WorldWideScience

Sample records for recessive cerebellar ataxias

  1. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Zamba-Papanicolaou Eleni

    2008-04-01

    Full Text Available Abstract Background Senataxin (chromosome 9q34 was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA, termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2 and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP. Here, we report a novel Senataxin mutation in a Cypriot ARCA family. Methods We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA families for linkage to known ARCA gene loci. We linked one family (909 to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing. Results Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients. Conclusion We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.

  2. Sleep disorders in cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    José L. Pedroso

    2011-04-01

    Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

  3. Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

    NARCIS (Netherlands)

    Thomas, Anna C.; Williams, Hywel; Setó-Salvia, Núria; Bacchelli, Chiara; Jenkins, Dagan; O'Sullivan, Mary; Mengrelis, Konstantinos; Ishida, Miho; Ocaka, Louise; Chanudet, Estelle; James, Chela; Lescai, Francesco; Anderson, Glenn; Morrogh, Deborah; Ryten, Mina; Duncan, Andrew J.; Pai, Yun Jin; Saraiva, Jorge M.; Ramos, Fabiana; Farren, Bernadette; Saunders, Dawn; Vernay, Bertrand; Gissen, Paul; Straatmaan-Iwanowska, Anna; Baas, Frank; Wood, Nicholas W.; Hersheson, Joshua; Houlden, Henry; Hurst, Jane; Scott, Richard; Bitner-Glindzicz, Maria; Moore, Gudrun E.; Sousa, Sérgio B.; Stanier, Philip

    2014-01-01

    Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three

  4. Falls and cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    I. V. Damulin

    2015-01-01

    Full Text Available The paper considers the main causes of falls. Whatever their cause is, falls may lead to severe maladjustment in everyday life. In nearly 1 out of 10 cases, they are accompanied by severe injuries, including fractures (most commonly those of the proximal femur and humerus, hands, pelvic bones, and vertebrae, subdural hematoma, and severe soft tissue and head injuries. This process is emphasized to be multifactorial. Particular emphasis is laid on the involvement of the cerebellum and its associations, which may be accompanied by falls. This is clinically manifested mainly by gait disorders. Walking is a result of an interaction of three related functions (locomotion, maintenance of balance and adaptive reactions. In addition to synergies related to locomotion and balance maintenance, standing at rest and walking are influenced bythe following factors: postural and environmental information (proprioceptive, vestibular, and visual, the capacity to interpret and integrate this information, the ability of the musculoskeletal system to make movements, and the capability to optimally modulate these movements in view of the specific situation and the ability to choose and adapt synergy in terms of external factors and the capacities and purposes of an individual. The clinical signs of damage to the cerebellum and its associations are considered in detail. These structures are emphasized to be involved not only in movements, but also in cognitive functions. The major symptoms that permit cerebellar dysfunction to be diagnosed are given. Symptoms in cerebellar injuries are generally most pronounced when suddenly changing the direction of movements or attempting to start walking immediately after a dramatic rise. The magnitude of ataxia also increases in a patient who tries to decrease the step size. Falling tendencies or bending to one side (in other symptoms characteristic of cerebellar diseases suggest injury of the corresponding

  5. Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed Espectro clínico da ataxia cerebelar de início precoce com reflexos mantidos: uma ataxia autossômica recessiva para não ser esquecida

    Directory of Open Access Journals (Sweden)

    José Luiz Pedroso

    2013-06-01

    Full Text Available Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.As ataxias cerebelares autossômicas recessivas são um grupo heterogêneo de doenças neurológicas. Em 1981, foi descrita uma entidade neurológica incluindo ataxia cerebelar progressiva de início precoce, disartria, liberação piramidal e manutenção ou aumento dos reflexos tendíneos nos membros superiores e inferiores. Essa síndrome é conhecida como ataxia cerebelar de início precoce com reflexos mantidos. Neste artigo, o objetivo foi chamar a atenção para o diagnóstico de ataxia cerebelar de início precoce com reflexos mantidos como a segunda causa mais comum de ataxia cerebelar autossômica recessiva, após a ataxia de Friedreich, e também realizar um estudo do espectro cl

  6. Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

    Science.gov (United States)

    Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

    2017-11-21

    Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

  7. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  8. Speech Prosody in Cerebellar Ataxia

    Science.gov (United States)

    Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

  9. Toxic agents causing cerebellar ataxias.

    Science.gov (United States)

    Manto, Mario

    2012-01-01

    The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

  10. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases.

    Science.gov (United States)

    Mallaret, Martial; Renaud, Mathilde; Redin, Claire; Drouot, Nathalie; Muller, Jean; Severac, Francois; Mandel, Jean Louis; Hamza, Wahiba; Benhassine, Traki; Ali-Pacha, Lamia; Tazir, Meriem; Durr, Alexandra; Monin, Marie-Lorraine; Mignot, Cyril; Charles, Perrine; Van Maldergem, Lionel; Chamard, Ludivine; Thauvin-Robinet, Christel; Laugel, Vincent; Burglen, Lydie; Calvas, Patrick; Fleury, Marie-Céline; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-07-01

    Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series. The correct gene was predicted in 61 and 78 % of the cases by the two assessors, respectively. There was a high inter-rater agreement [K = 0.85 (0.55-0.98) p < 0.001] confirming the algorithm's reproducibility. Phenotyping patients with proper clinical examination, imaging, biochemical investigations and nerve conduction studies remain crucial for the guidance of molecular analysis and to interpret next generation sequencing results. The proposed algorithm should be helpful for diagnosing ARCA in clinical practice.

  11. Ataxias and Cerebellar or Spinocerebellar Degeneration

    Science.gov (United States)

    ... and conducts a broad range of basic and clinical research on cerebellar and spinocerebellar degeneration, including work aimed at finding the cause(s) of ataxias and ways to ... Publications Definition Ataxia ...

  12. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  13. Cerebellar ataxia of early onset

    International Nuclear Information System (INIS)

    Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko; Yamada, Kazuhiko.

    1989-01-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author)

  14. Acute Cerebellar Ataxia Induced by Nivolumab

    Science.gov (United States)

    Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

    2017-01-01

    A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment. PMID:29249765

  15. Acute Cerebellar Ataxia Induced by Nivolumab

    OpenAIRE

    Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

    2017-01-01

    A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy follow...

  16. CT and MR imaging of acute cerebellar ataxia

    International Nuclear Information System (INIS)

    Shoji, H.; Hirai, S.; Ishikawa, K.; Aramaki, M.; Sato, Y.; Abe, T.; Kojima, K.

    1991-01-01

    An adult female showed mild cerebellar ataxia and CSF pleocytosis following an acute infection of the upper respiratory tract, and was diagnosed as having acute cerebellar ataxia (ACA). CT and MR appearances in the acute stage revealed moderate swelling of the cerebellum and bilaterally increased signal intensity in the cerebellar cortex. (orig.)

  17. Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia.

    Science.gov (United States)

    Hamza, Wahiba; Ali Pacha, Lamia; Hamadouche, Tarik; Muller, Jean; Drouot, Nathalie; Ferrat, Farida; Makri, Samira; Chaouch, Malika; Tazir, Meriem; Koenig, Michel; Benhassine, Traki

    2015-06-12

    Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with great genetic and phenotypic heterogeneity, over 30 genes/loci have been associated with more than 20 different clinical forms of ARCA. Genetic heterogeneity combined with highly variable clinical expression of the cerebellar symptoms and overlapping features complicate furthermore the etiological diagnosis of ARCA. The determination of the most frequent mutations and corresponding ataxias, as well as particular features specific to a population, are mandatory to facilitate and speed up the diagnosis process, especially when an appropriate treatment is available. We explored 166 patients (115 families) refered to the neurology units of Algiers central hospitals (Algeria) with a cerebellar ataxia phenotype segregating as an autosomal recessive pattern of inheritance. Genomic DNA was extracted from peripheral blood samples and mutational screening was performed by PCR and direct sequencing or by targeted genomic capture and massive parallel sequencing of 57 genes associated with inherited cerebellar ataxia phenotypes. In this work we report the clinical and molecular results obtained on a large cohort of Algerian patients (110 patients/76 families) with genetically determined autosomal recessive ataxia, representing 9 different types of ARCA and 23 different mutations, including 6 novel ones. The five most common ARCA in this cohort were Friedreich ataxia, ataxia with isolated vitamin E deficiency, ataxia with oculomotor apraxia type 2, autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1. We report here a large cohort of patients with genetically determined autosomal recessive ataxia and the first study of the genetic context of ARCA in Algeria. This study showed that in Algerian patients, the two most common types of ataxia (Friedreich ataxia and ataxia with isolated vitamin E deficiency) coexist with forms that may be

  18. Mitochondrial recessive ataxia syndrome mimicking dominant spinocerebellar ataxia.

    Science.gov (United States)

    Palin, Eino J H; Hakonen, Anna H; Korpela, Mari; Paetau, Anders; Suomalainen, Anu

    2012-04-15

    We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Transient cerebellopontine demyelinisation revealed by MRI in acute cerebellar ataxia

    International Nuclear Information System (INIS)

    Aufricht, C.A.; Tenner, W.; Rosenmayr, F.; Stiglbauer, R.

    1990-01-01

    An eight year old boy was admitted to our ward with a history of abrupt onset of rapidly progressive gait disorder, nausea, vertigo and vomiting. The clinical as well as the laboratory findings suggested the diagnosis of acute cerebellar ataxia. Magnetic resonance imaging (MRI), however, showed marked demyelinisation in the cerebellar region and visual evoked potentials were pathologic. After immunosuppression the patient promptly improved clinically and the lesions depicted by MRI disappeared almost completely. (orig.)

  20. Xeroderma pigmentosum complementation group F: A rare cause of cerebellar ataxia with chorea.

    Science.gov (United States)

    Carré, G; Marelli, C; Anheim, M; Geny, C; Renaud, M; Rezvani, H R; Koenig, M; Guissart, C; Tranchant, C

    2017-05-15

    The complementation group F of Xeroderma pigmentosum (XP-F) is rare in the Caucasian population, and usually devoid of neurological symptoms. We report two cases, both Caucasian, who exhibited progressive cerebellar ataxia, chorea, a mild subcortical frontal cognitive impairment, and in one case severe polyneuropathy. Brain MRI demonstrated cerebellar (2/2) and cortical (1/2) atrophy. Both patients had only mild sunburn sensitivity and no skin cancer. Mini-exome sequencing approach revealed in ERCC4, two heterozygous mutations, one of which was never described (c.580-584+1delCCAAGG, exon 3), in the first case, and an already reported homozygous mutation, in the second case. These cases emphasize that XP-F is a rare cause of recessive cerebellar ataxia and can in some cases clinically mimic Huntington's disease due to chorea and executive impairment. The association of ataxia, chorea, and sun hypersensitivity are major guidance for the diagnosis, which should not be missed, in order to prevent skin neoplastic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

    Directory of Open Access Journals (Sweden)

    Samira Abbasi

    2016-01-01

    Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels

  2. Ataxia cerebelar aguda na criança Acute cerebellar ataxia in children

    Directory of Open Access Journals (Sweden)

    Valeriana Moura Ribeiro

    1968-03-01

    Full Text Available São relatados os casos de 6 crianças com ataxia cerebelar aguda. Admitem os autores a presença de um fator etiológico de caráter viral comum a todos êles, discutindo os mecanismos patogênicos com base nos casos da literatura. A evolução foi favorável em todos os pacientes, com regressão completa da sintomatologia, dentro do período de 6 a 60 dias.Clinical observations of 6 children with acute cerebellar ataxia and respective laboratorial data are reported. Considerations are made in order to support the hypothesis of involving virus. The evolution of the disorder was a nonfatal one and the patients regained normal cerebellar function within a period of 6 to 60 days.

  3. Cerebellar ataxia of early onset. Clinical symptoms and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko (Kanagawa Children' s Medical Center, Yokohama (Japan)); Yamada, Kazuhiko

    1989-07-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author).

  4. Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI

    International Nuclear Information System (INIS)

    Tavani, F.; Zimmerman, R.A.; Gatti, R.; Bingham, P.; Berry, G.T.; Sullivan, K.

    2003-01-01

    We describe MRI of the brain in 19 patients with ataxia-telangiectasia (AT) and correlate the appearances with the degree of neurologic deficit. We examined 10 male and nine female patients; 17 were aged between 2 and 12 years (mean 8 years) but a woman and her brother were 35 and 38 years old, and had a variant of AT. Ataxia was the first recognized sign of the disease in every patient. We detected the following patterns of cerebellar atrophy: in the youngest patient, aged 2 years, the study was normal; in the five next youngest patients 3-7 years of age, the lateral cerebellum and superior vermis showed the earliest changes of atrophy; and all but one of the other patients had moderate to marked diffuse atrophy of vermis and cerebellar hemispheres. There were 12 patients aged 9 years and above; one, who was normal, was 9 years old. The five patients who at the time of examination were unable to walk all had diffuse atrophy involving both vermis and cerebellar hemispheres. (orig.)

  5. Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

    OpenAIRE

    Shneyder, Natalya; Lyons, Mark K.; Driver-dunckley, Erika; Evidente, Virgilio Gerald H.

    2012-01-01

    Background: Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers c...

  6. The effect of piracetam on ataxia: clinical observations in a group of autosomal dominant cerebellar ataxia patients.

    Science.gov (United States)

    Ince Gunal, D; Agan, K; Afsar, N; Borucu, D; Us, O

    2008-04-01

    Autosomal dominant cerebellar ataxias are clinically and genetically heterogeneous neurodegenerative disorders. There is no known treatment to prevent neuronal cell death in these disorders. Current treatment is purely symptomatic; ataxia is one of the most disabling symptoms and represents the main therapeutic challenge. A previous case report suggesting benefit from administration of high dose piracetam inspired the present study of the efficacy of this agent in patients with cerebellar ataxia. Piracetam is a low molecular weight derivative of gamma-aminobutyric acid. Although little is known of its mode of action, its efficacy has been documented in a wide range of clinical indications, such as cognitive disorders, dementia, vertigo and dyslexia, as well as cortical myoclonus. The present report investigated the role of high dose piracetam in patients with cerebellar ataxia. Eight patients with autosomal dominant cerebellar ataxia were given intravenous piracetam 60 g/day by a structured protocol for 14 days. The baseline and end-of-the study evaluations were based on the International Cooperative Ataxia Rating Scale. Statistical analysis demonstrated a significant improvement in the patients' total score (P = 0.018) and a subscale analysis showed statistical significance for only the posture and gait disturbances item (P = 0.018). This study is providing good clinical observation in favour of high dose piracetam infusion to reduce the disability of the patients by improving their gait ataxia.

  7. Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

    Directory of Open Access Journals (Sweden)

    Natalya V. Shneyder

    2012-04-01

    Full Text Available Background: Both hypothyroidism and Hashimoto's thyroiditis (HT can rarely be associated with cerebellar ataxia. Severe essential tremor (ET as well as bilateral thalamic deep brain stimulation (DBS may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion: Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual.

  8. Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.

    Science.gov (United States)

    H'mida-Ben Brahim, D; M'zahem, A; Assoum, M; Bouhlal, Y; Fattori, F; Anheim, M; Ali-Pacha, L; Ferrat, F; Chaouch, M; Lagier-Tourenne, C; Drouot, N; Thibaut, C; Benhassine, T; Sifi, Y; Stoppa-Lyonnet, D; N'Guyen, K; Poujet, J; Hamri, A; Hentati, F; Amouri, R; Santorelli, F M; Tazir, M; Koenig, M

    2011-01-01

    The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.

  9. Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Fellgiebel, Andreas; Siessmeier, Thomas; Winterer, Georg; Lüddens, Hartmut; Mann, Klaus; Schmidt, Lutz G; Bartenstein, Peter

    2004-01-01

    To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

  10. Preliminary Study of Intravenous Amantadine Treatment for Ataxia Management in Patients with Probable Multiple System Atrophy with Predominant Cerebellar Ataxia

    Directory of Open Access Journals (Sweden)

    Jinyoung Youn

    2012-05-01

    Full Text Available Background and Purpose: Multiple system atrophy with predominant cerebellar ataxia is a disabling neurologic disease. However, effective management has not yet been established. We conducted a short-term, open-label preliminary study to assess the benefits of intravenous amantadine treatment in patients with probable multiple system atrophy with predominant cerebellar ataxia. Methods: Twenty patients (10 male, 10 female with probable multiple system atrophy with predominant cerebellar ataxia received 400 mg of amantadine by intravenous per day for 5 days. Ataxia severity was evaluated by the International Cooperative Ataxia Rating Scale before and after intravenous amantadine therapy and all subjects reported subjective improvement after intravenous amantadine treatment using a patient global impression scale. We analyzed the total and subscale scores by the ataxia scale and patient global impression scale. Results: The mean age was 57.4 years (range: 47–72 and the mean disease duration was 30.8 months (range: 11–79. The ataxia severity significantly decreased after intravenous amantadine therapy from 42.5 to 37.3 (p < 0.001. The mean patient global impression scale for improvement was 2.9 and there were no side effects of intravenous amantadine treatment observed. When we assessed responders, the duration of intravenous amantadine effect was more than 1 month in 4 subjects of 7 responders. Conclusions: Our findings suggest that intravenous amantadine treatment can be a safe management option in cerebellar ataxia, although the mechanism is unclear. Thus, further double-blind, long-term studies with a larger sample size are needed.

  11. Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4

    Directory of Open Access Journals (Sweden)

    Saud Alsahli

    2018-02-01

    Full Text Available Background: Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait. Methods: We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members. Results: Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene ( ATP8A2 . A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI of the brain was normal in 60% of patients. Conclusions: We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.

  12. Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4.

    Science.gov (United States)

    Alsahli, Saud; Alrifai, Muhammad Talal; Al Tala, Saeed; Mutairi, Fuad Al; Alfadhel, Majid

    2018-01-01

    Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait. We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members. Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene ( ATP8A2 ). A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI) of the brain was normal in 60% of patients. We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.

  13. False-positive head-impulse test in cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Olympia eKremmyda

    2012-11-01

    Full Text Available Abstract:The objective of this study was to compare the findings of the bedside head impulse test (HIT, passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA. In 16 patients with CA and bilaterally pathological bedside HIT, VOR gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses. Those with normal calorics showed a slightly reduced HIT gain (mean±SD: 0.73±0.15. In those with pathological calorics, gains 80ms and 100 ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111±62 ms after onset of the HIT than in those with normal calorics. (191±17 ms, p=0.0064 We indentified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA.

  14. Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Erik; Johnson, B; Koefoed, Pernille

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  15. The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children.

    Science.gov (United States)

    Terracciano, Alessandra; Renaldo, Florence; Zanni, Ginevra; D'Amico, Adele; Pastore, Anna; Barresi, Sabina; Valente, Enza Maria; Piemonte, Fiorella; Tozzi, Giulia; Carrozzo, Rosalba; Valeriani, Massimiliano; Boldrini, Renata; Mercuri, Eugenio; Santorelli, Filippo Maria; Bertini, Enrico

    2012-05-01

    Childhood cerebellar ataxias, and particularly congenital ataxias, are heterogeneous disorders and several remain undefined. We performed a muscle biopsy in patients with congenital ataxia and children with later onset undefined ataxia having neuroimaging evidence of cerebellar atrophy. Significant reduced levels of Coenzyme Q10 (COQ10) were found in the skeletal muscle of 9 out of 34 patients that were consecutively screened. A mutation in the ADCK3/Coq8 gene (R347X) was identified in a female patient with ataxia, seizures and markedly reduced COQ10 levels. In a 2.5-years-old male patient with non syndromic congenital ataxia and autophagic vacuoles in the muscle biopsy we identified a homozygous nonsense mutation R111X mutation in SIL1 gene, leading to early diagnosis of Marinesco-Sjogren syndrome. We think that muscle biopsy is a valuable procedure to improve diagnostic assesement in children with congenital ataxia or other undefined forms of later onset childhood ataxia associated to cerebellar atrophy at MRI. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Yubin Wang

    2016-06-01

    Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  17. Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

    Directory of Open Access Journals (Sweden)

    Tiago Silva Aguiar

    Full Text Available ABSTRACT The enzyme glutamic acid decarboxylase (GAD, present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA. The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.

  18. Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias.

    Science.gov (United States)

    Deistung, Andreas; Stefanescu, Maria R; Ernst, Thomas M; Schlamann, Marc; Ladd, Mark E; Reichenbach, Jürgen R; Timmann, Dagmar

    2016-02-01

    Magnetic resonance imaging (MRI) of the brain is of high interest for diagnosing and understanding degenerative ataxias. Here, we present state-of-the-art MRI methods to characterize structural alterations of the cerebellum and introduce initial experiments to show abnormalities in the cerebellar nuclei. Clinically, T1-weighted MR images are used to assess atrophy of the cerebellar cortex, the brainstem, and the spinal cord, whereas T2-weighted and PD-weighted images are typically employed to depict potential white matter lesions that may be associated with certain types of ataxias. More recently, attention has also focused on the characterization of the cerebellar nuclei, which are discernible on spatially highly resolved iron-sensitive MR images due to their relatively high iron content, including T2 (*)-weighted images, susceptibility-weighted images (SWI), effective transverse relaxation rate (R2 (*)) maps, and quantitative susceptibility maps (QSM). Among these iron-sensitive techniques, QSM reveals the best contrast between cerebellar nuclei and their surroundings. In particular, the gyrification of the dentate nuclei is prominently depicted, even at the clinically widely available field strength of 3 T. The linear relationship between magnetic susceptibility and local iron content allows for determination of iron deposition in cerebellar nuclei non-invasively. The increased signal-to-noise ratio of ultrahigh-field MRI (B0 ≥ 7 T) and advances in spatial normalization methods enable functional MRI (fMRI) at the level of the cerebellar cortex and cerebellar nuclei. Data from initial fMRI studies are presented in three common forms of hereditary ataxias (Friedreich's ataxia, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6). Characteristic changes in the fMRI signal are discussed in the light of histopathological data and current knowledge of the underlying physiology of the fMRI signal in the cerebellum.

  19. Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.

    Science.gov (United States)

    Coutelier, Marie; Hammer, Monia B; Stevanin, Giovanni; Monin, Marie-Lorraine; Davoine, Claire-Sophie; Mochel, Fanny; Labauge, Pierre; Ewenczyk, Claire; Ding, Jinhui; Gibbs, J Raphael; Hannequin, Didier; Melki, Judith; Toutain, Annick; Laugel, Vincent; Forlani, Sylvie; Charles, Perrine; Broussolle, Emmanuel; Thobois, Stéphane; Afenjar, Alexandra; Anheim, Mathieu; Calvas, Patrick; Castelnovo, Giovanni; de Broucker, Thomas; Vidailhet, Marie; Moulignier, Antoine; Ghnassia, Robert T; Tallaksen, Chantal; Mignot, Cyril; Goizet, Cyril; Le Ber, Isabelle; Ollagnon-Roman, Elisabeth; Pouget, Jean; Brice, Alexis; Singleton, Andrew; Durr, Alexandra

    2018-05-01

    Molecular diagnosis is difficult to achieve in disease groups with a highly heterogeneous genetic background, such as cerebellar ataxia (CA). In many patients, candidate gene sequencing or focused resequencing arrays do not allow investigators to reach a genetic conclusion. To assess the efficacy of exome-targeted capture sequencing to detect mutations in genes broadly linked to CA in a large cohort of undiagnosed patients and to investigate their prevalence. Three hundred nineteen index patients with CA and without a history of dominant transmission were included in the this cohort study by the Spastic Paraplegia and Ataxia Network. Centralized storage was in the DNA and cell bank of the Brain and Spine Institute, Salpetriere Hospital, Paris, France. Patients were classified into 6 clinical groups, with the largest being those with spastic ataxia (ie, CA with pyramidal signs [n = 100]). Sequencing was performed from January 1, 2014, through December 31, 2016. Detected variants were classified as very probably or definitely causative, possibly causative, or of unknown significance based on genetic evidence and genotype-phenotype considerations. Identification of variants in genes broadly linked to CA, classified in pathogenicity groups. The 319 included patients had equal sex distribution (160 female [50.2%] and 159 male patients [49.8%]; mean [SD] age at onset, 27.9 [18.6] years). The age at onset was younger than 25 years for 131 of 298 patients (44.0%) with complete clinical information. Consanguinity was present in 101 of 298 (33.9%). Very probable or definite diagnoses were achieved for 72 patients (22.6%), with an additional 19 (6.0%) harboring possibly pathogenic variants. The most frequently mutated genes were SPG7 (n = 14), SACS (n = 8), SETX (n = 7), SYNE1 (n = 6), and CACNA1A (n = 6). The highest diagnostic rate was obtained for patients with an autosomal recessive CA with oculomotor apraxia-like phenotype (6 of 17 [35.3%]) or

  20. Epidemiology of Cerebellar Ataxia on the Etiological Basis: A Cross Sectional Study

    Directory of Open Access Journals (Sweden)

    Simindokht Hosseini Seyede

    2009-12-01

    Full Text Available Cerebellar ataxias are a heterogenous group of disorders, clinically and etiologically, that result in considerable health burden. Finding out about the various etiologies, and their relative prevalences in the population suffering from cerebellar ataxia helps the clinician to perform a better management, in treatment process. This is a cross sectional study designed to estimate the relative prevalence of each etiologic factor. One-hundred and thirty-five patients ,in the range of 6 to 73 years from march 1993 to march1999, were classified in different groups on the basis of etiological findings. Relative prevalence of each of the etiological factors , common accompanying disorders besides ataxia in the patients,CT and MRI changes,and CSF alterations are studied and recorded. A widely spread age group, and the extended number of the cases under study, are the advantages of the current study over the previously reported case series. Among the etiologic groups, multiple sclerosis, cerebrovascular accidents and hereditary cerebellar ataxia, were the most common etiologic factors associated with cerebellar ataxia respectively.

  1. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

    2012-01-01

    to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...

  2. Supporting a Youth with Cerebellar Ataxia into Adolescence.

    Science.gov (United States)

    Meneses, Veronica; Gonzalez-Castillo, Zurisadai; Edgar, Veronica B; Augustyn, Marilyn

    2017-04-01

    Zoe, a 13-year-old white girl, presents as a new patient to your pediatric clinic with complaints of frequent emesis, anxiety, and learning problems, and previous diagnosis of cerebellar ataxia. Parents accompany Zoe and state, "it is really hard for her to go out, she gets sick and falls easily." She was born full term by vaginal delivery without complications. Given globally delayed milestones, she received early intervention services. Feeding problems began at infancy, including gastroesophageal reflux and aspiration pneumonia.At age 2, Zoe saw a neurologist and brain MRI revealed cerebellar atrophy. She recently saw a geneticist and genetic studies are pending. Parents report receiving "little" information regarding prognosis; through their own research, they read about individuals having similar symptoms in adulthood, with a degenerative pattern. They worry that Zoe is "still very young and we do not know what her future will be like."Despite ongoing speech and feeding challenges, the parents report difficulty finding a speech and language therapist in their area. Zoe does see an otolaryngologist for frequent otitis media and hearing loss and an ophthalmologist for vision problems. Still, she continues to fall further behind in school. Furthermore, she is intensely afraid of falling at school and has few friends, resulting in the family being at a loss regarding "what to do about school."She lives with both parents and 2 healthy older sisters. Her mother has Crohn's disease and has been unable to work. Her maternal aunt is close to Zoe and has hypothyroidism. Her father works as an insurance agent and resources have been "tight." Zoe's mother describes "making" Zoe go out to the movies, "otherwise she just stays home." Zoe usually needs assistance to walk in public, to keep from stumbling. Parents share that simply being in a public place or meeting a new physician may trigger emesis. Zoe does enjoy interacting with neighborhood children and says she wants to

  3. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD machinery.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available Inherited ataxias are characterized by degeneration of the cerebellar structures, which results in progressive motor incoordination. Hereditary ataxias occur in many species, including humans and dogs. Several mutations have been found in humans, but the genetic background has remained elusive in dogs. The Finnish Hound suffers from an early-onset progressive cerebellar ataxia. We have performed clinical, pathological, and genetic studies to describe the disease phenotype and to identify its genetic cause. Neurological examinations on ten affected dogs revealed rapidly progressing generalized cerebellar ataxia, tremors, and failure to thrive. Clinical signs were present by the age of 3 months, and cerebellar shrinkage was detectable through MRI. Pathological and histological examinations indicated cerebellum-restricted neurodegeneration. Marked loss of Purkinje cells was detected in the cerebellar cortex with secondary changes in other cortical layers. A genome-wide association study in a cohort of 31 dogs mapped the ataxia gene to a 1.5 Mb locus on canine chromosome 8 (p(raw = 1.1x10(-7, p(genome = 7.5x10(-4. Sequencing of a functional candidate gene, sel-1 suppressor of lin-12-like (SEL1L, revealed a homozygous missense mutation, c.1972T>C; p.Ser658Pro, in a highly conserved protein domain. The mutation segregated fully in the recessive pedigree, and a 10% carrier frequency was indicated in a population cohort. SEL1L is a component of the endoplasmic reticulum (ER-associated protein degradation (ERAD machinery and has not been previously associated to inherited ataxias. Dysfunctional protein degradation is known to cause ER stress, and we found a significant increase in expression of nine ER stress responsive genes in the cerebellar cortex of affected dogs, supporting the pathogenicity of the mutation. Our study describes the first early-onset neurodegenerative ataxia mutation in dogs, establishes an ERAD-mediated neurodegenerative

  4. SACS gene-related autosomal recessive spastic ataxia of Charlevoix-Saguenay from South India

    Directory of Open Access Journals (Sweden)

    M Suraj Menon

    2016-01-01

    Full Text Available Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS is a neurodegenerative disorder characterized by late infantile onset spastic ataxia and other neurological features. Initially described in the Charlevoix-Saguenay region of Quebec, Canada, it is being increasingly reported from many other countries. Here, we present the case of a 20-year-old male from South India, who presented with progressive ataxia, spasticity, and peripheral neuropathy with imaging features and genetic testing suggestive of SACS gene-related ARSACS. The phenotypic variability from other cases and occurrence in a geographically distinct region is stressed upon to alert the clinicians to consider ARSACS in progressive ataxias.

  5. Postural responses to multidirectional stance perturbations in cerebellar ataxia

    NARCIS (Netherlands)

    Bakker, Maaike; Allum, John H J; Visser, Jasper E; Grüneberg, Christian; van de Warrenburg, Bart P; Kremer, H P H; Bloem, Bastiaan R

    Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar

  6. Postural responses to multidirectional stance perturbations in cerebellar ataxia

    NARCIS (Netherlands)

    Bakker, Maaike; Allum, John H J; Visser, Jasper E; Grüneberg, Christian; van de Warrenburg, Bart P; Kremer, H P H; Bloem, Bastiaan R

    2006-01-01

    Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar

  7. Genetics Home Reference: autosomal dominant cerebellar ataxia, deafness, and narcolepsy

    Science.gov (United States)

    ... may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to move (migrate) ... Ataxia Foundation National Sleep Foundation University of Kansas Medical Center Resource List: Deafness and Hard of Hearing ...

  8. Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia.

    Science.gov (United States)

    Benussi, Alberto; Dell'Era, Valentina; Cotelli, Maria Sofia; Turla, Marinella; Casali, Carlo; Padovani, Alessandro; Borroni, Barbara

    Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present study investigated whether a two-weeks' treatment with cerebellar anodal tDCS could improve symptoms in patients with neurodegenerative cerebellar ataxia and could modulate cerebello-motor connectivity, at short and long term. We performed a double-blind, randomized, sham controlled trial with cerebellar tDCS (5 days/week for 2 weeks) in twenty patients with ataxia. Each patient underwent a clinical evaluation pre- and post-anodal tDCS or sham stimulation. A follow-up evaluation was performed at one and three months. Cerebello-motor connectivity was evaluated using transcranial magnetic stimulation (TMS) at baseline and at follow-up. Patients who underwent anodal tDCS showed a significant improvement in all performance scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale, 9-hole peg test, 8-m walking time) and in cerebellar brain inhibition compared to patients who underwent sham stimulation. A two-weeks' treatment with anodal cerebellar tDCS improves symptoms in patients with ataxia and restores physiological cerebellar brain inhibition pathways. Cerebellar tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cerebellar Ataxia with Bilateral Vestibulopathy: Description of a Syndrome and Its Characteristic Clinical Sign

    Science.gov (United States)

    Migliaccio, Americo A.; Halmagyi, G. Michael; McGarvie, Leigh A.; Cremer, Phillip D.

    2004-01-01

    We report four patients with the syndrome of cerebellar ataxia with bilateral vestibulopathy (CABV) and, using search coil oculography, we validate its characteristic clinical sign, namely impairment of the visually enhanced vestibulo-ocular reflex (VVOR) or doll's head reflex. In our four patients, CABV began in the sixth decade of life; they are…

  10. Spinocerebellar Ataxia Type 6 Protein Aggregates Cause Deficits in Motor Learning and Cerebellar Plasticity

    NARCIS (Netherlands)

    Mark, Melanie D; Krause, Martin; Boele, Henk-Jan; Kruse, Wolfgang; Pollok, Stefan; Kuner, Thomas; Dalkara, Deniz; Koekkoek, Sebastiaan; De Zeeuw, Chris I; Herlitze, Stefan

    2015-01-01

    Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca(2+) channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that

  11. GAD Antibody-Associated Late-Onset Cerebellar Ataxia in Two Female Siblings

    Directory of Open Access Journals (Sweden)

    Joseph Kuchling

    2014-11-01

    Full Text Available Background: Anti-glutamic acid decarboxylase antibody (GAD-ab-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF. Case Report: We report on 2 female siblings (aged 74 and 76 years presenting with gradual progression of rotational vertigo, gait ataxia and vertical diplopia, continuously progressing for 6 months and 6 years, respectively. Autoimmune laboratory examinations showed remarkably increased serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1 diabetes mellitus (T1DM and other concomitant autoimmune disorders (Grave's disease, Hashimoto's thyroiditis. Cerebral MRI and laboratory examinations were unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with particular brainstem involvement was established in both women. After the exclusion of an underlying malignancy, immunosuppressive therapy has been initiated in both patients, which resulted in stabilization in one and in clinical improvement in the other patient. Discussion: The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. Moreover, the occurrence of continuous vertical diplopia broadens the clinical spectrum of GAD-ab-associated neurological syndromes.

  12. Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Tanja [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States); Thomalla, Goetz [University Medical Center Hamburg-Eppendorf, Department of Neurology, Hamburg (Germany); Goebell, Einar [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); Piotrowski, Anna [The Johns Hopkins University School of Medicine, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD (United States); Yousem, David Mark [The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States)

    2015-02-17

    Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis. (orig.)

  13. Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

    Science.gov (United States)

    Schneider, Tanja; Thomalla, Götz; Goebell, Einar; Piotrowski, Anna; Yousem, David Mark

    2015-06-01

    Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis.

  14. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  15. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

    Science.gov (United States)

    Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H; Hirano, Michio; Koenig, Michel

    2008-03-01

    Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.

  16. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    Science.gov (United States)

    ... Canada, but it has since been found in populations worldwide. Related Information What information about a genetic ... are involved in chemical signaling between nerve cells ( neurons ). SYNE1 gene mutations that cause ARCA1 result in ...

  17. Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Stinton Laura M

    2003-09-01

    Full Text Available Abstract Background Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. Methods Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL were detected by ELISA. Results Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. Conclusion This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

  18. Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics

    Directory of Open Access Journals (Sweden)

    Fujioka Shinsuke

    2011-05-01

    Full Text Available Abstract Type I autosomal dominant cerebellar ataxia (ADCA is a type of spinocerebellar ataxia (SCA characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA. Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical

  19. Cerebellar Ataxia and Coenzyme Q Deficiency Through Loss of Unorthodox Kinase Activity

    OpenAIRE

    Stefely, Jonathan A.; Licitra, Floriana; Laredj, Leila; Reidenbach, Andrew G.; Kemmerer, Zachary A.; Grangeray, Anais; Jaeg-Ehret, Tiphaine; Minogue, Catherine E.; Ulbrich, Arne; Hutchins, Paul D.; Wilkerson, Emily M.; Ruan, Zheng; Aydin, Deniz; Hebert, Alexander S.; Guo, Xiao

    2016-01-01

    The UbiB protein kinase-like (PKL) family is widespread—comprising one-quarter of microbial PKLs and five human homologs—yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical ana...

  20. Evaluation of acetazolamine response in patients with cerebellar ataxia using dynamic quantitative F-18-FDG PET

    International Nuclear Information System (INIS)

    Kim, Y. K.; Lee, D. S.; Lee, J. S.; Kim, M. H.; Lee, K. M.; Yeo, J. S.; Chung, J. K.; Lee, M. C.

    2001-01-01

    Cerebellar Ataxia (CA) usually shows dramatic response to acetazolamide treatment. But few cases of acetazolamide unresponse CA were reported recently. Using dynamic FDG PET, we tried to evaluate the metabolic abnormality and its drug response in CA. Quantitative F-18-FDG PET was performed prior and after treatment of acetazolamide (250 mg qid for 10 days) in two patient suspected episodic cerebellar ataxia. Using Model-based clustering method, the regional cerebral glucose metabolic rate (rCMRglu) was calculated. Two patients showed different treatment response to acetazolamide. In one patient who showed markedly reduced frequency of the ataxic attack after treatment. FDG PET showed that mean cerebellar glucose metabolism was increased after treatment (ΔrCMRglu:9%). However, in the other who showed poor response to acetazolamide, FDG PET showed the more decrease metabolism in cerebellar metabolism after treatment (ΔrCMRglu:-17%). The change of the cerebellar glucose metabolism on FDG PET reflected the symptomatic improvement after acetazolamide in these two CA patients. We could expected that FDG PET might be a very useful tool to quantitatively predict the treatment response in CA and other neurologic disorder

  1. Familial cosegregation of manic-depressive illness and a form of hereditary cerebellar ataxia

    Energy Technology Data Exchange (ETDEWEB)

    Piqueras, J.F.; Santos, J.; Puertollano, R. [Universidad Autonoma, Madrid (Spain)] [and others

    1995-06-19

    We report on a Spanish family with co-occurrence of manic-depression and a form of hereditary cerebellar ataxia. All affected individuals in the second generation showed cerebellar ataxia and manic-depression simultaneously. Since anticipation has been described in both disorders and the pattern of segregation may be autosomal as well as X-linked, we have searched for a possible involvement of two candidate genes which are located either on an autosome (SCA1) or on the X-chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1 gene cannot be considered as a disease-causing mutation, and this gene should be initially discarded. 19 refs., 3 figs.

