WorldWideScience

Sample records for dyskinesias

  1. Tardive dyskinesia

    Science.gov (United States)

    ... Tardive syndrome; Orofacial dyskinesia; Involuntary movement - tardive dyskinesia; Antipsychotic drugs - tardive dyskinesia; Neuroleptic drugs - tardive dyskinesia; Schizophrenia - tardive dyskinesia

  2. Sulpiride in tardive dyskinesia.

    Science.gov (United States)

    Casey, D E; Gerlach, J; Simmelsgaard, H

    1979-01-01

    Tardive dyskinesia can be suppressed by drugs that block dopaminergic receptors, but often at the cost of a concomitant increase in parkinsonism. Sulpiride (400 -- 2100 mg/day), a selective type-2 dopamine receptor antagonist, was evaluated in a blind, placebo-controlled trial in 11 patients with tardive dyskinesia. It significantly (P less than 0.01) reduced tardive dyskinesia without significantly affecting parkinsonism, although three patients had a increase in preexisting parkinsonian hypokinesia and tremor. During the placebo phase, the tardive dyskinesia and parkinsonian scores returned to the pretreatment values. There was no relationship between either tardive dyskinesia or parkinsonism and eye blinking rates. These results are consistent with the hypothesis that more than one population of dopamine receptors are involved in controlling extrapyramidal function. Sulpiride is an important tool for elucidating both the practical and heuristic aspects of subtypes of dopamine receptors and is a lead in the search for compounds that selectively affect dopaminergic mechanisms.

  3. Paroxysmal Nonkinesigenic Dyskinesia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-06-01

    Full Text Available A Canadian family of European descent with paroxysmal nonkinesigenic dyskinesia (PNKD, and a gene locus that links to a distinct region on chromosome 2q31, is reported by researchers at University of British Columbia, Canada.

  4. PESISTENT PARKINSONISM AND TARDIVE DYSKINESIA

    OpenAIRE

    Shaji, K S; Kishore, N.R. Arun

    1995-01-01

    Parkinsonism and tardive dyskinesia can coexist in patients taking antipsychotic drugs. Persistence of both parkinsonism and tardive dyskinesia during a two year follow up period after discontinuation of antipsychotic drugs is reported. Etiological significance of antipsychotic treatment is discussed.

  5. Tardive Dyskinesia and Covert Dyskinesia with Aripiprazole: A Case Series.

    Science.gov (United States)

    Patra, Suravi

    2016-01-01

    Aripiprazole, a dopamine stabilizing atypical antipsychotic is used in treatment of tardive dyskinesia caused by other neuroleptics. Tardive dyskinesia is rarely caused by Aripiprazole and has only been documented in high risk patients i.e., female gender, advanced age, affective illness, coexisting neurological disorders. Here the author describes two atypical cases of tardive dyskinesia associated with Aripiprazole. First case of tardive dyskinesia was observed in a neuroleptic naïve young adult male with paranoid illness after six months of treatment with Aripiprazole upon addition of Fluoxetine and the second case was a middle aged female with affective illness where dyskinetic movements appeared after stopping Aripiprazole. The role of Fluoxetine in causing tardive dyskinesia with Aripiprazole and covert dyskinesia due to Aripiprazole with appropriate management is discussed.

  6. Sulpiride in tardive dyskinesia.

    OpenAIRE

    Schwartz, M.; Moguillansky, L; Lanyi, G; Sharf, B

    1990-01-01

    The abnormal involuntary movements in tardive dyskinesia can be reduced by the dopamine antagonist drugs, phenothiazines and butyrophenones, but most cause an increase in Parkinsonian signs. Sulpiride, a benzamide derivative, and selective antagonist of D2 receptors had a significantly beneficial effect on most of 15 patients (p less than 0.01). In 12 patients the improvement was marked. The reduction of abnormal movements was observed even with low doses, and it was not necessary to increase...

  7. Tardive dyskinesia induced by sulpiride.

    Science.gov (United States)

    Achiron, A; Zoldan, Y; Melamed, E

    1990-06-01

    Although tardive dyskinesia is a known adverse reaction of sustained treatment with traditional neuroleptic agents, it was only rarely reported in association with sulpiride, a selective D2-receptor antagonist. We describe six patients who developed tardive dyskinesia after treatment with sulpiride for depression or gastrointestinal symptoms. In three patients, involuntary movements emerged during the course of treatment and in the others only after discontinuation of the drug. These cases indicate that sulpiride can cause tardive dyskinesia and that this drug should be administered with caution.

  8. An update on tardive dyskinesia.

    Science.gov (United States)

    Simpson, G M; Pi, E H; Sramek, J J

    1986-04-01

    The authors review recent research on definition, diagnosis, neuropathophysiology, treatment, management, and factors that increase risk of tardive dyskinesia, a severe and often unremitting movement disorder associated with neuroleptic treatment. Supersensitivity of dopamine receptors is believed to be the cause of tardive dyskinesia, and treatment strategies have consisted of pharmacologic blockade of dopamine receptors, depletion of dopamine, and restoration of the balance between the dopaminergic system and the neurotransmitter systems that regulate it. Several experimental neuroleptics that do not appear to cause tardive dyskinesia may be approved for use in the United States, but for now preventive measures, such as wise prescription and gradual tapering of neuroleptics, as well as careful monitoring for symptoms of tardive dyskinesia are the clinician's best defense.

  9. RISK FACTORS FOR TARDIVE DYSKINESIA

    OpenAIRE

    Datta, Sunil; Subhalakshmi, T.P.; Jeyaseelan, L; Kuruvilla, K.

    1994-01-01

    Three hundred and fifty three patients who had been on antipsychotics for three months or more were assessed using Simpson Tardive Dyskinesia Rating Scale. 40.2% of these patients, who merited a diagnosis of probable Tardive Dyskinesia (TD) by the Schooler and Kane criteria, were reassessed three months later and 25.5% of the total sample were found to have persistent TD. Age, total antipsychotic dosage and duration of antipsychotic exposure were found to be positively correlated with persist...

  10. Primary ciliary dyskinesia

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2004-01-01

    Full Text Available In patients with chronic respiratory diseases that last since the early childhood, primary ciliary dyskinesia (PCD needs to be considered. Four patients reviewed in this paper were with typical disease history and clinical picture, as well as clear ciliary axonema damage. Complete examination was performed in all the patients, including bronchoscopy with bronchography, and the examination of the biopsy samples of respiratory airways’ mucous membrane, obtained by transmission electron microscope (TEM. In two of the patients spermatozoa were also examined by TEM. Large anatomic deffects of airways were found in all the patients, but pulmonary function was normal (except in one case, representing one of PCD’s significant characteristics. First two cases fulfilled the criteria for Kartagener’s syndrome, which was initially sufficient for the diagnosis of PCD.

  11. Persistent akathisia associated with early tardive dyskinesia.

    OpenAIRE

    Barnes, T. R.; Braude, W M

    1984-01-01

    Two psychiatric patients developed moderate or severe oro-facial dyskinesia, and limb dyskinesia, at a relatively young age and within a year of starting antipsychotic drug-treatment. This early appearance of tardive dyskinesia was preceded by akathisia that had developed at the beginning of drug therapy and persisted, despite the reduction of their drug doses to maintenance levels. The possibility that persistent akathisia may herald the early onset of tardive dyskinesia, is discussed.

  12. CT study in tardive dyskinesia

    Energy Technology Data Exchange (ETDEWEB)

    Takamiya, M.; Tanoue, A.; Sakuma, K.; Itoh, H.; Nakazato, H.

    1987-03-01

    Fifteen schizophrenic patients having moderate tardive dyskinesia underwent computed tomography (CT). The CT findings were compared with those in the control nondyskinetic group matched for sex, age, clinical type, disease duration, length of antipychotropic treatment, and the total dosage. Regarding any of the variables studied, including area and density of the head of caudate nucleus and the lenticular nucleus, minimum distance between the bilateral caudate nuclei, maximum width of the third ventricle, and ventricle-brain ratio, there was no significant difference between the two groups. None of the variables were significantly different in the group with lobotomy (n = 5) and the group without it (n = 28). A review of the literature, in addition to these results, revealed that CT may be unhelpful in the detection of parenchymal changes in the brain, including the basal ganglia, contributing to the occurrence of tardive dyskinesia in patients with moderate symptoms.

  13. TARDIVE DYSKINESIA : CLINICAL PRESENTATION AND TREATMENT

    NARCIS (Netherlands)

    van Harten, Peter N.; Tenback, Diederik E.; Brotchie, J; Bezard, E; Jenner, P

    2011-01-01

    Tardive dyskinesia (TD) is a common and potentially irreversible side effect of dopamine blocking agents, most often antipsychotics. It is often socially and sometimes also physically disabling. The clinical picture can be divided into orofacial, limb-truncal, and respiratory dyskinesia. The clinica

  14. Dysphagia due to tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Pookala S Bhat

    2010-01-01

    Full Text Available Tardive dyskinesia (TD, neuroleptic-induced delayed onset movement disorder, remains an enigmatic phenomenon and a therapeutic challenge. Only a few cases of dysphagia also have been reported in world literature and to the best knowledge of the authors no case of TD manifesting as isolated dysphagia has been reported so far from India. We report a case of TD consequent to prolonged exposure to typical neuroleptics, manifesting as isolated dysphagia who responded well to a combination of Quetiapine, Donepezil and Vit E.

  15. Diagnosis of primary ciliary dyskinesia

    Directory of Open Access Journals (Sweden)

    Mary Anne Kowal Olm

    2015-06-01

    Full Text Available Primary ciliary dyskinesia (PCD is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures.

  16. Diagnosis of primary ciliary dyskinesia*

    Science.gov (United States)

    Olm, Mary Anne Kowal; Caldini, Elia Garcia; Mauad, Thais

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures. PMID:26176524

  17. Biliary Dyskinesia in Children: A Systematic Review.

    Science.gov (United States)

    Santucci, Neha R; Hyman, Paul E; Harmon, Carroll M; Schiavo, Julie H; Hussain, Sunny Z

    2017-02-01

    Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.

  18. NMDA receptor co-determines vulnerability to develop dyskinesia in Huntington's Disease and levodopa-induced dyskinesia but not tardive dyskinesia

    NARCIS (Netherlands)

    Loonen, A. J. M.; Ivanova, S. A.; Pechlivanoglou, P.; Rudikov, E.; Zhukova, I.; Al Hadithy, A. F. Y.; Alifirova, V.; Brouwers, J. R. B. J.; Semke, A.; Wilffert, B.

    2011-01-01

    Dyskinesia occurs as clinical feature of Huntington's Disease (HD) and as an adverse consequence of chronic exposure to levodopa in Parkinson's disease (levodopa-induced dyskinesia, LID) and to antipsychotic drugs in schizophrenia (tardive dyskinesia, TD). Arning et al. have reported that specific v

  19. A TRIAL OF SODIUM VALPROATE IN TARDIVE-DYSKINESIA

    OpenAIRE

    Chadda, R.; Kulhara, P.

    1986-01-01

    SUMMARY This study reports the results of an open trial of Sodium Valproate in tardive-dyskinesia. Fifteen patients identified having tardive dyskinesia by two psychiatrists independently were treated with Sodium Valproate in dosage of 1200 mg/day for 4 weeks. Assessments were made on abbreviated Dyskinesia Scale. There was statistically significant improvement after 2 and 4 weeks of treatment. Authors found Sodium Valproate quite effective in the management of tardive-dyskinesia.

  20. A TRIAL OF SODIUM VALPROATE IN TARDIVE-DYSKINESIA

    OpenAIRE

    Chadda, R.; Kulhara, P.

    1986-01-01

    SUMMARY This study reports the results of an open trial of Sodium Valproate in tardive-dyskinesia. Fifteen patients identified having tardive dyskinesia by two psychiatrists independently were treated with Sodium Valproate in dosage of 1200 mg/day for 4 weeks. Assessments were made on abbreviated Dyskinesia Scale. There was statistically significant improvement after 2 and 4 weeks of treatment. Authors found Sodium Valproate quite effective in the management of tardive-dyskinesia.

  1. New insights into the mechanism of drug-induced dyskinesia

    NARCIS (Netherlands)

    Loonen, Anton J. M.; Ivanova, Svetlana A.

    2013-01-01

    Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced wi

  2. Antipsychotic-induced life-threatening 'esophageal dyskinesia'.

    Science.gov (United States)

    Horiguchi, J; Shingu, T; Hayashi, T; Kagaya, A; Yamawaki, S; Horikawa, Y; Kitadai, Y; Inoue, M; Nishikawa, T

    1999-03-01

    We report two patients with lingual dyskinesia and complaints of food regurgitation following long-term antipsychotic therapy. Esophageal contrast radiography revealed dyskinetic movements extending from the pharynx to the upper portion of the esophagus. The elevation of intraesophageal pressure was confirmed by esophageal manometry. The dyskinetic movements almost disappeared along with improvement of lingual dyskinesia following the administration of sulpiride in one patient. Another patient suddenly died due to asphyxiation of foods before the beginning of treatment. We termed this life-threatening movement, 'esophageal dyskinesia'. It should be emphasized that 'esophageal dyskinesia' associated with lingual dyskinesia is a potentially fatal adverse reaction to antipsychotic therapy.

  3. Parkinson's disease: carbidopa, nausea, and dyskinesia

    Directory of Open Access Journals (Sweden)

    Hinz M

    2014-11-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole3 1Clinical Research, NeuroResearch Clinics, Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Cole Center for Healing, Cincinnati, OH, USA Abstract: When ʟ-dopa use began in the early 1960s for the treatment of Parkinson's disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to ʟ-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to ʟ-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not ʟ-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to ʟ-dopa and may be perceived as irreversible if proper corrective action is not taken. Keywords: vitamin B6, PLP, irreversible, pyridoxal 5'-phosphate

  4. A case of paliperidone-palmitate-induced tardive dyskinesia.

    LENUS (Irish Health Repository)

    Lally, John

    2012-06-13

    OBJECTIVES: This is one of the first cases reported in the literature of paliperidone-palmitate-induced prolonged dyskinesia. METHOD: Case report. RESULTS: We report the case of a 49-year-old woman with paranoid schizophrenia who developed orofacial dyskinesia some 4 months after the commencement of paliperidone long-acting injection. CONCLUSION: This case serves as a clinical reminder that dyskinesia can occur with all antipsychotic medications.

  5. Treatment of neurolept-induced tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Jankelowitz SK

    2013-09-01

    Full Text Available Stacey K Jankelowitz Central Clinical School, University of Sydney, Sydney, NSW, Australia Abstract: Tardive dyskinesia (TDK includes orobuccolingual movements and “piano-playing” movements of the limbs. It is a movement disorder of delayed onset that can occur in the setting of neuroleptic treatment as well as in other diseases and following treatment with other drugs. The specific pathophysiology resulting in TDK is still not completely understood but possible mechanisms include postsynaptic dopamine receptor hypersensitivity, abnormalities of striatal gamma-aminobutyric acid (GABA neurons, and degeneration of striatal cholinergic interneurons. More recently, the theory of synaptic plasticity has been proposed. Considering these proposed mechanisms of disease, therapeutic interventions have attempted to manipulate dopamine, GABA, acetylcholine, norepinephrine and serotonin pathways and receptors. The data for the effectiveness of each class of drugs and the side effects were considered in turn. Keywords: tardive dyskinesia, treatment, neuroleptic agents

  6. Anticholinergic Agents Can Induce Oromandibular Dyskinesia

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    Hee-Young Shin

    2009-10-01

    Full Text Available Background and Purpose: Oromandibular dyskinesia (OMD can occur spontaneously or they can be induced by the conventional dopamine receptor antagonists. Anticholinergic medications have rarely been reported to cause OMD in parkinsonian or non-parkinsonian patients. Methods: We analyzed the clinical features of two parkinsonian and one non-parkinsonian patients who experienced OMD after anticholinergic medication. Results: Each patient of our cases developed oromandibular symptoms in the temporal regions that were related to the addition of anticholinergic agents, and the symptoms were relieved following the discontinuation of the causative anticholinergic drugs. In one of our case, levodopa alone did not cause dyskinesia but augmented dyskinesia associated with anticholinergics. Conclusions: Here we report two parkinsonian and one non-parkinsonian patients with OMD induced by the use of anticholinergic agents. In our cases, we could not find any other precipitating or actual secondary causes for the OMD symptoms in our patients. Furthermore, the fact that the OMD in our cases were ameliorated with cessation of anticholinergics suggests that it may be anticholinergic-induced.

  7. State-dependent tardive dyskinesia in manic-depressive illness.

    OpenAIRE

    de Potter, R W; Linkowski, P; Mendlewicz, J.

    1983-01-01

    We report the occurrence of a drug-resistant tardive dyskinesia coexistent with Parkinsonism-like symptoms in a manic-depressive patient. The tardive dyskinesia completely disappeared during the manic phases and recurred after remission over the course of different mood-cycles.

  8. Tardive dyskinesia with low dose amisulpride.

    Science.gov (United States)

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

  9. Osteopathic manipulative treatment in the management of biliary dyskinesia.

    Science.gov (United States)

    Heineman, Katherine

    2014-02-01

    Biliary dyskinesia is a functional gastrointestinal disorder of the gallbladder and sphincter of Oddi. Diagnosis is made on the basis of symptoms of biliary colic in the absence of cholelithiasis and gallbladder inflammation. Palpatory findings of tissue texture changes at midthoracic levels (T6-T9) may correspond to visceral dysfunction related to the biliary system. Osteopathic manipulative treatment (OMT) of the T6-T9 segments can remove the feedback related to the somatic component, thereby affecting nociceptive facilitation at the spinal level and allowing the body to restore autonomic balance. Few reports in the current literature provide examples of treatment for patients with biliary dyskinesia using OMT. The author describes the case of a 51-year-old woman who presented with symptoms consistent with biliary dyskinesia. Her biliary colic completely resolved after OMT. Osteopathic evaluation and OMT should be considered a safe and effective option for conservative management of biliary dyskinesia.

  10. Tardive dyskinesia affected by occlusal treatment--a case report.

    Science.gov (United States)

    Kai, S; Kai, H; Tashiro, H

    1994-07-01

    The following is a case report of occlusal treatment for involuntary mandibular movement occurring in a 79-year old woman. This was diagnosed as sulpiride-induced tardive dyskinesia. The patient had been treated with sulpiride to improve gastrointestinal symptoms for five years until the onset of involuntary mandibular movement. The involuntary movement worsened even after discontinuation of the drug for 10 weeks. The dyskinesia improved in the course of treatment with an occlusal splint placed over her upper denture. After wearing the new denture with increased occlusal vertical dimension, the dyskinesia disappeared almost completely. Sirognathographic observation showed that previous denture wear evoked remarkable involuntary movement of the mandible once again. It is uncertain whether such improvement may result from discontinuation of the drug or from the occlusal treatment. However, it appears that occlusal factors played an important role in orofacial manifestation of tardive dyskinesia (TD) in this case.

  11. Relevance of animal models to human tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Blanchet Pierre J

    2012-03-01

    Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

  12. Methylphenidate-induced acute orofacial and extremity dyskinesia.

    Science.gov (United States)

    Yilmaz, Ayse Esra; Donmez, Ahsen; Orun, Emel; Tas, Tugba; Isik, Bunyamin; Sonmez, Fatma Mujgan

    2013-06-01

    Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors' knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug-receptor interactions via different mechanisms.

  13. Paroxysmal Hypnogenic Dyskinesia Responsive to Doxylamine: A Case Report

    OpenAIRE

    Williams, Daniel M.

    2012-01-01

    Paroxysmal hypnogenic dyskinesia is a rare clinical entity characterized by intermittent dystonia and choreoathetoid movements that begin exclusively during sleep, often with consciousness preserved once the patient is awakened during the episodes. They occur almost every night and are often misdiagnosed as sleeping disorders. Paroxysmal hypnogenic dyskinesia is currently known to be a form of frontal lobe epilepsy, but not in all cases. We present a 19-year-old male patient with paroxysmal h...

  14. [Primary ciliary dyskinesia: clinical and genetic aspects].

    Science.gov (United States)

    D'Auria, E; Palazzo, S; Argirò, S; El, Oksha S; Riva, E

    2012-01-01

    Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

  15. Primary ciliary dyskinesia: clinical and genetic aspects

    Directory of Open Access Journals (Sweden)

    E. D’Auria

    2012-06-01

    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

  16. Treatment of neurolept-induced tardive dyskinesia.

    Science.gov (United States)

    Jankelowitz, Stacey K

    2013-01-01

    Tardive dyskinesia (TDK) includes orobuccolingual movements and "piano-playing" movements of the limbs. It is a movement disorder of delayed onset that can occur in the setting of neuroleptic treatment as well as in other diseases and following treatment with other drugs. The specific pathophysiology resulting in TDK is still not completely understood but possible mechanisms include postsynaptic dopamine receptor hypersensitivity, abnormalities of striatal gamma-aminobutyric acid (GABA) neurons, and degeneration of striatal cholinergic interneurons. More recently, the theory of synaptic plasticity has been proposed. Considering these proposed mechanisms of disease, therapeutic interventions have attempted to manipulate dopamine, GABA, acetylcholine, norepinephrine and serotonin pathways and receptors. The data for the effectiveness of each class of drugs and the side effects were considered in turn.

  17. [Tardive dyskinesia: I. Physiopathology and treatment].

    Science.gov (United States)

    Andrade, L A; Bertolucci, P H; Pereira, J S

    1984-12-01

    The major breakthrough in the treatment of mental diseases was the introduction of neuroleptics in the early 50's. Soon after this an increasing number of patients under the use of these drugs presented involuntary abnormal orofacial movements which have been considered directly dependent on the drug action. The term "tardive dyskinesia" (TD) was coined for these movements. Many theories have been put forward to explain the pathophysiology of TD. The most prominent theory concerns with the possibility of denervation hypersensitivity occurring in striatal post-synaptic dopamine neurons. The authors review the most important theories and offer a new possibility based on the assumption that the post-synaptic dopamine receptors under chronic neuroleptic action develop a shift in its affinity towards the direction of agonist action. This means that the post-synaptic receptor increase its affinity, and possibly its number, to agonist drugs and dopamine. The paper includes a review of the main drugs used in this condition, attempting to explain the specific sites where they act, either in the dopaminergic, cholinergic or GABA--ergic systems.

  18. Recent advances in primary ciliary dyskinesia.

    Science.gov (United States)

    Takeuchi, Kazuhiko; Kitano, Masako; Ishinaga, Hajime; Kobayashi, Masayoshi; Ogawa, Satoru; Nakatani, Kaname; Masuda, Sawako; Nagao, Mizuho; Fujisawa, Takao

    2016-06-01

    Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

  19. Paroxysmal Hypnogenic Dyskinesia Responsive to Doxylamine: A Case Report

    Directory of Open Access Journals (Sweden)

    Daniel M. Williams

    2012-01-01

    Full Text Available Paroxysmal hypnogenic dyskinesia is a rare clinical entity characterized by intermittent dystonia and choreoathetoid movements that begin exclusively during sleep, often with consciousness preserved once the patient is awakened during the episodes. They occur almost every night and are often misdiagnosed as sleeping disorders. Paroxysmal hypnogenic dyskinesia is currently known to be a form of frontal lobe epilepsy, but not in all cases. We present a 19-year-old male patient with paroxysmal hypnogenic dyskinesia who responded to antihistamines. This supports an alternative theory from 1977 (before the cases had been adequately described that the disorder lies in dysregulation in the basal ganglia. This description now appears similar to acute dystonic reactions such as extrapyramidal symptoms from antipsychotic medications, which also respond to antihistamines.

  20. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke

    Science.gov (United States)

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-01-01

    Abstract Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases. This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance. During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization. The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia. PMID:26266368

  1. Paroxysmal hypnogenic dyskinesia responsive to doxylamine: a case report.

    Science.gov (United States)

    Williams, Daniel M

    2012-01-01

    Paroxysmal hypnogenic dyskinesia is a rare clinical entity characterized by intermittent dystonia and choreoathetoid movements that begin exclusively during sleep, often with consciousness preserved once the patient is awakened during the episodes. They occur almost every night and are often misdiagnosed as sleeping disorders. Paroxysmal hypnogenic dyskinesia is currently known to be a form of frontal lobe epilepsy, but not in all cases. We present a 19-year-old male patient with paroxysmal hypnogenic dyskinesia who responded to antihistamines. This supports an alternative theory from 1977 (before the cases had been adequately described) that the disorder lies in dysregulation in the basal ganglia. This description now appears similar to acute dystonic reactions such as extrapyramidal symptoms from antipsychotic medications, which also respond to antihistamines.

  2. Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Hideyuki Sawada

    Full Text Available BACKGROUND: Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson's disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson's disease patients suffering from dyskinesias. METHODS: In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson's disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg/day or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS during each treatment period. The secondary outcome measures were changes in the Unified Parkinson's Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias, part IVb (motor fluctuations, and part III (motor function. RESULTS: RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5. UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD of 1.83 (1.56] compared with placebo-treated patients [0.03 (1.51]. However, there were no significant effects on UPDRS-IVb or III scores. CONCLUSIONS: Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60-70% of patients. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000000780.

  3. Vitamin E in the treatment of tardive dyskinesia.

    OpenAIRE

    Akhtar S; Jajor T; Kumar S

    1993-01-01

    In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD) was studied in 32 patients. After a two week wash-out phase a baseline (0 week) TD rating was assessed on the tardive dyskinesia rating scale (TDRS). Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg) and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule da...

  4. Paroxysmal kinesigenic dyskinesia : Cortical or non-cortical origin

    NARCIS (Netherlands)

    van Strien, Teun W.; van Rootselaar, Anne-Fleur; Hilgevoord, Anthony A. J.; Linssen, Wim H. J. P.; Groffen, Alexander J. A.; Tijssen, Marina A. J.

    2012-01-01

    Paroxysmal kinesigenic dyskinesia (PKD) is characterized by involuntary dystonia and/or chorea triggered by a sudden movement. Cases are usually familial with an autosomal dominant inheritance. Hypotheses regarding the pathogenesis of PKD focus on the controversy whether PKD has a cortical or non-co

  5. Effectiveness of ivermectin in rats with haloperidol induced tardive dyskinesia.

    Directory of Open Access Journals (Sweden)

    Mauricio Palacios

    2009-11-01

    Full Text Available Introduction: Extrapiramidal symptoms and tardive dyskinesia are common problems associated with antypsychotic therapy. Basic and clinical research is warranted due to the lack of effective therapies aimed to the prevention and treatment of antipsychotic side effects. Objective: To evaluate the effect of ivermectin in rats with haloperidol induced tardive dyskinesia. Methods: The effect of ivermectin on motor behavior and abnormal movements was tested in Sprague-Dawley rats treated with a single dose of haloperidol. In addition, a chronic animal model known as VCM (vacuous chewing movements was implemented with the objective to evaluate the effect of ivermectin on the frequency of orofacial movements during a period of six months. Results: Ivermectin does not prevent the motor behavior and frequency of abnormal movements induced by haloperidol in the acute model. Orofacial movements were not reduced with ivermectin in the chronic model. In addition, ivermectin was not associated with changes in motor behavior and abnormal movements in the acute and chronic model. Conclusions: Ivermectin is not a good candidate for the treatment of tardive dyskinesia and the results of this study do not support the GABAergic hypothesis in the physiopathology of tardive dyskinesia. Additionally, ivermectin does not induce abnormal movements.

  6. Structural and functional lung disease in primary ciliary dyskinesia

    NARCIS (Netherlands)

    F. Santamaria (Francesca); S. Montella (Silvia); H.A.W.M. Tiddens (Harm); G. Guidi (Guido); V. Casotti (Valeria); M. Maglione (Marco); P.A. de Jong (Pim)

    2008-01-01

    textabstractBackground: High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. Study objectives: We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural ab

  7. Paroxysmal non-kinesigenic dyskinesia in antiphospholipid syndrome

    NARCIS (Netherlands)

    Engelen, M; Tijssen, MAJ

    2005-01-01

    We report on a patient with a mixed movement disorder classifiable as a paroxysmal nonkinesigenic dyskinesia, occurring as the first manifestation of primary antiphospholipid syndrome (PAPS). Possible pathophysiology is discussed based on recent literature, and we stress that PAPS must be considered

  8. Tardive dyskinesia in children treated with atypical antipsychotic medications.

    Science.gov (United States)

    Wonodi, Ikwunga; Reeves, Gloria; Carmichael, Dana; Verovsky, Ilene; Avila, Matthew T; Elliott, Amie; Hong, L Elliot; Adami, Helene M; Thaker, Gunvant K

    2007-09-15

    Recent years have witnessed increased antipsychotic treatment of children despite limited long-term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic-naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African-American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European-American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side-effect profile of the atypical antipsychotic drugs in children may be much different than that in adults.

  9. RISPERIDONE - INDUCED TARDIVE DYSKINESIA : CASE REPORT AND REVIEW OF LITERATURE

    OpenAIRE

    Kumar, P.N. Suresh; Andrade, Chittaranjan

    2001-01-01

    Risperidone is an atypical antipsychotic with broad spectrum of antipsychotic activity and lower potential for extrapyramidal side effects at therapeutic doses. This case report illustrates the development of tardive dyskinesia with therapeutic dose of risperidone in a paranoid schizophrenic patient who was not on any antipsychotic medication previously.

  10. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats.

    Science.gov (United States)

    Bordia, Tanuja; McIntosh, J Michael; Quik, Maryka

    2012-03-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

  11. Covert dyskinesia associated with aripiprazole: a case report and review of the literature.

    Science.gov (United States)

    Moseley, Carrie N; Simpson-Khanna, Heather A; Catalano, Glenn; Catalano, Maria C

    2013-01-01

    The atypical antipsychotic agents are felt by many to have a lower risk of inducing the development of dyskinetic movements than the conventional antipsychotic agents agents such as haloperidol and fluphenazine. However, that does not mean that treatment with the atypical antipsychotic agents carries no risk of developing dyskinesias. To the contrary, all of the atypical antipsychotic agents, including aripiprazole, have been associated with the induction of dyskinetic movements. We will present the case of a patient who developed a covert dyskinesia that manifested shortly after the discontinuation of aripiprazole. We will review the use of aripiprazole and the adverse effects most commonly associated with its use. We will also discuss the risk factors associated with the development of tardive dyskinesia and review the different clinical variations (withdrawal dyskinesia, covert dyskinesia, tardive diskinesia) of medication-induced dyskinesias.

  12. Clinical phenotype analysis of paroxysmal kinesigenic dyskinesia

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    Wo-tu TIAN

    2017-07-01

    Full Text Available Background Paroxysmal kinesigenic dyskinesia (PKD is a disorder characterized by recurrent and brief dystonic or choreoathetoid attacks that are induced by sudden voluntary movement with highly clinical and genetic heterogeneity. We aimed to investigate the clinical features of PKD in a large Chinese population. Methods One hundred and ninety five patients diagnosed as primary PKD were recruited. For all of the participants, neurological examinations were conducted and clinical manifestations were recorded and summarized in self - made uniform registration form for PKD patients. Clinical characteristics were statistically analyzed and compared between familial and sporadic PKD patients.  Results Among all of the 195 PKD patients in the present study, the gender ratio was 4.42∶1 (male∶ female. The average age of onset was (12.32 ± 3.49 years. There were 162 patients (83.08% manifestated with pure form and 33 (16.92% with complicated form of PKD. Among them 16 patients (8.21% had essential tremor (ET, and 144 patients (73.85% had premonitory symptom. The percentage of patients manifested as dystonia, chorea and mixed form during episodic attacks were 68.72% (134/195, 4.10% (8/195 and 27.18% (53/195 repectively. There were 134 cases (68.72% had facial involvement. It was recorded that 115 (58.97%, 54 (27.69% and 26 (13.33% patients had frequency of attack < 10 times/d, 10-20 times/d and > 20-30 times/d respectively. The percentages of patients whose duration of attack <10 s, 10-30 s and > 30-60 s were 60% (117/195, 29.74% (58/195 and 10.26% (20/195 respectively. There were 64 patietns (32.82% with family history of PKD and 131 (67.18% were sporadic PKD patients. Up to 40% (78/195 of patients did not require/take medications, as they had minor clinical manifestations or concerns about the side effects of anticonvulsants. Among 117 patients (60% prescribed with anticonvulsants, 114 patients showed a good response, including complete control (N

  13. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    Science.gov (United States)

    Quinn, N; Marsden, C D

    1984-08-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause tardive dyskinesia. Among currently available treatments, it may therefore be considered a drug of choice for treatment of tardive dyskinesia.

  14. Kindling: A Model for the Development of Tardive Dyskinesia?

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    B. Glenthøj

    1988-01-01

    Full Text Available Tardive dyskinesia (TD from long-term neuroleptic treatment may be irreversible; therefore prevention has become a major concern. A controversial issue with regard to the clinical use of neuroleptic drugs is the possible influence on the development of TD of drug holidays. The major characteristics of kindling, theories of TD and the role of multiplicity in the development of TD are described. Some clinical studies point to interruption of neuroleptic therapy being a risk factor for development of irreversible TD. Induction of dyskinesia in non-human primates has been demonstrated after repeated administration of haloperidol. Rodent studies have not been conclusive. Several experimental results link TD with kindling: both conditions involve repeated stimulations, both seem to involve increased receptor responsiveness and in both conditions does depression in GABA transmission in SNR (substantia nigra; pars reticulata play an important role. It is concluded that the kindling hypothesis is relevant to the investigation of TD.

  15. [A rare case of primary ciliary dyskinesia with heterotaxy].

    Science.gov (United States)

    Quintela, Cátia; Meireles, Cláudia; Bettencourt, Maria João; Ribeirinho, Augusto; Bentes, Teresa

    2009-01-01

    Primary ciliary dyskinesia is an autosomal recessive disease with a clinical history of upper and lowers respiratory infections, rhinosinusitis and bronquitis associated with complete or partial situs inversus. The authors present a 78 -year -old male caucasian patient with rhinosinusitis, lower respiratory tract infection and dyspnea, chronic otitis with hearing deficit and infertility followed in Gastroenterology for dyspepsia and constipation. The radiological studies revealed agenesis of right frontal sinus; bronchial wall thickening; bronchiectasis; cecum and ascending colon located on the left and small bowel occupies right side of abdomen. He had no immunodeficiency, allergies, cystic fibrosis and others. We concluded primary ciliary dyskinesia with heterotaxy. For the rarity of this case we decided to present it.

  16. A case of congenital myopathy masquerading as paroxysmal dyskinesia

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    Harsh Patel

    2014-01-01

    Full Text Available Gastroesophageal reflux (GER disease is a significant comorbidity of neuromuscular disorders. It may present as paroxysmal dyskinesia, an entity known as Sandifer syndrome. A 6-week-old neonate presented with very frequent paroxysms of generalized stiffening and opisthotonic posture since day 22 of life. These were initially diagnosed as seizures and he was started on multiple antiepileptics which did not show any response. After a normal video electroencephalogram (VEEG was documented, possibility of dyskinesia was kept. However, when he did not respond to symptomatic therapy, Sandifer syndrome was thought of and GER scan was done, which revealed severe GER. After his symptoms got reduced to some extent, a detailed clinical examination revealed abnormal facies with flaccid quadriparesis. Muscle biopsy confirmed the diagnosis of a specific congenital myopathy. On antireflux measures, those episodic paroxysms reduced to some extent. Partial response to therapy in GER should prompt search for an underlying secondary etiology.

  17. An Update on Tardive Dyskinesia: From Phenomenology to Treatment

    OpenAIRE

    Waln, Olga; Jankovic, Joseph

    2013-01-01

    Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a combination of different types of abnormal movements. In addition to movement disorders (including involuntary vocalizations), patients with TD may have a variety of sensory symptoms, such as urge to move (as in akathisia), paresthesias, and pain. TD is a form of tardive syndrome—a group of iatrogenic hyperkinetic and hypokinetic movement diso...

  18. Etiological characteristics and treatment of tardive dyskinesia

    Institute of Scientific and Technical Information of China (English)

    Zhe Li; Xueli Sun; Che Zhou

    2006-01-01

    OBJECTIVE:The pathogenesis of tardive dyskinesia(TD)is complicated and uncertain.Thus,there is not any effective treatment for it.The psychiatrists pay more and more attention to TD,which lasts for a long time and is difficult to treat.DATA SOURCES: A computer-based online search of Medline database was undertaken to jdentify articles about the feature of etiology and the progression of treatment for TD published in English by using the keywords of"TD,etiology.pathogenesis"and"TD,therapy,drug treatment".Meanwhile,Chinese articles about the feature of etiologY and the progression of treatment for TD were searched in Wanfang database and China joumal full-text database,and the keywords were"TD,etiology,pathogenesis"and"TD,therapy,drug Treatment".-in Chinese.STUDY SELECTION:Articles met the following inclusion cdteda were selected in this paper.Inclusion cdteda:①Researches of randomized blind control design,before and after control design and retrospective.②Researches of the feature of etiology and the progression of treatment for TD.Exclusion cdteda:the repetitive researches and individual reports,DATA EXTRACTION:Totally 65 articles related the feature of etiology and the progression of treatment for TD of randomized blind control design,before and after control design and retrospective studies were collected,and 53 of them were accorded with the inclusion criteda.Of the 12 excluded ones,8 were concerning with genetics,4 were repetitive researches.DATA SYNTHESIS:The feature of etiology for TD includes:①Hypothesis of dopamine receptor super-sensitivity:The dopamine recaptor is persistently blocked,so it wi¨result in functional disorder in CNS,and then TD may take place.②Hypothesis of neuronal degeneration:The concentration of aminosucoinic acid and glutamic acid wi¨;ncrease after the antipsychotic used for a Iong time and this wilI result in neuronal degeneration through glutamic acid receptor in the postsynaptic membrane;meanwhile with free radical

  19. CLINICAL AND SOCIAL RISK FACTORS OF TARDIVE DYSKINESIA IN PATIENTS WITH SCHIZOPHRENIA DURING ANTIPSYCHOTIC TREATMENT

    Directory of Open Access Journals (Sweden)

    Ye. G. Kornetova

    2015-01-01

    Full Text Available The purpose of the present work was to study the clinical features and risk factors of tardive dyskinesia among     the     schizophrenia     patients     who     durably     receive     the     antipsychotic     therapy. 180 of the 18 to 65 age bracket schizophrenia patients, who were treated in a residential psychiatric treatment facility, were examined with the use of the Positive and Negative Syndrome Scale (PANSS, Abnormal Involuntary Movement Scale (AIMS, and the basic chart of formalized sociodemographic and clinico-dynamic features developed at the Tomsk Mental Health Research Institute. The acquired data were processed by the Mann–Whitney U-Test and χ2. The average age of the tardive dyskinesia patients  turned out to be conclusively older than that of the patients without this derangement. People who have tardive dyskinesia statistically often happen to be single in comparison with other variants of marital status. It was found out that women happen to have tardive dyskinesia more often, which allows us to see the female gender as a risk factor. The tardive dyskinesia patients had certain negative symptoms. The patients were arranged into groups according to the prepotency of symptom-complexes over the subgroups: with orofacial, thoracolumbar and combined tardive dyskinesia. The average age of the orofacial dyskinesia patients turned out to be conclusively older than that of the patients without tardive dyskinesia. The negative symptoms level in the subgroup was conclusively higher than among those without tardive dyskinesia. The average age of the thoracolumbar dyskinesia patients was conclusively older than that of the patients without tardive dyskinesia. The average age of the combined dyskinesia patients was conclusively older than the patients without the tardive dyskinesia. The patients having schizophrenia for longer than 10 years prevailed in the combined dyskinesia group. Such characteristics as education

  20. Targeted to medication-induced dyskinesia and tardive dyskinesia: A role of 5-HT1A receptor

    Institute of Scientific and Technical Information of China (English)

    ZHEN Xue-chu

    2008-01-01

    Objective To outline the recent progress in drug discovery for medication-induced dyskinesia (Parkinson disease, PD) and tardive diskinesia (schizophrenia) with emphasizing the role of 5-HT1A receptor. Methods Development of extrapyramidal syndrome (EPS) followed either chronic L-DOPA administration in PD (L-DOPA-induced dyskinesia, LID) or antipsychotic treatment in schizophrenia (Tardive dyskinesia, TD) remains a challenge in the clinical practice and drug discovery. In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD, recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD. Results l-Stepholidine (l-SPD), isolated from the Chinese herb Stephania, is known as a dual dopamine receptor agent (D1 receptor agonistic and D2 antagonistic activity). In addition, we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity. In LID rat model, l-SPD not only attenuated the development of L-DOPA-induced dyskinesia (LID), but also relived the established LID. The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist, indicating the role of 5-HT1A receptor. Furthermore, we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135, which also exhibits a significant relief on LID while elicits its antiparkinsonian action. Conclusions 5-HT1A receptor plys an important role in the development of LID, targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.

  1. Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.

    NARCIS (Netherlands)

    Filipovic, S.R.; Rothwell, J.C.; Warrenburg, B.P.C. van de; Bhatia, K.P.

    2009-01-01

    In a placebo-controlled, single-blinded, crossover study, we assessed the effect of "real" repetitive transcranial magnetic stimulation (rTMS) versus "sham" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,8

  2. Genetic and phenotypic heterogeneity in sporadic and familial forms of paroxysmal dyskinesia

    NARCIS (Netherlands)

    Groffen, Alexander J. A.; Klapwijk, Thom; van Rootselaar, Anne-Fleur; Groen, Justus L.; Tijssen, Marina A. J.

    2013-01-01

    Paroxysmal dyskinesia (PxD) is a group of movement disorders characterized by recurrent episodes of involuntary movements. Familial paroxysmal kinesigenic dyskinesia (PKD) is caused by PRRT2 mutations, but a distinct etiology has been suggested for sporadic PKD. Here we describe a cohort of patients

  3. Movement parameters that distinguish between voluntary movements and levodopa-induced dyskinesia in Parkinson's disease.

    NARCIS (Netherlands)

    Keijsers, N.L.W.; Horstink, M.W.I.M.; Gielen, C.C.A.M.

    2003-01-01

    It is well known that long-term use of levodopa by patients with Parkinson's disease causes dyskinesia. Several methods have been proposed for the automatic, unsupervised detection and classification of levodopa induced dyskinesia. Recently, we have demonstrated that neural networks are highly

  4. Assessing self-awareness of dyskinesias in Parkinson’s disease through movie materials

    Science.gov (United States)

    Sitek, Emilia J.; Soltan, Witold; Wieczorek, Dariusz; Robowski, Piotr; Schinwelski, Michal; Slawek, Jaroslaw

    Summary The aim of our study was to determine self-awareness of dyskinesias and other core motor symptoms in Parkinson’s disease (PD) through the use of movie presentations. A scale based on 10 movies (five depicting dyskinesias and five showing core symptoms) and the Self-Assessment Parkinson’s Disease Disability Scale were administered to 21 patients (all with a Mini-Mental State Examination – MMSE score ≥25). Neurological assessment included the Unified Parkinson’s Disease Rating Scale and the Hoehn-Yahr and Schwab-England scales. In addition, the MMSE, Beck Depression Inventory and Stroop task were administered. Overall, patient and caregiver ratings of dyskinesias and core PD symptoms were consistent. Two patients (9%) completely denied dyskinesias, while four patients (19%) significantly underestimated their dyskinesias. Our results confirm that poor self-awareness of symptoms in PD may be selective and that denial of dyskinesias affects only a minority of patients with normal cognitive status (MMSE≥25). Most patients are aware of the presence of dyskinesias. Poor self-awareness of dyskinesias is associated with longer disease duration. PMID:22152432

  5. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis.

    Science.gov (United States)

    Boks, Marco P M; Liddle, Peter F; Russo, Sascha; Knegtering, Rikus; van den Bosch, Robert Jan

    2003-07-15

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of antipsychotic medication does not influence NSS, but that atypical antipsychotics are associated with less dyskinesia in the early stages of treatment.

  6. Resting-State Connectivity Predicts Levodopa-Induced Dyskinesias in Parkinson's Disease

    DEFF Research Database (Denmark)

    Herz, Damian M.; Haagensen, Brian N.; Nielsen, Silas H.;

    2016-01-01

    dyskinesias emerged. Levodopa-induced modulation of cortico-striatal resting-state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures......-state connectivity between the putamen and primary sensorimotor cortex in the most affected hemisphere predicted whether patients would develop dyskinesias with a specificity of 100% and a sensitivity of 91% (P putamen...... predicted interindividual differences in dyskinesia severity (R2 = 0.627, P = .004). Resting-state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity. Conclusions: The results corroborate the notion that altered dopaminergic...

  7. Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    Souza, Renan P; Remington, Gary; Meltzer, Herbert Y; Lieberman, Jeffrey A; Kennedy, James L; Wong, Albert H C

    2010-09-01

    Phosphodiesterase 4B (PDE4B) has been evaluated as a genetic risk factor for schizophrenia. Selective PDE4 inhibitor drugs have antipsychotic-like effects and reduce tardive dyskinesia-like movements in animal models. We investigated whether PDE4B genetic variants are associated with antipsychotic-induced tardive dyskinesia incidence and severity in schizophrenia patients. Our sample consisted of 169 Caucasian patients taking typical antipsychotic medication for at least 1 year. We found two PDE4B gene variants to be nominally associated with tardive dyskinesia (rs1338719 and rs7528545) in the overall population and two other variants nominally associated with the presence of tardive dyskinesia and severity in female patients (rs1890196 and rs783036). None of these results survived correction for multiple testing. Overall, our results do not support a genetic association between tardive dyskinesia and PDE4B.

  8. Treatment of scapula dyskinesia with botulin toxin: two case reports.

    Science.gov (United States)

    Fusaro, Isabella; Orsini, Stefania; Bellenghi, Chiara; Smeraldi, Silvia; Rotini, Roberto; Sinapi, Fabrizio

    2010-05-01

    We report two cases of scapula-thoracic dyskinesia with different etiologies where both patients complained of functional limitation and pain in the shoulder. The first case was caused by a road accident, the second by sequelae of surgery to remove aggressive scapula-axillary fibromatosis. In both patients, therapy with botulin toxin type A (Botox) was performed, which determined a reduction in pain. In the first case, there was also an improvement in function. There were no side effects in the two patients after the injections.

  9. Serotonergic neurons mediate dyskinesia side effects in Parkinson's patients with neural transplants.

    Science.gov (United States)

    Politis, Marios; Wu, Kit; Loane, Clare; Quinn, Niall P; Brooks, David J; Rehncrona, Stig; Bjorklund, Anders; Lindvall, Olle; Piccini, Paola

    2010-06-30

    Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by l-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT(1A)) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.

  10. Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics.

    Science.gov (United States)

    Koppel, Barbara S

    2015-10-01

    Cannabis has been used for many medicinal purposes, including management of spasms, dystonia, and dyskinesias, with variable success. Its use for tetanus was described in the second century BCE, but the literature continues to include more case reports and surveys of its beneficial effects in managing symptoms of hyperkinetic movement disorders than randomized controlled trials, making evidence-based recommendations difficult. This paper reviews clinical research using various formulations of cannabis (botanical products, oral preparations containing ∆(9)-tetrahydrocannabinol and/or cannabidiol) and currently available preparations in the USA (nabilone and dronabinol). This has been expanded from a recent systematic review of cannabis use in several neurologic conditions to include case reports and case series and results of anonymous surveys of patients using cannabis outside of medical settings, with the original evidence classifications marked for those papers that followed research protocols. Despite overlap in some patients, dyskinesias will be treated separately from dystonia and chorea; benefit was not established beyond individual patients for these conditions. Tics, usually due to Tourettes, did respond to cannabis preparations. Side effects reported in the trials will be reviewed but those due to recreational use, including the dystonia that can be secondary to synthetic marijuana preparations, are outside the scope of this paper.

  11. Vitamin E in the treatment of tardive dyskinesia.

    Directory of Open Access Journals (Sweden)

    Akhtar S

    1993-07-01

    Full Text Available In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD was studied in 32 patients. After a two week wash-out phase a baseline (0 week TD rating was assessed on the tardive dyskinesia rating scale (TDRS. Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week. All patients were rated on the TDRS at the end of each week. The baseline TDRS score in the vitamin E group was significantly higher than the placebo group. This was hence adjusted and the results were then subjected to analysis of co- variance. The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03.

  12. New and emerging treatments for symptomatic tardive dyskinesia

    Directory of Open Access Journals (Sweden)

    Rana AQ

    2013-11-01

    Full Text Available Abdul Qayyum Rana,1–4 Zishan M Chaudry,5 Pierre J Blanchet6 1Parkinson's Clinic of Eastern Toronto and Movement Disorders Centre, Toronto, ON, Canada; 2Scarborough Memory Program, Toronto, ON, Canada; 3Journal of Parkinsonism and RLS, Toronto, ON, Canada; 4Bulletin of World Parkinson's Program, Toronto, ON, Canada; 5Saba University School of Medicine, The Bottom, Saba, Dutch Caribbean; 6Department of Stomatology, University of Montreal, Montreal, QC, Canada Abstract: The aim of this review is to assess new, emerging, and experimental treatment options for tardive dyskinesia (TD. The methods to obtain relevant studies for review included a MEDLINE search and a review of studies in English, along with checking reference lists of articles. The leading explanatory models of TD development include dopamine receptor supersensitivity, GABA depletion, cholinergic deficiency, neurotoxicity, oxidative stress, changes in synaptic plasticity, and defective neuroadaptive signaling. As such, a wide range of treatment options are available. To provide a complete summary of choices we review atypical antipsychotics along with resveratrol, botulinum toxin, Ginkgo biloba, tetrabenazine, clonazepam, melatonin, essential fatty acids, zonisamide, levetiracetam, branched-chain amino acids, drug combinations, and invasive surgical treatments. There is currently no US Food and Drug Administration-approved treatment for TD; however, prudent use of atypical antipsychotics with routine monitoring remain the cornerstone of therapy, with experimental treatment options available for further management. Keywords: tardive dyskinesia, first-generation antipsychotics, motor symptoms, schizophrenia, Parkinson's, atypical antipsychotics

  13. Diagnosis by ultrastructural study of primary ciliary dyskinesia

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    Melgarejo-Moreno P

    2015-01-01

    Full Text Available Introduction and objective: Primary ciliary dyskinesia (PCD, also known as ciliary immotility (SIC syndrome is an inherited disorder that includes a group of diseases in which respiratory cilia are immobile, ciliary movement is dyskinetic and ineffective or no cilia . The aim of this study is to determine the ciliary ultrastructure in patients with suspected DCP. Method: In 8 patients with suspected DCP nasal mucosa biopsy is performed with endoscopy at the inferior turbinate in the middle third by the ENT service under local anesthesia. Results: Of the 8 cases studied in 2 cases no ciliary ultrastructural level defects were found. In two cases with abnormal ciliary ultrastructure is present Kartagener syndrome. In a case no cilia were observed in the nasal mucosa. Discussion: The DCP and SIC are synonymous terms from clinical and pathogenetic view: immobility and dyskinesia lead to an absence of mucociliary transport, stasis of respiratory secretions with their consequences: chronic infections of lower respiratory tract and from birth . The most common ultrastructural defect is the total or partial absence of dynein. Conclusions: The ultrastructural study allows the diagnosis of PCD because genetic diagnosis is complicated and therefore get an early diagnosis of this condition which serves to improve the morbidity and mortality of these patients.

  14. Dopaminergic stimulation of subthalamic nucleus elicits oral dyskinesia in rats.

    Science.gov (United States)

    Parry, T J; Eberle-Wang, K; Lucki, I; Chesselet, M F

    1994-08-01

    The effects of dopaminergic stimulation of the subthalamic nucleus (STh) on motor behavior were examined in conscious rats. Unilateral infusion of apomorphine (0.1 to 3.2 micrograms) into the STh induced a dose-dependent increase in abnormal, nondirected orofacial movements without altering turning, sniffing, grooming, or rearing behaviors. Orofacial movements elicited by local infusion of apomorphine (1.0 microgram) into the STh were blocked by peripheral administration of the D1 antagonist, SCH 23390 (0.1 mg/kg, sc), but not by the D2 antagonists haloperidol (1.0 mg/kg, sc) or sulpiride (50 mg/kg, sc). Furthermore, coinfusion of SCH 23390 (1.0 microgram), but not sulpiride (5.0 micrograms), with apomorphine (1.0 microgram) into the STh blocked oral dyskinesia. Oral movements could not be reelicited by an infusion of apomorphine into the STh after a kainic acid lesion of the STh. In addition, infusion of apomorphine (1.0 microgram) into sites proximal to but deliberately outside of the STh failed to elicit nondirected oral movements above baseline levels. The results indicate that stimulation of D1 dopaminergic receptors within the STh induces abnormal orofacial movements. This highlights the importance of the dopaminergic input to the STh in the regulation of motor function and suggests that D1 receptor antagonists could prove useful in the treatment of orofacial dyskinesia in humans.

  15. Treatment of tardive dyskinesia: a systematic review (1997-2011

    Directory of Open Access Journals (Sweden)

    M. Alimi

    2013-09-01

    Full Text Available Background and Objectives: Tardive dyskinesia (TD is a frequent and incapacitating side effect of first-generation antipsychotics. Although second-generation antipsychotics (SGAs seem to be associated with a decreased risk of TD, it remains a severe, unresolved iatrogenic condition. Moreover, there is no commonly accepted effective treatment for TD. We conducted a systematic review of the literature to assess evidence regarding the effectiveness of different therapeutic interventions for TD. Methods: We performed a systematic review focussing exclusively on randomised controlled trials (RCTs. We searched the MEDLINE database (1997 to 2011 using the keyword "tardive dyskinesia" within the "title" search field. Twenty-six RCTs were included. Based on the evidence from RCTs, we built a decision tree that healthcare professionals can use to choose an effective therapeutic intervention for TD. Results: Four therapeutic interventions were found to be effective in TD (vitamin B6, ginkgo biloba, branched-chain amino acids, and piracetam. Conclusions: Patients with TD could benefit from the therapeutic interventions supported by the data accumulated from RCTs.

  16. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    Science.gov (United States)

    Heitzmann, Edwige; Weiner, Luisa; Michel, Bruno

    2016-01-01

    Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsidering the real risk of tardive dyskinesia associated with aripiprazole, particularly in the elderly. PMID:27818825

  17. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    Directory of Open Access Journals (Sweden)

    Edwige Heitzmann

    2016-01-01

    Full Text Available Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsidering the real risk of tardive dyskinesia associated with aripiprazole, particularly in the elderly.

  18. Tardive dyskinesia, dehydroepiandrosterone sulfate and cytochrome P450c17a gene polymorphism in psychiatric inpatients

    NARCIS (Netherlands)

    Ivanova, S.A.; Geers, L.M.; Al Hadithy, A.F.Y.; Pechlivanoglou, P.; Semke, A.V.; Vyalova, N.M.; Fedorenko, O.Y.; Brouwers, J.R.B.J.; Wilffert, B.; Loonen, A.J.M.

    2014-01-01

    Tardive dyskinesia (TD) is a potentially irreversible antipsychoticinduced movement disorder with a prevalence of about 20-30% in psychiatric patients chronically exposed to antipsychotics. A wellknown theory states that TD is related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone

  19. Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Johansen, Helle Krogh; Aanaes, Kasper

    2015-01-01

    Conclusion: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD). The observed decrease in serum precipitating antibodies (precipitins) against Pseudomonas aeruginosa may indicate a beneficial...

  20. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

    DEFF Research Database (Denmark)

    Herz, Damian M.; Haagensen, Brian N.; Christensen, Mark S.

    2015-01-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy...... of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51–84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped...... later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation...

  1. PRRT2 phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions

    NARCIS (Netherlands)

    van Vliet, Rianne; Breedveld, Guido; de Rijk-van Andel, Johanneke; Brilstra, Eva; Verbeek, Nienke; Verschuuren-Bemelmans, Corien; Boon, Maartje; Samijn, Johnny; Diderich, Karin; van de Laar, Ingrid; Oostra, Ben; Bonifati, Vincenzo; Maat-Kievit, Anneke

    2012-01-01

    Objective: To describe the phenotypes and penetrance of paroxysmal kinesigenic dyskinesia (PKD), a movement disorder characterized by attacks of involuntary movements occurring after sudden movements, infantile convulsion and choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions

  2. Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation

    DEFF Research Database (Denmark)

    Gardella, Elena; Becker, Felicitas; Møller, Rikke S

    2015-01-01

    Objective: Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as infantile convulsions and paroxysmal choreoathetosis (ICCA)-are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified...

  3. INFLUENCE BILIARY DYSKINESIA ON RELIABLE CHAIR-TEST IN PATIENTS WITH CHRONIC NON-ATROPHIC GASTRITIS

    OpenAIRE

    Avramenko, A. A.; Korolenko, R N; Shuhtina, I. N.

