeks for a total of 18 robot therapy sessions. The Melbourne Scale (MS) and the upper-extremity subsection of the Fugl-Meyer Assessment (FMA) were used for measurement of impairment. Secondary outcome measurements were made through the Modified Ashworth Scale (MAS); the Reaching Performance Scale (RPS); Parent's Questionnaire, and robot-based evaluation measurements. Specifically, authors compared the smoothness, as measured by the jerk metric, and average speed of unconstrained reaching movements. Pre-post clinical evaluation revealed statistically significant gains for all primary and secondary metrics. In addition, significant improvement of robot-based metrics was observed. The primary outcome measurement mean (SEM) gains were 6.71 (1.29) for MS and 3.33 (0.80) for the FMA. RMT led to spasticity decreases in chronic cases, as shown by the reduction of MAS. It led to improved trunk-upper extremity postural attitude as demonstrated by improved RPS, and it was well accepted by parents and children as observed in the Parent's Questionnaire. This study suggests that RMT may hold rehabilitative benefits in children suffering from acquired and congenital hemiparesis.

  20. State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

    Science.gov (United States)

    Wagle Shukla, Aparna; Okun, Michael S

    2016-01-01

    Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

  1. Validation of an integrated software for the detection of rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Frauscher, Birgit; Gabelia, David; Biermayr, Marlene; Stefani, Ambra; Hackner, Heinz; Mitterling, Thomas; Poewe, Werner; Högl, Birgit

    2014-10-01

    Rapid eye movement sleep without atonia (RWA) is the polysomnographic hallmark of REM sleep behavior disorder (RBD). To partially overcome the disadvantages of manual RWA scoring, which is time consuming but essential for the accurate diagnosis of RBD, we aimed to validate software specifically developed and integrated with polysomnography for RWA detection against the gold standard of manual RWA quantification. Academic referral center sleep laboratory. Polysomnographic recordings of 20 patients with RBD and 60 healthy volunteers were analyzed. N/A. Motor activity during REM sleep was quantified manually and computer assisted (with and without artifact detection) according to Sleep Innsbruck Barcelona (SINBAR) criteria for the mentalis ("any," phasic, tonic electromyographic [EMG] activity) and the flexor digitorum superficialis (FDS) muscle (phasic EMG activity). Computer-derived indices (with and without artifact correction) for "any," phasic, tonic mentalis EMG activity, phasic FDS EMG activity, and the SINBAR index ("any" mentalis + phasic FDS) correlated well with the manually derived indices (all Spearman rhos 0.66-0.98). In contrast with computerized scoring alone, computerized scoring plus manual artifact correction (median duration 5.4 min) led to a significant reduction of false positives for "any" mentalis (40%), phasic mentalis (40.6%), and the SINBAR index (41.2%). Quantification of tonic mentalis and phasic FDS EMG activity was not influenced by artifact correction. The computer algorithm used here appears to be a promising tool for REM sleep behavior disorder detection in both research and clinical routine. A short check for plausibility of automatic detection should be a basic prerequisite for this and all other available computer algorithms. © 2014 Associated Professional Sleep Societies, LLC.

  2. Study on transcranial sonography in patients with idiopathic rapid eye movement sleep behavior disorder

    Directory of Open Access Journals (Sweden)