  2. Current concepts in the treatment of hereditary ataxias

    Directory of Open Access Journals (Sweden)

    Pedro Braga Neto

    2016-03-01

    Full Text Available ABSTRACT Hereditary ataxias (HA represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

  3. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

    Science.gov (United States)

    Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

    2015-10-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

  4. A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies.

    Science.gov (United States)

    Coutelier, Marie; Coarelli, Giulia; Monin, Marie-Lorraine; Konop, Juliette; Davoine, Claire-Sophie; Tesson, Christelle; Valter, Rémi; Anheim, Mathieu; Behin, Anthony; Castelnovo, Giovanni; Charles, Perrine; David, Albert; Ewenczyk, Claire; Fradin, Mélanie; Goizet, Cyril; Hannequin, Didier; Labauge, Pierre; Riant, Florence; Sarda, Pierre; Sznajer, Yves; Tison, François; Ullmann, Urielle; Van Maldergem, Lionel; Mochel, Fanny; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra

    2017-06-01

    Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic background, with mutations in 34 genes identified so far. This large amount of implicated genes accounts for heterogeneous clinical presentations, making genotype-phenotype correlations a major challenge in the field. While polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in large cohorts, there is a need for comprehensive assessment of frequency and phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine expansions in spinocerebellar ataxia genes in 412 index cases with dominantly inherited cerebellar ataxias, we aimed to establish the relative frequencies of mutations in other genes, with an approach combining panel sequencing and TaqMan® polymerase chain reaction assay. We found relevant genetic variants in 59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n = 16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11) were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001), though for similar functional stages, indicating slower progression of the disease. Of interest, intellectual deficiency was more frequent in channel spinocerebellar ataxias, while cognitive impairment in adulthood was similar among the three groups. Similar

  5. Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Sam P. Nayler

    2017-10-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1. RNA sequencing was used to classify differentiated cerebellar neurons generated from integration-free A-T and control induced pluripotent stem cells. Comparison of RNA sequencing data with datasets from the Allen Brain Atlas reveals in vitro-derived cerebellar neurons are transcriptionally similar to discrete regions of the human cerebellum, and most closely resemble the cerebellum at 22 weeks post-conception. We show that patient-derived cerebellar neurons exhibit disrupted gene regulatory networks associated with synaptic vesicle dynamics and oxidative stress, offering the first molecular insights into early cerebellar pathogenesis of ataxia-telangiectasia.

  6. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy

    NARCIS (Netherlands)

    Smets, Katrien; Duarri, Anna; Deconinck, Tine; Ceulemans, Berten; van de Warrenburg, Bart P.; Zuechner, Stephan; Gonzalez, Michael Anthony; Schuele, Rebecca; Synofzik, Matthis; Van der Aa, Nathalie; De Jonghe, Peter; Verbeek, Dineke S.; Baets, Jonathan

    2015-01-01

    Background: Identification of the first de novo mutation in potassium voltage-gated channel, shal-related subfamily, member 3 (KCND3) in a patient with complex early onset cerebellar ataxia in order to expand the genetic and phenotypic spectrum. Methods: Whole exome sequencing in a cerebellar ataxia

  7. Characteristics of Handwriting of People With Cerebellar Ataxia: Three-Dimensional Movement Analysis of the Pen Tip, Finger, and Wrist.

    Science.gov (United States)

    Fujisawa, Yuhki; Okajima, Yasutomo

    2015-11-01

    There are several functional tests for evaluating manual performance; however, quantitative manual tests for ataxia, especially those for evaluating handwriting, are limited. This study aimed to investigate the characteristics of cerebellar ataxia by analyzing handwriting, with a special emphasis on correlation between the movement of the pen tip and the movement of the finger or wrist. This was an observational study. Eleven people who were right-handed and had cerebellar ataxia and 17 people to serve as controls were recruited. The Scale for the Assessment and Rating of Ataxia was used to grade the severity of ataxia. Handwriting movements of both hands were analyzed. The time required for writing a character, the variability of individual handwriting, and the correlation between the movement of the pen tip and the movement of the finger or wrist were evaluated for participants with ataxia and control participants. The writing time was longer and the velocity profile and shape of the track of movement of the pen tip were more variable in participants with ataxia than in control participants. For participants with ataxia, the direction of movement of the pen tip deviated more from that of the finger or wrist, and the shape of the track of movement of the pen tip differed more from that of the finger or wrist. The severity of upper extremity ataxia measured with the Scale for the Assessment and Rating of Ataxia was mostly correlated with the variability parameters. Furthermore, it was correlated with the directional deviation of the trajectory of movement of the pen tip from that of the finger and with increased dissimilarity of the shapes of the tracks. The results may have been influenced by the scale and parameters used to measure movement. Ataxic handwriting with increased movement noise is characterized by irregular pen tip movements unconstrained by the finger or wrist. The severity of ataxia is correlated with these unconstrained movements. © 2015 American

  8. Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse

    Directory of Open Access Journals (Sweden)

    Maryam Rahimi Balaei

    2016-01-01

    Full Text Available Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2 mouse (nax—naked-ataxia mutant mouse correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5. In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.

  9. Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology.

    Science.gov (United States)

    Nóbrega, Clévio; Nascimento-Ferreira, Isabel; Onofre, Isabel; Albuquerque, David; Conceição, Mariana; Déglon, Nicole; de Almeida, Luís Pereira

    2013-08-01

    Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a fatal, dominant neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Clinical manifestations include cerebellar ataxia and pyramidal signs culminating in severe neuronal degeneration. Currently, there is no therapy able to modify disease progression. In the present study, we aimed at investigating one of the most severely affected brain regions in the disorder--the cerebellum--and the behavioral defects associated with the neuropathology in this region. For this purpose, we injected lentiviral vectors encoding full-length human mutant ataxin-3 in the mouse cerebellum of 3-week-old C57/BL6 mice. We show that circumscribed expression of human mutant ataxin-3 in the cerebellum mediates within a short time frame--6 weeks, the development of a behavioral phenotype including reduced motor coordination, wide-based ataxic gait, and hyperactivity. Furthermore, the expression of mutant ataxin-3 resulted in the accumulation of intranuclear inclusions, neuropathological abnormalities, and neuronal death. These data show that lentiviral-based expression of mutant ataxin-3 in the mouse cerebellum induces localized neuropathology, which is sufficient to generate a behavioral ataxic phenotype. Moreover, this approach provides a physiologically relevant, cost-effective and time-effective animal model to gain further insights into the pathogenesis of MJD and for the evaluation of experimental therapeutics of MJD.

  10. Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.

    Science.gov (United States)

    Stefely, Jonathan A; Licitra, Floriana; Laredj, Leila; Reidenbach, Andrew G; Kemmerer, Zachary A; Grangeray, Anais; Jaeg-Ehret, Tiphaine; Minogue, Catherine E; Ulbrich, Arne; Hutchins, Paul D; Wilkerson, Emily M; Ruan, Zheng; Aydin, Deniz; Hebert, Alexander S; Guo, Xiao; Freiberger, Elyse C; Reutenauer, Laurence; Jochem, Adam; Chergova, Maya; Johnson, Isabel E; Lohman, Danielle C; Rush, Matthew J P; Kwiecien, Nicholas W; Singh, Pankaj K; Schlagowski, Anna I; Floyd, Brendan J; Forsman, Ulrika; Sindelar, Pavel J; Westphall, Michael S; Pierrel, Fabien; Zoll, Joffrey; Dal Peraro, Matteo; Kannan, Natarajan; Bingman, Craig A; Coon, Joshua J; Isope, Philippe; Puccio, Hélène; Pagliarini, David J

    2016-08-18

    The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Hasegawa Akira

    2011-02-01

    Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

  12. Gaze stabilization in chronic vestibular-loss and in cerebellar ataxia: interactions of feedforward and sensory feedback mechanisms.

    Science.gov (United States)

    Sağlam, M; Lehnen, N

    2014-01-01

    During gaze shifts, humans can use visual, vestibular, and proprioceptive feedback, as well as feedforward mechanisms, for stabilization against active and passive head movements. The contributions of feedforward and sensory feedback control, and the role of the cerebellum, are still under debate. To quantify these contributions, we increased the head moment of inertia in three groups (ten healthy, five chronic vestibular-loss and nine cerebellar-ataxia patients) while they performed large gaze shifts to flashed targets in darkness. This induces undesired head oscillations. Consequently, both active (desired) and passive (undesired) head movements had to be compensated for to stabilize gaze. All groups compensated for active and passive head movements, vestibular-loss patients less than the other groups (P feedforward mechanisms substantially contribute to gaze stabilization. Proprioception alone is not sufficient (gain 0.2). Stabilization against active and passive head movements was not impaired in our cerebellar ataxia patients.

  13. DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

    Science.gov (United States)

    Oh, Myung Eun; Driever, Pablo Hernáiz; Khajuria, Rajiv K; Rueckriegel, Stefan Mark; Koustenis, Elisabeth; Bruhn, Harald; Thomale, Ulrich-Wilhelm

    2017-01-01

    Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long

  14. The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

    Science.gov (United States)

    Matsuda, Shunichi; Matsumoto, Hideyuki; Furubayashi, Toshiaki; Hanajima, Ritsuko; Tsuji, Shoji; Ugawa, Yoshikazu; Terao, Yasuo

    2015-01-01

    The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients. PMID:25706752

  15. A Rare Case of Cerebellar Ataxia Due to Voltage-Gated Calcium Channel and Glutamic Acid Decarboxylase Autoantibodies.

    Science.gov (United States)

    Annunziata, Giuseppe; Lobo, Pamela; Carbuccia, Cristian

    2017-11-27

    BACKGROUND Autoimmune cerebellar ataxia can be paraneoplastic in nature or can occasionally present without evidence of an ongoing malignancy. The detection of specific autoantibodies has been statistically linked to different etiologies. CASE REPORT A 55-year-old African-American woman with hypertension and a past history of morbid obesity and uncontrolled diabetes status post gastric bypass four years prior to the visit (with significantly improved body mass index and hemoglobin A1c controlled at the time of the clinical encounter) presented to the office complaining of gradual onset of unsteadiness and recurrent falls for the past three years, as well as difficulties coordinating routine daily activities. The neurologic exam showed moderate dysarthria and ataxic gait with bilateral dysmetria and positive Romberg test. Routine laboratory test results were only remarkable for a mild elevation of erythrocyte sedimentation rate, and most laboratory and imaging tests for common causes of ataxia failed to demonstrate an etiology. Upon further workup, evidence of anti-voltage-gated calcium channel and anti-glutamic acid decarboxylase antibody was demonstrated. She was then treated with intravenous immunoglobulins with remarkable clinical improvement. CONCLUSIONS We present a case of antibody-mediated ataxia not associated with malignancy. While ataxia is rarely related to autoantibodies, in such cases it is critical to understand the etiology of this disabling condition in order to treat it correctly. Clinicians should be aware of the possible association with specific autoantibodies and the necessity to rule out an occult malignancy in such cases.

  16. A Case of Ataxia with Isolated Vitamin E Deficiency Initially Diagnosed as Friedreich’s Ataxia

    Directory of Open Access Journals (Sweden)

    Michael Bonello

    2016-01-01

    Full Text Available Ataxia with isolated vitamin E deficiency (AVED is a rare autosomal recessive condition that is caused by a mutation in the alpha tocopherol transfer protein gene. It is almost indistinguishable clinically from Friedreich’s ataxia but with appropriate treatment its devastating neurological features can be prevented. Patients can present with a progressive cerebellar ataxia, pyramidal spasticity, and evidence of a neuropathy with absent deep tendon reflexes. It is important to screen for this condition on initial evaluation of a young patient presenting with progressive ataxia and it should be considered in patients with a long standing ataxia without any diagnosis in view of the potential therapeutics and genetic counselling. In this case report we present a patient who was initially diagnosed with Friedreich’s ataxia but was later found to have AVED.

  17. Effects of acetyl-DL-leucine on cerebellar ataxia (ALCAT trial): study protocol for a multicenter, multinational, randomized, double-blind, placebo-controlled, crossover phase III trial.

    NARCIS (Netherlands)

    Feil, K.; Adrion, C.; Teufel, J.; Bosch, S.; Claassen, J.; Giordano, I.; Hengel, H.; Jacobi, H.; Klockgether, T.; Klopstock, T.; Nachbauer, W.; Schols, L.; Stendel, C.; Uslar, E.; Warrenburg, B.P. van de; Berger, I.; Naumann, I.; Bayer, O.; Muller, H.H.; Mansmann, U.; Strupp, M.

    2017-01-01

    BACKGROUND: Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far,

  18. Speech changes after coordinative training in patients with cerebellar ataxia: a pilot study

    Czech Academy of Sciences Publication Activity Database

    Tykalová, T.; Pospíšilová, M.; Čmejla, R.; Jeřábek, J.; Mareš, Pavel; Rusz, J.

    2016-01-01

    Roč. 37, č. 2 (2016), s. 293-296 ISSN 1590-1874 Institutional support: RVO:67985823 Keywords : spinocerebellar ataxia * rehabilitation * physiotherapy * ataxic dysarthria * postural alignment * acoustic analysis Subject RIV: FH - Neurology Impact factor: 1.749, year: 2016

  19. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

    Science.gov (United States)

    Main, Stacey L; Kulesza, Randy J

    2017-01-06

    Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Autosomal recessive posterior column ataxia with retinitis pigmentosa caused by novel mutations in the FLVCR1 gene.

    Science.gov (United States)

    Shaibani, Aziz; Wong, Lee-Jun; Wei Zhang, Victor; Lewis, Richard Alan; Shinawi, Marwan

    2015-01-01

    Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive disorder characterized by severe sensory ataxia, muscle weakness and atrophy, and progressive pigmentary retinopathy. Recently, mutations in the FLVCR1 gene were described in four families with this condition. We investigated the molecular basis and studied the phenotype of PCARP in a new family. The proband is a 33-year-old woman presented with sensory polyneuropathy and retinitis pigmentosa (RP). The constellation of clinical findings with normal metabolic and genetic evaluation, including mitochondrial DNA (mtDNA) analysis and normal levels of phytanic acid and vitamin E, prompted us to seek other causes of our patient's condition. Sequencing of FLVCR1 in the proband and targeted mutation testing in her two affected siblings revealed two novel variants, c.1547G > A (p.R516Q) and c.1593+5_+8delGTAA predicted, respectively, to be highly conserved throughout evolution and affecting the normal splicing, therefore, deleterious. This study supports the pathogenic role of FLVCR1 in PCARP and expands the molecular and clinical spectra of PCARP. We show for the first time that nontransmembrane domain (TMD) mutations in the FLVCR1 can cause PCARP, suggesting different mechanisms for pathogenicity. Our clinical data reveal that impaired sensation can be part of the phenotypic spectrum of PCARP. This study along with previously reported cases suggests that targeted sequencing of the FLVCR1 gene should be considered in patients with severe sensory ataxia, RP, and peripheral sensory neuropathy.

  1. Sporadic Creutzfeldt–Jakob disease with cerebellar ataxia at onset in the UK

    Science.gov (United States)

    Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

    2006-01-01

    Objective To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods A retrospective review of autopsy‐proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)‐129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause. PMID:16835290

  2. hiPSC Disease Modeling of Rare Hereditary Cerebellar Ataxias: Opportunities and Future Challenges

    Czech Academy of Sciences Publication Activity Database

    Lukovic, D.; Moreno-Manzano, V.; Rodriquez; Jimenez, F.J.; Vilches, A.; Syková, Eva; Jendelová, Pavla; Stojkovic, M.; Erceg, Slaven

    2017-01-01

    Roč. 23, č. 5 (2017), s. 554-566 ISSN 1073-8584 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LO1309; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : 3D organoids * ataxia * disease modelling Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 7.391, year: 2016

  3. More Falls in Cerebellar Ataxia When Standing on a Slow Up-Moving Tilt of the Support Surface.

    Science.gov (United States)

    Paquette, Caroline; Franzén, Erika; Horak, Fay B

    2016-06-01

    We investigated how subjects with cerebellar ataxia (CA) adapt their postural stability and alignment to a slow and small tilt of the support surface allowing for online postural corrections. Eight subjects with CA and eight age- and gender-matched healthy control subjects participated in the study. Subjects stood eyes closed for 1 min after which the support surface was tilted 5° toes-up at a ramp velocity of 1°/s. The toes-up position was held for 2.5 min after which the surface rotated back down to level with identical tilt characteristics. As reflected by the large number of falls, subjects with CA had marked difficulty adapting their posture to the up-moving incline in contrast to control subjects. Subjects with CA who lost their balance had faster trunk velocity and excessive backward trunk reorientation beginning within the first second after onset of the tilting surface. In contrast, the down-moving tilt to level did not result in instability in CA subjects. These results suggest that instability and falls associated with CA derive from an inability to maintain trunk orientation to vertical while standing on a slow-moving or unstable surface. This study underscores the importance of the cerebellum in the online sensory control of the upper body orientation during small amplitude and slow velocity movements of the support surface.

  4. Maculopathy and spinocerebellar ataxia type 1

    DEFF Research Database (Denmark)

    Lebranchu, Pierre; Le Meur, Guylène; Magot, Armelle

    2013-01-01

    Autosomal dominant cerebellar ataxia is a rare heterogeneous group of diseases characterized by cerebellar symptoms, often associated with other multisystemic signs. Mild optic neuropathy has been associated with spinocerebellar ataxia type 1 (SCA1), but macular dysfunction has been reported...

  5. Harmony as a convergence attractor that minimizes the energy expenditure and variability in physiological gait and the loss of harmony in cerebellar ataxia.

    Science.gov (United States)

    Serrao, Mariano; Chini, Giorgia; Iosa, Marco; Casali, Carlo; Morone, Giovanni; Conte, Carmela; Bini, Fabiano; Marinozzi, Franco; Coppola, Gianluca; Pierelli, Francesco; Draicchio, Francesco; Ranavolo, Alberto

    2017-10-01

    The harmony of the human gait was recently found to be related to the golden ratio value (ϕ). The ratio between the duration of the stance and that of the swing phases of a gait cycle was in fact found to be close to ϕ, which implies that, because of the fractal property of autosimilarity of that number, the gait ratios stride/stance, stance/swing, swing/double support, were not significantly different from one another. We studied a group of patients with cerebellar ataxia to investigate how the differences between their gait ratios and the golden ratio are related to efficiency and stability of their gait, assessed by energy expenditure and stride-to-stride variability, respectively. The gait of 28 patients who were affected by degenerative cerebellar ataxia and of 28 healthy controls was studied using a stereophotogrammetric system. The above mentioned gait ratios, the energy expenditure estimated using the pelvis reconstructed method and the gait variability in terms of the stride length were computed, and their relationships were analyzed. Matching procedures have also been used to avoid multicollinearity biases. The gait ratio values of the patients were farther from the controls (and hence from ϕ), even in speed matched conditions (P=0.011, Cohen's D=0.76), but not when the variability and energy expenditure were matched between the two groups (Cohen's D=0.49). In patients with cerebellar ataxia, the farther the stance-swing ratio was from ϕ, the larger the total mechanical work (R 2 adj =0.64). Further, a significant positive correlation was observed between the difference of the gait ratio from the golden ratio and the severity of the disease (R=0.421, P=0.026). Harmony of gait appears to be a benchmark of physiological gait leading to physiological energy recovery and gait reliability. Neurorehabilitation of patients with ataxia might benefit from the restoration of harmony of their locomotor patterns. Copyright © 2017. Published by Elsevier Ltd.

  6. Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

    Science.gov (United States)

    Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

    2006-06-01

    The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

  7. Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.

    Science.gov (United States)

    Jazayeri, Roshanak; Hu, Hao; Fattahi, Zohreh; Musante, Luciana; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Wienker, Thomas F; Ropers, Hans Hilger; Najmabadi, Hossein; Kahrizi, Kimia

    2015-10-01

    Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes. We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms. We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study. Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).

  8. Cerebellar Degeneration

    Science.gov (United States)

    ... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

  9. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.

    Science.gov (United States)

    Moreira, Maria-Céu; Klur, Sandra; Watanabe, Mitsunori; Németh, Andrea H; Le Ber, Isabelle; Moniz, José-Carlos; Tranchant, Christine; Aubourg, Patrick; Tazir, Meriem; Schöls, Lüdger; Pandolfo, Massimo; Schulz, Jörg B; Pouget, Jean; Calvas, Patrick; Shizuka-Ikeda, Masami; Shoji, Mikio; Tanaka, Makoto; Izatt, Louise; Shaw, Christopher E; M'Zahem, Abderrahim; Dunne, Eimear; Bomont, Pascale; Benhassine, Traki; Bouslam, Naïma; Stevanin, Giovanni; Brice, Alexis; Guimarães, João; Mendonça, Pedro; Barbot, Clara; Coutinho, Paula; Sequeiros, Jorge; Dürr, Alexandra; Warter, Jean-Marie; Koenig, Michel

    2004-03-01

    Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.

  10. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres.

    Science.gov (United States)

    Infante, Jon; García, Antonio; Serrano-Cárdenas, Karla M; González-Aguado, Rocío; Gazulla, José; de Lucas, Enrique M; Berciano, José

    2018-04-25

    The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

  11. “Hot cross bun” sign in multiple system atrophy with predominant cerebellar ataxia: A comparison between proton density-weighted imaging and T2-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kasahara, Seiko, E-mail: nuun077@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Miki, Yukio, E-mail: yukio.miki@med.osaka-cu.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545–8585 (Japan); Kanagaki, Mitsunori, E-mail: mitsuk@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Kondo, Takayuki, E-mail: kondotak@kuhp.kyoto-u.ac.jp [Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Yamamoto, Akira, E-mail: yakira@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Morimoto, Emiko, E-mail: foresta@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Okada, Tomohisa, E-mail: tomokada@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Ito, Hidefumi, E-mail: itohid@kuhp.kyoto-u.ac.jp [Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); Takahashi, Ryosuke, E-mail: ryosuket@kuhp.kyoto-u.ac.jp [Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan); and others

    2012-10-15

    Objective: To investigate whether proton density-weighted imaging can detect the “hot cross bun” sign in the pons in multiple system atrophy with predominant cerebellar ataxia significantly better than T2-weighted imaging at 3 T. Methods: Sixteen consecutive patients with multiple system atrophy with predominant cerebellar ataxia according to the Consensus Criteria were reviewed. Axial unenhanced proton density-weighted imaging and T2-weighted imaging were obtained using a dual-echo fast spin-echo sequence at 3 T. Two neuroradiologists independently evaluated visualisation of the abnormal pontine signal using a 4-point visual grade from Grade 0 (no “hot cross bun” sign) to Grade 3 (prominent “hot cross bun” sign on two or more sequential slices). Differences in grade between proton density-weighted imaging and T2-weighted imaging were statistically analysed using the Wilcoxon signed-rank test. Results: In 11 patients (69%), a higher grade was given for proton density-weighted imaging than T2-weighted imaging. In 1 patient (6%), grades were the same (Grade 3) on both images. In the remaining 4 patients (25%), signal abnormalities were not detected on either image (Grade 0). The “hot cross bun” sign was thus observed significantly better on proton density-weighted imaging than on T2-weighted imaging (P = 0.001). Conclusions: The “hot cross bun” sign considered diagnostic for multiple system atrophy with predominant cerebellar ataxia is significantly better visualised on proton density-weighted imaging than on T2-weighted imaging at 3 T.

  12. Case Report: Neuro-Imaging Findings in Ataxia Telangiectasia

    Directory of Open Access Journals (Sweden)

    Farhad Mahvelati

    2004-06-01

    Full Text Available Ataxia Telangiectasia (AT is an autosomal recessive inherited disorder in which cutaneous and scleral Telangiectasia, cerebellar ataxia and immunodeficiency occur. There is a high incidence of development of malignant tumors, mainly lymphomas. Cerebellar atrophy is the most prominent abnormality and is shown better by magnetic resonance imaging (MRI than CT-Scan. Intracranial hemorrhage occurs rarely. We report a 7 years old boy who admitted for recurrent pulmonary infections. His examination showed ataxic gait with decreased deep tendon reflexes in lower extremities. He had telangiectasia in the eyes and his speech was slurred and difficult. Brain MRI showed cerebellar atrophy with diffuse hyperintensity in white matter, most prominent in occipital region, which was suggestive of leukodystrophy. This white matter change was not reported before in AT.

  13. A Family with Mental Retardation, Epilepsy and Cerebellar Hypoplasia Showing Linkage to Chromosome 20p11.21-q11.23

    Directory of Open Access Journals (Sweden)

    Fatih Bayrakli

    2014-01-01

    Full Text Available Background: Cerebellar hypoplasia (CH is a rare malformation caused by various etiologies, usually manifesting clinically as nonprogressive cerebellar ataxia with or without mental retardation. The molecular pathogenesis of the autosomal recessive cerebellar ataxias has a wide range of mechanisms. Differential diagnosis and categorization of the recessive cerebellar ataxias, however, need more specific, biochemical and genetic investigation. Methods: This study applied whole-genome linkage analysis to study a family with nonprogressive cerebellar ataxia and additional mental retardation, epilepsy, and facial dysmorphic features. Genotyping and linkage analysis was done using the GeneChip Mapping 250K NspI Array (Affymetrix Inc., Santa Clara, Calif., USA for genome-wide linkage analysis of the genotyping data from the affected children and their parents. Results: Allegro software version 1.2 was used for multipoint linkage analysis. We assumed an autosomal recessive inheritance pattern and assigned a penetrance of 0.999. Single-nucleotide polymorphism allele frequencies were estimated from the Affymetrix data of the Caucasian family studied. Using these parameters, a theoretical maximum logarithm of the odds score of 2.69 was identified at chromosome 20p11.21-q11.23. Conclusions: This chromosomal locus is unprecedented in autosomal recessive and nonprogressive ataxia disorder. Further investigation might reveal a new causative gene generating the CH phenotype.

  14. Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients.

    Science.gov (United States)

    Tazir, M; Ali-Pacha, L; M'Zahem, A; Delaunoy, J P; Fritsch, M; Nouioua, S; Benhassine, T; Assami, S; Grid, D; Vallat, J M; Hamri, A; Koenig, M

    2009-03-15

    Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX). We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade. Cerebellar ataxia was progressive, slowly leading to disability which was aggravated by axonal polyneuropathy present in almost all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor apraxia (OMA) was present in 32% of the patients while convergent strabismus was present in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more severe in the eldest patients; however it may also be an early sign since it was present in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in all but two patients who presented with head tremor and writer cramp, respectively. Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker to suggest molecular studies of the SETX gene.

  15. Cerebellar abiotrophy in a miniature schnauzer

    OpenAIRE

    Berry, Michelle L.; Blas-Machado, Uriel

    2003-01-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  16. Cerebellar abiotrophy in a miniature schnauzer.

    Science.gov (United States)

    Berry, Michelle L; Blas-Machado, Uriel

    2003-08-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  17. Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1.

    Science.gov (United States)

    Moghadam, Keivan Kaveh; Pizza, Fabio; Tonon, Caterina; Lodi, Raffaele; Carelli, Valerio; Poli, Francesca; Franceschini, Christian; Barboni, Piero; Seri, Marco; Ferrari, Simona; La Morgia, Chiara; Testa, Claudia; Cornelio, Ferdinando; Liguori, Rocco; Winkelmann, Juliane; Lin, Ling; Mignot, Emmanuel; Plazzi, Giuseppe

    2014-05-01

    We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. The two asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia

    Science.gov (United States)

    Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

    2015-01-01

    Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

  19. Spinocerebellar ataxias Ataxias espinocerebelares

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2009-12-01

    Full Text Available Spinocerebellar ataxias (SCAs constitute a heterogeneous group of neurodegenerative diseases characterized by progressive cerebellar ataxia in association with some or all of the following conditions: ophthalmoplegia, pyramidal signs, movement disorders, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. OBJECTIVE: To carry out a clinical and genetic review of the main types of SCA. METHOD: The review was based on a search of the PUBMED and OMIM databases. RESULTS: Thirty types of SCAs are currently known, and 16 genes associated with the disease have been identified. The most common types are SCA type 3, or Machado-Joseph disease, SCA type 10 and SCA types 7, 2, 1 and 6. SCAs are genotypically and phenotypically very heterogeneous. A clinical algorithm can be used to distinguish between the different types of SCAs. CONCLUSIONS: Detailed clinical neurological examination of SCA patients can be of great help when assessing them, and the information thus gained can be used in an algorithm to screen patients before molecular tests to investigate the correct etiology of the disease are requested.As ataxias espinocerebelares (AECs compreendem um grupo heterogeneo de enfermidades neurodegenerativas, que se caracterizam pela presença de ataxia cerebelar progressiva, associada de forma variada com oftalmoplegia, sinais piramidais, distúrbios do movimento, retinopatia pigmentar, neuropatia periférica, disfunção cognitiva e demência. OBJETIVO: Realizar uma revisão clínico-genética dos principais tipos de AECs. MÉTODO: A revisão foi realizada através da pesquisa pelo sistema do PUBMED e do OMIM. RESULTADOS: Na atualidade existem cerca de 30 tipos de AECs, com a descoberta de 16 genes. Os tipos mais comuns são a AEC tipo 3, ou doença de Machado-Joseph, a AEC tipo 10, e as AECs tipo 7, 2 1, e 6. As AECs apresentam grande heterogeneidade genotípica e fenotípica. Pode-se utilizar um algoritmo clínico para a

  20. Use of trunk stabilization and locomotor training in an adult with cerebellar ataxia: a single system design.

    Science.gov (United States)

    Freund, Jane E; Stetts, Deborah M

    2010-10-01

    The purpose of this study is to describe the effects of trunk stabilization training and locomotor training (LT) using body-weight support on a treadmill (BWST) and overground walking on balance, gait, self-reported function, and trunk muscle performance in an adult with severe ataxia secondary to brain injury. There are no studies on the effectiveness of these combined interventions in persons with ataxia. The subject was a 23-year-old male who had a traumatic brain injury 13 months prior. An A-B-A withdrawal single-system design was used. Outcome measures were Berg Balance Test (BBT), timed unsupported stance, Functional Ambulation Category (FAC), 10-meter walk test (10-MWT), Outpatient Physical Therapy Improvement in Movement Assessment Log (OPTIMAL), transverse abdominis (TrA) thickness, and isometric trunk endurance tests. Performance on the BBT, timed unsupported stance, FAC, 10-MWT, and OPTIMAL each improved after 10 weeks of intervention. In additions, TrA symmetry at rest improved as did right side-bridge endurance time. LT, using BWST and overground walking, and trunk stabilization training may be effective in improving balance, gait, function, and trunk performance in individuals with severe ataxia. Further research with additional subjects is indicated.

  1. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    Directory of Open Access Journals (Sweden)

    Sarah L. Nickerson

    2015-10-01

    Full Text Available Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*, establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS. Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

  2. Friedreich's ataxia and other hereditary ataxias in Greece: an 18-year perspective.

    Science.gov (United States)

    Koutsis, Georgios; Kladi, Athina; Karadima, Georgia; Houlden, Henry; Wood, Nicholas W; Christodoulou, Kyproula; Panas, Marios

    2014-01-15

    Limited data exist on the spectrum of heredoataxias in Greece, including the prevalence and phenotype of Friedreich's ataxia (FRDA) and the prevalence and subtypes of dominant spinocerebellar ataxias (SCAs). We analyzed clinically and investigated genetically for FRDA and triplet-repeat expansion SCAs a consecutive series of 186 patients with suspected heredoataxia referred to Athens over 18 years. For prevalence estimates we included patients with molecular diagnosis from Cyprus that were absent from the Athens cohort. The minimum prevalence of FRDA was ~0.9/100,000, with clusters of high prevalence in Aegean islands. FRDA was diagnosed in 73 probands. The genotypic and phenotypic spectrum of FRDA was similar to other populations, with one patient compound heterozygote for a known point mutation in FXN (Asn146Lys). Undiagnosed recessive ataxias included FRDA-like and spastic ataxias. The minimum prevalence of dominant SCAs was ~0.7/100,000. SCA1 (4), SCA7 (4), SCA2, SCA6, and SCA17 (1 each) probands were identified. A molecular diagnosis was reached in 31% of dominant cases. Undiagnosed dominant patients included a majority of type III autosomal dominant cerebellar ataxias. FRDA is the commonest heredoataxia in the Greek population with prevalence towards the lower end of other European populations. Dominant SCAs are almost as prevalent. SCA1, SCA2, SCA6, SCA7 and SCA17 patients complete the spectrum of cases with a specific molecular diagnosis. © 2013.

  3. Speech in spinocerebellar ataxia.

    Science.gov (United States)

    Schalling, Ellika; Hartelius, Lena

    2013-12-01

    Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant cerebellar ataxias clinically characterized by progressive ataxia, dysarthria and a range of other concomitant neurological symptoms. Only a few studies include detailed characterization of speech symptoms in SCA. Speech symptoms in SCA resemble ataxic dysarthria but symptoms related to phonation may be more prominent. One study to date has shown an association between differences in speech and voice symptoms related to genotype. More studies of speech and voice phenotypes are motivated, to possibly aid in clinical diagnosis. In addition, instrumental speech analysis has been demonstrated to be a reliable measure that may be used to monitor disease progression or therapy outcomes in possible future pharmacological treatments. Intervention by speech and language pathologists should go beyond assessment. Clinical guidelines for management of speech, communication and swallowing need to be developed for individuals with progressive cerebellar ataxia. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Clinical neurogenetics: friedreich ataxia.

    Science.gov (United States)

    Collins, Abigail

    2013-11-01

    Friedreich ataxia is the most common autosomal recessive ataxia. It is a progressive neurodegenerative disorder, typically with onset before 20 years of age. Signs and symptoms include progressive ataxia, ascending weakness and ascending loss of vibration and joint position senses, pes cavus, scoliosis, cardiomyopathy, and arrhythmias. There are no disease-modifying medications to either slow or halt the progression of the disease, but research investigating therapies to increase endogenous frataxin production and decrease the downstream consequences of disrupted iron homeostasis is ongoing. Clinical trials of promising medications are underway, and the treatment era of Friedreich ataxia is beginning. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  6. Very Late-Onset Friedreich Ataxia with Laryngeal Dystonia

    Directory of Open Access Journals (Sweden)

    Silvia Rota

    2014-12-01

    Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia, cerebellar, pyramidal and dorsal column involvement, visual defects, scoliosis, pes cavus and cardiomyopathy. It is caused by a homozygous guanine-adenine-adenine (GAA trinucleotide repeat expansion in intron 1 of the frataxin gene (FXN on chromosome 9q13-q21.1. Onset is usually in the first or second decade of life; however, late-onset cases of Freidreich ataxia (LOFA, after the age of 25 years, and very late-onset cases of Freidreich ataxia (VLOFA, after the age of 40 years, have been reported. VLOFA is quite rare and usually presents a milder progression of the disease. We report the case of a 64-year-old woman affected with VLOFA whose first symptoms (balance and gait disturbances occurred at the age of 44 years. At the age of 62 years, she started complaining of a slowly progressive dysphonia showing the clinical aspects of laryngeal dystonia. Molecular analysis showed a 210- and 230-trinucleotide GAA repeat expansion in the two alleles of the FXN gene. Laryngeal dystonia has been reported only in very few cases of ataxia syndrome and never before in FRDA patients. It may represent a rare clinical manifestation of VLOFA thus confirming the high variability of the clinical spectrum of FRDA.

  7. Frontal ataxia in childhood.

    Science.gov (United States)

    Erasmus, C E; Beems, T; Rotteveel, J J

    2004-12-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teenage patients presenting with headache after an ENT infection and on physical examination mild dysmetric function of the upper limbs and slight disequilibrium, due to right-sided frontal lobe abscesses. After neurosurgical and antibiotic therapy the symptoms were relieved. The frontal origin of ataxia should be considered in children presenting with a "cerebellar syndrome". Frontal gait disorders consist of a clinical pattern of different gait disorders. The syndrome has been mentioned in the literature under different names. Our patients show signs compatible with the term frontal disequilibrium, a clinical pattern of frontal gait disorder. This assumes walking problems characterized by loss of control of motor planning, leading to imbalance. Remarkably, frontal ataxia may mimic developmental delay as demonstrated in the first case and may be the leading mild symptom in extensive frontal lobe damage as demonstrated by the two other cases. We suppose that frontal ataxia is the result of a disturbance in the cerebellar-frontal circuitries and an impairment of executive and planning functions of the basal ganglia-frontal lobe circuitry.

  8. Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

    Directory of Open Access Journals (Sweden)

    Stefano Lise

    Full Text Available β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5, an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1. In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.

  9. A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.

    Science.gov (United States)

    Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

    2015-06-26

    The particular importance of Ca(2+) signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca(2+). A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca(2+) ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca(2+) transients generated by cell stimulation and impairs its Ca(2+) extrusion function under conditions of low resting cytosolic Ca(2+) as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca(2+)-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca(2+) homeostasis and the previous finding that PMCAs act as digenic modulators in Ca(2+)-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations*

    Science.gov (United States)

    Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

    2015-01-01

    The particular importance of Ca2+ signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca2+ ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca2+. A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca2+ ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca2+ transients generated by cell stimulation and impairs its Ca2+ extrusion function under conditions of low resting cytosolic Ca2+ as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca2+-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca2+ homeostasis and the previous finding that PMCAs act as digenic modulators in Ca2+-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. PMID:25953895

  11. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome

    International Nuclear Information System (INIS)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J.

    2003-01-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs

  12. Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8

    Science.gov (United States)

    Boycott, Kym M.; Beaulieu, Chandree L.; Kernohan, Kristin D.; Gebril, Ola H.; Mhanni, Aziz; Chudley, Albert E.; Redl, David; Qin, Wen; Hampson, Sarah; Küry, Sébastien; Tetreault, Martine; Puffenberger, Erik G.; Scott, James N.; Bezieau, Stéphane; Reis, André; Uebe, Steffen; Schumacher, Johannes; Hegele, Robert A.; McLeod, D. Ross; Gálvez-Peralta, Marina; Majewski, Jacek; Ramaekers, Vincent T.; Nebert, Daniel W.; Innes, A. Micheil; Parboosingh, Jillian S.; Abou Jamra, Rami

    2015-01-01

    Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development. PMID:26637978

  13. Ataxia telangiectasia: a review

    Directory of Open Access Journals (Sweden)

    Cynthia Rothblum-Oviatt

    2016-11-01

    Full Text Available Abstract Definition of the disease Ataxia telangiectasia (A-T is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome. Epidemiology The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births. Clinical description A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations. Etiology A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress. Diagnosis The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels. Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the

  14. Measuring Inhibition and Cognitive Flexibility in Friedreich Ataxia.

    Science.gov (United States)

    Corben, Louise A; Klopper, Felicity; Stagnitti, Monique; Georgiou-Karistianis, Nellie; Bradshaw, John L; Rance, Gary; Delatycki, Martin B

    2017-08-01

    Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact on cognition. Inhibitory processes and cognitive flexibility were examined in FRDA by assessing the ability to suppress a predictable verbal response. We administered the Hayling Sentence Completion Test (HSCT), the Trail Making Test, and the Stroop Test to 43 individuals with FRDA and 42 gender- and age-matched control participants. There were no significant group differences in performance on the Stroop or Trail Making Test whereas significant impairment in cognitive flexibility including the ability to predict and inhibit a pre-potent response as measured in the HSCT was evident in individuals with FRDA. These deficits did not correlate with clinical characteristics of FRDA (age of disease onset, disease duration, number of guanine-adenine-adenine repeats on the shorter or larger FXN allele, or Friedreich Ataxia Rating Scale score), suggesting that such impairment may not be related to the disease process in a straightforward way. The observed specific impairment of inhibition and predictive capacity in individuals with FRDA on the HSCT task, in the absence of impairment in associated executive functions, supports cerebellar dysfunction in conjunction with disturbance to cortico-thalamo-cerebellar connectivity, perhaps via inability to access frontal areas necessary for successful task completion.