    2017-01-01

    It was carried out a comprehensive survey of 45 patients with chronic non-atrophic gastritis with biliary dyskinesia, which included ultrasound diagnosis of abdominal organs, pH meters, esophagogastroduodenoscopy, double testing for H. pylori infection and histological examination of the gastric mucosa to 4 - m topographic zones, stool test and determine the level of antibodies to HP infection by ELISA. It was found that the presence of biliary dyskinesia reduces the reliability of the chair-...

  4. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia.

    OpenAIRE

    Quinn, N.; Marsden, C. D.

    1984-01-01

    Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause...

  5. Spontaneous dyskinesia in first-episode psychosis in a Southeast Asian population.

    Science.gov (United States)

    Lee, Jimmy; Poon, Lye-Yin; Chong, Siow-Ann

    2008-10-01

    Spontaneous dyskinesia in first-episode psychosis was described previously with varying incidence rates ranging from zero to 53%. Dyskinesia was also found to be more common in siblings of patients with both schizophrenia and dyskinesia. This condition was linked with structural brain abnormalities and posited to be another subtype of schizophrenia with striatal pathology. Whether there are ethnic variations in the rates of spontaneous dyskinesia is unknown because of the paucity of studies in this area. This study aims to establish the rates of spontaneous dyskinesia in a Southeast Asian population of drug-naive patients experiencing their first psychotic episode and to examine the clinical correlates. A total of 908 patients were examined, of which, 76.1% were Chinese; 15.4%, Malays; 6.2%, Indians; and 2.3%, from other minor ethnic groups. Schizophrenia was diagnosed in 48.9% of the population. There were 3 patients of Chinese descent who had "minimal" or "mild" dyskinetic movements when rated with the Abnormal Involuntary Movement Scale, but none fulfilled the Schooler and Kane criteria for spontaneous dyskinesia. Their dyskinetic movements resolved when reassessed 3 and 6 months after treatment with antipsychotic medications. Of the 3 patients, 2 were treatment resistant and subsequently treated with clozapine. This is the largest study to date examining the prevalence of spontaneous dyskinesia. We hypothesize that there is an ethnically based difference in the rates of spontaneous dyskinesia that could reflect underlying genetic variations. Patients with dyskinetic movements at baseline could have a more treatment refractory course of illness.

  6. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    OpenAIRE

    Edwige Heitzmann; Hervé Javelot; Luisa Weiner; Bruno Michel

    2016-01-01

    Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsi...

  7. Pharmacogenetics of tardive dyskinesia: an updated review of the literature.

    Science.gov (United States)

    Lanning, Rachel K; Zai, Clement C; Müller, Daniel J

    2016-08-01

    Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD. Recent promising findings were obtained with the HSPG2, DPP6, MTNR1A, SLC18A2, PIP5K2A and CNR1 genes. More research, including collection of well-characterized samples, enhancement of genome-wide strategies, gene-gene interaction and epigenetic analyses, is needed before genetic tests with clinical utility can be made available for TD.

  8. An update on tardive dyskinesia: from phenomenology to treatment.

    Science.gov (United States)

    Waln, Olga; Jankovic, Joseph

    2013-01-01

    Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a combination of different types of abnormal movements. In addition to movement disorders (including involuntary vocalizations), patients with TD may have a variety of sensory symptoms, such as urge to move (as in akathisia), paresthesias, and pain. TD is a form of tardive syndrome-a group of iatrogenic hyperkinetic and hypokinetic movement disorders caused by dopamine receptor-blocking agents. The pathophysiology of TD remains poorly understood, and treatment of this condition is often challenging. In this update, we provide the most current information on the history, nomenclature, etiology, pathophysiology, epidemiology, phenomenology, differential diagnosis, and treatment of TD.

  9. Tardive Dyskinesia, Oral Parafunction, and Implant-Supported Rehabilitation

    Science.gov (United States)

    Amore, M.

    2016-01-01

    Oral movement disorders may lead to prosthesis and implant failure due to excessive loading. We report on an edentulous patient suffering from drug-induced tardive dyskinesia (TD) and oral parafunction (OP) rehabilitated with implant-supported screw-retained prostheses. The frequency and intensity of the movements were high, and no pharmacological intervention was possible. Moreover, the patient refused night-time splint therapy. A series of implant and prosthetic failures were experienced. Implant failures were all in the maxilla and stopped when a rigid titanium structure was placed to connect implants. Ad hoc designed studies are desirable to elucidate the mutual influence between oral movement disorders and implant-supported rehabilitation. PMID:28050290

  10. Transient apical dyskinesia with a pacemaker: Electrocardiographic features.

    Science.gov (United States)

    Núñez-Gil, Iván J; Feltes, Gisela I; Mejía-Rentería, Hernán D; Biagioni, Corina; De Agustín, J Alberto; Vivas, David; Fernández-Ortiz, Antonio

    2015-04-01

    Transient apical dyskinesia syndromes present features similar to acute coronary syndromes, but with normal coronary arteries and rapid complete resolution of wall motion alterations. We report the case of a 73-year-old woman who was admitted to hospital because of typical chest pain at rest after her brother's death. She had had a pacemaker implanted in 2001. Troponin levels were elevated and apical hypokinesia was shown by ventriculography and echocardiography, with normal coronary arteries. Evolving ECG alterations were observed in spite of the continued pacing rhythm. All these alterations were fully resolved after discharge. This case shows that, even in the presence of a pacemaker, evolving ECG alterations can be observed in Takotsubo syndrome.

  11. Perinatal dyskinesia as a presenting feature in Prader Willi syndrome.

    Science.gov (United States)

    McSweeney, Niamh; Cowan, Frances; Manzur, Adnan; Robb, Stephanie; Muntoni, Francesco

    2009-07-01

    Prader Willi Syndrome (PWS) is a complex genetic disorder. Infants present with hypotonia and feeding difficulties, usually without respiratory symptoms, but with distinctive facial features. Early neonatal diagnosis can however be difficult in children with only subtle distinctive appearances or with atypical clinical signs, leading to a significant delay in the diagnosis. To highlight the diagnostic difficulties we reviewed our experience of infants with PWS referred to our tertiary centre. We describe 14 patients, 10 of whom presented in the neonatal period. All had axial hypotonia, and poor feeding. Twelve had a paucity of movement, 11 had distinctive features and 10 had a reduced level of alertness in the neonatal period. In addition to these typical features, four patients had prominent limb dyskinesia, which has only been reported once before in infants with PWS. We draw attention to this relatively common but poorly acknowledged sign that can be seen at presentation of PWS.

  12. Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

    Directory of Open Access Journals (Sweden)

    Veronica Ghiglieri

    2012-01-01

    Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

  13. Maladaptive synaptic plasticity in L-DOPA-induced dyskinesia

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2016-12-01

    Full Text Available The emergence of L-DOPA-induced dyskinesia (LID in patients with Parkinson disease (PD could be due to maladaptive plasticity of corticostriatal synapses in response to L-DOPA treatment. A series of recent studies has revealed that LID is associated with marked morphological plasticity of striatal dendritic spines, particularly cell type-specific structural plasticity of medium spiny neurons (MSNs in the striatum. In addition, evidence demonstrating the occurrence of plastic adaptations, including aberrant morphological and functional features, in multiple components of cortico-basal ganglionic circuitry, such as primary motor cortex (M1 and basal ganglia (BG output nuclei. These adaptations have been implicated in the pathophysiology of LID. Here, we briefly review recent studies that have addressed maladaptive plastic changes within the cortico-BG loop in dyskinetic animal models of PD and patients with PD.

  14. Patient and caregiver perceptions of the social impact of advanced Parkinson's disease and dyskinesias.

    Science.gov (United States)

    Khlebtovsky, Alexander; Rigbi, Amihai; Melamed, Eldad; Ziv, Ilan; Steiner, Israel; Gad, Alona; Djaldetti, Ruth

    2012-11-01

    Parkinson's disease (PD) exacts a physical and emotional toll on both patients and family. The aim of this study was to compare patient and caregiver perceptions of the social consequences of basic symptoms of PD and levodopa-induced dyskinesias. Forty patients with PD and dyskinesias and 35 of their caregivers completed a self-report questionnaire on the impact of PD and dyskinesias on their feelings of security and embarrassment and participation in family/social events, and indicated their preference for the "on" (with dyskinesias) or the "off" (without dyskinesias) state. The patients scored significantly higher than the caregivers did on the negative social impact of the disease in general (p = 0.002) and of the dyskinesias in particular (p = 0.03). Nevertheless, the patients expressed a significantly greater preference for the "on" state (83 %) than the caregivers (59 %) (p = 0.03). Preferences turned to be reverse in direction among spouse-caregivers who significantly preferred the "off" state (54 %) than the patients (25 %) (p = 0.04). Although patients have a worse perception of the effects of PD than their caregivers do, they prefer the more independent "on" state, whereas their caregivers prefer the "off" state.

  15. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome.

    Science.gov (United States)

    Leigh, Margaret W; Pittman, Jessica E; Carson, Johnny L; Ferkol, Thomas W; Dell, Sharon D; Davis, Stephanie D; Knowles, Michael R; Zariwala, Maimoona A

    2009-07-01

    Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate(dynein axonemal intermediate chain 1) chain dynein genes in ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for primary ciliary dyskinesia is available for the most common mutations. The respiratory manifestations of primary ciliary dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media)reflect impaired mucociliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with primary ciliary dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease),reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with primary ciliary dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with primary ciliary dyskinesia.

  16. VITAMINE E IN THE MANAGEMENT OF DRUG INDUCED TARDIVE DYSKINESIA: A DOUBLE BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    M KAR AHMADI

    2002-12-01

    Full Text Available Introduction. Expresssion of tardive dyskinesia as one of the side effects of antipsychotic drugs causes various problems in psychotic patients. It is the main cause of patient"s drug incompliance.Vitamine E with it"s antioxidants properties might be an effective treatment for tardive dyskinesia. Methods. In a randomized double blind clinical trial, thirty inpatients of the psychiatric hospital in Isfahan were studied. Patients were stratified according to their age, psychiatric disorder and duration, intensity of tardive dyskinesia and antipsychotic dosage. Then they were asssigned randomly into two groups. Vitamine E (600 mg/day was administered to interventional group (15 patients. Another group received placebo (15 patients. Treatment durated for 6 weeks. Abnormal Involuntary Movment Scale (AIMS was used to measure tardive dyskinesia intensity. Results. Average of disorder intensity in those who received vit. E, dropped down from 8.33/10 (befor treatment to 6.13/10 (after treatment. It means 26.3 percent reduction of tardive dyskinesia intensity. This difference was only 7.3 percent in control group. There were no statistical diffrence between two groups after treatment (P>0.05. Discussion. There is no statistical efficacy for vitamine E in the management of tardive dyskinesia. But it is recommended to make another study with more samples.

  17. Striatal activation by optogenetics induces dyskinesias in the 6-hydroxydopamine rat model of Parkinson disease.

    Science.gov (United States)

    F Hernández, Ledia; Castela, Ivan; Ruiz-DeDiego, Irene; Obeso, Jose A; Moratalla, Rosario

    2017-04-01

    Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle. For the optogenetic manipulation, we injected adeno-associated virus particles expressing channelrhodopsin to stimulate striatal medium spiny neurons with a laser source. Simultaneous optical activation of medium spiny neurons of the direct and indirect striatal pathways in the 6-hydroxydopamine lesion but l-dopa naïve rats induced involuntary movements similar to l-dopa-induced dyskinesias, labeled here as optodyskinesias. Noticeably, optodyskinesias were facilitated by l-dopa in animals that did not respond initially to the laser stimulation. In general, optodyskinesias lasted while the laser stimulus was applied, but in some instances remained ongoing for a few seconds after the laser was off. Postmortem tissue analysis revealed increased FosB expression, a molecular marker of l-dopa-induced dyskinesias, primarily in medium spiny neurons of the direct pathway in the dopamine-depleted hemisphere. Selective optogenetic activation of the dorsolateral striatum elicits dyskinesias in the 6-hydroxydopamine rat model of PD. This effect was associated with a preferential activation of the direct striato-nigral pathway. These results potentially open new avenues in the understanding of mechanisms involved in l-dopa-induced dyskinesias. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  18. Methylphenidate treatment and dyskinesia in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Balázs, Judit; Dallos, Gyöngyvér; Keresztény, Agnes; Czobor, Pál; Gádoros, Júlia

    2011-04-01

    Case reports suggest a relationship between methylphenidate treatment and dyskinesia in attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was (a) to investigate abnormal involuntary movements of children with ADHD before and after the administration of methylphenidate and (b) to investigate the effect of a provocative assessment method used to make latent dyskinesia visible, which is included in the Abnormal Involuntary Movement Scale (AIMS). Participants, aged 6-18, were recruited from a Child and Adolescent Psychiatric Hospital and Outpatient Clinic (Vadaskert Foundation), Budapest, Hungary. Using a structured diagnostic interview (Mini International Neuropsychiatric Interview Kid), 37 children were included in the ADHD group and 34 children in the control group. The AIMS was used to observe and score dyskinesia. There was a significant difference between the baseline total AIMS score in the ADHD and the control groups, with the ADHD subjects evidencing substantially higher severity than controls. Provocation, as applied with the administration of the AIMS, significantly increased the AIMS total score in both groups. The administration of methylphenidate had no effect on the total score of the AIMS. In the ADHD group, we observed a significant negative relationship between the patients' age and the overall severity on the AIMS. In contrast, in the control group we detected a significant positive relationship between the patients' age and the overall severity on the AIMS before and no relationship after provocation. Methylphenidate-treated children with ADHD had more dyskinesia than children in the control group. Dyskinesia did not worsen after a single dose of methylphenidate. Higher dyskinesia scores in the methylphenidate-treated younger age group warrant caution in the methylphenidate treatment of ADHD; however, further studies are needed to clarify the possible causal relationship between dyskinesia and methylphenidate treatment

  19. Tardive Dyskinesia Revisited: A Clinical Priority Perspective-Diagnosis and Assessment (Part A

    Directory of Open Access Journals (Sweden)

    Vernon M Neppe

    2016-06-01

    Full Text Available In this series of papers under the umbrella of tardive dyskinesia (TD, five major related issues are discussed pertaining to TD. These are integrated together. In Part A we evaluate how to diagnose, screen for physical signs and scales for tardive dyskinesia, and in Part B, we focus on the management. Tardive dyskinesia (TD is a relatively new condition associated with abnormal involuntary movements caused by or aggravated by so-called “neuroleptic” drugs. Neuroleptics are used to manage psychotic conditions, as well as nausea and acid reflux, and latterly are prescribed as adjunct medications to depression and anxiety. Tardive dyskinesia (TD has also become a major problem forensically, because of the challenge of management, the lack of patient’s being appropriately warned, and insufficient monitoring of patients at risk. In this Part A series of articles we examine several special important priorities in TD. a. First, what is tardive dyskinesia and how does one make the diagnosis? b. The second issue is the need to regularly evaluate patients on neuroleptics because they are at risk for tardive dyskinesia. Measuring and monitoring for symptoms of tardive dyskinesia allows ensuring early detection. The author’s clinical STRAW test has thus far been seldom used, but it may be the best way to monitor TD over time. It appears an improvement over the standard test, the AIMS, as it is broader in ranking (0-10 and is the only scale that measures both frequency and severity, so that monitoring of change is more sensitive. In the series that follows, Part B, we emphasize management and theory, particularly high dose buspirone management, justify the dopamine super sensitivity hypothesis, and re-evaluate the neuroleptics in that context. e1

  20. Crocin prevents haloperidol-induced orofacial dyskinesia: possible an antioxidant mechanism

    Science.gov (United States)

    Kamyar, Marzyeh; Razavi, Bibi Marjan; Hasani, Faezeh Vahdati; Mehri, Soghra; Foroutanfar, Amir; Hosseinzadeh, Hossein

    2016-01-01

    Objective(s): Long-term treatment with antipsychotics causes serious side effects such as tardive dyskinesia that characterized by abnormal movements in the orofacial region. Oxidative stress in the brain specific area is implicated in the pathophysiology of tardive dyskinesia. In this study the protective effect of crocin on haloperidol-induced orofacial dyskinesia was evaluated. Materials and Methods: Haloperidol (1 mg/kg, IP) and crocin (10, 20 and 40 mg/kg, IP) were administrated to rats for 21 days. Behavioral assessments such as orofacial dyskinesia movements, open field test and elevated plus maze (EPM) were evaluated every week. Malondealdehyde (MDA) and glutathione (GSH) levels in the hippocampus, cortex and striatum were also measured. Results: Haloperidol increased vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats and co-administration of crocin (20 and 40 mg/kg) significantly reduced them. Furthermore, haloperidol decreased the locomotor and exploratory activities (rearing) in the open field test and decreased the percentage of entries into open arms and the percentage of the time spent on open arms in the EPM. Pretreatment with crocin (10 mg/kg) modified haloperidol effects on these behavioral parameters. Haloperidol induced lipid peroxidation in three brain regions, whereas crocin co-administration reduced the MDA and restored the decreased GSH levels. Conclusion: Our finding suggests that oxidative stress has an important role in the development of tardive dyskinesia. Crocin showed protective effect against haloperidol induced tardive dyskinesia and as a potent naturally antioxidant could be a new and useful drug and a possible therapeutic option for the treatment of tardive dyskinesia. PMID:27872703

  1. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.

    Science.gov (United States)

    Luquin, M R; Scipioni, O; Vaamonde, J; Gershanik, O; Obeso, J A

    1992-01-01

    Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.

  2. L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated primates.

    Science.gov (United States)

    Kuoppamäki, M; Al-Barghouthy, G; Jackson, M J; Smith, L A; Quinn, N; Jenner, P

    2007-09-01

    Most patients with Parkinson's disease (PD) develop dyskinesia and other motor complications after prolonged L-dopa use. We now report on the relationship between L-dopa dose and the duration and severity of dyskinesia in L-dopa-primed MPTP-treated primates with marked nigral degeneration mimicking late stage PD. With increasing doses of L-dopa, locomotor activity increased and motor disability declined. The duration of dyskinesia following L-dopa administration increased dose-dependently, and showed a linear correlation with total locomotor activity. In addition, the time-course of dyskinesia paralleled closely that of locomotor activity in a dose-dependent manner. In contrast, severity of dyskinesia showed a non-linear correlation with total locomotor activity, low doses of L-dopa eliciting severe dyskinesia for short periods of time. The threshold for dyskinesia induction and the antiparkinsonian effects of L-dopa appear very similar in primed MPTP primates mimicking late stage PD. Reducing individual doses of L-dopa to avoid severe dyskinesia can markedly compromise the antiparkinsonian response. Our results extend the relevance of the dyskinetic MPTP-treated primate in studying the genesis of involuntary movements occurring in L-dopa treated patients with PD.

  3. Diagnosing primary ciliary dyskinesia: an international patient perspective

    Science.gov (United States)

    Dunn Galvin, Audrey; Rubbo, Bruna; Masefield, Sarah; Copeland, Fiona; Manion, Michele; Rindlisbacher, Bernhard; Redfern, Beatrice; Lucas, Jane S.

    2016-01-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sino-pulmonary disease, with symptoms starting soon after birth. A European Respiratory Society (ERS) Task Force aims to address disparities in diagnostics across Europe by providing evidence-based clinical practice guidelines. We aimed to identify challenges faced by patients when referred for PCD diagnostic testing. A patient survey was developed by patient representatives and healthcare specialists to capture experience. Online versions of the survey were translated into nine languages and completed in 25 countries. Of the respondents (n=365), 74% were PCD-positive, 5% PCD-negative and 21% PCD-uncertain/inconclusive. We then interviewed 20 parents/patients. Transcripts were analysed thematically. 35% of respondents visited their doctor more than 40 times with PCD-related symptoms prior to diagnostic referral. Furthermore, the most prominent theme among interviewees was a lack of PCD awareness among medical practitioners and failure to take past history into account, leading to delayed diagnosis. Patients also highlighted the need for improved reporting of results and a solution to the “inconclusive” diagnostic status. These findings will be used to advise the ERS Task Force guidelines for diagnosing PCD, and should help stakeholders responsible for improving existing services and expanding provision for diagnosis of this rare disease. PMID:27492837

  4. Clinical spectrum of primary ciliary dyskinesia in childhood

    Science.gov (United States)

    Fretzayas, Andrew; Moustaki, Maria

    2016-01-01

    Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder. PMID:26862502

  5. Primary ciliary dyskinesia: considerations regarding six cases of Kartagener syndrome.

    Science.gov (United States)

    Ortega, Hugo Alejandro Vega; Vega, Nelson de Araujo; Santos, Bruno Quirino Dos; Maia, Guilherme Tavares da Silva

    2007-01-01

    Primary ciliary dyskinesia (PCD), previously known as immotile cilia syndrome, is an autosomal recessive hereditary disease that includes various patterns of ciliary ultrastructural defects. The most serious form is Kartagener syndrome (KS), which accounts for 50% of all cases of PCD. The incidence of PCD ranges from 1:20,000 to 1:60,000. Since PCD causes deficiency or even stasis of the transport of secretions throughout the respiratory tract, it favors the growth of viruses and bacteria. As a result, patients have lifelong chronic and recurrent infections, typically suffering from bronchitis, pneumonia, hemoptysis, sinusitis, and infertility. Bronchiectasis and other chronic conditions infections can be the end result of the irreversible bronchial alterations, leading to chronic cor pulmonale and its consequences. Only half of the patients affected by PDC present all of the symptoms, a condition designated complete KS, compared with incomplete KS, typically defined as cases in which situs inversus does not occur. The diagnosis is made clinically and confirmed through transmission electron microscopy. Since there is no specific therapy for PCD, it is recommended that, upon diagnosis, secondary infections be treated with potent antibiotics and prophylactic interventions be implemented. In this paper, we report six cases of PCD (five cases of complete KS and one case of KS) and review the related literature, focusing on the diagnostic, therapeutic and clinical aspects of this disease.

  6. Relapse of tardive dyskinesia due to reduction in clozapine dose

    Directory of Open Access Journals (Sweden)

    Shrivastava Meena

    2009-01-01

    Full Text Available Clozapine is a second-generation (atypical antipsychotic agent, which has been proven efficient against the positive and negative symptoms of schizophrenia, with a low propensity to induce tardive dyskinesia (TD. Compared with typical antipsychotics, it has a greater affinity for dopamine D4 than D2 receptors and additional action on serotonin 5-HT 2A receptors. Due to its weak D 2 blocking action, it produces few extra pyramidal side effects and TD is rare. TD is one of the muscular side effects of antipsychotic drugs, especially the older generation like haloperidol. TD does not occur until after many months or years of taking antipsychotic drugs. TD is primarily characterized by abnormal involuntary movements of the tongue, lips or jaw, as well as facial grimacing or extremities that develop in association with the use of antipsychotic medications. TD can be embarrassing to the affected patient in public. The movements disappear during sleep and women are at greater risk than men for developing TD.

  7. Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Dammann Andersen, Andreas; Binzer, Michael

    2017-01-01

    L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered...... levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n=26) were...... clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 hours after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid...

  8. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke: Case Series.

    Science.gov (United States)

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-08-01

    Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases.This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance.During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization.The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia.

  9. Effects of sulpiride on persistent neuroleptic-induced dyskinesia in monkeys.

    Science.gov (United States)

    Häggström, J E

    1984-01-01

    Five Cebus apella monkeys with persistent neuroleptic-induced dyskinesia were given a single dose of sulpiride (20 mg/kg i.m.). The dyskinesia was reduced in all five although four developed attacks of acute dystonia which had to be reversed by anticholinergic medication in three animals. In one monkey the administration of classic neuroleptics had earlier been shown to induce a typical sequence of events. First there was a similar reduction of dyskinesia as seen in the other monkeys, 1-2 days later there was noticed a rebound deterioration lasting for several days. Metoclopramide 0.5 mg/kg, caused such a rebound effect (for 2 days), whereas sulpiride did not.

  10. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans.

    Science.gov (United States)

    Herz, Damian M; Haagensen, Brian N; Christensen, Mark S; Madsen, Kristoffer H; Rowe, James B; Løkkegaard, Annemette; Siebner, Hartwig R

    2015-06-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an

  11. Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.

    Science.gov (United States)

    Chotibut, Tanya; Meadows, Samantha; Kasanga, Ella A; McInnis, Tamara; Cantu, Mark A; Bishop, Christopher; Salvatore, Michael F

    2017-06-20

    Increased extracellular glutamate may contribute to l-dopa induced dyskinesia, a debilitating side effect faced by Parkinson's disease patients 5 to 10 years after l-dopa treatment. Therapeutic strategies targeting postsynaptic glutamate receptors to mitigate dyskinesia may have limited success because of significant side effects. Increasing glutamate uptake may be another approach to attenuate excess glutamatergic neurotransmission to mitigate dyskinesia severity or prolong the time prior to onset. Initiation of a ceftriaxone regimen at the time of nigrostriatal lesion can attenuate tyrosine hydroxylase loss in conjunction with increased glutamate uptake and glutamate transporter GLT-1 expression in a rat 6-hydroxydopamine model. In this article, we examined if a ceftriaxone regimen initiated 1 week after nigrostriatal lesion, but prior to l-dopa, could reduce l-dopa-induced dyskinesia in an established dyskinesia model. Ceftriaxone (200 mg/kg, intraperitoneal, once daily, 7 consecutive days) was initiated 7 days post-6-hydroxydopamine lesion (days 7-13) and continued every other week (days 21-27, 35-39) until the end of the study (day 39 postlesion, 20 days of l-dopa). Ceftriaxone significantly reduced abnormal involuntary movements at 5 time points examined during chronic l-dopa treatment. Partial recovery of motor impairment from nigrostriatal lesion by l-dopa was unaffected by ceftriaxone. The ceftriaxone-treated l-dopa group had significantly increased striatal GLT-1 expression and glutamate uptake. Striatal tyrosine hydroxylase loss in this group was not significantly different when compared with the l-dopa alone group. Initiation of ceftriaxone after nigrostriatal lesion, but prior to and during l-dopa, may reduce dyskinesia severity without affecting l-dopa efficacy or the reduction of striatal tyrosine hydroxylase loss. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  12. Paroxysmal Nonkinesigenic Dyskinesias Responsive to Carbamazepine in Fahr Syndrome: A Case Report.

    Science.gov (United States)

    Montilla-Uzcátegui, Verónica; Araujo-Unda, Hilarión; Daza-Restrepo, Anilú; Sáenz-Farret, Michel; Micheli, Federico

    2016-01-01

    This study aimed to report the case of a patient with paroxysmal nonkinesigenic dyskinesias and Fahr syndrome who had a marked response to carbamazepine. We present the case of a 57-year-old female patient with episodes of paroxysmal choreoathetoid dyskinesias in the oromandibular region and distal region of upper and lower extremities, with fluctuating dystonic postures in the same distribution; duration was variable ranging from 30 minutes to 3 hours. Laboratory studies were consistent with primary hyperparathyroidism with bilateral brain calcifications. Treatment with low doses of carbamazepine was successful.

  13. Effect of ethanolic extract of Coriandrum sativum L. on tacrine induced orofacial dyskinesia.

    Science.gov (United States)

    Mohan, Mahalaxmi; Yarlagadda, Sanjyothi; Chintala, Saritha

    2015-05-01

    The effect of ethanolic extract of Coriandrum sativum L. seeds (100, 200 mg/kg) was studied on tacrine induced orofacial dyskinesia. Tacrine (2.5 mg/kg, i.p.) treated animals were observed for vacuous chewing movements (VCM), tongue protrusions (TP) and orofacial bursts (OB) for 1 h followed by observations for locomotor changes and cognitive dysfunction. Sub-chronic administration of Coriandrum sativum L. seed extract (E-CS) (100, 200 mg/kg, p.o., for 15 days significantly (P Coriandrum sativum. L against tacrine induced orofacial dyskinesia.

  14. Somatosensory disinhibition in patients with paroxysmal kinesigenic dyskinesia

    Institute of Scientific and Technical Information of China (English)

    WEI Hua; SUN Ying; CHEN Hai; WANG De-quan; LI Li-ping; DING Yan; LIU Ai-hua; LU Chang-feng; WANG Yu-ping

    2012-01-01

    Background Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent brief episodes of chorea and dystonia induced by sudden movement.Whether the central nervous system is hyper- or hypoexcitable in PKD remains undetermined.The aim of our study was to compare the somatosensory evoked potential (SEP) recovery cycle,a marker of somatosensory system excitability,in PKD patients and controls.Methods Twenty-four PKD patients (mean age of (20.0±5.3) years; 21 males,3 females) and 18 control age-matched subjects (mean age of (22.0±5.0) years; 17 males,1 female) were studied.The stimuli were delivered to the median nerve in the affected dominant arm in patients and in the dominant arm in controls.The change in SEP amplitude was measured after paired electrical stimulation at interstimulus intervals (ISIs) of 5,20,and 40 ms.The SEPs evoked by S2 (test stimulus) were calculated by subtracting the response to S1 (the conditioning stimulus) from the response to a pair of stimuli (S1 + S2),and their amplitudes were compared with those of the control response (S1) at each ISI.Analysis of variance (ANOVA) or equivalent was used for non-parametric data.Results In patients,the P27 amplitude after the single stimulus (S1) was significantly larger than that after the control stimulus.The (S2/S1)x100 ratio for P14 and N30 SEPs did not differ significantly between PKD patients and normal subjects at ISI of 5 ms but were significantly higher in patients at ISIs of 20 and 40 ms (P<0.05).Conclusions Somatosensory system disinhibition takes place in PKD.The finding of reduced suppression of different SEPs,each thought to have a different origin,suggests an abnormality of intracortical and subcortical inhibitory circuits.

  15. PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

    Science.gov (United States)

    Cloarec, Robin; Bruneau, Nadine; Rudolf, Gabrielle; Massacrier, Annick; Salmi, Manal; Bataillard, Marc; Boulay, Clotilde; Caraballo, Roberto; Fejerman, Natalio; Genton, Pierre; Hirsch, Edouard; Hunter, Alasdair; Lesca, Gaetan; Motte, Jacques; Roubertie, Agathe; Sanlaville, Damien; Wong, Sau-Wei; Fu, Ying-Hui; Rochette, Jacques; Ptácek, Louis J; Szepetowski, Pierre

    2012-11-20

    Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

  16. Behavioral Relaxation Training for Parkinson's Disease Related Dyskinesia and Comorbid Social Anxiety

    Science.gov (United States)

    Lundervold, Duane A.; Pahwa, Rajesh; Lyons, Kelly E.

    2013-01-01

    Effects of brief Behavioral Relaxation Training (BRT) on anxiety and dyskinesia of a 57-year-old female, with an 11-year history of Parkinson's disease (PD) and 18-months post-deep brain stimulation of the subthalamic nucleus, were evaluated. Multiple process and outcome measures were used including the Clinical Anxiety Scale (CAS),…

  17. Gene polymorphism of dopaminergic, serotoninergic and glutamatergic receptors and tardive dyskinesia in schizophrenia

    NARCIS (Netherlands)

    Fedorenko, O.Y.; Ivanova, S.A.; Loonen, A.J.M.

    2016-01-01

    Introduction: For over six decades, antipsychotic drugs have remained the mainstay of schizophrenia treatment. Tardive dyskinesia (TD) is a potentially irreversible antipsychotic-induced. movement disorder with a prevalence of about 20-30% in psychiatric patients chronically exposed to antipsychotic

  18. Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

    NARCIS (Netherlands)

    Lee, Hsien-Yang; Huang, Yong; Bruneau, Nadine; Roll, Patrice; Roberson, Elisha D. O.; Hermann, Mark; Quinn, Emily; Maas, James; Edwards, Robert; Ashizawa, Tetsuo; Baykan, Betul; Bhatia, Kailash; Bressman, Susan; Bruno, Michiko K.; Brunt, Ewout R.; Caraballo, Roberto; Echenne, Bernard; Fejerman, Natalio; Frucht, Steve; Gurnett, Christina A.; Hirsch, Edouard; Houlden, Henry; Jankovic, Joseph; Lee, Wei-Ling; Lynch, David R.; Mohammed, Shehla; Mueller, Ulrich; Nespeca, Mark P.; Renner, David; Rochette, Jacques; Rudolf, Gabrielle; Saiki, Shinji; Soong, Bing-Wen; Swoboda, Kathryn J.; Tucker, Sam; Wood, Nicholas; Hanna, Michael; Bowcock, Anne M.; Szepetowski, Pierre; Fu, Ying-Hui; Ptacek, Louis J.

    2012-01-01

    Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majorit

  19. Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

    NARCIS (Netherlands)

    Lee, Hsien-Yang; Huang, Yong; Bruneau, Nadine; Roll, Patrice; Roberson, Elisha D. O.; Hermann, Mark; Quinn, Emily; Maas, James; Edwards, Robert; Ashizawa, Tetsuo; Baykan, Betul; Bhatia, Kailash; Bressman, Susan; Bruno, Michiko K.; Brunt, Ewout R.; Caraballo, Roberto; Echenne, Bernard; Fejerman, Natalio; Frucht, Steve; Gurnett, Christina A.; Hirsch, Edouard; Houlden, Henry; Jankovic, Joseph; Lee, Wei-Ling; Lynch, David R.; Mohammed, Shehla; Mueller, Ulrich; Nespeca, Mark P.; Renner, David; Rochette, Jacques; Rudolf, Gabrielle; Saiki, Shinji; Soong, Bing-Wen; Swoboda, Kathryn J.; Tucker, Sam; Wood, Nicholas; Hanna, Michael; Bowcock, Anne M.; Szepetowski, Pierre; Fu, Ying-Hui; Ptacek, Louis J.

    2012-01-01

    Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majorit

  20. The Acute Brain Response to Levodopa Heralds Dyskinesias in Parkinson Disease

    DEFF Research Database (Denmark)

    Herz, Damian M.; Haagensen, Brian N.; Christensen, Mark S.

    2014-01-01

    In Parkinson disease (PD), long‐term treatment with the dopamine precursor levodopa gradually induces involuntary “dyskinesia” movements. The neural mechanisms underlying the emergence of levodopa‐induced dyskinesias in vivo are still poorly understood. Here, we applied functional magnetic...

  1. Gene expression studies in cells from primary ciliary dyskinesia patients identify 208 potential ciliary genes

    NARCIS (Netherlands)

    Geremek, Maciej; Bruinenberg, Marcel; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Wijmenga, Cisca; Witt, Michal

    Cilia are small cellular projections that either act as sensors (primary cilia) or propel fluid over the epithelia of various organs (motile cilia). The organellum has gained much attention lately because of its involvement in a group of human diseases called ciliopathies. Primary ciliary dyskinesia

  2. A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    C. Alanin, M.; G. Nielsen, K.; von Buchwald, C.

    2015-01-01

    In patients with primary ciliary dyskinesia (PCD), impaired mucociliary clearance leads to an accumulation of secretions in the airways and susceptibility to repeated bacterial infections. The primary aim of this study was to investigate the bacterial flora in non-chronic and chronic infections i...

  3. [Kartagener sindrome (primary ciliary dyskinesia). Report of a case and literature review].

    Science.gov (United States)

    Pino Rivero, V; Pardo Romero, G; Iglesias González, R J; Rodríguez Carmona, M; del Castillo Beneyto, F

    2007-01-01

    Kartagener syndrome (a clinical variant of primary ciliary dyskinesia) is a recessive autossomical disease characterized by the triad of chronic sinusitis, bronchiectasis and situs inversus with dextrocardia. We report one case described in a 8 years old boy who besides presented a seromucous otitis and bronchitis of repetition. Finally we performed a short bibliographic review at respect of this uncommon pathology.

  4. N-ethyl-carboxamide adenosine inhibits perioral dyskinesias induced by sulpiride + SKF 38393 in rabbits.

    Science.gov (United States)

    Caporali, M G; Scotti de Carolis, A; Popoli, P

    1992-11-13

    A pattern of perioral dyskinesia was induced in adult male rabbits by concomitant stimulation of dopamine D1 receptors (SKF 38393) and blockade of dopamine D2 receptors (sulpiride). Rabbits treated with sulpiride (6 and 12.5 mg/kg i.v.) then, 90 min thereafter, with SKF 38393 (0.1, 1 and 10 mg/kg i.v.) showed a pattern of perioral dyskinesia characterized by compulsive and repetitive sniffing, licking and vacuous chewing. These effects were completely prevented by the administration of N-ethylcarboxamide adenosine (NECA), an A2 > A1 adenosine receptor agonist. The present results confirm that perioral dyskinesia is dependent on the activation of dopamine D1 receptors. They also show that, in order to induce perioral dyskinesia in rabbits, a concomitant blockade of dopamine D2 receptors is required. Finally, the antagonistic effect of NECA on the appearance of perioral movements confirms that adenosine receptors play a key role in the control of dopamine-mediated effects.

  5. Non-Therapeutic Risk Factors for Onset of Tardive Dyskinesia in Schizophrenia : A Meta-Analysis

    NARCIS (Netherlands)

    Tenback, Diederik E.; van Harten, Peter N.; van Os, Jim

    2009-01-01

    A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was' conducted in January 2008 for the years 19

  6. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis

    NARCIS (Netherlands)

    Boks, MPM; Liddle, PF; Russo, S; Knegtering, R; van den Bosch, RJ

    2003-01-01

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of

  7. Brief Report: Autistic Symptoms, Developmental Regression, Mental Retardation, Epilepsy, and Dyskinesias in CNS Folate Deficiency

    Science.gov (United States)

    Moretti, Paolo; Peters, Sarika U.; del Gaudio, Daniela; Sahoo, Trilochan; Hyland, Keith; Bottiglieri, Teodoro; Hopkin, Robert J.; Peach, Elizabeth; Min, Sang Hee; Goldman, David; Roa, Benjamin; Bacino, Carlos A.; Scaglia, Fernando

    2008-01-01

    We studied seven children with CNS folate deficiency (CFD). All cases exhibited psychomotor retardation, regression, cognitive delay, and dyskinesia; six had seizures; four demonstrated neurological abnormalities in the neonatal period. Two subjects had profound neurological abnormalities that precluded formal behavioral testing. Five subjects…

  8. Botulinum toxin in the treatment of orofacial tardive dyskinesia : A single blind study

    NARCIS (Netherlands)

    Slotema, Christina W.; van Harten, Peter N.; Bruggeman, Richard; Hoek, Hans W.

    2008-01-01

    Objective: Orofacial tardive dyskinesia (OTD) is difficult to treat and Botulinium Toxin A (BTA) may be an option. Methods: In a single blind (raters were blind) study (N= 12, duration 33 weeks) OTD was treated with Botulinum Toxin A in three consecutive sessions with increasing dosages. The severit

  9. Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Maglione, Marco; Bush, Andrew; Nielsen, Kim G

    2014-01-01

    BACKGROUND: No studies longitudinally, simultaneously assessed body mass index (BMI) and spirometry in primary ciliary dyskinesia (PCD). METHODS: We determined BMI and spirometry in 158 PCD children and adolescents from London, UK (n = 75), Naples, Italy (n = 23) and Copenhagen, Denmark (n = 60) ...

  10. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6

    DEFF Research Database (Denmark)

    Zariwala, Maimoona A; Gee, Heon Yung; Kurkowiak, Małgorzata

    2013-01-01

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the ...

  11. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Cui G

    2013-12-01

    Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

  12. IRC-082451, a novel multitargeting molecule, reduces L-DOPA-induced dyskinesias in MPTP Parkinsonian primates.

    Directory of Open Access Journals (Sweden)

    Romina Aron Badin

    Full Text Available The development of dyskinesias following chronic L-DOPA replacement therapy remains a major problem in the long-term treatment of Parkinson's disease. This study aimed at evaluating the effect of IRC-082451 (base of BN82451, a novel multitargeting hybrid molecule, on L-DOPA-induced dyskinesias (LIDs and hypolocomotor activity in a non-human primate model of PD. IRC-082451 displays multiple properties: it inhibits neuronal excitotoxicity (sodium channel blocker, oxidative stress (antioxidant and neuroinflammation (cyclooxygenase inhibitor and is endowed with mitochondrial protective properties. Animals received daily MPTP injections until stably parkinsonian. A daily treatment with increasing doses of L-DOPA was administered to parkinsonian primates until the appearance of dyskinesias. Then, different treatment regimens and doses of IRC-082451 were tested and compared to the benchmark molecule amantadine. Primates were regularly filmed and videos were analyzed with specialized software. A novel approach combining the analysis of dyskinesias and locomotor activity was used to determine efficacy. This analysis yielded the quantification of the total distance travelled and the incidence of dyskinesias in 7 different body parts. A dose-dependent efficacy of IRC-082451 against dyskinesias was observed. The 5 mg/kg dose was best at attenuating the severity of fully established LIDs. Its effect was significantly different from that of amantadine since it increased spontaneous locomotor activity while reducing LIDs. This dose was effective both acutely and in a 5-day sub-chronic treatment. Moreover, positron emission tomography scans using radiolabelled dopamine demonstrated that there was no direct interference between treatment with IRC-082451 and dopamine metabolism in the brain. Finally, post-mortem analysis indicated that this reduction in dyskinesias was associated with changes in cFOS, FosB and ARC mRNA expression levels in the putamen. The data

  13. Genetic, temporal and diurnal influences on L-dopa-induced dyskinesia in the 6-OHDA model.

    Science.gov (United States)

    Monville, Christelle; Torres, Eduardo M; Pekarik, Vladimir; Lane, Emma L; Dunnett, Stephen B

    2009-03-16

    Current treatments for Parkinson's disease rely on a dopamine replacement strategy and are reasonably effective, particularly in the early stages of the disease. However, chronic dopaminergic therapy is limited by the development of a range of side effects, including the onset of abnormal movements ('dyskinesia'). The neural mechanisms that underlie dyskinesia are far from clear but they have been associated with pulsatile stimulation of dopamine receptors, downstream changes in proteins and genes, and abnormalities in non-dopamine transmitter systems. However, there has been no pathophysiological explanation for the worsening motor symptoms in the afternoon and evening reported by Parkinsonian patients in long-term L-dopa therapy, and no direct relationship has been found with the pharmacokinetics of the drug. Moreover, there continues to be a debate about whether the development of dyskinesias in patients is dependent upon the duration of L-dopa treatment or on the degree of denervation/advanced stage of the disease, both factors that are difficult to resolve experimentally in the human disease. The objective of this study was to characterise, in an animal model, factors that predispose some individuals to develop dyskinesia after a prolonged treatment with L-dopa, whereas others continue to exhibit symptom alleviation without the side effects. We report that none of the parameters studied--genetic variation within and between strains, delay of treatment onset after lesion, or time of day of the drug treatment--were found to influence directly the formation of dyskinesias after L-dopa treatment. We conclude that a complex combination of individual factors are likely to interact to regulate the onset and development of abnormal movements in some animals but not others.

  14. Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: Possible neurotransmitters and neuroinflammation modulation.

    Science.gov (United States)

    Datta, Swati; Jamwal, Sumit; Deshmukh, Rahul; Kumar, Puneet

    2016-01-15

    Tardive Dyskinesia is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia. The study was designed to investigate the protective effect of lycopene against haloperidol induced orofacial dyskinesia possibly by neurochemical and neuroinflammatory modulation in rats. Rats were administered with haloperidol (1mg/kg, i.p for 21 days) to induce orofacial dyskinesia. Lycopene (5 and 10mg/kg, p.o) was given daily 1hour before haloperidol treatment for 21 days. Behavioral observations (vacuous chewing movements, tongue protrusions, facial jerking, rotarod activity, grip strength, narrow beam walking) were assessed on 0th, 7th(,) 14th(,) 21st day after haloperidol treatment. On 22nd day, animals were killed and striatum was excised for estimation of biochemical parameters (malondialdehyde, nitrite and endogenous enzyme (GSH), pro-inflammatory cytokines [Tumor necrosis factor, Interleukin 1β, Interleukin 6] and neurotransmitters level (dopamine, serotonin, nor epinephrine, 5-Hydroxyindole acetic acid (5-HIAA), Homovanillic acid, 3,4- dihydroxyphenylacetic acid. Haloperidol treatment for 21 days impaired muscle co-ordination, motor activity and grip strength with an increased in orofacial dyskinetic movements. Further free radical generation increases MDA and nitrite levels, decreasing GSH levels in striatum. Neuroinflammatory markers were significantly increased with decrease in neurotransmitters levels. Lycopene (5 and 10mg/kg, p.o) treatment along with haloperidol significantly attenuated impairment in behavioral, biochemical, neurochemical and neuroinflammatory markers. Results of the present study attributed the therapeutic potential of lycopene in the treatment (prevented or delayed) of typical antipsychotic induced orofacial dyskinesia.

  15. THE SYNDROME OF AUTOSOMAL RECESSIVE PONTOCEREBELLAR HYPOPLASIA, MICROCEPHALY, AND EXTRAPYRAMIDAL DYSKINESIA (PONTOCEREBELLAR HYPOPLASIA TYPE-2) - COMPILED DATA FROM 10 PEDIGREES

    NARCIS (Netherlands)

    BARTH, PG; BLENNOW, G; LENARD, HG; BEGEER, JH; VANDERKLEY, JM; HANEFELD, F; PETERS, ACB; Valk, J.

    1995-01-01

    The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, severely impaired mental and motor development, and extrapyramidal dyskinesia is a distinct system degeneration, previously designated pontocerebellar hypoplasia type 2 (PCH-2). To further characterize its clinical and neu

  16. TARDIVE DYSKINESIA AND OTHER EXTRAPYRAMIDAL SYMPTOMS ASSOCIATED WITH ARIPIPRAZOLE: A CASE SERIES

    Directory of Open Access Journals (Sweden)

    Nayana Sanjay

    2016-06-01

    Full Text Available BACKGROUND Aripiprazole is a third generation antipsychotic introduced in 2004 for treatment of Schizophrenia and bipolar disorders. It has partial agonist activity at dopamine D2 receptor and D2 antagonist activity under hyperdopaminergic condition. In addition, it is a partial agonist at serotonin 5HT1A receptor and antagonist at 5HT2A receptor. Because its pharmacological profile differs from other atypical antipsychotics, it was initially thought to produce lesser side effects and movement disorders. But over the years, there is a growing body of evidence in the form of case reports and case series of Aripiprazole induced movement disorders like Tardive dyskinesia, Parkinsonism, akathisia and dystonia. Of late it has been advocated for irritability associated with autism and as an augmenter for depressive disorder. It has lower potential for weight gain and sedation, as it has relatively low affinity for H1 [Histamine] receptor compared to clozapine, olanzapine and quetiapine. Based on this unique mechanism, it is claimed to have minimal or non-significant motor side effects like Tardive dyskinesia. We document a case series of 8 patients who developed Tardive dyskinesia, Parkinsonism and akathisia following treatment with Aripiprazole (ARP. METHODS This is both retrospective and observational study. Patients from outpatient and inpatient department of a tertiary psychiatric teaching hospital with an ICD-10 diagnosis of psychiatric disorder, who has experienced movement disorder while on treatment with Aripiprazole are included in this report. All these patients were under the care of authors as treating Psychiatrists. Rating scales like Abnormal Involuntary Movement Scale (AIMS, Naranjo’s Causality Scale, Barnes Akathisia Rating Scale (BARS and Simpson Angus extrapyramidal Scale (SAS were used. RESULTS Total of eight patients presented with various movement disorders associated with Aripiprazole, out of which three patients with tardive

  17. Improvement of chronic facial pain and facial dyskinesia with the help of botulinum toxin application

    Directory of Open Access Journals (Sweden)

    Ellies Maik

    2007-08-01

    Full Text Available Abstract Background Facial pain syndromes can be very heterogeneous and need individual diagnosis and treatment. This report describes an interesting case of facial pain associated with eczema and an isolated dyskinesia of the lower facial muscles following dental surgery. Different aspects of the pain, spasms and the eczema will be discussed. Case presentation In this patient, persistent intense pain arose in the lower part of her face following a dental operation. The patient also exhibited dyskinesia of her caudal mimic musculature that was triggered by specific movements. Several attempts at therapy had been unsuccessful. We performed local injections of botulinum toxin type A (BTX-A into the affected region of the patient's face. Pain relief was immediate following each set of botulinum toxin injections. The follow up time amounts 62 weeks. Conclusion Botulinum toxin type A (BTX-A can be a safe and effective therapy for certain forms of facial pain syndromes.

  18. PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking

    Science.gov (United States)

    Porras, Gregory; Berthet, Amandine; Dehay, Benjamin; Li, Qin; Ladepeche, Laurent; Normand, Elisabeth; Dovero, Sandra; Martinez, Audrey; Doudnikoff, Evelyne; Martin-Négrier, Marie-Laure; Chuan, Qin; Bloch, Bertrand; Choquet, Daniel; Boué-Grabot, Eric; Groc, Laurent; Bezard, Erwan

    2012-01-01

    l-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson’s patients. PMID:23041629

  19. Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia

    Science.gov (United States)

    Heiman, Myriam; Heilbut, Adrian; Francardo, Veronica; Kulicke, Ruth; Fenster, Robert J.; Kolaczyk, Eric D.; Mesirov, Jill P.; Surmeier, Dalton J.; Cenci, M. Angela; Greengard, Paul

    2014-01-01

    Levodopa treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). Although it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type–specific gene-expression changes that occur in subclasses of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes, the expression of which is correlated with levodopa dose, many of which are under the control of activator protein-1 and ERK signaling. Despite homeostatic adaptations involving several signaling modulators, activator protein-1–dependent gene expression remains highly dysregulated in direct pathway SPNs upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. PMID:24599591

  20. Orofacial dyskinesia induced by nasal Ritalin(R) (methylphenidate) sniffing: a rare case report from Switzerland.

    Science.gov (United States)

    Marti, G; Fattinger, K; Zimmermann, H; Exadaktylos, A

    2013-03-01

    Ritalin® (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults. Recently, the recreational use of Ritalin has increased, particularly among young adults. Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness. This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data.

  1. Cri du chat syndrome and primary ciliary dyskinesia: a common genetic cause on chromosome 5p.

    Science.gov (United States)

    Shapiro, Adam J; Weck, Karen E; Chao, Kay C; Rosenfeld, Margaret; Nygren, Anders O H; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A

    2014-10-01

    Cri du chat syndrome (CdCS) and primary ciliary dyskinesia (PCD) are rare diseases that present with frequent respiratory symptoms. PCD can be caused by hemizygous DNAH5 mutation in combination with a 5p segmental deletion attributable to CdCS on the opposite chromosome. Chronic oto-sino-pulmonary symptoms or organ laterality defects in CdCS should prompt an evaluation for PCD.

  2. Primary ciliary dyskinesia: a report from ATS 2001, May 18–23, San Francisco

    OpenAIRE

    Noone Peadar G

    2001-01-01

    Abstract Primary ciliary dyskinesia (PCD) is a genetic disorder of abnormal ciliary structure and function that leads to defective mucociliary clearance, resulting in oto-sino-pulmonary disease, and infertility. The disease is currently under intense investigation by a number of research groups worldwide. At the recent American Thoracic Society meeting in San Francisco in May 2001, two sessions focused on PCD; a symposium session on May 21 with several featured expert speakers was followed by...

  3. Assessment of cervical range of motion, cervical core strength and scapular dyskinesia in violin players.

    Science.gov (United States)

    Tawde, Pooja; Dabadghav, Rachana; Bedekar, Nilima; Shyam, Ashok; Sancheti, Parag

    2016-12-01

    Playing the violin can lead to asymmetric postures which can affect the cervical range of motion, cervical core strength and scapular stability. The objective of the study was to assess the cervical range of motion, cervical core strength and scapular dyskinesia in violin players and non-players of the same age group. An inclinometer was used to assess the cervical range of motion, pressure biofeedback was used to assess cervical core strength and scapular dyskinesia was also assessed in 30 professional violin players (18-40 years) compared with 30 age-matched non-players. Analysis was done using an unpaired t test. Significant change was seen with respect to extension (p = 0.051), cervical core strength (p = 0.005), right (Rt) superior angle 0° (p = 0.004), Rt superior angle 45° (p = 0.015) and Rt inferior angle 90° (p = 0.013). This study shows a significant difference in extension range of motion and cervical core strength of violin players. Also, there was scapular dyskinesia seen at 0° and 45° right-side superior angle of the scapula and 90° right-side inferior angle of the scapula.

  4. Loss of dopamine neuron terminals in antipsychotic-treated schizophrenia; relation to tardive dyskinesia.

    Science.gov (United States)

    Seeman, Philip; Tinazzi, Michele

    2013-07-01

    The in vivo labeling and brain imaging of dopamine transporters measure the density of dopamine neuron terminals in the human caudate/putamen. A review of such studies shows that the long-term use of antipsychotics had no major effect on the density of the dopamine terminals in individuals who had no tardive dyskinesia, but had reduced the density in those patients with tardive dyskinesia. In addition, the normal loss of dopamine terminals in healthy individuals was approximately 5% per decade. However, this rate of cell loss was apparently increased by approximately three-fold, to about 15% per decade, in schizophrenia patients using antipsychotics on a long-term basis, as measured by the in vivo imaging of the dopamine transporters in the dopamine neuron terminals. While an apparent reduction in dopamine transporters may result from reduced expression of the transporters secondary to antipsychotic treatment, the seemingly increased loss rate is consistent with the accumulation of antipsychotics in the neuromelanin of the substantia nigra, subsequent injury to the dopamine-containing neurons, and the development of extrapyramidal motor disturbances such as tardive dyskinesia or Parkinson's disease.

  5. LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.

    Directory of Open Access Journals (Sweden)

    Amjad Horani

    Full Text Available Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6 that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His. LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.

  6. Striatal overexpression of DeltaJunD resets L-DOPA-induced dyskinesia in a primate model of Parkinson disease.

    Science.gov (United States)

    Berton, Olivier; Guigoni, Céline; Li, Qin; Bioulac, Bernard H; Aubert, Incarnation; Gross, Christian E; Dileone, Ralph J; Nestler, Eric J; Bezard, Erwan

    2009-09-15

    Involuntary movements, or dyskinesia, represent a debilitating complication of dopamine replacement therapy for Parkinson disease (PD). The transcription factor DeltaFosB accumulates in the denervated striatum and dimerizes primarily with JunD upon repeated L-3,4-dihydroxyphenylalanine (L-DOPA) administration. Previous studies in rodents have shown that striatal DeltaFosB levels accurately predict dyskinesia severity and indicate that this transcription factor may play a causal role in the dyskinesia sensitization process. We asked whether the correlation previously established in rodents extends to the best nonhuman primate model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaque. We used western blotting and quantitative polymerase chain reaction (PCR) to compare DeltaFosB protein and messenger RNA (mRNA) levels across two subpopulations of macaques with differential dyskinesia severity. Second, we tested the causal implication of DeltaFosB in this primate model. Serotype 2 adeno-associated virus (AAV2) vectors were used to overexpress, within the motor striatum, either DeltaFosB or DeltaJunD, a truncated variant of JunD lacking a transactivation domain and therefore acting as a dominant negative inhibitor of DeltaFosB. A linear relationship was observed between endogenous striatal levels of DeltaFosB and the severity of dyskinesia in Parkinsonian macaques treated with L-DOPA. Viral overexpression of DeltaFosB did not alter dyskinesia severity in animals previously rendered dyskinetic, whereas the overexpression of DeltaJunD dramatically dropped the severity of this side effect of L-DOPA without altering the antiparkinsonian activity of the treatment. These results establish a mechanism of dyskinesia induction and maintenance by L-DOPA and validate a strategy, with strong translational potential, to deprime the L-DOPA-treated brain.

  7. Maladaptive plasticity in levodopa-induced dyskinesias and tardive dyskinesias: old and new insights on the effects of dopamine receptor pharmacology.

    Science.gov (United States)

    Cerasa, Antonio; Fasano, Alfonso; Morgante, Francesca; Koch, Giacomo; Quattrone, Aldo

    2014-01-01

    Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation, and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting, synaptogenesis, and neurogenesis. Recent evidence from human and animal models provided support to the hypothesis that these phenomena likely depend on altered dopamine turnover induced by long-term drug treatment. However, it is still unclear how and where these altered mechanisms of cortical plasticity may be localized. This study provides an up-to-date overview of these issues together with some reflections on future studies in the field, particularly focusing on two specific disorders (levodopa-induced dyskinesias in Parkinson's disease patients and tardive dyskinesias in schizophrenic patients) where the modern neuroimaging approaches have recently provided new fundamental insights.