    Xu-dong LI

    2016-04-01

    Full Text Available Objective To investigate the changes of transcranial sonography (TCS in patients with rapid eye movement sleep behavior disorder (RBD.  Methods Fifteen patients fulfilled the diagnostic criteria of RBD according to International Classification of Sleep Disorders (ICSD, 2nd edition. Under the monitor of polysomnography (PSG, the sleep architectures of all RBD cases were evaluated by Polysmith software and visual analysis. Furthermore, all RBD patients and 15 normal controls underwent TCS. Cases with substantia nigra echo intensity over Ⅲ grade and substantia nigra area over 0.20 cm2 were supposed to be hyperechogenicity. Additionally, the width of the third ventricle was measured and whether there was hyperechogenicity in basal ganglia was evaluated. The cognitive functions were evaluated by Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA.  Results RBD patients presented typical clinical manifestations and electrophysiologic changes. No significant difference (P = 0.080, 0.109 was found in the comparison of hyperechogenicity rate on substantia nigra (6/15 and basal ganglia (7/15 in RBD patients and normal controls (1/15, 2/15. No significant difference in the comparison of MoCA was found in RBD patients with or without substantia nigra hyperechogenicity (P = 0.075. The RBD patients with hyperechogenicity on basal ganglia had higher MMSE scores than those without hyperechogenicity on basal ganglia, and the difference was significant (P = 0.021.  Conclusions RBD which is suggested as the prodromal period of synucleinopathy may present hyperechogenicity in substantia nigra and basal ganglia on TCS. TCS could detect subclinical changes of brain and evaluate the risk of synucleinopathy. DOI: 10.3969/j.issn.1672-6731.2016.04.010

  3. Characterization of Movement Disorder Phenomenology in Genetically Proven, Familial Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Gasca-Salas, Carmen; Masellis, Mario; Khoo, Edwin; Shah, Binit B; Fisman, David; Lang, Anthony E; Kleiner-Fisman, Galit

    2016-01-01

    Mutations in granulin (PGRN) and tau (MAPT), and hexanucleotide repeat expansions near the C9orf72 genes are the most prevalent genetic causes of frontotemporal lobar degeneration. Although behavior, language and movement presentations are common, the relationship between genetic subgroup and movement disorder phenomenology is unclear. We conducted a systematic review and meta-analysis of the literature characterizing the spectrum and prevalence of movement disorders in genetic frontotemporal lobar degeneration. Electronic databases were searched using terms related to frontotemporal lobar degeneration and movement disorders. Articles were included when cases had a proven genetic cause. Study-specific prevalence estimates for clinical features were transformed using Freeman-Tukey arcsine transformation, allowing for pooled estimates of prevalence to be generated using random-effects models. The mean age at onset was earlier in those with MAPT mutations compared to PGRN (pphenomenology in genetic frontotemporal lobar degeneration. Standardized prospective collection of clinical information in conjunction with genetic characterization will be crucial for accurate clinico-genetic correlation.

  4. Laughing as a manifestation of rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Siclari, F; Wienecke, M; Poryazova, R; Bassetti, C L; Baumann, C R

    2011-06-01

    Among the range of sleep-related behavior displayed by patients with rapid eye movement (REM) sleep behavior disorder (RBD), aggressive acts are particularly common, while pleasant behaviors have rarely been reported. We aimed at identifying the frequency and characteristics of patients who displayed laughing as a pleasant, nonviolent manifestation of RBD. We reviewed 67 consecutive polysomnographic recordings of patients with RBD, obtained in our sleep laboratory between July 2004 and July 2009. We identified 14 patients (21% of our RBD patients with degenerative parkinsonism: 10 males, mean age 63 ± 11 years) who repeatedly laughed during REM sleep. Ten patients had idiopathic Parkinson's disease, 3 suffered from multisystem atrophy and 1 patient was diagnosed with dementia with Lewy bodies. Other RBD-associated behaviors included smiling, crying, aggressive behavior, screaming, and somniloquia. Nine of the 14 patients were depressed during daytime. Laughing belongs to the spectrum of behavioral manifestations of RBD. Many of our patients with RBD-associated laughter were depressed, suggesting a dissociation between emotional expression during daytime and REM sleep. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Path Planning Method for UUV Homing and Docking in Movement Disorders Environment

    Directory of Open Access Journals (Sweden)

    Zheping Yan

    2014-01-01

    Full Text Available Path planning method for unmanned underwater vehicles (UUV homing and docking in movement disorders environment is proposed in this paper. Firstly, cost function is proposed for path planning. Then, a novel particle swarm optimization (NPSO is proposed and applied to find the waypoint with minimum value of cost function. Then, a strategy for UUV enters into the mother vessel with a fixed angle being proposed. Finally, the test function is introduced to analyze the performance of NPSO and compare with basic particle swarm optimization (BPSO, inertia weight particle swarm optimization (LWPSO, EPSO, and time-varying acceleration coefficient (TVAC. It has turned out that, for unimodal functions, NPSO performed better searching accuracy and stability than other algorithms, and, for multimodal functions, the performance of NPSO is similar to TVAC. Then, the simulation of UUV path planning is presented, and it showed that, with the strategy proposed in this paper, UUV can dodge obstacles and threats, and search for the efficiency path.