  15. Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases

    Directory of Open Access Journals (Sweden)

    Albano Lilian M. J.

    2001-01-01

    Full Text Available INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a early age of onset (< 20 or 25 years, b autosomal recessive inheritance, c progressive ataxia of limbs and gait, and d absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68% - all typical cases. In 8 patients (32% (6 atypical and 2 typical, no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

  16. Imaging study of lymphoreticular tumor development in ataxia-telangiectasia and Nijmegen breakage syndrome; Estudio por imagen del desarrollo de tumores linforreticulares en la ataxia telangiectasia y el sindrome de Nijmegen

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Leon, M. I.; Ceres-Ruiz, L.; Cuesta, M. A.; Garcia-Martin, F. J. [Hospital Materno-Infantil C.H.U. Carlos Haya. Malaga (Spain)

    2003-07-01

    Ataxia-telangiectasia (AT), or Louis-Bar syndrome, is an autosomal recessive illness characterized by progressive cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency combined with susceptibility to sinopulmonary infections and high incidence of neoplastic development. Nijmegen breakage syndrome (NBS) is a variant of AT, is also an autosomal recessive illness that presents cerebellar ataxia, as well as combined immunodeficiency and a tendency toward tumor development. Contrary to Louis-Bar syndrome, it doesn't present telangiectasia and exhibits a characteristics phenotype (short stature, bird-like face and microcephaly). Both entities are classified as syndrome of chromosomal instability or chromosomal fragility, a group which also includes Bloom syndrome and Fanconi anemia. All of these show an increase in the frequency of neoplastic pathologies, mainly lymphoid tumors. We present three patients,two with AT and one with NBS, who developed different lymphoma types in the course of the illness. We highlight the most outstanding aspects from a clinical-radiological point of view. (Author) 17 refs.

  17. Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (POLG) Mutation.

    Science.gov (United States)

    Nicastro, Nicolas; Ranza, Emmanuelle; Antonarakis, Stylianos E; Horvath, Judit

    2016-12-01

    Progressive ataxia with palatal tremor (PAPT) is a syndrome caused by cerebellar and brainstem lesions involving the dentato-rubro-olivary tract and associated with hypertrophic olivary degeneration. Etiologies include acquired posterior fossa lesions (e.g. tumors, superficial siderosis, and inflammatory diseases) and genetic disorders, such as glial fibrillary acidic protein (GFAP) and polymerase gamma (POLG) mutations. We describe the case of a 52-year-old man who developed pure progressive ataxia and palatal tremor. Genetic analysis has shown that he is compound heterozygote for a known pathogenic (W748S) and a novel POLG variant (I1185N). Patients with POLG recessive mutations usually manifest a more complex clinical picture, including polyneuropathy and epilepsy; our case emphasizes the need to consider a genetic origin in a seemingly sporadic and pure PAPT.

  18. Xeroderma Pigmentosum/De Sanctis-Cacchione Syndrome: Unusual Cause of Ataxia

    Directory of Open Access Journals (Sweden)

    Robert Fekete

    2014-03-01

    Full Text Available Introduction: Xeroderma pigmentosum (XP is a rare autosomal recessive disorder of DNA repair, with a prevalence of 1 in 1 million. It may also be a cause of neurological symptoms including sensorineural hearing loss, peripheral neuropathy, ataxia, and chorea. Severe neurological symptoms including mental retardation, short stature, and hypogonadism invoke De Sanctis-Cacchione syndrome (DCS. Case Report: The patient was a 55-year-old woman with a history of mental retardation who developed chorea at age 32 and ataxia at age 37. She had numerous facial scars from 10 prior basal cell carcinoma excisions as well as diminished deep tendon reflexes, bilateral hearing loss, dysphagia, and skin freckling. Brain MRI revealed severe cortical, cerebellar, and brainstem atrophy. Supportive treatment and prevention of further damage from UV light is the mainstay of treatment in XP and DCS. Conclusion: XP and related disorders should be considered in the setting of neurological disorder and multiple cutaneous cancers.

  19. Movement disorders in hereditary ataxias.

    Science.gov (United States)

    Garcia Ruiz, Pedro J; Mayo, David; Hernandez, Jaime; Cantarero, Susana; Ayuso, Carmen

    2002-10-15

    Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA. Copyright 2002 Elsevier Science B.V.

  20. Cerebellar leukoencephalopathy: most likely histiocytosis-related

    NARCIS (Netherlands)

    van der Knaap, M.S.; Arts, W.F.M.; Garbern, J.Y.; Hedlund, G.; Winkler, F.; Barbosa, C.; King, M.D.; Bjornstad, A.; Hussain, N.; Beyer, M.K.; Gomez, C.; Patterson, M.C.; Grattan-Smith, P.; Timmons, M.; van der Valk, P.

    2008-01-01

    Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows

  1. Characterizing POLG ataxia: clinics, electrophysiology and imaging.

    Science.gov (United States)

    Synofzik, Matthis; Srulijes, Karin; Godau, Jana; Berg, Daniela; Schöls, Ludger

    2012-12-01

    Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich's ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.

  2. Spinocerebellar ataxia-10 with paranoid schizophrenia

    Directory of Open Access Journals (Sweden)

    Bhavesh Trikamji

    2015-01-01

    Full Text Available Spino-cerebellar ataxia type 10 (SCA10 is an autosomal dominant disorder that is characterized by cerebellar ataxia, seizures and nystagmus with a fragmented pursuit. Schizophrenia has been reported with SCAs 1 and 2 yet in SCA 10, psychiatric manifestations are uncommon. We report a Hispanic family involving a father and his four children with SCA10 genetic mutation. Two of his children, a 20-year-old female and a 23-year-old male, presented with gradually progressive spino-cerebellar ataxia and paranoid schizophrenia. Neurological examination revealed ocular dysmetria, dysdiadokinesia, impaired finger-to-nose exam, gait ataxia and hyperreflexia in both the cases. Additionally, they had a history of psychosis with destructive behavior, depression and paranoid delusions with auditory hallucinations. Serology and CSF studies were unremarkable and MRI brain revealed cerebellar volume loss. Ultimately, a test for ATAXIN-10 mutation was positive thus confirming the diagnosis of SCA10 in father and his four children. We now endeavor to investigate the association between schizophrenia and SCA10.

  3. Cognitive Functions in Ataxia with Oculomotor Apraxia Type 2

    Directory of Open Access Journals (Sweden)

    Péter eKlivényi

    2012-08-01

    Full Text Available Background: Ataxia with oculomotor apraxia type 2 (AOA2 is characterized by cerebellar atrophy, peripheral neuropathy, oculomotor apraxia, and elevated serum alpha-fetoprotein levels. The disease is caused by a recessive mutation in the senataxin gene. Since it is a very rare cerebellar disorder, no detailed examination of cognitive functions in AOA2 has been published to date. The aim of the present study was to investigate the neuropsychological profile of a 54-year-old patient with AOA2. Methods: A broad range of neuropsychological examination protocol was administered including the following domains: short-term, working- and episodic- memories, executive functions, implicit sequence learning, and the temporal parameters of speech. Results: The performance on the Listening Span, Letter Fluency, Serial Reaction Time Task and pause ratio in speech was 2 or more standard deviations (SD lower compared to controls, and 1 SD lower on Backward Digit Span, Semantic Fluency, articulation rate and speech tempo. Conclusions: These findings indicate that the pathogenesis of the cerebrocerebellar circuit in AOA2 is responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech and sequence learning.

  4. NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.

    Science.gov (United States)

    Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L; Scheibye-Knudsen, Morten; Marosi, Krisztina; Lu, Huiming; Shamanna, Raghavendra A; Kalyanasundaram, Sumana; Bollineni, Ravi Chand; Wilson, Mark A; Iser, Wendy B; Wollman, Bradley N; Morevati, Marya; Li, Jun; Kerr, Jesse S; Lu, Qiping; Waltz, Tyler B; Tian, Jane; Sinclair, David A; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A

    2016-10-11

    Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD + , and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD + reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD + also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. Published by Elsevier Inc.

  5. Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Choi, Seong-Jun [Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Shim, Hosup, E-mail: shim@dku.edu [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of)

    2014-10-03

    Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

  6. Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer

    International Nuclear Information System (INIS)

    Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung; Choi, Seong-Jun; Shim, Hosup

    2014-01-01

    Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies

  7. [Study of cerebellar infarction with isolated vertigo].

    Science.gov (United States)

    Utsumi, Ai; Enomoto, Hiroyuki; Yamamoto, Kaoru; Kimura, Yu; Koizuka, Izumi; Tsukuda, Mamoru

    2010-07-01

    Isolated vertigo is generally attributed to labyrinthine disease, but may also signal otherwise asymptomatic cerebellar infarction. Of 309 subjects admitted between April 2004 and March 2009 for the single symptom of acute vertigo initially thought to be labyrinthine, four were found to have cerebellar infarction of the posterior inferior cerebellar artery area (PICA). All were over 60 years old and had risk factors including hypertension, diabetes mellitus, arrhythmia, and/or hyperlipidemia. Two had trunk ataxia, with magnetic resonance imaging (MRI) showing infarction within a few days. The other two could walk without apparent trunk ataxia, however, it took 4 to 7 days to find the infarction, mainly through neurological, neurootological, and MRI findings. Neurologically, astasia, dysbasia or trunk ataxia were important signs. Neurootologically, nystagmus and electronystagmographic testing involving eye tracking, saccade, and optokinetic patttens were useful.

  8. Cardiopatía dilatada en ataxia de Friedreich: el punto sin retorno Dilated cardiomyopathy in Friedreich's ataxia: point of no return

    Directory of Open Access Journals (Sweden)

    Luis E Silva

    2012-04-01

    Full Text Available Las cardiopatías infiltrativas se caracterizan por el depósito de sustancias en el miocardio que causan un impacto negativo en la arquitectura de la pared ventricular. La ataxia espino-cerebelosa de Friedreich es una enfermedad degenerativa, heredada, con carácter autosómico recesivo. Clínicamente se caracteriza por ataxia de extremidades y tronco, hiporreflexia, neuropatía periférica, retinopatía y cardiopatía, entre otros. La afectación cardíaca es muy frecuente y se detectan alteraciones en estudios pos-mortem en 95% a 100% de los pacientes. La tasa de mortalidad es elevada y se considera una enfermedad incurable, a pesar de la existencia actual de múltiples medicamentos en estudio basados en los fundamentos fisiopatológicos de esta afección.Infiltrative heart diseases are characterized by deposit of substances in the myocardium that cause a negative impact on the architecture of the ventricular wall. Friedreich's spino-cerebellar ataxia is a degenerative disease, inherited in an autosomal recessive pattern. Clinically it is characterized by limb and trunk ataxia, hyporeflexia, peripheral neuropathy, retinopathy and heart disease among others. Cardiac involvement is common and on post-mortem studies cardiac abnormalities are found in 95% to 100% of patients. The mortality rate is high and it is considered an incurable disease, despite the current existence of multiple medications being studied, based on the pathophysiological basis of this condition.

  9. Degenerative cerebellar diseases and differential diagnoses

    International Nuclear Information System (INIS)

    Reith, W.; Roumia, S.; Dietrich, P.

    2016-01-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [de

  10. [Degenerative cerebellar diseases and differential diagnoses].

    Science.gov (United States)

    Reith, W; Roumia, S; Dietrich, P

    2016-11-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions.

  11. Spinocerebellar ataxia type 6: MRI of three Japanese patients

    International Nuclear Information System (INIS)

    Satoh, J.I.; Tokumoto, H.; Yukitake, M.; Matsui, M.; Kuroda, Y.; Matsuyama, Z.; Kawakami, H.; Nakamura, S.

    1998-01-01

    We describe the MRI findings in three Japanese patients with spinocerebellar ataxia type 6 (SCA6) in which a polymorphic CAG repeat was identified in the gene encoding the α 1A voltage-dependent P/Q-type Ca 2+ channel subunit (CACNL1A4). All showed slowly progressive cerebellar ataxia and mild pyramidal signs. Neuroradiologically, they had moderate cerebellar atrophy, most prominently in the superior vermis, whereas the brain stem appeared to be spared. No abnormal signal intensity was identified. (orig.)

  12. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Cristino de Albuquerque

    2015-01-01

    Full Text Available The spinocerebellar ataxias (SCA are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7 is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

  13. Cerebellar ataxia by enhanced Cav2.1 currents is alleviated by Ca2+-dependent K-channel activators in Cacna1aS218l mutant mice

    NARCIS (Netherlands)

    Z. Gao (Zhenyu); B. Todorov (Boyan); C.F. Barrett (Curtis); S. van Dorp (Stijn); M.D. Ferrari (Michel); M. Dichgans (Martin); C.I. de Zeeuw (Chris); F.E. Hoebeek (Freek)

    2012-01-01

    textabstractMutations in the CACNA1A gene are associated with neurological disorders, such as ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore-forming α1A-subunit of CaV2.1 channels and thereby either decrease or increase neuronal Ca2+ influx. A decreased CaV2.1-mediated

  14. A deletion in the VLDLR gene in Eurasier dogs with cerebellar hypoplasia resembling a Dandy-Walker-like malformation (DWLM.

    Directory of Open Access Journals (Sweden)

    Martina Gerber

    Full Text Available Dandy-Walker-like malformation (DWLM is the result of aberrant brain development and mainly characterized by cerebellar hypoplasia. DWLM affected dogs display a non-progressive cerebellar ataxia. Several DWLM cases were recently observed in the Eurasier dog breed, which strongly suggested a monogenic autosomal recessive inheritance in this breed. We performed a genome-wide association study (GWAS with 9 cases and 11 controls and found the best association of DWLM with markers on chromosome 1. Subsequent homozygosity mapping confirmed that all 9 cases were homozygous for a shared haplotype in this region, which delineated a critical interval of 3.35 Mb. We sequenced the genome of an affected Eurasier and compared it with the Boxer reference genome and 47 control genomes of dogs from other breeds. This analysis revealed 4 private non-synonymous variants in the critical interval of the affected Eurasier. We genotyped these variants in additional dogs and found perfect association for only one of these variants, a single base deletion in the VLDLR gene encoding the very low density lipoprotein receptor. This variant, VLDLR:c.1713delC is predicted to cause a frameshift and premature stop codon (p.W572Gfs*10. Variants in the VLDLR gene have been shown to cause congenital cerebellar ataxia and mental retardation in human patients and Vldlr knockout mice also display an ataxia phenotype. Our combined genetic data together with the functional knowledge on the VLDLR gene from other species thus strongly suggest that VLDLR:c.1713delC is indeed causing DWLM in Eurasier dogs.

  15. A 70-year-old male with peripheral neuropathy, ataxia and antigliadin antibodies shows improvement in neuropathy, but not ataxia, after intravenous immunoglobulin and gluten-free diet

    Directory of Open Access Journals (Sweden)

    Dharshan Anandacoomaraswamy

    2008-10-01

    Full Text Available Dharshan Anandacoomaraswamy1, Jagdeesh Ullal2, Aaron I Vinik21Department of Internal Medicine, Coney Island Hospital, Brooklyn, NY, USA; 2Strelitz Diabetes Center, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAAbstract: This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia. Keywords: celiac disease, peripheral neuropathy, autoimmune disease, cerebellar ataxia, type 2 diabetes

  16. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.

    LENUS (Irish Health Repository)

    Anheim, M

    2009-10-01

    Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg\\/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg\\/l, P = 0.0004; itself higher than the normal level (3.4 microg\\/l, range from 0.5 to 17.2 microg\\/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg\\/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia

  17. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.

    Science.gov (United States)

    Anheim, M; Monga, B; Fleury, M; Charles, P; Barbot, C; Salih, M; Delaunoy, J P; Fritsch, M; Arning, L; Synofzik, M; Schöls, L; Sequeiros, J; Goizet, C; Marelli, C; Le Ber, I; Koht, J; Gazulla, J; De Bleecker, J; Mukhtar, M; Drouot, N; Ali-Pacha, L; Benhassine, T; Chbicheb, M; M'Zahem, A; Hamri, A; Chabrol, B; Pouget, J; Murphy, R; Watanabe, M; Coutinho, P; Tazir, M; Durr, A; Brice, A; Tranchant, C; Koenig, M

    2009-10-01

    Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia

  18. Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?

    Directory of Open Access Journals (Sweden)

    Verhoeven WMA

    2011-05-01

    Full Text Available Willem MA Verhoeven1,2, Jos IM Egger1,3,4, Berry PH Kremer5, Boudewijn JHB de Pont1, Carlo LM Marcelis61Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands; 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The Netherlands; 3Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; 4Donders Institute for Brain, Cognition and Behaviour, Centre for Cognition, Radboud University Nijmegen, Nijmegen, The Netherlands; 5Department of Neurology, University Medical Centre Groningen, The Netherlands; 6Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsAbstract: At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (POLG have been indentified that are causally related to an array of neuropsychiatric diseases affecting multiple systems. Both autosomal recessive and autosomal dominant forms can be delineated, the latter being associated with Parkinsonism and depressive or psychotic syndromes. In this report, a middle-aged female patient with recurrent major depression with melancholic features, slowly progressive gait instability, and dilated cardiomyopathy is described. Detailed diagnostic evaluation was performed to elucidate the supposed relationship between ataxia, cardiomyopathy, and major depression with melancholia. After extensive genetic and metabolic investigation, a nucleotide substitution c.2207 A→G in the POLG gene resulting in amino acid change Asn 736Ser in exon 13 was demonstrated. This mutation was considered to be compatible with a mitochondrial disorder and implicated in the pathophysiology of the neuropsychiatric syndrome. It is concluded that this novel POLG mutation forms the most parsimonious etiological explanation for the here-described combination of ataxia, major depression, and cardiomyopathy. Therefore, in patients with a complex neuropsychiatric

  19. Spinocerebellar ataxia 36 (SCA36): «Costa da Morte ataxia».

    Science.gov (United States)

    Arias, M; García-Murias, M; Sobrido, M J

    To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24.

    Directory of Open Access Journals (Sweden)

    Caryline Agler

    2014-02-01

    Full Text Available Old English Sheepdogs and Gordon Setters suffer from a juvenile onset, autosomal recessive form of canine hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex. The clinical and histological characteristics are analogous to hereditary ataxias in humans. Linkage and genome-wide association studies on a cohort of related Old English Sheepdogs identified a region on CFA4 strongly associated with the disease phenotype. Targeted sequence capture and next generation sequencing of the region identified an A to C single nucleotide polymorphism (SNP located at position 113 in exon 1 of an autophagy gene, RAB24, that segregated with the phenotype. Genotyping of six additional breeds of dogs affected with hereditary ataxia identified the same polymorphism in affected Gordon Setters that segregated perfectly with phenotype. The other breeds tested did not have the polymorphism. Genome-wide SNP genotyping of Gordon Setters identified a 1.9 MB region with an identical haplotype to affected Old English Sheepdogs. Histopathology, immunohistochemistry and ultrastructural evaluation of the brains of affected dogs from both breeds identified dramatic Purkinje neuron loss with axonal spheroids, accumulation of autophagosomes, ubiquitin positive inclusions and a diffuse increase in cytoplasmic neuronal ubiquitin staining. These findings recapitulate the changes reported in mice with induced neuron-specific autophagy defects. Taken together, our results suggest that a defect in RAB24, a gene associated with autophagy, is highly associated with and may contribute to canine hereditary ataxia in Old English Sheepdogs and Gordon Setters. This finding suggests that detailed investigation of autophagy pathways should be undertaken in human hereditary ataxia.

  1. Genetics of Hereditary Ataxia in Scottish Terriers.

    Science.gov (United States)

    Urkasemsin, G; Nielsen, D M; Singleton, A; Arepalli, S; Hernandez, D; Agler, C; Olby, N J

    2017-07-01

    Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction. To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers. One hundred and fifty-three Scottish Terriers were recruited through the Scottish Terrier Club of America. Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome-wide mapping was performed using both linkage- and association-based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively. Linkage and genome-wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information. This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

    Science.gov (United States)

    Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

    2014-01-01

    Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

  3. From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

    Directory of Open Access Journals (Sweden)

    Georgios Koutsis

    2014-01-01

    Full Text Available Introduction. Spinocerebellar ataxia 17 (SCA 17 is a rare autosomal dominant cerebellar ataxia (ADCA caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

  4. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten

    2013-01-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective ...... of paternal germ-line repeat sequence instability of the expanded SCA2 locus.European Journal of Human Genetics advance online publication, 10 October 2012; doi:10.1038/ejhg.2012.231....

  5. Visuomotor learning in cerebellar patients.

    Science.gov (United States)

    Timmann, D; Shimansky, Y; Larson, P S; Wunderlich, D A; Stelmach, G E; Bloedel, J R

    1996-11-01

    The aim of the present study was to demonstrate that patients with pathology affecting substantial regions of the cerebellum can improve their performance in a series of two-dimensional tracing tasks, thus supporting the view that this type of motor behavior can be acquired even when the integrity of this structure is compromised. Eight patients with chronic, isolated cerebellar lesions and eight age- and sex-matched healthy controls were tested. Three patients had mild, five had moderate upper limb ataxia. The experiment was divided into two parts. In the first, subjects traced an irregularly shaped outline over 20 consecutive trials ('Trace 1' task). Next, subjects were asked to redraw the object without any underlying template as a guide ('Memory 1' task). In the second part of the study, subjects were asked to trace a different, irregularly shaped outline over 20 consecutive trials ('Trace 2' task). Next, they were required to redraw it by memory with its axis rotated 90 degrees ('Memory 2' task). In each of the memory tasks the template was placed over the drawn image after each trial and shown to the subjects. The error of performance was determined by calculating three different measurements, each focused on different aspects of the task. Based on these measurements, the cerebellar patients showed improvement in both memory tasks. In the 'Memory 1' task the calculated error decreased significantly for the patients with mild ataxia. In the 'Memory 2' task all cerebellar patients improved their performance substantially enough to reduce significantly the magnitude of all three error measurements. The experiments demonstrate that patients with cerebellar lesions are capable of improving substantially their performance of a complex motor task involving the recall of memorized shapes and the visuomotor control of a tracing movement.

  6. Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor and ataxia.

    Science.gov (United States)

    Kalus, Sarah; King, John; Lui, Elaine; Gaillard, Frank

    2016-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative movement disorder resulting from a fragile X "premutation", defined as 55-200 CGG repeats in the 5'-untranslated region of the FMR1 gene. The FMR1 premutation occurs in 1/800 males and 1/250 females, with FXTAS affecting 40-45% of male and 8-16% of female premutation carriers over the age of 50. FXTAS typically presents with kinetic tremor and cerebellar ataxia. FXTAS has a classical imaging profile which, in concert with clinical manifestations and genetic testing, participates vitally in its diagnosis. The revised FXTAS diagnostic criteria include two major radiological features. The "MCP sign", referring to T2 hyperintensity in the middle cerebellar peduncle, has long been considered the radiological hallmark of FXTAS. Recently included as a major radiological criterion in the diagnosis of FXTAS is T2 hyperintensity in the splenium of the corpus callosum. Other imaging features of FXTAS include T2 hyperintensities in the pons, insula and periventricular white matter as well as generalised brain and cerebellar atrophy. FXTAS is an under-recognised and misdiagnosed entity. In patients with unexplained tremor, ataxia and cognitive decline, the presence of middle cerebellar peduncle and/or corpus callosum splenium hyperintensity should raise suspicion of FXTAS. Diagnosis of FXTAS has important implications not only for the patient but also, through genetic counselling and testing, for future generations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Pedaleo de brazos en personas con lesión medular, parálisis cerebral o ataxia cerebelosa: Parámetros fisiológicos. [Armcrank pedaling in persons with spinal cord injury, cerebral palsy or cerebellar ataxia: Physiological parameters].

    Directory of Open Access Journals (Sweden)

    Iris González-Carbonell

    2016-10-01

    Full Text Available Los desórdenes neurológicos generan afectación física y derivan en sedentarismo, enfermedades coronarias y obesidad o diabetes, reduciendo tanto la esperanza como la calidad de vida. La oferta de actividad física adaptada es escasa por falta de información específica sobre la forma de adecuarlo y dosificarlo a las personas que presentan estos desórdenes. Con el fin de comparar el efecto del ejercicio de pedaleo de brazos sobre la respuesta fisiológica y la percepción del esfuerzo, en 8 personas con lesión medular, 4 con parálisis cerebral y 4 con ataxia de Friedreich, se analizó su respuesta fisiológica, así como su percepción subjetiva al esfuerzo, frente a un grupo Control (16 participantes. Para ello realizó un ejercicio normalizado de pedaleo de brazos en un ergómetro y se midieron frecuencia cardíaca, frecuencia respiratoria, volumen corriente, volumen espirado, consumo de Oxígeno relativo, pulso de Oxígeno y percepción del esfuerzo y se realizó un ANOVA con estas variables. Para el grupo con lesión medular, el estrés y gasto energético resultaron los más bajos. El grupo con parálisis cerebral mostró los niveles de estrés más altos, además percibiéndolo como una carga moderada. El grupo con ataxia de Friedreich, mostró respuestas cardiorrespiratorias altas intermedias. Se puede concluir que diferentes desórdenes neurológicos muestran respuestas fisiológicas muy diferentes frente al ejercicio y es importante su control. Abstract Neurological disorders produce physical impairment that result in physical inactivity, heart disease and obesity or diabetes, reducing both life expectancy and quality of life. The supply of adapted physical activity is limited by lack of specific information on how to adapt and dosed to people who have these disorders. In order to compare the effect of armcrank pedaling exercise on their physiological response and perception of effort, 8 people with spinal cord injury, 4 with

  8. Frontal ataxia in childhood.

    NARCIS (Netherlands)

    Erasmus, C.E.; Beems, T.; Rotteveel, J.J.

    2004-01-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial

  9. Ataxia with Vitamin E Deficiency in Norway

    Directory of Open Access Journals (Sweden)

    Areej Elkamil

    2015-01-01

    Full Text Available Objective Ataxia with vitamin E deficiency (AVED is a rare autosomal recessive neurological disorder which usually starts in childhood. The clinical presentation is very similar to Friedreich ataxia, most patients have progressive truncal and extremity ataxia, areflexia, positive Babinski sign, dysarthria and sensory neuropathy. Methods We made an inquiry to our colleagues in Norway, we included information from a prevalence study published southern Norway and added data from our own known case. Results A newly published prevalence study of hereditary ataxias (total of 171 subjects found only one subject with AVED in Southeast Norway. We describe two more patients, one from the Central part and one from the Northern part of Norway. All 3 cases had age of onset in early childhood (age of 4–5 years and all experienced gait ataxia and dysarthria. The genetic testing confirmed that they had pathogenic mutations in the α-tocopherol transfer protein gene (TTPA. All were carriers of the non-sense c.400C > T mutation, one was homozygous for that mutation and the others were compound heterozygous, either with c.358G > A or c.513_514insTT. The homozygous carrier was by far the most severely affected case. Conclusions We estimate the occurrence of AVED in Norway to be at least 0.6 per million inhabitants. We emphasize that all patients who develop ataxia in childhood should be routinely tested for AVED to make an early diagnosis for initiating treatment with high dose vitamin E to avoid severe neurological deficits.

  10. Neurological features of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome.

    OpenAIRE

    Cross, J. H.; Arora, R.; Heckemann, R. A.; Gunny, R.; Chong, K.; Carr, L.; Baldeweg, T.; Differ, A. M.; Lench, N.; Varadkar, S.; Sirimanna, T.; Wassmer, E.; Hulton, S. A.; Ognjanovic, M.; Ramesh, V.

    2013-01-01

    Recently, we reported a previously unrecognized symptom constellation comprising epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) associated with recessive mutations in the KCNJ10 gene. Here, we provide a detailed characterization of the clinical features of the syndrome to aid patient management with respect to diagnosis, prognostic counselling, and identification of best treatment modalities.

  11. Cell Signaling and Neurotoxicity: 3H-Arachidonic acid release (Phospholipase A2) in cerebellar granule neurons

    Science.gov (United States)

    Cell signaling is a complex process which controls basic cellular activities and coordinates actions to maintain normal cellular homeostasis. Alterations in signaling processes have been associated with neurological diseases such as Alzheimer's and cerebellar ataxia, as well as, ...

  12. Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

    Science.gov (United States)

    Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

    2013-01-01

    We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

  13. Cerebellar abiotrophy in a family of Border Collie dogs.

    Science.gov (United States)

    Sandy, J R; Slocombe, R E; Mitten, R W; Jedwab, D

    2002-11-01

    Cerebellar abiotrophies have a nonsex-linked, autosomal, recessively inherited basis in a number of species, and lesions typically reflect profound and progressive loss of Purkinje cells. In this report, an unusual form of abiotrophy is described for two sibling Border Collies. Extensive loss of the cerebellar granular cell layer was present with relative sparing of Purkinje cells of two female pups. The biochemical basis for this form of cerebellar abiotrophy is unknown, but the lack of disease in other siblings supports an autosomal recessive mode of inheritance.

  14. Genetic inactivation of mGlu5 receptor improves motor coordination in the Grm1crv4 mouse model of SCAR13 ataxia.

    Science.gov (United States)

    Bossi, Simone; Musante, Ilaria; Bonfiglio, Tommaso; Bonifacino, Tiziana; Emionite, Laura; Cerminara, Maria; Cervetto, Chiara; Marcoli, Manuela; Bonanno, Giambattista; Ravazzolo, Roberto; Pittaluga, Anna; Puliti, Aldamaria

    2018-01-01

    Deleterious mutations in the glutamate receptor metabotropic 1 gene (GRM1) cause a recessive form of cerebellar ataxia, SCAR13. GRM1 and GRM5 code for the metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, respectively. Their different expression profiles suggest they could have distinct functional roles. In a previous study, homozygous mice lacking mGlu1 receptors (Grm1 crv4/crv4 ) and exhibiting ataxia presented cerebellar overexpression of mGlu5 receptors, that was proposed to contribute to the mouse phenotype. To test this hypothesis, we here crossed Grm1 crv4 and Grm5 ko mice to generate double mutants (Grm1 crv4/crv4 Grm5 ko/ko ) lacking both mGlu1 and mGlu5 receptors. Double mutants and control mice were analyzed for spontaneous behavior and for motor activity by rotarod and footprint analyses. In the same mice, the release of glutamate from cerebellar nerve endings (synaptosomes) elicited by 12mM KCl or by α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was also evaluated. Motor coordination resulted improved in double mutants when compared to Grm1 crv4/crv4 mice. Furthermore, in in vitro studies, glutamate release elicited by both KCl depolarization and activation of AMPA autoreceptors resulted reduced in Grm1 crv4/crv4 mice compared to wild type mice, while it presented normal levels in double mutants. Moreover, we found that Grm1 crv4/crv4 mice showed reduced expression of GluA2/3 AMPA receptor subunits in cerebellar synaptosomes, while it resulted restored to wild type level in double mutants. To conclude, blocking of mGlu5 receptor reduced the dysregulation of glutamate transmission and improved motor coordination in the Grm1 crv4 mouse model of SCAR13, thus suggesting the possible usefulness of pharmacological therapies based on modulation of mGlu5 receptor activity for the treatment of this type of ataxia. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study.

    Science.gov (United States)

    Pommerening, H; van Dullemen, S; Kieslich, M; Schubert, R; Zielen, S; Voss, S

    2015-12-09

    Ataxia-telangiectasia (A-T) is a devastating human autosomal recessive disorder that causes progressive cerebellar ataxia, immunodeficiency, premature aging, chromosomal instability and increased cancer risk. Affected patients show growth failure, poor weight gain, low body mass index (BMI), myopenia and increased fatigue during adolescence. The prevalence of alterations in body composition, muscle strength and hormonal status has not been well described in classical A-T patients. Additionally, no current guidelines are available for the assessment and management of these changes. We analyzed body composition, manual muscle strength and hormonal status in 25 A-T patients and 26 age-matched, healthy controls. Bioelectrical impedance analysis (BIA) was performed to evaluate the body composition, fat-free mass (FFM), body cell mass (BCM), extracellular matrix (ECM), phase angle (PhA), fat mass (FM) and ECM to BCM ratio. Manual muscle strength was measured using a hydraulic hand dynamometer. The BMI, FFM and PhA were significantly lower in A-T patients than in controls (BMI 16.56 ± 3.52 kg/m(2) vs. 19.86 ± 3.54 kg/m(2); Z-Score: -1.24 ± 1.29 vs. 0.05 ± 0.92, p body composition, characterized by depleted BMI, PhA and BCM; by the need to sit in a wheelchair; by altered hormone levels; and by poor muscle strength, is a major factor underlying disease progression and increased fatigue in A-T patients. ClinicalTrials.gov NCT02345200.

  16. Frontal ataxia in childhood.

    OpenAIRE

    Erasmus, C.E.; Beems, T.; Rotteveel, J.J.

    2004-01-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teen...

  17. Video game-based coordinative training improves ataxia in children with degenerative ataxia.

    Science.gov (United States)

    Ilg, Winfried; Schatton, Cornelia; Schicks, Julia; Giese, Martin A; Schöls, Ludger; Synofzik, Matthis

    2012-11-13

    Degenerative ataxias in children present a rare condition where effective treatments are lacking. Intensive coordinative training based on physiotherapeutic exercises improves degenerative ataxia in adults, but such exercises have drawbacks for children, often including a lack of motivation for high-frequent physiotherapy. Recently developed whole-body controlled video game technology might present a novel treatment strategy for highly interactive and motivational coordinative training for children with degenerative ataxias. We examined the effectiveness of an 8-week coordinative training for 10 children with progressive spinocerebellar ataxia. Training was based on 3 Microsoft Xbox Kinect video games particularly suitable to exercise whole-body coordination and dynamic balance. Training was started with a laboratory-based 2-week training phase and followed by 6 weeks training in children's home environment. Rater-blinded assessments were performed 2 weeks before laboratory-based training, immediately prior to and after the laboratory-based training period, as well as after home training. These assessments allowed for an intraindividual control design, where performance changes with and without training were compared. Ataxia symptoms were significantly reduced (decrease in Scale for the Assessment and Rating of Ataxia score, p = 0.0078) and balance capacities improved (dynamic gait index, p = 0.04) after intervention. Quantitative movement analysis revealed improvements in gait (lateral sway: p = 0.01; step length variability: p = 0.01) and in goal-directed leg placement (p = 0.03). Despite progressive cerebellar degeneration, children are able to improve motor performance by intensive coordination training. Directed training of whole-body controlled video games might present a highly motivational, cost-efficient, and home-based rehabilitation strategy to train dynamic balance and interaction with dynamic environments in a large variety of young-onset neurologic

  18. Health risks for ataxia-telangiectasia mutated heterozygotes : a systematic review, meta-analysis and evidence-based guideline

    NARCIS (Netherlands)

    van Os, N J H; Roeleveld, N; Weemaes, C M R; Jongmans, M C J; Janssens, G O; Taylor, A M R; Hoogerbrugge, N; Willemsen, Michel A A P

    Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder with immunodeficiency and an increased risk of developing cancer, caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. Logically, blood relatives may also carry a pathogenic ATM mutation. Female carriers

  19. Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.

    Science.gov (United States)

    Perkins, Emma M; Suminaite, Daumante; Clarkson, Yvonne L; Lee, Sin Kwan; Lyndon, Alastair R; Rothstein, Jeffrey D; Wyllie, David J A; Tanaka, Kohichi; Jackson, Mandy

    2016-10-15

    Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III-/-). One function of β-III spectrin is the stabilization of the Purkinje cell-specific glutamate transporter EAAT4 at the plasma membrane. In β-III-/- mice EAAT4 levels are reduced from an early age. In contrast levels of the predominant cerebellar glutamate transporter GLAST, expressed in Bergmann glia, only fall progressively from 3 months onwards. Here we elucidated the roles of these two glutamate transporters in cerebellar pathogenesis mediated through loss of β-III spectrin function by studying EAAT4 and GLAST knockout mice as well as crosses of both with β-III-/- mice. Our data demonstrate that EAAT4 loss, but not abnormal AMPA receptor composition, in young β-III-/- mice underlies early Purkinje cell hyper-excitability and that subsequent loss of GLAST, superimposed on the earlier deficiency of EAAT4, is responsible for Purkinje cell loss and progression of motor deficits. Yet the loss of GLAST appears to be independent of EAAT4 loss, highlighting that other aspects of Purkinje cell dysfunction underpin the pathogenic loss of GLAST. Finally, our results demonstrate that Purkinje cells in the posterior cerebellum of β-III-/- mice are most susceptible to the combined loss of EAAT4 and GLAST, with degeneration of proximal dendrites, the site of climbing fibre innervation, most pronounced. This highlights the necessity for efficient glutamate clearance from these regions and identifies dysregulation of glutamatergic neurotransmission particularly within the posterior cerebellum as a key mechanism in SCA5 and SPARCA1 pathogenesis.

  20. Metabolic anatomy of paraneoplastic cerebellar degeneration

    International Nuclear Information System (INIS)

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-01-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18 F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis

  1. [A sporadic case of episodic ataxia with nystagmus (EA-2)].

    Science.gov (United States)

    Namekawa, M; Takiyama, Y; Ueno, N; Nishizawa, M

    1998-05-01

    A 39-year-old man with episodic ataxia with nystagmus (EA-2) was reported. He showed intermittent cerebellar dysfunction, i.e., ataxia, nystagmus, dysarthria and vertigo, since he was 10 years old. Although this attack lasted for several hours, he was normal with exception of interictal nystagmus. His parents and sister showed no episodic ataxia. We ruled out the diseases, which may cause episodic ataxia, such as multiple sclerosis, vascular disorders, metabolic disorders and congenital anomalies. He was released from the attack by treatment with acetazolamide. EA-2 has been associated with mutations in the alpha 1A-voltage dependent calcium channel gene (CACNL1A4), which is also affected in familial hemiplegic migraine (FMH) and spinocerebellar ataxia type 6 (SCA6). In EA-2, frame-shift mutation leading to premature stop and splice-site mutation leading to truncated, non-functional channel protein have been reported. However, our patient did not have the mutations in the CACNL1A4 gene that were previously reported. In addition, our patient did not have an expanded CAG allele in the CACNL1A4 gene which is responsible for SCA6. Further examination is required to address whether a new mutation exists in the CACNL1A4 gene in our patient.

  2. Prevalence of spinocerebellar ataxia 36 in a US population.

    Science.gov (United States)

    Valera, Juliana M; Diaz, Tatyana; Petty, Lauren E; Quintáns, Beatriz; Yáñez, Zuleima; Boerwinkle, Eric; Muzny, Donna; Akhmedov, Dmitry; Berdeaux, Rebecca; Sobrido, Maria J; Gibbs, Richard; Lupski, James R; Geschwind, Daniel H; Perlman, Susan; Below, Jennifer E; Fogel, Brent L

    2017-08-01

    To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States. A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the NOP56 gene. Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of NOP56 in 4 index cases. These 4 SCA36-positive families comprised 2 distinct ethnic groups: white (European) (2) and Asian (Japanese [1] and Vietnamese [1]). Individuals affected by SCA36 exhibited typical clinical features with gait ataxia and age at onset ranging between 35 and 50 years. Patients also suffered from ataxic or spastic limbs, altered reflexes, abnormal ocular movement, and cognitive impairment. In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort.