  8. MALADAPTIVE PLASTICITY IN LEVODOPA-INDUCED DYSKINESIAS AND TARDIVE DYSKINESIAS: OLD AND NEW INSIGHTS ON THE EFFECTS OF DOPAMINE RECEPTOR PHARMACOLOGY

    Directory of Open Access Journals (Sweden)

    Antonio eCerasa

    2014-04-01

    Full Text Available Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, either in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting, synaptogenesis and neurogenesis. Recent evidence from human and animal models provided support to the hypothesis that these phenomena likely depend upon altered dopamine turnover induced by long-term drug treatment. However, it is still unclear how and where these altered mechanisms of cortical plasticity may be localized. The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field, particularly focusing on two specific disorders (levodopa-induced dyskinesias in Parkinson’s disease patients and tardive dyskinesias in schizophrenic patients where the modern neuroimaging approaches have recently provided new fundamental insights.

  9. Dyskinesia induced by phenytoin Discinesia induzida por fenitoína

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    M. AUGUSTA MONTENEGRO

    1999-06-01

    Full Text Available Phenytoin is an effective antiepileptic drug, although, it can be associated with many side effects, including dyskinesia. OBJECTIVE: To describe the clinical characteristics of phenytoin induced dyskinesia. METHODS: We investigated the occurrence of involuntary movements in patients followed at our adult and pediatric epilepsy clinics during the period of one year. RESULTS: Three patients presented with phenytoin-induced dyskinesia: one adult with axial and orofacial dyskinesia, and two children with choreoathetosis. They did not have other signs of phenytoin intoxication and had complete recovery after phenytoin withdrawal. CONCLUSION: Phenytoin induced dyskinesia may occur during either chronic or initial treatment and with normal serum phenytoin levels. However, it occurs most often in patients on polytherapy, usually after increasing dosage and with toxic serum levels. Other signs of phenytoin intoxication may be present in these patients, but often the dyskinesia is the only side effect, which may delay the diagnosis and treatment. The clinical characteristics of the involuntary movements vary and may be focal or generalized, most often characterized by choreoathetosis and dyskinesias. These may last for hours, days or even years, but frequently disappear completely after phenytoin withdrawal.Fenitoína é droga anti-epiléptica eficaz, mas pode estar associada a vários efeitos colaterais, inclusive discinesia. OBJETIVO: Descrever as características clínicas da discinesia induzida por fenitoína. MÉTODO: Avaliamos a ocorrência de movimentos involuntários em pacientes seguidos nos ambulatórios de epilepsia durante o período de um ano. RESULTADOS: Três pacientes apresentaram discinesia induzida por fenitoína: um adulto com discinesia orofacial e duas crianças com coreoatetose. Eles não tinham outros sinais de intoxicação por fenitoína e apresentaram recuperação completa após a retirada da fenitoína. CONCLUSÃO: Discinesia

  10. Prolactin as a biomarker for treatment response and tardive dyskinesia in schizophrenia subjects: old thoughts revisited from a genetic perspective.

    Science.gov (United States)

    Souza, Renan P; Meltzer, Herbert Y; Lieberman, Jeffrey A; Voineskos, Aristotle N; Remington, Gary; Kennedy, James L

    2011-01-01

    Previous studies investigated whether prolactin (PRL) serum level was a biomarker of antipsychotic response, schizophrenia symptomatology, and tardive dyskinesia. Most of the findings support that antipsychotic drugs modulate PRL levels but PRL is not a steady indicator. Recent results suggest a genetic effect of PRL and PRL receptor (PRLR) polymorphisms in PRL levels indicating that independently of antipsychotic therapy subjects could have altered PRL levels due to their genetic background.We evaluated whether PRL and PRLR variants were associated with treatment outcome and tardive dyskinesia. We observed no association of PRL/PRLR polymorphism with treatment response (best genotypic results include PRL rs849885 and PRLR rs4703509 permuted p=0.326). Regarding tardive dyskinesia, the major allele of PRL rs37364 was nominally associated with risk for tardive dyskinesia in the European ancestry sub-sample (permuted p=0.183). Although we reported no significant associations, it is definitely worthy of investigation to see if together (genetic variants in the PRL system and PRL serum measures) could be a reliable biomarker for antipsychotic response and TD prevalence. Our results suggest that more studies in this context are required to shed light in the molecular mechanisms underlying antipsychotic response and tardive dyskinesia occurrence.

  11. The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates--evidence from in vivo neuroimaging studies

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Jenkins, Bruce G; Choi, Ji-Kyung

    2009-01-01

    exhibiting L-dopa-induced dyskinesia. Magnetic resonance imaging (MRI) performed before and after injection of Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) revealed an intact BBB in the basal ganglia showing that l-dopa-induced dyskinesia is not associated with a disrupted BBB in this model....

  12. CLINICAL OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE PLUS MANUAL REPOSITION FOR TREATMENT OF ACUTE LUMBAR VERTEBRAL ARTICULAR DYSKINESIA

    Institute of Scientific and Technical Information of China (English)

    骆钧梵

    2003-01-01

    Objective: To observe the therapeutic effect of acupuncture plus manual reposition for treatment of acute lumbar vertebral articular dyskinesia for choosing a better remedy. Methods: 66 cases of acute lumbar vertebral articular dyskinesia were randomly divided into acupuncture plus manual reposition group (treatment group, n= 33) and routine manual reposition group (control group, n = 33). Yaotong-point was punctured, when, the patient was asked to move his or her waist simultaneously. Results: After one session of treatment, of the two 33 cases in treatment and control groups, 28 (84.85%) and20 (60.61%) were cured, 4 (12.12%) and 9 (27.27%) were improved, and 1 (3.03%) and 4 (12.12%) failed in the treatment. The therapeutic effect of treatment group was significantly superior to that of control group ( P< 0.05). Conclusion: Acupuncture combined with manual reposition is apparently superior to simple routine manual reposition in relieving acute lumbar vertebral articular dyskinesia.

  13. Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease.

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    Ferrucci, Roberta; Cortese, Francesca; Bianchi, Marta; Pittera, Dario; Turrone, Rosanna; Bocci, Tommaso; Borroni, Barbara; Vergari, Maurizio; Cogiamanian, Filippo; Ardolino, Gianluca; Di Fonzo, Alessio; Padovani, Alessandro; Priori, Alberto

    2016-02-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex. This simple and safe neurostimulation technique for modulating motor functions in Parkinson's disease could extend treatment option for patients with movement disorders. We assessed whether tDCS applied daily over the cerebellum (cerebellar tDCS) and motor cortex (M1-tDCS) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Nine patients (aged 60-85 years; four women; Hoehn & Yahr scale score 2-3) diagnosed as having idiopathic PD were recruited. To evaluate how tDCS (cerebellar tDCS or M1-tDCS) affects motor and cognitive function in PD, we delivered bilateral anodal (2 mA, 20 min, five consecutive days) and sham tDCS, in random order, in three separate experimental sessions held at least 1 month apart. In each session, as outcome variables, patients underwent the Unified Parkinson's Disease Rating Scale (UPDRS III and IV) and cognitive testing before treatment (baseline), when treatment ended on day 5 (T1), 1 week later (T2), and then 4 weeks later (T3), at the same time each day. After patients received anodal cerebellar tDCS and M1-tDCS for five days, the UPDRS IV (dyskinesias section) improved (p  0.05). Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients' levodopa-induced dyskinesias.

  14. A Survey of the Tardive Dyskinesia Induced by Antipsychotic Drugs in Patients with Schizophrenia

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    Naser tabibi

    2010-11-01

    Full Text Available "nObjective: Tardive Dyskinesia (TD, is one of the important problems of the patients with schizophrenia. The emergence of these side effects depends on so many factors such as the patients' age and the duration of antipsychotic treatment. By discovering new drugs (Atypical, there has been an outstanding decrease in the emergence of these side effects. The present study investigates the symptoms of TD in the Patients with schizophrenia who were under  treatments for more than 6 months. "nMethod: The sample of this study was 200 Patients with schizophrenia of four wards in Razi hospital (two acute and two chronic wards who were hospitalized in the winter of 2006 and were qualified for this study. The subjects were 101 males and 99 females who were younger than 60 and had received antipsychotic drugs for at least 6 months. After psychiatric interview and filling the demographic questionnaire by the patients, the required information about the drugs and the intensity of the symptoms was acquired. Then clinical and physical examinations of tardive dyskinesia were done. Next, the tardive dyskinesia disorders' check list (AIMS was used. Findings of this cross-sectional, descriptive study were analyzed by SPSS. "nResults: There was a high ratio of 95% between TD and the age factor (P=0.05. There was no relationship between symptoms frequency and duration of treatment (P=0.68. Facial muscles and oral zones were mostly involved in T.D disorder (72%. "nConclusion: No significant difference was observed between nine fold symptoms of T.D in patients who were using traditional drugs and those who were using the new ones (typical and atypical. Findings showed that in the intensity of the symptoms, gender does not play a major role.

  15. Ictal SPECT in paroxysmal non-kinesigenic dyskinesia. Case report and review of the literature.

    Science.gov (United States)

    del Carmen García M; Intruvini; Vazquez; Beserra; Rabinowicz

    2000-04-01

    Purpose: Paroxysmal non-kinesigenic dyskinesia (PNKD) should be included in the list of differential diagnosis in patients with refractory epilepsy. Although the pathophysiological mechanisms that underlie this disorder remain controversial, it is now accepted that the basal ganglia are the anatomical substrate responsible for it.Material and methods: We report a 16-year-old mentally retarded male with PNKD admitted for video-EEG monitoring and ictal SPECT, which showed hyperperfusion on the right caudate and thalamus.Conclusion: This case supports more evidence for the involvement of the caudate nucleus and thalamus in the mechanisms responsible for the production of PNKD.

  16. Progress in the research of genetics and clinical manifestation of paroxysmal kinesigenic dyskinesia

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    HUANG Xiao-jun

    2013-05-01

    Full Text Available Paroxysmal kinesigenic dyskinesia (PKD is a disorder characterized by recurrent and brief attacks that are induced by sudden voluntary movement with highly clinical and genetic heterogeneity. Familial PKD are mostly autosomal dominant inherited and proline-rich transmembrare protein 2 (PRRT2 gene has been identified as the causative gene for PKD. So far 56 mutations have been documented and most of them are nonsense ones. No obvious genotype-phenotype correlation has been observed and the function of PRRT2 is still unclear, but the interaction between PRRT2 and synaptosomal-associated protein 25 (SNAP25 will shed the light on the research of PKD mechanism.

  17. Classification conundrums in paroxysmal dyskinesias: a new subtype or variations on classic themes?

    Science.gov (United States)

    Pourfar, Michael H; Guerrini, Renzo; Parain, Dominique; Frucht, Steven J

    2005-08-01

    Paroxysmal movement disorders are a group of heterogeneous entities that have been categorized based on their most salient features. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, hypnogenic, and exercise-induced. The phenotypic variability of these disorders, coupled with new insights into their possible etiologies, has made the task of classification increasingly problematic. We describe 4 cases that do not fit easily into the current classification scheme, compare them with four others recently described in the literature, and raise the question as to whether they constitute a new subtype.

  18. Atypical antipsychotic drugs and tardive dyskinesia: relevance of D2 receptor affinity.

    Science.gov (United States)

    Bressan, Rodrigo A; Jones, Hugh M; Pilowsky, Lyn S

    2004-03-01

    Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

  19. Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

    Science.gov (United States)

    Cenci, M Angela

    2014-01-01

    The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

  20. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

    Science.gov (United States)

    Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

    2012-01-01

    Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

  1. [Primary ciliary dyskinesia, immotile cilia syndrome, and Kartagener syndrome: diagnostic criteria].

    Science.gov (United States)

    Dombi, V H; Walt, H

    1996-03-16

    Primary ciliary dyskinesia is the generic term for a heterogeneous group of inherited diseases in which ciliary ultrastructure is defective and as a consequence ciliary motility is disturbed. An international consensus on the diagnostic criteria has not yet been reached. This paper reviews some recent findings which are useful in the diagnosis of the disease and attempts to establish the best diagnostic criteria. The marker symptoms are chronic bronchitis, otitis, and sinusitis since childhood. Additionally, one or more of the following criteria must be present: Kartagener syndrome, a dextrocardia situation, markedly reduced frequency in ciliary motility, or an essential ultrastructure deviation in more than 20% of the square cuts (e.g. reduced number of dynein arms). Biopsy of the ciliated mucosa is usually required for the above criteria and is studied by vital microscopy and transmission electron microscopy. Primary and secondary ciliary dyskinesia can be distinguished by these methods and the rare case of PCD without ultrastructure deficiency ruled out. In special cases a cell culture is recommended for the diagnosis. Practical aspects of the sampling methods and diagnostic pitfalls are reviewed.

  2. Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Møller, Maria E.; Alanin, Mikkel C.; Grønhøj, Christian

    2017-01-01

    Background: A correlation exists between the microbial flora of the upper and lower airways in patients with cystic fibrosis (CF) or with primary ciliary dyskinesia (PCD). The sinuses can function as a bacterial reservoir where gram-negative bacteria adapt to the airways and repeatedly are aspira......Background: A correlation exists between the microbial flora of the upper and lower airways in patients with cystic fibrosis (CF) or with primary ciliary dyskinesia (PCD). The sinuses can function as a bacterial reservoir where gram-negative bacteria adapt to the airways and repeatedly...... flora in the sinuses and nasal cavities of patients with CF or PCD.  Methods: A number of medical literature data bases were systematically searched between January 1960 and July 2016. We applied the following inclusion criteria: a minimum of one case of PCD (or Kartagener syndrome) or CF......, and microbiology analyses from the nose or paranasal sinuses.  Results: We included 46 studies (1823 patients) from 16 countries. Staphylococcus aureus was found in 30% of the noses and sinuses of patients with CF. Other common bacteria found included Pseudomonas aeruginosa, coagulase negative staphylococci...

  3. Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders

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    Chang FC

    2014-10-01

    Full Text Available Florence CF Chang, Victor SC Fung Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney Medical School, University of Sydney, Sydney, NSW, Australia Abstract: Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter, serotonin (receptor and transporter, and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research. Keywords: pharmacogenomics, tardive dyskinesia, cytochrome P450, pharmacogenetic, schizophrenia

  4. Clinical and familial correlates of tardive dyskinesia in India and Israel

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    Bhatia T

    2004-07-01

    Full Text Available Background: Antipsychotic drugs are widely used for the treatment of psychosis, especially schizophrenia. Their long-term use can result at times in serious side-effects such as Tardive Dyskinesia (TD. Since over 80% of schizophrenia sufferers (lifetime prevalence 1% receive long-term antipsychotic drug treatment, the extent of the problem is potentially large. Increasing age is the most consistently demonstrated risk factor for TD. Aims: To assess effect of different clinical factors and demographic variables in India and Israel and sib pair concordance of Tardive Dyskinesia (TD in India. Settings and Design: The study was conducted simultaneously among Indian and Israeli subjects: ascertainment was family-based in India and hospital-based in Israel. Methods and Material: In India the instruments used were: Diagnostic Interview for Genetic Studies (DIGS, Positive and Negative Syndrome Scale (PANSS, Abnormal Involuntary Movement Scale (AIMS, and Simpson Angus Scale (SAS. The last three instruments were also used in Israel. Statistical Analysis: Regression analysis and Pearson's correlation. Results and Conclusions: TD symptoms were present in 40.4% of 151 Israeli subjects and 28.7% of 334 Indian subjects. While age at onset and total scores on PANSS were significant predictors of TD in both the samples, lower scores on the Global Assessment of Functioning Scale (GAF, diagnostic sub-group and male gender were significant predictors among Indians. There was no concordance of TD symptoms among 33 affected sib-pairs from India.

  5. The incidence of tardive dyskinesia in the study of pharmacotherapy for psychotic depression.

    Science.gov (United States)

    Blumberger, Daniel M; Mulsant, Benoit H; Kanellopoulos, Dora; Whyte, Ellen M; Rothschild, Anthony J; Flint, Alastair J; Meyers, Barnett S

    2013-06-01

    Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

  6. Chromothripsis: Basis of a Concurrent Unusual Association between Myelodysplastic Syndrome and Primary Ciliary Dyskinesia

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    Abhinav Agrawal

    2014-01-01

    Full Text Available A 20 year old male was initially diagnosed suffering from Primary ciliary dyskinesia with symptoms of bronchiectasis, severe frontal, maxillary and ethmoid sinus disease. At the age of 20, the patient was also diagnosed with Myelodysplastic syndrome requiring Bone marrow transplant due to the advanced stage at time of presentation. Primary ciliary dyskinesia and Myelodsyplastic syndrome are both rare clinical conditions found in the general population, especially in young adults. This rare combination of disorders has never been reported in literature to the best of the author’s knowledge. The presence of an advanced cancer and a genetic abnormality due to two deletions occurring in two arms of the same chromosome can be explained on the base of chromothripsis. A number of evidences have been published in the literature, about multiple deletions in chromosome 5 and advanced stages of MDS being associated with chromothripsis however this is the first case report on two deletions in chromosome 7 giving rise to two different clinical entities requiring multiple modes of management.

  7. The effects of electroconvulsive therapy on tardive dystonia or dyskinesia induced by psychotropic medication: a retrospective study

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    Yasui-Furukori N

    2014-07-01

    Full Text Available Norio Yasui-Furukori,1 Atsuhiro Kikuchi,1 Hiroshi Katagai,1,2 Sunao Kaneko11Department of Neuropsychiatry, Hirosaki University School of Medicine, 2Department of Neuropsychiatry, Hirosaki-Aiseikai Hospital, Hirosaki, JapanBackground: Tardive dystonia and dyskinesia are potentially irreversible neurological syndromes. Successful electroconvulsive treatment (ECT has been reported by multiple sources; however, the existing retrospective reviews and open prospective trials provide little information on the response rate.Methods: Eighteen consecutive patients with tardive dystonia or dyskinesia received a standard course of ECT to treat abnormal movement. The severity of the tardive dystonia and dyskinesia was evaluated using the Abnormal Involuntary Movement Scale (AIMS before and after the course of ECT. The patients who displayed a greater than 50% improvement in the AIMS score were classified as the responders.Results: The mean AIMS score decreased from 19.1±4.7 to 9.6±4.2. There were seven responders among the 18 patients, which yielded a 39% response rate. Conclusion: ECT has a moderate but significant effect on tardive dystonia and dyskinesia. Keywords: tardive dystonia, tardive diskinesia, ECT, medication

  8. Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats

    DEFF Research Database (Denmark)

    OA, Andreassen; Weber, Christine; HA, Jorgensen

    1999-01-01

    dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL...... significantly increased the level of oral dyskinesias, and the increase persisted for 12 weeks after drug withdrawal. Cotreatment with CoQ10 did not attenuate the development of HAL-induced oral dyskinesia. Despite adequate absorption of orally administered CoQ10, shown by the increased serum levels of CoQ10......, no increase of either CoQ10 or coenzyme Q9 was detected in the brain. These results suggest that cotreatment with CoQ10 does not inhibit the development of HAL-induced oral dyskinesias in rats, and that further studies seem to be needed in order to clarify the pharmakokinetics of CoQ10 in rats...

  9. The role of the subthalamic nucleus in L-DOPA induced dyskinesia in 6-hydroxydopamine lesioned rats.

    Directory of Open Access Journals (Sweden)

    Asier Aristieta

    Full Text Available L-DOPA is the most effective treatment for Parkinson's disease (PD, but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in dyskinesia, using single-unit extracellular recording, behavioural and molecular approaches in hemi-parkinsonian rats rendered dyskinetic by chronic L-DOPA administration. Our results show that chronic L-DOPA treatment does not modify the abnormal STN activity induced by the 6-hydroxydopamine lesion of the nigrostriatal pathway in this model. Likewise, we observed a loss of STN responsiveness to a single L-DOPA dose both in lesioned and sham animals that received daily L-DOPA treatment. We did not find any correlation between the abnormal involuntary movement (AIM scores and the electrophysiological parameters of STN neurons recorded 24 h or 20-120 min after the last L-DOPA injection, except for the axial subscores. Nonetheless, unilateral chemical ablation of the STN with ibotenic acid resulted in a reduction in global AIM scores and peak-severity of dyskinesia. In addition, STN lesion decreased the anti-dyskinetogenic effect of buspirone in a reciprocal manner. Striatal protein expression was altered in dyskinetic animals with increases in ΔFosB, phosphoDARPP-32, dopamine receptor (DR D3 and DRD2/DRD1 ratio. The STN lesion attenuated the striatal molecular changes and normalized the DRD2/DRD1 ratio. Taken together, our results show that the STN plays a role, if modest, in the physiopathology of dyskinesias.

  10. Tardive Dyskinesia Revisited-A Clinical Management Priority Perspective: A Voyage into High Dose Buspirone Part B

    Directory of Open Access Journals (Sweden)

    Vernon M Neppe

    2016-06-01

    Full Text Available We discuss several major related and integrated issues in this two-part series of papers on tardive dyskinesia (TD. In this, the second paper, Part B, the management and mechanisms are emphasized; in Part A the diagnosis and assessment of tardive dyskinesia was discussed. In this Part B series of articles we examine several special important priorities in this condition associated with sometimes permanent involuntary abnormal movements associated with the neuroleptic drugs. We particularly examine the management of this enormously important condition. After the diagnosis and assessment of TD, comes the clinical approach to management and the options and theories behind that approach. There remain no approved medications for the management of tardive dyskinesia. Therefore, all treatments are “out of labeling”. The purpose of this paper is to shed light on high dose buspirone treatment, originally described by the author in 1989 [1], and which after more than a quarter century requires re-evaluation as it still appears, in the author’s opinion, to be the logical and most appropriate management for TD. A major issue focuses, on the updated experience of more than a quarter century with generally almost completely positive effects of high-dose buspirone (HDB treatment of tardive dyskinesia (TD and the next issue provides an important, major theoretical demonstration of the mechanism of tardive dyskinesia. The dopamine 2 or 2-3 supersensitivity hypothesis as a cause of TD is strongly supported by HDB. In Part B, the issue of choice of medication for psychosis and related medical conditions becomes pertinent. The choices relate to the newer second generation atypical neuroleptics (SGAs compared with the older typical, first generation neuroleptics (FGAs. The generally more expensive SGA drugs have become far the most used anti-psychotic agents in wealthy countries such as the United States, because of their efficacy and ostensible safety

  11. Aerobic fitness in children and young adults with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Madsen, Astrid Hellerup; Green, Kent; Buchvald, Frederik

    2013-01-01

    patients. CONCLUSION: One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease...... and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle......BACKGROUND: Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2...

  12. Cerebrospinal fluid biomarkers for Parkinson's disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas

    2015-01-01

    Parkinson’s disease (PD) is a common disease, affecting 1% of the population older than 60 years of age[1]. Neuropathological characteristics of the disease include the presence of alpha-synuclein containing Lewy bodies in the brain stem and loss of nigrostriatal dopaminergic neurons, which result...... in motor deficits that are used as diagnostic criteria for PD[2]. So far there is no treatment available slowing the progression of PD. The otherwise effective dopamine replacement therapy not only loses its effectiveness during the natural course of the disease but also increases the risk of developing...... of patients, who are also clinically rated using the Unified Parkinson’s Disease rating scale (UPDRS)[5] and the Unified Dyskinesia Rating Scale (UDysRS). 1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet neurology. 2006;5(6):525-35. 2. Rodriguez-Oroz MC, Jahanshahi M, Krack P, et al...

  13. Genetic factors contributing to human primary ciliary dyskinesia and male infertility.

    Science.gov (United States)

    Ji, Zhi-Yong; Sha, Yan-Wei; Ding, Lu; Li, Ping

    2016-06-07

    Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from the loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. However, only 15 PCD-associated genes have been identified to cause male infertility to date. Owing to the genetic heterogeneity of PCD, comprehensive molecular genetic testing is not considered the standard of care. Here, we provide an update of the progress on the identification of genetic factors related to PCD associated with male infertility, summarizing the underlying molecular mechanisms, and discuss the clinical implications of these findings. Further research in this field will impact the diagnostic strategy for male infertility, enabling clinicians to provide patients with informed genetic counseling, and help to adopt the best course of treatment for developing directly targeted personalized medicine.

  14. Oromandibular Dyskinesia as the Initial Manifestation of Late-Onset Huntington Disease

    Directory of Open Access Journals (Sweden)

    Dong-Seok Oh

    2011-10-01

    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder characterized by a triad of choreoathetosis, dementia and dominant inheritance. The cause of HD is an expansion of CAG trinucleotide repeats in the HD gene. Typical age at onset of symptoms is in the 40s, but the disorder can manifest at any time. Late-onset (≥ 60 years HD is clinically different from other adult or juvenile onset HD and characterized by mild motor problem as the initial symptoms, shorter disease duration, frequent lack of family history, and relatively low CAG repeats expansion. We report a case of an 80-year-old female with oromandibular dyskinesia as an initial manifestation of HD and 40 CAG repeats.

  15. Primary ciliary dyskinesia diagnosed by electron microscopy in one case of Kartagener syndrome.

    Science.gov (United States)

    Rugină, Aniela Luminiţa; Dimitriu, Alexandru Grigore; Nistor, Nicolai; Mihăilă, Doina

    2014-01-01

    Primary ciliary dyskinesia (PCD) is associated with abnormalities in the structure of a function of motile cilia, causing impairment of muco-ciliary clearence, with bacterial overinfection of the upper and lower respiratory tract (chronic oto-sino-pulmonary disease), heterotaxia (situs abnormalities), with/without congenital heart disease, abnormal sperm motility with male infertility, higher frequency of ectopic pregnancy and female subfertility. The presence of recurrent respiratory tract infections in the pediatric age requires differentiation between primary immunodeficiency, diseases with abnormal mucus (e.g., cystic fibrosis) and abnormal ciliary diseases. This case was hospitalized for recurrent respiratory tract infections and total situs inversus at the age of five years, which has enabled the diagnosis of Kartagener syndrome. The PCD confirmation was performed by electron microscopy examination of nasal mucosa cells through which were confirmed dynein arms abnormalities. The diagnosis and early treatment of childhood PCD allows a positive development and a good prognosis, thus improving the quality of life.

  16. A perspective on molecular genetic studies of tardive dyskinesia: one clue for individualized antipsychotic drug therapy.

    Science.gov (United States)

    Ohmori, Osamu; Shinkai, Takahiro; Hori, Hiroko; Matsumoto, Chima; Nakamura, Jun

    2003-06-01

    Interindividual genetic profile differences related to antipsychotic drug therapy may be determined based on molecular genetic studies of the pathogenesis of schizophrenia and studies of antipsychotic drug responses (therapeutic as well as adverse responses). In the present article, we review molecular genetic studies of tardive dyskinesia (TD), which is a representative adverse response to antipsychotic drugs. Such studies have been performed to explore the gene-associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs. Positive associations between several genes and TD have been reported. The accumulation of results from such studies will hopefully lead to individualized antipsychotic drug therapies that involve the application of new genomic techniques, including DNA microarrays. Subsequently, antipsychotic drugs may in the future be prescribed for smaller subgroups of patients who have been classified as having a particular genetic profile.

  17. Tardive dyskinesia occurring in a young woman after withdrawal of an atypical antipsychotic drug.

    Science.gov (United States)

    Alblowi, Mohammed A; Alosaimi, Fahad D

    2015-10-01

    Tardive dyskinesia (TD) is one of the most serious and disturbing side-effects of dopamine receptor antagonists. It affects 20-50% of patients on long-term antipsychotic therapy. The pathophysiology of TD remains poorly understood, and treatment is often challenging. Here, we present a 32-year-old woman presenting with a 9-month history of TD occurring after risperidone withdrawal, and characterized almost exclusively by tongue protrusion. After being seen by different specialties and undergoing multiple investigations, she was eventually correctly diagnosed with TD by a specialist team and successfully treated with amantadine. Vigilance and awareness of this condition and its risk factors are required to make the correct diagnosis, especially in cases with unusual presentations caused by atypical antipsychotics, and treatment can be challenging.

  18. Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

    Directory of Open Access Journals (Sweden)

    Hsien-Yang Lee

    2012-01-01

    Full Text Available Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25 of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

  19. Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia

    Science.gov (United States)

    Nevalainen, Nina; af Bjerkén, Sara; Lundblad, Martin; Gerhardt, Greg A.; Strömberg, Ingrid

    2011-01-01

    L-DOPA (3,4-dihydroxyphenyl-L-alanine) is the most commonly used treatment for symptomatic control in patients with Parkinson’s disease. Unfortunately, most patients develop severe side effects, such as dyskinesia, upon chronic L-DOPA treatment. The patophysiology of dyskinesia is unclear, however, involvement of serotonergic nerve fibers in converting L-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of L-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned L-DOPA naïve, and dopamine-denervated chronically L-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local L-DOPA administration into normal and intact hemisphere of dopamine-lesioned L-DOPA naïve animals significantly increased the potassium-evoked dopamine release. L-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted L-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, while no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local L-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared to those measured in L-DOPA naïve dopamine-denervated striatum. To conclude, L-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, L-DOPA loading does not increase the dopamine release in dyskinetic animals as found in L-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior. PMID:21534956

  20. Poor self-awareness of levodopa-induced dyskinesias in Parkinson's disease: clinical features and mechanisms.

    Science.gov (United States)

    Pietracupa, Sara; Fasano, Alfonso; Fabbrini, Giovanni; Sarchioto, Marianna; Bloise, Maria; Latorre, Anna; Altieri, Marta; Bologna, Matteo; Berardelli, Alfredo

    2013-11-01

    To study the factors and possible mechanisms associated with decreased self-awareness of levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD). We enrolled 30 PD patients with LIDs. Patients were video-recorded in an "on" phase while experiencing LIDs. LIDs were objectively rated by means of the Unified Dyskinesias Rating Scale (UDyRS) by two movement disorders specialists while examining the patients. Patients were asked to rate the body site and the severity of their LIDs according to the 5-point UDyRS. Patients then rated their own LIDs while watching the video recording of themselves. Lastly, the patients rated the LIDs of other reference PD patients on a video recording. The same reference video recordings were shown to 15 healthy individuals matched for age, gender and education. Seven of the 30 PD patients investigated were subjectively unaware of the presence of their LIDs. The majority of patients, however, recognized their LIDs when watching video recording of themselves. Patients displayed a specific poor self-awareness of trunk LIDs, in both the subjective evaluation and in the video recording-based subjective evaluation. By contrast PD patients correctly recognized LIDs in video recordings of reference PD patients. Poor self-awareness correlated with predominance of motor symptoms on the left body side. Poor self-awareness of LIDs is present in a proportion of PD patients as a form of anosognosia. The poor self-awareness of LIDs in the trunk is likely to be due to a complex interplay involving both anosognosic mechanisms and deficits in proprioceptive axial kinesthesia. Copyright © 2013. Published by Elsevier Ltd.

  1. Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs.

    Science.gov (United States)

    Tarsy, Daniel; Lungu, Codrin; Baldessarini, Ross J

    2011-01-01

    Late or tardive dyskinesias/dystonias (TD), contrary to expectation, have not disappeared with the use of expensive, modern antipsychotic drugs (APDs). Risk appears to be substantially lower than with older neuroleptics, and there is sparing of most acute movement disorders traditionally associated with APD treatment. However, risks of TD with modern APDs have been reduced much less than expected, by perhaps two- to threefold or even less, with substantial risks in the elderly. Major challenges in assessing prevalence or, preferably, incidence of TD arise from prolonged and erratic past exposure to various APDs, relatively recent use of modern APDs, and the occurrence of spontaneous movement disorders (about 5% and more in the elderly). TD risks associated with modern APDs may be similar to some older neuroleptics, especially those of low-moderate potency. Risperidone (and its active metabolite paliperidone), at high doses, may carry unusually high TD risk, whereas TD risk is low with clozapine, and perhaps quetiapine and aripiprazole. Optimistic expectations for the efficacy and neurological safety of modern APDs have encouraged their wide use in many conditions, sometimes off-label or in combinations, with little research support, increasing the chance of a higher prevalence of TD, especially at older ages. Measures to limit TD risk include: (1) critical, objective indications for APD use; (2) long-term use only for compelling or research-supported indications, primarily chronic psychotic illness that worsens when APD is slowly discontinued; (3) avoiding off-label indications; (4) using alternative treatments when APD treatment is elective, or early dyskinesia is identified; (5) using low but effective doses of single APDs, especially in the elderly; and (6) regular and specific examination for early TD.

  2. Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia.

    Science.gov (United States)

    Pifferi, M; Bush, A; Maggi, F; Michelucci, A; Ricci, V; Conidi, M E; Cangiotti, A M; Bodini, A; Simi, P; Macchia, P; Boner, A L

    2011-03-01

    No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency.

  3. Tardive Dyskinesia

    Science.gov (United States)

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  4. Variations of Aripiprazole-Induced Dyskinesia Existing with Concurrent Use of Amantadine and an Anticholinergic Agent in an Elderly Patient

    Directory of Open Access Journals (Sweden)

    I-Wen Sun

    2012-06-01

    Full Text Available Elderly patients are vulnerable to the adverse neurological effects of antipsychotics, particularly Parkinsonian symptoms and tardive dyskinesia. This vulnerability in the elderly becomes complex and unpredictable when aripiprazole is prescribed to replace other second-generation or first-generation antipsychotics. This report describes a 69-year-old female schizophrenic patient, who received aripiprazole after using a few antipsychotics, including the first- and second-generation ones. The tardive dyskinesia developed 6 weeks after switching to aripiprazole but subsided 4 weeks later when stopping the concurrent amantadine and decreasing the dosage of trihexyphenidyl. However, Parkinsonian symptoms developed insidiously thereafter, which remitted after the dosage of trihexyphenidyl was increased again. The possible mechanisms of the alternated adverse neurological events after a switch to aripiprazole in the chronic elderly psychosis are discussed.

  5. A Water Extract of Mucuna pruriens Provides Long-Term Amelioration of Parkinsonism with Reduced Risk for Dyskinesias

    OpenAIRE

    Lieu, Christopher A; Kunselman, Allen R.; Manyam, Bala V.; Venkiteswaran, Kala; Subramanian, Thyagarajan

    2010-01-01

    Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of Mucuna pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decar...

  6. Primary ciliary dyskinesia: Kartagener syndrome in a family with a novel DNAH5 gene mutation and variable phenotypes

    OpenAIRE

    2015-01-01

    Background: Primary ciliary dyskinesia is a genetically heterogeneous autosomal recessive disorder with variable clinical manifestations, including chronic rhinosinusitis, otitis media, bronchitis, pneumonia, bronchiectasis, situs inversus totalis, reduced fertility in female patients and male infertility. The condition occurs as a result of abnormal ciliary structure and function. It is presented in early life with an estimated incidence of approximately 1/16,000–20,000. About 50% of the aff...

  7. DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor

    OpenAIRE

    2016-01-01

    Summary Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson’s disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemog...

  8. Successful Fitting of a Complete Maxillary Denture in a Patient with Severe Alzheimer's Disease Complicated by Oral Dyskinesia

    Science.gov (United States)

    Hashimoto, Akie; Inoue, Ryosuke; Yoshimoto, Shohei; Hirofuji, Takao

    2016-01-01

    There is an increasing population of elderly patients suffering from Alzheimer's disease (AD), the most common form of dementia. In dentistry, a critical problem associated with these patients is the use of a new denture, as AD patients often refuse dental management and are disturbed by minor changes in their oral environment. Some AD patients have further complications associated with oral dyskinesia, a movement disorder that can make dental management difficult, including the stability of a complete denture. In this case, we successfully fitted a complete maxillary denture using modified bilateral balanced occlusion after multiple tooth extractions under intravenous sedation in a 66-year-old woman with severe AD complicated by oral dyskinesia. Following treatment, her appetite and food intake greatly improved. Providing a well-fitting complete denture applied by modified bilateral balanced occlusion, which removes lateral interference using zero-degree artificial teeth for movement disorder of the jaw in patients with severe AD complicated by oral dyskinesia, helps improve oral function. PMID:27822393

  9. Differential dopamine receptor occupancy underlies L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Gurdal Sahin

    Full Text Available Dyskinesia is a major side effect of an otherwise effective L-DOPA treatment in Parkinson's patients. The prevailing view for the underlying presynaptic mechanism of L-DOPA-induced dyskinesia (LID suggests that surges in dopamine (DA via uncontrolled release from serotonergic terminals results in abnormally high level of extracellular striatal dopamine. Here we used high-sensitivity online microdialysis and PET imaging techniques to directly investigate DA release properties from serotonergic terminals both in the parkinsonian striatum and after neuronal transplantation in 6-OHDA lesioned rats. Although L-DOPA administration resulted in a drift in extracellular DA levels, we found no evidence for abnormally high striatal DA release from serotonin neurons. The extracellular concentration of DA remained at or below levels detected in the intact striatum. Instead, our results showed that an inefficient release pool of DA associated with low D2 receptor binding remained unchanged. Taken together, these findings suggest that differential DA receptor activation rather than excessive release could be the underlying mechanism explaining LID seen in this model. Our data have important implications for development of drugs targeting the serotonergic system to reduce DA release to manage dyskinesia in patients with Parkinson's disease.

  10. A case of paroxysmal kinesigenic dyskinesia which exhibited the phenotype of anxiety disorder

    Directory of Open Access Journals (Sweden)

    Kunii Y

    2017-08-01

    Full Text Available Yasuto Kunii,1,2 Nozomu Matsuda,3 Hirooki Yabe1 1Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan; 2Department of Neuropsychiatry, Aizu Medical Center, School of Medicine, Fukushima Medical University, Fukushima, Japan; 3Department of Neurology, Fukushima Medical University School of Medicine, Fukushima, Japan Background: Paroxysmal kinesigenic dyskinesia (PKD is a rare heritable neurologic disorder characterized by attacks of involuntary movement induced by sudden voluntary movements. No previous reports have described cases showing comorbidity with psychiatric disease or symptoms. In this case, we showed a patient with PKD who exhibited several manifestations of anxiety disorder.Case: A 35-year-old Japanese man with PKD had been maintained on carbamazepine since he was 16 years of age without any attacks. However, 10 years before this referral, he became aware of a feeling of breakdown in his overall physical functions. He had then avoided becoming familiar with people out of concern that his physical dysfunctions might be perceived in a negative light. One day he was referred by the neurologic department at our hospital to the Department of Psychiatry because of severe anxiety and hyperventilation triggered by carbamazepine. We treated with escitalopram, aripiprazole, and ethyl loflazepate. Both his subjective physical condition and objective expressions subsequently showed gradual improvement. At last, the feelings of chest compression and anxiety entirely disappeared. Accordingly, increases in plasma monoamine metabolite levels were observed, and the c.649dupC mutation, which has been found in most Japanese PKD families, was detected in his proline-rich transmembrane protein 2 gene.Conclusion: This is the first report to describe psychiatric comorbidities or symptoms in a PKD case. The efficacy of psychotropic medication used in this case, the resulting changes in plasma monoamine metabolite

  11. Cerebellum in levodopa-induced dyskinesias: the unusual suspect in the motor network.

    Science.gov (United States)

    Kishore, Asha; Popa, Traian

    2014-01-01

    The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson's disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during "OFF" and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and "lock" the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information

  12. Tardive dyskinesia in a South Asian population with first episode psychosis treated with antipsychotics

    Directory of Open Access Journals (Sweden)

    Adam UU

    2014-10-01

    Full Text Available Usman Adam, Nusrat Husain, Peter M Haddad, Tariq Munshi, Fauzia Tariq, Farooq Naeem, Imran B ChaudhryBackground: Tardive dyskinesia (TD is a side effect of antipsychotic treatment that often only appears after months or years of treatment. A systematic review of randomized controlled trials lasting more than 1 year showed that second-generation antipsychotics (SGAs were associated with an approximately fivefold lower risk of TD compared to haloperidol in patients with chronic schizophrenia. In contrast, there is little research on the risk of TD with other first-generation antipsychotics (FGAs, and this applies especially to their use in the treatment of patients with first episode psychosis (FEP.Objectives: To determine the severity and point prevalence of TD in a naturalistic sample of patients with FEP in Pakistan treated with FGAs or SGAs.Methods: This was an observational study. TD was assessed by trained clinicians using the Abnormal Involuntary Movement Scale.Results: In the total sample (number =86 the mean age of patients was 26 years and the prevalence of TD (Schooler Kane criteria was 29% with no significant difference between those treated with FGAs and SGAs (31% FGAs versus 26% SGAs; P=0.805. The Abnormal Involuntary Movement Scale total score (items 1–7, a measure of the severity of TD, was significantly higher for patients treated with FGAs versus those treated with SGAs (P=0.033. Scores on specific items showed that this reflected higher scores for dyskinesia affecting the muscles of facial expression, as well as of the upper and lower limb, whereas scores did not differ significantly in other body areas. Conclusion: FGAs were associated with greater severity, though not prevalence, of TD than SGAs. The study highlights the relatively high rate of TD in Asian FEP patients and the need for clinicians to monitor for this and other potential antipsychotic side effects during treatment. Keywords: first-generation antipsychotic

  13. Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis.

    Science.gov (United States)

    Carbon, Maren; Hsieh, Cheng-Hsi; Kane, John M; Correll, Christoph U

    2017-03-01

    Comparison of tardive dyskinesia (TD) prevalence during contemporaneous treatment with first-generation antipsychotics (FGAs) and/or second-generation antipsychotics (SGAs). PubMed/MEDLINE/Google Scholar search (January 1, 2000-September 30, 2015) without language restriction using (tardive dyskinesia OR tardive) AND (antipsychotic*) plus specific names of SGAs. Of 8,895 hits, we screened 203 full-text articles for cross-sectional, rating scale-based TD rates during SGA, FGA, or FGA+SGA treatment. Forty-one studies were used for random effects meta-analysis and meta-regression. Two authors independently extracted data on overall and antipsychotic class-wise TD rates and on TD moderators. The global mean TD prevalence was 25.3% (95% CI = 22.7%-28.1%) across all 41 studies (N = 11,493, mean age = 42.8 years, male = 66.4%, schizophrenia-spectrum disorders = 77.1%). TD prevalence varied greatly: Rates were lower with current SGA treatment (20.7%; 95% CI = 16.6%-25.4%, N = 5,103) vs current FGA treatment (30.0%; 95% CI = 26.4%-33.8%, N = 5,062; Q = 9.17, P = .002). This difference remained significant after controlling for moderators: higher age (Z = 2.85, P = .004; number of studies = 39 ) and region (39 studies; Asia vs Europe, Z = 1.55, P = .12; Asia lower than United States, Z = 2.6, P = .009; Asia lower than other regions, Z = 2.42, P = .015). Additional moderators of TD prevalence included longer illness duration (R² = 0.15; P = .03; 21 studies) and frequency of parkinsonism (R² = 0.23, P = .017; number of studies = 19). Particularly low TD prevalence (7.2%; number of studies = 4) was found in the treatment arms with FGA-naive subjects relative to SGA-treated cohorts with likely prior FGA exposure (23.4%; P Z = -2.55, P = .011) and FGA + SGA vs FGAs (risk ratio = 0.80, 95% CI = 0.71-0.90, Z = -3.56, P < .001). Reports on TD severity, provided by 10 studies, were of insufficient quality for meta-analysis. Rating scale-based TD remains highly prevalent, with

  14. Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia: A comparison of genetic variants in two independent patient populations

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    Svetlana A Ivanova

    2016-04-01

    Full Text Available Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia. Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431 and a long-stay population from the Netherlands (N = 168. These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared. Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423 was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant. Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia.

  15. Pharmacological treatments inhibiting levodopa-induced dyskinesias in MPTP-lesioned monkeys: brain glutamate biochemical correlates

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    Nicolas eMorin

    2014-08-01

    Full Text Available Antiglutamatergic drugs can relieve Parkinson’s disease (PD symptoms and decrease L-3,4-dihydroxyphenylalanine (L-DOPA-induced dyskinesias (LID. This review reports relevant studies investigating glutamate receptor subtypes in relation to motor complications in PD patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-lesioned monkeys. Antagonists of the ionotropic glutamate receptors, such as NMDA and AMPA receptors, display antidyskinetic activity in PD patients and animal models such as the MPTP monkey. Metabotropic glutamate 5 (mGlu5 receptor antagonists were shown to reduce the severity of LID in PD patients as well as in already dyskinetic non-human primates and to prevent the development of LID in de novo treatments in non-human primates. An increase in striatal post-synaptic NMDA, AMPA and mGlu5 receptors is documented in PD patients and MPTP monkeys with LID. This increase can be prevented in MPTP monkeys with the addition of a specific glutamate receptor antagonist to the L-DOPA treatment and also with drugs of various pharmacological specificities suggesting multiple receptor interactions. This is yet to be well documented for presynaptic mGlu4 and mGlu2/3 and offers additional new promising avenues.

  16. The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results

    Science.gov (United States)

    Goutaki, Myrofora; Maurer, Elisabeth; Halbeisen, Florian S.; Amirav, Israel; Barbato, Angelo; Behan, Laura; Boon, Mieke; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Haarman, Eric; Hogg, Claire; Karadag, Bulent; Koerner-Rettberg, Cordula; Leigh, Margaret W.; Loebinger, Michael R.; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G.; Omran, Heymut; Schwerk, Nicolaus; Scigliano, Sergio; Werner, Claudius; Yiallouros, Panayiotis; Zivkovic, Zorica; Lucas, Jane S.

    2017-01-01

    Data on primary ciliary dyskinesia (PCD) epidemiology is scarce and published studies are characterised by low numbers. In the framework of the European Union project BESTCILIA we aimed to combine all available datasets in a retrospective international PCD cohort (iPCD Cohort). We identified eligible datasets by performing a systematic review of published studies containing clinical information on PCD, and by contacting members of past and current European Respiratory Society Task Forces on PCD. We compared the contents of the datasets, clarified definitions and pooled them in a standardised format. As of April 2016 the iPCD Cohort includes data on 3013 patients from 18 countries. It includes data on diagnostic evaluations, symptoms, lung function, growth and treatments. Longitudinal data are currently available for 542 patients. The extent of clinical details per patient varies between centres. More than 50% of patients have a definite PCD diagnosis based on recent guidelines. Children aged 10–19 years are the largest age group, followed by younger children (≤9 years) and young adults (20–29 years). This is the largest observational PCD dataset available to date. It will allow us to answer pertinent questions on clinical phenotype, disease severity, prognosis and effect of treatments, and to investigate genotype–phenotype correlations. PMID:28052956

  17. Primary ciliary dyskinesia: a report from ATS 2001, May 18–23, San Francisco

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    Noone Peadar G

    2001-06-01

    Full Text Available Abstract Primary ciliary dyskinesia (PCD is a genetic disorder of abnormal ciliary structure and function that leads to defective mucociliary clearance, resulting in oto-sino-pulmonary disease, and infertility. The disease is currently under intense investigation by a number of research groups worldwide. At the recent American Thoracic Society meeting in San Francisco in May 2001, two sessions focused on PCD; a symposium session on May 21 with several featured expert speakers was followed by a mini-symposium on Tuesday May 22, with one featured speaker and presentation of nine abstracts covering a range of research topics. Mattias Salathe (University of Miami, USA and Stephen Brody (Washington University, St Louis, USA chaired the symposium session. Presentations focused on the clinical spectrum of PCD, the genetics of PCD, a proteomics approach to detail the structure of cilia, the role of cilia in the embryology of situs laterality, and airway epithelial cell biology. The mini-symposium was chaired by Peadar Noone (University of North Carolina, USA and Malcolm King (University of Alberta, USA and included presentations on the use of PCD as a human disease model, accurate definition of the phenotype using clinical and cell biologic markers, and molecular studies. The latter reports ranged from isolation of a protein involved in ciliary structure and function to genetic studies using linkage analysis and the candidate gene approach. Clinicians and scientists alike displayed considerable interest at both sessions, and there were several lively question–answer sessions.

  18. Dyskinesias and impulse control disorders in Parkinson's disease: From pathogenesis to potential therapeutic approaches.

    Science.gov (United States)

    Jiménez-Urbieta, Haritz; Gago, Belén; de la Riva, Patricia; Delgado-Alvarado, Manuel; Marin, Concepció; Rodriguez-Oroz, María C

    2015-09-01

    Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor symptoms of the disease. However, its chronic use is associated with disabling motor and behavioral side effects, among which levodopa-induced dyskinesias (LID) and impulse control disorders (ICD) are the most common. The underlying mechanisms and pathological substrate of these dopaminergic complications are not fully understood. Recently, the refinement of imaging techniques and the study of the genetics and molecular bases of LID and ICD indicate that, although different, they could share some features. In addition, animal models of parkinsonism with LID have provided important knowledge about mechanisms underlying such complications. In contrast, animal models of parkinsonism and abnormal impulsivity, although useful regarding some aspects of human ICD, do not fully resemble the clinical phenotype of ICD in patients with PD, and until now have provided limited information. Studies on animal models of addiction could complement the previous models and provide some insights into the background of these behavioral complications given that ICD are regarded as behavioral addictions. Here we review the most relevant advances in relation to imaging, genetics, biochemistry and pharmacological interventions to treat LID and ICD in patients with PD and in animal models with a view to better understand the overlapping and unique maladaptations to dopaminergic therapy that are associated with LID and ICD.

  19. Levodopa-induced dyskinesias in Parkinson’s disease: emerging treatments

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    Bargiotas P

    2013-10-01

    Full Text Available Panagiotis Bargiotas, Spyridon KonitsiotisDepartment of Neurology, University of Ioannina, Ioannina, GreeceAbstract: Parkinson’s disease therapy is still focused on the use of l-3,4-dihydroxyphenylalanine (levodopa or l-dopa for the symptomatic treatment of the main clinical features of the disease, despite intensive pharmacological research in the last few decades. However, regardless of its effectiveness, the long-term use of levodopa causes, in combination with disease progression, the development of motor complications termed levodopa-induced dyskinesias (LIDs. LIDs are the result of profound modifications in the functional organization of the basal ganglia circuitry, possibly related to the chronic and pulsatile stimulation of striatal dopaminergic receptors by levodopa. Hence, for decades the key feature of a potentially effective agent against LIDs has been its ability to ensure more continuous dopaminergic stimulation in the brain. The growing knowledge regarding the pathophysiology of LIDs and the increasing evidence on involvement of nondopaminergic systems raises the possibility of more promising therapeutic approaches in the future. In the current review, we focus on novel therapies for LIDs in Parkinson’s disease, based mainly on agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in testing or clinical development.Keywords: motor fluctuations, dopaminergic/nondopaminergic systems, pharmacotherapy

  20. Familial paroxysmal nonkinesigenic dyskinesia: clinical and genetic analysis of a Taiwanese family.

    Science.gov (United States)

    Yeh, Tu-Hsueh; Lin, Juei-Jueng; Lai, Szu-Chia; Wu-Chou, Yah-Huei; Chen, An-Chih; Yueh, Kuo-Chu; Chen, Rou-Shayn; Lu, Chin-Song

    2012-12-15

    Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder in autosomal dominant inheritance. The clinical features and genetic findings of PNKD, rarely described in the Asians, were mostly delineated from European families. The present study characterized the clinical and genetic findings of a Taiwanese PNKD family. The clinical features of our five patients in successive three generations included onset age less than 10 years, attack duration between 3 min and 4h, and a variety of aura symptoms. The attacks were provoked not by sudden action but by emotional stress, caffeine, fatigue, heavy exercise and sleep deprivation. Sleep could abolish or diminish the attack and the attacks responded well to clonazepam. Sequencing the whole coding region of PNKD/MR-1 gene identified a heterozygous c.20 C>T (p.Ala7Val) mutation which was clearly segregated in the five affected patients. Comparing our patients with previously reported 18 families with PNKD/MR-1 mutations, the majority of the patients exhibited quite similar manifestations in attack patterns and precipitating factors. The recurrent conservative mutations in different ethnicities indicate importance in the pathogenesis of PNKD.

  1. Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

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    Nisreen Rumman

    2017-01-01

    Full Text Available Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise. In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics. We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

  2. Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia

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    Sylvia Navailles

    2012-01-01

    Full Text Available L-DOPA-induced dyskinesias (LIDs are one of the main motor side effects of L-DOPA therapy in Parkinson's disease. The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain. The consequences are an ectopic and aberrant release of dopamine that follows the serotonergic innervation of the brain. After mid- to long-term treatment with L-DOPA, the pattern of L-DOPA-induced dopamine release is modified. In several brain regions, its effect is dramatically reduced while, in the striatum, its effect is quite preserved. LIDs could appear when the dopaminergic effects of L-DOPA fall in brain areas such as the cortex, enhancing the subcortical impact of dopamine and promoting aberrant motor responses. The consideration of the serotonergic system in the core mechanism of action of L-DOPA opens an important reserve of possible strategies to limit LIDs.

  3. PRRT2 mutation causes paroxysmal kinesigenic dyskinesia and hemiplegic migraine in monozygotic twins.

    Science.gov (United States)

    Castiglioni, Claudia; López, Isabel; Riant, Florence; Bertini, Enrico; Terracciano, Alessandra

    2013-05-01

    PRRT2 gene mutations have recently been identified as a causative gene of Paroxysmal kinesigenic dyskinesia (PKD), a rare movement disorder characterised by the occurrence of chorea, dystonia or athetosis triggered by sudden action. Some patients have additional intermittent neurologic disorders like infantile convulsions. The association with migraine has been rarely reported in this condition. Here we report the coexistence of PKD and hemiplegic migraine in twins harbouring a heterozygous mutation in PRRT2. Two monozygotic twins manifesting PKD together with repeated episodes of migraine with some severe attacks of hemiplegic migraine have been followed and treated for more than 10 years. Molecular genetic analysis disclosed the c.649_650insC, p.R217Pfs*8 heterozygous mutation in both twins. This mutation was segregating from the mother who likewise harboured the same mutation c.649dupC although she had never manifested PKD but complained of rare common migraine attacks in her past history. The association of PKD and hemiplegic migraine has been previously reported in one large family, associated to febrile convulsions and afebrile seizures in some individuals, but our report relates this association of symptoms to a mutation in PRRT2. The co-occurrence of both hemiplegic migraine and PKD in monozygotic twins expands the phenotypic spectrum of intermittent manifestations related to PRRT2 and perhaps suggests an additional causing gene for hemiplegic migraine. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  4. Late onset of atypical paroxysmal non-kinesigenic dyskinesia with remote history of Graves′ disease

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    Abdul Qayyum Rana

    2013-01-01

    Full Text Available Paroxysmal non-kinesigenic dyskinesia (PNKD is a rare hyperkinetic movement disorder and falls under the category of paroxysmal movement disorders. In this condition, episodes are spontaneous, involuntary, and involve dystonic posturing with choreic and ballistic movements. Attacks last for minutes to hours and rarely occur more than once per day. Attacks are not typically triggered by sudden movement, but may be brought on by alcohol, caffeine, stress, fatigue, or chocolate. We report a patient with multiple atypical features of PNKD. She had a 7-year history of this condition with onset at the age of 59, and a remote history of Graves′ disease requiring total thyroidectomy. The frequency of attacks in our case ranged from five to six times a day to a minimum of twice per week, and the duration of episode was short, lasting not more than 2 min. Typically, PNKDs occur at a much younger age and have longer attack durations with low frequency. Administering clonazepam worked to reduce her symptoms, although majority of previous research suggests that pharmacological interventions have poor outcomes.

  5. Late onset of atypical paroxysmal non-kinesigenic dyskinesia with remote history of Graves' disease.

    Science.gov (United States)

    Rana, Abdul Qayyum; Nadeem, Ambreen; Yousuf, Muhammad Saad; Kachhvi, Zakerabibi M

    2013-10-01

    Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare hyperkinetic movement disorder and falls under the category of paroxysmal movement disorders. In this condition, episodes are spontaneous, involuntary, and involve dystonic posturing with choreic and ballistic movements. Attacks last for minutes to hours and rarely occur more than once per day. Attacks are not typically triggered by sudden movement, but may be brought on by alcohol, caffeine, stress, fatigue, or chocolate. We report a patient with multiple atypical features of PNKD. She had a 7-year history of this condition with onset at the age of 59, and a remote history of Graves' disease requiring total thyroidectomy. The frequency of attacks in our case ranged from five to six times a day to a minimum of twice per week, and the duration of episode was short, lasting not more than 2 min. Typically, PNKDs occur at a much younger age and have longer attack durations with low frequency. Administering clonazepam worked to reduce her symptoms, although majority of previous research suggests that pharmacological interventions have poor outcomes.