  6. Movement disorders secondary to long-term treatment with cyclosporine A.

    Science.gov (United States)

    Munhoz, Renato P; Teive, Helio A G; Germiniani, Francisco M B; Gerytch, Júlio C; Sá, Daniel S; Bittencourt, Marco A; Pasquini, Ricardo; Camargo, Carlos H F; Werneck, Lineu César

    2005-09-01

    To analyze the prevalence, severity and functional interference of movement disorders (MD) secondary to chronic use of cyclosporine A (CsA). We conducted a cross-sectional study of 60 patients (58.3% male) with mean age 23.1 (3-75) years, followed at the Bone Marrow Transplantation Service of the Hospital de Clínicas of the Federal University of Paraná, Brazil, taking CsA for at least six months. Our protocol included clinical data, assessment of functional interference of symptoms and neurological examination including observation and grading of MD. Eight (13.3%) subjects reported the presence of tremor at the moment of interview and 29 (48.3%) recalled this symptom at some point during treatment. Neurological examination identified 14 (23.3%) subjects with MD: upper limb symmetric action tremor in 13 (21.6%) and parkinsonism (rigidity and bradykinesia) in 1 (1.7%). No other MD was detected. The mean scores indicated mild clinical signs in all cases. Symptoms were considered subjectively mild with no functional interference. Almost one quarter of patients using CsA chronically presented MD, almost always mild and transitory action tremor, with minimal interference on daily living activities, not requiring any form of intervention in the majority of cases.

  7. REM sleep behavior disorder and periodic leg movements during sleep in ALS.

    Science.gov (United States)

    Lo Coco, D; Puligheddu, M; Mattaliano, P; Congiu, P; Borghero, G; Fantini, M L; La Bella, V; Ferri, R

    2017-02-01

    To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS). A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography. A total of 22 patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total sleep time, increased wakefulness after sleep onset, shortened REM and slow-wave sleep, and decreased sleep efficiency, compared to controls. Polysomnographic abnormalities were not different in patients reporting good or poor sleep and were not correlated to clinical and demographic variables. The PLMS index was significantly higher in patients with ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index > 15/h, vs 4 (15.4%) controls (P ALS (4.9%) had RBD, and two more patients presented RSWA (4.9%), whereas no controls showed abnormalities of REM sleep. Patients with ALS frequently present abnormalities of sleep that can be documented both at the clinical interview and at the polysomnographic evaluation, including insomnia, fragmented sleep, and increased PLMS. Moreover, abnormalities of REM sleep can be found in some of these patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Effectiveness of rhythmic movement therapy for disordered eating behaviors and obesity.

    Science.gov (United States)

    Malkina-Pykh, Irina G

    2012-11-01

    The aims of the present study were: a) to examine associations between pre-treatment BMI, body dissatisfaction, perfectionism, alexithymia, and restraint, emotional and external eating behaviour in obese patients; b) to analyze the impact of the pre-treatment measures in psychological variables on the outcome of cognitive-behavioral therapy (CBT) program; c) to test the effectiveness of rhythmic movement therapy (RMT) in the treatment of disordered eating behaviors and obesity with the CBT non-responders. At the first stage of treatment a total of 104 patients (32 males and 72 females, mean age was 37.6 +/- 6.7 years) self-referred or referred by professionals to CBT weight management program were selected at random. At the second stage 58 obese CBT-non-responders were randomly divided among the continuing CBT individual treatment group and RMT group. Control group was included. Results revealed that: a) significant associations existed between pre-treatment BMI, external eating and two dimensions of perfectionism, as well as between emotional and external eating and all dimensions of perfectionism, alexithymia and body image dissatisfaction; b) pre-treatment means of psycholog