  3. [Progressive ataxia and cognitive deficits caused by premutation in the fragile-X-mental retardation gene

    NARCIS (Netherlands)

    Roks, G.; Sistermans, E.A.; Vries, L.B.A. de; Nijssen, P.C.

    2005-01-01

    A 75-year-old man had progressive difficulty with walking, intention tremor, ataxia, and mild cognitive deficits. MRI scan ofthe brain showed symmetrical hyperintensities in the middle cerebellar peduncles. DNA analysis ofthe fragile-X gene revealed an expansion of 150-200 repetitions in the

  4. Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Huang Lijia

    2012-09-01

    Full Text Available Abstract Background Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family. Methods and Results Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified. Conclusions ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.

  5. Cerebellar atrophy related to chronic exposure to toluene: case report

    Directory of Open Access Journals (Sweden)

    Benito Pereira Damasceno

    1994-03-01

    Full Text Available A 31-year-old woman presented slowly progressing ataxia and neurasthenic symptoms after 14-year occupational exposure to low concentration toluene vapour. Examination disclosed only cerebellar signs. Cognitive functions were normal except moderate visuo-spatial and constructive deficit CT imaging showed severe pancerebellar atrophy without pathological signs in other brain structures. Two years after she was removed from workplace, CT imaging and ataxia showed no worsening, while visuo-constructive function improved. The authors warn against possible neurotoxic risk associated with this kind of exposure.

  6. Genetic and cellular features of ataxia telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, A M.R.; Byrd, P J; McConville, C M; Thacker, S [Birmingham Univ. (United Kingdom). CRC Dept. of Cancer Studies

    1994-01-01

    Ataxia telangiectasia (AT) is a developmental disorder in which many organ systems are affected. The children are recognized by a progressive cerebellar deterioration. The gene for AT has now been localized to a region of chromosome 11q22-23 of no more than 3Mb in size and its product appears to be involved directly or indirectly in some form of DNA recombination. Patients and their cells are unusually sensitive to ionizing radiation and various radiometric drugs. Observations on the progressive nature of the disorder, with loss of selected cells or failure to develop normally, might be compatible with the pathological effect of an inability to correctly regulate apoptosis in some cell lineages. While this is an intriguing speculation, there is, at present, no evidence for such a defect in AT. (author).

  7. Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this emerging congenital ataxia.

    Science.gov (United States)

    Zambonin, Jessica L; Bellomo, Allison; Ben-Pazi, Hilla; Everman, David B; Frazer, Lee M; Geraghty, Michael T; Harper, Amy D; Jones, Julie R; Kamien, Benjamin; Kernohan, Kristin; Koenig, Mary Kay; Lines, Matthew; Palmer, Elizabeth Emma; Richardson, Randal; Segel, Reeval; Tarnopolsky, Mark; Vanstone, Jason R; Gibbons, Melissa; Collins, Abigail; Fogel, Brent L; Dudding-Byth, Tracy; Boycott, Kym M

    2017-06-28

    Spinocerebellar ataxia type 29 (SCA29) is an autosomal dominant, non-progressive cerebellar ataxia characterized by infantile-onset hypotonia, gross motor delay and cognitive impairment. Affected individuals exhibit cerebellar dysfunction and often have cerebellar atrophy on neuroimaging. Recently, missense mutations in ITPR1 were determined to be responsible. Clinical information on 21 individuals from 15 unrelated families with ITPR1 mutations was retrospectively collected using standardized questionnaires, including 11 previously unreported singletons and 2 new patients from a previously reported family. We describe the genetic, clinical and neuroimaging features of these patients to further characterize the clinical features of this rare condition and assess for any genotype-phenotype correlation for this disorder. Our cohort consisted of 9 males and 12 females, with ages ranging from 28 months to 49 years. Disease course was non-progressive with infantile-onset hypotonia and delays in motor and speech development. Gait ataxia was present in all individuals and 10 (48%) were not ambulating independently between the ages of 3-12 years of age. Mild-to-moderate cognitive impairment was present in 17 individuals (85%). Cerebellar atrophy developed after initial symptom presentation in 13 individuals (72%) and was not associated with disease progression or worsening functional impairment. We identified 12 different mutations including 6 novel mutations; 10 mutations were missense (with 4 present in >1 individual), 1 a splice site mutation leading to an in-frame insertion and 1 an in-frame deletion. No specific genotype-phenotype correlations were observed within our cohort. Our findings document significant clinical heterogeneity between individuals with SCA29 in a large cohort of molecularly confirmed cases. Based on the retrospective observed clinical features and disease course, we provide recommendations for management. Further research into the natural

  8. White matter damage is related to ataxia severity in SCA3.

    Science.gov (United States)

    Kang, J-S; Klein, J C; Baudrexel, S; Deichmann, R; Nolte, D; Hilker, R

    2014-02-01

    Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

  9. Disease: H01204 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01204 Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CA...MRQ) Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CAMRQ) is autosomal recessive,... Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium

  10. A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis.

    Science.gov (United States)

    Tabatabaiefar, Mohammad Amin; Alipour, Paria; Pourahmadiyan, Azam; Fattahi, Najmeh; Shariati, Laleh; Golchin, Neda; Mohammadi-Asl, Javad

    2017-08-15

    Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics. Copyright © 2017. Published by Elsevier B.V.

  11. Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

    Science.gov (United States)

    2017-09-28

    -Hirschhorn Syndrome; 4p16.3 Microduplication Syndrome; 4p Deletion Syndrome, Non-Wolf-Hirschhorn Syndrome; Autosomal Recessive Stickler Syndrome; Stickler Syndrome Type 2; Stickler Syndrome Type 1; Stickler Syndrome; Mucolipidosis Type 4; X-linked Spinocerebellar Ataxia Type 4; X-linked Spinocerebellar Ataxia Type 3; X-linked Intellectual Disability - Ataxia - Apraxia; X-linked Progressive Cerebellar Ataxia; X-linked Non Progressive Cerebellar Ataxia; X-linked Cerebellar Ataxia; Vitamin B12 Deficiency Ataxia; Toxic Exposure Ataxia; Unclassified Autosomal Dominant Spinocerebellar Ataxia; Thyroid Antibody Ataxia; Sporadic Adult-onset Ataxia of Unknown Etiology; Spinocerebellar Ataxia With Oculomotor Anomaly; Spinocerebellar Ataxia With Epilepsy; Spinocerebellar Ataxia With Axonal Neuropathy Type 2; Spinocerebellar Ataxia Type 8; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 5; Spinocerebellar Ataxia Type 4; Spinocerebellar Ataxia Type 37; Spinocerebellar Ataxia Type 36; Spinocerebellar Ataxia Type 35; Spinocerebellar Ataxia Type 34; Spinocerebellar Ataxia Type 32; Spinocerebellar Ataxia Type 31; Spinocerebellar Ataxia Type 30; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 29; Spinocerebellar Ataxia Type 28; Spinocerebellar Ataxia Type 27; Spinocerebellar Ataxia Type 26; Spinocerebellar Ataxia Type 25; Spinocerebellar Ataxia Type 23; Spinocerebellar Ataxia Type 22; Spinocerebellar Ataxia Type 21; Spinocerebellar Ataxia Type 20; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 19/22; Spinocerebellar Ataxia Type 18; Spinocerebellar Ataxia Type 17; Spinocerebellar Ataxia Type 16; Spinocerebellar Ataxia Type 15/16; Spinocerebellar Ataxia Type 14; Spinocerebellar Ataxia Type 13; Spinocerebellar Ataxia Type 12; Spinocerebellar Ataxia Type 11; Spinocerebellar Ataxia Type 10; Spinocerebellar Ataxia Type 1 With Axonal Neuropathy; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia - Unknown; Spinocerebellar Ataxia - Dysmorphism

  12. Cerebellar and cerebral atrophy in trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye-Kyung; Sargent, Michael A.; Poskitt, Kenneth J. [British Columbia Children' s Hospital, Department of Radiology, Vancouver, BC (Canada); Prendiville, Julie S. [British Columbia Children' s Hospital, Division of Paediatric Dermatology, Department of Paediatrics, Vancouver, BC (Canada)

    2005-10-01

    Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy. (orig.)

  13. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction

    Science.gov (United States)

    Abulnaga, S. Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi U.; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  14. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction.

    Science.gov (United States)

    Abulnaga, S Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M; Onyike, Chiadi U; Ying, Sarah H; Prince, Jerry L

    2016-02-27

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  15. Ataxia-telangiectasia: future prospects

    Directory of Open Access Journals (Sweden)

    Chaudhary MW

    2014-09-01

    Full Text Available Mohammed Wajid Chaudhary, Raidah Saleem Al-Baradie Pediatric Neurology, Neurosciences Centre, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia Abstract: Ataxia-telangiectasia (A-T is an autosomal recessive multi-system disorder caused by mutation in the ataxia-telangiectasia mutated gene (ATM. ATM is a large serine/threonine protein kinase, a member of the phosphoinositide 3-kinase-related protein kinase (PIKK family whose best-studied function is as master controller of signal transduction for the DNA damage response (DDR in the event of double strand breaks (DSBs. The DDR rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell-cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence. DSBs can be generated by exposure to ionizing radiation (IR or various chemical compounds, such as topoisomerase inhibitors, or can be part of programmed generation and repair of DSBs via cellular enzymes needed for the generation of the antibody repertoire as well as the maturation of germ cells. AT patients have immunodeficiency, and are sterile with gonadal dysgenesis as a result of defect in meiotic recombination. In the cells of nervous system ATM has additional role in vesicle dynamics as well as in the maintenance of the epigenetic code of histone modifications. Moderate levels of ATM are associated with prolonged lifespan through resistance to oxidative stress. ATM inhibitors are being viewed as potential radiosensitizers as part of cancer radiotherapy. Though there is no cure for the disease at present, glucocorticoids have been shown to induce alternate splicing site in the gene for ATM partly restoring its activity, but their most effective timing in the disease natural history is not yet known. Gene therapy is promising but large size of the gene makes it technically difficult

  16. The history of spinocerebellar ataxia type 10 in Brazil: travels of a gene A história da ataxia espinocerebelar tipo 10 no Brasil: as viagens de um gene

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2007-12-01

    Full Text Available The authors report the history of spinocerebellar ataxia 10 (SCA10, since its first report in a large Portuguese-ancestry Family with autosomal dominant pure cerebellar ataxia, till the final identification of further families without Mexican ancestry. These families present a quite different phenotype from those SCA10 families described in Mexico.Os autores apresentam a história da descoberta da ataxia espinocerebelar tipo 10 (AEC10 no Brasil, desde o primeiro relato em uma família com ancestrais portugueses com ataxia cerebelar pura, autossômica dominante, até a identificação de famílias sem ancestrais mexicanos. Essas famílias apresentam um fenótipo de AEC10, com ataxia cerebelar "pura", distinta daquele descrito nas famílias no México.

  17. Questioning the cerebellar doctrine

    NARCIS (Netherlands)

    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells

  18. Spinocerebellar ataxia type 7: Report of an Indian family

    Directory of Open Access Journals (Sweden)

    Gurusidheshwar M Wali

    2013-01-01

    Full Text Available Spinocerebellar ataxia type 7 (SCA7 is a form of autosomal dominant cerebellar ataxia which is associated with pigmentary retinal degeneration. It is known for its world-wide rarity except in the Scandinavian countries. It is very rarely reported from India and the neighbouring Asian countries . The present report describes the neurogenetic findings of a family of SCA7, from the northern part of Karnataka in South India. It documents the wide intrafamilial phenotypic variability, which could be correlated with the CAG repeat counts and phenomenon of anticipation. Genotype phenotype correlation highlighted certain disparities in comparison with the previous studies. The report highlights the need for multiethnic population studies and the role of genetic counseling and prenatal testing in SCA7 patients.

  19. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    International Nuclear Information System (INIS)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun

    2007-01-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder

  20. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder.

  1. Cell biological study on ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Ohta, Shigeru; Katsura, Tadahiko; Shimada, Morimi; Shima, Akihiro; Chishiro, Hiroko; Kasahara, Yoshitaka.

    1985-01-01

    Diagnosis of ataxia-telangiectasia (AT) has largely been dependent on the clinical findings such as cerebellar ataxia, telangiectasia, and immunological deficiency. However, diagnosis of AT by these ordinary criteria is sometimes not sufficient because of the lack of immunological abnormalities. We examined three cases of AT by ordinary clinical criteria and also by X-ray sensitivity of cultured skin fibroblasts. Case 1, a 9-year-old boy, revealed typical clinical features of AT. However, he had no abnormality in serum IgA or IgE. Case 2, a 10-year-old boy, showed decreased serum IgA level. Case 3, a 19-year-old female, had typical clinical features of AT with normal serum IgA, and developed papillary adenocarcinoma of thyroid which was surgically removed. Fibroblast strains derived from these three cases of AT and from the parents of Case 3 were examined with regard to X-ray sensitivity. Three fibroblast strains derived from AT patients (AT homozygotes) showed remarkable hypersensitivity to X-ray. Fibroblast strains derived from the parents (AT heterozygotes) of Case 3, however, showed normal X-ray sensitivity. Recently, AT fibroblasts have been known to show hypersensitivity also to some mutagen like neocarzinostazin as reported by Shiloh et al. Fibroblasts from Case 3 revealed hypersensitivity to neocarzinostazin. However, the sensitivity of the strains from AT heterozygotes (the parents of Case 3) showed no apparent difference from that of control cells. The assay system for mutagen is quite unstable and proper conditioning of the seeding cell number is important for the carrier detection. However, the diagnosis of AT homozygotes was definitely established by X-ray irradiation to cultured fibroblasts from patients. (author)

  2. Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke

    Directory of Open Access Journals (Sweden)

    Catherine J. Stoodley

    2016-01-01

    Full Text Available Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome. We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20–66 years old were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III–VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX, spatial (bilateral Crus I, Crus II, and right lobule VIII, and executive function measures (lobules VII–VIII. These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

  3. Autosomal dominant hereditary ataxia in Sri Lanka

    OpenAIRE

    Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

    2013-01-01

    Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

  4. A Survey on 100 Children with Acute Ataxia in Mofid Children Hospital Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Parvaneh Karim-Zadeh

    2003-04-01

    Full Text Available Objective: The term “Ataxia” is used to denote disturbances of the body posture and its movement that are normally controlled by the cerebellum. frontal lobes and the posterior columns of the spinal cord. The initial symptom and the most prominent feature of ataxia is abnormal gait which is characterized by lurching and wide base walking. Knowing that, the acute ataxia is among those problems that brings very soon the child to pediatrics neurology department and in view of lack of any survey in this neid in our country, we decided to investigate the etiology of acute ataxia in Islamic Republic of Iran. Materials & Methods: Our patients were recruited from 100 children who were brought to neurology service of Mofid children hospital with the chief complaint of acute ataxia over 2 years period. (sep 2001 to sep 2003. All of those 100 patients were admitted and required investigations were performed. Results: Results of our workup revealed that the most common cause of acute ataxia is acute cerebellar one, which all of them preceded by viral febrile illness. The second frequent cause of acute. Ataxia is due to drug intoxication, which commonly was observed between 2 – 4 years period. Conclusion: The remaining etiologies in descending frequency were as follow, Infectious polyneuropathy, Migraine, Opsoclonus – Myoclonus, Brain tumor, ADEM,MS and Epilepsy.

  5. Purkinje Cell Signaling Deficits in Animal Models of Ataxia

    Directory of Open Access Journals (Sweden)

    Eriola Hoxha

    2018-04-01

    synaptic signals or the way they are processed by the repertoire of ionic channels responsible for intrinsic membrane properties. Although the PC is a final common pathway of ataxia, the link between specific firing alterations and neurologic symptoms has not yet been systematically studied and the alterations of the cerebellar contribution to motor signals are still unknown.

  6. Questioning the cerebellar doctrine.

    Science.gov (United States)

    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the cerebellar doctrine. © 2014 Elsevier B.V. All rights reserved.

  7. Progression of brain atrophy in spinocerebellar ataxia type 2: a longitudinal tensor-based morphometry study.

    Science.gov (United States)

    Mascalchi, Mario; Diciotti, Stefano; Giannelli, Marco; Ginestroni, Andrea; Soricelli, Andrea; Nicolai, Emanuele; Aiello, Marco; Tessa, Carlo; Galli, Lucia; Dotti, Maria Teresa; Piacentini, Silvia; Salvatore, Elena; Toschi, Nicola

    2014-01-01

    Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender-matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM) to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray matter (GM) in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials.

  8. Progression of brain atrophy in spinocerebellar ataxia type 2: a longitudinal tensor-based morphometry study.

    Directory of Open Access Journals (Sweden)

    Mario Mascalchi

    Full Text Available Spinocerebellar ataxia type 2 (SCA2 is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years and 16 age- and gender-matched healthy controls (mean interval 3.3 years on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM and cortical gray matter (GM in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials.

  9. The Diagnostic Accuracy of Truncal Ataxia and HINTS as Cardinal Signs for Acute Vestibular Syndrome

    Directory of Open Access Journals (Sweden)

    Sergio Carmona

    2016-08-01

    Full Text Available The head impulse, nystagmus type, test of skew (HINTS protocol set a new paradigm to differentiate peripheral vestibular disease from stroke in patients with acute vestibular syndrome (AVS. The relationship between degree of truncal ataxia and stroke has not been systematically studied in patients with AVS. We studied a group of 114 patients who were admitted to a General Hospital due to AVS, 72 of them with vestibular neuritis (based on positive head impulse, abnormal caloric tests and negative MRI, and the rest with Stroke: 32 in the PICA territory (positive HINTS findings, positive MRI and 10 in the AICA territory (variable findings and grade 3 Ataxia, positive MRI. Truncal ataxia was measured by independent observers as grade 1, mild to moderate imbalance with walking independently; grade 2, severe imbalance with standing, but cannot walk without support; and grade 3, falling at upright posture.When we applied the HINTS protocol to our sample, we obtained 100% sensitivity and 94.4% specificity, similar to previously published findings. Only those patients with stroke presented with grade 3 ataxia. Of those with grade 2 ataxia (n = 38, 11 had cerebellar stroke and 28 had vestibular neuritis, not related to the patient's age. Grade 2-3 ataxia was 92.9% sensitive and 61.1% specific to detect AICA/PICA stroke in patients with AVS, with 100% sensitivity to detect AICA stroke. In turn, two signs (nystagmus of central origin and grade 2-3 Ataxia had 100% sensitivity and 61.1% specificity. Ataxia is less sensitive than HINTS but much easier to evaluate.

  10. Gastric outlet obstruction due to adenocarcinoma in a patient with Ataxia-Telangiectasia syndrome: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Hammond Sue

    2009-03-01

    Full Text Available Abstract Background Ataxia-Telangiectasia syndrome is characterized by progressive cerebellar dysfunction, conjuctival and cutaneous telangiectasias, severe immune deficiencies, premature aging and predisposition to cancer. Clinical and radiographic evaluation for malignancy in ataxia-telangiectasia patients is usually atypical, leading to delays in diagnosis. Case presentation We report the case of a 20 year old ataxia-telangiectasia patient with gastric adenocarcinoma that presented as complete gastric outlet obstruction. Conclusion A literature search of adenocarcinoma associated with ataxia-telangiectasia revealed 6 cases. All patients presented with non-specific gastrointestinal complaints suggestive of ulcer disease. Although there was no correlation between immunoglobulin levels and development of gastric adenocarcinoma, the presence of chronic gastritis and intestinal metaplasia seem to lead to the development of gastric adenocarcinoma. One should consider adenocarcinoma in any patient with ataxia-telangiectasia who presents with non-specific gastrointestinal complaints, since this can lead to earlier diagnosis.

  11. Hashimoto thyroiditis associated with ataxia telangiectasia.

    Science.gov (United States)

    Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem; Kurtoglu, Selim; Yikilmaz, Ali; Patiroglu, Tahir

    2012-01-01

    Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.

  12. Adult onset sporadic ataxias: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2014-03-01

    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

  13. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes.

    Science.gov (United States)

    Vogel, Adam P; Folker, Joanne; Poole, Matthew L

    2014-10-28

    low dose of the intervention), in heterogenous groups of degenerative cerebellar ataxias. Three compounds were studied in two trials each: a levorotatory form of 5-hydroxytryptophan (L-5HT), idebenone and thyrotropin-releasing hormone tartrate (TRH-T); each of the other compounds (riluzole, varenicline, buspirone, betamethasone, coenzyme Q10 with vitamin E, α-tocopheryl quinone and erythropoietin) were studied in one trial. The 14th trial, involving a mixed group of participants with spinocerebellar ataxia, compared the effectiveness of nonspecific physiotherapy and occupational therapy within an inpatient hospital setting to no treatment. No studies utilised traditional speech therapies. We defined the primary outcome measure in this review as the percentage change (improvement) in overall speech production immediately following completion of the intervention or later, measured by any validated speech assessment tool. None of the trials included speech as a primary outcome or examined speech using any validated speech assessment tool. Eleven studies reported speech outcomes derived from a subscale embedded within disease rating scales. The remaining three studies used alternative assessments to measure speech, including mean time to produce a standard sentence, a subjective rating of speech on a 14-point analogue scale, patient-reported assessment of the impact of dysarthria on activities of daily living and acoustic measures of syllable length. One study measured speech both subjectively as part of a disease rating scale and with further measures of speech timing. Three studies utilised the Short Form-36 Health Survey (SF-36) and one used the Child Health Questionnaire as measures of general quality of life. A further study utilised the Functional Independence Measure to assess functional health.Five studies reported statistically significant improvement on an overall disease rating scale in which a speech subscale was included. Only three of those studies provided

  14. Increased protein kinase C gamma activity induces Purkinje cell pathology in a mouse model of spinocerebellar ataxia 14.

    Science.gov (United States)

    Ji, Jingmin; Hassler, Melanie L; Shimobayashi, Etsuko; Paka, Nagendher; Streit, Raphael; Kapfhammer, Josef P

    2014-10-01

    Spinocerebellar ataxias (SCAs) are hereditary diseases leading to Purkinje cell degeneration and cerebellar dysfunction. Most forms of SCA are caused by expansion of CAG repeats similar to other polyglutamine disorders such as Huntington's disease. In contrast, in the autosomal dominant SCA-14 the disease is caused by mutations in the protein kinase C gamma (PKCγ) gene which is a well characterized signaling molecule in cerebellar Purkinje cells. The study of SCA-14, therefore, offers the unique opportunity to reveal the molecular and pathological mechanism eventually leading to Purkinje cell dysfunction and degeneration. We have created a mouse model of SCA-14 in which PKCγ protein with a mutation found in SCA-14 is specifically expressed in cerebellar Purkinje cells. We find that in mice expressing the mutated PKCγ protein the morphology of Purkinje cells in cerebellar slice cultures is drastically altered and mimics closely the morphology seen after pharmacological PKC activation. Similar morphological abnormalities were seen in localized areas of the cerebellum of juvenile transgenic mice in vivo. In adult transgenic mice there is evidence for some localized loss of Purkinje cells but there is no overall cerebellar atrophy. Transgenic mice show a mild cerebellar ataxia revealed by testing on the rotarod and on the walking beam. Our findings provide evidence for both an increased PKCγ activity in Purkinje cells in vivo and for pathological changes typical for cerebellar disease thus linking the increased and dysregulated activity of PKCγ tightly to the development of cerebellar disease in SCA-14 and possibly also in other forms of SCA. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Clinical and genetic features of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Bundey, S.

    1994-01-01

    There are several variants of ataxia-telangiectasia (A-T): classical A-T with marked radiation sensitivity; classical A-T with intermediate levels of radiation sensitivity; mild A-T with intermediate levels of radiation sensitivity; A-T without telangiectasia; A-T without oculomoto apraxia; and A-T with microcephaly. These disorders are probably caused by different allelic mutations, because affected sibs resemble the index patients, and because there is an association of certain haplo-types of 11q22-23 with specific phenotypes. The Nijmegen Breakage Syndrome, with its lack of ataxia, seems on clinical grounds to be a different disorder. Although A-T is almost always inherited as an autosomal recessive, there are some unusual features; an unexpectedly low parental consanguinity rate, an incidence in sibs that is < 0.25, and occurrence of disease in many different races and in the offspring of mixed race unions. Moreover, looking at haplotypes from 63 UK patients, there is a remarkably low incidence of homozygosity. An autosomal recessive condition that is deficient in parental consanguinity, and in homozygosity for the region around the gene, can be explained by J.H. Edwards' hypothesis that homozygosity for alleles at a neighbouring locus are lethal early in embryogenesis. Other possible mechanisms to explain the unusual genetic features are discussed. (author)

  16. Forecasting US Recessions

    DEFF Research Database (Denmark)

    Christiansen, Charlotte; Eriksen, Jonas Nygaard; Møller, Stig Vinther

    2014-01-01

    We study the role of sentiment variables as predictors for US recessions. We combine sentiment variables with either classical recession predictors or common factors based on a large panel of macroeconomic and financial variables. Sentiment variables hold vast predictive power for US recessions...

  17. Degenerative cerebellar diseases and differential diagnoses; Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W.; Roumia, S.; Dietrich, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-11-15

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [German] Klinisch imponieren Kleinhirnsyndrome durch Ataxie, Dysarthrie, Dysmetrie, Intentionstremor und Augenbewegungsstoerungen. Neben der Anamnese und klinischen Untersuchung ist die Bildgebung v. a. wichtig um andere Erkrankungen wie Hydrozephalus und Multiinfarktdemenz von degenerativen Kleinhirnerkrankungen zu differenzieren. Zu den degenerativen Erkrankungen mit Kleinhirnbeteiligung gehoeren der Morbus Parkinson, die Multisystematrophie sowie weitere Erkrankungen einschliesslich der spinozerebellaeren Ataxien. Neben der MRT sind auch nuklearmedizinische Untersuchungen zur Differenzierung hilfreich. Axiale Fluid-attenuated-inversion-recovery(FLAIR)- und T2-gewichtete Sequenzen koennen mitunter eine Signalsteigerung im Pons als Ausdruck einer Degeneration der pontinen Neuronen und transversalen Bahnen im Brueckenfuss zeigen. Die Bildgebung ist aber v. a. notwendig, um andere Erkrankungen wie Normaldruckhydrozephalus

  18. Operation of a P300-based brain-computer interface by patients with spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Yoji Okahara

    Full Text Available Objective: We investigated the efficacy of a P300-based brain-computer interface (BCI for patients with spinocerebellar ataxia (SCA, which is often accompanied by cerebellar impairment. Methods: Eight patients with SCA and eight age- and gender-matched healthy controls were instructed to input Japanese hiragana characters using the P300-based BCI with green/blue flicker. All patients depended on some assistance in their daily lives (modified Rankin scale: mean 3.5. The chief symptom was cerebellar ataxia; no cognitive deterioration was present. A region-based, two-step P300-based BCI was used. During the P300 task, eight-channel EEG data were recorded, and a linear discriminant analysis distinguished the target from other nontarget regions of the matrix. Results: The mean online accuracy in BCI operation was 82.9% for patients with SCA and 83.2% for controls; no significant difference was detected. Conclusion: The P300-based BCI was operated successfully not only by healthy controls but also by individuals with SCA. Significance: These results suggest that the P300-based BCI may be applicable for patients with SCA. Keywords: BCI, BMI, P300, Visual stimuli, Spinocerebellar ataxia

  19. Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

    Science.gov (United States)

    Di Siena, Sara; Campolo, Federica; Gimmelli, Roberto; Di Pietro, Chiara; Marazziti, Daniela; Dolci, Susanna; Lenzi, Andrea; Nussenzweig, Andre; Pellegrini, Manuela

    2018-02-22

    Hereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.

  20. Dementia in Fragile X-associated Tremor/Ataxia Syndrome

    Directory of Open Access Journals (Sweden)

    Ricardo Nitrini

    Full Text Available Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS is a cause of movement disorders and cognitive decline which has probably been underdiagnosed, especially if its prevalence proves similar to those of progressive supranuclear palsy and amyotrophic lateral sclerosis. We report a case of a 74-year-old man who presented with action tremor, gait ataxia and forgetfulness. There was a family history of tremor and dementia, and one of the patient's grandsons was mentally deficient. Neuropsychological evaluation disclosed a frontal network syndrome. MRI showed hyperintensity of both middle cerebellar peduncles, a major diagnostic hallmark of FXTAS. Genetic testing revealed premutation of the FMR1 gene with an expanded (CGG90 repeat. The diagnosis of FXTAS is important for genetic counseling because the daughters of the affected individuals are at high risk of having offspring with fragile X syndrome. Tremors and cognitive decline should raise the diagnostic hypothesis of FXTAS, which MRI may subsequently reinforce, while the detection of the FMR1 premutation can confirm the condition.

  1. Cerebellar anatomy as applied to cerebellar microsurgical resections

    Directory of Open Access Journals (Sweden)

    Alejandro Ramos

    2012-06-01

    Full Text Available OBJECTIVE: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. METHODS: Twenty cerebellar hemispheres were studied. RESULTS: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. CONCLUSIONS: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.

  2. Spinocerebellar Ataxia Type 2: Clinicogenetic Aspects, Mechanistic Insights, and Management Approaches

    Directory of Open Access Journals (Sweden)

    Luis C. Velázquez-Pérez

    2017-09-01

    Full Text Available Spinocerebellar ataxia type 2 (SCA2 is an autosomal dominant cerebellar ataxia that occurs as a consequence of abnormal CAG expansions in the ATXN2 gene. Progressive clinical features result from the neurodegeneration of cerebellum and extra-cerebellar structures including the pons, the basal ganglia, and the cerebral cortex. Clinical, electrophysiological, and imaging approaches have been used to characterize the natural history of the disease, allowing its classification into four distinct stages, with special emphasis on the prodromal stage, which is characterized by a plethora of motor and non-motor features. Neuropathological investigations of brain tissue from SCA2 patients reveal a widespread involvement of multiple brain systems, mainly cerebellar and brainstem systems. Recent findings linking ataxin-2 intermediate expansions to other neurodegenerative diseases such as amyotrophic lateral sclerosis have provided insights into the ataxin-2-related toxicity mechanism in neurodegenerative diseases and have raised new ethical challenges to molecular predictive diagnosis of SCA2. No effective neuroprotective therapies are currently available for SCA2 patients, but some therapeutic options such as neurorehabilitation and some emerging neuroprotective drugs have shown palliative benefits.

  3. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    Science.gov (United States)

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  4. 5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor?

    Science.gov (United States)

    Maximov, G K; Maximov, K G; Chokoeva, A A; Lotti, T; Wollina, U; Patterson, J W; Guarneri, C; Tana, C; Fioranelli, M; Roccia, M G; Kanazawa, N; Tchernev, G

    2016-01-01

    Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently.

  5. Two in one: report of a patient with spinocerebellar ataxia types 2 and 10.

    Science.gov (United States)

    Kapur, Sachin S; Goldman, Jennifer G

    2012-09-01

    To report a rare case of the coexistence of 2 spinocerebellar ataxia (SCA) mutations in a single patient. Case report. University hospital, Movement Disorders Center. A 54-year-old man of Mexican, American Indian, and French descent with an 11-year history of gait and limb ataxia. Findings of clinical examination, magnetic resonance imaging, and video electroencephalographic monitoring. Neurologic history revealed a gradually progressive gait and limb ataxia along with muscle cramps and sensory symptoms in his distal extremities; examination revealed executive dysfunction, dysarthria, ataxia, and sensory neuronopathy. Episodes of loss of awareness were reported, but electroencephalograms were negative. Brain imaging demonstrated severe cerebellar and brainstem atrophy. Genetic evaluation of the case revealed mutations in both the SCA2 and SCA10 genes. Our patient has a unique combination of genetic mutations for 2 different SCAs, types 2 and 10, which to our knowledge, has not been previously reported. His clinical phenotype is largely consistent with SCA2, but his possible seizures and Mexican heritage suggest influences of SCA10.

  6. Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders.

    Science.gov (United States)

    Robertson, Erin E; Hall, Deborah A; McAsey, Andrew R; O'Keefe, Joan A

    2016-08-01

    The purpose of this paper is to review the typical cognitive and motor impairments seen in fragile X-associated tremor/ataxia syndrome (FXTAS), essential tremor (ET), Parkinson disease (PD), spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in order to enhance diagnosis of FXTAS patients. We compared the cognitive and motor phenotypes of FXTAS with each of these other movement disorders. Relevant neuropathological and neuroimaging findings are also reviewed. Finally, we describe the differences in age of onset, disease severity, progression rates, and average lifespan in FXTAS compared to ET, PD, SCAs, MSA, and PSP. We conclude with a flow chart algorithm to guide the clinician in the differential diagnosis of FXTAS. By comparing the cognitive and motor phenotypes of FXTAS with the phenotypes of ET, PD, SCAs, MSA, and PSP we have clarified potential symptom overlap while elucidating factors that make these disorders unique from one another. In summary, the clinician should consider a FXTAS diagnosis and testing for the Fragile X mental retardation 1 (FMR1) gene premutation if a patient over the age of 50 (1) presents with cerebellar ataxia and/or intention tremor with mild parkinsonism, (2) has the middle cerebellar peduncle (MCP) sign, global cerebellar and cerebral atrophy, and/or subcortical white matter lesions on MRI, or (3) has a family history of fragile X related disorders, intellectual disability, autism, premature ovarian failure and has neurological signs consistent with FXTAS. Peripheral neuropathy, executive function deficits, anxiety, or depression are supportive of the diagnosis. Distinct profiles in the cognitive and motor domains between these movement disorders may guide practitioners in the differential diagnosis process and ultimately lead to better medical management of FXTAS patients.

  7. Cerebellar atrophy is frequently associated with non-paraneoplastic sensory neuronopathy

    Directory of Open Access Journals (Sweden)

    Alfredo Damasceno

    2011-08-01

    Full Text Available Sensory neuronopathies (SN are peripheral nervous system disorders associated with degeneration of dorsal root ganglion neurons. Despite the evidence of a defective proprioceptive sensory input in SN,the prominent gait and truncal ataxia raises the question of a concomitant involvement of the cerebellum. OBJECTIVE: To evaluate cerebellar atrophy in SN. METHOD: We analyzed MRI-based volumetry of anterior lobe (paleocerebellum and total cerebellum in patients with non-paraneoplastic chronic SN and compared to age- and gender-matched controls. RESULTS: Cerebellum and anterior lobe MRI volumetry were performed in 20 patients and nine controls. Mean anterior lobe and cerebellar volume were not statistically different. Three patients (15%, however, had an abnormal anterior lobe and cerebellar volume index (values outside 2.5 standard deviations. One of them also had a specific atrophy of the anterior lobe. All these patients had infectious or dysimmune associated SN. CONCLUSION: Cerebellar atrophy is infrequently associated with SN, but can be found in some patients with SN related to infectious or immune mediated conditions. It can be more prominent in the anterior lobe and may contribute to the ataxia seen in these patients.

  8. Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice.

    Science.gov (United States)

    Hoxha, Eriola; Gabriele, Rebecca M C; Balbo, Ilaria; Ravera, Francesco; Masante, Linda; Zambelli, Vanessa; Albergo, Cristian; Mitro, Nico; Caruso, Donatella; Di Gregorio, Eleonora; Brusco, Alfredo; Borroni, Barbara; Tempia, Filippo

    2017-01-01

    Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5 . The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

  9. Recurrent Ataxia in Children and Adolescents.

    Science.gov (United States)

    Salman, Michael S; Klassen, Samantha F; Johnston, Janine L

    2017-07-01

    Recurrent ataxia is encountered infrequently in clinical pediatric neurology practise and presents with diagnostic challenges. It is caused by several disorders. Our aims were to describe the epidemiology and clinical features in children with recurrent ataxia. A retrospective review was undertaken in 185 children with chronic ataxia, who presented during 1991 to 2008. Several databases were searched to ensure optimum ascertainment. Patients with brain tumors or isolated disorders of the peripheral nerves or vestibular system were excluded. Recurrent ataxia was reported in 21 patients. Their age range was between 6 and 32.75 years (males=12). The crude period prevalence rate for the 18-year study period was 7.44/100,000. Eight patients had episodic ataxia and seven had inflammatory and metabolic disorders. In the rest the etiology was unknown. Many patients presented with ataxia, dizziness, and vertigo. The frequency and duration of the ataxic episodes varied from several per day to one every few months. Other clinical features included developmental delay and seizures. Neuroimaging in episodic ataxia was normal and abnormal in inflammatory or metabolic disorders. Acetazolamide provided symptomatic relief in patients with episodic ataxia, while steroids were beneficial in patients with an inflammatory etiology. One child with a metabolic disorder died. Recurrent ataxia is an uncommon presentation in children and mortality is rare. Genetic, metabolic, and inflammatory disorders should be considered in these patients. Neuroimaging is essential. Acetazolamide in selected patients provides good symptomatic relief.

  10. In children with Friedreich ataxia, muscle and ataxia parameters are associated

    NARCIS (Netherlands)

    Sival, Deborah A.; Pouwels, Maria E.; van Brederode, Agnes; Maurits, Natasha M.; Verschuuren - Bemelmans, Corien C.; Brunt, Ewout R.; Sarvaas, Gideon J. Du Marchie; Verbeek, Renate J.; Brouwer, Oebele F.; van der Hoeven, Johannes H.

    Aim In children with Friedreich ataxia (FRDA), ataxia is assessed using the surrogate marker the International Cooperative Ataxia Rating Scale (ICARS). We aimed to determine whether ICARS scores in children with FRDA are confounded by muscle weakness. Method In 12 children with FRDA (10 males, two

  11. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Conditions Ataxia with vitamin E deficiency Ataxia with vitamin E deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Ataxia with vitamin E deficiency is a disorder that impairs the body's ...

  12. Genetics Home Reference: X-linked sideroblastic anemia and ataxia

    Science.gov (United States)

    ... linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open All Close All ... the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare condition characterized by ...

  13. Critical role of cerebellar fastigial nucleus in programming sequences of saccades

    Science.gov (United States)

    King, Susan A.; Schneider, Rosalyn M.; Serra, Alessandro; Leigh, R. John

    2011-01-01

    The cerebellum plays an important role in programming accurate saccades. Cerebellar lesions affecting the ocular motor region of the fastigial nucleus (FOR) cause saccadic hypermetria; however, if a second target is presented before a saccade can be initiated (double-step paradigm), saccade hypermetria may be decreased. We tested the hypothesis that the cerebellum, especially FOR, plays a pivotal role in programming sequences of saccades. We studied patients with saccadic hypermetria due either to genetic cerebellar ataxia or surgical lesions affecting FOR and confirmed that the gain of initial saccades made to double-step stimuli was reduced compared with the gain of saccades to single target jumps. Based on measurements of the intersaccadic interval, we found that the ability to perform parallel processing of saccades was reduced or absent in all of our patients with cerebellar disease. Our results support the crucial role of the cerebellum, especially FOR, in programming sequences of saccades. PMID:21950988

  14. Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

    Science.gov (United States)

    Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

    2013-08-01

    One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. © 2013 International Society for Neurochemistry.