  6. Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

    Science.gov (United States)

    Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

    2011-02-01

    Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

  7. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

    Science.gov (United States)

    Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

    2007-07-01

    Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

  8. Endothelial Proliferation and Increased Blood - Brain Barrier Permeability in the Basal Ganglia in a Rat Model of 3,4-Dihydrozyphenyl-L-Alanine-Induced Dyskinesia

    DEFF Research Database (Denmark)

    Westin, Jenny E.; Lindgren, Hanna S.; Gardi, Jonathan Eyal

    2006-01-01

    3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia is associated with molecular and synaptic plasticity in the basal ganglia, but the occurrence of structural remodeling through cell genesis has not been explored. In this study, rats with 6-hydroxydopamine lesions received injections of th...... of angiogenesis and blood-brain barrier dysfunction in an experimental model of L-DOPA-induced dyskinesia. These microvascular changes are likely to affect the kinetics of L-DOPA entry into the brain, favoring the occurrence of motor complications....

  9. Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Aanaes, Kasper; Høiby, Niels;

    2016-01-01

    BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway...... patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated...

  10. Immunofluorescence Analysis and Diagnosis of Primary Ciliary Dyskinesia with Radial Spoke Defects.

    Science.gov (United States)

    Frommer, Adrien; Hjeij, Rim; Loges, Niki T; Edelbusch, Christine; Jahnke, Charlotte; Raidt, Johanna; Werner, Claudius; Wallmeier, Julia; Große-Onnebrink, Jörg; Olbrich, Heike; Cindrić, Sandra; Jaspers, Martine; Boon, Mieke; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Sauer, Sascha; Marthin, June K; Nielsen, Kim G; Amirav, Israel; Elias, Nael; Kerem, Eitan; Shoseyov, David; Haeffner, Karsten; Omran, Heymut

    2015-10-01

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder caused by several distinct defects in genes responsible for ciliary beating, leading to defective mucociliary clearance often associated with randomization of left/right body asymmetry. Individuals with PCD caused by defective radial spoke (RS) heads are difficult to diagnose owing to lack of gross ultrastructural defects and absence of situs inversus. Thus far, most mutations identified in human radial spoke genes (RSPH) are loss-of-function mutations, and missense variants have been rarely described. We studied the consequences of different RSPH9, RSPH4A, and RSPH1 mutations on the assembly of the RS complex to improve diagnostics in PCD. We report 21 individuals with PCD (16 families) with biallelic mutations in RSPH9, RSPH4A, and RSPH1, including seven novel mutations comprising missense variants, and performed high-resolution immunofluorescence analysis of human respiratory cilia. Missense variants are frequent genetic defects in PCD with RS defects. Absence of RSPH4A due to mutations in RSPH4A results in deficient axonemal assembly of the RS head components RSPH1 and RSPH9. RSPH1 mutant cilia, lacking RSPH1, fail to assemble RSPH9, whereas RSPH9 mutations result in axonemal absence of RSPH9, but do not affect the assembly of the other head proteins, RSPH1 and RSPH4A. Interestingly, our results were identical in individuals carrying loss-of-function mutations, missense variants, or one amino acid deletion. Immunofluorescence analysis can improve diagnosis of PCD in patients with loss-of-function mutations as well as missense variants. RSPH4A is the core protein of the RS head.

  11. DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia

    Science.gov (United States)

    Onuoha, Ezenwa Obi; Damerla, Rama Rao; Francis, Richard; Furutani, Yoshiyuki; Tariq, Muhammad; King, Stephen M.; Hendricks, Gregory; Cui, Cheng; Saydmohammed, Manush; Lee, Dong Min; Zahid, Maliha; Sami, Iman; Leatherbury, Linda; Pazour, Gregory J.; Ware, Stephanie M.; Nakanishi, Toshio; Goldmuntz, Elizabeth; Tsang, Michael; Lo, Cecilia W.

    2016-01-01

    Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer’s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease

  12. DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

    Directory of Open Access Journals (Sweden)

    You Li

    2016-02-01

    Full Text Available Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD, a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer's vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an

  13. [Value of nasal nitric oxide in the diagnosis of primary ciliary dyskinesia].

    Science.gov (United States)

    Moreno Galdó, A; Vizmanos Lamotte, G; Reverte Bover, C; Gartner, S; Cobos Barroso, N; Rovira Amigo, S; Liñán Cortés, S; Lloreta Trull, J; Busquets Monge, R

    2010-08-01

    The aim of this study is to report nasal nitric oxide (nNO) values in children with primary ciliary dyskinesia (PCD) and to compare them with nNO values in healthy children, asthmatic children, children with cystic fibrosis and children with post infectious bronchiectasis. We determined nNO values in 9 children with PCD, 36 asthmatic children, 31 children with cystic fibrosis, 8 children with post infectious bronchiectasis and 37 healthy children. We compared nNO values between these different conditions and calculated sensitivity and specificity of nNO to diagnose PCD. All children with PCD - except one (nNO 348 ppb) - had nNO values below 112 ppb, mean 88 ppb (95%CI 9.6-166). The nNO mean was 898 ppb (95%CI 801-995) in healthy children, 1023 ppb (95%CI 911-1137) in asthmatic children, 438 ppb (95%CI 367-508) in cystic fibrosis children and 361 ppb (95%CI 252-470) in children with post infectious bronchiectasis. The mean concentration of nNO was lower (Pgroups. The measurement of nasal NO in our study population showed, at a cut-off level of ppb, a sensitivity of 88.9% and a specificity of 99.1% in the diagnosis of PCD [ROC 0.98 (95%CI 0.94-0.99); Pppb suggests the disease, although nNO above 112 ppb does not exclude PCD. 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Nasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis.

    Science.gov (United States)

    Collins, Samuel A; Gove, Kerry; Walker, Woolf; Lucas, Jane S A

    2014-12-01

    Nasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test. We conducted a systematic review of the literature to examine the utility of nNO in screening for PCD, in particular 1) different respiratory manoeuvres during sampling (velum closure, tidal breathing, etc.), 2) accuracy in screening young/uncooperative children, 3) stationary versus portable analysers, and 4) nNO in "atypical" PCD. 96 papers were assessed according to modified PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and 22 were included in this review. Meta-analysis of 11 studies comparing nNO during a velum closure breath hold gave a mean±SD nNO of 19.4±18.6 nL·min(-1) in PCD (n = 478) and 265.0±118.9 nL·min(-1) in healthy controls (n = 338). Weighted mean difference for PCD versus healthy controls was 231.1 nL·min(-1) (95% CI 193.3-268.9; n = 338) and 114.1 nL·min(-1) (95% CI 101.5-126.8; n = 415) for PCD versus cystic fibrosis. Five studies of nNO measurement during tidal breathing demonstrated that this is an acceptable manoeuvre in young children where velum closure is not possible, but the discriminatory value was reduced. Four small studies of portable NO analysers suggest these are reliable tools for screening for PCD. However, nNO must be interpreted alongside clinical suspicion. Future studies should focus on standardising sampling techniques and reporting.

  15. Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands

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    Maaike Cockx

    2017-09-01

    Full Text Available Primary ciliary dyskinesia (PCD, cystic fibrosis (CF, and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary damage in PCD might be aggravated by abnormal functioning neutrophils either as a primary consequence of the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic responses and chemoattractant receptor expression profiles of peripheral blood neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults. We stimulated peripheral blood monocytes from patients and healthy controls and measured CXCL8 and IL-1β production with ELISA. PCD neutrophils displayed reduced migration toward CXCR2 ligands (CXCL5 and CXCL8 in the shape change, microchamber and microslide chemotaxis assays, whereas leukotriene B4 and complement component 5a chemotactic responses were not significantly different. The reduced response to CXCL8 was observed in all subgroups of patients with PCD (displaying either normal ultrastructure, dynein abnormalities or central pair deficiencies and correlated with lung function. CXCR2 was downregulated in about 65% of the PCD patients, suggestive for additional mechanisms causing CXCR2 impairment. After treatment with the TLR ligands lipopolysaccharide and peptidoglycan, PCD monocytes produced more CXCL8 and IL-1β compared to controls. Moreover, PCD monocytes also responded stronger to IL-1β stimulation in terms of CXCL8 production. In conclusion, we revealed a potential link between CXCR2 and its ligand CXCL8 and the pathogenesis of PCD.

  16. CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia.

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    Amjad Horani

    Full Text Available BACKGROUND: Primary ciliary dyskinesia (PCD is a genetic disorder characterized by impaired ciliary function, leading to chronic sinopulmonary disease. The genetic causes of PCD are still evolving, while the diagnosis is often dependent on finding a ciliary ultrastructural abnormality and immotile cilia. Here we report a novel gene associated with PCD but without ciliary ultrastructural abnormalities evident by transmission electron microscopy, but with dyskinetic cilia beating. METHODS: Genetic linkage analysis was performed in a family with a PCD subject. Gene expression was studied in Chlamydomonas reinhardtii and human airway epithelial cells, using RNA assays and immunostaining. The phenotypic effects of candidate gene mutations were determined in primary culture human tracheobronchial epithelial cells transduced with gene targeted shRNA sequences. Video-microscopy was used to evaluate cilia motion. RESULTS: A single novel mutation in CCDC65, which created a termination codon at position 293, was identified in a subject with typical clinical features of PCD. CCDC65, an orthologue of the Chlamydomonas nexin-dynein regulatory complex protein DRC2, was localized to the cilia of normal nasal epithelial cells but was absent in those from the proband. CCDC65 expression was up-regulated during ciliogenesis in cultured airway epithelial cells, as was DRC2 in C. reinhardtii following deflagellation. Nasal epithelial cells from the affected individual and CCDC65-specific shRNA transduced normal airway epithelial cells had stiff and dyskinetic cilia beating patterns compared to control cells. Moreover, Gas8, a nexin-dynein regulatory complex component previously identified to associate with CCDC65, was absent in airway cells from the PCD subject and CCDC65-silenced cells. CONCLUSION: Mutation in CCDC65, a nexin-dynein regulatory complex member, resulted in a frameshift mutation and PCD. The affected individual had altered cilia beating patterns, and

  17. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

    Science.gov (United States)

    Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

    2016-12-01

    Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos(+) D2 MSNs and decreased c-Fos(+) non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off.

    Science.gov (United States)

    Rajput, Ali H; Fenton, Mark E; Di Paolo, Thérèse; Sitte, Harold; Pifl, Christian; Hornykiewicz, Oleh

    2004-06-01

    The objective of this study was to identify dopamine (DA) metabolism pattern in Lewy body Parkinson's disease (PD) patients with dyskinesia (Dysk) only, with wearing-off (WO) only, or no motor complications (NMC) induced by levodopa (LD). DA, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxytyramine (3-MT) were measured individual basal ganglia nuclei of nine PD patients who received LD for 6-18 years. Three patients had only Dysk, three only WO, and three had neither Dysk nor WO. Biochemical measurements in PD brains were compared with four non-neurological control brains from individuals matched for age and post-mortem retrieval time. DA levels in the PD were reduced in the caudate by 87% and putamen by 99%. In the caudates, the HVA/DA molar ratio as an index of DA metabolism was similar in the WO and the Dysk patients. However, in the putamen, the ratio of HVA/DA was significantly higher in the WO compared with the Dysk (p = 0.03)and the NMC (p = 0.04) groups of patients. In the putamen, the DOPAC levels were higher in the WO cases while in the Dysk cases, 3-MT levels were higher. The results suggest that in the WO only cases, the putaminal DA was in large measure metabolized intraneuronally while the DA metabolism in our Dysk only patients was mainly extraneuronal. We conclude that the magnitude and the site (intra vs. extraneuronal) of the synaptic DA metabolism in the putamen plays a significant role in LD-induced Dysk and WO.

  19. Cerebellum in levodopa-induced dyskinesias: the unusual suspect in the motor network

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    Asha eKishore

    2014-08-01

    Full Text Available The exact mechanisms that generate levodopa-induced dyskinesias (LID during chronic levodopa therapy for Parkinson’s disease (PD are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the corticostriatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1 as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1 which are crucial for the maintenance of this synergy are disrupted both during OFF and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the sub thalamic nucleus to the cerebellum and lock the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory

  20. Ciliary genes are down-regulated in bronchial tissue of primary ciliary dyskinesia patients.

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    Maciej Geremek

    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis and male infertility. The pulmonary phenotype in PCD is caused by the impaired motility of cilia in the respiratory epithelium, due to ultrastructural defects of these organelles. We hypothesized that defects of multi-protein ciliary complexes should be reflected by gene expression changes in the respiratory epithelium. We have previously found that large group of genes functionally related to cilia share highly correlated expression pattern in PCD bronchial tissue. Here we performed an explorative analysis of differential gene expression in the bronchial tissue from six PCD patients and nine non-PCD controls, using Illumina HumanRef-12 Whole Genome BeadChips. We observed 1323 genes with at least 2-fold difference in the mean expression level between the two groups (t-test p-value <0.05. Annotation analysis showed that the genes down-regulated in PCD biopsies (602 were significantly enriched for terms related to cilia, whereas the up-regulated genes (721 were significantly enriched for terms related to cell cycle and mitosis. We assembled a list of human genes predicted to encode ciliary proteins, components of outer dynein arms, inner dynein arms, radial spokes, and intraflagellar transport proteins. A significant down-regulation of the expression of genes from all the four groups was observed in PCD, compared to non-PCD biopsies. Our data suggest that a coordinated down-regulation of the ciliome genes plays an important role in the molecular pathomechanism of PCD.

  1. The Dyskinesia Impairment Scale: a new instrument to measure dystonia and choreoathetosis in dyskinetic cerebral palsy.

    Science.gov (United States)

    Monbaliu, Elegast; Ortibus, Els; De Cat, Jos; Dan, Bernard; Heyrman, Lieve; Prinzie, Peter; De Cock, Paul; Feys, Hilde

    2012-03-01

    The aim of this study was to examine the reliability and validity of the Dyskinesia Impairment Scale (DIS). The DIS consists of two subscales: dystonia and choreoathetosis. It measures both phenomena in dyskinetic cerebral palsy (CP). Twenty-five participants with dyskinetic CP (17 males; eight females; age range 5–22y; mean age 13y 6mo; SD 5y 4mo), recruited from special schools for children with motor disorders, were included. Exclusion criteria were changes in muscle relaxant medication within the previous 3 months, orthopaedic or neurosurgical interventions within the previous year, and spinal fusion. Interrater reliability was verified by two independent raters. For interrater reliability, intraclass correlation coefficients were assessed. Standard error of measurement, the minimal detectable difference, and Cronbach’s alpha for internal consistency were determined. For concurrent validity of the DIS dystonia subscale, the Barry–Albright Dystonia Scale was administered. The intraclass correlation coefficient for the total DIS score and the two subscales ranged between 0.91 and 0.98 for interrater reliability. The reliability of the choreoathetosis subscale was found to be higher than that of the dystonia subscale. The standard error of the measurement and minimal detectable difference values were adequate. Cronbach’s alpha values ranged from 0.89 to 0.93. Pearson’s correlation between the dystonia subscale and Barry–Albright Dystonia Scale was 0.84 (p<0.001). Good to excellent reliability and validity were found for the DIS. The DIS may be promising for increasing insights into the natural history of dyskinetic CP and evaluating interventions. Future research on the responsiveness of the DIS is warranted.

  2. [New approaches to diagnosing and treating hyperkinetic biliary dyskinesia associated with chronic acalculous cholecystitis].

    Science.gov (United States)

    Bartosh, L F; Balakina, I V; Gridneva, L M

    2004-01-01

    Ninety patients aged 21 to 56 years who had chronic non-calculous cholecystitis (CNCC) concurrent with hyperkinetic dyskinesia (HKD) detectable by a stepwise duodenal probing and sonography, by using a choleretic breakfast and by determining the relaxation coefficient (RC) that was equal to the ratio of the volume of the gallbladder (GB) after the use of a spasmolytic to the baseline GB volume. The patients were divided into 3 groups. The authors used as a spasmolytic agent pinaverium bromide (dicetel) in a dose of 50 mg (1 tablet) in Group 1), octylonium bromide (spasmomen) in a dose of 40 mg (1 dragee) in Group 2, and drotaverine (no-spa) in a dose of 40 mg (1 tablet). There was a more significant sonographic increase in the size of GB in Groups 1 and 2 as compared with Group 3. In the acute drug test and during long-term treatment as well, the highest spasmolytic effect was noted in patients receiving dicetel (Group 1) and spasmomen (Group 2) as compared with that in Group 3 patients taking drotaverine. With this, RC was 1.25 +/- 0.2, 1.6 +/- 0.15, and 1.08 +/- 0.1, respectively. No adverse reactions occurred in the patients having selective calcium blockers (SCBs) whereas the patients receiving no-spa were found to have the following side effects: dry mouth (n = 3), transient constipation (n = 1), and numb tongue (n = 1). Thus, the study has provided evidence for the fact that SCBs have some advantage over myotropic spasmolytic agents in the treatment of CNCC with the signs of HKD.

  3. PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine.

    Science.gov (United States)

    Gardiner, Alice R; Bhatia, Kailash P; Stamelou, Maria; Dale, Russell C; Kurian, Manju A; Schneider, Susanne A; Wali, G M; Counihan, Tim; Schapira, Anthony H; Spacey, Sian D; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A G; Raskin, Salmo; Sander, Josemir W; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M; Wood, Nicholas W; Hanna, Michael; Houlden, Henry

    2012-11-20

    The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders.

  4. Analysis of genetic variations in the RGS9 gene and antipsychotic-induced tardive dyskinesia in schizophrenia.

    Science.gov (United States)

    Liou, Ying-Jay; Chen, Mao-Liang; Wang, Ying-Chieh; Chen, Jen-Yeu; Liao, Ding-Lieh; Bai, Ya-Mei; Lin, Chao-Cheng; Chen, Tzu-Ting; Mo, Geng-Han; Lai, I-Ching

    2009-03-05

    Some patients treated chronically with antipsychotics develop tardive dyskinesia (TD), an abnormal involuntary movement disorder. Typical antipsychotics block D(2) dopamine receptors (D(2)DR) and produce D(2)DR supersensitivity. On contrary, regulators of G-protein signaling (RGS) can enhance the signal termination of G-protein-coupled D(2)DR. Besides, after prolonged inhibition of dopaminergic transmission, dopaminergic agonists induced severe dyskinesia only in RGS9 knock-out mice but not in normal mice. Therefore, variety in the human RGS9 gene may be related to susceptibility to TD. In this study, schizophrenic inpatients receiving long-term antipsychotic treatment were assessed using the Abnormal Involuntary Movement Scale twice over a 3-month interval. Only patients in whom abnormal involuntary movements were absent (non-TD group) and those who showed persistent TD (TD group) were enrolled. There were 407 patients in the study sample (TD = 252; non-TD = 155) and seven single nucleus polymorphisms (SNPs) in the RGS9 gene were genotyped for each subject. Genotype and allelic distributions of SNPs did not differ between the TD and non-TD groups in this study, with the exception that a weak trend of allelic association was seen with rs4790953 (P = 0.0399). In the haplotype analysis, a significant association of the AGG haplotype (rs8077696-rs8070231-rs2292593) of the RGS9 gene was found (permutation P = 0.007), and this is worthy of replication and further study.

  5. Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease

    NARCIS (Netherlands)

    Flamez, Anja; Cordenier, Ann; De Raedt, Sylvie; Michiels, Veronique; Smetcoren, Sara; Van Merhaegen-Wieleman, Annick; Parys, Eva; De Keyser, Jacques; Baeken, Chris

    2016-01-01

    Background: In late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS

  6. Missense polymorphisms in three oxidative-stress enzymes (GSTP1, SOD2, and GPX1) and dyskinesias in Russian psychiatric inpatients from Siberia

    NARCIS (Netherlands)

    Al Hadithy, A. F. Y.; Ivanova, S. A.; Pechlivanoglou, P.; Wilffert, B.; Semke, A.; Fedorenko, O.; Kornetova, E.; Ryadovaya, L.; Brouwers, J. R. B. J.; Loonen, A. J. M.

    2010-01-01

    Neuronal degeneration due to oxidative stress (OS) has been proposed as a mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms against OS may involve detoxification enzymes (e.g., glutathione peroxidase-1, GPX1; superoxide dismutase-2, SOD2 [also commonly known as MnSOD];

  7. Incidence of tardive dyskinesia and tardive dystonia in African Caribbean patients on long-term antipsychotic treatment : The Curacao Extrapyramidal Syndromes Study V

    NARCIS (Netherlands)

    van Harten, Peter N.; Hoek, Hans W.; Matroos, Glenn E.; van Os, Jim

    2006-01-01

    Objective: Tardive dyskinesia (TD) and tardive dystonia (TDt) syndromes represent severe side effects of first-generation antipsychotics (FGAs). Although second-generation antipsychotics (SGAs) confer a lower risk for tardive syndromes, many patients continue to use FGAs alone or in combination with

  8. Dyskinesia and Parkinsonism in Antipsychotic-Naive Patients With Schizophrenia, First-Degree Relatives and Healthy Controls : A Meta-analysis

    NARCIS (Netherlands)

    Koning, Jeroen P. F.; Tenback, Diederik E.; van Os, Jim; Aleman, Andre; Kahn, Rene S.; van Harten, Peter N.

    2010-01-01

    Background: Several studies have reported the presence of dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia as well as in their first-degree relatives. These movement disorders may therefore form an integral part of the illness and its (genetic) liability. Method: A syst

  9. Test-retest reliability of UPDRS-III, dyskinesia scales, and timed motor tests in patients with advanced Parkinson's disease: an argument against multiple baseline assessments.

    Science.gov (United States)

    Metman, Leo Verhagen; Myre, Brian; Verwey, Niek; Hassin-Baer, Sharon; Arzbaecher, Jean; Sierens, Diane; Bakay, Roy

    2004-09-01

    The primary objective of this study was to assess the intra-rater reliability of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) in patients with advanced Parkinson's disease (PD). The secondary objective was to assess the intra-rater reliability of standard timed motor tests and dyskinesia scales to determine the necessity of multiple baseline core evaluations before surgery for PD. We carried out two standardized preoperative core evaluations of patients with advanced PD scheduled to undergo deep brain stimulation. Patients were examined in the defined off and on conditions by the same rater. UPDRS-III, timed tests, and dyskinesia scores from the two evaluations were compared using Wilcoxon Signed Ranks tests and intraclass correlation coefficients (ICC). Differences in UPDRS-III scores for the two visits were clinically and statistically nonsignificant, and the ICC was 0.9. Similarly, there were no significant differences in timed motor tests or dyskinesia scores, with a median ICC of 0.8. The results indicate that previous findings of high test-retest reliability of UPDRS-III in early untreated PD patients can now be extended to those with advanced disease complicated by motor fluctuations. In addition, test-retest reliability of dyskinesia scales and timed motor tests was high. Taken together, these findings challenge the need for multiple baseline assessments as currently stipulated in core assessment protocols for surgical intervention in PD.

  10. A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression

    DEFF Research Database (Denmark)

    Feyder, Michael; Södersten, Erik; Santini, Emanuela

    2014-01-01

    BACKGROUND: Abnormal regulation of extracellular signal-regulated kinases 1 and 2 has been implicated in 3,4-dihydroxy-l-phenylalanine (L-DOPA)-induced dyskinesia (LID), a motor complication affecting Parkinson's disease patients subjected to standard pharmacotherapy. We examined the involvement ...

  11. Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

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    Anna Ljungdahl

    Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

  12. Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study

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    Papon Jean-François

    2012-10-01

    Full Text Available Abstract Background Primary ciliary dyskinesia (PCD is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded. Methods Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the “gold standard” used to establish the diagnosis of PCD. Results This “gold standard” excluded PCD in 15 patients (non-PCD patients, confirmed PCD in 10 patients (PCD patients and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the “gold standard”, while the qualitative evaluation was discordant with the “gold standard” in 3/10 cases. Among the patients with an inconclusive “gold standard”, the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease

  13. Aerobic fitness in children and young adults with primary ciliary dyskinesia.

    Directory of Open Access Journals (Sweden)

    Astrid Madsen

    Full Text Available BACKGROUND: Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2peak in a large well-characterized cohort of PCD patients, and explored whether VO2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level. METHODS: VO2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N2 MBW were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference. RESULTS: Forty-four PCD patients aged 6-29 years exhibited reduced VO2peak compared to healthy controls (P<0.001 and the national reference. VO2peak was abnormal (z-score <-1.96 in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal, but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001, exhibited by 39% of PCD patients. CONCLUSION: One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD

  14. Can the Dyskinesia Impairment Scale be used by inexperienced raters? A reliability study.

    Science.gov (United States)

    Monbaliu, Elegast; Ortibus, Els; Prinzie, Peter; Dan, Bernard; De Cat, Josse; De Cock, Paul; Feys, Hilde

    2013-05-01

    The Dyskinesia Impairment Scale (DIS) is a new scale for measuring dystonia and choreoathetosis in dyskinetic Cerebral Palsy (CP). Previously, reliability of this scale has only been assessed for raters highly experienced in discriminating between dystonia and choreoathetosis. The aims of this study are to examine the reliability of the DIS used by inexperienced raters, new to discriminating between dystonia and choreoathetosis and to determine the effect of clinical expertise on reliability. Twenty-five patients (17 males; 8 females; age range 5-22 years; mean age = 13 years 6 months; SD = 5 years 4 months) with dyskinetic CP were filmed with the DIS standard video protocol. Two junior physiotherapists (PTs) and three senior PTs, all of whom were new to discriminating between dystonia and choreoathetosis, were trained in scoring the DIS. Afterward, they independently scored all patients from the video recordings using the DIS. Reliability was assessed by (1) Intraclass Correlation Coefficient (ICC), (2) Standard Error of Measurement (SEM) and Minimal Detectable Difference (MDD) and (3) Cronbach's alpha for internal consistency. Interrater reliability for the total DIS, and for the dystonia and choreoathetosis subscales was good for the junior PTs and moderately high to excellent for the senior PTs. SEM and MDD values for the total DIS were 6% and 15% respectively for the junior PTs and 4% and 12% respectively for the senior PTs. Cronbach's alpha ranged between 0.87 and 0.95 for the junior PTs and between 0.76 and 0.93 for the senior PTs. Reliability of the DIS scores for the inexperienced junior and senior PTs was sufficient in comparison with scores from the experienced raters in the previous study, indicating that the DIS can be used by inexperienced PTs new to discriminating between dystonia and choreoathetosis, and also that its reliability is not dependent on clinical expertise. However, based on the measurement errors and questionnaire data, familiarity

  15. Excessive sensitivity to uncertain visual input in L-dopa induced dyskinesias in Parkinson’s disease: further implications for cerebellar involvement

    Directory of Open Access Journals (Sweden)

    James eStevenson

    2014-02-01

    Full Text Available When faced with visual uncertainty during motor performance, humans rely more on predictive forward models and proprioception and attribute lesser importance to the ambiguous visual feedback. Though disrupted predictive control is typical of patients with cerebellar disease, sensorimotor deficits associated with the involuntary and often unconscious nature of L-dopa-induced dyskinesias in Parkinson’s disease (PD suggests dyskinetic subjects may also demonstrate impaired predictive motor control. Methods: We investigated the motor performance of 9 dyskinetic and 10 non-dyskinetic PD subjects on and off L-dopa, and of 10 age-matched control subjects, during a large-amplitude, overlearned, visually-guided tracking task. Ambiguous visual feedback was introduced by adding ‘jitter’ to a moving target that followed a Lissajous pattern. Root mean square (RMS tracking error was calculated, and ANOVA, robust multivariate linear regression and linear dynamical system analyses were used to determine the contribution of speed and ambiguity to tracking performance. Results: Increasing target ambiguity and speed contributed significantly more to the RMS error of dyskinetic subjects off medication. L-dopa improved the RMS tracking performance of both PD groups. At higher speeds, controls and PDs without dyskinesia were able to effectively de-weight ambiguous visual information. Conclusions: PDs’ visually-guided motor performance degrades with visual jitter and speed of movement to a greater degree compared to age-matched controls. However, there are fundamental differences in PDs with and without dyskinesia: subjects without dyskinesia are generally slow, and less responsive to dynamic changes in motor task requirements but, PDs with dyskinesia there was a trade-off between overall performance and inappropriate reliance on ambiguous visual feedback. This is likely associated with functional changes in posterior parietal-ponto-cerebellar pathways.

  16. High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations.

    Science.gov (United States)

    Shoemark, Amelia; Moya, Eduardo; Hirst, Robert A; Patel, Mitali P; Robson, Evelyn A; Hayward, Jane; Scully, Juliet; Fassad, Mahmoud R; Lamb, William; Schmidts, Miriam; Dixon, Mellisa; Patel-King, Ramila S; Rogers, Andrew V; Rutman, Andrew; Jackson, Claire L; Goggin, Patricia; Rubbo, Bruna; Ollosson, Sarah; Carr, Siobhán; Walker, Woolf; Adler, Beryl; Loebinger, Michael R; Wilson, Robert; Bush, Andrew; Williams, Hywel; Boustred, Christopher; Jenkins, Lucy; Sheridan, Eamonn; Chung, Eddie M K; Watson, Christopher M; Cullup, Thomas; Lucas, Jane S; Kenia, Priti; O'Callaghan, Christopher; King, Stephen M; Hogg, Claire; Mitchison, Hannah M

    2017-08-08

    Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal. To determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive. Next-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay. Sixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed. The CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model.

    Science.gov (United States)

    Tronci, Elisabetta; Lisci, Carlo; Stancampiano, Roberto; Fidalgo, Camino; Collu, Maria; Devoto, Paola; Carta, Manolo

    2013-12-01

    The serotonin system has recently emerged as an important player in the appearance of L-DOPA-induced dyskinesia (LID) in experimental models of Parkinson's disease, as it provides an unregulated source of L-DOPA-derived dopamine release in the dopamine-depleted striatum. Accordingly, toxin lesion or pharmacological silencing of serotonin neurons suppressed LID in the rat and monkey models of Parkinson's disease. However, 5-HT1 receptor agonists were also found to partially reduce the therapeutic effect of L-DOPA. In this study, we evaluated whether enhancement of the serotonin tone induced by the administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) could affect induction and expression of LID, as well as the therapeutic effect of L-DOPA, in 6-OHDA-lesioned rats. Drug naïve and L-DOPA-primed 6-OHDA-lesioned rats were chronically treated with a daily injection of L-DOPA (6 mg/kg plus benserazide, s.c.) alone, or in combination with 5-HTP (24-48 mg/kg, i.p.). The abnormal involuntary movements (AIMs) test, as well as the stepping and the motor activity tests, were performed during the chronic treatments. Results showed that 5-HTP reduced the appearance of LID of about 50% at both tested doses. A partial reduction of the therapeutic effect of L-DOPA was seen with the higher but not with the lower dose of 5-HTP. 5-HTP 24 mg/kg was also able to reduce the expression of dyskinesia in L-DOPA-primed dyskinetic rats, to a similar extent than in L-DOPA-primed rats. Importantly, the antidyskinetic effect of 5-HTP 24 mg/kg does not appear to be due to a competition with L-DOPA for crossing the blood-brain barrier; in fact, similar L-DOPA striatal levels were found in L-DOPA only and L-DOPA plus 5-HTP 24 mg/kg treated animals. These data further confirm the involvement of the serotonin system in the appearance of LID, and suggest that 5-HTP may be useful to counteract the appearance of dyskinesia in Parkinson's disease patients.

  18. Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Kobbernagel, Helene E; Buchvald, Frederik F; Haarman, Eric G

    2016-01-01

    BACKGROUND: Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chr...

  19. Cerebrospinal fluid levels of catecholamine metabolites in Parkinson’s disease and L-DOPA-induced dyskinesia

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;

    Levodopa (L-DOPA) is effective in the symptomatic treatment of Parkinson’s disease (PD), but chronic use is associated with L-DOPA-induced dyskinesia (LID). In the 6-hydroxydopamine rat model of PD, L-DOPA treatment increases dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC...... fasting and 1 hour after intake of medication. Results and conclusion: PD patients receiving levodopa had 10-20 fold higher L-DOPA levels and about 100 fold higher levels of 3-OMD than age-matched controls or PD not receiving L-DOPA. DOPAC levels were not different among controls and subgroups of PD. HVA...... levels were significantly lower in non-DOPA-treated PD. Ratios of DOPAC/DOPA or HVA/DOPA were much lower in levodopa-treated patients, not distinguishing dyskinetic (N=6) from non-dyskinetic PD patients (N=5). More patients need to be included. Tryptophan/kynurenine metabolites will be analysed using LC...

  20. Paroxysmal non-kinesigenic dyskinesia caused by the mutation of MR-1 in a large Polish kindred.

    Science.gov (United States)

    Friedman, Andrzej; Zakrzewska-Pniewska, Beata; Domitrz, Izabela; Lee, Hsien-Yang; Ptacek, Louis; Kwiecinski, Hubert

    2009-01-01

    Paroxysmal non-kinesigenic dyskinesia (PNKD) is a clinical syndrome of sudden involuntary movements, mostly of dystonic type, which may be triggered by alcohol or coffee intake, stress and fatigue. The attacks of PNKD may consist of various combinations of dystonia, chorea, athetosis and balism. They can be partial and unilateral, but mostly the hyperkinetic movements are bilateral and generalized. We present a large Polish family with 7 symptomatic members of the family in 6 generations. In all affected persons, the onset of clinical symptoms was in early childhood. All male cases showed an increase in severity and frequency of the attacks with ageing, while the only living female patient noticed an improvement of PNKD during both her pregnancies and also after menopause. In addition, at the age of 55 years, she developed symptoms of Parkinson's disease with good response to levodopa treatment. 2008 S. Karger AG, Basel.

  1. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G;

    2014-01-01

    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  2. Clinical value of measurement of pulmonary radioaerosol mucociliary clearance in the work up of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Nielsen, Kim Gjerum; Mortensen, Jann

    2015-01-01

    BACKGROUND: We aimed to evaluate and define the general clinical applicability and impact of pulmonary radioaerosol mucociliary clearance (PRMC) on the work up of patients suspected of having primary ciliary dyskinesia (PCD). In addition, we wanted to evaluate the accuracy of the reference values...... primarily to results from nasal ciliary function testing, to electron microscopic (EM) examination of the ultrastructure of the cilia, and to the final clinical diagnosis. RESULTS: Of the 239 patients, 27 ended up with a final clinical diagnosis of definitive PCD. No patients with a PRMC test...... that was normal or otherwise not consistent with PCD ended up with PCD as final clinical diagnosis (though a minority of patients in this group ended up unresolved in regard to PCD). Forty percent of patients with an abnormal PRMC test ended up with PCD as final clinical diagnosis. Furthermore, the PRMC test had...

  3. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats

    Directory of Open Access Journals (Sweden)

    Yang X

    2012-04-01

    Full Text Available Xinxin Yang1*, Ruiyuan Zheng2*, Yunpeng Cai2, Meiling Liao2, Weien Yuan1,2, Zhenguo Liu11Department of Neurology, Xinhua Hospital (affiliated to Shanghai Jiaotong University School of Medicine, 2School of Pharmacy, Shanghai Jiaotong University, Shanghai, People's Republic of China*Xinxin Yang and Ruiyuan Zheng contributed equally to this workBackground: Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood.Methods: In this study, we prepared levodopa methyl ester (LDME/benserazide-loaded nanoparticles, which can release LDME and benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus benserazide or the same dose of LDME/benserazide-loaded nanoparticles. Apomorphine-induced rotations and abnormal involuntary movements (AIMs were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay.Results: Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20

  4. [The role of biliary dyskinesia in the mechanism of the damage to the protective properties of the mucosal barrier in peptic ulcer].

    Science.gov (United States)

    Oparin, A G; Demerchian, T I; Korenovskiĭ, I P; Chonka, V Iu; Iakovenko, E L; Pandeĭ, I

    1993-01-01

    Mucous barrier resistance was studied in 232 duodenal ulcer patients with signs of exacerbation as shown by PAS-positive substances and acid mucopolysaccharides in antral mucosa of the stomach and duodenum as well as by gastric juice levels of gastromucoproteins, fucose and sialic acids. In addition, measurements were performed of biliary motility. The tests indicated that half of the ulcer patients developed biliary dyskinesia manifesting as hyperkinesia or hypokinesia. The resultant decrease in gastric mucins requires individual correction.

  5. Evaluation of residual functional lung volume on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy in primary ciliary dyskinesia (Kartagener syndrome).

    Science.gov (United States)

    Chen, Yu-Wen; Chang, Chin-Chuan; Lai, Yung-Chuang; Lu, Chia-Ying; Dai, Zen-Kong

    2008-12-01

    Kartagener syndrome is diagnosed as sinusitis, bronchitis (bronchiectasis), and situs inversus by the clinical features. It is a subclass of primary ciliary dyskinesia (PCD) disease. A 12-year-old girl who had frequent upper and lower airway infections since birth, which was confirmed as Kartagener syndrome by HRCT imaging. We present the residual functional lung volume and mucociliary clearance findings seen on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy.

  6. Mutation Analysis of MR-1, SLC2A1, and CLCN1 in 28 PRRT2-negative Paroxysmal Kinesigenic Dyskinesia Patients

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Wang; Hong-Fu Li; Gong-Lu Liu; Xiao-Dan Wen; Zhi-Ying Wu

    2016-01-01

    Background:Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene.The majority of familial PKD was identified to harbor PRRT2 mutations.However,over two-third of sporadic PKD patients did not carry anyPRRT2 mutation,suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.Methods:A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited.Clinical features were evaluated,and all subjects were screened for MR-1,SLC2A1,and CLCN1 genes,which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD),paroxysmal exertion-induced dyskinesia,and myotonia congenita (MC),respectively.In addition,200 genetically matched healthy individuals were recruited as controls.Results:A total of 16 genetic variants including 4 in MR-1 gene,8 in SLC2A1 gene,and 4 in CLCN1 gene were detected.Among them,SLC2A1 c.363G>A mutation was detected in one case,and CLCN1 c.1205C>T mutation was detected in other two cases.Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database.Both mutations were predicted to be pathogenic by SIFT and PolyPhen2.The SLC2A1 c.363G>A mutation was novel.Conclusions:The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC.For those PRRT2-negative PKD cases,screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.

  7. Abnormal expression of connexin 36 plays a role in the pathogenesis of levodopa induced dyskinesia in rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    高冕

    2014-01-01

    Objective To expore whether gap junction disturbances are involved in the pathogenesis of levodopa-induced dyskinesia(LID).Methods The hemi-parkinsonian(PD)rat was treated intraperitoneally with L-dopa methylester(20 mg/kg)and benserazid(10 mg/kg)for21 days and abnormal involuntary movement was evaluated to establish LID rat model.The experimental animals were divided into three groups:LID group,PD group

  8. Rehabilitative treatment of drugs-related tardive dyskinesia%药物性迟发性运动障碍的康复治疗

    Institute of Scientific and Technical Information of China (English)

    孙敬烈; 王爱华; 白雪光; 罗小年

    2002-01-01

    Background: Long-term use of antipsychotic may cause tardive dyskinesia in patients with mental disease.Many researchers once managed the condition with drugs but the therapeutic effect is unsatisfying.From February 1999 to February 2001,patients with clinically defined mental disease were managed with large-dose phenergan for 3 months.AIMS was used to evaluate the patients before and after treatment.Results showed therapeutic effect was satisfying.

  9. Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: reduced synthesis or increased catabolism?

    Science.gov (United States)

    Sancesario, Giuseppe; Morrone, Luigi Antonio; D'Angelo, Vincenza; Castelli, Valentina; Ferrazzoli, Davide; Sica, Francesco; Martorana, Alessandro; Sorge, Roberto; Cavaliere, Federica; Bernardi, Giorgio; Giorgi, Mauro

    2014-12-01

    Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of levodopa/dopamine stimulated cAMP and cGMP levels, and/or with changes of their catabolism by phosphodiesterase activity in rats with experimental hemiparkinsonism. Microdialysis and tissue homogenates of the striatal tissues demonstrated that extracellular and intracellular cAMP/cGMP levels were lower in dyskinetic animals during the increasing phase of dyskinesias compared to eukinetic animals, but cAMP/cGMP levels increased in dyskinetic animals during the phase of decreasing and extinction of dyskinesias. Dyskinesias and the abnormal lowering of striatal cGMP and cAMP after levodopa were prevented by pretreatment with the multipotent drug amantadine, outlining the inverse relationship of cAMP/cGMP to dyskinesias. Moreover, dyskinetic animals showed higher striatal hydrolyzing cGMP-phosphodiesterase but not hydrolyzing cAMP-phosphodiesterase activity, suggesting that low cGMP but not cAMP levels could be due to increased catabolism. However, expressions of isozyme phosphodiesterase-1B and -10A highly and specifically located in the basal ganglia were not changed after levodopa in dyskinetic and eukinetic animals: accordingly, selective inhibitors of phosphodiesterase-1B and -10A were ineffective on levodopa dyskinesias. Therefore, the isozyme(s) expressing higher cGMP-phosphodiesterase activity in the striatum of dyskinetic animal should be determined. These observations suggest that dopamine-mediated processes of synthesis and/or degradation of cAMP/cGMP could be acutely impaired in levodopa dyskinesias, opening new ways to understanding physiopathology and treatment.

  10. Intrastriatal injections of KN-93 ameliorates levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Yang X

    2013-08-01

    Full Text Available Xinxin Yang, Na Wu, Lu Song, Zhenguo Liu Department of Neurology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Background: Levodopa remains the most effective drug for the treatment of Parkinson’s disease (PD. However, long-term levodopa treatment is associated with the emergence of levodopa-induced dyskinesia (LID, which has hampered its use for PD treatment. The mechanisms of LID are only partially understood. A previous study showed that KN-93, a Ca2+/calmodulin-dependent protein kinase II (CaMKII inhibitor, could be used to ameliorate LID in rats. However, the precise mechanisms by which KN-93 acts as an antidyskinetic are not fully understood. Methods: In the present study, a rat model of PD was induced by 6-hydroxydopamine (OHDA injections. Then, the successfully lesioned rats were intrastriatally administered with a different dose of KN-93 (1 µg, 2 µg, or 5 µg prior to levodopa treatment. Abnormal involuntary movements (AIMs scores and apomorphine-induced rotations were measured in PD rats. Phosphorylated levels of GluR1 at Serine-845 (pGluR1S845 levels were determined by western blot. Arc and Penk levels were measured by real-time polymerase chain reaction (PCR. Results: We found that both 2 µg and 5 µg KN-93 treatment lowered AIMs scores in levodopa priming PD rats without affecting the antiparkinsonian effect of levodopa. In agreement with behavioral analysis, KN-93 treatment (2 µg reduced pGluR1S845 levels in PD rats. Moreover, KN-93 treatment (2 µg reduced the expression of Gad1 and Nur77 in PD rats. Conclusion: These data indicated that intrastriatal injections of KN-93 were beneficial in reducing the expression of LID by lowering the expression of pGluR1S845 via suppressing the activation of CaMKII in PD rats. Decreased expression of pGluR1S845 further reduced the expression of Gad1 and Nur77 in PD rats. Keywords: Parkinson’s disease, levodopa

  11. Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    Yan FU; Chang-he FAN; He-huang DENG; San-hong HU; De-peng LV; Li-hua LI; Jun-jie WANG; Xin-qiao LU

    2006-01-01

    Aim:To investigate the possible association of the CYP2D6 gene C100T polymorphism and the CYP1A2 gene C163A polymorphism with tardive dyskinesia (TD) in Chinese patients with schizophrenia.Methods:The recruited schizophrenic patients were assessed with the Abnormal Involuntary Movement Scale (AIMS),and divided into groups with TD(n=91)and without TD(n=91)according to the AIMS score.Polymorphisms of the CYP2D6 and CYP1A2 genes were determined by polymerase chain reaction(PER)-restriction fragment length polymorphism(RFLP).Results:No allele frequencies deviated from Hardy-Weinberg equilibrium.No significant differences in genotypes frequencies of the CYP2D C100T polymorphism were observed between patients with TD and without TD (x2=4.078,P>0.05),but patients with TD had a significant excess of the T allele compared with those without TD(x2=4.28,P<0.05).Moreover,the frequency of the CYP1A2 C allele in patients with TD was significantly higher than that in those without TD(x2=6.38,P<0.05).An association between TD and the CyP2D6 100T and CYP1A2 163C alleles was observed.Additionally,there were no differences in the mean AIMS scores among different genotypes in TD patients as a group or in smokers.The results of logistic regression anatysls demonstrated that mean age and duration of illness were risk factors for TD,but not sex,cumulative exposure to neuroleptic drugs in years,CYP2D6 or CYP1A2 genotype.Conclusion:The C100T polymorphism of the CYP2D6 gene and the C163A polymorphism of the CYP1A2 gene may be associated with neuroleptic drug-induced tardive dyskinesia in Chinese patients with schizophrenia.However,genetic factors have a weaker association with susceptibility to TD compared with mean age and duration of illness.

  12. Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio).

    Science.gov (United States)

    Stocchi, Fabrizio; Marconi, Stefano

    2010-07-01

    Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra. Of unknown etiology, Parkinson disease is characterized by 4 cardinal symptoms: tremor at rest, bradykinesia, postural instability, and rigidity. The current criterion-standard drug used in the management of parkinsonian symptoms is levodopa (l-dopa). However, long-term l-dopa therapy is associated with the development of motor complications; approximately 50% to 80% of patients will develop motor complications within 5 to 10 years of l-dopa treatment initiation. Motor complications can be divided into motor fluctuations, caused largely through pulsatile dopamine stimulation and low l-dopa concentrations, and dyskinesia, associated more often with peak l-dopa concentrations. Ultimately, the main goal was to provide steady l-dopa concentrations, without peaks and troughs. Empirical investigations using parenteral infusions of l-dopa and highly soluble l-dopa prodrugs have shown that there is benefit in ameliorating the peaks and troughs associated with traditional oral l-dopa formulations. Recently, the development of highly soluble oral l-dopa prodrugs has facilitated rapid, regular, and reliable l-dopa availability. This review evaluates some of the pharmacologic strategies in the management of motor complications in Parkinson disease and therapy optimization, with a focus on the use of CHF 1512 (Sirio), a combination of melevodopa (l-dopa methylester, a highly soluble prodrug of l-dopa) plus carbidopa in an effervescent tablet formulation.

  13. Polymorphisms of Dopamine Receptor Genes and Risk of L-Dopa–Induced Dyskinesia in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Cristoforo Comi

    2017-01-01

    Full Text Available L-dopa–induced dyskinesia (LID is a frequent motor complication of Parkinson’s disease (PD, associated with a negative prognosis. Previous studies showed an association between dopamine receptor (DR gene (DR variants and LID, the results of which have not been confirmed. The present study is aimed to determine whether genetic differences of DR are associated with LID in a small but well-characterized cohort of PD patients. To this end we enrolled 100 PD subjects, 50 with and 50 without LID, matched for age, gender, disease duration and dopaminergic medication in a case-control study. We conducted polymerase chain reaction for single nucleotide polymorphisms (SNP in both D1-like (DRD1A48G; DRD1C62T and DRD5T798C and D2-like DR (DRD2G2137A, DRD2C957T, DRD3G25A, DRD3G712C, DRD4C616G and DRD4nR VNTR 48bp analyzed genomic DNA. Our results showed that PD patients carrying allele A at DRD3G3127A had an increased risk of LID (OR 4.9; 95% CI 1.7–13.9; p = 0.004. The present findings may provide valuable information for personalizing pharmacological therapy in PD patients.

  14. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

    Science.gov (United States)

    Olcese, Chiara; Patel, Mitali P.; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J.; Vaughan, Cara K.; Hayward, Jane; Goldenberg, Alice; Emes, Richard D.; Munye, Mustafa M.; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean- François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R.; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M. K.; Antonarakis, Stylianos E.; Loebinger, Michael R.; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Beales, Philip L.; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Allan, Daly; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; McCarthy, Shane; Muddyman, Dawn; Muntoni, Francesco; Parker, Victoria; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter J.; Schmidts, Miriam; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M.

    2017-01-01

    By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins. PMID:28176794

  15. Progress in Study on Tardive Dyskinesia%迟发性运动障碍的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 孙宇新; 于相芬

    2016-01-01

    迟发性运动障碍(Tardive dyskinesia,TD)是一组由多巴胺(DA)受体阻滞剂引起的迟发的医源性运动障碍,部分病例在运动障碍的基础上伴发感觉症状,如感觉异常、疼痛等。本文对TD的概念由来、病因学、发生率、危险因素、病理生理机制、临床表现、诊断、鉴别诊断、治疗及预防等作一综述。%Tardive dyskinesia(TD)is a group of delayed-onset iatrogenic movement disorders of various phenomenology caused by dopamine receptor-blocking agents. In some cases,the movement disorder may be accompanied by sensory phenomenon such as paresthesias and pain. This paper reviews the origin of concept,etiology, incidence,risk factors,pathological and physiological mechanisms,clinical manifestations,diagnosis,differential diagnosis,prevention and treatment of TD.

  16. Lipoic acid and haloperidol-induced vacuous chewing movements: Implications for prophylactic antioxidant use in tardive dyskinesia.

    Science.gov (United States)

    Lister, Joshua; Andreazza, Ana C; Navaid, Bushra; Wilson, Virginia S; Teo, Celine; Nesarajah, Yasika; Wilson, Alan A; Nobrega, José N; Fletcher, Paul J; Remington, Gary

    2017-01-04

    Tardive dyskinesia (TD), a potentially irreversible antipsychotic (AP)-related movement disorder, is a risk with all currently available antipsychotics. AP-induced vacuous chewing movements (VCMs) in rats, a preclinical model of TD, can be attenuated by antioxidant-based treatments although there is a shortage of well-designed studies. Lipoic acid (LA) represents a candidate antioxidant for the treatment of oxidative stress-related nervous system disorders; accordingly, its effects on AP-induced VCMs and striatal oxidative stress were examined. Rats treated with haloperidol decanoate (HAL; 21mg/kg every 3weeks, IM) for 12weeks were concurrently treated with LA (10 or 20mg/kg, PO). VCMs were assessed weekly by a blinded rater, and locomotor activity was evaluated as were striatal lipid peroxidation markers and serum HAL levels. VCMs were decreased by the lower dose (nonsignificant), whereas a significant increase was recorded with the higher dose of LA. HAL decreased locomotor activity and this was unaffected by LA. Striatal malondialdehyde (MDA) levels in HAL-treated rats were reduced by both LA doses, while 4-hydroxynonenal (4-HNE) levels were predictive of final VCM scores (averaged across weeks 10-12). Study limitations include differences between antipsychotics in terms of oxidative stress, LA dosing, choice of biomarkers for lipid peroxidation, and generalizability to TD in humans. Collectively, current preclinical evidence does not support a "protective" role for antioxidants in preventing TD or its progression, although clinical evidence offers limited evidence supporting such an approach.

  17. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome).

    Science.gov (United States)

    Guichard, C; Harricane, M C; Lafitte, J J; Godard, P; Zaegel, M; Tack, V; Lalau, G; Bouvagnet, P

    2001-04-01

    Kartagener syndrome (KS) is a trilogy of symptoms (nasal polyps, bronchiectasis, and situs inversus totalis) that is associated with ultrastructural anomalies of cilia of epithelial cells covering the upper and lower respiratory tracts and spermatozoa flagellae. The axonemal dynein intermediate-chain gene 1 (DNAI1), which has been demonstrated to be responsible for a case of primary ciliary dyskinesia (PCD) without situs inversus, was screened for mutation in a series of 34 patients with KS. We identified compound heterozygous DNAI1 gene defects in three independent patients and in two of their siblings who presented with PCD and situs solitus (i.e., normal position of inner organs). Strikingly, these five patients share one mutant allele (splice defect), which is identical to one of the mutant DNAI1 alleles found in the patient with PCD, reported elsewhere. Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS).

  18. The role of nerve growth factor inducible protein B in the pathogenesis of levodopa-induced dyskinesias

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the role of the expression of nerve growth factor inducible protein B gene (NGFI-B) in striatum in the pathogenesis of levodopa-induced dyskinesias (LID). Methods: The rat model of LID was treated with SCH 23390( 1 mg/kg ip,a dopamine D1 antagonist) and haloperidol (1 mg/kg ip, a dopamine D2 antagonist) respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the expression of NGFI-B mRNA in striatum and the behavior changes were observed. Results: After treatment with SCH23390, abnormal involuntary movement (AIM) in LID rats was decreased ( P <0.05) and the expression of NGFI-B mRNA in striatum did not change significantly. After treatment with haloperidol, the changes of AIM in LID rats were not significant and the expression of NGFI-B mRNA was increased significantly( P < 0.01). Conclusion: LID is associated with over-expression of NGFI-B in striatum. Abnormal activity in the direct pathway and the basal ganglia circuit could be involved in the occurrence of LID.

  19. Prolonged consumption of trans fat favors the development of orofacial dyskinesia and anxiety-like symptoms in older rats.

    Science.gov (United States)

    Pase, Camila Simonetti; Teixeira, Angélica Martelli; Dias, Verônica Tironi; Quatrin, Andréia; Emanuelli, Tatiana; Bürger, Marilise Escobar

    2014-09-01

    Polyunsaturated fatty acids (FAs) are cell membrane components involved in brain functions. We hypothesized that long-term trans fat consumption is able to modify the membrane FAs composition impairing behavioral parameters related to aging. In this study, a comparison of behavioral parameters at 10 and 15 months of trans fat consumption by male Wistar rats was made. Animals were fed for 10 and 15 months from weaning with diets containing either 20% w/w soybean oil (SO), rich in n-6 PUFA, hydrogenated vegetable fat (HVF), rich in trans FAs, or a standard diet (control - C). At both evaluation times, HVF-fed rats showed progressively increased parameters of orofacial dyskinesia, fear and anxiety-like symptoms. The HVF diet reduced locomotor and exploratory activities progressively over 10 and 15 months of supplementation, while the standard and SO diets did not. In this study, we showed that chronic trans FAs consumption from weaning is able to favor the development of neuromotor and neuropsychiatric diseases, whose intensity was time dependent.

  20. Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia

    Science.gov (United States)

    Fieblinger, Tim; Graves, Steven M.; Sebel, Luke E.; Alcacer, Cristina; Plotkin, Joshua L.; Gertler, Tracy S.; Chan, C. Savio; Heiman, Myriam; Greengard, Paul; Cenci, M. Angela; Surmeier, D. James

    2015-01-01

    Summary The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses. PMID:25360704

  1. DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor.

    Science.gov (United States)

    Aldrin-Kirk, Patrick; Heuer, Andreas; Wang, Gang; Mattsson, Bengt; Lundblad, Martin; Parmar, Malin; Björklund, Tomas

    2016-06-01

    Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.

  2. L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia

    Science.gov (United States)

    Suarez, Luz M; Solis, Oscar; Aguado, Carolina; Lujan, Rafael; Moratalla, Rosario

    2016-01-01

    Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. PMID:27613437

  3. L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2 Striatal Projection Neurons in Dyskinesia.

    Science.gov (United States)

    Suarez, Luz M; Solis, Oscar; Aguado, Carolina; Lujan, Rafael; Moratalla, Rosario

    2016-10-17

    Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. © The Author 2016. Published by Oxford University Press.

  4. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Moore, Daniel J; Onoufriadis, Alexandros; Shoemark, Amelia

    2013-01-01

    Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger...... resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia...

  5. Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome.

    Science.gov (United States)

    Weber, Axel; Köhler, Angelika; Hahn, Andreas; Neubauer, Bernd; Müller, Ulrich

    2013-11-01

    Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes.

  6. A case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorder.

    LENUS (Irish Health Repository)

    Casey, Jillian P

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterised by abnormal ciliary motion and impaired mucociliary clearance, leading to recurrent respiratory infections, sinusitis, otitis media and male infertility. Some patients also have laterality defects. We recently reported the identification of three disease-causing PCD genes in the Irish Traveller population; RSPH4A, DYX1C1 and CCNO. We have since assessed an additional Irish Traveller family with a complex phenotype involving PCD who did not have any of the previously identified PCD mutations.

  7. Infantile convulsions with paroxysmal dyskinesia (ICCA syndrome and copy number variation at human chromosome 16p11.

    Directory of Open Access Journals (Sweden)

    Patrice Roll

    Full Text Available BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome; the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105 located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions.

  8. Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.

    Science.gov (United States)

    Zappia, Mario; Annesi, Grazia; Nicoletti, Giuseppe; Arabia, Gennarina; Annesi, Ferdinanda; Messina, Demetrio; Pugliese, Pierfrancesco; Spadafora, Patrizia; Tarantino, Patrizia; Carrideo, Sara; Civitelli, Donatella; De Marco, Elvira V; Cirò-Candiano, Innocenza C; Gambardella, Antonio; Quattrone, Aldo

    2005-04-01

    Several factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD. To examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease. Cohort study. Referral center for Parkinson disease in Calabria, southern Italy. Patients Two hundred fifty patients with Parkinson disease were screened for the presence or absence of PDD following a short-term levodopa administration, and 215 subjects were available for further evaluations, including genotypic analysis of the CA dinucleotide short tandem repeat (CAn-STR) polymorphism located in the dopamine receptor D2 gene (DRD2). One hundred five patients (48.8%) exhibited PDD following short-term levodopa administration, and 110 patients (51.2%) did not. Multivariate logistic regression analysis showed that independent predictors for the occurrence of PDD were female sex, earlier age at onset of Parkinson disease, longer duration of treatment, and higher dose of levodopa. Genetic factors related to the DRD2 CAn-STR polymorphism were not independent predictors for PDD in the total population, but they had a strong protective effect on the appearance of PDD when the multivariate analysis was performed in men (odds ratio, 0.34 [95% confidence interval, 0.14-0.84]). In women, a genetic protective effect on PDD was not evident. Risk factors for PDD, both clinical and genetic, act in different ways for men and women. Genetic factors related to the DRD2 polymorphic status have a protective effect on PDD development in men but not in women. A female sex-related effect for the risk of PDD may be so strong that it overcomes any protective effect due to genetic factors.

  9. Aberrant transcriptional networks in step-wise neurogenesis of paroxysmal kinesigenic dyskinesia-induced pluripotent stem cells.

    Science.gov (United States)

    Li, Chun; Ma, Yu; Zhang, Kunshan; Gu, Junjie; Tang, Fan; Chen, Shengdi; Cao, Li; Li, Siguang; Jin, Ying

    2016-08-16

    Paroxysmal kinesigenic dyskinesia (PKD) is an episodic movement disorder with autosomal-dominant inheritance and marked variability in clinical manifestations.Proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD, but the molecular mechanism underlying the pathogenesis of PKD still remains a mystery. The phenotypes and transcriptional patterns of the PKD disease need further clarification. Here, we report the generation and neural differentiation of iPSC lines from two familial PKD patients with c.487C>T (p. Gln163X) and c.573dupT (p. Gly192Trpfs*8) PRRT2 mutations, respectively. Notably, an extremely lower efficiency in neural conversion from PKD-iPSCs than control-iPSCs is observed by a step-wise neural differentiation method of dual inhibition of SMAD signaling. Moreover, we show the high expression level of PRRT2 throughout the human brain and the expression pattern of PRRT2 in other human tissues for the first time. To gain molecular insight into the development of the disease, we conduct global gene expression profiling of PKD cells at four different stages of neural induction and identify altered gene expression patterns, which peculiarly reflect dysregulated neural transcriptome signatures and a differentiation tendency to mesodermal development, in comparison to control-iPSCs. Additionally, functional and signaling pathway analyses indicate significantly different cell fate determination between PKD-iPSCs and control-iPSCs. Together, the establishment of PKD-specific in vitro models and the illustration of transcriptome features in PKD cells would certainly help us with better understanding of the defects in neural conversion as well as further investigations in the pathogenesis of the PKD disease.

  10. FORWARD HEAD POSTURE CORRECTION VERSUS SHOULDER STABILIZATION EXERCISES EFFECT ON SCAPULAR DYSKINESIA AND SHOULDER PROPRIOCEPTION IN ATHLETES AN EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Deepmala Thakur

    2016-04-01

    Full Text Available Background: Forward head posture (FHP, the most common deviation from the normal curvature in cervical spine. Craniocervical flexor muscle strengthening is frequently used treatment for FHP. Scapular dykinesia (SD is the alteration in the normal static or dynamic motion of the scapula during coupled scapulohumeral movements. Shoulder stabilization exercises are an effective treatment for SD. As both FHP and SD are related to each other, the objective of the study was to find and compare the effect of FHP correction and shoulder stabilization exercises on SD and shoulder proprioception. Methods: 40 athletes (18-30yrs were recruited. Subjects were randomly allocated into two groups. Group A received deep neck flexor strengthening and anterior scalene stretch, group B received shoulder stabilizing exercises. Paired t test and chi-square test were used to judge the statistical significant difference. The level of significance was set at p <0.05. All data was analyzed using SPSS program version 12. Result: No statistical significant difference was found between the groups for the 4 outcome variables, but significant improvement was seen within the groups. Shoulder proprioception was found to be significant between the groups where group B (p =<0.001 showed better improvement than group A (p = <0.017. Conclusion: Both FHP correction as well as shoulder stabilization exercises were equally effective in correction of scapular dyskinesia and shoulder proprioception. Shoulder stabilization exercises showed slightly better improvement than FHP correction group in reducing proprioception errors. Also neck strength values were found to be clinically significant for deep neck strengthening group.

  11. Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid.

    Directory of Open Access Journals (Sweden)

    Robert A Hirst

    Full Text Available BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD requires the analysis of ciliary function and ultrastructure. Diagnosis can be complicated by secondary effects on cilia such as damage during sampling, local inflammation or recent infection. To differentiate primary from secondary abnormalities, re-analysis of cilia following culture and re-differentiation of epithelial cells at an air-liquid interface (ALI aids the diagnosis of PCD. However changes in ciliary beat pattern of cilia following epithelial cell culture has previously been described, which has brought the robustness of this method into question. This is the first systematic study to evaluate ALI culture as an aid to diagnosis of PCD in the light of these concerns. METHODS: We retrospectively studied changes associated with ALI-culture in 158 subjects referred for diagnostic testing at two PCD centres. Ciliated nasal epithelium (PCD n = 54; non-PCD n  111 was analysed by high-speed digital video microscopy and transmission electron microscopy before and after culture. RESULTS: Ciliary function was abnormal before and after culture in all subjects with PCD; 21 PCD subjects had a combination of static and uncoordinated twitching cilia, which became completely static following culture, a further 9 demonstrated a decreased ciliary beat frequency after culture. In subjects without PCD, secondary ciliary dyskinesia was reduced. CONCLUSIONS: The change to ciliary phenotype in PCD samples following cell culture does not affect the diagnosis, and in certain cases can assist the ability to identify PCD cilia.

  12. Brain morphometry and the neurobiology of levodopa-induced dyskinesias: current knowledge and future potential for translational pre-clinical neuroimaging studies.

    Directory of Open Access Journals (Sweden)

    Clare eFinlay

    2014-06-01

    Full Text Available Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson's disease (PD developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography (PET and functional magnetic resonance imaging (fMRI. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry (VBM. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID.

  13. Brain morphometry and the neurobiology of levodopa-induced dyskinesias: current knowledge and future potential for translational pre-clinical neuroimaging studies.

    Science.gov (United States)

    Finlay, Clare J; Duty, Susan; Vernon, Anthony C

    2014-01-01

    Dopamine replacement therapy in the form of levodopa results in a significant proportion of patients with Parkinson's disease developing debilitating dyskinesia. This significantly complicates further treatment and negatively impacts patient quality of life. A greater understanding of the neurobiological mechanisms underlying levodopa-induced dyskinesia (LID) is therefore crucial to develop new treatments to prevent or mitigate LID. Such investigations in humans are largely confined to assessment of neurochemical and cerebrovascular blood flow changes using positron emission tomography and functional magnetic resonance imaging. However, recent evidence suggests that LID is associated with specific morphological changes in the frontal cortex and midbrain, detectable by structural MRI and voxel-based morphometry. Current human neuroimaging methods however lack sufficient resolution to reveal the biological mechanism driving these morphological changes at the cellular level. In contrast, there is a wealth of literature from well-established rodent models of LID documenting detailed post-mortem cellular and molecular measurements. The combination therefore of advanced neuroimaging methods and rodent LID models offers an exciting opportunity to bridge these currently disparate areas of research. To highlight this opportunity, in this mini-review, we provide an overview of the current clinical evidence for morphological changes in the brain associated with LID and identify potential cellular mechanisms as suggested from human and animal studies. We then suggest a framework for combining small animal MRI imaging with rodent models of LID, which may provide important mechanistic insights into the neurobiology of LID.

  14. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 4: Case Report Data.

    Science.gov (United States)

    Macaluso, Matthew; Flynn, Alexandra; Preskorn, Sheldon

    2016-05-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients who develop abnormal movements during treatment with antipsychotics. The first column in the series presented a patient who developed abnormal movements while being treated with aripiprazole as an augmentation strategy for major depressive disorder and reviewed data concerning the historical background, incidence, prevalence, and risk factors for tardive and spontaneous dyskinesias, the clinical presentations of which closely resemble each other. The second column in the series reviewed the unique mechanism of action of aripiprazole and reviewed preclinical studies and an early-phase human translational study that suggest a low, if not absent, risk of TD with aripiprazole. The third column in this series reviewed the registration trial data for aripiprazole across all of its indications and found a raw incidence of TD ranging from 0.004 (4 out of 987) in long-term studies of the drug as an augmentation strategy for major depressive disorder to 0.0016 (19 out of 11,897) based on all short-term (ie, weeks to causal relationship between aripiprazole and TD exists.

  15. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment

    NARCIS (Netherlands)

    Wilffert, B.; Al Hadithy, A.F.; Sing, V.J.; Matroos, G.; Hoek, H.W.; van Os, J.; Bruggeman, R.; Brouwers, J.R.; van Harten, P.N.

    2009-01-01

    Abstract Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D3, serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (

  16. A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias.

    Science.gov (United States)

    Lieu, Christopher A; Kunselman, Allen R; Manyam, Bala V; Venkiteswaran, Kala; Subramanian, Thyagarajan

    2010-08-01

    Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug

  17. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder: Part 1.

    Science.gov (United States)

    Preskorn, Sheldon; Flynn, Alexandra; Macaluso, Matthew

    2015-09-01

    This series of columns has 2 main goals: (1) to explain the use of class warnings by the US Food and Drug Administration and (2) to increase clinicians' awareness of movement disorders that may occur in patients being treated with antipsychotic medications and why it is appropriate and good practice to refrain from immediately assuming the diagnosis is tardive dyskinesia/dystonia (TD). This first column in the series will focus on the second goal, which will then serve as a case example for the first goal. Clinicians should refrain from jumping to a diagnosis of TD because a host of other causes need to be ruled out first before inferring iatrogenic causation. The causal relationship between chronic treatment with dopamine antagonists and TD is based on pharmacoepidemiology (ie, the prevalence of such movement disorders is higher in individuals receiving chronic treatment with such agents than in a control group). There is nothing pathognomonic about movement disorders, nor is there any test that can currently prove a drug caused a movement disorder in a specific individual. Another goal of this series is to describe the types of research that would be needed to establish whether a specific agent has a meaningful risk of causing TD. In this first column of the series, we present the case of a patient who developed orofacial dyskinesia while being treated with aripiprazole. In this case, the movement disorder was prematurely called TD, which led to a malpractice lawsuit. This case highlights a number of key questions clinicians are likely to encounter in day-to-day practice. We then review data concerning the historical background, incidence, prevalence, and risk factors for 2 movement disorders, TD and spontaneous dyskinesia. Subsequent columns in this series will review: (1) unique aspects of the psychopharmacology of aripiprazole, (2) the limited and inconsistent data in the literature concerning the causal relationship between aripiprazole and TD, (3) the use of

  18. NEUROBIOLOGICAL CHARACTERIZATION OF BIPOLAR AFFECTIVE DISORDERS : A FOCUS ON TARDIVE DYSKINESIA AND SOFT NEUROLOGICAL SIGNS IN RELATION TO SERUM DOPAMINE BETA HYDROXYLASE ACTIVITY

    Science.gov (United States)

    Goswami, Utpal; Basu, S.; Khastgir, U.; Kumar, Unnati; Chandrasekaran, R.; Gangadhar, B.N.; Sagar, Rajesh; Bapna, J.S.; Channabasavanna, S.M.; Moore, P. Brain; Ferrier, I. Nicol

    1998-01-01

    In this study, the prognostic determinants were investigated involving bipolar patients classified into two groups-one with favourable course and outcome, and the other with clearly unfavourable prognosis, based on certain recommended criteria, with intermediate prognosis were excluded. As compared to the poor prognosis group, the good prognosis group had lower social dysfunctions, lower ratings on psychopathotogy fewer indicators of neurodysfunction in form of neurological soft signs (NSS) and tardive dyskinesia (TD). The poor prognosis group was characterized by: (i) older age at onset; (ii) more manic than depressive episodes (5:1) and (HI) lower levels of serum dopamine-β-hydroxylase activity (DBH). The association between poor prognosis bipolar disorder having neuroleptic intolerance (TD and NSS) with low serum DBH, suggests that it is genetically governed. Further research in this direction seems in order, particularly the follow up of first episode manic disorders. PMID:21494474

  19. Hand-held tidal breathing nasal nitric oxide measurement--a promising targeted case-finding tool for the diagnosis of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Nielsen, Kim Gjerum

    2013-01-01

    BACKGROUND: Nasal nitric oxide (nNO) measurement is an established first line test in the work-up for primary ciliary dyskinesia (PCD). Tidal breathing nNO (TB-nNO) measurements require minimal cooperation and are potentially useful even in young children. Hand-held NO devices are becoming...... at flow rates 2 ml/s or 5 ml/s, and two stationary chemiluminescence devices, applying both tidal breathing and velum closure techniques. RESULTS: Measurements were done in 16 PCD patients, 21 patients with CF and 20 HS aged between 3.8 and 60.9 years. Hand-held TB-nNO showed high success rate (96...

  20. Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation.

    Science.gov (United States)

    Urbizu, Aintzane; Cuenca-León, Ester; Raspall-Chaure, Miquel; Gratacòs, Margarida; Conill, Joan; Redecillas, Susana; Roig-Quilis, Manuel; Macaya, Alfons

    2010-08-15

    We report two monochorionic twins that progressively developed, between ages 5 and 10, a combination of episodic neurological disorders including paroxysmal exercise-induced dyskinesia, migraine without or with aura, absence seizures and writer's cramp. CSF/serum glucose ratio was moderately decreased in both patients. Mutational analysis of SLC2A1 gene identified a de novo heterozygous missense mutation in exon 4. This novel mutation has been previously showed to disrupt glucose transport in vitro. Both patients showed immediate and near-complete response to ketogenic diet. This clinical observation suggests that a high index of suspicion for GLUT1 deficiency syndrome is warranted in evaluating patients with multiple neurological paroxysmal events.

  1. Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: Effect of L-DOPA treatment and changes in levodopa-induced dyskinesia.

    Science.gov (United States)

    Andersen, A D; Blaabjerg, M; Binzer, M; Kamal, A; Thagesen, H; Kjaer, T W; Stenager, E; Gramsbergen, J B

    2017-02-28

    Levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to L-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily L-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID (PD-LID, n=8)) as compared to non-dyskinetic PD patients receiving L-DOPA (PD-L, n=6), or not receiving L-DOPA (PD-N, n=7) as well as non-PD controls (n=16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 hours after oral intake of L-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (1) decreased levels of dihydroxyphenylacetic acid and homovanillic acid in PD patients not receiving L-DOPA (2) higher DA levels in LID as compared to controls (3) higher DA/L-DOPA and lower DOPAC/DA ratio's in LID as compared to PDL and (4) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of L-DOPA-treated PD patients may help identify patients at risk of developing LID. This article is protected by copyright. All rights reserved.

  2. Subcellular redistribution of the synapse-associated proteins PSD-95 and SAP97 in animal models of Parkinson's disease and L-DOPA-induced dyskinesia.

    Science.gov (United States)

    Nash, J E; Johnston, T H; Collingridge, G L; Garner, C C; Brotchie, J M

    2005-04-01

    Abnormalities in subcellular localization and interaction between receptors and their signaling molecules occur within the striatum in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). Synapse-associated proteins (SAPs), for example, PSD-95 and SAP97 organize the molecular architecture of synapses and regulate interactions between receptors and downstream-signaling molecules. Here, we show that expression and subcellular distribution of PSD-95 and SAP97 are altered in the striatum of unilateral 6-OHDA-lesioned rats following repeated vehicle (a model of PD) or L-DOPA administration (a model of L-DOPA-induced dyskinesia). Furthermore, following dopamine-depletion and development of behavioral deficits in Rotorod performance, indicative of parkinsonism, we observed a dramatic decrease in total striatal levels of PSD-95 and SAP97 (to 25.6 +/- 9.9% and 19.0 +/- 5.0% of control, respectively). The remaining proteins were redistributed from the synapse into vesicular compartments. L-DOPA (6.5mg/kg twice a day, 21 days) induced a rotational response, which became markedly enhanced with repeated treatment (day 1: -15.8+/-7.3 rotations cf day 21: 758.2+/-114.0 rotations). Post L-DOPA treatment, PSD-95 and SAP97 levels increased (367.4 +/- 43.2% and 159.9 +/- 9.5% from control values, respectively), with both being redistributed toward synaptic membranes from vesicular compartments. In situ hybridization showed that changes in total levels of PSD-95, but not SAP97, were accompanied by qualitatively similar changes in mRNA. These data highlight the potential role of abnormalities in the subcellular distribution of SAPs in the pathophysiology of a neurological disease.

  3. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.

    Science.gov (United States)

    Bakker, P R; van Harten, P N; van Os, J

    2008-05-01

    Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT(val158met), using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR=0.63, 95% CI: 0.46-0.86, P=0.004) and Met carriers (OR=0.66, 95% CI: 0.49-0.88, P=0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037); (3) in MnSOD Ala-9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR=0.37, 95% CI: 0.17-0.79, P=0.009) and for Val carriers (OR=0.49, 95% CI: 0.24-1.00, P=0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge. Molecular Psychiatry (2008) 13, 544-556; doi:10.1038/sj.mp.4002142; published online 8 January 2008.

  4. NR2B antagonist CP-101,606 inhibits NR2B phosphorylation at tyrosine-1472 and its interactions with Fyn in levodopa-induced dyskinesia rat model.

    Science.gov (United States)

    Kong, Min; Ba, Maowen; Liu, Chuanyu; Zhang, Yanxiang; Zhang, Hongli; Qiu, Haiyan

    2015-04-01

    The augmented tyrosine phosphorylation of NR2B subunit of N-methyl-d-aspartate receptors (NMDAR) dependent on Fyn kinase has been associated with levodopa (l-dopa)-induced dyskinesia (LID). CP-101,606, one selective NR2B subunit antagonist, can improve dyskinesia. Yet, the accurate action mechanism is less well understood. In the present study, the evidences were investigated. Valid 6-hydroxydopamine-lesioned parkinsonian rats were treated with l-dopa intraperitoneally for 22 days to induce LID rat model. On day 23, rats received either CP-101,606 (0.5mg/kg) or vehicle with each l-dopa dose. On the day of 1, 8, 15, 22, and 23 during l-dopa treatment, we determined abnormal involuntary movements (AIMs) in rats. The levels of NR2B phosphorylation at tyrosine-1472 (pNR2B-Tyr1472) and interactions of NR2B with Fyn in LID rat model were detected by immunoblotting and immunoprecipitation. Results showed that CP-101,606 attenuated l-dopa-induced AIMs. In agreement with behavioral analysis, CP-101,606 reduced the augmented pNR2B-Tyr1472 and its interactions with Fyn triggered during the l-dopa administration in the lesioned striatum of parkinsonian rats. Moreover, CP-101,606 also decreased the level of Ca(2+)/calmodulin-dependent protein kinase II at threonine-286 hyperphosphorylation (pCaMKII-Thr286), which was the downstream signaling amplification molecule of NMDAR overactivation and closely associated with LID. However, the protein level of NR2B and Fyn had no difference under the above conditions. These data indicate that the inhibition of the interactions of NR2B with Fyn and NR2B tyrosine phosphorylation may contribute to the CP-101,606-induced downregulation of NMDAR function and provide benefit for the therapy of LID. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Association between monoamine oxidase A gene promoter 30 bp repeat polymorphism and tardive dyskinesia in Chinese schizophrenics

    Institute of Scientific and Technical Information of China (English)

    Changhe Fan; Lihua Li; Yan Fu; Hehuang Deng; Xiangjiao Liao; Youcai Zhou

    2006-01-01

    BACKGROUND: The pathophysiology of tardive dyskinesia (TD) is not yet fully understood. With the hypothesis of altered dopaminergic neurotransmission, altered activities of dopamine degrading enzymes such as monoamine oxidase A (MAOA) and their coding genes are supposed to be related to the pathophysiology of TD.OBJECTIVE: To investigate possible association between 30 bp variable number tandem repeat (VNTR) polymorphism in the promoter of MAOA gene and susceptibility, severity of neuroleptic induced TD in Chinese Han people in Guandong Province.DESIGN: Non-randomization-synchronization controlled study. SETTING: Guangdong Mental Health Institute, Guangdong Provincial People's Hospital; Guangzhou Psychiatric Hospital; Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration. PARTICIPANTS: A total of 179 subjects were enrolled in the study. All subjects were sporadic and genetically unrelated Chinese schizophrenic patients who were hospitalizing in Guangzhou Psychiatric Hospital or Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration during January to April 2005. The diagnosis of schizophrenia was made according to the criteria of Diagnostic and Statistic Manual of Mental Disorder-the third edition-revised (DSM-Ⅲ-R). Among all patients, 88 were diagnosed as with TD and 91 without TD according to the research diagnostic criteria described by Schooler-Kane. Informed consent was obtained from all subjects or their relatives.METHODS: ① TD severity was assessed with the AIMS which was a 5-degree rating scale from 0 to 4 (corresponding to none, minimal, mild, moderate and severe, respectively). The study was approved by the Ethics Committees of the two hospitals and informed consent was obtained from all subjects or their relatives. ② The polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) techniques were used to detect MAOA gene 30 bp VNTR polymorphism in schizophrenic patients

  6. The role of dopamine D-3, 5-HT2(A) and 5-HT2(C) receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment Curacao extrapyramidal syndromes study IX

    NARCIS (Netherlands)

    Wilffert, B.; Al Hadithy, A. F. Y.; Sing, V. J.; Matroos, G.; Hoek, H. W.; van Os, J.; Bruggeman, R.; Brouwers, J. R. B. J.; van Harten, P. N.

    2009-01-01

    Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D-3, serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) i

  7. Antipsychotic drug binding in the substantia nigra: an examination of high metoclopramide binding in the brains of normal, Alzheimer's disease, Huntington's disease, and Multiple Sclerosis patients, and its relation to tardive dyskinesia.

    Science.gov (United States)

    Chen, Sheng; Seeman, Philip; Liu, Fang

    2011-02-01

    This project was done in order to determine why the annual incidence of metoclopramide-associated tardive dyskinesia is much higher than that for the commonly used antipsychotics. To test the hypothesis that metoclopramide tardive dyskinesia may be associated with high concentrations of metoclopramide in the substantia nigra under clinical conditions, the nonspecific binding of tritiated antipsychotics to the dissected melaninized regions of postmortem human substantia nigra was measured. The nonspecific binding at 1 nM [³H]ligand was 7.3, 4.2, 2.6, 0.91 and 0.66 fmoles/mg for [³H]haloperidol, [³H]clozapine, [³H]raclopride, [³H]metoclopramide, and [³H]olanzapine, respectively. After adjusting these values for the known free concentrations of these drugs in plasma or spinal fluid, the amounts that would be bound under clinical conditions would be 231, 113, 15, 11, and 3.4 fmoles/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively. Using rat striatum as baseline to define antipsychotic binding to nonnigral tissue, the excess amount of binding to the Alzheimer nigral tissue under clinical conditions would be 209, 19, 0, 3.4 and 0.8 fmole/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively, with a similar pattern for nigral tissues from Huntington and Multiple Sclerosis patients. The high accumulation of metoclopramide is sufficiently high to cause nigral nerve cell membrane damage by metoclopramide's detergent-like action, possibly explaining metoclopramide's toxic ability to elicit early tardive dyskinesia. In addition, the nonspecific binding of metoclopramide was much higher in Alzheimer-diseased substantia nigra, consistent with the fact that older individuals are relatively more vulnerable to metoclopramide tardive dyskinesia.

  8. 运动减少性运动障碍急症及其诊治%Diagnosis and treatment for hypokinetic dyskinesia emergencies

    Institute of Scientific and Technical Information of China (English)

    严芳; 王宇卉

    2013-01-01

    Hypokinetic movement disorders include antipsychiatric drugs-induced syndromes, such as neuroleptic malignant syndrome, serotonin syndrome and emergency complications related to Parkinson disease, such as motor fluctuations, dyskinesias, psychiatric issues and parkinsonism hyperpyrexia syndrome, which need to be diagnosed and treated promptly and correctly. This review describes the characteristics and treatment of hypokinetic movement disorders emergencies.%运动减少性运动障碍急症主要包括抗精神失常药物引起的综合征如抗精神病药恶性综合征、5-羟色胺综合征,以及与帕金森病治疗相关的一些急性并发症如运动波动现象、异动症、精神障碍和帕金森病撤药恶性综合征,需要及时正确诊断及处理.本文主要综述运动减少性运动障碍急症的特点及临床诊治.

  9. Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

    Science.gov (United States)

    Austin-Tse, Christina; Halbritter, Jan; Zariwala, Maimoona A.; Gilberti, Renée M.; Gee, Heon Yung; Hellman, Nathan; Pathak, Narendra; Liu, Yan; Panizzi, Jennifer R.; Patel-King, Ramila S.; Tritschler, Douglas; Bower, Raqual; O’Toole, Eileen; Porath, Jonathan D.; Hurd, Toby W.; Chaki, Moumita; Diaz, Katrina A.; Kohl, Stefan; Lovric, Svjetlana; Hwang, Daw-Yang; Braun, Daniela A.; Schueler, Markus; Airik, Rannar; Otto, Edgar A.; Leigh, Margaret W.; Noone, Peadar G.; Carson, Johnny L.; Davis, Stephanie D.; Pittman, Jessica E.; Ferkol, Thomas W.; Atkinson, Jeffry J.; Olivier, Kenneth N.; Sagel, Scott D.; Dell, Sharon D.; Rosenfeld, Margaret; Milla, Carlos E.; Loges, Niki T.; Omran, Heymut; Porter, Mary E.; King, Stephen M.; Knowles, Michael R.; Drummond, Iain A.; Hildebrandt, Friedhelm

    2013-01-01

    Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia function remain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an in vivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a flagellar matrix protein that accumulates specifically when cilia motility is impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential component of the nexin-dynein regulatory complex. Analysis of 295 individuals with PCD identified recessive truncating mutations of C21orf59 in four families and CCDC65 in two families. Similar to findings in zebrafish and planaria, mutations in C21orf59 caused loss of both outer and inner dynein arm components. Our results characterize two genes associated with PCD-causing mutations and elucidate two distinct mechanisms critical for motile cilia function: dynein arm assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for CCDC65. PMID:24094744

  10. Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care

    Energy Technology Data Exchange (ETDEWEB)

    Jain, K. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom); Padley, S.P.G. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom)], E-mail: s.padley@ic.ac.uk; Goldstraw, E.J.; Kidd, S.J. [Department of Radiology, Royal Brompton and Harefield NHS Trust, London (United Kingdom); Hogg, C.; Biggart, E.; Bush, A. [Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Trust, London (United Kingdom)

    2007-10-15

    Aim: To investigate the clinical range and severity of radiological findings in a cohort of patients with primary ciliary dyskinesia (PCD) receiving tertiary care. Materials and methods: The case notes and clinical test results of 89 children attending the paediatric respiratory disease clinic at our institution were retrospectively analysed. Demographic details including age at diagnosis and common presenting signs and symptoms were studied. Results of chest radiographs, microscopy, and high-resolution computed tomography (HRCT) for quantification of lung damage were analysed. Results: In a cohort of 89 children with PCD, a presentation chest radiograph was available in 62% of patients (n = 55), with all but one demonstrating changes of bronchial wall thickening. HRCT of the lungs, available in 26 patients, were scored using the system described by Brody et al. analysing five specific features of lung disease, including bronchiectasis, mucus plugging, peribronchial thickening, parenchymal changes of consolidation, and ground-glass density, and focal air-trapping in each lobe. Peribronchial thickening was observed using HRCT in 25 patients, while 20 patients had bronchiectasis. Severity scores were highest for the middle and the lingular lobes. Conclusion: The radiographic findings of the largest reported cohort of patients with PCD are presented, with associated clinical findings. Dextrocardia remains the commonest finding on chest radiography. HRCT demonstrates peribronchial thickening and bronchiectasis, which is most marked in the lower zones. Radiological scoring techniques developed for assessment of cystic fibrosis can also be applied for the assessment of disease severity in this patient population.

  11. From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.

    Science.gov (United States)

    Alsaadi, Muslim M; Gaunt, Tom R; Boustred, Christopher R; Guthrie, Philip A I; Liu, Xuan; Lenzi, Luca; Rainbow, Lucille; Hall, Neil; Alharbi, Khalid K; Day, Ian N M

    2012-05-01

    Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal recessive, causing early respiratory disease and later subfertility. Whole exome sequencing may enable efficient analysis for locus heterogeneous disorders such as PCD. We whole-exome-sequenced one consanguineous Saudi Arabian with clinically diagnosed PCD and normal laterality, to attempt ab initio molecular diagnosis. We reviewed 13 known PCD genes and potentially autozygous regions (extended homozygosity) for homozygous exon deletions, non-dbSNP codon, splice-site base variants or small indels. Homozygous non-dbSNP changes were also reviewed exome-wide. One single molecular read representing RSPH9 p.Lys268del was observed, with no wild-type reads, and a notable deficiency of mapped reads at this location. Among all observations, RSPH9 was the strongest candidate for causality. Searching unmapped reads revealed seven more mutant reads. Direct assay for p.Lys268del (MboII digest) confirmed homozygosity in the affected individual, then confirmed homozygosity in three siblings with bronchiectasis. Our finding in southwest Saudi Arabia indicates that p.Lys268del, previously observed in two Bedouin families (Israel, UAE), is geographically widespread in the Arabian Peninsula. Analogous with cystic fibrosis CFTR p.Phe508del, screening for RSPH9 p.Lys268del (which lacks sentinel dextrocardia) in those at risk would help in early diagnosis, tailored clinical management, genetic counselling and primary prevention.

  12. Management of primary ciliary dyskinesia/Kartagener's syndrome in infertile male patients and current progress in defining the underlying genetic mechanism

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    Yan-Wei Sha

    2014-02-01

    Full Text Available Kartagener's syndrome (KS is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia (PCD. As it is accompanied by many complications, PCD/KS severely affects the patient's quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.

  13. Reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS for tardive dyskinesia in Brazilian patients

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    H. Tonelli

    2003-04-01

    Full Text Available The objective of the present study was to evaluate the reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS. Videotaped interviews with 16 psychiatric inpatients treated with antipsychotic drugs for at least 5 years were evaluated. Reliability was assessed by the intraclass correlation coefficient (ICC between three raters, two with and one without clinical training in psychopathology. Clinical utility was assessed by the difference between the scores of patients with (N = 11 and without (N = 5 tardive dyskinesia (TD. Patients with TD exhibited a higher severity of global evaluation by the AIMS (sum of scores: 4.2 ± 0.9 vs 0.4 ± 0.2; score on item 8: 2.3 ± 0.3 vs 0.4 ± 0.2, TD vs controls. The ICC for the global evaluation was fair between the two skilled raters (0.58-0.62 and poor between these raters and the rater without clinical experience (0.05-0.29. Thus, we concluded that the Portuguese version of the AIMS shows an acceptable inter-rater reliability, but only between clinically skilled raters, and that it is clinically useful.

  14. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX.

    Science.gov (United States)

    Wilffert, B; Al Hadithy, A F Y; Sing, V J; Matroos, G; Hoek, H W; van Os, J; Bruggeman, R; Brouwers, J R B J; van Harten, P N

    2009-08-01

    Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D(3), serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or -1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and -1438A carriership increased TD. The study clearly shows that the African-Caribbean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT(2C) and probably of the 5-HT(2A) receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.

  15. 儿童阵发性运动诱发的运动障碍二例报告及文献复习%To report 2 cases of childrenwith paroxysmal kinesigenic dyskinesia and review of literature.

    Institute of Scientific and Technical Information of China (English)

    江亮亮; 赵忠礼; 杨斌

    2011-01-01

    目的 报告2例阵发性运动诱发的运动障碍( paroxysmal kinesigenic dyskinesia,PKD)并复习相关文献.方法 通过复习阵发性运动诱发的运动障碍的相关文献,结合报告的2例该病,总结阵发性运动诱发的运动障碍的临床特点、发病机制及目前分子生物学的研究进展.结果 临床上阵发性运动诱发的运动障碍多由运动触发,发作持续时间一般<1 min,发作过程中无意识障碍或疼痛,神经系统检查正常,无其他器质性疾病,拉莫三嗪、苯妥英或卡马西平等抗癫痫药物治疗有效等特点.PKD的临床表现与离子通道源性神经系统疾病存在许多相似之处,离子通道学说被认为是PKD最可能的一种发病机制.结论 PKD由运动触发,病史是明确诊断的唯一依据.临床可应用抗癫痫药物治疗,预后一般良好.%Objective; To report 2 patients with paroxysmal kinesigenic dyskinesia (PKD) and the review of the literature. Meth-ods : Review of paroxysmal kinesigenic dyskinesia in the literature, combined with reports of 2 cases of the disease, to summarize the clinical features, pathogenesis and progress in molecular biology of PKD. Results:Clinically, paroxysmal kinesigenic dyskinesia trig-gered by the involuntary movement more, generally short duration of attack, generally < lmin, no pain or unconscious barriers during attack, neurological examination was normal, no other organic diseases, lamotrigine, phenytoin or carbamazepine and other antiepilep-tic drug treatment is effective and so on. The clinical manifestations of PKD are similarities with the nervous system disorders with en-dogenous ion channels, ion channel theory is considered the most likely kind of PKD pathogenesis. Conclusion PKD triggered by the involuntary movement. Therefore, diagnosis is based solely on history. Antiepileptic drug can be applied to clinical therapeutics, the prognosis is generally better.

  16. Associação entre discinesia escapular e dor no ombro de praticantes de natação Association between scapular dyskinesia and shoulder pain in swimmers

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    Elis Passos Santana

    2009-10-01

    Full Text Available A escápula possui funções essenciais no ombro do atleta de arremesso. Qualquer desequilíbrio presente entre as estruturas responsáveis pela sua estabilidade originará uma condição denominada discinesia escapular, a qual é comumente acompanhada de dor no ombro. Este estudo tem o objetivo de verificar se há associação entre a discinesia escapular e a dor no ombro de praticantes de natação. Foi realizado um estudo analítico observacional de corte transversal, incluindo 36 praticantes de natação do sexo masculino, com idade de 18 a 36 anos. Como métodos diagnósticos sugestivos de discinesia escapular foram utilizados o Slide Lateral Scapular Test e a filmagem proposta por Kibler. A existência de proporções significativas entre as variáveis nominais foi comprovada pelo teste do qui-quadrado ou pelo teste exato de Fisher. Para identificar associações entre as variáveis contínuas e os grupos de estudo foi utilizado o teste t de Student. Um p The scapula plays an essential role in the throwing motion performed by athletes. Scapular dyskinesia is a condition characterized by imbalance in the structures responsible for the joint stability, which is often accompanied by shoulder pain. The main objective of this study is to assess the relationship between scapular dyskinesia and shoulder pain in swimmers. A total of 36 male swimmers aged between 18 and 36 years were diagnosed for scapular dyskinesia utilizing two different methods: the Lateral Slide Scapular Test and the video recording method suggested by Kibler. Statistical analysis was performed using the Chi-square test or Fisher's exact test. Comparisons between groups were performed using the t-test. The degree of p< 0.05 was considered statistically significant. Significance was set at α=0.05. There was a high inter-rate reliability concerning the video analysis (Kappa; p<0.0001, corresponding to 86.1% (0.7656 on the right shoulder and 83.3% (0.6412 on the left shoulder

  17. Levodopa/benserazide microspheres reduced levodopa-induced dyskinesia by downregulating phosphorylated GluR1 expression in 6-OHDA-lesioned rats

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    Song L,Yuan W

    2012-11-01

    Full Text Available Xinxin Yang,1,* Yinghui Chen,2,* Xiaoyun Hong,3 Na Wu,1 Lu Song,1 Weien Yuan,3 Zhenguo Liu11Department of Neurology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China; 2Department of Neurology, Jinshan Hospital, Fudan University, JinShan District, Shanghai, China; 3School of Pharmacy, Shanghai Jiaotong University, Shanghai, China*These authors contributed equally to this workBackground: Levodopa is the gold standard in the treatment of Parkinson’s disease (PD. However, long-term levodopa replacement therapy is accompanied by abnormal involuntary movements (AIMs, known as levodopa-induced dyskinesia (LID. Until now, the precise mechanisms of LID were only partially understood. Previous studies have shown that continuous dopamine stimulation was helpful in reducing the expression of LID. In addition to dopamine D1 receptor, glutamatergic receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor also contribute to the expression of LID. The current authors have previously reported that levodopa/benserazide-loaded microspheres could ameliorate the expression of LID by reducing the protein kinase A signaling pathway in dyskinetic rats. However, whether AMPA receptor is involved in the mechanism by which levodopa/benserazide-loaded microspheres ameliorate the expression of LID in dyskinetic rats was unknown.Methods: In the present study, as reported previously, levodopa and benserazide were loaded by poly(lactic-co-glycolic acid microspheres, which can release levodopa and benserazide in a sustained manner. 6-Hydroxydopamine was injected into the right medial forebrain bundle to produce a rat model of PD. Then valid PD rats were treated with levodopa plus benserazide for 3 weeks to induce a rat model of LID. Dyskinetic rats were treated with levodopa/beserazide-loaded microspheres containing levodopa (6 mg/kg plus benserazide (15 mg/kg or same dose of levodopa plus benserazide

  18. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 3: Clinical Trial Data.

    Science.gov (United States)

    Preskorn, Sheldon H; Macaluso, Matthew

    2016-03-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients who develop abnormal movements during treatment with antipsychotics. The first column in the series presented a patient who developed abnormal movements while being treated with aripiprazole as an augmentation strategy for major depressive disorder (MDD) and reviewed data concerning the historical background, incidence, prevalence, and risk factors for tardive and spontaneous dyskinesias, the clinical presentations of which closely resemble each other. The second column in the series reviewed the unique mechanism of action of aripiprazole and preclinical studies and an early-phase human translational study that suggest a low, if not absent, risk of TD with aripiprazole. This column reviews clinical trial data to assess whether those data support the conclusion that aripiprazole has a low to absent risk of causing TD when used as an augmentation strategy to treat MDD. To date, no randomized, placebo-controlled trials have established a definitive link between exposure to aripiprazole and TD in patients with MDD. One long-term, open-label, safety trial examined aripiprazole as an augmentation strategy in individuals with MDD and found a rare occurrence (4/987, 0.4%, the confidence interval of which overlaps with zero) of an adverse event termed TD. In all 4 cases, the observed movements resolved within weeks of aripiprazole discontinuation, suggesting that they were either amenable to treatment or represented an acute syndrome rather than TD. No cases of TD were reported in the registration trials for the MDD indication for aripiprazole. These data were presented in a pooled analysis of

  19. Altered neuronal firing pattern of the basal ganglia nucleus plays a role in levodopa-induced dyskinesia in patients with Parkinson's disease

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    Xiaoyu eLi

    2015-11-01

    Full Text Available Background: Levodopa therapy alleviates the symptoms of Parkinson's disease (PD, but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID. Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1±11.0 years; disease duration, 8.7±5.6 years were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr scores ranged from 2 to 4 and their UPDRS III scores were 28.5±5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7±1.6. Microelectrode recording was performed in the globus pallidus internus (GPi and subthalamic nucleus (STN during pallidotomy (n=12 or STN deep brain stimulation (DBS; bilateral, n=12; unilateral, n=6. The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs and the corresponding coefficient of variation (CV. Results: A total of 295 neurons were identified from the GPi (n=12 and STN (n=18. These included 26 (8.8% highly grouped discharge, 30 (10.2% low frequency firing, 78 (26.4% rapid tonic discharge, 103 (34.9% irregular activity, and 58 (19.7% tremor-related activity. There were significant differences between the two groups (P<0.05 for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.

  20. Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of L-DOPA-induced dyskinesia in 6-OHDA-lesioned rats.

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    Padovan-Neto, Fernando Eduardo; Cavalcanti-Kiwiatkoviski, Roberta; Carolino, Ruither Oliveira Gomes; Anselmo-Franci, Janete; Del Bel, Elaine

    2015-02-01

    It is well known that nitric oxide (NO) interacts with dopamine (DA) within the striatal circuitry. The anti-dyskinetic properties of NO synthase (NOS) inhibitors demonstrate the importance of NO in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID). Here, we investigated the ability of a daily co-treatment of the preferential neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg), with L-DOPA (30 mg/kg) to counteract LID in unilaterally 6-OHDA-lesioned rats. We analyzed striatal nNOS-expressing interneurons, DA and 5-HT neurochemistry in the striatum and alterations of the Fos-B/ΔFosB expression in the corticostriatal, nigrostriatal and mesolimbic pathways. Prolonged administration of 7-NI inhibited the manifestation of chronic L-DOPA treatment-induced abnormal involuntary movements (AIMs). LID was associated with an up-regulation in the number of nNOS-expressing interneurons in the lateral but not medial striatum. nNOS inhibition reduced the number of nNOS-expressing interneurons. The anti-dyskinetic effects of 7-NI correlated with a reduction in DA and 5-HT turnover in the striatum. At postsynaptic striatal sites, 7-NI prevented L-DOPA-induced Fos-B/ΔFosB up-regulation in the motor cortex, nucleus accumbens and striatum. Finally, 7-NI blocked Fos-B/ΔFosB expression in nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive interneurons in the striatum. These results provide further evidence of the molecular mechanisms by which NOS-inhibiting compounds attenuate LID. The involvement of NO with DA and 5-HT neurochemistry may contribute to the understanding of this new, non-dopaminergic therapy for the management of LID. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Effect of selective and non-selective serotonin receptor activation on L-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats.

    Science.gov (United States)

    Tronci, E; Fidalgo, C; Stancampiano, R; Carta, M

    2015-10-01

    Selective activation of 5-HT1 receptors has been shown to produce near to full suppression of L-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease; however, a reduction of the therapeutic effect of L-DOPA has been reported in several studies. Conversely, we recently found that increasing the serotonergic tone with chronic administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) can reduce LID in 6-OHDA-lesioned rats, without affecting L-DOPA efficacy. To directly compare the effects of selective versus non-selective serotonin receptor activation, here we first tested different acute doses of the 5-HT1A/1B receptor agonist eltoprazine and 5-HTP on LID in order to identify doses of the individual compounds showing similar anti-dyskinetic efficacy in L-DOPA-primed dyskinetic rats. About 50% reduction of LID was observed with 0.1 mg/kg and 24 mg/kg of eltoprazine and 5-HTP, respectively; we then compared the effect of the two drugs, individually and in combination, on L-DOPA-induced stepping test in L-DOPA-naïve parkinsonian animals and LID over three weeks of L-DOPA treatment. Results showed that eltoprazine induced significant worsening of L-DOPA-mediated performance in the stepping test, while 5-HTP did not. Interestingly, combination of 5-HTP with eltoprazine prevented the reduction in the forelimb use induced by eltoprazine. Moreover, 5-HTP and eltoprazine given individually showed similar efficacy also upon chronic treatment, and had additive effect in dampening the appearance of LID when given in combination. Finally, chronic administration of eltoprazine and/or 5-HTP did not affect striatal serotonin innervation, compared to l-DOPA alone, as measured by serotonin transporter expression.

  2. Mechanism of over-activation in direct pathway mediated by dopamine D1 receptor in rats with levodopa-induced dyskinesias

    Institute of Scientific and Technical Information of China (English)

    Xue-Bing CAO; Qiang GUAN; Yan XU; Lan WANG; Sheng-Gang SUN

    2006-01-01

    Objective To study the changes of prodynorphin (PDyn) gene expression and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) phosphorylation in rats with levodopa-induced dyskinesias (LID), and to explore the mechanism of over-activation in direct pathway mediated by dopamine D1 receptor. Methods Parkinson's disease (PD) rats were received levodopa (10 mg/kg, i.p.) for 28 d to get the LID rats. According to the behavior scale, LID rats were divided into mild (n=8) and severe (n=16) groups. On day 29, 8 rats in severe LID group were given an acute intraperitoneal injection of MK-801 (0.1 mg/kg) 15 min before levodopa treatment (MK-801 group, n=8). The normal rats received same course and dosage of levodopa as the control group (n=8). Hybridization in situ was used to measure the expression of PDyn mRNA in striatum. Protein and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 level were measured by immunoblotting and RT-PCR, respectively. Results The levels of PDyn mRNA and phospho-Thr-34DARPP-32 increased significantly in LID rats compared with control rats (P<0.01), and they also increased markedly in severe LID group compared with mild group (P<0.01). Conclusion Phospho-Thr-34 DARPP-32 level was increased in LID rats, which contributed to the over-activation of direct pathway mediated by dopamine D1 receptor.

  3. Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: thirty-six-month results from the European schizophrenia outpatient health outcomes study.

    Science.gov (United States)

    Novick, Diego; Haro, Josep Maria; Bertsch, Jordan; Haddad, Peter M

    2010-10-01

    The incidence of treatment-emergent extrapyramidal symptoms (EPSs) and tardive dyskinesia (TD) in schizophrenic patients, and the clinical characteristics associated with an increased risk of developing EPSs and TD were examined. Patients (N = 7728) in the 3-year, prospective, observational Schizophrenia Outpatient Health Outcomes study were examined according to baseline antipsychotic drug exposure. At baseline, 4893 patients (63.3%) had no EPS, and 6921 (89.6%) had no TD. Extrapyramidal symptoms and TD were assessed separately during follow-up: frequency and time to appearance from Kaplan-Meier survival curves and factors associated with time to appearance using Cox proportional hazard regression models. The cumulative incidence of EPS ranged from 7.7% (olanzapine) to 32.8% (depot typical drugs). Compared with olanzapine, patients taking depot typical drugs, oral typical drugs, risperidone, and amisulpride had a significantly higher risk of developing EPS. Differences from clozapine were marginally significant. High baseline clinical severity was associated with a significantly higher risk of developing EPS. The incidence of TD ranged from 2.8% (olanzapine) to 11.1% (depot typical agent). Compared with olanzapine, patients taking depot typical agents, oral typical agents, and risperidone had a significantly higher risk of developing TD. Baseline factors associated with a significantly higher risk of developing TD were age, EPS, a higher negative Clinical Global Impression score, and presence of gynecomastia. In summary, patients treated with typical antipsychotic agents (oral and depot) and risperidone had a higher risk of developing EPS and TD than patients treated with olanzapine. Higher baseline clinical severity was associated with EPS development, whereas age, presence of EPS, a higher negative Clinical Global Impression score, and presence of gynecomastia were associated with TD development.

  4. 长期服抗精神病药病人的隐性运动障碍%Covert dyskinesia in patients who chronically use antipsychotic medication

    Institute of Scientific and Technical Information of China (English)

    朱凤艳; 费立鹏; 吉中孚; Jeffery Lieberman

    2000-01-01

    目的 评估抗精神病药对迟发性运动障碍(TD)的掩盖,即隐性运动障碍(covert dyskinesia)状况.方法 应用Simpson运动障碍评分表评定TD.入组的69例病人有23例病人完成了减药之前、停药三周后和再服药四个月后的TD评定,69例次检查都给于录像,并且两个评定者按照录像独立评定TD是否存在,评定TD的一致性良好(ICC=0.75).结果 完成整个调查的23例病人中,减药前TD出现率为21.7%(5/23,CI=7.4%~43.4%),停药三周后TD出现率显著上升到78.3%(18/23,CI=56.3%~92.6%),然后再服药四个月后下降至43.5%(10/23,CI=23.6%~65.5%).减药前无TD的18例病人中停药三周后有14例出现TD,隐性运动障碍的出现率非常高,为77.8%(14/18,CI=52.3%~93.6%).结论 评估正在服抗精神病药病人TD时,其出现率偏低,因此评估TD的危险因素很容易出现错误的结论.

  5. Lung disease assessment in primary ciliary dyskinesia: a comparison between chest high-field magnetic resonance imaging and high-resolution computed tomography findings

    Directory of Open Access Journals (Sweden)

    Iacotucci Paola

    2009-08-01

    Full Text Available Abstract Background Primary ciliary dyskinesia (PCD is associated with pulmonary involvement that requires periodical assessment. Chest high-resolution computed tomography (HRCT has become the method of choice to evaluate chronic lung disease, but entails exposure to ionizing radiation. Magnetic resonance imaging (MRI has been proposed as a potential radiation-free technique in several chest disorders. Aim of our study is to evaluate whether high-field MRI is as effective as HRCT in identifying PCD pulmonary abnormalities. We also analyzed the relationships between the severity and extension of lung disease, and functional data. Methods Thirteen PCD patients (8 children/5 adults; median age, 15.2 yrs underwent chest HRCT and high-field 3T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified version of the Helbich system. Results HRCT and MRI total scores were 12 (range, 6–20 and 12 (range, 5–17, respectively. Agreement between HRCT and MRI scores was good or excellent (r > 0.8. HRCT and MRI total scores were significantly related to forced vital capacity (r = -0.5, p = 0.05; and r = -0.7, p = 0.009, respectively and forced expiratory volume at 1 second (r = -0.6, p = 0.03; and r = -0.7, p = 0.009, respectively. Conclusion Chest high-field 3T MRI appears to be as effective as HRCT in assessing the extent and severity of lung abnormalities in PCD. MRI scores might be used for longitudinal assessment and be an outcome surrogate in future studies.

  6. Hand-held tidal breathing nasal nitric oxide measurement--a promising targeted case-finding tool for the diagnosis of primary ciliary dyskinesia.

    Directory of Open Access Journals (Sweden)

    June Kehlet Marthin

    Full Text Available BACKGROUND: Nasal nitric oxide (nNO measurement is an established first line test in the work-up for primary ciliary dyskinesia (PCD. Tidal breathing nNO (TB-nNO measurements require minimal cooperation and are potentially useful even in young children. Hand-held NO devices are becoming increasingly widespread for asthma management. Therefore, we chose to assess whether hand-held TB-nNO measurements reliably discriminate between PCD, and Healthy Subjects (HS and included Cystic Fibrosis (CF patients as a disease control group known to have intermediate nNO levels. METHODS: In this cross sectional, single centre, single occasion, proof-of-concept study in children and adults with PCD and CF, and in HS we compared feasibility, success rates, discriminatory capacity, repeatability and agreement between a hand-held electrochemical device equipped with a nNO software application sampling at flow rates 2 ml/s or 5 ml/s, and two stationary chemiluminescence devices, applying both tidal breathing and velum closure techniques. RESULTS: Measurements were done in 16 PCD patients, 21 patients with CF and 20 HS aged between 3.8 and 60.9 years. Hand-held TB-nNO showed high success rate (96.5-100% vs. velum closure nNO techniques (70.2-89.5%. Hand-held TB-nNO sampling at flow rate 5 ml/s showed equally high discriminative power (PCD vs. HS [p<0.0001] and PCD vs. CF [p<0.0001] and reaching close to 100% sensitivity and specificity, superior repeatability (CV% = 10% and equal limits of agreement compared to TB-nNO by stationary devices and even compared to velum closure sampling. CONCLUSION: Hand-held TB-nNO discriminates significantly between PCD, CF and HS and shows promising potential as a widespread targeted case-finding tool for PCD, although further studies are warranted before implementation.

  7. Recent advances of diagnostic approaches in primary ciliary dyskinesia%原发性纤毛不动综合征诊断方法研究进展

    Institute of Scientific and Technical Information of China (English)

    刘娇(综述); 刘恩梅; 邓昱(审校)

    2016-01-01

    Primary ciliary dyskinesia (PCD) is an autosomal recessive or x-linked disorder of cilia structure and (or) function, with a morbidity of 1:10 000–1:50 000 from foreign reports, while epidemic data of PCD in China is not available yet. PCD is due to cilia biallelic gene mutations leading to impaired tissue structure and organ function. Clinical phenotypes include chronic infections of the respiratory tract, fertility problems, disorders of organ laterality, etc, and the percent age of Kartagener syndrome is about 50%. The frequently used diagnostic methods are nasal NO examination, high-speed video microscopy, electron microscopy, genetic tests, chest high-resolution computed tomography and spirometry at present. Each method has its highlights and disadvantages, meanwhile, effective diagnostic algorithm and therapeutic protocols are needed for further research.%原发性纤毛不动综合征是一种常染色体隐性遗传或X染色体相关的遗传疾病,国外发病率为1∶50000~1∶10000,国内尚无相关流行病学资料。该病发生机制为纤毛的双等位基因突变,导致组织器官的结构和/或功能改变,从而引起一系列相关临床表现,其中约50%为Kartagener综合征。目前常用的检查方法有鼻呼出气一氧化氮检测、透射电镜法、免疫荧光分析法、高频数字视频成像和基因诊断,但每种检查方法均有其优点及弊端。同时,统一的诊断思路及确切有效的治疗方案也处于探索研究阶段。

  8. Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naïve patients.

    Science.gov (United States)

    Woerner, Margaret G; Correll, Christoph U; Alvir, Jose Ma J; Greenwald, Blaine; Delman, Howard; Kane, John M

    2011-07-01

    Tardive dyskinesia (TD) rates with second-generation antipsychotics (SGAs) are considered to be low relative to first-generation antipsychotics (FGAs), even in the particularly vulnerable elderly population. However, risk estimates are unavailable for patients naïve to FGAs. Therefore, we aimed to determine the TD incidence in particularly vulnerable, antipsychotic-naïve elderly patients treated with the SGA risperidone or olanzapine. The present work describes a prospective inception cohort study of antipsychotic-naïve elderly patients aged 55 years identified at New York Metropolitan area in-patient and out-patient geriatric psychiatry facilities and nursing homes at the time of risperidone or olanzapine initiation. At baseline, 4 weeks, and at quarterly periods, patients underwent assessments of medical and medication history, abnormal involuntary movements, and extra-pyramidal signs. TD was classified using Schooler-Kane criteria. Included in the analyses were 207 subjects (age: 79.8 years, 70.0% female, 86.5% White), predominantly diagnosed with dementia (58.9%) or a major mood disorder (30.9%), although the principal treatment target was psychosis (78.7%), with (59.4%) or without (19.3%) agitation. With risperidone (n=159) the cumulative TD rate was 5.3% (95% confidence interval (CI): 0.7, 9.9%) after 1 year (mean dose: 1.0±0.76 mg/day) and 7.2% (CI: 1.4, 12.9%) after 2 years. With olanzapine (n=48) the cumulative TD rate was 6.7% (CI: 0, 15.6%) after 1 year (mean dose: 4.3±1.9 mg/day) and 11.1% (CI: 0, 23.1%) after 2 years. TD risk was higher in females, African Americans, and patients without past antidepressant treatment or with FGA co-treatment. The TD rates for geriatric patients treated with risperidone and olanzapine were comparable and substantially lower than previously reported for similar patients in direct observation studies using FGAs. This information is relevant for all patients receiving antipsychotics, not just the especially

  9. 伴迟发性运动障碍的慢性精神分裂症患者临床特征分析%Analysis of clinical characteristics in chronic schizophrenic patients with tardive dyskinesia.

    Institute of Scientific and Technical Information of China (English)

    胡卫红; 陆光华; 谢帆; 江开达

    2013-01-01

    Objective To explore the clinical characteristics in chronic schizophrenic patients with tardive dyskinesia (TD). Methods A total of 126 chronic schizophrenic patients with TD were assessed with Abnormal Involuntary Movement Scale (AIMS) to evaluate their dyskinesia movement and the Positive and Negative Symptom Scale (PANSS) to evaluate their psychiatric symptoms. Their clinical characteristics were compared with 116 chronic schizophrenic patients without TD. Results Compared with those without TD, schizophrenic patients with TD showed older age, longer duration of illness, higher total score of PANSS, higher score of negative symptoms and higher score of general psychopathology (P <0. 01 or P <0.05). There was no significant correlation between severity of TD with age, gender, total duration of illness, smoking, clinical psychopathology. Conclusion Chronic schizophrenic patients with TD have different clinical characteristics such as older age, longer duration of illness, more severe clinical psychopathology when compared with those without TD.%目的 探讨伴迟发性运动障碍(tardive dyskinesia,TD)的慢性精神分裂症患者的临床特征.方法 采用异常不自主运动评定量表(AIMS)对126例伴TD的慢性精神分裂症患者的不自主运动进行评定,运用阳性和阴性综合征量表(PANSS)对精神症状进行评估,并与1 16例不伴TD的慢性精神分裂症患者相对照.结果 与非TD患者相比较,TD患者相对年龄更大、病程更长(P<0.01),具有更高的PANSS总分、阴性症状评分及一般病理评分(P<0.01或P<0.05).TD严重程度与年龄、性别、总病程、吸烟、临床精神病理无显著相关性(P>0.05).结论 伴TD与不伴TD的慢性精神分裂症患者有不一样的临床特征,伴TD的患者年龄更大,病程更长,具有更严重的临床精神病理.