  15. ATM (ataxia-telangiectasia mutated) abnormality and diseases

    International Nuclear Information System (INIS)

    Takagi, Masatoshi; Nakata, Shinichiro; Mizutani, Shuki

    2007-01-01

    Ataxia-Telangiectasia (A-T) is an autosomal recessive inherited disease due to mutation of ATM gene on chromosome 11q22.3, with major symptoms of ataxia, telangiectasia, immunodeficiency and frequent complication of cancer, and the cells have characters of chromosomal break, high sensitivity to radiation and inappropriate continuation of DNA synthesis after radiation. This review describes past and present studies of ATM functions with clinical features in the following order: Clinical symptoms and epidemiology; ATM gene mutation in A-T patients, mainly by frame-shift (80-90%); ATM, whose gene consisted from 66 exons (150 kb), functions in phosphoinositide-3-kinase related kinase family which protecting cells from stress and integrating their system, at response to DNA double strand break, and in the cell cycle checkpoints at G1/S, S and G2/M phases; ATM nonsense/missense mutations in embryonic cells leading to carcinogenesis and role of ATM in the suppression of carcinogenesis in somatic cells; Chromosomal translocation which relating to carcinogenesis, by functional defect of ATM; and Other functions of ATM in neuronal growth, immunodeficiency, carbohydrate and lipid metabolism, early senescence, and virus infection. ATM is thus an essential molecule to maintain growth and homeostasis. (T.I.)

  16. Radiosensitivity in ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Lavin, M.F.; Khanna, K.K.; Watters, D.

    1998-01-01

    Full text: Radiosensitivity is a major hallmark of the human genetic disorder ataxia-telangiectasia. This hypersensitivity to ionizing radiation has been demonstrated in vitro after exposure of patients to therapeutic thought to be the major factor contculture. Clearly an understanding of the nature of the molecular defect in ataxia-telangiectasia will be of considerable assistance in delineating additional pathways that determine cellular radiosensitivity/radioresistance. Furthermore, since patients with this syndrome are also predisposed to developing a number of leukaemias and lymphomas the possible connection between radiosensitivity and cancer predisposition is of interest. Now that the gene (ATM) responsible for this genetic disease has been cloned and identified, progress is being made in determining the role of the ATM protein in mediating the effects of cellular exposure to ionizing radiation and other forms of redox stress. Proteins such as the product of the tumour suppressor gene p53 and the proto-oncogene c-Abl (a protein tyrosine kinase) have been shown to interact with ATM. Since several intermediate steps in both the p53 and c-Abl pathways, activated by ionizing radiation, are known it will be possible to map the position of ATM in these pathways and describe its mechanism of action. What are the clinical implications of understanding the molecular basis of the defect in ataxia-telangiectasia? As outlined above since radiosensitivity is a universal characteristic of A-T understanding the mechanism of action of ATM will provide additional information or radiation signalling in human cells. With this information it may be possible to sensitize tumour cells to radiation and thus increase the therapeutic benefit of radiotherapy. This might involve the use of small molecules that would interfere with the normal ATM controlled pathways and thus sensitize cells to radiation or alternatively it might involve the efficient introduction of ATM anti-sense c

  17. Radiosensitivity in ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Lavin, M.F. [Royal Brisbane Hospital, QLD (Australia). Queensland Institute of Medical Research and The Department of Surgery; Khanna, K.K.; Watters, D. [Royal Brisbane Hospital, QLD (Australia). Queensland Institute of Medical Research

    1998-12-31

    Full text: Radiosensitivity is a major hallmark of the human genetic disorder ataxia-telangiectasia. This hypersensitivity to ionizing radiation has been demonstrated in vitro after exposure of patients to therapeutic thought to be the major factor contculture. Clearly an understanding of the nature of the molecular defect in ataxia-telangiectasia will be of considerable assistance in delineating additional pathways that determine cellular radiosensitivity/radioresistance. Furthermore, since patients with this syndrome are also predisposed to developing a number of leukaemias and lymphomas the possible connection between radiosensitivity and cancer predisposition is of interest. Now that the gene (ATM) responsible for this genetic disease has been cloned and identified, progress is being made in determining the role of the ATM protein in mediating the effects of cellular exposure to ionizing radiation and other forms of redox stress. Proteins such as the product of the tumour suppressor gene p53 and the proto-oncogene c-Abl (a protein tyrosine kinase) have been shown to interact with ATM. Since several intermediate steps in both the p53 and c-Abl pathways, activated by ionizing radiation, are known it will be possible to map the position of ATM in these pathways and describe its mechanism of action. What are the clinical implications of understanding the molecular basis of the defect in ataxia-telangiectasia? As outlined above since radiosensitivity is a universal characteristic of A-T understanding the mechanism of action of ATM will provide additional information or radiation signalling in human cells. With this information it may be possible to sensitize tumour cells to radiation and thus increase the therapeutic benefit of radiotherapy. This might involve the use of small molecules that would interfere with the normal ATM controlled pathways and thus sensitize cells to radiation or alternatively it might involve the efficient introduction of ATM anti-sense c

  18. Ataxias agudas en la infancia

    Directory of Open Access Journals (Sweden)

    Yaline Betancourt Fursow

    2013-09-01

    Full Text Available La ataxia cerebelosa aguda infantil (ACAI es la forma más frecuente de complicación neurológica por el virus de la varicela.Descritas dentro del grupo de las cerebelitis agudas. Los objetivos de este estudio fueron: evaluar la presentación clínica, manejo y seguimiento de niños hospitalizados con ACAI en un hospital pediátrico terciario donde la inmunización para varicela no está disponible (parte I y describir los diagnósticos diferenciales de la cerebelitis aguda (parte II. Estudiamos 95 pacientes. Los criterios diagnósticos de ataxia aguda se basaron en: pérdida aguda de la coordinación o dificultad para la marcha con o sin nistagmo asociado y duración menor de 48 horas, en un niño previamente sano. Estos criterios se cumplían en todos los casos valorados, excepto en las ataxias secundarias a ingesta de tóxicos, en los que la duración debía ser menor de 24 horas para su inclusión en el estudio. Se registraron los datos en una historia clínica pediátrica y neurológica. Entre los pacientes inmunosuprimidos la incidencia mayor fue la complicación por varicela. La mayoría de los pacientes fueron varones. El rango de edad fue la preescolar, 5 años . El intervalo entre la presentación del rash y el ingreso fue de 1 a 3 días. El estudio de LCR se practicó en 59.5% de los casos. La TAC y la resonancia magnética cerebral (RM presentaron edema en el 33.3%. El aciclovir endovenoso fue utilizado en 23 pacientes; pero no hubo diferencias significativas en las manifestaciones clínicas y seguimiento entre tratados y no tratados. La ataxia fue la primera manifestación clínica. La estadía hospitalaria fue de 4 días (rango: 2-11 días.

  19. [123I]-IMP SPECT findings in spinocerebellar ataxia type 6

    International Nuclear Information System (INIS)

    Ito, Yasuhiko; Nakabayashi, Haruo; Iguchi, Yasuyuki; Suzuki, Masahiko; Kobayashi, Masayuki; Nakajima, Takashi

    2000-01-01

    To study the dynamics of metabolic function in the cerebellar hemispheres, vermis and brain stem of patients with spinocerebellar ataxia type 6 (SCA6), we used single photon emission computed tomography (SPECT) with N-isopropyl-p-[ 123 I] iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) in six Japanese patients with SCA6 and nine normal control subjects. All patients with SCA6 were found to have expanded CAG repeats (from 22 to 24 repeats). The SPECT data were also analyzed semiquantitatively. The rCBF in the cerebellar hemisphere, vermis and brain stem was not significantly lower in patients with SCA6 than in normal controls. However, the ratio of the cerebellar hemisphere to occipital lobe (C/O ratio) was significantly lower in patients. The ratio of the vermis and brain stem to occipital lobe (V/O, P/O ratio) were not significantly lower in patients. The C/O, V/O and P/O ratio were especially sensitive indexes for regional cerebral function in patients with SCA6. Results of this study suggest that the functional decrease in SCA6 may begin in the cerebellar hemispheres. IMP SPECT was useful for evaluating rCBF in patients with SCA6. (author)

  20. Spinocerebellar ataxia type 2 neurodegeneration differentially affects error-based and strategic-based visuomotor learning.

    Science.gov (United States)

    Vaca-Palomares, Israel; Díaz, Rosalinda; Rodríguez-Labrada, Roberto; Medrano-Montero, Jacqeline; Vázquez-Mojena, Yaimé; Velázquez-Pérez, Luis; Fernandez-Ruiz, Juan

    2013-12-01

    There are different types of visuomotor learning. Among the most studied is motor error-based learning where the sign and magnitude of the error are used to update motor commands. However, there are other instances where individuals show visuomotor learning even if the sign or magnitude of the error is precluded. Studies with patients suggest that the former learning is impaired after cerebellar lesions, while basal ganglia lesions disrupt the latter. Nevertheless, the cerebellar role is not restricted only to error-based learning, but it also contributes to several cognitive processes. Therefore, here, we tested if cerebellar ataxia patients are affected in two tasks, one that depends on error-based learning and the other that prevents the use of error-based learning. Our results showed that cerebellar patients have deficits in both visuomotor tasks; however, while error-based learning tasks deficits correlated with the motor impairments, the motor error-dependent task did not correlate with any motor measure.

  1. Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment

    Directory of Open Access Journals (Sweden)

    Deborah A. Hall

    2012-05-01

    Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a progressive degenerative movement disorder characterized by kinetic tremor, cerebellar gait ataxia, parkinsonism, and cognitive decline. This disorder occurs in both males and females, frequently in families with children who have fragile X syndrome. The clinical features of this disorder, both classic and newly described, are summarized in this paper. In screening studies, fragile X mental retardation 1 (FMR1 gene premutation (55–200 CGG expansions are most frequently seen in men with ataxia who have tested negative for spinocerebellar ataxias. Since the original description, the classic FXTAS phenotype has now been reported in females and in carriers of smaller (45–54 CGG and larger (>200 CGG expansions in FMR1. Premutation carriers may present with a Parkinson disease phenotype or hypotension, rather than with tremor and/or ataxia. Parkinsonism and gait ataxia may also be seen in individuals with gray zone (41–54 CGG expansions. Studies regarding medication to treat the symptoms in FXTAS are few in number and suggest that medications targeted to specific symptoms, such as kinetic tremor or gait ataxia, may be most beneficial. Great progress has been made in regards to FXTAS research, likely given the readily available gene test and the screening of multiple family members, including parents and grandparents, of fragile X syndrome children. Expansion of genotypes and phenotypes in the disorder may suggest that a broader disease definition might be necessary in the future.

  2. The Recession Squeezes Training.

    Science.gov (United States)

    Geber, Beverly

    1991-01-01

    Recession is having an impact on training departments. Besides a slowdown, it provides managers with a chance to reevaluate programs to ensure they are attuned to the specific goals of the company. (JOW)

  3. The mechanism of ipsilateral ataxia in lacunar hemiparesis: SPECT perfusion imaging.

    Science.gov (United States)

    Yamamoto, Ryoo; Johkura, Ken; Nakae, Yoshiharu; Tanaka, Fumiaki

    2015-01-01

    Although ataxic hemiparesis is a common lacunar syndrome, the precise mechanism underlying hemiataxia is not clear. We attempted to identify ataxia-related, cerebral blood flow changes in patients presenting with ataxic hemiparesis after acute capsular infarct. We used 99mTc-ECD brain perfusion single-photon emission computed tomography to evaluate regional cerebral blood flow in 12 patients with ataxic hemiparesis caused by capsular infarct, and we compared the regional blood flow of these patients with that of 11 patients with pure motor hemiparesis caused by similar lesions. The ipsilateral red nucleus blood flow was significantly decreased in the ataxic hemiparesis patients, whereas the ipsilateral red nucleus blood flow was increased in the pure motor hemiparesis patients. Crossed cerebellar diaschisis (decreased contralateral cerebellar blood flow) was seen in ataxic hemiparesis patients; similarly, it was seen in pure motor hemiparesis patients. Our findings suggest that ataxia in hemiparetic patients with capsular infarct can be caused by ipsilateral red nucleus dysfunction secondary to cortico-rubral pathway disruption at the internal capsule.

  4. WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

    Science.gov (United States)

    Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Superior cerebellar artery infarction in endovascular treatment for tentorial dural arteriovenous fistulas

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jingbo; Lv Xianli; Jiang Chuhan; Li Youxiang [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan, Xili, Chongwen, 100050, Beijing (China); Wu Zhongxue, E-mail: ttyyzjb@sina.co [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan, Xili, Chongwen, 100050, Beijing (China)

    2010-06-15

    Background: Superior cerebellar artery (SCA) syndrome shows ipsilateral cerebellar ataxia and Horner's syndrome, contralateral superficial sensory disturbance, as well as nystagmus toward the impaired side, vertigo, and nausea. Occasionally, unilateral lesions may produce bilateral hypogeusia and contralateral hypoacusia. Objective: To report 2 patients with unilateral lower midbrain ischemic lesions of the inferior colliculus level caused by transarterial embolization for tentorial dural arteriovenous fistulas (TDAVFs). Methods: Hospital records for 21 patients with TDAVFs mainly treated by endovascular techniques between 2005 and 2008 were reviewed. Two patients with MRI evidence of unilateral SCA territory infarction were investigated. Results: Of 21 patients, 2 treated transarterially with Onyx-18 (a nonahesive liquid embolic agent) developed infarctions in the territory of SCA. One patient had lateral SCA infarction characterized by ipsilateral gait ataxia, contralateral hemihypoesthesia, with additional ipsilateral ocular motor palsy and bilateral gustatory loss. And the other patient had medial SCA infarction characterized by ipsilateral ataxia contralateral hemihypoesthesia with additional contralateral hypoacusia. Conclusion: SCA infarction can be caused by transarterial injection of Onyx-18 via SCA or the posterior cerebral artery (PCA) for TDAVFs and additionally presented with gustatory loss and deafness, which is generally not a feature of the SCA syndrome.

  6. Aspectos moleculares das ataxias espinocerebelares autossomicas recessivas

    OpenAIRE

    Flavia Chagas Costa

    2000-01-01

    Resumo: As ataxias espinocerebelares (ABC) formam um grupo heterogêneo de doenças degenerativas que envolvem o sistema nervoso central. Esse grupo se caracteriza clinicamente por apresentar disfunção cerebelar manifestada por ataxia de marcha, incoordenação e disartria. Nos casos familiares, o padrão de herança é variável, podendo ser compatível com herança autossômica dominante (HAD) ou herança autossômica recessiva (HAR). Para as ataxias espinocerebelares com HAR existem três lócus identifi...

  7. [Anaesthesia for correction of scoliosis in pediatric patient with Friedreich's ataxia].

    Science.gov (United States)

    Agámez Medina, G L; Pantin, E J; Lorthé, J; Therrien, P J

    2015-01-01

    Friedreich ataxia (FA) is an inherited autosomal recessive disease characterized by a neurological degenerative process of the cerebellum, spinal cord, and peripheral nerves. FA is associated with ataxia, dysarthria, motor and sensory impairment, scoliosis, cardiomyopathy, and diabetes. There is a significant risk of perioperative major complications during the anesthetic management of these patients. We present the case of a fourteen-year-old patient with FA, who had a posterior spinal fusion and instrumentation underwent to total intravenous anesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Modifications of resting state networks in spinocerebellar ataxia type 2.

    Science.gov (United States)

    Cocozza, Sirio; Saccà, Francesco; Cervo, Amedeo; Marsili, Angela; Russo, Cinzia Valeria; Giorgio, Sara Maria Delle Acque; De Michele, Giuseppe; Filla, Alessandro; Brunetti, Arturo; Quarantelli, Mario

    2015-09-01

    We aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables. Resting-state functional magnetic resonance imaging (RS-fMRI) data from 19 SCA2 patients and 29 healthy controls were analyzed using an independent component analysis and dual regression, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Correlations between the resting state networks alterations and disease duration, age at onset, number of triplets, and clinical score were assessed by Spearman's coefficient, for each cluster which was significantly different in SCA2 patients compared with healthy controls. In SCA2 patients, disruption of the cerebellar components of all major resting state networks was present, with supratentorial involvement only for the default mode network. When controlling at voxel level for gray matter volume, the reduction in functional connectivity in supratentorial regions of the default mode network, and in cerebellar regions within the default mode, executive and right fronto-parietal networks, was still significant. No correlations with clinical variables were found for any of the investigated resting state networks. The SCA2 patients show significant alterations of the resting state networks, only partly explained by the atrophy. The default mode network is the only resting state network that shows also supratentorial changes, which appear unrelated to the cortical gray matter volume. Further studies are needed to assess the clinical significance of these changes. © 2015 International Parkinson and Movement Disorder Society.

  9. Ataxia espinocerebelosa 7: Investigación clínica y genética en una familia argentina Spinocerebellar ataxia 7: Clinical and genetic investigation in an Argentine family

    Directory of Open Access Journals (Sweden)

    Juan I. Rojas

    2007-04-01

    Full Text Available Las ataxias espino cerebelosas (AEC, constituyen un grupo de trastornos hereditarios neurodegenerativos de herencia autosómica dominante. Se caracterizan principalmente por la presencia clínica de ataxia cerebelosa asociada a oftalmoplejía, disartria, signos piramidales o extrapiramidales y pérdida de la sensibilidad profunda. La AEC 7 pertenece al grupo de las ataxias espinocerebelosas en la cual el trastorno es consecuencia de la expansión del triplete CAG localizado en el cromosoma 3 p12-p21. La característica clínica de dicha ataxia es la pérdida de la agudeza visual y posterior ceguera. Presentamos tres individuos de una familia con ataxia cerebelosa, pérdida de la agudeza visual y otros signos neurológicos. El diagnóstico fue confirmado por medio del análisis genético en el cual se observó la anormalidad característica de la AEC 7. Este es el primer caso de AEC 7 en Argentina confirmado por estudio genético. En la revisión de la literatura (hasta enero 2006 se hallaron sólo dos familias notificadas en América Latina. El objetivo del trabajo es el de enfocar la atención en el diagnóstico de esta enfermedad degenerativa en pacientes que se presentan con ataxia cerebelosa progresiva asociada con disminución de la agudeza visual e historia familiar positiva.Spino cerebellar ataxia (SCA are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis

  10. Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent.

    Science.gov (United States)

    Paradisi, Irene; Ikonomu, Vassiliki; Arias, Sergio

    2016-03-01

    Dominantly inherited ataxias (spinocerebellar ataxias, SCAs) are a genetically heterogeneous group of neurologic diseases characterized by progressive cerebellar and spinal tract degeneration with ataxia and other signs, common to all known subtypes. Several types are relatively frequent worldwide, but in several countries, one specific SCA may show a higher prevalence owing to founder phenomena. In Venezuela, genetic epidemiological features of SCAs have been assessed during the last 30 years; mutations in ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), ATXN8 (SCA8), ATXN10 (SCA10), TBP (SCA17) and ATN1 (dentatorubral pallidoluysian atrophy, DRPLA) loci were searched among 115 independent families. SCA7 was the most frequent subtype (26.6%), followed by SCA3 (25.0%), SCA2 (21.9%), SCA1 (17.2%), SCA10 (4.7%) and DRPLA (3.1%); in 43% of the families, the subtype remained unidentified. SCA7 mutations displayed strong geographic aggregation in two independent founder foci, and SCA1 showed a very remote founder effect for a subset of families. SCA10 families were scattered across the country, but all had an identical in-phase haplotype carried also by Mexican, Brazilian and Sioux patients, supporting a very old common Amerindian origin. Prevalence for dominant SCAs in Venezuela was estimated as 1:25 000 nuclear families, provenances of which are either Caucasoid, African or Amerindian.

  11. Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

    Science.gov (United States)

    Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

    2016-04-01

    Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

  12. Genetic testing for clinically suspected spinocerebellar ataxias ...

    Indian Academy of Sciences (India)

    Mahesh

    Research Article. Genetic ... Melbourne, Australia and Department of Animal Science, School of Life .... The patients were assessed according to the International Cooperative Ataxia Rating ..... The Indian Journal of Medical Research 126(5):.

  13. Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids

    Directory of Open Access Journals (Sweden)

    M. Grazia Cotticelli

    2013-01-01

    Full Text Available Friedreich ataxia is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, dysarthria, areflexia, sensory loss, skeletal deformities, and hypertrophic cardiomyopathy. Most disease alleles have a trinucleotide repeat expansion in the first intron of the FXN gene, which decreases expression of the encoded protein frataxin. Frataxin is involved in iron–sulfur-cluster (ISC assembly in the mitochondrial matrix, and decreased frataxin is associated with ISC-enzyme and mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. To assess the role of oxidative stress in lipid peroxidation in Friedreich ataxia we used the novel approach of treating Friedreich ataxia cell models with polyunsaturated fatty acids (PUFAs deuterated at bis-allylic sites. In ROS-driven oxidation of PUFAs, the rate-limiting step is hydrogen abstraction from a bis-allylic site; isotopic reinforcement (deuteration of bis-allylic sites slows down their peroxidation. We show that linoleic and α-linolenic acids deuterated at the peroxidation-prone bis-allylic positions actively rescue oxidative-stress-challenged Friedreich ataxia cells. The protective effect of the deuterated PUFAs is additive in our models with the protective effect of the CoQ10 analog idebenone, which is thought to decrease the production of free radicals. Moreover, the administration of deuterated PUFAs resulted in decreased lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY (581/591 probe. Our results are consistent with a role for lipid peroxidation in Friedreich ataxia pathology, and suggest that the novel approach of oral delivery of isotope-reinforced PUFAs may have therapeutic potential in Friedreich ataxia and other disorders involving oxidative stress and lipid peroxidation.

  14. Gingival Recessions and Biomechanics

    DEFF Research Database (Denmark)

    Laursen, Morten Godtfredsen

    Gingival recessions and biomechanics “Tissue is the issue, but bone sets the tone.“ A tooth outside the cortical plate can result in loss of bone and development of a gingival recession. The presentation aims to show biomechanical considerations in relation to movement of teeth with gingival...... by moving the root back in the alveolus. The tooth movement is accompanied by bone gain and thus increase the success rate for soft tissue augmentation. The choice of biomechanical system influences the treatment outcome. If a standard straight wire appliance is used, a biomechanical dilemma can arise...

  15. [Ataxia telangiectasia: review of 13 new cases].

    Science.gov (United States)

    Valbuena, O; Póo, P; Campistol, J; Vernet, A; Fernández-Alvarez, E; Sierra, I; Gean, E

    1996-01-01

    We report the review of 13 patients who were diagnosed of ataxia telangiectasia before 6 years of age. All of them manifested cerebelous ataxia, oculocutaneus telangiectasias (11), sinopulmonary infections (9), dystonia (9), oculomotor apraxia (9) and Burkitt linfoma (1). We analyse the most common presentation of the disease in early stages and the complementary studies performed. The prompt diagnosis allow us a better control of infections, malignant process and finally the possibility of genetic counseling.

  16. Caffeine alleviates progressive motor deficits in a transgenic mouse model of spinocerebellar ataxia.

    Science.gov (United States)

    Gonçalves, Nélio; Simões, Ana T; Prediger, Rui D; Hirai, Hirokazu; Cunha, Rodrigo A; Pereira de Almeida, Luís

    2017-03-01

    Machado-Joseph disease (MJD) is a neurodegenerative spinocerebellar ataxia (SCA) associated with an expanded polyglutamine tract within ataxin-3 for which there is currently no available therapy. We previously showed that caffeine, a nonselective adenosine receptor antagonist, delays the appearance of striatal damage resulting from expression of full-length mutant ataxin-3. Here we investigated the ability of caffeine to alleviate behavioral deficits and cerebellar neuropathology in transgenic mice with a severe ataxia resulting from expression of a truncated fragment of polyglutamine-expanded ataxin-3 in Purkinje cells. Control and transgenic c57Bl6 mice expressing in the mouse cerebella a truncated form of human ataxin-3 with 69 glutamine repeats were allowed to freely drink water or caffeinated water (1g/L). Treatments began at 7 weeks of age, when motor and ataxic phenotype emerges in MJD mice, and lasted up to 20 weeks. Mice were tested in a panel of locomotor behavioral paradigms, namely rotarod, beam balance and walking, pole, and water maze cued-platform version tests, and then sacrificed for cerebellar histology. Caffeine consumption attenuated the progressive loss of general and fine-tuned motor function, balance, and grip strength, in parallel with preservation of cerebellar morphology through decreasing the loss of Purkinje neurons and the thinning of the molecular layer in different folia. Caffeine also rescued the putative striatal-dependent executive and cognitive deficiencies in MJD mice. Our findings provide the first in vivo demonstration that caffeine intake alleviates behavioral disabilities in a severely impaired animal model of SCA. Ann Neurol 2017;81:407-418. © 2016 American Neurological Association.

  17. Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study.

    Science.gov (United States)

    Mascalchi, Mario; Toschi, Nicola; Giannelli, Marco; Ginestroni, Andrea; Della Nave, Riccardo; Tessa, Carlo; Piacentini, Silvia; Dotti, Maria Teresa; Aiello, Marco; Nicolai, Emanuele; Soricelli, Andrea; Salvi, Fabrizio; Diciotti, Stefano

    2016-01-01

    Imaging biomarkers of disease progression are desirable in inherited ataxias. MRI has demonstrated brain damage in Friedreich ataxia (FRDA) in form of regional atrophy of the medulla, peridentate cerebellar white matter (WM) and superior cerebellar peduncles (visible in T1-weighted images) and of change of microstructural characteristics of WM tracts of the brainstem, cerebellar peduncles, cerebellum, and supratentorial structures (visible through diffusion-weighted imaging). We explored the potential of brain MR morphometry and diffusion tensor imaging (DTI) to track the progression of neurodegeneration in FRDA. Eight patients (5F, 3M; age 13.4-41.2 years) and 8 healthy controls (2F, 6M; age 26.2-48.3 years) underwent 2 MRI examinations (mean 3.9 and 4.1 years apart, respectively) on the same 1.5T scanner. The protocol included 3D T1-weighted images and axial diffusion-weighted images (b-value 1,000 s/mm(2)) for calculating maps of fractional anisotropy, mean, axial and radial diffusivity, and mode of anisotropy. Tensor-based morphometry was used to investigate regional volume changes and tract-based spatial statistics was used to investigate microstructural changes in WM tracts. Longitudinal analyses showed no differences in regional volume changes but a significant difference in axial diffusivity changes in cerebral and corpus callosum WM of patients as compared to controls (mean longitudinal rate of change for axial diffusivity: -.02 × 10(-3) mm(2)/s/year in patients vs. .01 × 10(-3) mm(2)/s/year in controls). No correlation with number of triplets, disease duration, and worsening of the clinical deficit was observed. DTI can track brain microstructural changes in FRDA and can be considered a potential biomarker of disease progression. Copyright © 2015 by the American Society of Neuroimaging.

  18. Excision of gamma-ray induced thymine lesions by preparations from ataxia telangiectasia fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Remsen, J F; Cerutti, P A [Florida Univ., Gainesville (USA). Inst. of Food and Agricultural Sciences; Florida Univ., Gainesville (USA). Dept. of Biochemistry)

    1977-04-01

    The capacity of whole cell sonicates of skin fibroblasts of normal individuals and patients with the autosomal recessive disease Ataxia telangiectasia (AT) to remove aerobic gamma-ray products of the 5,6-dihydroxydihydrothymine type (tsub(O/sub 2/)sup(..gamma..)) from exogenous DNA substrates was investigated. All four AT strains (AT CRL 1312, AT CRL 1343, AT GM 367, AT 4BI) possessed normal capabilities to excise tsub(O/sub 2/)sup(..gamma..) from irradiated bacteriophage DNA and irradiated chromatin isolated from normal and AT-skin fibroblasts.

  19. Complex partial seizures: cerebellar metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Theodore, W.H.; Fishbein, D.; Deitz, M.; Baldwin, P.

    1987-07-01

    We used positron emission tomography (PET) with (/sup 18/F)2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

  20. Selected missense mutations impair frataxin processing in Friedreich ataxia.

    Science.gov (United States)

    Clark, Elisia; Butler, Jill S; Isaacs, Charles J; Napierala, Marek; Lynch, David R

    2017-08-01

    Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. Immunocytochemical studies and subcellular fractionation were performed to study FXN import into the mitochondria and examine the mechanism by which mutations impair FXN processing. Coimmunoprecipitation was performed to study the interaction between FXN and mitochondrial processing peptidase. A proteasome inhibitor was used to model traditional therapeutic strategies. In addition, clinical profiles of subjects with and without point mutations were compared in a large natural history study. FXN I 154F and FXN G 130V missense mutations decrease FXN 81-210 levels compared with FXN WT , FXN R 165C , and FXN W 155R , but do not block its association with mitochondria. FXN I 154F and FXN G 130V also impair FXN maturation and enhance the binding between FXN 42-210 and mitochondria processing peptidase. Furthermore, blocking proteosomal degradation does not increase FXN 81-210 levels. Additionally, impaired FXN processing also occurs in fibroblasts from patients with FXN G 130V . Finally, clinical data from patients with FXN G 130V and FXN I 154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia. These data suggest that the effects on processing associated with FXN G 130V and FXN I 154F mutations lead to higher levels of partially processed FXN, which may contribute to the milder clinical phenotypes in these patients.

  1. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    Science.gov (United States)

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. First report of cerebellar abiotrophy in an Arabian foal from Argentina

    Directory of Open Access Journals (Sweden)

    S.A. Sadaba

    2016-12-01

    Full Text Available Evidence of cerebellar abiotrophy (CA was found in a six-month-old Arabian filly with signs of incoordination, head tremor, wobbling, loss of balance and falling over, consistent with a cerebellar lesion. Normal hematology profile blood test and cerebrospinal fluid analysis excluded infectious encephalitis, and serological testing for Sarcocystis neurona was negative. The filly was euthanized. Postmortem X-ray radiography of the cervical cephalic region identified not abnormalities, discounting spinal trauma. The histopathological analysis of serial transverse cerebellar sections by electron microscopy revealed morphological characteristics of apoptotic cells with pyknotic nuclei and degenerate mitochondria, cytoplasmic condensation and areas with absence of Purkinje cells, matching with CA histopathological characteristics. The indirect DNA test for CA was positive in the filly, and DNA test confirmed the CA carrier state in the parents and the recessive inheritance of the disease. To our knowledge this is the first report of a CA case in Argentina.

  3. Understanding the Pathophysiology of Spinocerebellar Ataxias through genetics, neurophysiology, structural and functional neuroimaging

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Pal

    2015-12-01

    Full Text Available Over the past 10 years a large cohort of 656 index patients with clinically suspected degenerative ataxias were clinically evaluated under various research projects. Of these, 625 index patients underwent genetic tests for the clinically suspected most probable diagnosis. A diagnosis could be achieved in 218 patients (34.9%. Among these 218 index patients, 82 each were SCA1 and SCA2, 32 were SCA3, 4 were SCA12, and 18 were Friedreich's Ataxia. Thus among the Autosomal Dominant Ataxias (SCAs there was equal prevalence of SCA1 and SCA2 (41% each followed by SCA3 (16% and SCA12 (2%. This high prevalence of SCA1 is in contrast to the available National and International literature. The rate of clinical disease progression, especially in SCA2, was dependent on the CAG repeat size, and may commence linearly from birth.Apart from cerebellar involvement, a comprehensive evaluation of the neuroaxis in various subsets of this genetically proved cohort showedsubclinicalinvolvement of the cerebral cortex, central motor and sensory pathways, peripheral nervous system and autonomic nervous system. Important findings include: (aAmixedsensorimotor and pure sensory neuropathy was seen in all the three subtypes of SCAs, while pure motor neuropathy was uncommon; (b There was reduced cortical excitability and prolonged central motor conduction time, most evident in SCA1 and least in SCA2; (c Cardiac autonomic dysfunction, predominantly parasympathetic, was seen in SCA, and the severity correlated with the duration of illness in SCA1; (d In SCA1 there was a global impairment of balance, with greater instability in anterior–posterior than medio–lateral directions; (e In all the three SCAs there was a significant loss of gray matter in both cerebellar hemispheres and vermis. Vermian atrophy was more pronounced in SCA3, while SCA1 and SCA2 had significant white matter atrophy. Pontine white matter atrophy was more pronounced in SCA2; (f Cerebellar activity was

  4. Morphometric magnetic resonance imaging and genetic testing in cerebellar abiotrophy in Arabian horses

    Science.gov (United States)

    2013-01-01

    Background Cerebellar abiotrophy (CA) is a rare but significant disease in Arabian horses caused by progressive death of the Purkinje cells resulting in cerebellar ataxia characterized by a typical head tremor, jerky head movements and lack of menace response. The specific role of magnetic resonance imaging (MRI) to support clinical diagnosis has been discussed. However, as yet MR imaging has only been described in one equine CA case. The role of MR morphometry in this regard is currently unknown. Due to the hereditary nature of the disease, genetic testing can support the diagnosis of CA. Therefore, the objective of this study was to perform MR morphometric analysis and genetic testing in four CA-affected Arabian horses and one German Riding Pony with purebred Arabian bloodlines in the third generation. Results CA was diagnosed pathohistologically in the five affected horses (2 months - 3 years) supported by clinical signs, necropsy, and genetic testing which confirmed the TOE1:g.2171G>A SNP genotype A/A in all CA-affected horses. On MR images morphometric analysis of the relative cerebellar size and relative cerebellar cerebrospinal fluid (CSF) space were compared to control images of 15 unaffected horses. It was demonstrated that in MR morphometric analyses, CA affected horses displayed a relatively smaller cerebellum compared to the entire brain mass than control animals (P = 0.0088). The relative cerebellar CSF space was larger in affected horses (P = 0.0017). Using a cut off value of 11.0% for relative cerebellar CSF space, the parameter differentiated between CA-affected horses and controls with a sensitivity of 100% and a specificity of 93.3%. Conclusions In conclusion, morphometric MRI and genetic analysis could be helpful to support the diagnosis of CA in vivo. PMID:23702154

  5. Genetics Home Reference: neuropathy, ataxia, and retinitis pigmentosa

    Science.gov (United States)

    ... Twitter Home Health Conditions NARP Neuropathy, ataxia, and retinitis pigmentosa Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that causes a variety ...

  6. Novel Mitochondrial Homoplasmic T4216C Mutation in Iranian Patients with Friedreich Ataxia

    Directory of Open Access Journals (Sweden)

    M Heidari

    2010-06-01

    Full Text Available Introduction: The mitochondrial defects in Friedreich ataxia (FRDA have been reported in many researches. Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by decreased expression of the Frataxin protein. Frataxin deficiency leads to excessive free radical production and dysfunction of respiratory chain complexes. Mitochondrial DNA (mtDNA could be considered as a candidate modifier factor for FRDA disease. It prompted us to focus on the mtDNA and monitor the nucleotide changes of genome which are probably the cause of respiratory chain defects and reduced ATP generation. Methods: We searched the mitochondrial NADH dehydroganase I (ND1 gene by PCR-TTGE and DNA fragments showing abnormal banding patterns were sequenced for the identification of exact mutations. Results: In 20 patients, we detected 3 mtDNA mutations which is novel in Friedreich ataxia. T4216C mutation results in conversion of Tyrosine to Histidine in 313 amino acid locations in ND1 and bioinformatics studies show that ND1 protein loses sixth intramembrane α chain. Conclusion: Our results showed that ND1 gene mutations in FRDA samples are higher than normal controls (P<0.001. It is possible that mutations in mtDNA could constitute a predisposing factor in combination with environmental risk factors that could affect the age of onset and rate of disease progression.

  7. Friedreich's ataxia cardiomyopathy: case based discussion and management issues.

    LENUS (Irish Health Repository)

    Hanley, A

    2010-04-01

    Cardiac involvement is common in Friedreich\\'s Ataxia and is a common cause of premature death. Evidence regarding treatment of congestive heart failure in patients with Friedreich\\'s Ataxia is lacking. The case of a 31-year-old male with advanced Friedreich\\'s Ataxia who presented with an acute diarrhoeal illness and features of acute heart failure is discussed. We then review the reported cardiac manifestations of Friedreich\\'s Ataxia and discuss management options.

  8. Clinical neurogenetics: autosomal dominant spinocerebellar ataxia.

    Science.gov (United States)

    Shakkottai, Vikram G; Fogel, Brent L

    2013-11-01

    The autosomal dominant spinocerebellar ataxias are a diverse and clinically heterogeneous group of disorders characterized by degeneration and dysfunction of the cerebellum and its associated pathways. Clinical and diagnostic evaluation can be challenging because of phenotypic overlap among causes, and a stratified and systematic approach is essential. Recent advances include the identification of additional genes causing dominant genetic ataxia, a better understanding of cellular pathogenesis in several disorders, the generation of new disease models that may stimulate development of new therapies, and the use of new DNA sequencing technologies, including whole-exome sequencing, to improve diagnosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.

    Science.gov (United States)

    Levite, Mia

    2014-08-01

    .g., chronic progressive limbic Encephalitis, Paraneoplastic Encephalitis or Herpes Simplex Virus Encephalitis), Schizophrenia, Mania, Stroke, or Sjorgen syndrome. In some patients, the anti-NMDA-NR2A/B antibodies are present in both the serum and the CSF. Some of the anti-NMDA-NR2A/B antibodies cross-react with dsDNA, while others do not. Some of the anti-NMDA-NR2A/B antibodies associate with neuropsychiatric/cognitive/behavior/mood impairments in SLE patients, while others do not. The anti-NMDA-NR2A/B antibodies can undoubtedly be very pathogenic, since they can kill neurons by activating NMDA receptors and inducing 'Excitotoxicity', damage the brain, cause dramatic decrease of membranal NMDA receptors expressed in hippocampal neurons, and also induce behavioral cognitive impairments in animal models. Yet, the concentration of the anti-NMDA-NR2A/B antibodies seems to determine if they have positive or negative effects on the activity of glutamate receptors and on the survival of neurons. Thus, at low concentration, the anti-NMDA-NR2A/B antibodies were found to be positive modulators of receptor function and increase the size of NMDA receptor-mediated excitatory postsynaptic potentials, whereas at high concentration they are pathogenic as they promote 'Excitotoxcity' through enhanced mitochondrial permeability transition. (4) Anti-mGluR1 antibodies were found thus far in very few patients with Paraneoplastic Cerebellar Ataxia, and in these patients they are produced intrathecally and therefore present in much higher levels in the CSF than in the serum. The anti-mGluR1 antibodies can be very pathogenic in the brain since they can reduce the basal neuronal activity, block the induction of long-term depression of Purkinje cells, and altogether cause cerebellar motor coordination deficits by a combination of rapid effects on both the acute and the plastic responses of Purkinje cells, and by chronic degenerative effects. Strikingly, within 30 min after injection of anti-mGluR1

  10. Hypertensive cerebellar hemorrhage and cerebellar hemorrhage caused by cryptic angioma

    International Nuclear Information System (INIS)

    Yoshida, Shinichi; Sano, Keiji; Kwak, Suyong; Saito, Isamu.