  10. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 2: Preclinical and Early Phase Human Proof of Concept Studies.

    Science.gov (United States)

    Macaluso, Matthew; Flynn, Alexandra; Preskorn, Sheldon

    2016-01-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients treated with antipsychotics. The first column in this series began with the case of a 76-year-old man with major depressive disorder who developed orofacial dyskinesias while being treated with aripiprazole as an antidepressant augmentation strategy. It was alleged that a higher than intended dose of aripiprazole (ie, 20 mg/d for 2 wk followed by 10 mg/d for 4 wk instead of the intended dose of 2 mg/d) was the cause of the dyskinetic movements in this man, and the authors were asked to review the case and give their opinion. The principal basis for this theory of causation was the class warning about TD in the package insert for aripiprazole. The rationale for concluding aripiprazole caused TD in the 76-year-old man led to this series of columns about aripiprazole, its potential--if any--to cause TD, and the presence of a class warning about TD in its package insert. The central point is to illustrate why class warnings exist and their implications for practice. The first column in this series focused on the historical background, incidence, prevalence, risk factors, and clinical presentations of tardive and spontaneous dyskinesias and concluded with a discussion of diagnostic considerations explaining why clinicians should avoid making a diagnosis of TD until a thorough differential diagnosis has been considered. This second column in the series reviews the pharmacology of aripiprazole and the preclinical and phase I translational human studies that suggest aripiprazole should have a low to nonexistent risk of causing TD compared with other antipsychotics. The third column in the series

  11. 伴发迟发性运动障碍的精神分裂症患者血清脑源性神经营养因子水平的对照研究%Comparative study on serum levels of brain-derived neurotrophic factors between schizophrenic patients with tardive dyskinesia and those without tardive dyskinesia

    Institute of Scientific and Technical Information of China (English)

    陈大春; 修梅红; 张保华; 卞清涛; 李占江; 张向阳

    2011-01-01

    目的 探讨外周血清脑源性神经营养因子(brain derived neurotrophic factor,BDNF)浓度与精神分裂症伴发的迟发性运动障碍(tadrive dyskinesia,TD)的关系.方法 收集精神分裂症伴发TD患者61例、不伴发TD的患者78例,以及正常对照102名.用酶联免疫吸附法检测BDNF水平,采用不自主运动量表(abnormal involuntary movement scale,AIMS)评估TD的严重程度,阳性和阴性症状量表(positive and negative symptom scale,PANSS)评估患者精神症状.结果 TD组、非TD组和对照组的BDNF水平分别为(9.35±1.60)μg/L、(10.12±2.03)μg/L、(12.27±2.7)μg/L,3组的差异有统计学意义(F=37.8,P0.05).TD组BDNF水平与AIMS总分、年龄、总病程负相关(r分别为-0.24、-0.32、-0.22,P均小于0.05),而在非TD组BDNF水平与上述因素均无相关(P>0.05).结论 精神分裂症伴发TD患者外周BDNF浓度下降,且其水平与异常运动严重程度相关,提示BDNF可能在TD的病理生理中发挥作用.%Objective To explore relationship between serum levels of brain-derived neurotrophic factors (BD-NF) and tardive dyskinesia (TD) in schizophrenic patients with TD and those without TD. Methods All patients satisfied DSM-IV criteria for schizophrenia. The serum BDNF levels were examined by using enzyme linked immunosorbent assay in patients with TD (n = 61) and patients without TD (n = 78) and controls (n = 102). The severity of TD and psychopathology were assessed using the abnormal involuntary movement scale (AIMS) and positive and negative symptom scale (PANSS), respectively. Results The patients with TD [(9.35 ± 1.60)μg/L] and those without TD [(10.12 ± 2.03)μg/L] had lower serum BDNF levels than normal controls [(12.27 ± 2.7)μg/L] (F = 37.8,P < 0.01). The patients with TD had markedly lower serum BDNF levels than those without TD (P = 0.04). The serum BDNF levels of patients with TD was inversely correlated with AIMS total score, age and duration of illness. In all patients

  12. Clinical characteristics of primary ciliary dyskinesia in children%儿童原发性纤毛运动障碍的临床研究

    Institute of Scientific and Technical Information of China (English)

    徐保平; 申昆玲; 胡英惠; 冯雪莉; 李惠民; 郎志奇

    2008-01-01

    目的 系统性研究儿童原发性纤毛运动障碍(primary ciliarydyskinesia,PCD)的临床特点,探讨PCD的诊断和鉴别诊断流程.方法 对PCD患儿的临床资料进行分析.结果 确诊PCD患儿26例,男11例,女15例.来自25个家族,1个家族诊断2例Kartagener综合征同胞姐弟.起病年龄为生后第2天~15岁,确诊时病程中位数为3.5年.所有患儿有咳嗽症状,24例有咯痰,7例有体格发育落后.23例接受支气管黏膜和(或)鼻黏膜的电镜检查,可见纤毛动力臂缺失6例,动力臂数目减少、微管排列紊乱、外周微管和(或)中央微管异常各4例,1例纤毛结构正常.经胸部CT证实,支气管扩张症8例,肺实变6例.20例存在鼻窦炎.15份痰或支气管肺泡灌洗液培养阳性标本中,铜绿假单胞菌8份,肺炎链球菌5份,白色念珠菌2份.其中1例培养出2种微生物.肺功能检查的16例中9例为阻塞性通气功能障碍.4例听力检测中3例异常,食管24 h pH值测定的5例患儿中3例有胃食管反流.结论 PCD起病年龄从新生儿期到青春期,呈慢性病程.主要临床表现为咳嗽、咯痰,可出现体格发育落后.PCD患儿中最多见的纤毛结构异常是动力臂缺失.部分患儿纤毛结构正常.影像学异常包括肺实变、支气管扩张症和鼻窦炎.常见的细菌病原为铜绿假单胞菌、肺炎链球菌,并可能存在混合感染.PCD患儿肺功能异常主要为阻塞性通气功能障碍,听力损害、胃食管反流出现率较高.%Objective Although primary cihary dyskinesia (PCD) is a group of inherited diseases,accurate diagnosis and appropriate clinical care to prevent and treat the complications could maintain patients' quality of life and normal life span.The diagnosis of PCD may often be delayed because it is frequently misdiagnosed as bronchitis,sinusitis and otitis.This study aimed to analyze and summarize the clinical features of PCD and explore diagnostic and differential diagnostic procedures in

  13. Discinesia ciliar primária: quando o pediatra deve suspeitar e como diagnosticar? Primary ciliary dyskinesia: when the pediatrician must suspect and how to do the diagnosis?

    Directory of Open Access Journals (Sweden)

    Mary Anne K. Olm

    2007-12-01

    Full Text Available OBJETIVO: Revisar a discinesia ciliar primária (DCP quanto aos seus aspectos ultra-estruturais, discriminar os defeitos ciliares primários dos secundários, descrever o quadro clínico, os testes laboratoriais de triagem e de diagnóstico disponíveis, bem como seu manejo clínico. FONTE DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, no período de 1980 a 2007. SÍNTESE DOS DADOS: A DCP é uma doença autossômica recessiva que compromete a estrutura e/ou a função ciliar e, conseqüentemente, o transporte mucociliar. As manifestações clínicas envolvem o trato respiratório superior e inferior, com infecções recorrentes do ouvido médio, seios paranasais e pulmonares, que podem evoluir para bronquiectasias. Outras manifestações incluem situs inversus totalis e infertilidade masculina. O diagnóstico deve ser suspeitado pelos pediatras em várias situações: recém-nascidos de termo com desconforto respiratório sem causa aparente; neonatos portadores de dextrocardia; lactentes com tosse persistente e/ou infecções otorrinolaringológicas de repetição, excluindo-se as imunodeficiências e a fibrose cística; crianças com asma atípica e as com bronquiectasias sem causa definida. Os testes de triagem diagnóstica são os da sacarina e do óxido nítrico nasal. As avaliações do defeito ultra-estrutural e funcional exigem análise por microscopia eletrônica e da freqüência e formato da onda de batimento ciliar. CONCLUSÕES: A DCP, apesar da baixa prevalência, é pouco diagnosticada pelas dificuldades de estabelecer o diagnóstico definitivo do defeito ciliar devido à complexidade da investigação laboratorial e pela falta de reconhecimento da doença pelos médicos. A suspeita clínica e o diagnóstico precoce são fundamentais para reduzir a morbidade e prevenir o desenvolvimento de complicações.OBJECTIVE: To review primary ciliary dyskinesia (PCD and its ultrastructural aspects, to differentiate primary

  14. Characteristics and Evaluation of Oral Dyskinesia and Dysarthria in Children with Cerebral Palsy%脑性瘫痪患儿口运动与构音障碍特征及其临床评定

    Institute of Scientific and Technical Information of China (English)

    纪静丽; 李欣; 侯梅; 李淑秋; 乔卫卫

    2015-01-01

    Objective To observe the efficacy of Complex Oral Motor Scoring (COMS) and diadochokinetic rate (DR) on evaluation of oral motor dysfunction and speech disorders in children with cerebral palsy. Methods 107 children with cerebral palsy were tested with Chi-nese-version Articulation Test, Simple Oral Motor Scoring (SOMS), COMS and DR. The correlation among SOMS, COMS and DR was analysesd. Results 85 children were abnormal in SOMS and 94 in COMS. Oral dyskinesia was found in all the children with spastic quadri-plegia, dyskinetic, ataxia and mixed type of cerebral palsy, and less in the type of spastic diplegia and hemiplegia. DR was the least in spas-tic quadriplegia, dyskinetic, mixed type of cerebral palsy, more in the type of ataxia and spastic diplegia, and the most in hemiplegia. The co-efficient of correlation among the SOMS, COMS, the longest pronunciation and DR were more than 0.8 (P0.8(P<0.01)。结论脑瘫患儿口运动障碍及构音障碍的发生率和严重程度与脑瘫类型有关。SOMS、COMS与DR、最长发音评估相关性良好。

  15. Dopamine-Induced Changes in Gαolf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of l-DOPA-Induced Dyskinesia in Parkinsonian Mice

    Science.gov (United States)

    Morigaki, Ryoma; Okita, Shinya; Goto, Satoshi

    2017-01-01

    The dopamine precursor, l-3,4-dihydroxyphenylalanine (l-DOPA), exerts powerful therapeutic effects but eventually generates l-DOPA-induced dyskinesia (LID) in patients with Parkinson’s disease (PD). LID has a close link with deregulation of striatal dopamine/cAMP signaling, which is integrated by medium spiny neurons (MSNs). Olfactory type G-protein α subunit (Gαolf), a stimulatory GTP-binding protein encoded by the GNAL gene, is highly concentrated in the striatum, where it positively couples with dopamine D1 (D1R) receptor and adenosine A2A receptor (A2AR) to increase intracellular cAMP levels in MSNs. In the striatum, D1Rs are mainly expressed in the MSNs that form the striatonigral pathway, while D2Rs and A2ARs are expressed in the MSNs that form the striatopallidal pathway. Here, we examined the association between striatal Gαolf protein levels and the development of LID. We used a hemi-parkinsonian mouse model with nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Using quantitative immunohistochemistry (IHC) and a dual-antigen recognition in situ proximity ligation assay (PLA), we here found that in the dopamine-depleted striatum, there appeared increased and decreased levels of Gαolf protein in striatonigral and striatopallidal MSNs, respectively, after a daily pulsatile administration of l-DOPA. This leads to increased responsiveness to dopamine stimulation in both striatonigral and striatopallidal MSNs. Because Gαolf protein levels serve as a determinant of cAMP signal-dependent activity in striatal MSNs, we suggest that l-DOPA-induced changes in striatal Gαolf levels in the dopamine-depleted striatum could be a key event in generating LID.

  16. Ginkgo biloba leaf extract and alpha-tocopherol attenuate haloperidol-induced orofacial dyskinesia in rats: Possible implication of antiapoptotic mechanisms by preventing Bcl-2 decrease and Bax elevation.

    Science.gov (United States)

    An, Hui Mei; Tan, Yun Long; Shi, Jing; Wang, Zhiren; Lv, Meng Han; Soares, Jair C; Zhou, Dongfeng; Yang, Fude; Zhang, Xiang Yang

    2016-12-01

    Tardive dyskinesia (TD) is a serious side effect of long-term administration of typical neuroleptics, such as haloperidol. The pathophysiology of TD remains unclear, but the experimental evidence suggests that free radical-induced neuronal apoptosis in the basal ganglia may play an important role. This study was to investigate changes in Bax and Bcl-2 expression levels in TD-associated brain regions and the effects of the antioxidant EGb761 on Bax and Bcl-2 levels in an animal model of TD. Thirty-two rats were randomly divided into four study groups: saline control (saline), haloperidol-alone (haloperidol), EGb761-haloperidol (EGb), and alpha-tocopherol-haloperidol (vitamin E). Rats were treated with daily intraperitoneal haloperidol injections (2 mg/kg/day) for 5 weeks. EGb761 (50 mg/kg/day) and alpha-tocopherol (20 mg/kg/day) were then administered for another 5 weeks during the withdrawal period. Behavioral assessments were performed, and Bax and Bcl-2 protein expression levels were immunohistochemically analyzed in four brain regions, including the prefrontal cortex, striatum, substantia nigra, and globus pallidum. We found that increased vacuous chewing movements (VCMs) were associated with increased proapoptotic Bax protein expression, decreased antiapoptotic Bcl-2 protein expression, and an increased Bax/Bcl-2 ratio. EGb761 and alpha-tocopherol treatment reversed the increase in VCMs, decreased Bax expression, increased Bcl-2 expression, and decreased the Bax/Bcl-2 ratio. These results demonstrate that long-term haloperidol administration may affect Bcl-2 protein family expression and promote neuronal apoptosis in the basal ganglia. In combination with their antioxidant capacity, EGb761 and alpha-tocopherol's antiapoptotic effects through Bcl-2 might account for the symptom improvement observed in haloperidol-induced TD rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Progress on NMDA receptors and Parkinson dyskinesia%N-甲基-D-天冬氨酸受体与帕金森异动症关系研究进展

    Institute of Scientific and Technical Information of China (English)

    缪茂军; 陈志斌

    2015-01-01

    帕金森病(PD)的治疗一直受到国内外神经科的关注,一度成为研究热点,主要是治疗PD会出现许多副作用,比如运动并发症(包括异动症),精神障碍和认知功能下降等,而异动症的出现限制了PD的治疗,但是异动症的发病机制甚为复杂,尚未阐明,N-甲基-D-天冬氨酸受体(NMDAR)与异动症的发生关系密切,因此阐明NMDAR与异动症的关系,寻找其潜在的靶点,很有可能代表一个有前途的治疗手段,本文就NMDAR与异动症的研究进展进行综述,为临床治疗提供参考.%On the treatment of Parkinson's disease (PD) has been attracting the attention of domestic and foreign neurologists, it has became a research hotspot, mainly in the treatment of PD can appear many side effects, complications such as sports [including L-DOPA-induced dyskinesia (LID)], psychiatric disorders and cognitive function decline, etc., and the appearance of movement disorder limits the treatment of PD, but the pathogenesis of movement disorder is complex and has not been clarified, N-methyl-D-aspartate receptor (NMDAR) is closely associated with the occurrence of different movement disorder, thus illustrating NMDAR relations with different movement disorder and looking for the potential targets are likely to represent a promising treatment, this article summarized research progress on NMDA receptor with LID to provide reference for clinical treatment.

  18. Incidence of Dyskinesia and Motor Fluctuations in Patients With Parkinson′s Disease and the Influencing Factors%帕金森病患者异动症及症状波动发生情况及其影响因素研究

    Institute of Scientific and Technical Information of China (English)

    车雁芳; 蔡春生; 曾明旋; 邱金华

    2016-01-01

    Objective To analyze the incidence of dyskinesia and motor fluctuations in patients with parkinson′s disease,to explore the influencing factors. Methods From October 2014 to September 2015,a total of 130 patients with parkinson′s disease were selected in the Department of Neurology,the First people′s Hospital of Huizhou,the clinical data was retrospectively analyzed,including onset age,gender,initial symptom,disease course,levodopa agents treatment time, levodopa equivalents,H-Y grade and UpDRS score. Incidence of dyskinesia and motor fluctuations in patients with parkinson′s disease were recorded,and the influencing factors was analyzed by multivariate logistic regression analysis. Results Of the 130 patients with parkinson′s disease,20 cases(accounting for 15. 38% )occurred dyskinesia,43 cases(accounting for 33. 08% ) occurred motor fluctuations. No statistically significant differences of gender or initial symptom was found in parkinson′s disease patients complicated with dyskinesia and did not complicated with dyskinesia(P > 0. 05);compared with parkinson′s disease patients did not complicated with dyskinesia,the onset age of parkinson′s disease patients complicated with dyskinesia was statistically significantly lower,disease course and levodopa agents treatment time were statistically significantly longer,levodopa equivalents was statistically significantly more,H-Y grade and UpDRS score were statistically significantly higher(P 0. 05);compared with parkinson′s disease patients did not complicated with motor fluctuations,the onset age of parkinson′ s disease patients complicated with motor fluctuations was statistically significantly lower,disease course and levodopa agents treatment time of were statistically significantly longer, levodopa equivalents was statistically significantly more,H-Y grade and UpDRS score were statistically significantly higher(P 0.05);发生异动症的患者发病年龄小于无异动症的患者,病程

  19. 多巴胺β羟化酶基因G444A多态性可能与慢性精神分裂症患者迟发性运动障碍关联%The G444A Polymorphism in the Dopamine-β-Hydroxylase Gene May Be Associated with Neuroleptic-Induced Tardive Dyskinesia in Chronic Schizophrenia

    Institute of Scientific and Technical Information of China (English)

    施佳军; 范长河; 邓河晃; 郭扬波; 冯容妹; 韩海英; 阳琼; 马崔

    2004-01-01

    目的:观察广州地区汉族人群中有或无迟发性运动障碍(TD)精神分裂症患者中,多巴胺β羟化酶基因(dopamineβ-hydroxylase gene,DBH)外显子2单核苷酸多态性G444A的分布,并探讨该多态与迟发性运动障碍发生的关系.方法:以196例慢性精神分裂症患者(67例伴TD,129例不伴TD)为对象进行病例-对照研究.用聚合酶链反应-限制性片段长度多态性方法分析DgH基因G444A多态性.结果:TD组等位基因DBH44G频率显著高于非TD组(x2=12.71,P<0.001),TD组GG及GA基因型频率也显著高于非TD组(P均<0.05).结论:DBH基因G444A多态性可能与慢性精神分裂症患者TD的发生关联.%Objective:To investigate the relationship of a G→A variation (G444A) in exon 2 of the dopamine-βhydroxylase gene (DBH) and tardive dyskinesia (TD) in chronic schizophrenia. Methods: Schizophrenic patients (67with and 129 without tardive dyskinesia) were genotyped for the G444A polymorphism in DBH gene by PCR-RFLP.The relationship of DBH variation to TD was analyzed. Results: No significant differences were observed in gender,age, duration of illness or total score on Abnormal Involuntary Movements Scale in patients with the three DBH genotypes while there was significant difference in current neuroleptic dosage. The frequency of DBH 444G allele in patients with TD was significantly higher than that in those without TD. An association of TD with the G allele was observed. Conclusions: The G444A polymorphism in DBH gene may confer susceptibility to neuroleptic-induced tardive dyskinesia in schizophrenia. To confirm these findings and to explore the possible role of dopamine βhydroxylase in the pathogenesis of TD, further studies are needed.

  20. Discinesia ciliar primária: considerações sobre seis casos da síndrome de Kartagener Primary ciliary dyskinesia: considerations regarding six cases of Kartagener syndrome

    Directory of Open Access Journals (Sweden)

    Hugo Alejandro Vega Ortega

    2007-10-01

    Full Text Available A discinesia ciliar primária (DCP, anteriormente conhecida como síndrome dos cílios imóveis, é uma doença hereditária autossômica recessiva que inclui vários padrões de defeitos em sua ultra-estrutura ciliar. Sua forma clínica mais grave é a síndrome de Kartagener (SK, a qual é encontrada em 50% dos casos de DCP. A DCP causa deficiência ou mesmo estase no transporte de secreções em todo o trato respiratório, favorecendo a proliferação de vírus e bactérias. Sua incidência varia de 1:20.000 a 1:60.000. Como conseqüência, os pacientes apresentam infecções crônicas e repetidas desde a infância e geralmente são portadores de bronquite, pneumonia, hemoptise, sinusite e infertilidade. As bronquiectasias e outras infecções crônicas podem ser o resultado final das alterações irreversíveis dos brônquios, podendo progredir para cor pulmonale crônico e suas conseqüências. Somente a metade dos pacientes afetados pela DCP apresenta todos os sintomas, condição denominada SK completa; no restante, não ocorre situs inversus, condição denominada SK incompleta. O diagnóstico é feito com base no quadro clínico e confirmado por meio da microscopia eletrônica de transmissão. Como não há tratamento especifico para a DCP, recomenda-se que, tão logo seja feito o diagnóstico, as infecções secundárias sejam tratadas com antibióticos potentes e medidas profiláticas sejam adotadas. Neste trabalho, relatamos seis casos de DCP (cinco casos de SK completa e um caso de SK incompleta e revisamos a literatura sobre o assunto, tendo como foco os aspectos diagnósticos, terapêuticos e clínicos desta doença.Primary ciliary dyskinesia (PCD, previously known as immotile cilia syndrome, is an autosomal recessive hereditary disease that includes various patterns of ciliary ultrastructural defects. The most serious form is Kartagener syndrome (KS, which accounts for 50% of all cases of PCD. The incidence of PCD ranges from 1

  1. 伴迟发性运动障碍精神分裂症患者脑铁沉积的对照研究%A comparative study of brain iron deposition in schizophrenia with and without tardive dyskinesia

    Institute of Scientific and Technical Information of China (English)

    陈方斌; 金梅; 徐乐平; 周菲菲; 汪莉; 纪菊英

    2012-01-01

    Objective To explore the relationship between brain iron deposition and pathogenesis of tardive dyskinesia (TD) in schizophrenia.Methods The corrected phase (CP) of basal ganglia was measured in schizophrenia with TD( n=18) and without TD( n =18 ) using susceptibility weighted imaging MRI.Abnormal Involuntary Movement Scale (AIMS) was applied for clinical assessment of TD.Results After adjusting for age,sexual,and antipsychotic dosage,the mean CP of substantia nigra (SN) and caudate nucleus (CN) were significantly lower in schizophrenia patients with TD ( ( - 0.194 ± 0.040 ) rad,( - 0.089 ± 0.023 ) rad) than those without TD ( ( - 0.163 ± 0.033 ) rad,( - 0.076 ± 0.013 ) rad ; P =0.022,0.023 ).Lower mean CP in CN correlated with higher severity score of AIMS in TD patients ( r =- 0.468,P =0.034).Logistic regression analysis showed that the lower CP vaule in SN (β=-72.12,P=0.029) and CN(β=- 156.43,P=0.037),aging (β=0.379,P=0.042)were associated with the onset of TD.Conclusion The results imply that the excess iron accumulation in basal ganglia may be associated with pathogenesis of TD in schizophrenia.%目的 探讨脑铁沉积与迟发性运动障碍(TD)的关系.方法 利用磁敏感加权成像技术,测定伴TD(TD组,n=18)、不伴TD(非TD组,n=18)的精神分裂症患者基底节灰质核团的校正相位值(CP);采用异常不自主运动量表(AIMS)评定TD症状.结果 (1)调整年龄、性别、药物因素后,TD组黑质、尾状核CP值[分别(-0.194±0.040)rad,(-0.089±0.023)md]低于非TD组[分别(-0.163±0.033) rad,(-0.076 ±0.013)rad;P=0.022,0.023];(2)TD组尾状核CP值与AIMS严重程度评分负相关(r=-0.486,P=0.034);Logistic回归显示,黑质、尾状核CP值低(分别β=-72.12,- 156.43;P=0.029,0.037)、年龄高(β=0.370,P=0.042)与TD的发生有关.结论 TD患者基底节有脑铁过量沉积,并可能与TD的发生有关.

  2. Genetics Home Reference: primary ciliary dyskinesia

    Science.gov (United States)

    ... Med Genet. 2009 Apr;46(4):281-6. doi: 10.1136/jmg.2008.061176. Citation on PubMed Failly M, Saitta A, Muñoz A, Falconnet E, Rossier C, Santamaria F, de Santi MM, Lazor R, ... doi: 10.1159/000128567. Epub 2008 Apr 23. Citation ...

  3. Genetics Home Reference: familial paroxysmal kinesigenic dyskinesia

    Science.gov (United States)

    ... Med Genet. 2008 Dec;45(12):773-9. doi: 10.1136/jmg.2008.059519. Review. Citation on PubMed Silveira- ... Pract Neurol. 2009 Apr;9(2):102-9. doi: 10.1136/jnnp.2009.172213. Review. Citation on PubMed Reviewed : ...

  4. An international registry for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Werner, Claudius; Lablans, Martin; Ataian, Maximilian

    2016-01-01

    patients have been collected so far. The database is comprised of a basic data form including demographic and diagnostic information, and visit forms designed to monitor the disease course.To establish a definite PCD diagnosis, we used strict diagnostic criteria, which required two to three diagnostic...

  5. Genetics Home Reference: ADCY5-related dyskinesia

    Science.gov (United States)

    ... 27. Citation on PubMed Chen DH, Méneret A, Friedman JR, Korvatska O, Gad A, Bonkowski ES, Stessman ... or Free article on PubMed Central Chen YZ, Friedman JR, Chen DH, Chan GC, Bloss CS, Hisama ...

  6. Genetics Home Reference: familial paroxysmal nonkinesigenic dyskinesia

    Science.gov (United States)

    ... This Page Bruno MK, Lee HY, Auburger GW, Friedman A, Nielsen JE, Lang AE, Bertini E, Van ... DA, Lang AE, Nielsen JE, Averyanov Y, Servidei S, Friedman A, Van Bogaert P, Abramowicz MJ, Bruno MK, ...

  7. Clinical efficacy of different frequency repetitive transcranial magnetic stimulation for tardive dyskinesia%不同频率重复经颅磁刺激治疗迟发性运动障碍的疗效研究

    Institute of Scientific and Technical Information of China (English)

    张保华; 谭云龙; 王志仁; 张五芳; 杨甫德; 卞清涛; 韩笑乐; 江述荣; 杨贵刚

    2014-01-01

    目的 探讨不同频率重复经颅磁刺激(rTMS)治疗迟发性运动障碍(TD)的疗效.方法 长期服用抗精神病药所致迟发性运动障碍的精神分裂症患者,随机给予1 Hz(低频)和10 Hz(高频)的rTMS治疗4周,每周治疗5d.中间休息2周.分别在治疗前和治疗后进行异常不自主运动评定量表(AIMS)和锥体外系副反应量表(RESES)评定,评分变化作为疗效和副反应评价指标.结果 低频组经rTMS治疗后只有上肢的不自主运动改善[治疗前(2.6±1.0)分,治疗后(1.8±1.1)分],差异有统计学意义(P<0.05).高频组经rTMS治疗后多个量表分下降,其中上肢[治疗前(1.9±1.2)分,治疗后(0.8±0.9)分]、唇及口周[治疗前(1.0±0.8)分,治疗后(0.3±0.5)分]和舌[治疗前(2.6±0.9)分,治疗后(1.7±0.9)分]及总量表分[治疗前(7.7±3.0)分,治疗后(4.2±1.7)分]评分治疗前后差异有统计学意义(P< 0.05或<0.01).另外,两组间在下肢和总量表分减分率方面差异有统计学意义(P<0.05).结论 rTMS治疗TD有效,且高频(10 Hz)组治疗TD效果好.%Objective To investigate the effect of different frequency of repetitive transcranial magnetic stimulation (rTMS)on tardive dyskinesia (TD).Methods Schizophrenia combined with antipsychotic-induced TD were screened.All patients were planed to receive 1Hz or 10Hz rTMS for 4 weeks in which two weeks' break was inserted at end of 2nd weekend.The curative effect and side effects were assessed by abnormal involuntary movement scale(AIMS) and rating scale for extrapyramidal side effects(RSESE) respectively at before and after treatment.Results In the 1Hz group,only Involuntary movements of the upper extremities were improved after rTMS treatment (before treatment 2.6± 1.0,after treatment 1.8 ± 1.1),the difference was statistically significant (P<0.05).But in 10Hz group,upper extremities (before treatment 1.9 ± 1.2,0.8 ± 0.9 after treatment),mouth (before treatment 1.0±0.8,after treatment 0.3±0

  8. 音乐结合强制性使用运动疗法治疗脑梗塞上肢运动障碍疗效观察%Efficacy Observation on Music Therapy Combined with Constraint-Induced Movement Therapy for Upper Extremity Dyskinesia after Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    王飞; 王建华; 张丽娟; 谢立娟; 史艳

    2014-01-01

    目的:探讨音乐疗法结合强制性使用运动疗法治疗脑梗塞上肢运动功能障碍的疗效及机理。方法:将120例脑梗塞亚急性期上肢功能障碍患者随机分为观察组(50例)和对照组(50例),两组患者在入院后均接受常规康复训练及内科治疗;2周后,对照组在常规康复训练、治疗基础上给予强制性使用运动疗法治疗,观察组则给予音乐疗法结合强制性使用运动疗法,干预14天后观察两组患者上肢动作研究量表(ARAT)评分、Fugl-Meyer量表(FMA)评分、汉密尔顿焦虑量表(HAMA)评分的改善情况。结果:干预14天后,观察组ARAT评分、FMA评分均显著高于对照组(P<0.01),HAMA评分显著低于对照组(P<0.01)。结论:音乐结合强制性使用运动疗法可有效改善脑梗塞亚急性期上肢功能障碍及焦虑状态,值得临床推广应用。%Objective:To investigate the efficacy and mechanism of music therapy combined with constraint-induced movement therapy (CIMT) for upper extremity dyskinesia after cerebral infarction. Methods:120 cases of patients with upper extremity dyskinesia at sub-acute phase of cerebral in-farction were randomly divided into observation group (50 cases) and control group (50 cases), both groups were received conventional rehabilitation training and medical treatment after hospitalization;2 weeks later, on the basis of conventional rehabilitation training and medical treatment, the con-trol group treated by CIMT, while the observation group by music therapy combined with CIMT, then observed the improvement of ARAT, FMA and HAMA scores of two groups after 14 days. Results:After 14 days' intervention, the ARAT and FMA scores of observation group were both signifi-cantly higher than those of control group (P<0.01), while HAMA score was significantly lower than that of control group (P<0.01). Conclusion:Mu-sic therapy combined with CIMT can effectively improve upper

  9. 3个单纯型发作性运动诱发性运动障碍家系的致病基因定位%Mapping of the gene responsible for pure paroxysmal kinesigenic dyskinesia in three Chinese Han families

    Institute of Scientific and Technical Information of China (English)

    陈素琴; 王一鸣; 李洵桦; 梁秀龄; 周珏倩; 方莹莹

    2011-01-01

    目的 在3个中国汉族单纯型发作性运动诱发性运动障碍(paroxysmall kinesigenic dyskinesia,PKD)家系中确定其疾病基因所在区域.方法 在已知的PKD连锁区域16p12.2-q22.3选取14个微卫星遗传标记对37位家庭成员进行基因分型,用Linkage和Genehunter等软件进行连锁分析并构建疾病单倍型.结果 连锁分析及单倍型分析将致病基因定位于D16S3133~D16S3044(16p12.1-q12.1)之间11.2 cM的区域.结论 3个汉族单纯型PKD家系的致病基因被定位于D16S3133~D16S3044(16p12.1-q12.1)之间,与最初的婴儿惊厥及阵发性舞蹈手足徐动症(infantile convulsions and paroxysmal clboreoathetosis,ICCA)的位点重叠.%Objective To map the gene responsible for pure paroxysmal kinesigenic dyskinesia in three Chinese Han families. Methods Fourteen microsatellite markers flanking 16pl2.2-q22.3 were selected for genotyping in 37 family members. Parameter and non-parameter analysis were performed using Linkage and Genehunter softwares and haplotypes were constructed. Results A maximum two-lod score 2.97 at D16S3080 (θ = 0) and 2.53 at D16S3068 (θ = 0) were obtained when penetrance set to 0.7. A maximum multi-lod score 2.75 and maximum NPL score 3.85 (P = 0.002) were obtained at D16S3068-D16S3131. Haplotype analysis localized PKD to the region D16S3133 - D16S3044 (16p12.1-q12.1). Conclusions The gene responsible for PKD in three Chinese Han families was mapped to 16p12.1-q12.1, which was the same as the original ICCA (infantile convulsions and paroxysmal choreoathetosis) region.

  10. A clinical study of MECT in the treatment of chronic schizo-phrenia with tardive dyskinesia%无抽搐电休克治疗慢性精神分裂症伴迟发性运动障碍临床研究

    Institute of Scientific and Technical Information of China (English)

    谢舟明; 王跃升; 龚毅

    2014-01-01

    目的:探讨无抽搐电休克治疗慢性精神分裂症伴迟发性运动障碍患者的临床疗效。方法对58例慢性精神分裂症伴迟发性运动障碍患者在维持原用抗精神病药物治疗的基础上联合无抽搐电休克治疗,观察6周。采用不自主运动评定量表评定临床效果。结果本组经无抽搐电休克治疗6周后不自主运动评定量表评分较治疗前显著下降( t=18.34,P<0.01),不自主运动症状明显改善,总有效率达93.1%。结论无抽搐电休克治疗能显著改善慢性精神分裂症伴迟发性运动障碍患者的不自主运动症状。%Objective To explore the efficacy of modified electroconvulsive thera-py (MECT) in the treatment of chronic schizophrenia with tardive dyskinesia (TD) .Methods Fifty-eight chronic schizophrenics with TD were treated with MECT on the basis of maintaining antipsychotic treat-ment for 6 weeks .Efficacies were assessed with the Abnormal Involuntary Movement Scale (AIMS) .Re-sults After 6-week MECT the AIMS score lowered more significantly compared with pre-treatment (t=18 .34 ,P< 0 .01) ,involuntary movement symptoms improved notably ,total effective rate was 93 .1% . Conclusion MECT could improve involuntary movement symptoms of chronic schizophrenic with TD sig-nificantly .

  11. 传统抗精神病药物所致迟发性运动障碍的药理遗传学初步研究%Pharmacogenetic assessment of antipsychotic-induced tardive dyskinesia: contribution of 5-hydroxytryptamine 2C receptor gene and of a combination of dopamine D3 variant allele (Gly) and MnSOD wild allele (Val)

    Institute of Scientific and Technical Information of China (English)

    张珺; 侯钢; 张晓斌; 姚辉; 沙维伟; 张心保

    2003-01-01

    目的进一步探讨多巴胺D2、D3受体(dopamine D2,D3 receptor, DRD2,DRD3)功能基因多态性与迟发性运动障碍(tardive dyskinesia, TD)的相关性及各候选基因,同时包括五羟色胺2C受体(5-hydroxytryptamine 2C receptor, HTR2C)和锰超氧化物歧化酶(manganese superoxide dismutase, MnSOD)基因的相互作用对TD发生的影响.方法使用异常不自主运动量表(abnormal involuntary movement scale, AIMS)评定精神分裂症(schizophrenia, SCH)患者有无TD及其严重程度,并采用简明精神病评定量表评定患者精神症状;应用聚合酶链反应-限制性片段长度多态性技术分析TD组和非TD组各候选基因等位基因和(或)基因型分布频率及其结合分布频率,并分析对AIMS总分值的影响.结果各候选基因在SCH患者组以及TD和非TD组基因型分布均符合Hardy-Weinberg平衡定律;TD组HTR2C基因-697C(突变型)等位基因频率高于非TD组,差异有显著性(P0.05);仅DRD3突变型(Gly)和MnSOD野生型(Val)结合分布频率高于其它结合型,差异有显著性(P0.05).结论 HTR2C基因启动区-697G→C单碱基置换可能是中国汉族男性SCH患者TD发生的易感因素;而SCH患者若同时携带DRD3基因9Gly突变型和MnSOD基因-9Val 野生型等位基因可能增加了TD的易感性.

  12. β-arrestin1 mediates the effect of MK-801 on levodopa-induced dyskinesia in Parkinson ', s disease%β-arrestin1参与MK-801治疗帕金森病异动症的研究

    Institute of Scientific and Technical Information of China (English)

    吴娜; 宋璐; 杨新新; 刘振国

    2011-01-01

    目的 探讨MK-801缓解帕金森病(PD)异动症的治疗机制。方法 建立PD运动并发症大鼠模型,25只大鼠随机分为3组:异动症(LID)组10只、MK-801处理组10只、PD组5只,另设假手术组5只为对照组。观察MK-801治疗左旋多巴诱导的异动症大鼠模型的行为学变化,并采用免疫组织化学方法和Western blot印迹法检测大鼠纹状体区β-arrestin1的表达情况。结果 MK-801处理后,LID大鼠模型异常不自主运动评分降低和剂峰旋转行为减弱。免疫组织化学结果显示LID组损伤侧β-arrestin1阳性细胞指数[(2.95±0.44) ×104]明显较未损伤侧[(3.78 ±0.37)×104]降低,差异有统计学意义(t =5.415,P<0.05)。Western blot结果显示,PD模型组损毁侧与未损毁侧纹状体区β-arrestin1含量比值为81.02% ±2.23%;LID组(64.88%±3.10%)蛋白表达量进一步减少,与PD组比较,差异有统计学意义(t=9.47,P<0.01);而MK-801组蛋白表达量增高至89.26%±1.90%,与LID组相比,差异有统计学意义(t=14.82,P<0.01)。结论 MK-801能缓解LID大鼠的行为学变化,其机制可能与β-arrestin1表达增多抑制了谷氨酸受体的过度活化有关。%Objective To investigate the effect of MK-801 on levodopa-induced dyskinesia (LID)in Parkinson' s disease (PD). Methods Rat models ( n = 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n = 10), MK801 treatment group (n = 10) and PD group (n =5). Another 5 rats were served as control group. The behaviors of LID rats treated with MK-801 were observed. Immunohistochemistry and Western blot analysis were used to determine the expression of β-arrestin1 in the striate of rats. Results After MK-801 treatment, abnormal involuntary movement scores and peak turning were decreased in LID rats.Immunohistochemistry showed that β-arrestin1-positive cells of the lesioned side ((2

  13. Efficacy on Affective Disorder and Dyskinesia Treated with Modified Sini San and Music Therapy in the Patients of Post - Stroke Depression%加味四逆散联合音乐疗法对脑卒中后合并抑郁症状患者的情感和肢体运动障碍的疗效观察

    Institute of Scientific and Technical Information of China (English)

    梁迪赛

    2016-01-01

    Objective To explore the efficacy on the affective disorder and dyskinesia treated with modified sini san and music therapy in the patients of post - stroke depression(PSD). Methods One hun-dred and eighty PSD patients were randomized into a combined treatment of modified sini san and music ther-apy(combined therapy group,64 cases),a modified sini san group(TCM control group,62 cases)and a rou-tine western medicine group(western medicine control group,54 cases). The basic treatment was given in the three groups. In the western medicine control group,besides the basic treatment,fluoxetine was used. In the TCM control group,besides the basic treatment,the granules of modified sini san were added. In the combined therapy group,on the basis of the treatment as the TCM control group,music therapy was added. The different music types were selected in accordance with the syndrome differentiation. Hamilton depression scale (HAMD),scale of activities of daily living(ADL)and national institute of health stroke scale(NIHSS)as well as the relevant adverse reactions were observed 8 weeks after treatment in the three groups. Results In the 4th and 8th weeks of the treatment in the three groups,HAMD score was reduced significantly(P ﹤ 0. 05), ADL score was increased significantly(P ﹤ 0. 05)and NIHSS score was reduced significant only in the 8th week(P ﹤ 0. 05). In the 4th week of treatment,HAMD and ADL scores in the combined treatment group were different significantly as compared with the western medicine control group(P ﹤ 0. 05,P ﹤ 0. 01). In the 8th week group,HAMD and NIHSS scores were lower significantly than those in the TCM control group and the western medicine control group(P ﹤ 0. 05). The difference in the incidence of adverse reactions was not sig-nificant among the three groups(P ﹥ 0. 05). Conclusion The combined treatment of modified sini san and music therapy is safe and effective in affective order and dyskinesia in PSD patients and the effects are

  14. Dyskinesias evoked in monkeys by weekly administration of haloperidol

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.; Santelli, S.

    1978-05-19

    In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

  15. Dyskinesias evoked in monkeys by weekly administration of haloperidol.

    Science.gov (United States)

    Weiss, B; Santelli, S

    1978-05-19

    In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

  16. Ventilation inhomogeneity in children with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Green, Kent; Buchvald, Frederik F; Marthin, June Kehlet

    2012-01-01

    The lung clearance index (LCI) derived from the multiple breath inert gas washout (MBW) test reflects global ventilation distribution inhomogeneity. It is more sensitive than forced expiratory volume in 1 s (FEV(1)) for detecting abnormal airway function and correlates closely with structural lun...

  17. Primary ciliary dyskinesia: Kartagener syndrome in a family with a ...

    African Journals Online (AJOL)

    Makia J. Marafie

    2014-12-22

    Dec 22, 2014 ... ter management of the affected family members, which in turn could significantly improve overall .... for three times, in both ears with pressure equalization tubes. .... We have identified a disease-causing mutation in exon 58.

  18. MALADAPTIVE PLASTICITY IN LEVODOPA-INDUCED DYSKINESIAS AND TARDIVE DYSKINESIAS: OLD AND NEW INSIGHTS ON THE EFFECTS OF DOPAMINE RECEPTOR PHARMACOLOGY

    OpenAIRE

    Antonio eCerasa; Alfonso eFasano; Francesca eMorgante; Giacomo eKoch; Aldo eQuattrone

    2014-01-01

    Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, either in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting...

  19. Maladaptive Plasticity in Levodopa-Induced Dyskinesias and Tardive Dyskinesias: Old and New Insights on the Effects of Dopamine Receptor Pharmacology

    OpenAIRE

    Cerasa, Antonio; Fasano, Alfonso; Morgante, Francesca; Koch, Giacomo; Quattrone, Aldo

    2014-01-01

    Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation, and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting, syna...

  20. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

    DEFF Research Database (Denmark)

    Herz, Damian M.; Haagensen, Brian N.; Christensen, Mark S.

    2015-01-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy...

  1. Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome

    Science.gov (United States)

    Mongin, Marie; Mezouar, Nicolas; Dodet, Pauline; Vidailhet, Marie; Roze, Emmanuel

    2016-01-01

    Background Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Phenomenology Shown Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. Educational Value Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable. PMID:27351150

  2. A longitudinal evaluation of hearing and ventilation tube insertion in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Andersen, Tobias Nicolai; Alanin, Mikkel Christian; von Buchwald, Christian;

    2016-01-01

    audiometries were evaluated. The median number of audiometries per patient was 3 (range 1-29) and the median follow-up was 60 months (range 0-351 months). The mean PTA was 34 dB HL in patients below six years of age and improved significantly (p

  3. [Neurosurgical treatment for dopamine-induced dyskinesias in Parkinson's disease patients].

    Science.gov (United States)

    Sugiyama, K; Yokoyama, T; Namba, H

    2000-10-01

    The effects of current neurosurgical interventions for levodopa-induced dyskiensias (DID) in Parkinson's disease are reviewed. Thalamotomy has been reported to be effective for DID when the lesions include Vo or CM-Pf nucleus, while thalamic deep brain stimulation(DBS) is less effective than thalamotomy. Both pallidotomy and pallidal DBS are probably the most effective neurosurgical treatment for DID, because they significantly improve all of the DID, including off-period dystonia, without reduction of levodopa dosage. Subthalamic DBS has no direct therapeutic effects on DID, but substantially can improve DID as a result of decreased levodopa dosage. The effects of cerebral transplantation on DID remain undefined. More researches are expected to clarify the pathophysiology of DID.

  4. Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Marthin, J K; Nielsen, K G

    2011-01-01

    as first-line tests for PCD. Healthy subjects, confirmed PCDs, consecutive referrals with PCD-like symptoms and patients with cystic fibrosis (CF) had nNO sampled during breath hold (BH-nNO), oral exhalation against resistance (OE-R-nNO) and tidal breathing (TB-nNO) aiming to expand age range into infancy...

  5. The classical genetic and genomic approach to the pathogenesis of primary ciliary dyskinesia

    NARCIS (Netherlands)

    Geremek, Maciej

    2012-01-01

    Trilharen (of cilia) zijn sterk gedifferentieerde structuren die specifieke cellulaire functies vervullen, zoals voortbeweging, waarneming van omgevingssignalen, of het geleidelijk naar buiten werken van de slijmlaag in de luchtwegen. Positionering van organen in het lichaam is deels ook afhankelijk

  6. Primary ciliary dyskinesia: Kartagener syndrome with central giant cell granuloma. A case report.

    Science.gov (United States)

    Türkoğlu, Kivanç; Orhan, Kaan; Demir, Pinar; Karabulut, Bariş; Can-Karabulut, Deniz C

    2010-10-01

    This paper describes a clinical case of both giant cell granuloma and Kartagener syndrome in a 15-year-old male patient, with emphasis on the radiographic aspects of this extremely unusual pathology. To our knowledge, the presence of these 2 rare clinical conditions in the same patient has not been previously reported.

  7. Dyskinesia, cardiac arrhythmia and partial seizure associated with paliperidone overdose: a case report

    Directory of Open Access Journals (Sweden)

    Antonio Villa

    2015-12-01

    Full Text Available Paliperidone is a new atypical antipsychotic agent. There are few literature reports of paliperidone overdoses and we report a case of these. A 32-year-old man was admitted to Emergency Department for occurrence of opisthotonus, muscular spasms and rigidity. Twenty hours before, he had an ingestion of 168 mg of paliperidone. He had hypotension and tachycardia. The dystonic reaction completely resolved within a few minutes after diazepam. Nine hours after admission, he sudden showed a right hemisoma partial seizure. The peculiar interest of our case is that three different and rare symptoms occurred in successive times after overdose. Some symptoms occurred after several hours following overdose. Oral paliperidone is available as an osmotic release delivery system that results in a gradual rise in plasma concentrations. According to this limited experience in which delayed onset of toxicity has been observed, it may be prudent to recommend prolonged observation after overdose of paliperidone.

  8. Health-Related Quality of Life and Healthcare Utilisation in Patients with Parkinson's Disease: Impact of Motor Fluctuations and Dyskinesias

    OpenAIRE

    Richard C. Dodel; Karin Berger; Oertel, Wolfgang H

    2001-01-01

    Idiopathic Parkinson's disease (PD) is a common chronic progressive neurodegenerative disorder associated with the progressive loss of dopaminergic neurons in the substantia nigra. The natural course of the disease may lead to severe disability despite a variety of pharmacological and surgical treatment options. Levodopa is still the most effective symptomatic treatment for PD; however, long term use can cause a number of adverse effects including motor complications, nausea and vomiting, pos...

  9. CCDC151 Mutations Cause Primary Ciliary Dyskinesia by Disruption of the Outer Dynein Arm Docking Complex Formation

    NARCIS (Netherlands)

    Hjeij, R.; Onoufriadis, A.; Watson, C.M.; Slagle, C.E.; Klena, N.T.; Dougherty, G.W.; Kurkowiak, M.; Loges, N.T.; Diggle, C.P.; Morante, N.F.; Gabriel, G.C.; Lemke, K.L.; Li, Y.; Pennekamp, P.; Menchen, T.; Konert, F.; Marthin, J.K.; Mans, D.A.; Letteboer, S.J.F.; Werner, C.; Burgoyne, T.; Westermann, C.; Rutman, A.; Carr, I.M.; O'Callaghan, C.; Moya, E.; Chung, E.M.; Consortium, U.K.; Sheridan, E.; Nielsen, K.G.; Roepman, R.; Bartscherer, K.; Burdine, R.D.; Lo, C.W.; Omran, H.; Mitchison, H.M.

    2014-01-01

    A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, p

  10. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation

    DEFF Research Database (Denmark)

    Hjeij, Rim; Onoufriadis, Alexandros; Watson, Christopher M

    2014-01-01

    disorder of ciliary and flagellar dysmotility characterized by chronic upper and lower respiratory infections and defects in laterality. Here, by combined high-throughput mapping and sequencing, we identified CCDC151 loss-of-function mutations in five affected individuals from three independent families...... whose cilia showed a complete loss of ODAs and severely impaired ciliary beating. Consistent with the laterality defects observed in these individuals, we found Ccdc151 expressed in vertebrate left-right organizers. Homozygous zebrafish ccdc151(ts272a) and mouse Ccdc151(Snbl) mutants display a spectrum...... of situs defects associated with complex heart defects. We demonstrate that CCDC151 encodes an axonemal coiled coil protein, mutations in which abolish assembly of CCDC151 into respiratory cilia and cause a failure in axonemal assembly of the ODA component DNAH5 and the ODA-DC-associated components CCDC114...

  11. Primary ciliary dyskinesia: Kartagener syndrome in a family with a novel DNAH5 gene mutation and variable phenotypes

    Directory of Open Access Journals (Sweden)

    Makia J. Marafie

    2015-01-01

    Conclusion: Molecular test helped in confirmation of the clinical diagnosis and in providing better management of the affected family members, which in turn could significantly improve overall quality of their life. Consequently, preimplantation genetic diagnosis, which is the most acceptable procedure in the Islamic countries, was offered to the heterozygous-carrier couple in order to prevent recurrence of the disease in their future generations.

  12. Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia.

    Science.gov (United States)

    Gerlach, J; Bjørndal, N; Christensson, E

    1984-01-01

    In eight monkeys (Cercopithecus aethiops), previously treated with haloperidol for 4-14 months, we have examined the behavioral effect of: (1) methylphenidate vs apomorphine; (2) 4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol(THIP, a GABA agonist) vs diazepam; and (3) THIP and diazepam in methylphenidate-induced behavior. Methylphenidate (0.5-5.0 mg/kg) and apomorphine (0.1-0.5 mg/kg) both increased locomotion, but otherwise exhibited different behavioral profiles. Methylphenidate induced repetitive movements of head, limbs, and trunk, and hallucinatory-like behavior, but not oral hyperkinesia (licking and gnawing), whereas apomorphine preferentially caused oral hyperkinesia. THIP produced a syndrome of bradykinesia, dystonia, ataxia, myoclonus, sedation, and decreased responsiveness, whereas diazepam produced only bradykinesia, ataxia, sedation, and decreased responsiveness, but not dystonia and myoclonus. Methylphenidate-induced locomotion and repetitive movements were reduced by THIP and diazepam, whereas hallucinatory-like behavior was markedly aggravated by THIP, but not by diazepam.

  13. Tardive dyskinesia attributed to sulpiride%舒必利致迟发性运动障碍

    Institute of Scientific and Technical Information of China (English)

    李丽华; 赵祎镭; 姜维

    2010-01-01

    1例34岁男性精神病患者,给予舒必利100 mg,2次/d.4周后患者出现不自主吐舌,伴流涎.立即停用舒必利,给予东莨菪碱及地西泮.3 h后症状缓解,3 d后症状消失.随后改用奥氮平控制精神病.随访2个月余无复发.

  14. Tardive Dyskinesia and Intellectual Disability: An Examination of Demographics and Topography in Adults with Dual Diagnosis and Atypical Antipsychotic Use

    Science.gov (United States)

    Fodstad, Jill C.; Bamburg, Jay W.; Matson, Johnny L.; Mahan, Sara; Hess, Julie A.; Neal, Daniene; Holloway, Jodie

    2010-01-01

    Atypical antipsychotic medications are commonly used in large-scale residential care facilities for adults with developmental disabilities. While the benefits of this class of psychotropics are noted, debate exists whether the side effect profile of these medications outweigh their therapeutic benefit, especially in those who use them long-term.…

  15. An Atypical Case of Anti-NMDA Receptor Encephalitis: Predominant Parkinsonism and Persisting Micrographia without Oro-facial Dyskinesia.

    Science.gov (United States)

    Kadoya, Masato; Kadoya, Akiko; Onoue, Hiroyuki; Ikewaki, Katsunori; Kaida, Kenichi

    2015-01-01

    We describe the case of a 46-year-old man with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with prominent parkinsonism. The patient presented with psychiatric symptoms followed by epileptic seizure and parkinsonism including micrographia. Magnetic resonance imaging (MRI) revealed lesions in the bilateral medial temporal lobes and basal ganglia on fluid-attenuated inversion recovery images. His symptoms and MRI findings were ameliorated by immunotherapy but then relapsed. After retreatment, his parkinsonism gradually improved except for the micrographia. This is an atypical case of anti-NMDAR encephalitis in that the patient showed prominent and refractory parkinsonism, thus indicating that the clinical diversity of anti-NMDAR encephalitis is greater than expected.

  16. Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

    OpenAIRE

    Shin, Eunju; Rogers, James R.; Devoto, Paola; Björklund, Anders; Carta, Manolo

    2014-01-01

    Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains have shown that not only DA neurons but also the noradrenergic (NA) neurons in the locus coeruleus degenerate, and that the NA neurodegeneration may be as profound, and also precede degeneration of the midbrain DA neurons. Previous studies in animal models of PD have suggested that loss of forebrain NA will add to the development of ...

  17. Cardiopulmonary Exercise Testing in Fontan Patients With and Without Isomerism (Heterotaxy) as Compared to Patients With Primary Ciliary Dyskinesia and Subjects With Structurally Normal Hearts

    DEFF Research Database (Denmark)

    Loomba, Rohit S; Danduran, Michael; Nielsen, Kim G

    2017-01-01

    Isomerism, also known as heterotaxy, is a clinical entity that impacts multiple organ systems both anatomically and functionally. The airways and lungs are involved in a great number of these patients, leading to increased sinopulmonary symptoms, increased need for oxygenation, and increased post...

  18. Acupuncture for treatment of dyskinesias of Parkinson's disease%针刺治疗帕金森病运动障碍的临床观察

    Institute of Scientific and Technical Information of China (English)

    张汉樑; 祝维峰

    2003-01-01

    目的:探讨提高帕金森病运动障碍疗效的有效方法.方法:治疗组和对照组同时服用美多巴,治疗组则加用梅花针轻叩四肢的曲肌群、伸肌群以及背肌群,然后再分别针刺四肢关节的穴位.结果:经过3个疗程治疗,治疗组的总有效率为95.0%,运动障碍明显改善,与对照组比较,差异有显著性意义(P<0.05).结论:针灸能提高西药治疗原发性帕金森病运动障碍的疗效,并能减少西药用量.

  19. Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda P; Werge, Thomas

    2011-01-01

    81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.......0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated...

  20. Neuroleptics up-regulate adenosine A2a receptors in rat striatum: implications for the mechanism and the treatment of tardive dyskinesia.

    Science.gov (United States)

    Parsons, B; Togasaki, D M; Kassir, S; Przedborski, S

    1995-11-01

    Neuroleptics, which are potent dopamine receptor antagonists, are used to treat psychosis. In the striatum, dopamine subtype-2 (D2) receptors interact with high-affinity adenosine subtype-2 (A2a) receptors. To examine the effect of various neuroleptics on the major subtypes of striatal dopamine and adenosine receptors, rats received 28 daily intraperitoneal injections of these drugs. Haloperidol (1.5 mg/kg/day) increased the density of striatal D2 receptors by 24% without changing their affinity for [3H]sulpiride. Haloperidol increased the density of striatal A2a receptors by 33% (control, 522.4 +/- 20.7 fmol/mg of protein; haloperidol, 694.6 +/- 23.6 fmol/mg of protein; p sulpiride (100 mg/kg/day) and clozapine (20 mg/kg/day) did not (control, 290.3 +/- 8.7 fmol/mg of protein; haloperidol, 358.1 +/- 6.9 fmol/mg of protein; fluphenazine, 381.3 +/- 13.6 fmol/mg of protein; sulpiride, 319.8 +/- 18.9 fmol/mg of protein; clozapine, 309.2 +/- 13.7 fmol/mg of protein).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Diagnosis and Treatment of Tardive Dyskinesia%迟发性运动障碍的诊断和治疗进展

    Institute of Scientific and Technical Information of China (English)

    凤华

    2013-01-01

      迟发性运动障碍(tardive dyskinesia,TD)又称为迟发性多动症,是1968年由Crane首先提出的一种疾病。该病多见于大剂量长期服用抗精神病药物之后的患者,临床主要特点为不自主、有节律的重复刻板式运动。本文对TD的临床诊断、表现特征以及治疗进行相关综述。%TD also known as tardive ADHD,a disease,first proposed in 1968 by Crane.The disease is more common after long-term use of antipsychotics in the high-dose patients,clinically characterized by involuntary,rhythmic repeat stereotyped movement.The clinical diagnosis of TD, performance characteristics,and treatment-related are overviewed.