    1981-01-01

    A series of 44 patients with hypertensive cerebellar hemorrhage and nine patients with cerebellar hemorrhage caused by small angiomas is described. Hypertensive hemorrhage occurred most frequently in the patients in their seventies, whereas the onset of angioma-caused hemorrhage was often seen below the age of 40. Clinical syndromes of cerebellar hemorrhages can be categorized into three basic types: the vertigo syndrome, cerebellar dysfunction syndrome and brain stem compression syndrome. Patients with small (>= 2 cm in diameter in CT scans) and medium-sized (2 cm = 3 cm) hematomas deteriorated into unresponsive conditions and developed signs of brain stem compression. Surgical mortality was 32% in the hypertensive group, while it was 0% in the angioma group. Mortality as well as morbidity in both groups was strongly influenced by the preoperative status of consciousness. Our results suggest that substantial improvement could be obtained in the overall outcome of this disease by emergency craniectomy and removal of hematomas in all patients with large hematomas regardless of the levels of consciousness and regardless of the causes of bleeding. Furthermore, when clinical information and CT findings are suggestive of a ''cryptic'' angioma as the causative lesion, posterior fossa surgery may be indicated to extirpate the lesion, even if the hematoma is small. (author)

  11. Epigenetic remodelling and dysregulation of DLGAP4 is linked with early-onset cerebellar ataxia

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Hansen, Claus; Kim, Hyung-Goo

    2014-01-01

    Genome instability, epigenetic remodelling and structural chromosomal rearrangements are hallmarks of cancer. However, the coordinated epigenetic effects of constitutional chromosomal rearrangements that disrupt genes associated with congenital neurodevelopmental diseases are poorly understood. T...

  12. Myoclonus epilepsy and ataxia due to KCNC1 mutation

    DEFF Research Database (Denmark)

    Oliver, Karen L.; Franceschetti, Silvana; Milligan, Carol J.

    2017-01-01

    generalized spike and polyspike wave discharges, with documented photosensitivity in most. Polygraphic EEG–electromyographic studies demonstrated a cortical origin for myoclonus and striking coactivation of agonist and antagonist muscles. Magnetic resonance imaging revealed symmetrical cerebellar atrophy...... data for 20 patients with MEAK due to recurrent KCNC1 p.R320H mutation. In vitro electrophysiological studies were conducted using whole cell patch-clamp to explore biophysical properties of wild-type and mutant KV3.1 channels. Results: Symptoms began at between 3 and 15 years of age (median = 9.......5), with progressively severe myoclonus and rare tonic–clonic seizures. Ataxia was present early, but quickly became overshadowed by myoclonus; 10 patients were wheelchair-bound by their late teenage years. Mild cognitive decline occurred in half. Early death was not observed. Electroencephalogram (EEG) showed...

  13. Cerebellar arteriovenous malformations in children

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, P.D. [Sheffield Univ. (United Kingdom). Acad. Dept. of Radiol.; Blaser, S.; Armstrong, D.; Chuang, S.; Harwood-Nash, D. [Division of Neuroradiology, The Hospital for Sick Children and University of Toronto, Toronto (Canada); Humphreys, R.P. [Division of Neurosurgery, The Hospital for Sick Children and University of Toronto, Toronto (Canada)

    1998-05-01

    We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.) With 4 figs., 4 tabs., 23 refs.

  14. Cerebellar arteriovenous malformations in children

    International Nuclear Information System (INIS)

    Griffiths, P.D.; Humphreys, R.P.

    1998-01-01

    We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.)

  15. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

  16. ATP1A3 Mutation in Adult Rapid-Onset Ataxia.

    Directory of Open Access Journals (Sweden)

    Kathleen J Sweadner

    Full Text Available A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the α3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid-onset dystonia-parkinsonism (RDP with a similar age and speed of onset, as well as severe diseases of infancy. The patient's ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4, a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1 deletes a motif with multiple copies and is unlikely to be causative.

  17. Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): revisited.

    Science.gov (United States)

    Niu, Yu-Qiong; Yang, Jin-Chen; Hall, Deborah A; Leehey, Maureen A; Tassone, Flora; Olichney, John M; Hagerman, Randi J; Zhang, Lin

    2014-04-01

    Parkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures. Thirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). The FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor. Parkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. [Local ice application in therapy of kinetic limb ataxia. Clinical assessment of positive treatment effects in patients with multiple sclerosis].

    Science.gov (United States)

    Albrecht, H; Schwecht, M; Pöllmann, W; Parag, D; Erasmus, L P; König, N

    1998-12-01

    Upper limb ataxia is one of the most disabling symptoms of patients with multiple sclerosis (MS). There are some clinically tested therapeutic strategies, especially with regard to cerebellar tremor. But most of the methods used for treatment of limb ataxia in physiotherapy and occupational therapy are not systematically evaluated, e.g. the effect of local ice applications, as reported by MS patients and therapists, respectively. We investigated 21 MS patients before and in several steps 1 up to 45 min after cooling the most affected forearm. We used a series of 6 tests, including parts of neurological status and activities of daily living as well. At each step skin temperature and nerve conduction velocity were recorded. All tests were documented by video for later offline analysis. Standardized evaluation was done by the investigators and separately by an independent second team, both of them using numeric scales for quality of performance. After local cooling all patients showed a positive effect, especially a reduction of intentional tremor. In most cases this effect lasted 45 min, in some patients even longer. We presume that a decrease in the proprioceptive afferent inflow-induced by cooling-may be the probable cause of this reduction of cerebellar tremor. Patients can use ice applications as a method of treating themselves when a short-time reduction of intention tremor is required, e.g. for typing, signing or self-catheterization.

  19. A V1143F mutation in the neuronal-enriched isoform 2 of the PMCA pump is linked with ataxia.

    Science.gov (United States)

    Vicario, Mattia; Zanni, Ginevra; Vallese, Francesca; Santorelli, Filippo; Grinzato, Alessandro; Cieri, Domenico; Berto, Paola; Frizzarin, Martina; Lopreiato, Raffaele; Zonta, Francesco; Ferro, Stefania; Sandre, Michele; Marin, Oriano; Ruzzene, Maria; Bertini, Enrico; Zanotti, Giuseppe; Brini, Marisa; Calì, Tito; Carafoli, Ernesto

    2018-04-12

    The fine regulation of intracellular calcium is fundamental for all eukaryotic cells. In neurons, Ca 2+ oscillations govern the synaptic development, the release of neurotransmitters and the expression of several genes. Alterations of Ca 2+ homeostasis were found to play a pivotal role in neurodegenerative progression. The maintenance of proper Ca 2+ signaling in neurons demands the continuous activity of Ca 2+ pumps and exchangers to guarantee physiological cytosolic concentration of the cation. The plasma membrane Ca 2+ ATPases (PMCA pumps) play a key role in the regulation of Ca 2+ handling in selected sub-plasma membrane microdomains. Among the four basic PMCA pump isoforms existing in mammals, isoforms 2 and 3 are particularly enriched in the nervous system. In humans, genetic mutations in the PMCA2 gene in association with cadherin 23 mutations have been linked to hearing loss phenotypes, while those occurring in the PMCA3 gene were associated with X-linked congenital cerebellar ataxias. Here we describe a novel missense mutation (V1143F) in the calmodulin binding domain (CaM-BD) of the PMCA2 protein. The mutant pump was present in a patient showing congenital cerebellar ataxia but no overt signs of deafness, in line with the absence of mutations in the cadherin 23 gene. Biochemical and molecular dynamics studies on the mutated PMCA2 have revealed that the V1143F substitution alters the binding of calmodulin to the CaM-BD leading to impaired Ca 2+ ejection. Copyright © 2018. Published by Elsevier Inc.

  20. A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia.

    Science.gov (United States)

    Tsoi, Ho; Yu, Allen C S; Chen, Zhefan S; Ng, Nelson K N; Chan, Anne Y Y; Yuen, Liz Y P; Abrigo, Jill M; Tsang, Suk Ying; Tsui, Stephen K W; Tong, Tony M F; Lo, Ivan F M; Lam, Stephen T S; Mok, Vincent C T; Wong, Lawrence K S; Ngo, Jacky C K; Lau, Kwok-Fai; Chan, Ting-Fung; Chan, H Y Edwin

    2014-09-01

    Spinocerebellar ataxias (SCAs) are a group of clinically and genetically diverse and autosomal-dominant disorders characterised by neurological deficits in the cerebellum. At present, there is no cure for SCAs. Of the different distinct subtypes of autosomal-dominant SCAs identified to date, causative genes for only a fraction of them are currently known. In this study, we investigated the cause of an autosomal-dominant SCA phenotype in a family that exhibits cerebellar ataxia and pontocerebellar atrophy along with a global reduction in brain volume. Whole-exome analysis revealed a missense mutation c.G1391A (p.R464H) in the coding region of the coiled-coil domain containing 88C (CCDC88C) gene in all affected individuals. Functional studies showed that the mutant form of CCDC88C activates the c-Jun N-terminal kinase (JNK) pathway, induces caspase 3 cleavage and triggers apoptosis. This study expands our understanding of the cause of autosomal-dominant SCAs, a group of heterogeneous congenital neurological conditions in humans, and unveils a link between the JNK stress pathway and cerebellar atrophy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Functional interaction and cross-tolerance between ethanol and Δ9-THC: possible modulation by mouse cerebellar adenosinergic A1/GABAergic-A receptors.

    Science.gov (United States)

    Dar, M Saeed

    2014-08-15

    We have previously shown a functional motor interaction between ethanol and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) that involved cerebellar adenosinergic A1 and GABAergic A receptor modulation. We now report the development of cross-tolerance between intracerebellar Δ(9)-THC and intraperitoneal ethanol using ataxia as the test response in male CD-1 mice. The drugs [Δ(9)-THC (20 μg), N(6)-cyclohexyladenosine, CHA (12 ng), muscimol (20 ng)] used in the study were directly microinfused stereotaxically via guide cannulas into the cerebellum except ethanol. Δ(9)-THC, infused once daily for 5 days followed 16 h after the last infusion by acute ethanol (2g/kg) and Rotorod evaluation, virtually abolished ethanol ataxia indicating development of cross-tolerance. The cross-tolerance was also observed when the order of ethanol and Δ(9)-THC treatment was reversed, i.e., ethanol injected once daily for 5 days followed 16 h after the last ethanol injection by Δ(9)-THC infusion. The cross-tolerance appeared within 24-48 h, lasted over 72 h and was maximal in 5-day ethanol/Δ(9)-THC-treated animals. Finally, tolerance in chronic ethanol/Δ(9)-THC/-treated animals developed not only to ethanol/Δ(9)-THC-induced ataxia, respectively, but also to the ataxia potentiating effect of CHA and muscimol, indicating modulation by cerebellar adenosinergic A1 and GABAA receptors. A practical implication of these results could be that marijuana smokers may experience little or no negative effects such as ataxia following alcohol consumption. Clinically, such antagonism of ethanol-induced ataxia can be observed in marijuana users thereby encouraging more alcohol consumption and thus may represent a risk factor for the development of alcoholism in this segment of population. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Directory of Open Access Journals (Sweden)

    Matthis Synofzik

    2014-01-01

    Full Text Available The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”. The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability. Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease.

  3. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice.

    Science.gov (United States)

    Foote, Molly; Arque, Gloria; Berman, Robert F; Santos, Mónica

    2016-10-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

  4. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Science.gov (United States)

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  5. Ataxia with Parkinsonism and dystonia after intentional inhalation of liquefied petroleum gas

    Directory of Open Access Journals (Sweden)

    Godani M

    2015-05-01

    Full Text Available Massimiliano Godani,1 Francesca Canavese,1 Sonia Migliorini,2 Massimo Del Sette1 1Neurology Unit, 2Department of Neuroradiology, Sant’Andrea Hospital, La Spezia, Italy Abstract: The practice of inhaling liquefied petroleum gas (LPG to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication. Keywords: ataxia, Parkinsonism, dystonia, liquefied petroleum gas

  6. Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

    Science.gov (United States)

    McFarland, Karen N.; Liu, Jilin; Landrian, Ivette; Zeng, Desmond; Raskin, Salmo; Moscovich, Mariana; Gatto, Emilia M.; Ochoa, Adriana; Teive, Hélio A. G.; Rasmussen, Astrid; Ashizawa, Tetsuo

    2014-01-01

    Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confers a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling. PMID:24318420

  7. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice

    Science.gov (United States)

    Foote, Molly; Arque, Gloria; Berman, Robert F.; Santos, Mónica

    2016-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that affects some carriers of the Fragile X premutation (PM). In PM carriers there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the Fragile X Mental Retardation Protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that cause PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically we will discuss the construct, face and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms and potential treatments. PMID:27255703

  8. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7.

    Science.gov (United States)

    Rüb, Udo; Schöls, Ludger; Paulson, Henry; Auburger, Georg; Kermer, Pawel; Jen, Joanna C; Seidel, Kay; Korf, Horst-Werner; Deller, Thomas

    2013-05-01

    The spinocerebellar ataxias type 1 (SCA1), 2 (SCA2), 3 (SCA3), 6 (SCA6) and 7 (SCA7) are genetically defined autosomal dominantly inherited progressive cerebellar ataxias (ADCAs). They belong to the group of CAG-repeat or polyglutamine diseases and share pathologically expanded and meiotically unstable glutamine-encoding CAG-repeats at distinct gene loci encoding elongated polyglutamine stretches in the disease proteins. In recent years, progress has been made in the understanding of the pathogenesis of these currently incurable diseases: Identification of underlying genetic mechanisms made it possible to classify the different ADCAs and to define their clinical and pathological features. Furthermore, advances in molecular biology yielded new insights into the physiological and pathophysiological role of the gene products of SCA1, SCA2, SCA3, SCA6 and SCA7 (i.e. ataxin-1, ataxin-2, ataxin-3, α-1A subunit of the P/Q type voltage-dependent calcium channel, ataxin-7). In the present review we summarize our current knowledge about the polyglutamine ataxias SCA1, SCA2, SCA3, SCA6 and SCA7 and compare their clinical and electrophysiological features, genetic and molecular biological background, as well as their brain pathologies. Furthermore, we provide an overview of the structure, interactions and functions of the different disease proteins. On the basis of these comprehensive data, similarities, differences and possible disease mechanisms are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. A rare neurocutaneous syndrome and a rare association | Ali ...

    African Journals Online (AJOL)

    Among the many causes of ataxia, Ataxia -telangictasia is an autosomal recessive1, multi system disease affecting the skin, nervous system & immune system. It's prevalence has been estimated at 1 to 2 per 100,000 It is a neurodegenerative disorder2 in which there is progressive cerebellar ataxia, occulocutaneous ...

  10. Characteristics of gait ataxia in δ2 glutamate receptor mutant mice, ho15J.

    Directory of Open Access Journals (Sweden)

    Eri Takeuchi

    Full Text Available The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.

  11. The "butterfly diagram": A gait marker for neurological and cerebellar impairment in people with multiple sclerosis.

    Science.gov (United States)

    Kalron, Alon; Frid, Lior

    2015-11-15

    People with multiple sclerosis (PwMS) frequently experience walking and balance impairments. In our previous report, we demonstrated that spatio-temporal gait parameters, collected by the Zebris FDM-T instrumented treadmill (Zebris Medical GmbH, Germany), serve as valid markers of neurological impairment in the MS population. In the current study, we focused on a unique outcome statistic of the instrumented treadmill, the "butterfly" diagram which reflects the variability of the center of pressure trajectory during walking. Therefore, the aim of the study was to examine the relationship between parameters related to the gait butterfly diagram and the level of neurological impairment in PwMS. Specifically we examined whether the gait butterfly parameters can differentiate between MS patients with normal cerebellar function and those suffering from ataxia. Demographic, neurological and gait parameters were collected from 341 PwMS, 213 women, aged 42.3 (S.D.=13.8). MS participants with ataxia demonstrated higher scores relating to the butterfly gait variability parameters compared to PwMS with normal or slightly abnormal cerebellar function. According to the results of the binary regression analysis, gait variability in the ant-post direction was found to explain 18.1% of the variance related to cerebellar function; R(2)=0.181, χ(2)(1)=67.852, P<0.001. Measurements derived from the butterfly diagram are proper estimators for important neurological functions in PwMS and should be considered in order to improve diagnosis and assessment of the MS population. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Cerebellar mutism--report of four cases.

    Science.gov (United States)

    Ozimek, A; Richter, S; Hein-Kropp, C; Schoch, B; Gorissen, B; Kaiser, O; Gizewski, E; Ziegler, W; Timmann, D

    2004-08-01

    The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

  13. Massive cerebellar infarction: a neurosurgical approach

    Directory of Open Access Journals (Sweden)

    Salazar Luis Rafael Moscote

    2015-12-01

    Full Text Available Cerebellar infarction is a challenge for the neurosurgeon. The rapid recognition will crucial to avoid devastating consequences. The massive cerebellar infarction has pseudotumoral behavior, should affect at least one third of the volume of the cerebellum. The irrigation of the cerebellum presents anatomical diversity, favoring the appearance of atypical infarcts. The neurosurgical management is critical for massive cerebellar infarction. We present a review of the literature.

  14. Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.

    Science.gov (United States)

    Kopelman, M D; Reed, L J; Marsden, P; Mayes, A R; Jaldow, E; Laing, H; Isaac, C

    2001-01-01

    A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.

  15. Copper : recession and recovery

    International Nuclear Information System (INIS)

    Warwick-Ching, T.

    2002-01-01

    In 2002, the world output for copper will fall for the first time in nearly a decade because of financial pressure and voluntary constraints. Cutbacks at copper mines amount to 760,000 tonnes per year. These cutbacks have occurred mostly in the United States which holds the largest share of high cost mines. This paper discussed recent developments in both copper supply and demand. The United States is unique as both a large consumer and producer of copper. At 1.35 million tonnes, US mine output in 2001 was at its lowest since 1987. The cutbacks in mining in general were described in this paper with particular reference to the huge loss of mining and metallurgical activity in the United States during a prolonged period of low prices in the mid 1980s. The author noted that this period was followed by an exceptional decade when much of the industry rebounded. Only 8 mines closed outright in the United States and a handful in Canada since the recession of the 1980s, but that is partly because mines got bigger and there are fewer small mines in North America. There are only 4 electrolytic refineries and 3 smelters still active in the entire United States, of which 2 are operating at a fraction of capacity. It was noted that only the buoyancy of China prevented a much bigger decline in copper demand on a global scale

  16. Treatment for ataxia in multiple sclerosis.

    Science.gov (United States)

    Mills, R J; Yap, L; Young, C A

    2007-01-24

    Disabling tremor or ataxia is common in multiple sclerosis (MS) and up to 80% of patients experience tremor or ataxia at some point during their disease. A variety of treatments are available, ranging from pharmacotherapy or stereotactic neurosurgery to neurorehabilitation. To assess the efficacy and tolerability of both pharmacological and non-pharmacologic treatments of ataxia in patients with MS. The following electronic resources were searched: Cochrane MS Group trials register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2006), National Health Service National Research Register (NRR) including the Medical Research Council Clinical Trials Directory (Issue 2, 2006), MEDLINE (January 1996 to June 2006), and EMBASE (Jan 1988 to June 2006). Manual searches of bibliographies of relevant articles, pertinent medical and neurology journals and abstract books of major neurology and MS conferences (2001-2006) were also performed. Direct communication with experts and drug companies was sought. Blinded, randomised trials which were either placebo-controlled or which compared two or more treatments were included. Trials testing pharmacological agents must have had both participant and assessor blinding. Trials testing surgical interventions or effects of physiotherapy, where participants could not have been blinded to the treatment, must have had independent assessors who were blinded to the treatment. Cross-over trials were included. Three independent reviewers extracted data and the findings of the trials were summarised. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. Ten randomised controlled trials met the inclusion criteria. Six placebo-controlled studies (pharmacotherapy) and four comparative studies (one stereotactic neurosurgery and three neurorehabilitation) were reviewed. No standardised outcome measures were used across the studies. In

  17. Gait rehabilitation in a patient affected with Charcot-Marie-Tooth disease associated with pyramidal and cerebellar features and blindness.

    Science.gov (United States)

    Vinci, Paolo

    2003-05-01

    Charcot-Marie-Tooth (CMT) disease, an inherited neuropathy characterized by length-dependent degeneration of the motor and sensory nerve fibers with consequent distal muscle atrophy and sensory reduction, can be associated with symptoms and signs of involvement of the central nervous system and/or cranial nerves. We present a patient with relatively severe CMT, cerebellar ataxia, pyramidal involvement, and blindness due to Leber's hereditary optic neuropathy. The patient presented with poor standing and gait, with consequent severe disability. Factors responsible for the patient's functional impairment (plantarflexor failure, footdrop, foot rotation, knee flexor contracture, poor proprioception, cerebellar dysfunction, spastic paraparesis, blindness) were identified and addressed by a rehabilitation management, which included, as a main intervention, ankle stabilization by drop-foot boots instead of ankle-foot orthoses. Improved balance and independent ambulation resulted from rehabilitation.

  18. Headache and Central Positioning Vertigo in a Middle Aged Female-a Case of Solitary Cerebellar Tuberculoma Involving Left Cerebellar Hemisphere

    Directory of Open Access Journals (Sweden)

    Shakya Bhattacharjee

    2012-03-01

    Full Text Available A 48 year old female presented with headache and an illusory sensation of spinning of head in respect to environment for last 8 weeks. Her head spinning or vertigo had no particular direction or not precipitated by any specific head posture. Headache is non- specific in nature and intensified in last few days.Her neurological examination revealed a central positional vertigo with horizontal gaze evoked nystagmus and ataxia. Her MRI scan brain showed the presence of a large solitary ring enhancing lesion in the left cerebellar hemisphere. The lesion was surgically excised and was examined histopathologicaliy that revealed a chronic inflammatory granuloma with caseation necrosis and multinucleated giant cells suggestive of tuberculosis

  19. What Caused the Great Recession?

    OpenAIRE

    Homburg, Stefan

    2014-01-01

    This paper examines five possible explanations for the Great Recession of 2008 and 2009, using data for the United States and the eurozone. Of these five hypotheses, four are not supported by the data, while the fifth appears reasonable.

  20. An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study

    DEFF Research Database (Denmark)

    Steenweg, Marjan E; Jakobs, Cornelis; Errami, Abdellatif

    2010-01-01

    L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of ...

  1. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA

    NARCIS (Netherlands)

    van Berge, Laura; Dooves, Stephanie; van Berkel, Carola G. M.; Polder, Emiel; van der Knaap, Marjo S.; Scheper, Gert C.

    2012-01-01

    LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the

  2. Cognitive Impairments in Multiple System Atrophy of the Cerebellar Type

    Directory of Open Access Journals (Sweden)

    Hyun J. Hong

    2011-05-01

    Full Text Available Background and Purpose We investigated the cognitive profiles in a large sample of patients with multiple system atrophy-cerebellar ataxia (MSA-C and compared directly them in patients with clinical diagnosis of probable MSA-C without dementia and control subjects with intact cognition. Methods We prospectively enrolled 26 patients with clinical diagnosis of probable MSA-C. All patients underwent a standardized neuropsychological test of the Seoul Neuropsychological Screening Battery. Results The score of Korean version of the Mini- Mental State Examination was significantly lower in patients with MSA-C (27.2 ± 2.5 than in control subjects (28.9 ± 1.0, p = 0.003. Patients with MSA-C showed a significantly worse performance in visuospatial function, 3 words recall, verbal immediate, delayed and recognition memory, visual delayed memory, phonemic and sementic Controlled Oral Word Association Test, and ideomotor praxis (p < 0.05. Conclusions Patients with MSA-C show more severe and more widespread cognitive dysfunctions than controls. Our results also indicate that cognitive dysfunction in patients with MCA-C is suggestive of disruption of the cerebellocortical circuits.

  3. Cerebellar neurodegeneration in the absence of microRNAs

    Science.gov (United States)

    Schaefer, Anne; O'Carroll, Dónal; Tan, Chan Lek; Hillman, Dean; Sugimori, Mutsuyuki; Llinas, Rodolfo; Greengard, Paul

    2007-01-01

    Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell–specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders. PMID:17606634

  4. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

    International Nuclear Information System (INIS)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

    1997-01-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  5. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi`s anemia

    Energy Technology Data Exchange (ETDEWEB)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F. [Institut Curie-Recherche, UMR 218, CNRS, 75 - Paris (France)

    1997-03-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to {gamma}-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  6. MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Vahid Ezzatizadeh

    Full Text Available Friedreich ataxia (FRDA, the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions.To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription.Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.

  7. MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia

    Science.gov (United States)

    Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Anjomani-Virmouni, Sara; Al-Mahdawi, Sahar; Pook, Mark A.

    2014-01-01

    Background Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. PMID:24971578

  8. Investigation of Exon 1 in FXN Gene in Patients with Clinical Symptomatic of Friedreich Ataxia

    Directory of Open Access Journals (Sweden)

    Naseroleslami M

    2013-01-01

    Full Text Available Background and Objectives: Friedreich’s ataxia (FRDA is an autosomal recessive disorder that is typically associated with dysarthria, muscle weakness, spasticity in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Approximately two-thirds of these patients suffer from cardiomyopathy and more than 30% have diabetes mellitus. Individuals with FRDA have identifiable mutations in the FXN gene. The most common type of mutation which is observed on both alleles in more than 98% of patients is an expansion of a GAA triplet-repeat in intron of FXN gene. Approximately 2% of individuals with FRDA are compound heterozygotes, who have a GAA expansion in the disease-causing range in one FXN allele and an inactivating FXN mutation in another allele. Aim of the present study was to investigate exon 1 in FRDA gene in patients with clinical symptoms of Friedreich’s Ataxia that have not GAA triplet-repeat expansion in intron 1 of FXN gene.Methods: In this study, exon 1 in 5 patients suspected of FRDA analyzed using PCR and sequencing. Results: An A to G transition at nucleotide number 815284, in exon 1 was observed in all patients. Conclusion: The results of this study showed that disease-causing homozygous mutations could be because of consanguinity marriage in Iran. Therefore, sequencing of all exons of the gene is necessary.

  9. The Great Recession was not so Great

    NARCIS (Netherlands)

    van Ours, J.C.

    2015-01-01

    The Great Recession is characterized by a GDP-decline that was unprecedented in the past decades. This paper discusses the implications of the Great Recession analyzing labor market data from 20 OECD countries. Comparing the Great Recession with the 1980s recession it is concluded that there is a

  10. Cerebellar atrophy in epileptic patients

    International Nuclear Information System (INIS)

    Taneva, N.

    1991-01-01

    52 patients with epileptic seizures of different form, frequency and duration who had received long term treatment with anticonvulsive drugs were examined on Siretom 2000, a brain scanner of II generation. 6 standard incisions were made in all patients in the area of cerebellum, side ventricules and high convexity. Additional scanning with an incision width of 5 mm was made when pathological changes were detected. There were found 3 cases of cerebellar atrophy, 3 - cerebral atrophy, 1 - combined atrophy and 4 - with other changes. It was difficult to establish any relation between the rerebellar atrophy and the type of anticonvulsant used because treatment had usually been complex. 1 fig., 1 tab., 4 refs

  11. Learning of Sensory Sequences in Cerebellar Patients

    Science.gov (United States)

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  12. Ataxia caused by amiodarone in older people.

    Science.gov (United States)

    Hindle, J V; Ibrahim, Amin; Ramaraj, Radhakrishnan

    2008-05-01

    Amiodarone is recommended for the cardioversion of atrial fibrillation and prevention of paroxysmal atrial fibrillation in patients with structural heart disease, coronary artery disease or left ventricular dysfunction. It has well-recognised side-effects on the skin, lungs, liver, thyroid and eyes. Neurological side-effects, including ataxia and neuropathy, also occur, and may be more prevalent in older patients. These side-effects are reversible after cessation of amiodarone. Monitoring of amiodarone therapy should include assessment of the central and peripheral nervous system especially in older patients.

  13. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  14. The bihemispheric posterior inferior cerebellar artery

    International Nuclear Information System (INIS)

    Cullen, Sean P.; Ozanne, Augustin; Alvarez, Hortensia; Lasjaunias, Pierre

    2005-01-01

    Rarely, a solitary posterior inferior cerebellar artery (PICA) will supply both cerebellar hemispheres. We report four cases of this variant. We present a retrospective review of clinical information and imaging of patients undergoing angiography at our institution to identify patients with a bihemispheric PICA. There were four patients: three males and one female. One patient presented with a ruptured arteriovenous malformation, and one with a ruptured aneurysm. Two patients had normal angiograms. The bihemispheric PICA was an incidental finding in all cases. The bihemispheric vessel arose from the dominant left vertebral artery, and the contralateral posterior inferior cerebellar artery was absent or hypoplastic. In all cases, contralateral cerebellar supply arose from a continuation of the ipsilateral PICA distal to the choroidal point and which crossed the midline dorsal to the vermis. We conclude that the PICA may supply both cerebellar hemispheres. This rare anatomic variant should be considered when evaluating patients with posterior fossa neurovascular disease. (orig.)

  15. Ataxia rating scales are age-dependent in healthy children

    NARCIS (Netherlands)

    Brandsma, Rick; Spits, Anne H.; Kuiper, Marieke J.; Lunsing, Roelinka J.; Burger, Huibert; Kremer, Hubertus P.; Sival, Deborah A.

    AIM: To investigate ataxia rating scales in children for reliability and the effect of age and sex. METHOD: Three independent neuropaediatric observers cross-sectionally scored a set of paediatric ataxia rating scales in a group of 52 healthy children (26 males, 26 females) aged 4 to 16 years (mean

  16. Ataxia rating scales are age-dependent in healthy children

    NARCIS (Netherlands)

    Brandsma, Rick; Spits, Anne H.; Kuiper, Marieke J.; Lunsing, Roelinka J.; Burger, Huibert; Kremer, Hubertus P.; Sival, Deborah A.; Barisic, N.; Baxter, P.; Brankovic-Sreckovic, V.; Calabrò, G. E.; Catsman-Berrevoets, C.; de Coo, Ifm; Craiu, D.; Dan, B.; Gburek-Augustat, J.; Kammoun-Feki, F.; Kennedy, C.; Mancini, F.; Mirabelli-Badenier, M.; Nemeth, A.; Newton, R.; Poll-The, B. T.; Steinlin, M.; Synofzik, M.; Topcu, M.; Triki, C.; Valente, E. M.

    2014-01-01

    To investigate ataxia rating scales in children for reliability and the effect of age and sex. Three independent neuropaediatric observers cross-sectionally scored a set of paediatric ataxia rating scales in a group of 52 healthy children (26 males, 26 females) aged 4 to 16 years (mean age 10y 5mo

  17. Fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Hoem, Gry; Koht, Jeanette

    2017-10-31

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a hereditary neurodegenerative disorder caused by a mutation on the X chromosome. The major signs and symptoms are tremor, ataxia and parkinsonism. Up to one in 2 000 persons over 50 years of age will develop the syndrome. There is reason to believe that too few individuals in Norway undergo testing for this condition.

  18. Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

    Science.gov (United States)

    Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

    2002-11-01

    Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

  19. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    2015-01-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar

  20. Etiology, Localization and Prognosis in Cerebellar Infarctions

    Directory of Open Access Journals (Sweden)

    Yavuz Yücel

    2006-01-01

    Full Text Available Cerebrovasculer disease are the most frequent disease of the brain. Cerebellar infarct remains % 1.5-4.2 of these diseases. Etiological factors, lesion localization, symptoms and findings and relationship with prognosis of our patients with cerebellar infarct were investigated in our study. For this purpose, 32 patients were evaluated who were admitted to the Dicle University Medical School Department of Neurology in 1995-2001 hospitalized with the diagnosis of clinically and radiological confirmed cerebellar infarction.All of patients in the study group, 21 (%65.6 were male and 11 (%34.3 female. Age of overall patients ranged between 40 and 75 years with a mean of 57.8±10.2 years. Atherothrombotic infarct was the most frequent reason at the etiologic clinical classification. The most frequently found localization was the posterior inferior cerebellar artery infarct (%50. The leading two risk factors were hypertension (%78.1 and cigarette smoking (%50. The most common sign and symptoms were vertigo (%93.7, vomiting (%75, headache (%68.7 and cerebellar dysfunction findings (%50. The mean duration of hospitalization was 16.3±7.6 days. Overall mortality rate was found to be % 6.2. Finally, the most remarkable risk factors at cerebellar infarct patients are hypertension and atherosclerosis at etiology. We are considering that, controlling of these factors will reduce the appearance frequency of cerebellar infarcts.

  1. Origin, lineage and function of cerebellar glia.

    Science.gov (United States)

    Buffo, Annalisa; Rossi, Ferdinando

    2013-10-01

    The glial cells of the cerebellum, and particularly astrocytes and oligodendrocytes, are characterized by a remarkable phenotypic variety, in which highly peculiar morphological features are associated with specific functional features, unique among the glial cells of the entire CNS. Here, we provide a critical report about the present knowledge of the development of cerebellar glia, including lineage relationships between cerebellar neurons, astrocytes and oligodendrocytes, the origins and the genesis of the repertoire of glial types, and the processes underlying their acquisition of mature morphological and functional traits. In parallel, we describe and discuss some fundamental roles played by specific categories of glial cells during cerebellar development. In particular, we propose that Bergmann glia exerts a crucial scaffolding activity that, together with the organizing function of Purkinje cells, is necessary to achieve the normal pattern of foliation and layering of the cerebellar cortex. Moreover, we discuss some of the functional tasks of cerebellar astrocytes and oligodendrocytes that are distinctive of cerebellar glia throughout the CNS. Notably, we report about the regulation of synaptic signalling in the molecular and granular layer mediated by Bergmann glia and parenchymal astrocytes, and the functional interaction between oligodendrocyte precursor cells and neurons. On the whole, this review provides an extensive overview of the available literature and some novel insights about the origin and differentiation of the variety of cerebellar glial cells and their function in the developing and mature cerebellum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. [Memory transfer in cerebellar motor learning].

    Science.gov (United States)

    Nagao, Soichi

    2012-01-01

    Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

  3. [Investigation of Genetic Aetiology in Neurodegenerative Ataxias: Recommendations from the Group of Neurogenetics of Centro Hospitalar São João, Portugal].

    Science.gov (United States)

    Gomes, Tiago; Guimaraes, Joana; Leão, Miguel

    2017-06-30

    In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information) and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

  4. Investigation of Genetic Aetiology in Neurodegenerative Ataxias: Recommendations from the Group of Neurogenetics of Centro Hospitalar São João, Portugal

    Directory of Open Access Journals (Sweden)

    Tiago Gomes

    2017-06-01

    Full Text Available In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

  5. The Great Recession: a comparison of recession magnitudes in Europe, USA and Japan

    OpenAIRE

    Mazurek, Jiří

    2013-01-01

    In this article recession magnitudes in Europe, the USA and Japan during the Great Recession are compared. The strongest recessions (of severe category) occurred in Latvia, Lithuania and Estonia, while recessions in Japan and the USA were significantly weaker. Even the strongest recession (in Latvia) was found smaller in its magnitude than the Great Depression 1929-1933 in the USA. Hence, comparisons of the Great Recession to the Great Depression in the literature are somewhat exaggerated.

  6. Expression of Caytaxin protein in Cayman Ataxia mouse models correlates with phenotype severity.

    Directory of Open Access Journals (Sweden)

    Kristine M Sikora

    Full Text Available Caytaxin is a highly-conserved protein, which is encoded by the Atcay/ATCAY gene. Mutations in Atcay/ATCAY have been identified as causative of cerebellar disorders such as the rare hereditary disease Cayman ataxia in humans, generalized dystonia in the dystonic (dt rat, and marked motor defects in three ataxic mouse lines. While several lines of evidence suggest that Caytaxin plays a critical role in maintaining nervous system processes, the physiological function of Caytaxin has not been fully characterized. In the study presented here, we generated novel specific monoclonal antibodies against full-length Caytaxin to examine endogenous Caytaxin expression in wild type and Atcay mutant mouse lines. Caytaxin protein is absent from brain tissues in the two severely ataxic Atcay(jit (jittery and Atcay(swd (sidewinder mutant lines, and markedly decreased in the mildly ataxic/dystonic Atcay(ji-hes (hesitant line, indicating a correlation between Caytaxin expression and disease severity. As the expression of wild type human Caytaxin in mutant sidewinder and jittery mice rescues the ataxic phenotype, Caytaxin's physiological function appears to be conserved between the human and mouse orthologs. Across multiple species and in several neuronal cell lines Caytaxin is expressed as several protein isoforms, the two largest of which are caused by the usage of conserved methionine translation start sites. The work described in this manuscript presents an initial characterization of the Caytaxin protein and its expression in wild type and several mutant mouse models. Utilizing these animal models of human Cayman Ataxia will now allow an in-depth analysis to elucidate Caytaxin's role in maintaining normal neuronal function.

  7. Computed tomography in alcoholic cerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Haubek, A; Lee, K [Hvidovre Hospital Copenhagen (Denmark). Dept. of Radiology; Municipal Hospital, Copenhagen (Denmark). Dept. of Neurology)

    1979-01-01

    This is a controlled CT evaluation of the infratentorial region in 41 male alcoholics under age 35. Criteria for the presence of atrophy are outlined. Twelve patients had cerebellar atrophy. Vermian atrophy was present in all. Atrophy of the cerebellar hemispheres was demonstrated in eight patients as well. The results are statistically significant when compared to an age-matched group of 40 non-alcoholic males among whom two cases of vermian atrophy were found. There were clinical signs of alcoholic cerebellar atrophy in one patient only. The disparity between the clinical and the radiological data are discussed with reference to previous pneumoencephalographic findings. (orig.) 891 AJ/orig. 892 MKO.

  8. Cerebellar injury in preterm infants.

    Science.gov (United States)

    Tam, Emily W Y

    2018-01-01

    Although preterm birth is best known to result in adverse neurodevelopmental outcomes through injury of the supratentorial structures, including intraventricular hemorrhage and periventricular leukomalacia, the cerebellum has become increasingly recognized as an important target for injury and adverse motor and cognitive outcomes. Undergoing the most dramatic growth during the preterm period, the cerebellum is vulnerable to large and small hemorrhages, as well as hypoplasia resulting from a number of potentially modifiable risk factors. These factors include contact with intraventricular blood, crossed cerebrocerebellar diaschisis, postnatal glucocorticoid exposure, pain and opioid exposure, nutrition and somatic growth, cardiorespiratory factors, and socioeconomic status. Strategies targeting these factors may result in prevention of the motor and cognitive deficits seen after cerebellar hemorrhage or hypoplasia. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Ataxia espinocerebelar tipo 6: relato de caso

    Directory of Open Access Journals (Sweden)

    Bianca Simone Zeigelboim

    2014-10-01

    Full Text Available O objetivo deste estudo foi verificar as alterações vestibulococleares observadas em um caso de ataxia espinocerebelar tipo 6. O caso foi encaminhado do Hospital de Clínicas para o Laboratório de Otoneurologia de uma Instituição de Ensino e foi submetido aos seguintes procedimentos: anamnese, inspeção otológica, avaliações audiológica e vestibular. O caso retrata uma paciente com diagnóstico genético de ataxia espinocerebelar tipo 6, do sexo feminino, com 57 anos de idade, que referiu desequilíbrio à marcha com tendência a queda para a esquerda, disartria e disfonia. Na avaliação audiológica apresentou configuração audiométrica descendente a partir da frequência de 4kHz e curva timpanométrica do tipo "A" com presença dos reflexos estapedianos bilateralmente. No exame vestibular observou-se na pesquisa da vertigem posicional presença de nistagmo vertical inferior e oblíquo, espontâneo e semiespontâneo múltiplo com características centrais (ausência de latência, paroxismo, fatigabilidade e vertigem, nistagmooptocinético abolido e hiporreflexia à prova calórica. Constataram-se alterações labirínticas que indicaram afecção do sistema vestibular central evidenciando-se a importância dessa avaliação. A existência da possível relação entre os achados com os sintomas vestibulares apresentados pela paciente apontou a relevância do exame labiríntico neste tipo de ataxia uma vez que a presença do nistagmo vertical inferior demonstrou ser frequente neste tipo de patologia.