  2. Movement Disorders

    Science.gov (United States)

    ... t want them to. If you have a movement disorder, you experience these kinds of impaired movement. Dyskinesia ... movement and is a common symptom of many movement disorders. Tremors are a type of dyskinesia. Nerve diseases ...

  3. 多巴胺转运体基因与迟发性运动障碍的关联性%An association study between dopamine transporter gene and tardive dyskinesia in schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    龙彬; 朱丽萍; 张野; 江三多; 高哲石

    2004-01-01

    目的:探讨多巴胺转运体(DAT1)基因小卫星多态与迟发性运动障碍(TD)的关联性. 方法:采用Amp-FLP技术,对99例精神分裂症伴TD患者和120名正常人的DAT1基因多态性进行检测,比较各组间等位基因和基因型频率分布的差异. 结果:共观察到5种等位基因:320 bp、360 bp、440 bp、480 bp和520 bp.经吻合度检验,TD组和正常对照组DAT1基因各基因型的分布均符合Hardy-Weinberg平衡法则.与正常对照组相比较,TD组中仅360 bp等位基因频率显著减少(P0.05). 结论:DAT1基因该位点多态可能与TD的发生无关.

  4. DISCINESIA ÁNTERO-APICAL TRANSITORIA O SÍNDROME DE TAKO-TSUBO. PRESENTACIÓN DE UN CASO / Transient antero-apical dyskinesia or tako-tsubo syndrome. A case report

    Directory of Open Access Journals (Sweden)

    Dayán A. García Cuesta

    2011-09-01

    Full Text Available Transient apical ballooning, Tako-tsubo syndrome (and other synonyms, is a clinical condition first described in Japan, and then in other countries, that mimics acute myocardial infarction. Disorders of left ventricular contractility recover within a few weeks. The fatality rate is very low compared with infarction, but it should be known by professionals that see patients with acute coronary syndrome in the emergency department. A patient who was discharged from our department with this diagnosis is presented, and electrocardiographic, echocardiographic and angiographic images are shown.

  5. Modified Constraint-induced Movement Therapy on Lower Extremity Dyskinesia of Stroke Patients%改良强制性运动疗法治疗脑卒中后下肢运动功能障碍

    Institute of Scientific and Technical Information of China (English)

    梁天佳; 龙耀斌; 曹锡忠

    2011-01-01

    Objective: To explore the efficacy of modified constraint-induced movement therapy (mCIMT) on motor function recovery of lower extremity of stroke patients. Methods: Ninety-six patients with stable stroke were randomly divided into the enhanced group (48 cases) and control group (48 cases). The enhanced group was given mCIMT, and the control group received routine rehabilitation treatment. The two groups were treated for 4 h every day, 5 times a week for 8 weeks. The therapeutic efficacy was evaluated with Berg balance scale (BBS), Fugl-Meyer scale for evaluating lower-extremity function (FMA-L), functional ambulation category scale (FAC) and functional independence measure (F1M) before and 8 weeks after treatment. Results; Before treatment, the difference had no statistically significant between the two groups. After treatment, the scores of BBS, FMA-L, FCA and FIM had significant difference between the two groups. The proportion of patients with independent walking in the enhanced group reached 72. 9% after treatment, and that in the control group reached 54. 2% (P<0. 05). Conclusion; mCI-MT can promote recovery of lower limb function in stroke-induced hemiplegia patients to a great extent.%研究改良强制性运动疗法对脑卒中后下肢运动功能障碍的康复效果.方法:稳定型脑卒中偏瘫患者96例,随机分为强化组和对照组各48例,均在常规治疗基础上,强化组给予改良强制性运动疗法,对照组给予常规康复治疗.治疗前后2组均采用Berg平衡量表(BBS)评价平衡能力;简式Fugl-Meyer评价法(FMA-L)评价下肢功能;Holden步行功能分级量表(FAC)评价行走能力,独立功能量表(FIM)评价ADL.结果:治疗8周后,2组FMA-L、BBS、FAC及FIM评分与治疗前比较均有明显上升(P<0.05,0.01),且强化组较对照组更显著(P<0.05).治疗后2组能独立步行的比例较治疗前明显提升,强化组更高于对照组(72.9%与54.2%,P<0.05).结论:配合改良强制性运动疗法能够最大程度促进脑卒中偏瘫患者下肢功能的恢复.

  6. Advances of Cannabinoid System in the Research of Parkinson's Disease and Levodopa-Induced Dyskinesia%大麻素系统与帕金森病及其运动并发症关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    马雅萍; 刘振国

    2008-01-01

    近来研究显示,非多巴胺代偿机制在帕金森病及其运动并发症的发展过程中起着重要作用,大麻素系统即其中热点之一,尤其是大麻素CB1受体在运动活动的调节枢纽基底节中具有大量分布.本文对大麻素CB1系统在帕金森病及左旋多巴诱导异动症中作用的研究进展进行阐述,同时简要分析了其作用机制.

  7. 大麻素受体与帕金森病及异动症相关性研究进展%Research Progress in the Cannabinoid Receptors in Parkinson's Disease and Levodopa- induced Dyskinesia

    Institute of Scientific and Technical Information of China (English)

    滕龙; 何建成

    2012-01-01

    帕金森病(PD)是严重影响中老年人的生活质量的中枢神经退行性疾病,其发病机制目前仍不明确.目前认为,与遗传因素、环境因素、兴奋性氨基酸毒性、氧化应激、免疫学异常、线粒体功能障碍、炎症反应、细胞凋亡等因素密切相关.新近的研究发现,非多巴胺代偿机制在PD及其异动症(LID)的发展过程中起着重要作用,内源性大麻素系统已成为其中的热点之一,尤其是大麻素CB1受体的研究备受关注.本文通过对近年来国内外有关大麻素研究的总结,对大麻素受体在PD及左旋多巴诱导LID中作用机制及研究进展的阐述,得出大麻素CB1受体在PD和LID的病理发展过程中起着重要的作用,但不同部位的大麻素CB1受体被不同的eCB激活,可能会对不同的神经递质产生不同的作用.因此,对大麻素CB1受体在基底节不同部位的具体作用机制的深入研究,为PD和LID的发病机制开辟了新的认识途径.

  8. 抗精神病药物所致迟发性运动障碍临床资料分析%Analyses of clinical data of tardive dyskinesia due to antipsychotic drugs

    Institute of Scientific and Technical Information of China (English)

    李清泉

    2016-01-01

    目的 了解抗精神病药物所致迟发性运动障碍的临床特征.方法 对110例迟发性运动障碍患者应用Simpson迟发性运动障碍专用量表和异常不自主运动量表评定不自主运动的发生状况及严重程度.结果 本组患者上肢、下肢和舌部的异常不自主运动发生率较高,均≥80.9%.不同性别、年龄段、应用抗精神病药物类型患者异常不自主运动量表总分及各项分值和比较差异无显著性(P>0.05).结论 抗精神病药物所致迟发性运动障碍主要表现为四肢末端和舌部的异常不自主运动,严重程度不存在性别、年龄段、应用药物差别.

  9. Progress of Treatment for Antipsychotics Induced Tardive Dyskinesia and Its Integrative Medical Therapy%抗精神病药物所致迟发性运动障碍的中西医结合治疗

    Institute of Scientific and Technical Information of China (English)

    苏健民; 曹延筠

    2010-01-01

    @@ 迟发性运动障碍(tardivedyskinesia,TD)是由于长期大量服用抗精神病药后引起的一种特殊而持久的不自主运动综合征,一般包括刻板样动作、舞蹈样手足徐动症,主要累及口面颌、四肢或躯干.许多研究结果说明TD发病率一般随抗精神病药物使用时间延长而增长.TD的致残性较明显,严重影响患者的康复和生活. 1 TD的流行病学研究进展 普遍认为,传统的抗精神病药物出现TD的比率较高,患病率3%~62%.按年代划分,20世纪60年代13.5%,70年代28.6%,80年代25.1%.国外学者Sehooler Kane[1]长时间观察850例服用抗精神病药物患者,结果发现该人群TD发病率第1年为5%,第2年10%,第3年15%,第4年19%,第6年26%.证明了其发病率随抗精神病药物使用的延长而增长.

  10. 迟发性运动障碍与抗精神病药物治疗关系的研究%Study of relationship between tardive dyskinesia and antipsychotics

    Institute of Scientific and Technical Information of China (English)

    李永刚; 谭云龙; 周东丰; 曹连元; 杨甫德; 苏建民

    2008-01-01

    目的 观察迟发性运动障的发生与长期应用抗精神病药物的关系.方法 选取北京回龙观医院长期住院的患者,符合CCMD-3精神分裂症的诊断标准,抗精神病药剂量恒定维持治疗6个月.排除器质性疾病及其它神经精神疾患.先用Simpson迟发性运动专业量表进行全院患者筛选,最终选出合乎要求病例109例,再用AIMS量表评定,依据患者用药情况分为三组,典型抗精神病药组(包括氯丙嗪、奋乃静、氟哌啶醇、安棕酯)、氯氮平组、利培酮组,使用SPSS10.0,采用独立样本t检验、单因素方差分析,分析三组药物与TD的相关性. 结果 利培酮组的AIMS总分显著低于典型抗精神病药组(p=0.032),与氯氮平组无显著差异(P=0.275).结论 利培酮组,氯氮平组致TD症状的严重程度偏低,或对TD症状有一定抑制或治疗作用.

  11. Dyskinesier ved Parkinsons sygdom:

    DEFF Research Database (Denmark)

    Thomsen, Birgitte Liang Chen; Herz, Damian Marc; Siebner, Hartwig Roman

    2017-01-01

    Dyskinesia in Parkinson’s disease: an update on new neuroimaging methods and treatment possibilities Levodopa-induced dyskinesia (LID) represents a severe adverse effect of long-term treatment of Parkinson’s disease with levodopa. Neuroimaging studies have contributed to our understanding of LID...

  12. Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

    Science.gov (United States)

    Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

    2011-01-01

    Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

  13. Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

    Science.gov (United States)

    Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

    2011-01-01

    Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

  14. Dyskinetic Movement Disorder among Adults with Mental Retardation: Phenomenology and Co-occurrence with Stereotypy.

    Science.gov (United States)

    Bodfish, James W.; And Others

    1996-01-01

    The occurrence of dyskinetic movement disorder and its co-occurrence with stereotypic behavior among adults with mental retardation were studied in 98 adults with mental retardation. Results indicated that stereotypic movement disorder was associated with increased dyskinesia scores and that dyskinesia and stereotypy may be related by common…

  15. 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…

  16. Antipsychotic-Induced Movement Disorders in Long-Stay Psychiatric Patients and 45 Tag SNPs in 7 Candidate Genes: A Prospective Study

    NARCIS (Netherlands)

    P.R. Bakker (Roberto); A.F.Y. Al Hadithy (Asmar); N. Amin (Najaf); C.M. van Duijn (Cock); J. van Os (Jim); P.N. van Harten (Peter)

    2012-01-01

    textabstractObjective: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-fac

  17. Primary ciliary dyskinesiatwo cases reports

    Directory of Open Access Journals (Sweden)

    Mohammad Sadegh Rezaee1

    2009-01-01

    Full Text Available (Received 22 December, 2009 ; Accepted 10 March, 2010AbstractPrimary ciliary dyskinesia and Kartagener's syndrome are rare genetic disorders. There is a ciliary dysfunction in these disorders that cause recurrent infections in respiratory and sinus tracts associated with dextrocardia, chronic vasomotor rhinitis and dextrocardia. The aim of this paper is to report two rare cases of Primary ciliary dyskinesia, including one case of primary ciliary dyskinesia and Kartagener's syndrome for additional knowledge. J Mazand Univ Med Sci 2009; 19(73: 85-89 (Persian.

  18. Duodopa pump treatment in patients with advanced Parkinson's disease

    DEFF Research Database (Denmark)

    Karlsborg, Merete; Korbo, Lise; Regeur, Lisbeth

    2010-01-01

    Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump...

  19. Parkinson’s Disease and Its Management: Part 4: Treatment of Motor Complications

    OpenAIRE

    DeMaagd, George; Philip, Ashok

    2015-01-01

    Parkinson’s motor complications include wearing-off, a delayed or absent response to carbidopa/levodopa therapy, freezing of gait, dyskinesias, and dystonias. Treatment may include medication adjustments, such as increased dopaminergic stimulation.

  20. Disease: H00831 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available degeneration, dystonia-parkinsonism with brain degeneration (i.e. DYT3), and paroxysmal dyskinesias. Nervous...ided into Primary torsin dystonias (PTDs), dystonia-plus syndromes without brain

  1. Free-living energy expenditure reduced after deep brain stimulation surgery for Parkinson's disease

    DEFF Research Database (Denmark)

    Jørgensen, Hans Ulrik; Werdelin, Lene; Lokkegaard, Annemette

    2012-01-01

    The clinical picture in Parkinson's disease (PD) is characterized by bradykinesia, rigidity, resting tremor and postural instability. In advanced stages of the disease, many patients will experience reduced efficacy of medication with fluctuations in symptoms and dyskinesias. Surgical treatment...

  2. Restorative treatment program with physical exercise of patients with dysfunction of the biliary tract.

    Directory of Open Access Journals (Sweden)

    Parhotik I.I.

    2011-06-01

    Full Text Available In the thesis there has been shown that biliary dyskinesia takes a leading position among hepatobiliary diseases. 54 women and 14 men aged between 19 and 64 years old, who suffered from hypo kinetic and hyper kinetic forms of dyskinesia, took part in the research. Based on the character of the functional disorders, it was defined that at hyper kinetic form of dyskinesia the best rehabilitation effects were achieved at the application of physical exercises promoting relaxation of the gallbladder, sphincter and biliary duct musculature combined with the stimulation of bile formation. It was proved that means and methods of motion therapy for patients with hyper kinetic dyskenisia had to be aimed at the restoration of the gallbladder till its full reduction. It was defined that application of different forms of therapeutic physical training considering the type of biliary dyskinesia promoted the improvement of the patients' clinical condition, motor and evacuator function of the biliary ducts.

  3. Reduced Penetrance of PRRT2 Mutation in a Chinese Family With Infantile Convulsion and Choreoathetosis Syndrome.

    Science.gov (United States)

    Zhang, L M; An, Y; Pan, G; Ding, Y F; Zhou, Y F; Yao, Y H; Wu, B L; Zhou, S Z

    2015-09-01

    Paroxysmal kinesigenic dyskinesia is a rare episodic movement disorder that can be isolated or associated with benign infantile seizures as part of choreoathetosis syndrome. Mutations in the PRRT2 gene have been recently identified as a cause of paroxysmal kinesigenic dyskinesia and infantile convulsion and choreoathetosis (ICCA). We reported a PRRT2 heterozygous mutation (c.604-607delTCAC, p.S202Hfs*25) in a 3-generation Chinese family with infantile convulsion and choreoathetosis and paroxysmal kinesigenic dyskinesia. The mutation was present in 5 family members, of which 4 were clinically affected and 1 was an obligate carrier with reduced penetrance of PRRT2. The affected carriers of this mutation presented with a similar type of infantile convulsion during early childhood and developed additional paroxysmal kinesigenic dyskinesia symptoms later in life. In addition, they all had a dramatic clinical response to oxcarbazepine/phenytoin therapy. Reduced penetrance of the PRRT2 mutation in this family could warrant genetic counseling.

  4. Tardive Dystonia: Clinical Spectrum and Novel Manifestations

    Directory of Open Access Journals (Sweden)

    R. Jeffrey Davis

    1988-01-01

    Full Text Available Tardive dystonia was identified in 25 patients: involvement of the face and neck was most common; truncal and limb dystonia were also observed. There were 3 cases of laryngospasm and 2 of spasmodic dysphonia. The latter has not been previously reported as a manifestation of tardive dystonia. In all cases, movements typical of classic tardive dyskinesia could be demonstrated. This group illustrates the variety of dystonic disorders that may occur in conjunction with tardive dyskinesia.

  5. EFFECT OF SCAPULAR STABILISATION EXERCISES FOR TYPE 2 SCAPULAR DYSKINESIS IN SUBJECTS WITH SHOULDER IMPINGEMENT

    Directory of Open Access Journals (Sweden)

    Pradeep Shankar

    2016-02-01

    Full Text Available Background: Abnormal altered scapular position during rest or motion have been termed as Scapular Dyskinesia. Scapula Dyskinesia Type-2 is one type of dyskinesia in which there is a visual prominence of entire medial border of scapula that occurs due to weakness of the serratus anterior and tightness of posterior shoulder joint capsule that results in reduction in glenohumeral flexion and abduction, resulting in decreased acromial elevation. This type of dyskinesia is commonly seen in Secondary impingement of shoulder. Rehabilitation generally begins and focused on axio-humeral and scapula- humeral than axio-scapular muscle. Early application of closed kinetic exercises on scapular stabilization and its effect of application on scapular dyskinesia type 2 is unknown. The study was proposed to find the effect of scapular stabilization exercise for type 2 Scapular Dyskinesia in subjects with shoulder impingement. Methods: An experimental study design, 7 male patients with mean age 37 years diagnosed with Shoulder impingement associated with Type 2 scapular dyskinesia were included in the study. The protocol includes closed kinematic chain exercises (scapula clock, Black burn exercises, Sleepers stretch, and thera band exercises aimed to balance force couple of upper, lower trapezius and serratus anterior. Duration of intervention was 3 sessions per week for 2 weeks. Outcome measurements such as Lateral scapular slide test and SPADI were measured pre and post interventions. Results: Analysis using Paired ‘t’ test as a parametric test found that there is statistically significant difference p<0.000 when pre to post interventions means were compared within the groups showing significant improvement in post SPADI and lateral scapular slide test. Conclusion: It is concluded that Scapula stabilization exercise protocol found to be effective in Scapular type-2 Dyskinesia.

  6. 5-羟色胺2C受体基因启动子区多态性与迟发性运动障碍的关联分析%Association of a polymorphism in the promoter region of the serotonin 2C receptor gene with tardive dyskinesia in schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    张晓斌; 张志珺; 侯钢; 姚辉; 沙维伟; 张心保

    2002-01-01

    目的探讨5-羟色胺2C(5-HT2C)受体基因启动区-759C/T和-697G/C单碱基置换多态性与精神分裂症伴迟发性运动障碍(TD)的相关性.方法先用异常不自主运动量表(AIMS)评定精神分裂症男性患者有无TD及其严重程度,再对42例符合TD(AIMS总分≥3分)者和与TD组严格相匹配的50例非TD者,采用简明精神病评定量表(BPRS)评定精神症状,并应用聚合酶链反应-限制性片段长度多态性方法分析5-HT2C受体基因的分布频率.结果 (1)TD组的-697C(突变型)半合子型频率(38%)高于非TD组(18%;χ2=4.7,P=0.03,OR=2.8).TD组-759T(突变型)半合子型频率和-759T/-697C突变型单倍体频率虽高于非TD组,但差异均无显著性(χ2值分别为2.9和4.9,P=0.09).(2)TD组的AIMS和BPRS评分分别为(6.5±1.8)分和(51.2±7.8)分,非TD组分别为0分和(50.0±7.3)分,差异无显著性(P>0.05).结论 5-HT2C受体基因启动控制区的-697G/T单碱基置换突变可能是精神分裂症患者发生TD的易感因素之一.

  7. The association study between catechol - O - methyltransferase gene polymorphism and cognitive function in schizophrenic patients with tardive dyskinesia%COMT基因多态性与伴TD的精神分裂症患者认知功能的相关性研究

    Institute of Scientific and Technical Information of China (English)

    胡卫红; 江开达; 汪栋祥; 钱伊萍; 陈红芳; 丁会蓉

    2007-01-01

    目的 探讨中国汉族人口中儿茶酚胺氧位甲基转移酶(COMT)基因Val108/158Met多态性与伴迟发性运动障碍(TD)的精神分裂症患者认知功能的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对82例伴TD的精神分裂症患者COMT基因多态性进行检测,并选用连线测验(TMT)、韦氏记忆测验(WMS)、威斯康星卡片分类测验(WCST)对其认知功能进行评定.结果 (1)COMT基因与TMT成绩显著相关,其中高活性G/G基因型PartA成绩显著低于中等活性G/A基因型,PartB成绩也显著低于低活性A/A基因型及中等活性G/A基因型.(2)COMT基因与记忆商数、背数成绩显著相关,其中G/G基因型记忆商数分显著低于A/A及G/A基因型,背数分也显著低于A/A基因型.(3)COMT基因与WCST成绩无显著相关性.结论 COMT基因与伴TD的精神分裂症患者认知功能具有显著相关性,其中高活性G/G基因型患者认知损害更明显.

  8. Clinical observation of acupoint injection combined with integrated physiotherapy of TCM in upper extremity dyskinesia after stroke%穴位注射联合中医综合理疗治疗脑卒中后上肢运动功能障碍的临床观察

    Institute of Scientific and Technical Information of China (English)

    查天柱; 陈思宇; 唐素珍

    2016-01-01

    目的:观察穴位注射联合中医综合理疗治疗脑卒中后上肢运动功能障碍的临床疗效.方法:临床纳入脑卒中后上肢运动功能障碍患者90例,根据康复训练方案的不同分为治疗组与对照组.治疗组进行穴位注射联合中医综合理疗,对照组进行肌电生物反馈.结果:治疗前,两组患者FMA、MBI、IEMG评分差异均无显著性(P>0.05);治疗后,治疗组FMA、MBI评分明显高于对照组,差异均有显著性(P<0.05);治疗后,治疗组患侧肱二、三头肌最大等长收缩时IEMG评分明显高于对照组,差异有显著性(P<0.05).结论:穴位注射联合中医综合理疗治疗对改善脑卒中后上肢运动功能障碍患者有着较好的临床效果,能够显著提高偏瘫患者上肢功能以及生活质量,值得应用.

  9. Expression pattern of cannabinoid receptor 1 in the basal ganglia of Parkinson disease rat model with levodopa-induced dyskinesia%大麻素CB1受体在左旋多巴诱导的异动症大鼠基底节的表达研究

    Institute of Scientific and Technical Information of China (English)

    马雅萍; 宋璐; 刘振国

    2010-01-01

    目的 观察大麻素CB1受体在长期左旋多巴治疗诱导的异动症(LID)大鼠模型基底节表达的特点,探讨LID与CB1受体表达变化的关系.方法 帕金森病(PD)模型大鼠接受左旋多巴腹腔注射21 d,建立LID大鼠模型.采用免疫组化和Western Blot方法检测基底节不同部位CB1受体表达.结果 经左旋多巴治疗的PD大鼠出现类似人类LID的行为学表现.免疫组化结果显示LID组纹状体CB1受体损伤侧与未损侧的累积吸光度(IOD)比值下降,而苍白球和黑质网状部该比值升高(均P<0.01);Western blot检测结果与免疫组化显示了相同变化趋势, LID组纹状体CB1受体损伤侧/未损侧条带密度比值降低(P<0.01).结论 长期左旋多巴治疗可引起基底节纹状体CB1受体表达下调,这种改变可能与LID的发生发展有关.

  10. Analysis on association between COMT gene polymorphism and tardive dyskinesia induced by antipsychotic drugs%抗精神分裂症药物诱发迟发性运动障碍与COMT基因多态性的关联性分析

    Institute of Scientific and Technical Information of China (English)

    刘姗姗; 张逸远; 于跃; 孙颖; 赵刚; 孙世龙; 王宝贵; 刘颖

    2011-01-01

    目的:通过分析中国北方汉族人群中精神分裂症患者COMT基因多态性Val158Met 分布,研究COMT基因多态性与精神分裂症及迟发性运动障碍(TD)发生的关系.方法:采集356例并发TD的精神分裂症患者( TD组)、419例不发生TD的精神分裂症患者(非TD组)及471例正常健康人 (正常对照组)的全血样本,提取基因组DNA,应用TaqMan探针检测COMT基因多态性Val158Met基因型和等位基因的分布.结果:正常对照组与精神分裂症组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=3.08,df=3,P=0.21;χ2=2.067,df=2,P=0.15).TD组与正常对照组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=1.857,df=3,P=0.40;χ2 =1.281,df=2,P=0.26).非TD组与正常对照组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=2.505,df=3,P=0.29;χ2=1.709,df=2,P=0.19).TD组与非TD组比较,基因型与等位基因频数分布差异均无统计学意义(χ2=0.021,df=3,P=0.99;χ2=0.013,df=2,P=0.91).结论:精神分裂症的发生与COMT基因多态性Val158Met无关联性,精神分裂症患者并发TD与COMT基因多态性Val158Met无关联性.

  11. Metabotropic glutamate receptor type 5 in levodopa-induced motor complications.

    Science.gov (United States)

    Ouattara, Bazoumana; Grégoire, Laurent; Morissette, Marc; Gasparini, Fabrizio; Vranesic, Ivo; Bilbe, Graeme; Johns, Donald R; Rajput, Alex; Hornykiewicz, Oleh; Rajput, Ali H; Gomez-Mancilla, Baltazar; Di Paolo, Thérèse

    2011-07-01

    Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of synaptic plasticity and learning, and were the focus of our investigation in human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys with dyskinesias. Using the selective mGluR5 ligand [(3)H]ABP688 autoradiography, we measured mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys, in relation to motor complications (dyskinesias and wearing-off) associated with treatment with l-dopa. In 16 monkeys with a bilateral MPTP lesion and four controls, [(3)H]ABP688 specific binding was elevated in the striatum of dyskinetic l-dopa-treated MPTP monkeys but not in MPTP monkeys without dyskinesias compared to controls. PD patients with motor complications (either dyskinesias or wearing-off) had higher [(3)H]ABP688 specific binding compared to those without motor complications and controls in putamen, external and internal globus pallidus. Elevated glutamatergic transmission as measured with increased mGluR5 specific binding was associated with motor complications and its antagonism could be targeted for their treatment.

  12. Risk factors in development of motor complications in Chinese patients with idiopathic Parkinson's disease.

    Science.gov (United States)

    Kum, Wan Fung; Gao, Jing; Durairajan, Siva Sundara Kumar; Man, Sui Cheung; Xie, Li Xia; Lu, Jia Hong; Fong, Wai Leuk; Li, Min

    2009-08-01

    Motor complications induced by levodopa (L-dopa) treatment in Parkinson's disease (PD) are not well documented in patients of Chinese ethnicity. We performed a cross-sectional study to investigate the prevalence of dyskinesias and motor fluctuations, and the factors determining their development, in a population of Chinese patients with PD. Among 137 patients with PD, 98 (71.5%) had received a L-dopa preparation. Motor fluctuations were found in 74.5% and dyskinesias in 77.6% of the 98 patients. Patients with dyskinesias were younger at onset of disease than those without. Patients with dyskinesias and motor fluctuations had significantly longer duration of PD and L-dopa treatment, higher daily doses of L-dopa, and higher scores in the 39-item Parkinson's Disease Questionnaire (PDQ-39), when compared to patients without motor complications. Among these factors, motor fluctuations were best predicted by duration of L-dopa treatment and dyskinesias by disease duration. We conclude that motor complications are closely related to disease and treatment parameters, especially the treatment and disease duration.

  13. The H3 receptor agonist immepip does not affect l-dopa-induced abnormal involuntary movements in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Papathanou, Maria; Jenner, Peter; Iravani, Mahmoud; Jackson, Michael; Stockwell, Kim; Strang, Isabel; Zeng, Bai-Yun; McCreary, Andrew C; Rose, Sarah

    2014-10-15

    The treatment of dyskinesia in Parkinson׳s disease remains poor but H3 receptor agonists have been suggested as a novel pharmacological approach. We examined the effects of the H3 agonist, immepip, in 6-OHDA-lesioned rats exhibiting AIMs (abnormal involuntary movements), a rat analogue of dyskinesia, in response to l-dopa compared to the known anti-dyskinetic agents amantadine, MK-801 and 8-OHDPAT. We then attempted to extend these studies in to dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated common marmosets. Amantadine, MK-801 and 8-OHDPAT all dose-dependently reduced l-dopa-induced axial, lingual and oral (ALO) AIMs in 6-OHDA-lesioned animals accompanied by a reduction in contralateral rotation with higher doses of amantadine and MK-801. By contrast, immepip had no effect on AIMs expression or contralateral rotation. In the MPTP-treated common marmoset exhibiting dyskinesia to l-dopa, immepip alone induced retching and in combination with l-dopa administered subcutaneously or orally induced the rapid onset of retching and vomiting which was not controlled by pretreatment with domperidone. Administration of the unrelated H3 agonist, imetit had the same effect. Despite causing negative side-effects, it appears that both agonists reduced the antiparkinsonian response to l-dopa resulting in reduced dyskinesia. H3 agonists appear unlikely candidates for the treatment of dyskinesia in PD based on lack of evidence of efficacy and potential adverse effects.

  14. A conditioned response as a measure of impulsive-compulsive behaviours in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Andrew H Evans

    Full Text Available OBJECTIVES: Parkinson's Disease patients wore a device on the wrist that gave reminders to take levodopa and also measured bradykinesia and dyskinesia. Consumption of medications was acknowledged by placing the thumb on the device. Some patients performed this acknowledgement repeatedly and unconsciously. This study examines whether this behaviour reflected increased impulsivity. METHODS AND RESULTS: Twenty five participants were selected because they had i excess acknowledgements described above or ii Impulsive-Compulsive Behaviours or iii neither of these. A blinded assessor applied clinical scales to measure Impulsive-Compulsive Behaviours, cognition, depression, anxiety and apathy. A Response Ratio, representing the number of acknowledgements/number of doses (expressed as a percentage was tightly correlated with ratings of Impulsive-Compulsive Behaviours (r² = 0.79 in 19/25 subjects. Some of these patients had dyskinesia, which was higher with extraneous responses than with response indicating medication consumption. Six of the 25 subjects had high Impulsive-Compulsive Behaviour Scores, higher apathy scores, low levels of dyskinesia and normal Response Ratios. Patients without ICB (low RR also had low dyskinesia levels regardless of the relevance of the response. CONCLUSION: An elevated Response Ratio is a specific measure of a type of ICB where increased incentive salience is attributed to cues by the presence of high striatal dopamine levels, manifested by high levels of dyskinesia. This study also points to a second form of ICBs which occur in the absence of dyskinesia, has normal Response Ratios and higher apathy scores, and may represent prefrontal pathology.

  15. Cerebral Abscess and Extraaxial Empyema in a Patient with Kartagener Syndrome

    Directory of Open Access Journals (Sweden)

    Idil Gunes Tatar

    2013-06-01

    Full Text Available The triad of situs inversus totalis, bronchiectasis and sinusitis is known as Kartagener syndrome which is among the diseases with ciliopathies. Herein we present a case of cerebral abscess and extraaxial empyema detected in a 21-year-old male patient with Kartagener syndrome and a 10-year history of substance abuse. Preoperative CT, MRI findings and postoperative complications are presented with clinical and radiological review of primary ciliary dyskinesia. The consideration of primary ciliary dyskinesia in the differential diagnosis of frequent occurence of cough, rhinitis and otitis media in children is crucial since early diagnosis is known to affect the short term and long term morbidity.

  16. Kartagener syndrome with focal segmental glomerulosclerosis.

    Science.gov (United States)

    Momeni, Ali; Doroushi, Behzad; Taheri, Nadia

    2013-11-01

    Primary ciliary dyskinesia is characterized by congenital impairment of mucociliary clearance. Kartagener syndrome (KS) is a clinical variant of primary ciliary dyskinesia which is involved in situs inversus associated with chronic respiratory infections. In addition, glomerular disease in KS syndrome is rare and reported cases are limited. We had a 27-year-old female patient with KS who presented with proteinuria, hematuria, normal kidney function, and a family history of systemic lupus erythematosus. Kidney biopsy showed segmental scar with adhesion to Bowman capsule, which was indicative of focal segmental glomerulosclerosis.

  17. Effects of compound rehmannia prescription on the cannabinoid receptor 1 in rats with wind syndrome due to deficiency of Yin in levodopa-induced dyskinesia (LID) in Parkinson's disease%阴虚动风证帕金森病异动症大鼠大麻素CB1受体变化及复方地黄方的干预作用

    Institute of Scientific and Technical Information of China (English)

    滕龙; 洪芳; 何建成

    2016-01-01

    目的 探讨阴虚动风证帕金森病(PD)异动症(LID)大鼠纹状体内大麻素CB1受体的表达及复方地黄方的干预作用.方法 采用6-羟基多巴胺(6-OHDA)偏侧损毁黑质制备帕金森病大鼠模型,进一步腹腔注射左旋多巴+苄丝肼(50 mg/kg左旋多巴和12.5 mg/kg苄丝肼)制备LID大鼠模型,并随机分为LID组、复方地黄方组,另取正常对照组、假手术组大鼠为对照,每组6只.分别在4周、6周进行神经行为学检测后,处死大鼠并取纹状体,应用Western blot法测定各组大鼠纹状体内大麻素CB1受体的表达情况.结果 LID大鼠随造模时间延长,AIM评分呈增加趋势(P<0.05),旋转启动时间呈缩短趋势(P>0.05),旋转持续时间呈增加趋势(P<0.01),剂峰旋转圈数呈减少趋势(P>0.05),复方地黄方可改善上述变化.LID大鼠大麻素CB1受体表达增加,且随造模时间延长呈现减少趋势(P<0.01),而复方地黄方干预后大麻素CB1受体的表达呈现逐渐增加的趋势(P<0.01).结论 LID模型大鼠大麻素CB1受体的含量明显升高,其变化能够较好的反映阴虚动风证的严重程度,复方地黄方干预LID模型大鼠可能是通过激活纹状体内大麻素CB1受体,抑制兴奋性氨基酸(主要是谷氨酸)的释放和诱导细胞发生级联反应来减弱神经元的兴奋性,从而起到减轻L-dopa的兴奋毒性的作用.

  18. The changes of plasma superoxide dismutase,catalase,glutathione peroxidase,maleic dialdehyde in patients with antipsychotics-induced tardive dyskinesia%抗精神病药所致迟发性运动障碍患者血浆超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化酶活性及丙二醛浓度的改变

    Institute of Scientific and Technical Information of China (English)

    谭云龙; 周东丰; 曹连元; 邹义壮; 张向阳; 苏建民

    2005-01-01

    目的探讨抗精神病药所致迟发性运动障碍(TD)患者体内自由基代谢状况与TD的关系.方法测定119例TD(TD组)、46例非TD(非TD组)慢性精神分裂症患者及44名正常人(对照组)血浆超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(Gpx)、过氧化氢酶(CAT)活性及丙二醛(MDA)浓度,并在TD组中选取46例一般状况与非TD组、对照组匹配的患者进行三组间方差分析;生化指标与异常不自主运动量表(AIMS)总分间的相关性采用直线相关分析.结果 (1)对照组血浆SOD活性[(98±11)×103U/L]、Gpx活性[(143±31) ×103U/L] 高于TD患者[44例,SOD(85±15)×103U/L,Gpx(101±29)×103U/L]及非TD组[SOD(93±16)×103U/L,Gpx(117±39)×103U/L];对照组MDA浓度[(2.6±1.5)mmol/L]低于TD患者[44例,(13.5±8.8)mmol/L]及非TD组[(7.3±6.5)mmol/L],差异均有统计学意义(均P<0.05);(2)TD患者(44例)血浆SOD活性、MDA浓度与非TD组间的差异均有统计学意义(均P<0.05);(3)AIMS总分与SOD、MDA均有显著相关(r=- 0.225,r=0.225,均P<0.05).结论 TD患者的血浆抗氧化酶、脂质过氧化物异常,自由基代谢障碍可能与TD关系密切.

  19. Long term motor complications of levodopa: clinical features, mechanisms, and management strategies

    OpenAIRE

    Thanvi, B; Lo, T

    2004-01-01

    Levodopa is the most effective symptomatic treatment of Parkinson's disease. However, after an initial period of dramatic benefit, several limitations become apparent including, "dopa resistant" motor symptoms (postural abnormalities, freezing episodes, speech impairment), "dopa resistant" non-motor signs (autonomic dysfunction, mood and cognitive impairment, etc), and/or drug related side effects (especially psychosis, motor fluctuations, and dyskinesias). Motor complications include fluctua...

  20. Treatment of Advanced Parkinson's Disease

    OpenAIRE

    Sara Varanese; Zoe Birnbaum; Roger Rossi; Alessandro Di Rocco

    2010-01-01

    Patients at late stage Parkinson's disease (PD) develop several motor and nonmotor complications, which dramatically impair their quality of life. These complications include motor fluctuations, dyskinesia, unpredictable or absent response to medications, falls, dysautonomia, dementia, hallucinations, sleep disorders, depression, and psychosis. The therapeutic management should be driven by the attempt to create a balance between benefit and side effects of the pharmacological treatments avai...

  1. Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

    NARCIS (Netherlands)

    Koning, Jeroen P.; Vehof, Jelle; Burger, Huibert; Wilffert, Bob; Al Hadithy, Asmar; Alizadeh, Behrooz; van Harten, Peter N.; Snieder, Harold

    2012-01-01

    Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. T

  2. Prepontine Schwannoma Presenting With Atypical Facial Symptoms - A Case Report

    Directory of Open Access Journals (Sweden)

    Rishi Kumar Bali

    2005-01-01

    Full Text Available Face is an important landmark and any pathological condition affecting it has tremendous bearing on psychological make up of the patient. This report describes a rare case of a young female who presented with Hemifacial dysaesthesia complicated by ipsilateral masticatory complex dyskinesia.

  3. Disease: H01258 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01258 Generalized epilepsy and paroxysmal dyskinesia (GEPD) Epilepsy is one of the...ment often requiring life-long treatment. GEPD is a syndrome of coexistent generalized epilepsy...icherson GB, Wang QK Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 37:733-8 (2005) ...

  4. RPGR mutations might cause reduced orientation of respiratory cilia

    NARCIS (Netherlands)

    Bukowy-Bieryllo, Zuzanna; Zietkiewicz, Ewa; Loges, Niki Tomas; Wittmer, Mariana; Geremek, Maciej; Olbrich, Heike; Fliegauf, Manfred; Voelkel, Katarzyna; Rutkiewicz, Ewa; Rutland, Jonathan; Morgan, Lucy; Pogorzelski, Andrzej; Martin, James; Haan, Eric; Berger, Wolfgang; Omran, Heymut; Witt, Michal

    2013-01-01

    RPGR gene encodes retinitis pigmentosa guanosine triphosphatase regulator protein, mutations of which cause 70% of the X-linked retinitis pigmentosa (XLRP) cases. Rarely, RPGR mutations can also cause primary ciliary dyskinesia (PCD), a multisystem disorder characterized by recurrent respiratory tra

  5. Abbreviation modalities of nitrogen multiple-breath washout tests in school children with obstructed lung disease

    DEFF Research Database (Denmark)

    Green, Kent; Ejlertsen, Jacob S; Madsen, Astrid;

    2016-01-01

    , the lung clearance index, calculated as lung volume turnovers required to reach 2.5% of the starting N2 concentration (LCI2.5 ). METHODS: Cross-sectional study of triplicate N2 MBW measurements obtained in cystic fibrosis (CF) patients (N = 60), primary ciliary dyskinesia (PCD) patients (N = 28...

  6. Impulse control disorders in Parkinson's disease

    OpenAIRE

    Stacy, Mark

    2009-01-01

    Since the original descriptions of hedonistic homeostatic dysregulation syndrome and pathological gambling in Parkinson's disease, impulse control disorders, such as compulsive spending, punding, or binge eating, are increasingly recognized. Although the term hedonistic homeostatic dysregulation syndrome has been supplanted by the concept of the dopamine dysregulation syndrome, the features of severe dyskinesias, cyclical mood disorder with hypomania or manic psychosis, and impairment of soci...

  7. DYX1C1 is required for axonemal dynein assembly and ciliary motility

    NARCIS (Netherlands)

    Tarkar, A.; Loges, N.T.; Slagle, C.E.; Francis, R.; Dougherty, G.W.; Tamayo, J.V.; Shook, B.; Cantino, M.; Schwartz, D.; Jahnke, C.; Olbrich, H.; Werner, C.; Raidt, J.; Pennekamp, P.; Abouhamed, M.; Hjeij, R.; Kohler, G.; Griese, M.; Li, Y.; Lemke, K.; Klena, N.; Liu, X.; Gabriel, G.; Tobita, K.; Jaspers, M.; Morgan, L.C.; Shapiro, A.J.; Letteboer, S.J.F.; Mans, D.A.; Carson, J.L.; Leigh, M.W.; Wolf, W.E.; Chen, S.; Lucas, J.S.; Onoufriadis, A.; Plagnol, V.; Schmidts, M.; Boldt, K.; Uk10K, .; Roepman, R.; Zariwala, M.A.; Lo, C.W.; Mitchison, H.M.; Knowles, M.R.; Burdine, R.D.; Loturco, J.J.; Omran, H.

    2013-01-01

    DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2-4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and mal

  8. SUBJECT INDEX

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    1, 25-dihydroxyvitamin D3, growth hormone,acromegaly, 9202551-methyl-4phenyl-1, 2, 3, 6-tetra-hydropy-ridine, dyskinesia, 920599201TL planar imaging, myocardial disease,9202165-fluorouracil, pharmacokinetics, 9200165-hydroxyindoleacetic acid, congestive heartfailure, 5-hydroxytryptamine, norepinephrine,9204785-hydroxytryptamine, epidemic hemorrhagicfever, 9200355-hydroxytryptamine, congestive heart failure,

  9. Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Blaabjerg, Morten; Binzer, Michael

    2017-01-01

    -DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l...

  10. KARTAGENER’S SYNDROME: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Satish Prasad

    2015-01-01

    Full Text Available Kartagener syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive condition characterized by abnormal ciliary structure or function leading to impaired mucociliary clearance. The findings of CT thorax, abdomen and PNS support the clinical diagnosis of the Kartageners Syndrome. We report the CT findings of this rare syndrome.

  11. Linkage analysis localises a Kartagener syndrome gene to a 3.5 cM region on chromosome 15q24-25

    NARCIS (Netherlands)

    Geremek, M; Zietkiewicz, E; Diehl, S R; Alizadeh, B Z; Wijmenga, C; Witt, M

    2006-01-01

    BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by ciliary immotility/dysmotility due to ultrastructural defects of the cilia. Kartagener syndrome (KS), a subtype of PCD, is characterised by situs inversus accompanying the typical PCD symptoms of bronchiectasis and chronic

  12. Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome

    NARCIS (Netherlands)

    M.W. Wessels (Marja); N.S. den Hollander (Nicolette); P.J. Willems (Patrick)

    2003-01-01

    textabstractPrimary ciliary dyskinesia (PCD), also referred to as immotile-cilia syndrome or Kartagener syndrome, is a group of genetic disorders caused by defective cilia leading to chronic sinupulmonary infection, situs inversus and reduced fertility. Some PCD patients also have cerebral ventricul

  13. A case of Kartagener syndrome with rhinolalia clausa.

    Science.gov (United States)

    Raoufi, Mohammed; Sator, Hicham; Lahma, Jawad; El Ayoubi, Ali; Nitassi, Sophia; Oujilal, Abdelilah; Benbouzid, Mohammed Anas; Essakalli, Leila; Elouazzani, Hanane; Rhorfi, Ismail Abderrahmane; Abid, Ahmed

    2016-01-01

    Kartagener syndrome is an autosomal recessive genetic ciliary disorder comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. It's the one of primary ciliary dyskinesia disorders with manifestations present from childhood. Most patients of PCD have situs inversus. We present a case of 18 year-old women with recurrent lower and upper respiratory tracts infections, and rhinolalia clausa.

  14. Linkage analysis localises a Kartagener syndrome gene to a 3.5 cM region on chromosome 15q24-25.

    NARCIS (Netherlands)

    Geremek, M.; Zietkiewicz, E.; Diehl, S.R.; Alizadeh, B.Z.; Wijmenga, C.; Witt, M.

    2006-01-01

    Background: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by ciliary immotility/dysmotility due to ultrastructural defects of the cilia. Kartagener syndrome (KS), a subtype of PCD, is characterised by situs inversus accompanying the typical PCD symptoms of bronchiectasis and chronic

  15. Kartagener′s syndrome in a fertile male - An uncommon variant

    Directory of Open Access Journals (Sweden)

    Barthwal M

    2006-01-01

    Full Text Available Primary ciliary dyskinesia, with Kartagener′s syndrome as one of the subsets, is an autosomal recessive disorder with significant genetic heterogeneity. A 26-year old male with this syndrome, presenting with recurrent upper and lower respiratory tract infection, was found to be fertile. The case is being reported for uncommon occurrence of this syndrome with male fertility.

  16. Linkage analysis localises a Kartagener syndrome gene to a 3.5 cM region on chromosome 15q24-25.

    NARCIS (Netherlands)

    Geremek, M.; Zietkiewicz, E.; Diehl, S.R.; Alizadeh, B.Z.; Wijmenga, C.; Witt, M.

    2006-01-01

    BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disorder caused by ciliary immotility/dysmotility due to ultrastructural defects of the cilia. Kartagener syndrome (KS), a subtype of PCD, is characterised by situs inversus accompanying the typical PCD symptoms of bronchiectasis and chronic

  17. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q

    NARCIS (Netherlands)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-01-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, whil

  18. Kartagener syndrome and rheumatoid arthritis.

    Science.gov (United States)

    Rébora, Martin Esteban; Cuneo, Julia Ana; Marcos, Josefina; Marcos, Juan Carlos

    2006-02-01

    We report the case of a 38-year-old female patient, affected with Kartagener syndrome (primary ciliary dyskinesia), who developed seropositive and erosive rheumatoid arthritis. According to our review, there are only 6 cases reported so far with this association without a definite etiopathogenic linkage recognized in common. Chronic infections resulting from the ciliary dysfunction might be a trigger for rheumatoid arthritis.

  19. The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate

    Directory of Open Access Journals (Sweden)

    Christopher A. Lieu

    2012-01-01

    Full Text Available Chronic treatment with levodopa (LD in Parkinson's disease (PD can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD, and LD+CD in hemiparkinsonian (HP monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR and subthalamic nucleus (STN in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

  20. [A strong man with a weak shoulder].

    Science.gov (United States)

    Henket, Marjolijn; Lycklama á Nijeholt, Geert J; van der Zwaal, Peer

    2013-01-01

    A 47-year-old former olympic athlete had pain and weakness of his left shoulder. There was no prior trauma. He had full range-of-motion and a scapular dyskinesia. There was atrophy of the trapezius and sternocleidomastoideus muscles. He was diagnosed with 'idiopathic neuritis of the accessorius nerve'.

  1. Stereotypy and Motor Control: Differences in the Postural Stability Dynamics of Persons with Stereotyped and Dyskinetic Movement Disorders.

    Science.gov (United States)

    Bodfish, James W.; Parker, Dawn E.; Lewis, Mark H.; Sprague, Robert L.; Newell, Karl M.

    2001-01-01

    This study examined whether dynamic measures of postural stability differentiated stereotyped movement disorder from dyskinetic movement disorder in a severely mentally retarded population. Participants (N=20) with either stereotypy or dyskinesia movement disorders and a control group were given a goal-oriented postural stability task. Both groups…

  2. Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

    NARCIS (Netherlands)

    Koning, Jeroen P; Vehof, Jelle; Burger, Huibert; Wilffert, Bob; Al Hadithy, Asmar; Alizadeh, Behrooz; van Harten, Peter N; Snieder, Harold

    2012-01-01

    RATIONALE: Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamin

  3. The Effects of Nicotine on MK-801-induced Attentional Deficits: An Animal Model of Schizophrenia

    Science.gov (United States)

    2002-01-01

    antipsychotic effects when used in schizophrenic patients. Chlorpromazine (Thorazine) is a “conventional antipsychotic ,” or a neuroleptic - a class of...drugs that also includes Haloperidol (Haldol) (Dixon, Lehman, & Levine, 1995; Love, 1996; Stahl, 2000). Conventional antipsychotics are rarely...prescribed now because of their negative side effects including: cognitive and neurologic deficits (such as sedation, confusion, and tardive dyskinesia

  4. [Intercultural adaptation of the AIMS in German language: A scale for abnormal involuntary movements].

    Science.gov (United States)

    Buhmann, C; Rizos, A; Emmans, D; Jost, W H

    2016-04-01

    Dyskinesias are abnormal involuntary movements and occur across many movement disorders. In Parkinson's disease dyskinesias can be troublesome and are a determinant of the quality of life throughout the course of the disease. Assessment and rating of dyskinesias is thus important for clinical assessment of patients, as well as for academic studies and clinical trials. The abnormal involuntary movement scale (AIMS) is an English language standardised, reliable and validated scale to evaluate dyskinesias. In this article we present a linguistically validated German version of AIMS. The intercultural adaptation of the German translation was performed following an internationally accepted procedure. Firstly, two neurologists independently translated the original into German. Taking both versions into account, a consensus version was agreed on by both translators and was tested on 10 patients. This preliminary German version was then independently translated back into the original language by two different neurologists, and again, a consensus version was agreed on. All translators then compared this English version to the original. Subsequently, the German version was linguistically modified until it resulted in a final German version, which was agreed on by all translators, deemed linguistically acceptable, and the translation back into English was considered to be as unambiguous as possible. This final German version of AIMS was applied to 50 patients in two different hospitals for diagnostic purposes and tested for feasibility and comprehension. In this paper, we present an intercultural adaptation of a linguistically validated German version of AIMS.

  5. Physiotherapy and bronchial mucus transport

    NARCIS (Netherlands)

    Schans, Cornelis Peter van der

    1991-01-01

    The use of physiotherapeutic techniques may increase mucus transport in patients with airways disease including COPD, asthma, cystic fibrosis and primary ciliary dyskinesia. The most effective parts of the treatment are probably forced expirations with open glottis and coughing. However, in patients

  6. Pharmacognostical and Phytochemical investigation of aerial parts of Lagenaria siceraria (Mol.) Standley

    OpenAIRE

    Nithya R; Jayshree N

    2013-01-01

    Lagenaria siceraria (Mol.) Standley is a large pubescent, climbing or tailing herb with stout 5- angledstems and bifid tendrils belonging to the family Cucurbitaceae. Various parts of Lagenaria siceraria(Mol.) Standley has traditional and folklore claims in the treatment of diabetes, obesity, cardiovasculardiseases, urolithiasis, adenopathy, cancer, hypercholesterolemia, dyskinesia, hepatosis, jaundice,diarrhoea, dysuria, fever, rheumatism, myalgia, ophthalmia, uterosis, scabies, ulcer. In th...

  7. Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody encephalitis in a male adolescent with a large mediastinal teratoma.

    Science.gov (United States)

    Sommeling, Charlotte; Santens, Patrick

    2014-05-01

    We present a case of a 16-year-old boy with Klinefelter syndrome who presented with a syndrome of impaired alertness, orofacial dyskinesias, choreiform movements, epileptic seizures, and autonomic instability, pointing to a diagnosis of anti-N-methyl-Daspartate (anti-NMDA) receptor antibody encephalitis.

  8. Carbidopa/levodopa/entacapone: the evidence for its place in the treatment of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Markos Poulopoulos

    2009-12-01

    Full Text Available Markos Poulopoulos, Cheryl WatersDepartment of Neurology, Division of Movement Disorders, Columbia University Medical Center, Neurological Institute of New York, Center of Parkinson’s Disease and Other Movement Disorders, New York, NY, USAIntroduction: Parkinson’s disease (PD is a common neurodegenerative disease. In the 1960s, it was shown that the degeneration of dopamine producing neurons in the substantia nigra (SN caused the motor features of PD. Dopamine replacement with levodopa, a dopamine precursor, resulted in remarkable benefit. Yet, the intermittent administration of levodopa is a major cause of motor complications, such as “wearing-off ” of levodopa’s benefit and involuntary movements, known as dyskinesia. Therefore, agents that prolong levodopa’s half-life were employed, such as carbidopa, an aromatic amino acid decarboxylase (AADC inhibitor, and entacapone, a catechol-O-methyltransferase (COMT inhibitor. The combination product carbidopa/levodopa/entacapone (CLE was approved in 2003 for the treatment of PD patients.Aims: To assess the evidence for the place of CLE in the treatment of PD.Evidence review: CLE has a good efficacy, safety and tolerability profile, similar to that of entacapone taken separately with carbidopa/levodopa (CL. Compared to CL alone, it prolongs levodopa’s benefit, and improves the quality of life but not the motor performance in PD patients with nondebilitating “wearing-off ” or dyskinesia. However, it increases the dyskinesia rate in early PD patients, and has adverse events in advanced patients with significant motor complications. There is insufficient evidence regarding cost-effectiveness.Place in therapy: CLE is an attractive alternative for patients with nondisabling “wearing-off ” or dyskinesia taking CL with or without entacapone. It cannot be recommended for early PD patients, as it can induce more dyskinesia than CL alone, or in any patients who seem to have more adverse

  9. Therapeutic strategies to prevent motor complications in Parkinson's disease.

    Science.gov (United States)

    Kieburtz, Karl

    2008-08-01

    Dopaminergic treatment of Parkinson's disease (PD) leads to significant improvement in Parkinsonian features; however, the treatment response is hampered by the appearance of motor complications, including dyskinesias and motor fluctuations. These motor complications have a significant negative impact on quality-of-life. Therapeutic strategies using different types and timing of dopaminergic therapy may influence the emergence of motor complications. While sustained release preparations of levodopa have not shown benefit over immediate release preparations, the early combination of a dopamine agonist with levodopa appears to reduce the onset of motor fluctuations. An even larger body of evidence has found that initiating treatment with a dopamine receptor agonist (as compared to immediate release levodopa) is associated with a reduction in motor fluctuations, particularly dyskinesias. These data have led to evidence-based medicine evaluations indicating that the use of dopamine agonists is efficacious and clinically useful for the prevention of motor complications.

  10. CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic Drug-Induced Side Effects.

    Science.gov (United States)

    Ivanova, S A; Filipenko, M L; Vyalova, N M; Voronina, E N; Pozhidaev, I V; Osmanova, D Z; Ivanov, M V; Fedorenko, O Yu; Semke, A V; Bokhan, N A

    2016-03-01

    Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

  11. EFFECT OF ACUPUNCTURE PLUS MOXIBUSTION OF YONGQUAN POINT ON DYSCINESIA AND BLOOD RHEOLOGY IN STROKE PATIENTS

    Institute of Scientific and Technical Information of China (English)

    李佩芳

    2001-01-01

    ABSTRACT Objective: To observe the therapeutic effect of acupuncture plus moxibustion of Yongquan (KI 1 ) in improving stroke patients' dyskinesia and blood rheology. Methods: 78 cases of stroke patients were treated by acupuncture and moxibustion of Yongquan (KI 1), once daily, with 20 days being a therapeutic course. Indexes of whole blood viscosity, plasma viscosity, platelet aggregation rate, packed cell volume and fibrinogen were detected before and after treatment. Changes of the functional activity were assessed using Barthel marking method. Results: After 2 courses of acupuncture treatment, all the above-mentioned indexes and functional activity were improved significantly (P<0.05~0.01). Conclusion: Acupuncture and moxibustion of Yongquan (KI 1 ) has an active effect in improving stroke patients' dyskinesia and blood rheology.

  12. Levodopa in the treatment of Parkinson's disease: an old drug still going strong.

    Science.gov (United States)

    Poewe, Werner; Antonini, Angelo; Zijlmans, Jan Cm; Burkhard, Pierre R; Vingerhoets, François

    2010-09-07

    After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

  13. Atypical Manifestations in Glut1 Deficiency Syndrome.

    Science.gov (United States)

    De Giorgis, V; Varesio, C; Baldassari, C; Piazza, E; Olivotto, S; Macasaet, J; Balottin, U; Veggiotti, P

    2016-08-01

    Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis. © The Author(s) 2016.

  14. Neuropsychiatric phenotype in a child with pseudohypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Paola Visconti

    2016-01-01

    Full Text Available Pseudohypoparathyroidism (PHP is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.

  15. Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression.

    Science.gov (United States)

    Ranjan, R; Meltzer, H Y

    1996-08-15

    The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.

  16. [Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

    Science.gov (United States)

    Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

    2013-10-01

    A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  17. Kartagener Syndrome: A Rare Genetic Disorder

    Directory of Open Access Journals (Sweden)

    Kunjan Shakya

    2009-01-01

    Full Text Available Kartagener Syndrome is a rare autosomal recessive disorder consisting of triad of sinusitis, bronchiectasis and situs inversus with dextrocardia. It is the subset of disorder called primary ciliary dyskinesia in which the cilia have abnormal structure and/or function resulting in multisystem diseases of various severity. Clinical manifestations include lifelong, chronic upper and lower respiratory tract diseases secondary to ineffective mucociliary clearance. Early diagnosis and management of chest infections can prevent irreversible damage to lungs and prevent potential lifelong complications. This case report is on a patient who presented with long standing history of sinusitis, bronchiectasis and on examination situs inversus with dextrocardia. Key Words:bronchiectasis, dextrocardia, kartagener syndrome, primary ciliary dyskinesia, situs inversus

  18. [Specific features of centriole formation and ciliogenesis in ciliary epithelium cells of respiratory tracts in patients with Kartagener syndrome].

    Science.gov (United States)

    Domaratskiĭ, K E; Uvakina, E V; Volkov, I K; Onishchenko, G E

    2005-01-01

    An electron microscopic study of the ciliary epithelium of respiratory tracts was carried out in children (members of the same family) with Kartagener syndrome, which is a variant of ciliary dyskinesia. It was shown that in the case of both mobile cilia and ciliary dyskinesia in man, centrioles are formed during formation of the ciliary basal bodies predominantly de novo, involving deuterosomes. A wide spectrum of pathological changes was described in literature, such as the absence of dynein arms in the axoneme and disorganization of axoneme structure. In addition to these changes in the ciliary system, we found integration of several ciliary axonemes by the same plasma membrane, running of microtubules from the plasma membrane as bundles, different orientation of basal legs, etc.

  19. A case of Kartagener′s syndrome: Importance of early diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Sanjay Gupta

    2013-01-01

    Full Text Available Kartagener′s syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present from early life and this distinguishes it from acquired mucociliary disorders. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus are having Kartagener syndrome. We present a case of 12 year old boy with sinusitis, situs inversus and bronchiectasis. The correct diagnosis of this rare congenital autosomal recessive disorder in early life is important in the overall prognosis of the syndrome, as many of the complications can be prevented if timely management is instituted, as was done in this in this case.

  20. A case of Kartagener′s syndrome: Importance of early diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Sanjay Gupta

    2012-01-01

    Full Text Available Kartagener′s syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present from early life and this distinguishes it from acquired mucociliary disorders. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus are having Kartagener syndrome. We present a case of 12 year old boy with sinusitis, situs inversus and bronchiectasis. The correct diagnosis of this rare congenital autosomal recessive disorder in early life is important in the overall prognosis of the syndrome, as many of the complications can be prevented if timely management is instituted, as was done in this in this case.

  1. Self-mutilation in neurodegeneration with brain iron accumulation

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2015-01-01

    Full Text Available Neurodegeneration with brain iron accumulation (NBIA is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.

  2. [High dosage therapy of Parkinson disease. New dopamine agonist pramipexol allows reduction of L-dopa dose down to zero].

    Science.gov (United States)

    Arnold, G; Kupsch, A

    1999-08-01

    We report a 63-years old patient with Parkinson's disease, who experienced slight fluctuations 10 years after first signs of the disease and two years after initiation of levodopa/carbidopa and biperiden therapy. He was enrolled in a double blind, placebo controlled study with the dopamine agonist pramipexole. This study was extended to an open phase. During this phase we were able to reduce levodopa/carbidopa down to zero, while fluctuations and peak dose dyskinesias ceased. The most important adverse event were hypersomnia and very slight persistent dyskinesias, which were reported tolerable by the patient. Treatment without levodopa/carbidopa could be maintained for 31 months. We conclude that in selected cases patients in Hoehn and Yahrs stages II to III and with mild fluctuations might be treated with pramipexole without levodopa.

  3. Kartagener's syndrome presented with nasal obstruction: A case report

    Directory of Open Access Journals (Sweden)

    Suna Asilsoy

    2014-08-01

    Full Text Available The nasal polyposis is a chronic inflammatory process of the nasal mucosa. Although it is rare in children, there may be also association with cystic fibrosis and primary ciliary dyskinesia. About 50% of primary ciliary dyskinesia patients develop situs inversus and it is known as Kartagener's syndrome. The Kartagener's sydrome is a rare autosomal recessive disorder characterized by sinusitis, bronchiectasis, situs inversus. Clinically, patients present to the otolaryngologist with nasal obstruction. We as pediatricians, should consider nasal polyposis as a rare cause of nasal obstruction in children. In the presence of recurrent upper and lower respiratory tract infections accompanying nasal polyposis, Kartagener's syndrome must be kept in mind as a rare reason. [Cukurova Med J 2014; 39(4.000: 942-945

  4. Atopic dermatitis severity in the patients with hepatobilliary pathology

    Directory of Open Access Journals (Sweden)

    T. V. Melnikova

    2014-01-01

    Full Text Available The aim of the research was to define severity of atopic dermatitis (AtD in the patients with hepatobiliary pathology. 221 patients with AtD were under investigation. 51 of them had associated biliary dyskinesia, 45 patients had chronic viral hepatitis (CVH without replecative kinesis, 65 patients had chronic viral hepatitis (CVH with replecative kinesis, and 50 patients had no hepatobiliary pathology. The results obtained showed marked effect of the hepato-biliary system pathology on the severity of the AtD pathology. The patients with biliary dyskinesia have a lichenoid kind of AtD and patients with deep-rooted viral hepatitis have an eczematous kind of AtD.

  5. Primary Parkinson's disease: the use of Tuina and acupuncture in accord with an evolving hypothesis of its cause from the perspective of Chinese traditional medicine--Part 2.

    Science.gov (United States)

    Walton-Hadlock, J

    1999-01-01

    In Part II of this series, the author continues the discussion of a hypothesis based on acupuncture channel theory regarding the cause of Parkinson's disease (PD). A system of Yin-type Tuina, termed FSR (forceless spontaneous response) evolved from this theory; its clinical application has resulted in various degrees of relief from PD symptoms, (e.g., tremor, rigidity, decreased dyskinesia; improved balance, circulation) regardless of the stage of the disease, and in several cases enabled a reduction of conventional medication. This installment includes basic instruction in the technique, and a discussion of the dyskinesia which occurs during restoration of Qi to the Large Intestine and Stomach channels during treatment. A case study chronicles the weekly changes in symptoms typically experienced by patients during FSR therapy.

  6. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism

    DEFF Research Database (Denmark)

    Södersten, Erik; Feyder, Michael; Lerdrup, Mads

    2014-01-01

    Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. ...... and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease....

  7. Gallbladder disease in children.

    Science.gov (United States)

    Rothstein, David H; Harmon, Carroll M

    2016-08-01

    Biliary disease in children has changed over the past few decades, with a marked rise in incidence-perhaps most related to the parallel rise in pediatric obesity-as well as a rise in cholecystectomy rates. In addition to stone disease (cholelithiasis), acalculous causes of gallbladder pain such as biliary dyskinesia, also appear to be on the rise and present diagnostic and treatment conundrums to surgeons. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Paediatrisk pulmonologi

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S E; Schiøtz, P O

    2001-01-01

    Paediatric pulmonology (paediatric respiratory medicine) concerns such lung diseases in children as asthma, pneumonia, cystic fibrosis, primary ciliary dyskinesia, chronic interstitial pneumonia, bronchopulmonary dysplasia and congenital abnormalities. This specialty has been approved...... paediatric organisations. The training syllabus emphasises routine in the clinical diagnosis and treatment of the diseases, as well as methods such as lung function in all age groups, bronchoscopy, biopsy, and others. This article summarises the status of this specialty, and the training syllabus...

  9. Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

    Directory of Open Access Journals (Sweden)

    Wafa Gati

    2012-12-01

    Full Text Available We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions.

  10. 5th National Congress of the Italian Society of Physiotherapy

    OpenAIRE

    Alessandro Aina; Barbara Cagnie; Elena Castelli; Chad Cook; Andrea Foglia; Paolo Bizzarri; Donatella Giraudo; Chris Littlewood; Andrea Tettamanti; Stefano Vercelli; Lennard Voogt; Aceto Maria; Spina Emanuele; Paone Paolo; Silvestre Francesco

    2016-01-01

    Table of contents S1 Criteria for exercises selection in subjects with low back pain Alessandro Aina S2 Recent advances in pathophysiology and treatment of myofascial trigger points Marco Barbero S3 Rehabilitation of scapular dyskinesia Barbara Cagnie S4 Musculoskeletal rehabilitation in subjects affected by neurological disorders Elena Castelli S5 Which examination tests suggest the best candidates for manual therapy Chad Cook S6 Case study: the role of the measurements for the identificatio...

  11. Evaluation of the safety of high-frequency chest wall oscillation (HFCWO) therapy in blunt thoracic trauma patients

    OpenAIRE

    Becker Brian; Ney Arthur L; Palmer Cassandra A; Anderson Casandra A; Schaffel Steven D; Quickel Robert R

    2008-01-01

    Abstract Background Airway clearance is frequently needed by patients suffering from blunt chest wall trauma. High Frequency Chest Wall Oscillation (HFCWO) has been shown to be effective in helping to clear secretions from the lungs of patients with cystic fibrosis, bronchiectasis, asthma, primary ciliary dyskinesia, emphysema, COPD, and many others. Chest wall trauma patients are at increased risk for development of pulmonary complications related to airway clearance. These patients frequent...

  12. Antipsychotic-induced movement disorders in long-stay psychiatric patients and 45 tag SNPs in 7 candidate genes: a prospective study.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia, subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia, as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1. METHODS: Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater 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. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. RESULTS: Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained. CONCLUSIONS: The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.

  13. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis.

    LENUS (Irish Health Repository)

    Barry, Helen

    2012-02-01

    We present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.

  14. Adaptive gene regulation in the Striatum of RGS9-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kathy Busse

    Full Text Available BACKGROUND: RGS9-deficient mice show drug-induced dyskinesia but normal locomotor activity under unchallenged conditions. RESULTS: Genes related to Ca2+ signaling and their functions were regulated in RGS9-deficient mice. CONCLUSION: Changes in Ca2+ signaling that compensate for RGS9 loss-of-function can explain the normal locomotor activity in RGS9-deficient mice under unchallenged conditions. SIGNIFICANCE: Identified signaling components may represent novel targets in antidyskinetic therapy. The long splice variant of the regulator of G-protein signaling 9 (RGS9-2 is enriched in striatal medium spiny neurons and dampens dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its overexpression prevents drug-induced dyskinesia. Other animal models of drug-induced dyskinesia rather pointed towards overactivity of dopamine receptor-mediated signaling. To evaluate changes in signaling pathways mRNA expression levels were determined and compared in wild-type and RGS9-deficient mice. Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9-deficient mice, while several genes related to Ca2+ signaling and long-term depression were differentially expressed when compared to wild type animals. Detailed investigations at the protein level revealed hyperphosphorylation of DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell patch clamp recordings showed that spontaneous synaptic events are increased (frequency and size in RGS9-deficient mice while long-term depression is reduced in acute brain slices. These changes are compatible with a Ca2+-induced potentiation of dopamine receptor signaling which may contribute to the drug-induced dyskinesia in RGS9-deficient mice.

  15. Late-Onset Neurodegeneration with Brain Iron Accumulation with Diffusion Tensor Magnetic Resonance Imaging

    OpenAIRE

    Syed Omar Shah; Hasit Mehta; Robert Fekete

    2012-01-01

    Introduction: Neuroferritinopathy is an autosomal dominant neurodegenerative disorder that includes a movement disorder, cognitive decline, and characteristic findings on brain magnetic resonance imaging (MRI) due to abnormal iron deposition. Here, we present a late-onset case, along with diffusion tensor imaging (DTI). Case Presentation: We report the case of a 74-year-old Caucasian female with no significant past medical history who presented for evaluation of orofacial dyskinesia, suspecte...

  16. [The semiotics of the pain and dyspeptic syndromes in motor disorders of the digestive organs in children and adolescents].

    Science.gov (United States)

    Dmytriieva, S M

    1999-06-01

    Overall 304 children and adolescents with gastro-duodenal pathology were studied for some aspects of clinical manifestations of the pain and dyspeptic syndromes as related to the character of disordered gastroduodenal motility by making use of techniques of phase polygastroduodenometry. Pathogenetic interrelationship was disclosed of clinical manifestations of the pain and dyspeptic syndromes according to the variant of gastroduodenal dysmotility (dysphasic hyper- or hypomotile dyskinesia of the stomach and duodenum).

  17. Kroniske lungeforandringer hos børn med langvarig produktiv hoste

    DEFF Research Database (Denmark)

    Foghsgaard, Jakob; Nir, Marta; Marthin, June K;

    2009-01-01

    A productive (sounding) cough is always abnormal, and suppurative lung disease should be considered. A chronic suppurative cough may be associated with the destruction of the bronchial wall (bronchiectasis). The most commonly identifiable cause of suppurative cough is cystic fibrosis. This article......, which is accompamied by an illustrative CT-scan, describes two paediatric cases of cystic fibrosis and primary ciliary dyskinesia and suggests appropriate avenues of clinical investigation, when chronic suppurative cough presents in children. Udgivelsesdato: 2009-Jan-26...

  18. Situs inversus totalis with azoospermia in a patient presenting with liver abscess

    Directory of Open Access Journals (Sweden)

    P. Mohan Rao

    2014-04-01

    Full Text Available Situs inversus with dextrocardia is a rare congenital anomaly. Azoospermia and situs inversus may be encountered in ciliary dyskinesia syndromes. We report the case of a 30-year-old male who manifested situs inversus totalis, dextrocardia and azoospermia with maturation arrest at primary spermatogenesis who presented with liver abscess. The patient responded well to treatment with i.v. metronidazole and oral chloroquine.

  19. Geç Tanı Konulan Nadir Bir Kartagener Sendromu Olgusu

    OpenAIRE

    NURAL, Serkan; HALICI, Bilal; Günay, Ersin

    2015-01-01

    Kartagener’s syndrome is an autosomal recessive inherited, primary ciliary dyskinesia syndrome, which is characterized by situs inversus, bronchiectasis, and chronic sinusitis. Symptoms usually emerge during childhood period. Ninety percent of cases are diagnosed prior to 15 years of age. In patients with Kartagener’s syndrome, respiratory infections are encountered such as chronic coughing, mucoid sputum, and recurrent pneumonia attacks. Bronchiectasis develops as a result of recurrent lung ...

  20. Bronchiolitis as a feature of kartagener syndrome: a case report.

    Science.gov (United States)

    Ozkaya, Sevket; Sahin, Unal; Gumus, Aziz; Taşç, Filiz; Cnarka, Halit; Yavuz, Asiye

    2011-01-01

    Kartagener syndrome (KS), also known as immotile cilia syndrome or as a primary ciliary dyskinesia, is characterized by the triad of situs inversus, bronchiectasis, and chronic pansinusitis. A few studies reported that diffuse bronchiolitis might be one of the characteristic features of the lung in KS. We aimed to present the radiologic characteristics of KS, including diffuse bronchiolitis, sinus aplasia, and situs inversus totalis in a single case.

  1. Effect of Levodopa Chronic Administration on Behavioral Changes and Fos Expression in Basal Ganglia in Rat Model of PD

    Institute of Scientific and Technical Information of China (English)

    徐岩; 孙圣刚; 曹学兵

    2003-01-01

    To study behavioral character and changes of neuronal activity in the basal ganglia of ratmodel of levodopa-induced dyskinesia, unilateral 6-hydroxydopamine lesioned rat model of Parkin-son disease (PD) was treated with levodopa/benserazide twice daily for 4 weeks and the behaviorobserved on the 1st, 3rd, 4th, 7th, 9th, 10th, 14th, 21st and 28th day. The animals were sacri-ficed and immunohistochemical technique was used to measure the changes of Fos expression in thecaudate putamen (CPU), globus pallidus (GP) and sensorimotor area of cerebral cortex 2 h afterthe last treatment. The results showed that pulsatile treatment with a subthreshold dose of levodo-pa gradually induced abnormal involuntary movement (AIM), including stereotypy (limb dyskine-sia, axial dystonia and masticatory dyskinesia) towards the side contralateral to the dopamine-den-ervated striatum and increased contraversive rotation. The motor pattern of each subtype was highlystereotypic across individual rats, and the proportion of each subtype was not consistent among in-dividual rats. Fos positive nuclei in the CPU and GP were increased by levodopa acute administra-tion, and more remarkably in the CPU, but not in the cerebral cortex. After repeated levodopatreatment, Fos positive nuclei were reduced remarkably in the CPU, but were increased in the GPand cerebral cortex. It was concluded that the neural mechanisms underlying levodopa induced AIMin rat model of PD was very similar to those seen in levodopa-induced dyskinesia (LID) in PD pa-tients and MPTP-lesioned monkeys, and increased striatopallidal neuronal activity might be involvedin occurrence of LID.

  2. Acute chorea associated with metoclopramide use.

    Science.gov (United States)

    Dubow, Jordan S; Leikin, Jerrold; Rezak, Michael

    2006-01-01

    Metoclopramide is a dopamine receptor antagonist that is used to treat diabetic gastroparesis, chemotherapy-induced nausea, and migraines. It is known to cause extrapyramidal side effects such as tardive dyskinesia, parkinsonism, dystonia, and akithisia, but not chorea. We describe a patient who presented with choreiform movements shortly after the administration of intravenous metoclopramide. Her work-up for secondary causes of chorea was otherwise negative and her symptoms abated with the administration of oral quetiapine and intravenous diazepam.

  3. Treatment of 43 Cases of Lateral Femoral Cutaneous Neuritis with Pricking and Cupping Therapy

    Institute of Scientific and Technical Information of China (English)

    王秀珍; 朱冬霞; 洪珏

    2009-01-01

    @@ Lateral femoral cutaneous neuritis, also named as meralgia paresthetica or Roth syndrome, is marked by cutaneous pain or paresthesia such as formication or numbness in one or both thighs, which can be aggravated by prolonged standing or walking; it is also characterized by hypoesthesia or skin sensibility without muscular atrophy or dyskinesia. Forty-three cases of lateral femoral cutaneous neuritis have been treated by pricking and cupping therapy since 1996. Now it was reported as follows.

  4. Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats

    OpenAIRE

    Peres, Fernanda F.; Levin, Raquel; Suiama, Mayra A.; Diana, Mariana C.; Gouvêa, Douglas A.; Almeida, Valéria; Santos, Camila M.; Lungato, Lisandro; Zuardi,Antônio W.; Jaime E. C. Hallak; CRIPPA, José A; Vânia, D’Almeida; Silva, Regina H.; Abílio, Vanessa C.

    2016-01-01

    Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The pre...

  5. Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

    OpenAIRE

    Mariana Babayeva; Haregewein Assefa; Paramita Basu; Sanjeda Chumki; Zvi Loewy

    2016-01-01

    Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore,...

  6. Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats

    OpenAIRE

    Fernanda Fiel Peres; Raquel Levin; Mayra Akimi Suiama; Mariana Cepollaro Diana; Douglas Albuquerque Gouvêa; Valéria Almeida; Camila Maurício Santos; Lisandro Lungato; Antonio Waldo Zuardi; Jaime Eduardo Hallak; José Alexandre Crippa; Vânia D'Almeida; Silva, Regina H.; Vanessa Costhek Abilio

    2016-01-01

    Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The pres...

  7. Catechol-O-methyltransferase and Parkinson's disease.

    OpenAIRE

    Tai CH; Wu RM

    2002-01-01

    Parkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. C...

  8. Respiratory medicines for children: current evidence, unlicensed use and research priorities

    DEFF Research Database (Denmark)

    Smyth, A R; Barbato, A; Beydon, N

    2010-01-01

    . Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular...... disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune...

  9. 5th National Congress of the Italian Society of Physiotherapy

    OpenAIRE

    Alessandro Aina; Barbara Cagnie; Elena Castelli; Chad Cook; Andrea Foglia; Paolo Bizzarri; Donatella Giraudo; Chris Littlewood; Andrea Tettamanti; Stefano Vercelli; Lennard Voogt; Aceto Maria; Spina Emanuele; Paone Paolo; Silvestre Francesco

    2016-01-01

    Table of contents S1 Criteria for exercises selection in subjects with low back pain Alessandro Aina S2 Recent advances in pathophysiology and treatment of myofascial trigger points Marco Barbero S3 Rehabilitation of scapular dyskinesia Barbara Cagnie S4 Musculoskeletal rehabilitation in subjects affected by neurological disorders Elena Castelli S5 Which examination tests suggest the best candidates for manual therapy Chad Cook S6 Case study: the role of the measurements for the identificatio...

  10. Candidate gene-based association study of antipsychotic-induced movement disorders in long-stay psychiatric patients: a prospective study.

    Directory of Open Access Journals (Sweden)

    P Roberto Bakker

    Full Text Available OBJECTIVE: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia, subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia, as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 10 candidate genes (PPP1R1B, BDNF, DRD3, DRD2, HTR2A, HTR2C, COMT, MnSOD, CYP1A2, and RGS2. METHODS: Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater 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. The authors genotyped 31 SNPs, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. RESULTS: VARIOUS SNPS REACHED NOMINAL SIGNIFICANCE: TD and orofacial dyskinesia with rs6265 and rs988748, limb truncal dyskinesia with rs6314, rest tremor with rs6275, rigidity with rs6265 and rs4680, bradykinesia with rs4795390, akathisia with rs4680, tardive dystonia with rs1799732, rs4880 and rs1152746. After controlling for multiple testing, no significant results remained. CONCLUSIONS: The findings suggest that selected SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account.

  11. Triazolam: An Abstracted Bibliography.

    Science.gov (United States)

    1989-11-01

    DRUGS: Benzodiazepines - doses vary SIBarbiturates - doses vary Antipsychotics - doses vary SUBJECTS: Rats PROCEDURES: The study used the pull-up test... antipsychotics and mor- phine showed little effect. "We consider...the test has a useful place in the psychopharmacology. laboratory." INDEX...vomiting (1) disturbances in conc.entration (25, itching (1) tachycardia Zl), tiredness (6), hangover (2), and dyskinesia (1). The side effects

  12. Quantitative analysis of gait and balance response to deep brain stimulation in Parkinson's disease

    OpenAIRE

    Mera, Thomas O.; Filipkowski, Danielle E.; Riley, David E.; Whitney, Christina M.; Walter, Benjamin L.; Gunzler, Steven A; Giuffrida, Joseph P

    2012-01-01

    Gait and balance disturbances in Parkinson’s disease (PD) can be debilitating and may lead to increased fall risk. Deep brain stimulation (DBS) is a treatment option once therapeutic benefits from medication are limited due to motor fluctuations and dyskinesia. Optimizing DBS parameters for gait and balance can be significantly more challenging than for other PD motor symptoms. Furthermore, inter-rater reliability of the standard clinical PD assessment scale, Unified Parkinson’s Disease Ratin...

  13. Metabotropic glutamate receptors: From the workbench to the bedside

    OpenAIRE

    Nicoletti, F.; Bockaert, J; Collingridge, G L; Conn, P. J.; Ferraguti, F.; Schoepp, D. D.; Wroblewski, J T; Pin, J P

    2010-01-01

    Metabotropic glutamate (mGlu) receptors were discovered in the mid 1980s and originally described as glutamate receptors coupled to polyphosphoinositide hydrolysis. Almost 6500 articles have been published since then, and subtype-selective mGlu receptor ligands are now under clinical development for the treatment of a variety of disorders such as Fragile-X syndrome, schizophrenia, Parkinson’s disease and L-DOPA-induced dyskinesias, generalized anxiety disorder, chronic pain, and gastroesophag...

  14. GENDER DIFFERENCES IN PARKINSON'S DISEASE: CLINICAL CHARACTERISTICS AND COGNITION

    OpenAIRE

    Miller, Ivy N.; Cronin-Golomb, Alice

    2010-01-01

    More men than women are diagnosed with Parkinson's disease (PD), and a number of gender differences have been documented in this disorder. Examples of clinical characteristics that appear in men more often than women include rigidity and rapid eye movement behavior disorder, whereas more women than men exhibit dyskinesias and depression. Differences between men and women in cognition have not been extensively examined, though there are reports of deficits in men in aspects of cognition that c...

  15. CHEST PHYSIOTHERAPY FOR INFANTS

    OpenAIRE

    2014-01-01

    In the normal lung, secretions are removed by Mucociliary activity, normal breathing cycles, and cough. In disease, increased secretion viscosity and volume, dyskinesia of the cilia, and ineffective cough combine to reduce the ability to clear secretions, and may increase exacerbations and infections. Many chest physiotherapy techniques like postural drainage, percussion and vibration are used since many years. These techniques are derived from adult studies but these techniques are quite str...

  16. What factors influence motor complications in Parkinson disease?: a 10-year prospective study.

    Science.gov (United States)

    García-Ruiz, Pedro J; Del Val, Javier; Fernández, Ignacio Mahillo; Herranz, Antonio

    2012-01-01

    The causes and mechanism behind motor complications in Parkinson disease (PD) are still a subject of debate. Several factors including age at onset, evolution in years, and initial medication can influence the onset and severity of motor complications in PD.We studied patients with recent diagnosis of PD who were followed up prospectively for 10 years. Analysis included the progression of these patients, as measured by the Unified Parkinson Disease Rating Scale scores and the presence of motor complications (motors fluctuations, dyskinesias, and gait freezing) over time. The patient group was studied as a whole and by subgroups classified according to age at onset, initial treatment, and sex.By the end of the first decade, most patients exhibited dyskinesias (91%), motor fluctuations (62%), and freezing of gait (68%). An association was found between several patients' characteristics and presence of motor complications by 5 years, though not after 10 years of follow up. The apparition of motor fluctuations was mainly related to initial treatment (odds ratio [OR], 3.87). The development of dyskinesias was linked to initial treatment (OR, 8.31), age at onset (OR, 0.90), and sex (OR, 12.87).

  17. Oral and infusion levodopa-based strategies for managing motor complications in patients with Parkinson's disease.

    Science.gov (United States)

    Antonini, Angelo; Chaudhuri, K Ray; Martinez-Martin, Pablo; Odin, Per

    2010-02-01

    Levodopa is the most effective treatment for Parkinson's disease (PD) signs and symptoms, and patients invariably will require it during the course of the disease. It also provides benefits in activities of daily living, quality of life and life expectancy. However, after a few years of levodopa treatment the majority of patients will experience motor fluctuations and dyskinesia. Initial use of a dopamine receptor agonist may delay the emergence of motor fluctuations but at the cost of reduced symptomatic control compared with the use of levodopa in some cases. Adequate management of motor fluctuations and dyskinesia is essential to maintaining satisfactory quality of life at the advanced stage of disease. Various levodopa-based strategies are currently available that aim to control motor complications (wearing-off and dyskinesia) in PD and each approach has its own unique benefit and risk profile. Strategies such as dose fragmentation (smaller, more frequent dosing) or the use of orally administered, liquid levodopa formulations or melevodopa can reduce off-time intervals or facilitate absorption. More recently introduced, continuous delivery of dopaminergic medications may represent a more effective approach to treat motor complications in advanced PD and its effect can be perceived from improvement in clinical scales, as well as in health-related items. Indeed, continuous levodopa delivery by duodenal infusion may stabilize and significantly improve motor function as well as patients' quality of life. We propose a treatment algorithm that takes into account all currently available levodopa-based treatment strategies for motor complications in patients with PD.

  18. From the MPTP-treated primate to the treatment of motor complications in Parkinson's disease.

    Science.gov (United States)

    Jenner, Peter

    2009-12-01

    The MPTP-treated primate has proved to be a highly predictive model of the effects of dopaminergic drugs in the symptomatic treatment of Parkinson's disease (PD) and for the avoidance of motor complications. Using MPTP-treated primates, new dopaminergic therapies have been devised alongside novel treatment strategies and novel routes of administration while providing knowledge on how to use dopaminergic drugs in a manner that avoids the onset of motor complications. The use of MPTP-treated primates led to the concept of continuous dopaminergic stimulation (CDS) and the early introduction of dopamine receptor agonists as monotherapy for PD for the prevention of dyskinesia. However, CDS does not explain the differences in dyskinesia induction that exist between L-dopa and dopamine receptor agonists, and a more rationale approach to therapy involves continuous drug delivery (CDD). CDD has been explored in the MPTP-treated primate and this review focuses on some of the evidence showing that the delivery of dopaminergic drugs in PD is key to the avoidance of dyskinesia while maintaining therapeutic efficacy. Other types of motor complication, such as "wearing off" and "on-off" remain to be explored in MPTP-treated primates and the model has yet to be used to examine non-motor components of PD. Despite having been employed for almost 25 years, the MPTP-treated primate has many potential uses in the future that will further improve the treatment of PD.

  19. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong

    Directory of Open Access Journals (Sweden)

    Werner Poewe

    2010-08-01

    Full Text Available Werner Poewe1, Angelo Antonini2, Jan CM Zijlmans3, Pierre R Burkhard4, François Vingerhoets51Department of Neurology, Medical University of Innsbruck, Austria; 2Parkinson Department, IRCCS San Camillo, Venice, and University of Padua, Italy; 3Department of Neurology, Amphia Hospital, Breda, The Netherlands; 4Department of Neurology, Faculty of Medicine and University Hospitals of Geneva, Switzerland; 5Neurodegenerative Disorders Unit, Neurology Department, CHUV, Lausanne, SwitzerlandAbstract: After more than 40 years of clinical use, levodopa (LD remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson’s disease (PD. Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug’s propensity to induce motor complications.Keywords: levodopa, motor fluctuations, dyskinesia, Parkinson’s disease

  20. Transdermal delivery of dopamine receptor agonists.

    Science.gov (United States)

    Reichmann, Heinz

    2009-12-01

    Conceptually, continuous dopaminergic stimulation is universally accepted to be the preferred therapeutic strategy to prevent or postpone dyskinesia in Parkinson's disease (PD). L-dopa has a short half-life of 2 hours and causes dyskinesia, whereas dopamine receptor agonists usually have a much longer half-life. Of the latter agents, cabergoline has the longest half-life of 68 hours and is ideal for the prevention of dyskinesia; but this is also true for other dopamine receptor agonists such as ropinirole or pramipexole, which have a shorter half-life of about 6-8 hours. Due to the possible development of valvular fibrosis, cabergoline is, however, only approved as a second-line treatment in PD, and patch technology has therefore gained major interest. So far, rotigotine is the only dopamine receptor agonist available as a patch. There is good evidence that once-daily patch usage provides patients with constant dopaminergic stimulation, and that patches are of equal potency to other oral non-ergot derivatives such as ropinirole and pramipexole. The disadvantages of patches are skin irritation and crystallization of the drug if not kept in the refrigerator. Copyright 2009 Elsevier Ltd. All rights reserved.

  1. Clinical features and gene analysis in Korean patients with early-onset Parkinson disease.

    Science.gov (United States)

    Chung, Eun Joo; Ki, Chang-Seok; Lee, Won Yong; Kim, In-Suk; Kim, Ji-Youn

    2006-08-01

    Systematic analysis of clinical features and gene mutations has not been performed in Korean patients with early-onset Parkinson disease (PD). To investigate the clinical characteristics and genetic background of Korean patients with early-onset PD. Clinical and genetic study. University hospital. Ninety-four patients with early-onset PD (mean +/- SD age at onset, 39.8 +/- 7.3 years) of 1100 patients with PD. Analysis of clinical characteristics and mutation analysis of the parkin and PTEN-induced kinase (PINK1) genes by direct sequencing and gene-dosage analysis using the multiplex ligation-dependent probe amplification technique. The correlation between age at onset and clinical characteristics and the clinical features of patients with onset before age 30 years vs patients with onset after age 30 years. Because age at onset was younger, levodopa-induced dyskinesia and off-dystonia were more frequently observed (P=.008). Patients affected before age 30 years showed more frequent levodopa-induced dyskinesia and off-dystonia (P=.002). We identified 3 patients (5%) with parkin gene mutations but none with the PINK1 mutation. Earlier onset of levodopa-induced dyskinesia and off-dystonia were characteristic features of early-onset PD, especially before an onset age of 30 years. However, parkin gene mutations were less frequent in these patients than in Japanese groups reported elsewhere.

  2. Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety.

    Science.gov (United States)

    Dhall, Rohit; Kreitzman, David L

    2016-04-01

    Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease. Immediate-release and controlled-release formulations have been used with success, but motor fluctuations remain a problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release therapy composed of carbidopa-levodopa microbeads designed to dissolve at various rates that allows for quick absorption and sustained levodopa release over an extended period. In development studies, RYTARY improved symptoms in patients with both early and advanced PD and offered significantly improved Unified Parkinson Disease Rating Scale scores and "on" times, without worsening troublesome dyskinesias when compared to other levodopa formulations. Tolerability and safety were comparable to other formulations. This section reviews the data that support the use of RYTARY in the treatment of PD.

  3. Safinamide: A Review in Parkinson's Disease.

    Science.gov (United States)

    Blair, Hannah A; Dhillon, Sohita

    2017-02-01

    Safinamide (Xadago(®)) is an orally active, selective, reversible monoamine oxidase-B inhibitor with both dopaminergic and non-dopaminergic (glutamatergic) properties. In the EU, safinamide is approved for the treatment of mid- to late-stage fluctuating Parkinson's disease (PD) as add-on therapy to a stable dose of levodopa alone or in combination with other PD medications. Safinamide 50-100 mg/day administered as a fixed or flexible dose significantly increased daily 'on' time without dyskinesia (primary endpoint) in patients with mid- to late-stage PD with motor fluctuations in 24-week, placebo-controlled clinical trials. Other outcomes, including motor function, overall clinical status and health-related quality of life, were also generally improved with safinamide. Furthermore, in an 18-month extension of one study, although dyskinesia (primary endpoint) was not significantly improved with safinamide relative to placebo, treatment benefits in other outcomes were generally sustained over 24 months of treatment. Safinamide was generally well tolerated in clinical trials; dyskinesia was the most common adverse event. Although further studies are needed, including comparative and long-term studies, current evidence indicates that safinamide extends the treatment options available for use as add-on therapy to levodopa and other PD medications in patients with mid- to late-stage PD experiencing motor fluctuations.

  4. Medical image of the week: Kartagener syndrome

    Directory of Open Access Journals (Sweden)

    Chan NH

    2013-10-01

    Full Text Available No abstract available. Article truncated at 150 words. A 52 year old woman was admitted for dyspnea and fatigue. Kartagener syndrome had been diagnosed at age 3 with situs inversus totalis (Figures 1 and 2. She has bronchiectasis (Figure 3 with chronic Pseudomonas colonization, chronic sinusitis, and nasal polyposis. Kartagener syndrome is a type of primary cilia dyskinesia or immotile-cilia syndrome. When primary ciliary dyskinesia is combined with situs inversus it is known as Kartagener syndrome (KS after the Swiss internist who recognized the association of situs inversus, bronchiectasis and sinusitis (1. It is popular in case presentations especially with the chest x-ray or CT scans deliberated presented inverted. KS is an autosomal recessive disorder of the ciliary axoneme with incomplete penetrance and extensive heterogeneity (2. The typical ciliary axoneme consists of 2 central microtubules surrounded by 9 microtubular doublets. Patients with primary ciliary dyskinesia exhibit a wide range of defects in ciliary ultrastructure and motility, which ultimately …

  5. Nicotine and Nicotinic Receptor Drugs: Potential for Parkinson's Disease and Drug-Induced Movement Disorders.

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    Quik, Maryka; Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A

    2015-01-01

    Parkinson's disease is a progressive neurodegenerative disorder associated with tremor, rigidity, and bradykinesia, as well as nonmotor symptoms including autonomic impairments, olfactory dysfunction, sleep disturbances, depression, and dementia. Although the major neurological deficit is a loss of nigrostriatal dopaminergic neurons, multiple neurotransmitters systems are compromised in Parkinson's disease. Consistent with this observation, dopamine replacement therapy dramatically improves Parkinson's disease motor symptoms. Additionally, drugs targeting the serotonergic, glutamatergic, adenosine, and other neurotransmitter systems may be beneficial. Recent evidence also indicates that nicotinic cholinergic drugs may be useful for the management of Parkinson's disease. This possibility initially arose from the results of epidemiological studies, which showed that smoking was associated with a decreased incidence of Parkinson's disease, an effect mediated in part by the nicotine in smoke. Further evidence for this idea stemmed from preclinical studies which showed that nicotine administration reduced nigrostriatal damage in parkinsonian rodents and monkeys. In addition to a potential neuroprotective role, emerging work indicates that nicotinic receptor drugs improve the abnormal involuntary movements or dyskinesias that arise as a side effect of l-dopa treatment, the gold standard therapy for Parkinson's disease. Both nicotine and nicotinic receptor drugs reduced l-dopa-induced dyskinesias by over 50% in parkinsonian rodent and monkey models. Notably, nicotine also attenuated the abnormal involuntary movements or tardive dyskinesias that arise with antipsychotic treatment. These observations, coupled with reports that nicotinic receptor drugs have procognitive and antidepressant effects, suggest that central nervous system (CNS) nicotinic receptors may represent useful targets for the treatment of movement disorders.

  6. REM sleep behavior disorder: association with motor complications and impulse control disorders in Parkinson's disease.

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    Kim, Young Eun; Jeon, Beom S; Yang, Hui-Jun; Ehm, Gwanhee; Yun, Ji Young; Kim, Han-Joon; Kim, Jong-Min

    2014-10-01

    Clinical phenotypes such as old age, longer disease duration, motor disability, akineto-rigid type, dementia and hallucinations are known to be associated with REM sleep behavior disorder (RBD) in Parkinson's disease (PD). However, the relationship between motor fluctuations/impulse control and related behaviors (ICRB) and RBD is not clear. We designed this study to elucidate the clinical manifestations associated with RBD to determine the implications of RBD in PD. In a cross-sectional study, a total of 994 patients with PD were interviewed to determine the presence of RBD and their associated clinical features including motor complications and ICRB. Of the 944 patients, 578 (61.2%) had clinical RBD. When comparing the clinical features between patients with RBD (RBD group) and without RBD (non-RBD group), older age, longer disease duration, higher Hoehn and Yahr stage (H&Y stage), higher levodopa equivalent daily dose (LEDD), and the existence of wearing off, dyskinesia, freezing, and ICRB, especially punding, were associated with the RBD group compared to the non-RBD group (P motor complications including wearing off, peak dose dyskinesia, and diphasic dyskinesia were the only relevant factors for RBD after adjusting for age and disease duration. Motor complications and ICRB are more frequent in patients with RBD than in patients without RBD. In addition, motor complications are related to RBD even after adjusting for age and disease duration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Why do patients with Parkinson’s disease fall? A cross-sectional analysis of possible causes of falls

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    Schrag, Anette; Choudhury, Mahbuba; Kaski, Diego; Gallagher, David A

    2017-01-01

    Background Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life. Aims To identify modifiable medical causes of falls in a cohort of PD patients. Methods Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities. Results Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P falls. Conclusions The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD.

  8. The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa.

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    Cilia, Roberto; Akpalu, Albert; Sarfo, Fred Stephen; Cham, Momodou; Amboni, Marianna; Cereda, Emanuele; Fabbri, Margherita; Adjei, Patrick; Akassi, John; Bonetti, Alba; Pezzoli, Gianni

    2014-10-01

    During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. Study design included a cross-sectional case-control analysis of data collected between December 2008 and November 2012, and a prospective study of patients followed-up for at least 6 months after the initiation of levodopa therapy. Ninety-one patients fulfilled criteria for clinical diagnosis of idiopathic Parkinson's disease (58 males, mean age at onset 60.6 ± 11.3 years). Demographic data were compared to those of 2282 consecutive Italian patients recruited during the same period, whereas nested matched subgroups were used to compare clinical variables. Demographic features, frequency and severity of motor and non-motor symptoms were comparable between the two populations, with the only exception of more frequent tremor-dominant presentation in Ghana. At baseline, the proportion of Ghanaian patients with motor fluctuations and dyskinesias was 56% and 14%, respectively. Although levodopa therapy was introduced later in Ghana (mean disease duration 4.2 ± 2.8 versus 2.4 ± 2.1 years, P disease duration at the occurrence of motor fluctuations and dyskinesias was similar in the two populations. In multivariate analysis, disease duration and levodopa daily

  9. Study on motor complications in patients with Parkinson's disease%帕金森病患者运动并发症的调查分析

    Institute of Scientific and Technical Information of China (English)

    周明珠; 刘振国; 干静; 陆丽霞; 吴佳英; 陈伟

    2008-01-01

    Objective To survey the prevalence and distribution of dyskinesia and motor fluctuations, and to investigate the factors related to the dyskinesia and motor fluctuations. Methods The detailed information were recorded, patients were rated by Unified Parkinson's disease rating scald (UPDRS) and Hoehn-Yahn stage. The occurrence of dyskinesia and motor fluctuations were recorded according to UPDRS Ⅳ. Results One hundred and twenty-two patients receiving levodopa treatment for at lease 6 months were involved. Fifteen (12.3%) were experiencing dyskinesia and 41(33.6%) motor fluctuations. The age of onset(OR=0.907,P<0.01) and daily levodopa dose (95% CI 1.000-1.004, OR=1.002, P<0.05) were independent factors with dyskinesia; while the age of onset (OR=0.922, P<0.05), levodopa treatment duration (OR=1.234, P<0.05), daily levodopa dose (95% CI 1.002-1.008, OR=1.005, P<0.01) and Hoehn-Yahn stage (OR=1.869, P<0.05) were independent factors of motor fluctuations. Conclusions The rate of motor complications was lower than the results surveyed in European countries. The likelihood of occurrence of dyskinesia and motor fluctuations is increased in those on high daily levedopa dose. The concomitant use of other medication to reduce levedopa dose might delay the motor complications.%目的 调查帕金森病(PD)患者中异动症及症状波动的发生率、分布情况以及影响因素.方法 详细记录患者资料,并进行统一帕会森病评分量表(UPDRS)、Hoehn&Yahn(H-Y)分级评分.根据UPDRS Ⅳ记录患者有无异动症及症状波动.结果 122例患者接受左旋多巴治疗,疗程至少6个月.其中15例(12.3%)合并异动症,41例(33.6%)合并症状波动.异动症的独立影响因素为:发病年龄(OR=0.907,P<0.01)和左旋多巴总量(95%C/1.000~1.004,OR=1.002,P<0.05);症状波动的独立影响因素为:发病年龄(OR=0.922,P<0.05),接受左旋多巴治疗的时间(OR=1.234,P<0.05),左旋多巴总量(95%CI 1.002~1.008,OR=1.005,P<0.01)

  10. Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications.

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    Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Rajput, Alex; Rajput, Ali H; Di Paolo, Thérèse

    2015-12-01

    L-DOPA-induced dyskinesias (LID) are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease. Serotonin receptors are implicated in the development of LID and modulation of basal ganglia 5-HT1B receptors is a potential therapeutic alternative in Parkinson's disease. In the present study, we used receptor-binding autoradiography of the 5-HT1B-selective radioligand [3H]GR125743 to investigate possible contributions of changes in ligand binding of this receptor in LID in post-mortem brain specimens from Parkinson's disease patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist and has been shown to reduce the development of LID in these monkeys in a chronic treatment of one month. [3H]GR125743 specific binding to striatal and pallidal 5-HT1B receptors respectively were only increased in L-DOPA-treated MPTP monkeys (dyskinetic monkeys) as compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesias scores correlated positively with this binding. Parkinson's disease patients with motor complications (L-DOPA-induced dyskinesias and wearing-off) had higher [3H]GR125743 specific binding compared to those without motor complications and controls in the basal ganglia. Reduction of motor complications was associated with normal striatal 5-HT1B receptors, suggesting the potential of this receptor for the management of motor complications in Parkinson's disease.

  11. Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and biochemical deficits in levodopa-induced dyskinetic rats model.

    Science.gov (United States)

    Ba, Maowen; Kong, Min; Guan, Lina; Yi, Maoli; Zhang, Hongli

    2016-09-13

    Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model. The effect of rTMS on abnormal involuntary movements (AIMs) was assessed. After ending the experiments, we further determined tyrosine hydroxylase (TH)-positive dopaminergic neurons number by immunohistochemistry, dopamine levels by HPLC, glial cell line-derived neurotrophic factor (GDNF) levels by ELISA, NR2B tyrosine phosphorylation and interactions of NR2B with Fyn by immunoblotting and immunoprecipitation. The results demonstrated that rTMS obviously attenuated AIMs scores, reduced the loss of nigral dopaminergic neurons and the fluctuations of striatal dopamine levels. Meanwhile, rTMS significantly increased the expression of GDNF, which couldrestore the damage of dopaminergic neurons. Additionally, rTMS also reduced the levels of the NR2B tyrosine phosphorylation andits interactions with Fyn in the lesioned striatum of LID rats model. Thus, these data indicate that rTMS can provide benefit for the therapy of LID by improving the key biochemical deficits related to dyskinesia.

  12. Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy.

    Directory of Open Access Journals (Sweden)

    Brigitte Chhin

    2009-03-01

    Full Text Available Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1 gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1-deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT-PCR and western blot, respectively. Human airway epithelial cells that were DNAI1-deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.

  13. Correlation of Quantitative Motor State Assessment Using a Kinetograph and Patient Diaries in Advanced PD: Data from an Observational Study.

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    Ossig, Christiana; Gandor, Florin; Fauser, Mareike; Bosredon, Cecile; Churilov, Leonid; Reichmann, Heinz; Horne, Malcolm K; Ebersbach, Georg; Storch, Alexander

    2016-01-01

    Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson's disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson's kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia. To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries. Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient's individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm. From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson's correlations coefficients: 0.404-0.658), but inter-rating method agreements on the single-hour-level were only low-to-moderate (Cohen's κ: 0.215-0.324). The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to-hour diary and PKG recordings should be addressed in further studies.

  14. Quantitative cholescintigraphy with fatty meal in the diagnosis of sphincter of Oddi dysfunction and acalculous cholecystopathy.

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    Santhosh, Sampath; Mittal, Bhagwant Rai; Arun, Sasikumar; Sood, Ashwani; Bhattacharya, Anish; Kochhar, Rakesh

    2012-07-01

    To evaluate the role of quantitative cholescintigraphy with fatty meal in the management of biliary dyskinesia and to describe the findings according to Sostre score (SS) criteria in patients with gallbladder (GB) in-situ and biliary pain. We performed a retrospective analysis of the hepatobiliary (HIDA) studies (n = 35) performed for evaluation of biliary dyskinesia either due to biliary pain, opioid induced sphincter of Oddi dysfunction (SOD), recurrent pancreatitis (RP) or post cholecystectomy syndrome (PCS). Gallbladder ejection fraction (GBEF) was calculated from the post fatty meal HIDA images (excluding PCS patients). Studies with GBEF ≤40 % and SS >4 were considered to have cholecystopathy and SOD respectively. Three of the 13 patients with PCS had SS of 6 each, suggestive of SOD. Delayed biliary visualization (>15 min) and activity in common bile duct 60 min > liver 15 min were the specific features in these cases. Opioid induced SOD patients had SS >4 with retrograde refilling of GB in one patient and normalization of the SS parameters after nifedipine challenge in the other patient. Patients with RP and biliary pain were stratified into four groups, normal (GBEF >40 % and SS ≤4), cholecystopathy (GBEF ≤40 % and SS ≤4), normal with SOD (GBEF >40 % and SS >4) and cholecystopathy with SOD (GBEF ≤40 % and SS >4). Four patients with intact GB had cholecystopathy with scintigraphic features of SOD. Quantitative cholescintigraphy with fatty meal and SS scoring identified biliary dyskinesia and SOD in patients with biliary pain, recurrent pancreatitis and post-cholecystectomy syndrome.

  15. Modern treatment in Parkinson's disease, a personal approach.

    Science.gov (United States)

    Reichmann, Heinz

    2016-01-01

    There are many guidelines available concerning the treatment of Parkinson's disease. Most of these advocate treating young-onset patients with a dopamine agonist and older patients with levodopa. The rationale behind this recommendation has its origins in the side effects associated with each of these drug classes: whilst levodopa leads to dyskinesia, which may not be relevant for patients with a limited life-expectancy, dopamine agonists have a much longer plasma half life which probably leads to more continuous dopamine receptor stimulation and thus decreases the occurrence and severity of dyskinesia. However, the side effects associated with the use of dopamine agonists, such as sleepiness, orthostatic problems, hallucinations and impulse control disorders are a drawback. In this overview, the hypothesis will be put forward that perhaps such a strict distinction is no longer needed. A new idea may be the early combination of levodopa with a dopamine agonist which would provide good clinical efficacy and, because of the relatively low doses involved, would reduce the side effects associated with both substances. MAO-B inhibitors may be a good option for early treatment and especially for patients who experience first motor fluctuations. Similarly, and particularly if a wearing-off symptom is present, COMT inhibitors smoothen and prolong the action of levodopa. More invasive escalation therapy comes into play when patients reach the advanced stages with problems of insufficient motor control, such as bradykinesia, rigidity and resting tremor, combined with on-time dyskinesia. The use of all oral and invasive treatment has to be individualized to gain a good motor and non-motor control and especially a good quality of life.

  16. Different patterns of medication change after subthalamic or pallidal stimulation for Parkinson's disease: target related effect or selection bias?

    Science.gov (United States)

    Minguez-Castellan..., A; Escamilla-Sevilla, F; Katati, M; Martin-Linares, J; Meersmans, M; Ortega-Moreno, A; Arjona, V

    2005-01-01

    Background: Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is favoured over bilateral globus pallidus internus (Gpi) DBS for symptomatic treatment of advanced Parkinson's disease (PD) due to the possibility of reducing medication, despite lack of definitive comparative evidence. Objective: To analyse outcomes after one year of bilateral Gpi or STN DBS, with consideration of influence of selection bias on the pattern of postsurgical medication change. Methods: The first patients to undergo bilateral Gpi (n = 10) or STN (n = 10) DBS at our centre were studied. They were assessed presurgically and one year after surgery (CAPIT protocol). Results: Before surgery the Gpi DBS group had more dyskinesias and received lower doses of medication. At one year, mean reduction in UPDRS off medication score was 35% and 39% in the Gpi and STN groups, respectively (non-significant difference). Dyskinesias reduced in proportion to presurgical severity. The levodopa equivalent dose was significantly reduced only in the STN group (24%). This study high-lights the absence of significant differences between the groups in clinical scales and medication dose at one year. In the multivariate analysis of predictive factors for off-state motor improvement, the presurgical levodopa equivalent dose showed a direct relation in the STN and an inverse relation in the Gpi group. Conclusion: Differences in the patterns of medication change after Gpi and STN DBS may be partly due to a patient selection bias. Both procedures may be equally useful for different subgroups of patients with advanced PD, Gpi DBS especially for patients with lower threshold for dyskinesia. PMID:15607992

  17. Bilateral globus pallidus internus deep brain stimulation for dyskinetic cerebral palsy supports success of cochlear implantation in a 5-year old ex-24 week preterm twin with absent cerebellar hemispheres.

    Science.gov (United States)

    Lin, Jean-Pierre; Kaminska, Margaret; Perides, Sarah; Gimeno, Hortensia; Baker, Lesley; Lumsden, Daniel E; Britz, Anzell; Driver, Sandra; Fitzgerald-O'Connor, Alec; Selway, Richard

    2017-01-01

    Early onset dystonia (dyskinesia) and deafness in childhood pose significant challenges for children and carers and are the cause of multiple disability. It is particularly tragic when the child cannot make use of early cochlear implantation (CI) technology to relieve deafness and improve language and communication, because severe cervical and truncal dystonia brushes off the magnetic amplifier behind the ears. Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) neuromodulation can reduce dyskinesia, thus supporting CI neuromodulation success. We describe the importance of the order of dual neuromodulation surgery for dystonia and deafness. First with bilateral GPi DBS using a rechargeable ACTIVA-RC neurostimulator followed 5 months later by unilateral CI with a Harmony (BTE) Advanced Bionics Hi Res 90 K cochlear device. This double neuromodulation was performed in series in a 12.5 kg 5 year-old ex-24 week gestation-born twin without a cerebellum. Relief of dyskinesia enabled continuous use of the CI amplifier. Language understanding and communication improved. Dystonic storms abated. Tolerance of sitting increased with emergence of manual function. Status dystonicus ensued 10 days after ACTIVA-RC removal for infection-erosion at 3 years and 10 months. He required intensive care and DBS re-implantation 3 weeks later together with 8 months of hospital care. Today he is virtually back to the level of functioning before the DBS removal in 2012 and background medication continues to be slowly weaned. This case illustrates that early neuromodulation with DBS for dystonic cerebral palsy followed by CI for deafness is beneficial. Both should be considered early i.e. under the age of five years. The DBS should precede the CI to maximise dystonia reduction and thus benefits from CI. This requires close working between the paediatric DBS and CI services. Copyright © 2016. Published by Elsevier Ltd.

  18. The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset.

    Science.gov (United States)

    Tayarani-Binazir, Kayhan A; Jackson, Michael J; Fisher, Ria; Zoubiane, Ghada; Rose, Sarah; Jenner, Peter

    2010-06-10

    Dopa decarboxylase inhibitors are routinely used to potentiate the effects of L-DOPA in the treatment of Parkinson's disease. However, neither in clinical use nor in experimental models of Parkinson's disease have the timing and dose of dopa decarboxylase inhibitors been thoroughly explored. We now report on the choice of dopa decarboxylase inhibitors, dose and the time of dosing relationships of carbidopa, benserazide and L-alpha-methyl dopa (L-AMD) in potentiating the effects of L-DOPA in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated common marmoset. Pre-treatment with benserazide for up to 3h did not alter the motor response to L-DOPA compared to simultaneous administration with L-DOPA. There was some evidence of a relationship between carbidopa and benserazide dose and increased locomotor activity and the reversal of motor disability. But in general, commonly used dose levels of dopa decarboxylase inhibitors appeared to produce a maximal motor response to L-DOPA. In contrast, dyskinesia intensity and duration continued to increase with both carbidopa and benserazide dose. The novel dopa decarboxylase inhibitor, L-AMD, increased locomotor activity and improved motor disability to the same extent as carbidopa or benserazide but importantly this was accompanied by significantly less dyskinesia. This study shows that currently, dopa decarboxylase inhibitors may be routinely employed in the MPTP-treated primate at doses which are higher than those necessary to produce a maximal potentiation of the anti-parkinsonian effect of L-DOPA. This may lead to excessive expression of dyskinesia in this model of Parkinson's disease and attention should be given to the dose regimens currently employed.

  19. Late-Onset Neurodegeneration with Brain Iron Accumulation with Diffusion Tensor Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Syed Omar Shah

    2012-12-01

    Full Text Available Introduction: Neuroferritinopathy is an autosomal dominant neurodegenerative disorder that includes a movement disorder, cognitive decline, and characteristic findings on brain magnetic resonance imaging (MRI due to abnormal iron deposition. Here, we present a late-onset case, along with diffusion tensor imaging (DTI. Case Presentation: We report the case of a 74-year-old Caucasian female with no significant past medical history who presented for evaluation of orofacial dyskinesia, suspected to be edentulous dyskinesia given her history of ill-fitting dentures. She had also developed slowly progressive dysarthria, dysphagia, visual hallucinations as well as stereotypic movements of her hands and feet. Results: The eye-of-the-tiger sign was demonstrated on T2 MRI. Increased fractional anisotropy and T2 hypointensity were observed in the periphery of the globus pallidus, putamen, substantia nigra, and dentate nucleus. T2 hyperintensity was present in the medial dentate nucleus and central globus pallidus. Discussion: The pallidal MRI findings were more typical of pantothenate kinase-associated neurodegeneration (PKAN, but given additional dentate and putamenal involvement, lack of retinopathy, and advanced age of onset, PKAN was less likely. Although the patient’s ferritin levels were within low normal range, her clinical and imaging features led to a diagnosis of neuroferritinopathy. Conclusion: Neurodegeneration with brain iron accumulation (NBIA is a rare cause of orofacial dyskinesia. DTI MRI can confirm abnormal iron deposition. The location of abnormal iron deposits helps in differentiating NBIA subtypes. Degeneration of the dentate and globus pallidus may occur via an analogous process given their similar T2 and DTI MRI appearance.

  20. Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro.

    Science.gov (United States)

    Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Röpke, Jivago; Boligon, Aline Augusti; Meinerz, Daiane; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

    2013-04-01

    Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC50 = 12.08 μg/mL) and Fe(2+)/EDTA (IC50 = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.