  10. Algebra, Home Mortgages, and Recessions

    Science.gov (United States)

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  11. Genetic Counselors' Experiences Regarding Communication of Reproductive Risks with Autosomal Recessive Conditions found on Cancer Panels.

    Science.gov (United States)

    Mets, Sarah; Tryon, Rebecca; Veach, Patricia McCarthy; Zierhut, Heather A

    2016-04-01

    The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.

  12. Ataxia heredo-degenerativa associada a hipoacusia

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1964-06-01

    Full Text Available São estudados três irmãos, respectivamente com 16, 8 e 6 anos de idade, todos do sexo masculino, com ataxia heredo-degenerativa associada, em dois dêles, a hipoacusia. Nos antecedentes há referência a moléstia semelhante em um avô e um tio-avô. É discutido o diagnóstico diferencial com a moléstia de Pièrre Marie, a doença de Charcot-Marie-Tooth, a síndrome de Refsum e a neurite intersticial hipertrófica, sendo acentuada a semelhança dos casos estudados com a moléstia de Friedreich. São feitos comentários à associação da doença de Friedreich com distúrbios da audição.

  13. Research progress of spinocerebellar ataxia type 1

    Directory of Open Access Journals (Sweden)

    Lin-wei ZHANG

    2014-05-01

    Full Text Available Spinocerebellar ataxia type 1 (SCA1 is a kind of autosomal dominant genetic neurodegenerative disorder. To date, the pathogenesis of SCA1 remains unclear. Studies in numerous SCA1 experimental models, including transgenic mice, transgenic drosophila and induced pluripotent stem cells, have shown that phosphorylation of S776 in mutant ataxin-1, molecular chaperones, ubiquitin-proteasome system and down-regulation of several components of RAS-MAPK-MSK1 pathway may involve in the pathogenesis of SCA1. In this review, the clinical and pathological features of SCA1, and the latest advances of pathogenesis, model systems and therapeutic exploration will be briefly summarized. doi: 10.3969/j.issn.1672-6731.2014.05.017

  14. Complementation analysis of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Jaspers, N.G.; Painter, R.B.; Paterson, M.C.; Kidson, C.; Inoue, T.

    1985-01-01

    In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect

  15. Social and cultural elements associated with neurocognitive dysfunctions in Spinocerebellar Ataxia Type 2 patients

    Directory of Open Access Journals (Sweden)

    Roberto Emmanuele Mercadillo

    2015-06-01

    Full Text Available Spinocerebellar Ataxia Type 2 (SCA2 is a rare genetic disorder producing cerebellar degeneration and affecting motor abilities. Neuroimaging studies also show neurodegeneration in subcortical and cortical regions related to emotional and social processes. From social neuroscience it is suggested that motor and social abilities can be influenced by particular cultural dynamics so, culture is fundamental to understand the effect of brain related alterations. Here we present the first analysis about the cultural elements related to the SCA2 disorder in 15 patients previously evaluated with neuroimaging and psychometric instruments, and their nuclear relationships distributed in six geographical and cultural regions in Mexico. Ethnographic records and photographic and video archives about the quotidian participant’s routine were obtained from the patients, their relatives and their caregivers. The information was categorized and interpreted taking into consideration cultural issues and patients’ medical files. Our analyses suggest that most of the participants do not understand the nature of the disease and this misunderstanding favors magic and non-medical explanations. Patients’ testimonies suggest a decrease in pain perception as well as motor alterations that may be related to interoceptive dysfunctions. Relatives’ testimonies indicate patients’ lack of social and emotional interests that may be related to frontal, temporal and cerebellar degeneration. In general, participants use their religious beliefs to deal with the disease and only a few of them trust the health system. Patients and their families are either openly rejected and ignored, tolerated or even helped by their community accordingly to different regional traits. We propose that ethnography can provide social representations to understand the patients’ alterations, to formulate neurobiological hypotheses, to develop neurocognitive interventions, and to improve the

  16. Cerebellar mutism: review of the literature

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

    2011-01-01

    Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

  17. Neuroprotective effects of thymoquinone against cerebellar ...

    African Journals Online (AJOL)

    cerebellum mainly functions to coordinate motor functions and control ... development of the brain and life-long cognitive function [2]. ... and serial equidistant sections of the right cerebellar ... Cells outside of the left vertical and bottom bars ...

  18. Non-neoplastic gliotic cerebellar cysts

    International Nuclear Information System (INIS)

    Weisberg, L.A.

    1982-01-01

    The clinical and CT findings in 3 patients with non-neoplastic gliotic cerebellar cyst are described. CT does not permit accurate preoperative differentiation of these lesions from neoplastic disorders. (orig.)

  19. Cerebellar medulloblastoma presenting with skeletal metastasis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2004-04-01

    Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

  20. Cerebellar mutism: review of the literature

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

    2011-01-01

    Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention.......Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

  1. Recessed floating pier caps for highway bridges.

    Science.gov (United States)

    1973-01-01

    Presented are alternate designs for two existing bridges in Virginia - one with steel beams and the other with prestressed concrete beams - whereby the pier caps are recessed within the depth of the longitudinal beams. The purpose of this recession i...

  2. Differences in Physical Activity during School Recess

    Science.gov (United States)

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

    2011-01-01

    Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

  3. Efavirenz as a cause of ataxia in children

    African Journals Online (AJOL)

    more side-effects of these drugs. We report ... negative; however, a CT scan of her brain was suggestive of possible ... posterior fossa structures revealed a normal brain. .... reported dizziness, ataxia, insomnia, bad dreams and hallucinations.

  4. Seasonal ataxia: a case report of a disappearing disease

    African Journals Online (AJOL)

    Seasonal ataxia: a case report of a disappearing disease. Adebiyi Ayoade ... ological profiles of the disease. ... low serum albumin levels [8] act as a potentiating factor to trigger the ... 65% neutrophils, 25% lymphocytes,eosinophils 5% and.

  5. Electrophysiological evidence of cerebellar fiber system involvement in the Miller Fisher syndrome.

    Science.gov (United States)

    Lo, Y L; Fook-Chong, S; Chan, L L; Ong, W Y; Ratnagopal, P

    2010-01-15

    In the Miller Fisher syndrome (MFS), ataxia may be due involvement of Ia afferents and the cerebellum. Transcranial magnetic stimulation (TMS) over the cerebellum is known to interfere transiently with normal function. In this study, we utilized a previously described TMS protocol over the cerebellum in combination with ballistic movements to investigate cerebellar dysfunction in MFS patients. The agonist (biceps) reaction time in MFS patients during a motor cancellation task was not significantly reduced during the initial TMS study. However, during the repeat TMS study, significant reduction was seen for all patients, in tandem with clinical recovery. There was significant correlation between anti-GQ1b IgG titers and change in agonist reaction time between the initial and repeat TMS studies. TMS likely affected horizontally orientated parallel fibers in the cerebellar molecular layer. During disease onset, antibody binding may have interfered with facilitation of reaction time during motor cancellation tasks seen in normal subjects. Normalization of reaction time facilitation corresponded to resolution of antibody-mediated interference in the molecular layer. Our study has provided evidence suggesting parallel fiber involvement in MFS, and suggested a role of anti-GQ1b IgG antibody in these changes.

  6. Gerstmann's syndrome and unilateral optic ataxia in the emergency department

    Science.gov (United States)

    Barbosa, Breno José Alencar Pires; de Brito, Marcelo Houat; Rodrigues, Júlia Chartouni; Kubota, Gabriel Taricani; Parmera, Jacy Bezerra

    2017-01-01

    ABSTRACT. A 75-year-old right-handed woman presented to the emergency department with simultanagnosia and right unilateral optic ataxia. Moreover, the patient had agraphia, acalculia, digital agnosia and right-left disorientation, consistent with complete Gerstmann's syndrome. This case highlights the concurrence of Gerstmann's syndrome and unilateral optic ataxia in the acute phase of a left middle cerebral artery stroke. PMID:29354229

  7. Gerstmann's syndrome and unilateral optic ataxia in the emergency department

    Directory of Open Access Journals (Sweden)

    Breno José Alencar Pires Barbosa

    Full Text Available ABSTRACT. A 75-year-old right-handed woman presented to the emergency department with simultanagnosia and right unilateral optic ataxia. Moreover, the patient had agraphia, acalculia, digital agnosia and right-left disorientation, consistent with complete Gerstmann's syndrome. This case highlights the concurrence of Gerstmann's syndrome and unilateral optic ataxia in the acute phase of a left middle cerebral artery stroke.

  8. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    Science.gov (United States)

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-04-01

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits. Copyright © 2017. Published by Elsevier Inc.

  9. Genetics of recessive cognitive disorders

    OpenAIRE

    Musante, Luciana; Ropers, H. Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elu...

  10. Bilateral Cerebellar Cortical Dysplasia without Other Malformations: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Seok; Ahn Kook Jin; Kim, Jee Young; Lee, Sun Jin; Park, Jeong Mi [Catholic University Yeouido St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Recent advances in MRI have revealed congenital brain malformations and subtle developmental abnormalities of the cerebral and cerebellar cortical architecture. Typical cerebellar cortical dysplasia as a newly categorized cerebellar malformation, has been seen in patients with Fukuyama congenital muscular dystrophy. Cerebellar cortical dysplasia occurs at the embryonic stage and is often observed in healthy newborns. It is also incidentally and initially detected in adults without symptoms. To the best of our knowledge, cerebellar dysplasia without any related disorders is very rare. We describe the MRI findings in one patient with disorganized foliation of both cerebellar hemispheres without a related disorder or syndrome

  11. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

    Directory of Open Access Journals (Sweden)

    Egidio eD‘Angelo

    2013-01-01

    Full Text Available Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive and emotional functions (at least partially segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis: from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the timing and learning machine capabilities long attributed to the cerebellum, which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia and depression.

  12. Spontaneous shaker rat mutant - a new model for X-linked tremor/ataxia.

    Science.gov (United States)

    Figueroa, Karla P; Paul, Sharan; Calì, Tito; Lopreiato, Raffaele; Karan, Sukanya; Frizzarin, Martina; Ames, Darren; Zanni, Ginevra; Brini, Marisa; Dansithong, Warunee; Milash, Brett; Scoles, Daniel R; Carafoli, Ernesto; Pulst, Stefan M

    2016-05-01

    The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca(2+) transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3(R35C) function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes. © 2016. Published by The Company of Biologists Ltd.

  13. Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia

    Directory of Open Access Journals (Sweden)

    Karla P. Figueroa

    2016-05-01

    Full Text Available The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF/Brown Norwegian (BN F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm. In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R to cysteine (C change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3 gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes.

  14. Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia

    Science.gov (United States)

    Figueroa, Karla P.; Paul, Sharan; Calì, Tito; Lopreiato, Raffaele; Karan, Sukanya; Frizzarin, Martina; Ames, Darren; Zanni, Ginevra; Brini, Marisa; Dansithong, Warunee; Milash, Brett; Scoles, Daniel R.; Carafoli, Ernesto; Pulst, Stefan M.

    2016-01-01

    ABSTRACT The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes. PMID:27013529

  15. Ataxia telangiectasia: LET dependence of cellular inactivation

    International Nuclear Information System (INIS)

    Blakely, E.A.; Tobias, C.A.

    1984-01-01

    Human Ataxia telangiectasia cells (AT 2SF line) have been irradiated in vitro under aerobic and hypoxic conditions with heavy-ion beams accelerated at the Berkeley Bevalac as a part of a study to characterize the radiation responses of genetically sensitive and resistant cell lines to high LET radiations. Results from track-segment exposures to neon, silicon, argon and iron ion beams accelerated to initial energies of from 225 to 670 MeV/amu provided an LET range between 30 to 1,000 KeV/μm. The data indicate: (1) The sensitivity of AT cells increases with increasing LET, similar to resistant human lines (e.g., T-1 cells). However, due to efficient repair, T-1 cells are more resistant than AT cells at LET values below 200 keV/μm; (2) Maximum cell kill occurs for both lines at 100-200 keV/μm; at higher LET the sensitivity of the two lines approach each other; (3) There is only small variation in the sensitivity of AT cells to particles of various atomic numbers at the same LET; differences are more pronounced in the LET domain between 50 and 200 keV/μm; and (4) AT cells have slightly lower OER values than T-1 cells in the range of LET studied below 200 keV/μm

  16. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    Science.gov (United States)

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    Science.gov (United States)

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  18. Cerebellar contribution to feedforward control of locomotion.

    Science.gov (United States)

    Pisotta, Iolanda; Molinari, Marco

    2014-01-01

    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed.

  19. The trauma of a recession.

    LENUS (Irish Health Repository)

    Murphy, S M

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home\\/DIY cases and deliberate self-harm presenting in their stead.

  20. The trauma of a recession.

    Science.gov (United States)

    Murphy, S M; Kieran, I; Shaughnessy, M O

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home/DIY cases and deliberate self-harm presenting in their stead.

  1. Ataxia crónica en pediatría

    Directory of Open Access Journals (Sweden)

    Ricardo Erazo Torricelli

    2013-09-01

    Full Text Available Las ataxias crónicas constituyen un grupo heterogéneo de enfermedades, que afectan al niño a diferentes edades. Así las formas congénitas, generalmente no progresivas, se observan desde los primeros meses de vida y se expresan por hipotonía y retraso motor, mucho antes de que la ataxia se haga evidente. La resonancia magnética cerebral puede ser diagnóstica en algunos cuadros, como ocurre con el síndrome de Joubert. El grupo de ataxias hereditarias progresivas, en constante expansión, suelen comenzar después del período del lactante. Los signos clínicos destacables son la apraxia ocular y la inestabilidad de la marcha que pueden asociarse a telangiectasias oculocutáneas (ataxia-telangiectasia o a neuropatía sensitiva (ataxia de Friedreich. En esta revisión se describen en forma sucinta las ataxias congénitas y en forma más detallada las causas principales de ataxias hereditarias progresivas autosómicas recesivas, autosómicas dominantes y mitocondriales. Se destaca la importancia del estudio genético, que es la clave para lograr el diagnóstico en la mayoría de estas enfermedades. Aunque aún no hay tratamiento para la mayoría de las ataxias hereditarias progresivas, algunas sí lo tienen, como la enfermedad de Refsum, déficit de vitamina E, déficit de Coenzima Q10, por lo cual el diagnóstico en estos casos es aún más relevante. En la actualidad, el diagnóstico de los cuadros de ataxia hereditaria del niño aún no tratable es fundamental para lograr un manejo adecuado, determinar un pronóstico preciso y dar a la familia un consejo genético oportuno.

  2. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of

  3. Crossed cerebellar diaschisis in ischemic stroke

    DEFF Research Database (Denmark)

    Meneghetti, G; Vorstrup, S; Mickey, B

    1984-01-01

    Seventy measurements of CBF were performed in 12 stroke patients by 133Xe inhalation and a rapidly rotating single photon emission computerized tomograph. CBF was measured every other day during the acute phase and at 2- and 6-month follow-up visits. A persistent contralateral cerebellar blood flow....... It is concluded from this serial study that crossed cerebellar diaschisis is a common finding in completed stroke. It is probably caused by disconnection of the corticopontine pathways, a disconnection that tends to persist. The phenomenon is in fact less variable than the stroke-related CBF changes...

  4. Vascular Risk Factors and Clinical Progression in Spinocerebellar Ataxias

    Directory of Open Access Journals (Sweden)

    Raymond Y. Lo

    2015-02-01

    Full Text Available Background: The contributions of vascular risk factors to spinocerebellar ataxia (SCA are not known.Methods: We studied 319 participants with SCA 1, 2, 3, and 6 and repeatedly measured clinical severity using the Scale for Assessment and Rating of Ataxia (SARA for 2 years. Vascular risk factors were summarized by CHA2DS2-VASc scores as the vascular risk factor index. We employed regression models to study the effects of vascular risk factors on ataxia onset and progression after adjusting for age, sex, and pathological CAG repeats. Our secondary analyses took hyperlipidemia into account.Results: Nearly 60% of SCA participants were at low vascular risks with CHA2DS2-VASc = 0, and 31% scored 2 or greater. Higher CHA2DS2-VASc scores were not associated with either earlier onset or faster progression of ataxia. These findings were not altered after accounting for hyperlipidemia. Discussion: Vascular risks are not common in SCAs and are not associated with earlier onset or faster ataxia progression.

  5. Pulmonary function in adolescents with ataxia telangiectasia.

    Science.gov (United States)

    McGrath-Morrow, Sharon; Lefton-Greif, Maureen; Rosquist, Karen; Crawford, Thomas; Kelly, Amber; Zeitlin, Pamela; Carson, Kathryn A; Lederman, Howard M

    2008-01-01

    Pulmonary complications are common in adolescents with ataxia telangiectasia (A-T), however objective measurements of lung function may be difficult to obtain because of underlying bulbar weakness, tremors, and difficulty coordinating voluntary respiratory maneuvers. To increase the reliability of pulmonary testing, minor adjustments were made to stabilize the head and to minimize leaks in the system. Fifteen A-T adolescents completed lung volume measurements by helium dilution. To assess for reproducibility of spirometry testing, 10 A-T adolescents performed spirometry on three separate occasions. Total lung capacity (TLC) was normal or just mildly decreased in 12/15 adolescents tested. TLC correlated positively with functional residual capacity (FRC), a measurement independent of patient effort (R2=0.71). The majority of individuals had residual volumes (RV) greater than 120% predicted (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) values were reproducible in the 10 individuals who underwent testing on three separate occasions (R=0.97 and 0.96 respectively). Seven of the 10 adolescents had FEV1/FVC ratios>90%. Lung volume measurements from A-T adolescents revealed near normal TLC values with increased RV and decreased VC values. These findings indicate a decreased ability to expire to residual volume rather then a restrictive defect. Spirometry was also found to be reproducible in A-T adolescents suggesting that spirometry testing may be useful for tracking changes in pulmonary function over time in this population. Copyright (c) 2007 Wiley-Liss, Inc.

  6. Radiation-induced cerebellar chondrosarcoma. Case report

    International Nuclear Information System (INIS)

    Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

    1984-01-01

    The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation

  7. Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

    Directory of Open Access Journals (Sweden)

    Anatoly Buchin

    2016-08-01

    Full Text Available Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR. While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing.

  8. Cerebellar Plasticity in Health and Disease

    NARCIS (Netherlands)

    M.P.H. Coesmans (Michiel)

    2004-01-01

    textabstractThe cerebellum helps fine-tuning movements by evaluating disparities between intention and action, in order to adjust the execution of movements ‘online’, and to keep movements calibrated in the long term. The cerebellar capacity to store information, which provides the ‘memory’ needed

  9. Cerebellar malformations alter regional cerebral development.

    Science.gov (United States)

    Bolduc, Marie-Eve; Du Plessis, Adre J; Evans, Alan; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

    2011-12-01

    The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  10. Improving cerebellar segmentation with statistical fusion

    Science.gov (United States)

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-03-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  11. Ultrasonically detectable cerebellar haemorrhage in preterm infants.

    LENUS (Irish Health Repository)

    McCarthy, Lisa Kenyon

    2011-07-01

    To determine the frequency and pattern of cerebellar haemorrhage (CBH) on routine cranial ultrasound (cUS) imaging in infants of ≤32 weeks gestation, and to investigate how extremely preterm infants with CBH differ from those with severe intraventricular haemorrhage (IVH).

  12. Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Hall, Deborah A; O'Keefe, Joan A

    2013-11-01

    This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists. Copyright © 2013. Published by Elsevier Inc.

  13. Enfermedad cardiovascular en pacientes cubanos afectados por Ataxia de Friedreich.

    OpenAIRE

    Tania Cruz Mariño; Ana Luz Portelles Caminero; William Áreas Zalazar; Luís Velázquez Pérez

    2010-01-01

    Al describir la ataxia de Friedreich, Nicholaus hizo referencia a la patología cardiaca. Esta enfermedad autosómica recesiva se debe a una mutación dinámica en el gen FRDA, codificándose deficientemente la proteína Frataxina, conduciendo a estrés oxidativo y muerte celular cardiaca. La presente investigación se desarrolló con el objetivo de describir las anomalías cardiovasculares presentes en los pacientes cubanos afectados por ataxia de Friedreich. A los individuos con diagnóstico molecular...

  14. Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

    Science.gov (United States)

    Toelle, Sandra P; Poretti, Andrea; Weber, Peter; Seute, Tatjana; Bromberg, Jacoline E C; Scheer, Ianina; Boltshauser, Eugen

    2015-12-01

    Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients. Two patients had cerebellar hypoplasia (diffusely enlarged cerebellar interfoliar spaces) and three cerebellar dysmorphias involving mainly one cerebellar hemisphere. In NF1, malformative cerebellar anomalies are rare (estimated prevalence of about 1%), but most likely underestimated and easily overlooked, because physicians tend to focus on more prevalent, obvious, and well-known findings such as optic pathway gliomas, other tumors, and UBO. This kind of cerebellar anomaly in NF1 has most likely a malformative origin, but the exact pathogenesis is unknown. The individual clinical significance is difficult to determine. We suggest that cerebellar anomalies should be systematically evaluated in neuroimaging studies of NF1 patients.

  15. Subacute Cerebellar Degeneration due to a Paraneoplastic Phenomenon Associated with Metastatic Merkel Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Angelos Sharobeam

    2017-08-01

    Full Text Available Purpose: The aim of this article is to illustrate the diagnostic challenges and management of paraneoplastic neurological syndromes in Merkel cell carcinoma. Materials and Methods: We describe a previously functionally independent 85-year-old woman who presented with subacute onset of dizziness and gait ataxia in the setting of metastatic Merkel cell carcinoma. Results: Diagnosis was made on biopsy after positron emission tomography imaging revealed increased metabolic activity in 2 left inguinofemoral lymph nodes. Cerebrospinal fluid analysis was positive for anti-Hu on subsequent admission. Her functional status improved with methylprednisolone treatment and radiotherapy. Conclusion: The case highlights the challenge of the evaluation of patients who present with progressive cerebellar signs and the need to consider a paraneoplastic syndrome, especially in the setting of previous malignancy.

  16. Magnetic resonance imaging of cerebellar Schistosomiasis mansoni

    International Nuclear Information System (INIS)

    Braga, Bruno Perocco; Costa Junior, Leodante Batista da; Lambertucci, Jose Roberto

    2003-01-01

    A 15-year-old boy was admitted to hospital with a history of headache, dizziness, vomiting and double vision that started two weeks before. His parents denied any previous disease. During clinical examination he presented diplopia on lateral gaze to the left and horizontal nystagmus. No major neurological dysfunction was detected. He was well built, mentally responsive and perceptive. Laboratory findings revealed a leukocyte count of 10,000/mL, a normal red blood cell count and no eosinophilia. The magnetic resonance images (MRI) of the brain showed a left cerebellar lesion with mass effect compressing the surrounding tissues. Contrast-enhanced images showed a mass like structure and punctate nodules (Figures A and B: axial and coronal contrast-enhanced T1-weighted MR images showed the nodular - yellow arrows - enhancement pattern of a left cerebellar intraxial lesion). The lesion extended to the vermis and brachium pons and compressed the medulla. There was no hydrocephalus. He was taken to the operating room with the presumptive diagnosis of a neuroglial tumor, and submitted to a lateral suboccipital craniectomy. A brown, brittle tumoral mass without a clearly defined margin with the cerebellar tissue was removed. Microscopic examination revealed schistosomal granulomas in the productive phase in the cerebellum (Figure C). After surgery, treatment with praziquantel (50 mg/kg/dia, single dose) and prednisone (1 mg/kg/day) was offered and the patient improved quickly. Thirty days later he was seen again at the outpatient clinic: he was asymptomatic and with no neurological impairment. This is the eighth case of cerebellar involvement in schistosomiasis mansoni and the second report of a tumoral form of cerebellar schistosomiasis documented by magnetic resonance images. (author)

  17. Genetics of recessive cognitive disorders.

    Science.gov (United States)

    Musante, Luciana; Ropers, H Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Identification of ataxia telangiectasia heterozygotes by flow cytometric analysis of X-ray damage

    International Nuclear Information System (INIS)

    Rudolph, N.S.

    1989-01-01

    Flow cytometry was used to identify heterozygotes for the autosomal recessive DNA-repair deficiency disease ataxia telangiectasia (AT). Confluent G 0 /G 1 fibroblasts from 4 homozygotes (at/at), 5 obligate heterozygates (at/+) and 7 presumed normal (+/+) were X-irradiated with 200 Rad and subcultured immediately in medium containing 5-bromodeoxyuridine (BrdU). Cells were harvested 72 h later and stained with fluoresceinated anti-BrdU antibody to identify cells that had entered S phase. They were counterstained with propidium iodide to measure total DNA content. On the basis of relative release from G 0 /G 1 , the at/+ strains as a group were distinguished from both the presumed +/+ strains and at/at strains, although the individual values for some strains did show overlap between genotypes. When 10 cell strains were coded and analyzed in 'blind' experiments, all 4 heterozygotes were correctly assigned. By a similar assay in which exponentially growing cultures were pulsed briefly with BrdU 8 h after irradiation with 400 Rad and then harvested immediately, presumed +/+ cells as a group could be distinguished from at/at cells but not from at/- cells. This combination of assays assists in the identification of all 3 AT genotypes. This should be of both basic and diagnostic use, particularly in families known to segregate AT. (author). 37 refs.; 3 figs.; 5 tabs

  19. The Effect of Recessions on Firms’ Boundaries

    DEFF Research Database (Denmark)

    Knudsen, Eirik Sjåholm; Foss, Kirsten

    2014-01-01

    The economic theory of the firm offers conflicting predictions of how the two major effects of recessions, changes in demand and access to credit, affect firm boundaries. Using data on Norwegian firms in the recent recession, we find support for both increased and reduced vertical integration...... explanation for the conflicting theoretical predictions regarding vertical integration in response to demand and credit shocks....

  20. Friedreich's Ataxia: a review from a cardiology perspective.

    LENUS (Irish Health Repository)

    Bourke, T

    2011-12-01

    Neuromuscular disorders are not among the common causes of cardiomyopathy in the general population; however, cardiomyopathy is known to occur in several neuromuscular disorders including Friedreich\\'s Ataxia (FA). In patients with neuromuscular disorders, concomitant cardiac involvement contributes significantly to morbidity and mortality and often leads to premature death.

  1. Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).

    Science.gov (United States)

    O'Keefe, Joan A; Robertson-Dick, Erin; Dunn, Emily J; Li, Yan; Deng, Youping; Fiutko, Amber N; Berry-Kravis, Elizabeth; Hall, Deborah A

    2015-12-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" size 55-200 CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Core motor features include cerebellar gait ataxia and kinetic tremor, resulting in progressive mobility disability. There are no published studies characterizing balance deficits in FMR1 premutation carriers with and without FXTAS using a battery of quantitative measures to test the sensory integration underlying postural control, automatic postural reflexes, and dynamic postural stability limits. Computerized dynamic posturography (CDP) and two performance-based balance measures were administered in 44 premutation carriers, 21 with FXTAS and 23 without FXTAS, and 42 healthy controls to compare balance and functional mobility between these groups. Relationships between FMR1 molecular variables, age, and sex and CDP scores were explored. FXTAS subjects demonstrated significantly lower scores on the sensory organization test (with greatest reductions in the vestibular control of balance), longer response latencies to balance perturbations, and reduced stability limits compared to controls. Premutation carriers without FXTAS also demonstrated significantly delayed response latencies and disrupted sensory weighting for balance control. Advancing age, male sex, increased CGG repeat size, and reduced X activation of the normal allele in premutation carrier women predicted balance dysfunction. These postural control deficits in carriers with and without FXTAS implicate dysfunctional cerebellar neural networks and may provide valuable outcome markers for tailored rehabilitative interventions. Our findings suggest that CDP may provide sensitive measures for early detection of postural control impairments in at-risk carriers and better characterize balance dysfunction and progression in FXTAS.

  2. Tremor in neurodegenerative ataxias, Huntington disease and tic disorder.

    Science.gov (United States)

    Rudzińska, M; Krawczyk, M; Wójcik-Pędziwiatr, M; Szczudlik, A; Tomaszewski, T

    2013-01-01

    Tremor is the most prevalent movement disorder, defined as rhythmic oscillations of a body part, caused by alternating or synchronic contractions of agonistic or antagonistic muscles. The aim of the study was to assess prevalence and to characterize parameters of tremor accompanying de-generative ataxias, Huntington disease (HD) and tic disorders in comparison with a control group. Forty-three patients with degenerative ataxias, 28 with HD and 26 with tic disorders together with 51 healthy controls were included in the study. For each participant, clinical and instrumental assessment (accelerometer, electromyography [EMG], graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor), with hands extended (postural tremor), during the 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, the type of tremor was determined as essential tremor type or enhanced physiological tremor type. The incidence of tremor in the accelerometry in patients with degenerative ataxia (50%) significantly differs from controls (10%) (p = 0.001). The dominant tremor was postural, low-intense, with 7-Hz frequency, essential tremor (23%) or other tremor type (23%), while enhanced physiological tremor was the least frequent (2%). Tremor in patients with HD and tic disorders was found in 10% and 20% of patients, respectively, similarly to the control group. Tremor was mild, postural and of essential tremor type, less frequently of enhanced physiological tremor type. No correlation between severity of tremor and severity of disease was found. The prevalence of tremor is considerably higher among patients with degenerative ataxias compared with HD, tic disorder and the control group. The most common type of tremor accompanying ataxias, HD and tic disorders is essential tremor type.

  3. Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

    Science.gov (United States)

    Corbett, Mark A; Bellows, Susannah T; Li, Melody; Carroll, Renée; Micallef, Silvana; Carvill, Gemma L; Myers, Candace T; Howell, Katherine B; Maljevic, Snezana; Lerche, Holger; Gazina, Elena V; Mefford, Heather C; Bahlo, Melanie; Berkovic, Samuel F; Petrou, Steven; Scheffer, Ingrid E; Gecz, Jozef

    2016-11-08

    To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. The 7 family members had episodic ataxia (5), self-limited infantile seizures (5), evolving to genetic generalized epilepsy (4), focal seizures (2), and EE (1). They had a segregating novel mutation in the shaker type voltage-gated potassium channel KCNA2 (CCDS_827.1: c.765_773del; p.255_257del). A rare missense SCN2A (rs200884216) variant was also found in 2 affected siblings and their unaffected mother. The p.255_257del mutation caused dominant negative loss of channel function. Molecular modeling predicted repositioning of critical arginine residues in the voltage-sensing domain. KCNA2 sequencing revealed 1 de novo mutation (CCDS_827.1: c.890G>A; p.Arg297Gln) in a girl with EE, ataxia, and tremor. A KCNA2 mutation caused dominantly inherited episodic ataxia, mild infantile-onset seizures, and later generalized and focal epilepsies in the setting of normal intellect. This observation expands the KCNA2 phenotypic spectrum from EE often associated with chronic ataxia, reflecting the marked variation in severity observed in many ion channel disorders. © 2016 American Academy of Neurology.

  4. Isolated rhomboencephalosynapsis – a rare cerebellar anomaly

    International Nuclear Information System (INIS)

    Paprocka, Justyna; Jamroz, Ewa; Ścieszka, Ewa; Kluczewska, Ewa

    2012-01-01

    Rhomboencephalosynapsis (RES, RS) is a unique entity usually recognized in infancy based on neuroimaging. Cerebellar fusion and absence of cerebellar vermis is often associated with supratentorial findings. Since now there are about 50 cases described worldwide, with approximately 36 patients diagnosed by MRI. The authors present the first in Poland case of this uncommon malformation and review the literature. The authors describe a 28-month-old-girl with microcephaly and proper psychomotor development. The family history was unrelevant. Based on MRI the congenital malformation of posterior fossa-rhombencephalosynapsis was confirmed Presented patient is a typical example of MRI usefulness especially in patients with RES. RES symptoms are mild and that is why the diagnosis is usually made only in adulthood

  5. Cerebellar interaction with the acoustic reflex.

    Science.gov (United States)

    Jastreboff, P J

    1981-01-01

    The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

  6. Studying cerebellar circuits by remote control of selected neuronal types with GABA-A receptors

    Directory of Open Access Journals (Sweden)

    William Wisden

    2009-12-01

    Full Text Available Although GABA-A receptor-mediated inhibition of cerebellar Purkinje cells by molecular layer interneurons (MLIs has been studied intensely on the cellular level, it has remained unclear how this inhibition regulates cerebellum-dependent behaviour. We have implemented two complementary approaches to investigate the function of the MLI-Purkinje cell synapse on the behavioral level. In the first approach we permanently disrupted inhibitory fast synaptic transmission at the synapse by genetically removing the postsynaptic GABA-A receptors from Purkinje cells (PC-Δγ2 mice. We found that chronic disruption of the MLI-Purkinje cell synapse strongly impaired cerebellar learning of the vestibular occular reflex (VOR, presumably by disrupting the temporal patterns of Purkinje cell activity. However, in PC-Δγ2 mice the baseline VOR reflex was only mildly affected; indeed PC-Δγ2 mice showed no ataxia or gait abnormalities suggesting that MLI control of Purkinje cell activity is either not involved in ongoing motor tasks or that the system has found a way to compensate for its loss. To investigate the latter possibility we have developed an alternative genetic technique; we made the MLI-Purkinje cell synapse selectively sensitive to rapid manipulation with the GABAA receptor modulator zolpidem (PC-γ2-swap mice. Minutes after intraperitoneal zolpidem injection, these PC-γ2-swap mice developed severe motor abnormalities, revealing a substantial contribution of the MLI-Purkinje cell synapse to real time motor control. The cell-type selective permanent knockout of synaptic GABAergic input, and the fast reversible modulation of GABAergic input at the same synapse illustrate how pursuing both strategies gives a fuller view.

  7. CT evaluation of the anterior epitympanic recess

    International Nuclear Information System (INIS)

    Yamasoba, Tatsuya; Kikuchi, Shigeru; Takeuchi, Naonobu; Harada, Takehiko; Nomura, Yasuya

    1991-01-01

    The structures of the anterior epitympanic recess and its surrounding tissues were examined among non-inflammatory ear, chronic otitis media with central perforation and cholesteatoma, using axial scans of high resolution computed tomography. The length and width of the recess, as well as the number of the slices where the cog was determined, had no significant differences among them. Thus, the bony structure of the recess was considered to be seldom influenced by inflammatory processes. In the non-inflammatory ear, the degree of pneumatization around the recess was similar to that of the petrous apex cells and lower than that of the mastoid cells. In the chronic otitis media with central perforation and cholesteatoma, the pneumatization of the whole temporal bones was suppressed and the tendency was also found that the cells around the recess were less pneumatized than the mastoid cells. When cholesteatoma invaded into the anterior epitympanic recess, the destruction of the bony protrusion of the lateral wall between the recess and the epitympanum was recognized, as well as the disappearance of the cog. The bony protrusion was considered to be an inferior extention of the cog toward the anterior tympanic spine. (author)

  8. Computed tomography in hypertensive cerebellar hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Nose, T; Maki, Y; Ono, Y; Yoshizawa, T; Tsuboi, K [Tsukuba Univ., Sakura, Ibaraki (Japan)

    1981-11-01

    Fourteen cases of cerebellar hemorrhage were analysed from the point of CT-scan, and the following results were obtained. 1. The number of cases of cerebellar hemorrhage forms 4.4% of that of total intracranial hemorrhage. 2. Most of the cerebellar hematomas extend upward. Downward extension is rare. 3. In acute dead cases hematomas are 5 cm or more in diameter and lie over bilateral hemispheres with the extension to third or fourth ventricles in CT-scans. 4. Slowly progressive cases are detriorated by the secondary hydrocephalus. 5. In mild cases hematomas are 3cm or less in diameter on CT-scans and the hematoma evacuation is not indicated for these cases. 6. The shunt operation alone is sufficient for the life saving of the slowly progressive cases, but the hematoma evacuation is indicated in these cases if the functional prognosis is taken into consideration. 7. Immediate hematoma evacuation together with the ventricular drainage is considered to be effective for the life saving of the acute fulminant cases.

  9. Computed tomography in hypertensive cerebellar hemorrhage

    International Nuclear Information System (INIS)

    Nose, Tadao; Maki, Yutaka; Ono, Yukio; Yoshizawa, Takashi; Tsuboi, Kohji

    1981-01-01

    Fourteen cases of cerebellar hemorrhage were analysed from the point of CT-scan, and the following results were obtained. 1. The number of cases of cerebellar hemorrhage forms 4.4% of that of total intracranial hemorrhage. 2. Most of the cerebellar hematomas extend upward. Downward extension is rare. 3. In acute dead cases hematomas are 5 cm or more in diameter and lie over bilateral hemispheres with the extension to third or fourth ventricles in CT-scans. 4. Slowly progressive cases are detriorated by the secondary hydrocephalus. 5. In mild cases hematomas are 3cm or less in diameter on CT-scans and the mematoma evacuation is not indicated for these cases. 6. The shunt operation alone is sufficient for the life saving of the slowly progressive cases, but the hematoma evacuation is indicated in these cases if the functional prognosis is taken into consideration. 7. Immediate hematoma evacuation togather with the ventricular dranage is considered to be effective for the life saving of the acute fulminant cases. (author)

  10. Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.

    Science.gov (United States)

    Huang, Ying-Zu; Chang, Yao-Shun; Hsu, Miao-Ju; Wong, Alice M K; Chang, Ya-Ju

    2015-01-01

    Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.).

  11. A Patient with Fragile X-Associated Tremor/Ataxia Syndrome Presenting with Executive Cognitive Deficits and Cerebral White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Kensaku Kasuga

    2011-05-01

    Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a late-onset neurodegenerative disorder that primarily affects males who are carriers of a premutation of a CGG expansion in the FMR1 gene. In Asian populations, FXTAS has rarely been reported. Here, we report the case of a Japanese FXTAS patient who showed predominant executive cognitive deficits as the main feature of his disease. In contrast, the patient exhibited only very mild symptoms of intention tremor and ataxia, which did not interfere with daily activities. A gene analysis revealed that the patient carried a premutation of a CGG expansion (111 CGG repeats in the FMR1 gene. The mRNA expression level of FMR1 in the patient was 1.5-fold higher than in controls. On brain MRI scans, fluid-attenuated inversion recovery images showed high-intensity lesions in the middle cerebellar peduncles and the cerebral white matter, with a frontal predominance. The present case extends previous notions regarding the cognitive impairment in FXTAS patients. Recognizing FXTAS patients with predominant cognitive impairment from various ethnic backgrounds would contribute to our understanding of the phenotypic variation of this disease.

  12. Cerebellar transcranial static magnetic field stimulation transiently reduces cerebellar brain inhibition.

    Science.gov (United States)

    Matsugi, Akiyoshi; Okada, Y

    The aim of this study was to investigate whether transcranial static magnetic field stimulation (tSMS) delivered using a compact cylindrical NdFeB magnet over the cerebellum modulates the excitability of the cerebellum and contralateral primary motor cortex, as measured using cerebellar brain inhibition (CBI), motor evoked potentials (MEPs), and resting motor threshold (rMT). These parameters were measured before tSMS or sham stimulation and immediately, 5 minutes and 10 minutes after stimulation. There were no significant changes in CBI, MEPs or rMT over time in the sham stimulation condition, and no changes in MEPs or rMT in the tSMS condition. However, CBI was significantly decreased immediately after tSMS as compared to that before and 5 minutes after tSMS. Our results suggest that tSMS delivered to the cerebellar hemisphere transiently reduces cerebellar inhibitory output but does not affect the excitability of the contralateral motor cortex.

  13. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

    Science.gov (United States)

    Martinelli, Paola; Cherukuri, Praveen F.; Teer, Jamie K.; Hansen, Nancy F.; Cruz, Pedro; Mullikin for the NISC Comparative Sequencing Program, James C.; Blakesley, Robert W.; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I.; Langer, Thomas; Gahl, William A.; Toro, Camilo

    2011-01-01

    We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284

  14. Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases.

    Directory of Open Access Journals (Sweden)

    Tyler Mark Pierson

    2011-10-01

    Full Text Available We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7. Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28, a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial" features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.

  15. Cerebro-cerebellar circuits in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Anila M. D'Mello

    2015-11-01

    Full Text Available The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. In contrast, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

  16. Cerebro-cerebellar circuits in autism spectrum disorder.

    Science.gov (United States)

    D'Mello, Anila M; Stoodley, Catherine J

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

  17. Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder.

    Science.gov (United States)

    Hegarty, John P; Weber, Dylan J; Cirstea, Carmen M; Beversdorf, David Q

    2018-05-23

    Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy ( 1 H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.

  18. Ataxia, dystonia and myoclonus in adult patients with Niemann-Pick type C.

    Science.gov (United States)

    Koens, L H; Kuiper, A; Coenen, M A; Elting, J W J; de Vries, J J; Engelen, M; Koelman, J H T M; van Spronsen, F J; Spikman, J M; de Koning, T J; Tijssen, M A J

    2016-09-01

    Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin

  19. Hospital Capital Investment During the Great Recession.

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

  20. Andhidrotic ectodermal dysplasia-autosomal recessive form

    Directory of Open Access Journals (Sweden)

    Inamadar Arun

    1994-01-01

    Full Text Available Anhidrotic ectodermal dysplasia with classical features in 2 sisters is reported. The mode of inheritance in these seems to be autosomal recessive; which is a very rare occurrence.

  1. The Great Recession and confidence in homeownership

    OpenAIRE

    Anat Bracha; Julian Jamison

    2013-01-01

    Confidence in homeownership shifts for those who personally experienced real estate loss during the Great Recession. Older Americans are confident in the value of homeownership. Younger Americans are less confident.

  2. Bond return predictability in expansions and recessions

    DEFF Research Database (Denmark)

    Engsted, Tom; Møller, Stig Vinther; Jensen, Magnus David Sander

    We document that over the period 1953-2011 US bond returns are predictable in expansionary periods but unpredictable during recessions. This result holds in both in-sample and out-of-sample analyses and using both univariate regressions and combination forecasting techniques. A simulation study...... but negative in recessions. The results are also consistent with tests showing that the expectations hypothesis of the term structure holds in recessions but not in expansions. However, the results for bonds are in sharp contrast to results for stocks showing that stock returns are predictable in recessions...... but not in expansions. Thus, our results indicate that there is not a common predictive pattern of stock and bond returns associated with the state of the economy....

  3. The Great Recession and Workers' Health Benefits.

    Science.gov (United States)

    Koh, Kanghyock

    2018-03-01

    During a recession, cost-sharing of employer-sponsored health benefits could increase to reduce labor costs in the U.S. Using a variation in the severity of recession shocks across industries, I find evidence that the enrollment rate of high deductible health plans (HDHPs) among workers covered by employer-sponsored health benefits increased more among firms in industries that experienced severe recession shocks. As potential mechanisms, I study employer-side and worker-side mechanisms. I find that employers changed health benefit offerings to force or incentivize workers to enroll in HDHPs. But I find little evidence of an increase in workers' demand for HDHPs due to a reduction in income. These results suggest that the HDHP enrollment rate increased during the Great Recession, as employers tried to save costs of offering health benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Recessive Dystrophic Epidermolysis Bullosa and Pregnancy.

    Science.gov (United States)

    Boria, F; Maseda, R; Martín-Cameán, M; De la Calle, M; de Lucas, R

    2017-12-01

    Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis bullosa) is characterized by the absence or considerably reduced expression of type VII collagen, which leads to marked fragility of the skin and mucous membranes and subsequent blister formation, whether spontaneously or following minimal injury. There have been very few reports of this disease in pregnant women. We present 2 cases of pregnant women with recessive dystrophic epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean delivery, with no further complications for mother or child. Although recessive dystrophic epidermolysis bullosa increases the risk of maternal complications, a patient is not advised against pregnancy. With adequate monitoring, these patients can fulfil their desire to become mothers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Hospital Capital Investment During the Great Recession

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal. PMID:28617202

  6. The diverse impacts of the great recession

    OpenAIRE

    Makoto Nakajima

    2013-01-01

    The Great Recession had a large negative impact on the U.S. economy. Asset prices, most notably stock and house prices, declined substantially, resulting in a loss in wealth for many American households. In this article, Makoto Nakajima documents how diverse households were affected in a variety of dimensions during the Great Recession, in particular between 2007 and 2009, using newly available data from the 2007-2009 Survey of Consumer Finances. He discusses why it is important to look at th...

  7. Academic Performance and the Great Recession

    OpenAIRE

    Adamopoulou, Effrosyni; Tanzi, Giulia M.

    2014-01-01

    In this paper we study how the Great Recession affected university students in terms of performance, with a special focus on the dropout probability. To do so, we use individual-level data on a representative sample of university students in Italy in 2007 and 2011. We measure the severity of the recession in terms of increases in adult and youth unemployment rate and we exploit geographical variation to achieve identification. On the one hand, an increase in adult male unemployment rate deter...

  8. HYDRORECESSION: A toolbox for streamflow recession analysis

    Science.gov (United States)

    Arciniega, S.

    2015-12-01

    Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

  9. [Spinocerebellar ataxia type 2 associated to pigmentary retinitis].

    Science.gov (United States)

    Jiménez-Caballero, Pedro Enrique; Serviá, Mónica

    2010-07-01

    Ocular disorders are useful in the characterisation of the different types of spinocerebellar ataxias (SCA); pigmentary retinitis is an alteration that is specifically associated to SCA type 7 and is characterised by night blindness, sensitivity to glare and progressive narrowing of the visual field. A 34-year-old woman with clinical symptoms of progressive ataxia and visual impairment secondary to pigmentary retinitis. The patient had a personal history with an autosomal dominant pattern of a similar disorder in her father and paternal grandmother. In the genetic study she presented a triplet expansion in the SCA type 2 gene. CONCLUSIONS; Although pigmentary retinitis belongs to the SCA type 7 phenotype, our patient presented this retinal disorder, as in other cases of SCA type 2. A genetic study for SCA type 2 must therefore be conducted in patients with a degenerative ataxic clinical picture and who present evidence of pigmentary retinitis.

  10. Progression of Dysphagia in Spinocerebellar Ataxia Type 6.

    Science.gov (United States)

    Isono, Chiharu; Hirano, Makito; Sakamoto, Hikaru; Ueno, Shuichi; Kusunoki, Susumu; Nakamura, Yusaku

    2017-06-01

    Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant triplet repeat disease, predominantly affects the cerebellum with a late onset and generally good prognosis. Dysphagia is commonly associated with the outcomes of neurodegenerative diseases such as SCA6. Although the characteristics of dysphagia have been rarely reported in SCA6, our previous study indicated that dysphagia is generally milder in SCA6 than in SCA3, another inherited ataxia with multisystem involvement. However, abnormalities in the pharyngeal phase in SCA6 were indistinguishable from those in SCA3, with no explainable reason. To determine the reason, we repeatedly performed videofluoroscopic examinations (VF) in 14 patients with SCA6. The results showed that the gross progression of dysphagia was apparently slow, but four patients had progressive dysphagia at an early disease stage; dysphagia began within 10 years from the onset of ataxia and rapidly progressed. A common clinical feature of the four patients was a significantly older age at the onset of ataxia (74.0 vs. 60.3 years), associated with significantly shorter triplet repeats. This finding surprisingly indicated that patients who had shorter repeats and thereby later onset and potentially better prognoses were at risk for dysphagia-associated problems. Ischemic changes, homozygous mutation, and diabetes mellitus as well as aging might have contributed to the observed progressive dysphagia. We found that conventionally monitored somatosensory evoked potentials at least partly reflected progressive dysphagia. Despite the small study group, our findings suggest that clinicians should carefully monitor dysphagia in patients with SCA6 who are older at disease onset (>60 years).

  11. The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Andrs, M.; Kobarecny, J.; Nepovimova, E.; Jun, D.; Hodný, Zdeněk; Moravcová, Simona; Hanzlíková, Hana; Kuca, K.

    2014-01-01

    Roč. 14, č. 10 (2014), s. 805-811 ISSN 1389-5575 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/30.0044 Grant - others:MH CZ - DRO (University Hospital Hradec Kralove(CZ) 00179906 Institutional support: RVO:68378050 Keywords : Ataxia telangiectasia mutated * cancer * chemosensitization * DNA damage response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.903, year: 2014

  12. Excessive blinking and ataxia in a child with occult neuroblastoma and voltage-gated potassium channel antibodies.

    LENUS (Irish Health Repository)

    Allen, Nicholas M

    2012-05-01

    A previously healthy 9-year-old girl presented with a 10-day history of slowly progressive unsteadiness, slurred speech, and behavior change. On examination there was cerebellar ataxia and dysarthria, excessive blinking, subtle perioral myoclonus, and labile mood. The finding of oligoclonal bands in the cerebrospinal fluid prompted paraneoplastic serological evaluation and search for an occult neural crest tumor. Antineuronal nuclear autoantibody type 1 (anti-Hu) and voltage-gated potassium channel complex antibodies were detected in serum. Metaiodobenzylguanidine scan and computed tomography scan of the abdomen showed a localized abdominal mass in the region of the porta hepatis. A diagnosis of occult neuroblastoma was made. Resection of the stage 1 neuroblastoma and treatment with pulsed corticosteroids resulted in resolution of all symptoms and signs. Excessive blinking has rarely been described with neuroblastoma, and, when it is not an isolated finding, it may be a useful clue to this paraneoplastic syndrome. Although voltage-gated potassium channel complex autoimmunity has not been described previously in the setting of neuroblastoma, it is associated with a spectrum of paraneoplastic neurologic manifestations in adults, including peripheral nerve hyperexcitability disorders.

  13. A longitudinal study of the Friedreich Ataxia Impact Scale.

    Science.gov (United States)

    Tai, Geneieve; Yiu, Eppie M; Corben, Louise A; Delatycki, Martin B

    2015-05-15

    Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years. One hundred and four individuals with FRDA, homozygous for the GAA expansion in intron 1 of FXN, completed the FAIS at baseline. Seventy individuals completed the FAIS again 12 months later and 49 completed the FAIS at 24 months. Clinical parameters and neurologic scales (Friedreich Ataxia Rating Scale (FARS)) were also recorded. The total FARS score, onset age and disease duration correlated significantly with FAIS subscales measuring symptoms and physical functioning. The physical and mental summary measures of the SF-36 V2 also correlated well with the FAIS subscales. Speech was the only subscale that demonstrated significant change over one and two years. The FAIS provides valuable insight into the perspective of individuals with FRDA on their health status, and is an important measure of morbidity. It has, however, limited responsiveness to change and its use in intervention studies is questionable. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Case report of novel CACNA1A gene mutation causing episodic ataxia type 2

    Directory of Open Access Journals (Sweden)

    David Alan Isaacs

    2017-05-01

    Full Text Available Background: Episodic ataxia type 2 (OMIM 108500 is an autosomal dominant channelopathy characterized by paroxysms of ataxia, vertigo, nausea, and other neurologic symptoms. More than 50 mutations of the CACNA1A gene have been discovered in families with episodic ataxia type 2, although 30%–50% of all patients with typical episodic ataxia type 2 phenotype have no detectable mutation of the CACNA1A gene. Case: A 46-year-old Caucasian man, with a long history of bouts of imbalance, vertigo, and nausea, presented to our hospital with 2 weeks of ataxia and headache. Subsequent evaluation revealed a novel mutation in the CACNA1A gene: c.1364 G > A Arg455Gln. Acetazolamide was initiated with symptomatic improvement. Conclusion: This case report expands the list of known CACNA1A mutations associated with episodic ataxia type 2.

  15. Mathematical models of human cerebellar development in the fetal period.

    Science.gov (United States)

    Dudek, Krzysztof; Nowakowska-Kotas, Marta; Kędzia, Alicja

    2018-04-01

    The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development. © 2018 Anatomical Society.

  16. Cerebellar transcranial direct current stimulation modulates verbal working memory.

    Science.gov (United States)

    Boehringer, Andreas; Macher, Katja; Dukart, Juergen; Villringer, Arno; Pleger, Burkhard

    2013-07-01

    Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

    Science.gov (United States)

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2012-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

  18. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

    Science.gov (United States)

    Buijink, A W G; Broersma, M; van der Stouwe, A M M; van Wingen, G A; Groot, P F C; Speelman, J D; Maurits, N M; van Rootselaar, A F

    2015-04-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Time estimation in Parkinson's disease and degenerative cerebellar disease

    NARCIS (Netherlands)

    Beudel, Martijin; Galama, Sjoukje; Leenders, Klaus L.; de Jong, Bauke M.

    2008-01-01

    With functional MRI, we recently identified fronto-cerebellar activations in predicting time to reach a target and basal ganglia activation in velocity estimation, that is, small interval assessment. We now tested these functions in patients with Parkinson's disease (PD) and degenerative cerebellar

  20. Cerebellar cortical infarct cavities and vertebral artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Cocker, Laurens J.L. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Kliniek Sint-Jan Radiologie, Brussels (Belgium); Compter, A.; Kappelle, L.J.; Worp, H.B. van der [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Luijten, P.R.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2016-09-15

    Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI. (orig.)

  1. Humor and laughter in patients with cerebellar degeneration.

    Science.gov (United States)

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

  2. Cerebellar involvement in metabolic disorders: a pattern-recognition approach

    International Nuclear Information System (INIS)

    Steinlin, M.; Boltshauser, E.; Blaser, S.

    1998-01-01

    Inborn errors of metabolism can affect the cerebellum during development, maturation and later during life. We have established criteria for pattern recognition of cerebellar abnormalities in metabolic disorders. The abnormalities can be divided into four major groups: cerebellar hypoplasia (CH), hyperplasia, cerebellar atrophy (CA), cerebellar white matter abnormalities (WMA) or swelling, and involvement of the dentate nuclei (DN) or cerebellar cortex. CH can be an isolated typical finding, as in adenylsuccinase deficiency, but is also occasionally seen in many other disorders. Differentiation from CH and CA is often difficult, as in carbohydrate deficient glycoprotein syndrome or 2-l-hydroxyglutaric acidaemia. In cases of atrophy the relationship of cerebellar to cerebral atrophy is important. WMA may be diffuse or patchy, frequently predominantly around the DN. Severe swelling of white matter is present during metabolic crisis in maple syrup urine disease. The DN can be affected by metabolite deposition, necrosis, calcification or demyelination. Involvement of cerebellar cortex is seen in infantile neuroaxonal dystrophy. Changes in DN and cerebellar cortex are rather typical and therefore most helpful; additional features should be sought as they are useful in narrowing down the differential diagnosis. (orig.)

  3. Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions

    DEFF Research Database (Denmark)

    Sönmezoğlu, K; Sperling, B; Henriksen, T

    1993-01-01

    Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using 99mTc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduct...

  4. The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration

    Science.gov (United States)

    Stoodley, Catherine J.; Schmahmann, Jeremy D.

    2009-01-01

    Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

  5. Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.

    Science.gov (United States)

    Piguet, Françoise; de Montigny, Charline; Vaucamps, Nadège; Reutenauer, Laurence; Eisenmann, Aurélie; Puccio, Hélène

    2018-05-28

    Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  6. New evidence for the cerebellar involvement in personality traits

    Directory of Open Access Journals (Sweden)

    Eleonora ePicerni

    2013-10-01

    Full Text Available Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI. High resolution T1-weighted and Diffusion Tensor Images of 100 healthy subjects aged 18-59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM or White Matter (WM volumes, GM Mean Diffusivity (MD, and WM Fractional Anisotropy (FA were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty.

  7. Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

    International Nuclear Information System (INIS)

    Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S.

    2006-01-01

    We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)

  8. Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan)

    2006-03-15

    We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)

  9. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Arvind Chaturvedi

    2011-01-01

    Full Text Available Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  10. Prolonged vertigo and ataxia after mandibular nerve block for treatment of trigeminal neuralgia.

    Science.gov (United States)

    Chaturvedi, Arvind; Dash, Hh

    2011-07-01

    Common complications of neurolytic mandibular nerve block are hypoesthesia, dysesthesia, and chemical neuritis. We report a rare complication, prolonged severe vertigo and ataxia, after neurolytic mandibular blockade in a patient suffering from trigeminal neuralgia. Coronoid approach was used for right sided mandibular block. After successful test injection with local anesthetic, absolute alcohol was given for neurolytic block. Immediately after alcohol injection, patient developed nausea and vomiting along with severe vertigo, ataxia and hypertension. Neurological evaluation was normal except for the presence of vertigo and ataxia. Computerised tomography scan brain was also normal. Patient was admitted for observation and symptomatic treatment was given. Vertigo and ataxia gradually improved over 24 hours.

  11. Abnormal brain MRI in a case of acute ataxia as the only sign of abdominal neuroblastoma

    International Nuclear Information System (INIS)

    Molla Mohammadi, M.; Karimzadeh, P.; Khatami, A.; Jadali, F.

    2010-01-01

    Ataxia is a movement disorder that may manifest an acute, intermittent, non progressive or chronic progressive course. Ataxia alone is rare as a para neoplastic sign, especially if it is due to neuroblastoma (abdominal or chest). We report an abdominal neuroblastoma in a two-year-old girl presenting with only acute ataxia and abnormal neuroimaging. Brain MRI showed abnormal signal finding in the medulla, pons, cortico spinal tract and the periventricular space. In the abdominal CT, a mass was detected in the right adrenal gland with calcification and the histopathologic examination re-vealed neuroblastoma. We suggest in children with acute ataxia, with or without opalescence-myoclonus, neuroblastoma should be considered.

  12. Aeroacoustical Study of the Tgv Pantograph Recess

    Science.gov (United States)

    NOGER, C.; PATRAT, J. C.; PEUBE, J.; PEUBE, J. L.

    2000-03-01

    The general focus of this aerodynamic noise research, induced by turbulent incompressible flow, is to improve our knowledge of acoustic production mechanisms in the TGV pantograph recess in order to be able to reduce the radiated noise. This work is performed under contract with SNCF as a part of the German-French Cooperation DEUFRAKO K2, and is supported by French Ministries for Transport and Research. Previous studies on TGV noise source locations (DEUFRAKO K) have identified the pantograph recess as one of the important aerodynamic noise sources, for speeds higher than 300 km/h, due to flow separation. The pantograph recess is a very complex rectangular cavity, located both on the power car and the first coach roofs of the TGV, and has not been studied before due to the complex shapes. Its aeroacoustic features are investigated experimentally in a low-subsonic wind tunnel, on a realistic 1/7th scale mock-up both with and without pantographs. Flow velocities, estimated with hot-wire anemometry, and parietal visualizations show the flow to reattach on the recess bottom wall and to separate again at the downstream face. Wall pressure fluctuations and “acoustic” measurements using 14 and 12 in microphones respectively are also measured to qualify the flow: no aerodynamic or acoustic oscillations are observed. The study indicates that the pantograph recess has a different behaviour compared to the usual cavity grazing flows.

  13. Ataxia Telangiectasia-Mutated (ATMPolymorphisms and Risk of Lung Cancer in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Ajay A. Myneni

    2017-06-01

    Full Text Available BackgroundThe ataxia telangiectasia-mutated (ATM gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer.MethodsA population-based case–control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR and 95% confidence intervals (CIs. Adjusted models controlled for age, sex, and smoking status.ResultsThe study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06–2.35 and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08–2.08 in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT, ATMrs228589 (AA, and p53rs1042522 (CC concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43–9.45 of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer.ConclusionThis study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples.

  14. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Sara Anjomani Virmouni

    Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats, YG8R (90 and 190 GAA repeats and YG22R (190 GAA repeats.We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.

  15. Disorganized foliation of unilateral cerebellar hemisphere as cerebellar cortical dysplasia in patients with recurrent seizures: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Hye Jin [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2013-09-15

    We present a rare case of abnormal foliation for one cerebellar hemisphere on MR imaging, showing vertically-oriented folia. Foliation of contralateral cerebellar hemisphere and other structures in the posterior fossa were normal, and the patient has no neurologic deficits. This rare and unique abnormality is considered a kind of developmental error of the cerebellum.

  16. Insights into cerebellar development and medulloblastoma.

    Science.gov (United States)

    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  17. Remote cerebellar hemorrhage after lumbar spinal surgery

    International Nuclear Information System (INIS)

    Cevik, Belma; Kirbas, Ismail; Cakir, Banu; Akin, Kayihan; Teksam, Mehmet

    2009-01-01

    Background: Postoperative remote cerebellar hemorrhage (RCH) as a complication of lumbar spinal surgery is an increasingly recognized clinical entity. The aim of this study was to determine the incidence of RCH after lumbar spinal surgery and to describe diagnostic imaging findings of RCH. Methods: Between October 1996 and March 2007, 2444 patients who had undergone lumbar spinal surgery were included in the study. Thirty-seven of 2444 patients were scanned by CT or MRI due to neurologic symptoms within the first 7 days of postoperative period. The data of all the patients were studied with regard to the following variables: incidence of RCH after lumbar spinal surgery, gender and age, coagulation parameters, history of previous arterial hypertension, and position of lumbar spinal surgery. Results: The retrospective study led to the identification of two patients who had RCH after lumbar spinal surgery. Of 37 patients who had neurologic symptoms, 29 patients were women and 8 patients were men. CT and MRI showed subarachnoid hemorrhage in the folia of bilateral cerebellar hemispheres in both patients with RCH. The incidence of RCH was 0.08% among patients who underwent lumbar spinal surgery. Conclusion: RCH is a rare complication of lumbar spinal surgery, self-limiting phenomenon that should not be mistaken for more ominous pathologic findings such as hemorrhagic infarction. This type of bleeding is thought to occur secondary to venous infarction, but the exact pathogenetic mechanism is unknown. CT or MRI allowed immediate diagnosis of this complication and guided conservative management.

  18. Recession-An issue for organizations

    Directory of Open Access Journals (Sweden)

    Daniel GEORGESCU

    2009-12-01

    Full Text Available The reality in all organization is that the directors and board are in the position of highest influence and their primary responsibility is leadership. As such, considering the consequences of a recession such as we currently face is not the time for directors to abdicate their responsibilities – it is time for governance leadership. The directors and the board must think and respond strategically. The article shows a matrix for positioning the general manager in recession that is similarly with BCG matrix and in the final a table with a set of essential questions for helping the board in new strategies building.

  19. Contribution of cerebellar sensorimotor adaptation to hippocampal spatial memory.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Passot

    Full Text Available Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

  20. DNA-repair synthesis in ataxia telangiectasia lymphoblastoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Ford, M.D.; Houldsworth, J.; Lavin, M.F. (Queensland Univ., Brisbane (Australia). Dept. of Biochemistry)

    1981-12-01

    The ability of a number of Epstein-Barr virus-transformed lymphoblastoid cells from ataxia telangiectasia (AT) patients to repair ..gamma..-radiation damage to DNA was determined. All of these AT cells were previously shown to be hypersensitive to ..gamma..-radiation. Two methods were used to determine DNA-repair synthesis: isopycnic gradient analysis and a method employing hydroxyurea to inhibit semiconservative DNA synthesis. Control, AT heterozygote and AT homozygote cells were demonstrated to have similar capacities for repair of radiation damage to DNA. In addition at high radiation doses (10-40 krad) the extent of inhibition of DNA synthesis was similar in the different cell types.

  1. Ataxia cerebelar aguda na criança

    Directory of Open Access Journals (Sweden)

    Valeriana Moura Ribeiro

    1968-03-01

    Full Text Available São relatados os casos de 6 crianças com ataxia cerebelar aguda. Admitem os autores a presença de um fator etiológico de caráter viral comum a todos êles, discutindo os mecanismos patogênicos com base nos casos da literatura. A evolução foi favorável em todos os pacientes, com regressão completa da sintomatologia, dentro do período de 6 a 60 dias.

  2. The cardiomyopathy in Friedreich's ataxia: isotopic ventriculography and myocardial imaging with thallium-201

    International Nuclear Information System (INIS)

    Therriault, L.; Lamoureux, G.; Cote, M.; Plourde, G.; Lemieux, B.

    1984-01-01

    Myocardial scanning after the intravenous administration of Thallium 201 was used to evaluate regional myocardial perfusion in 14 patients with Friedreich's ataxia. Isotopic ventriculography was also used to assess left ventricular contractility. Myocardial images in patients with Friedreich's ataxia were found to be precociously abnormal irrespective of the degree of neurological impairment or of the severity of myocardial hypertrophy

  3. There May Be More to Reaching than Meets the Eye: Re-Thinking Optic Ataxia

    Science.gov (United States)

    Jackson, Stephen R.; Newport, Roger; Husain, Masud; Fowlie, Jane E.; O'Donoghue, Michael; Bajaj, Nin

    2009-01-01

    Optic ataxia (OA) is generally thought of as a disorder of visually guided reaching movements that cannot be explained by any simple deficit in visual or motor processing. In this paper we offer a new perspective on optic ataxia; we argue that the popular characterisation of this disorder is misleading and is unrepresentative of the pattern of…

  4. Genetics Home Reference: fragile X-associated tremor/ataxia syndrome

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions FXTAS Fragile X-associated tremor/ataxia syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated tremor/ataxia syndrome ( FXTAS ) is characterized by ...

  5. Pattern of Glacier Recession in Indian Himalaya

    Science.gov (United States)

    Singh, Ajay; Patwardhan, Anand

    All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate — for example, on the frequency of heat waves — this increase in surface temperatures has important consequences for the cryosphere subsequently hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. The Indian Himalayan region occupies a special place in the mountain ecosystems of the world. These geodynamically young mountains are not only important from the standpoint of climate and as a provider of life, giving water to a large part of the Indian subcontinent, but they also harbor a rich variety of flora, fauna, human communities and cultural diversity. Glaciers in this region are changing in area as well as in volume like those in other parts of the world. Studies have been carried out for recession in some of these glaciers using remote sensing as well as field observation techniques. Spatiotemporal pattern in the recession rate of the studied glaciers has been presented in this paper. Plausible causes for the recession have been also discussed. Finally, future scopes for observation and analysis in glaciers recession have been suggested.

  6. Nevada, the Great Recession, and Education

    Science.gov (United States)

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  7. The Labor Market and the Great Recession

    NARCIS (Netherlands)

    Hobijn, B.; Elsby, M.W.L.; Sahin, A.

    2010-01-01

    From the perspective of a wide range of labor market outcomes, the recession that began in 2007 represents the deepest downturn in the postwar era. Early on, the nature of labor market adjustment displayed a notable resemblance to that observed in past severe downturns. During the latter half of

  8. ECONOMIC RECESSION A CALL FOR COMPETITIVE INTELLIGENCE

    OpenAIRE

    Lucian Marius IVANOV

    2011-01-01

    Global recession brought about a significant growth in competition, stressing the need for relevant and reliable intelligence as a support for making efficient strategic decisions. The recent circumstances draw the attention far more earnestly this time on the need for an intelligence structure within companies to be ready for sustaining business management endeavours in line with increasing competitiveness, protection and promotion of their interests.

  9. Recess for Students with Visual Impairments

    Science.gov (United States)

    Lucas, Matthew D.

    2010-01-01

    During recess, the participation of a student with visual impairments in terms of movement can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with visual impairments and present basic solutions to improve the participation of these students in the…

  10. Recessive Epidermolysis Bullosa simplex- A case report

    African Journals Online (AJOL)

    Ademu

    Abstract: Background:Epidermolysis bullosa simplex (EBS) is characterized by intraepidermal blister formation, most commonly appearing in early infancy. Many variants of EBS exist; the four most common variants are inherited in an autosomal dominant fashion. The recessive forms are rare and less reported in our ...

  11. Results after gastrocnemius recession in 73 patients.

    Science.gov (United States)

    Molund, Marius; Paulsrud, Øyvind; Ellingsen Husebye, Elisabeth; Nilsen, Fredrik; Hvaal, Kjetil

    2014-12-01

    Very few studies describe the clinical results and complications following the surgical procedure of gastrocnemius recession. To survey the patient reported outcomes in patients operated with gastrocnemius recession as single procedure for various foot conditions. 93 patients operated with gastrocnemius recession as single procedure between 2006 and 2011 were detected in the database. 73 patients responded to the invitation for study participation. Questionnaires containing patient reported satisfaction, complications, plantar flexion power and visual analog pain score were used for evaluation of the postoperative result. 45/73 (62%) patients reported a good or excellent result. 8/73 (11%) patients reported a significant postoperative complication. 16/73 (22%) patients noted reduced or severely reduced plantar flexion power after surgery. VAS pain score significantly decreased from 7.0 before surgery to 1.8 (p=0.015) after surgery for patients with plantar fasciitis (n=18) and from 5.6 to 2.3 (p<0.01) for patients with metatarsalgia (n=28). Patients treated with gastrocnemius recession for plantar fasciitis demonstrated good clinical results. The complication rate was higher than reported by others. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  12. The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

    Science.gov (United States)

    Neubauer, Vera; Djurdjevic, Tanja; Griesmaier, Elke; Biermayr, Marlene; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula

    2018-01-01

    Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains. © 2017 S. Karger AG, Basel.

  13. Exploration of transitional life events in individuals with Friedreich ataxia: Implications for genetic counseling

    Directory of Open Access Journals (Sweden)

    Farmer Jennifer M

    2010-10-01

    age of 37 years 21. Currently, there are no treatments or cures for FRDA. Little is known about the specific psychological or psychosocial effects of the condition. FRDA is an autosomal recessive condition. The typical molecular basis of Friedreich ataxia is the expansion of a GAA trinucleotide repeat in both copies of the FXN gene 22. Age of onset usually occurs in late childhood or early adolescence. However, the availability of genetic testing has identified affected individuals with an adult form of the condition. This late-onset form is thought to represent approximately 10-15% of the total FRDA population 23. Health care providers of individuals with progressive, neurodegenerative disorders can help facilitate their patients' progression through transitional events. Data suggest that improvements should be made in the care of these individuals. Shaw et al. 24 found that individualized care that helps to prepare patients for transition is beneficial. Beisecker et al. 25 found that patients desire not only physical care from their providers, but also emotional and psychosocial support. Genetic counselors have an important opportunity to help patients with neuromuscular disorders progress through transitional events, as several of these conditions have a genetic etiology. Genetic counselors in pediatric and adult settings often develop long-term relationships with patients, due to follow-up care. This extended relationship is becoming increasingly common as genetic counselors move into various medical sub-specialties, such as neurology, ophthalmology, oncology and cardiology. The role of the genetic counselor in addressing the psychosocial needs of patients has been advocated, but rarely framed in the context of developmental events 26. Data suggest that patients may not expect a genetic counselor to address psychosocial needs 27. In a survey of genetic counseling patients, Wertz 28 found a majority of respondents understood genetic conditions to have a moderate to

  14. Formulating the spring discharge-function for the recession period ...

    Indian Academy of Sciences (India)

    College of Agricultural Engineering & Post Harvest Technology (CAEPHT),. Central Agricultural ... during the recession period is the key to its proper management. The spring .... In equation (1), Q is the recession flow, t is time, and a, b are ...

  15. Diffusion tensor imaging of the cortico-ponto-cerebellar pathway in patients with adult-onset ataxic neurodegenerative disease

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Kaeko; Nakayama, Keiko; Yamada, Eiji; Inoue, Yuichi [Osaka City University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Kosaka, Satoru; Shimada, Hiroyuki; Miki, Takami [Osaka City University Graduate School of Medicine, Department of Neurology, Osaka (Japan)

    2008-04-15

    We sought to determine whether diffusion-tensor imaging (DTI) can detect in vivo axonal damage in the corticopontocerebellar pathway of patients with adult-onset ataxic neurodegenerative disease. Conventional MRI and DTI were performed on 18 patients with adult-onset ataxic neurodegenerative disease and 28 age-matched control subjects. Fractional anisotropy (FA) and the mean diffusivity (MD) were measured in the ventral, central, and dorsal pons, middle cerebellar peduncle (MCP) and internal capsule to evaluate corticopontocerebellar projection. Changes in FA and MD values were compared between patients and controls. Clinical disability was assessed according to the International Cooperative Ataxia Rating Scale (ICARS). The relationship between DTI measurements and ICARS was studied. Follow-up MRI was performed in five patients approximately 1 year later. FA values were significantly lower in the ventral and central portions of the pons, MCP, and internal capsules than in these areas in control subjects (P < 0.05) with the lower FA values correlating with poorer ICARS (r > -0.57, P < 0.05). MD values were elevated in these areas, but the differences were smaller than for the FA values. No relationship was observed between the MD and ICARS. In the five patients who underwent the follow-up study, there were significant decreases between the initial study and the follow-up DTI study for FA in the MCP and internal capsule (P < 0.05). DTI can demonstrate a degenerated corticopontocerebellar pathway in patients, and FA values can be correlated with ataxia severity. DTI may be a clinically useful tool as a quantitative surrogate marker for monitoring disease progression. (orig.)

  16. Diffusion tensor imaging of the cortico-ponto-cerebellar pathway in patients with adult-onset ataxic neurodegenerative disease

    International Nuclear Information System (INIS)

    Kitamura, Kaeko; Nakayama, Keiko; Yamada, Eiji; Inoue, Yuichi; Kosaka, Satoru; Shimada, Hiroyuki; Miki, Takami

    2008-01-01

    We sought to determine whether diffusion-tensor imaging (DTI) can detect in vivo axonal damage in the corticopontocerebellar pathway of patients with adult-onset ataxic neurodegenerative disease. Conventional MRI and DTI were performed on 18 patients with adult-onset ataxic neurodegenerative disease and 28 age-matched control subjects. Fractional anisotropy (FA) and the mean diffusivity (MD) were measured in the ventral, central, and dorsal pons, middle cerebellar peduncle (MCP) and internal capsule to evaluate corticopontocerebellar projection. Changes in FA and MD values were compared between patients and controls. Clinical disability was assessed according to the International Cooperative Ataxia Rating Scale (ICARS). The relationship between DTI measurements and ICARS was studied. Follow-up MRI was performed in five patients approximately 1 year later. FA values were significantly lower in the ventral and central portions of the pons, MCP, and internal capsules than in these areas in control subjects (P -0.57, P < 0.05). MD values were elevated in these areas, but the differences were smaller than for the FA values. No relationship was observed between the MD and ICARS. In the five patients who underwent the follow-up study, there were significant decreases between the initial study and the follow-up DTI study for FA in the MCP and internal capsule (P < 0.05). DTI can demonstrate a degenerated corticopontocerebellar pathway in patients, and FA values can be correlated with ataxia severity. DTI may be a clinically useful tool as a quantitative surrogate marker for monitoring disease progression. (orig.)

  17. Ataxia cerebelosa persistente despues de la administracion toxica de difenilhidantoina

    Directory of Open Access Journals (Sweden)

    Andrés M. Villa

    1994-12-01

    Full Text Available La intoxicacion cronica con difenilhidantoina (DFH es bien conocida como causa de ataxia irreversible en pacientes epilépticos debida a atrofia cerebelosa con perdida de células de Purkinje. No es asi con la intoxicación aguda, puesto que sus signos y síntomas son reversibles. Presentamos un paciente con convulsiones parciales complejas, secundarias a un quiste temporal, que habia sido tratado irregularmente con DFH durante dos años con dosis variables que oscilaban en los 100 mg/dia. Dada la refractariedad de su cuadro convulsivo en una entrevista previa a su ingreso se le indico un aumento brusco de la dosis del fármaco que alcanzo a los 400 mg/dia. Ello ocasiono un sindrome pancerebeloso severo que motivo su internación. Posteriormente a la suspension de la DFH y la exeresis del quiste temporal mejoro su cuadro convulsivo, aunque quedo con ataxia de miembros inferiores y asinergia de tronco, cuadro con el que fue dado de alta. Un año despues, el paciente se encontraba libre de convulsiones, pero su sindrome cerebeloso no se habia modificado. El estudio por imágenes no evidencio atrofia cerebelosa.

  18. Enfermedad cardiovascular en pacientes cubanos afectados por Ataxia de Friedreich.

    Directory of Open Access Journals (Sweden)

    Tania Cruz Mariño

    2010-01-01

    Full Text Available Al describir la ataxia de Friedreich, Nicholaus hizo referencia a la patología cardiaca. Esta enfermedad autosómica recesiva se debe a una mutación dinámica en el gen FRDA, codificándose deficientemente la proteína Frataxina, conduciendo a estrés oxidativo y muerte celular cardiaca. La presente investigación se desarrolló con el objetivo de describir las anomalías cardiovasculares presentes en los pacientes cubanos afectados por ataxia de Friedreich. A los individuos con diagnóstico molecular confirmatorio de la enfermedad se les realizó electrocardiograma y ecocardiograma, así como evaluación clínica mediante escalas validadas internacionalmente: ICARS y SARA. Los trastornos de repolarización ventricular difusos, los trastornos de conducción intraauricular, así como los trastornos de la función diastólica resultaron hallazgos frecuentes. El patrón restrictivo apreciado provee evidencia invivo de que la enfermedad conduce a disfunción diastólica del ventrículo izquierdo. La ocurrencia de un Infarto Agudo del Miocardio silente indica la importancia de identificar formas incipientes de afectación miocárdica.

  19. Cerebellar blood flow in methylmercury poisoning (Minamata disease)

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, K.; Korogi, Y.; Tomiguchi, S.; Takahashi, M. [Dept. of Radiology, Kumamoto University School of Medicine (Japan); Okajima, T. [Dept. of Neurology, Johnan Hospital, Maihara, Johnan-mochi (Japan); Sato, H. [Dept. of Neurology, Minamata City General Hospital and Medical Centre (Japan)

    2001-04-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99 m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part. (orig.)

  20. Bilateral cerebellar activation in unilaterally challenged essential tremor

    Directory of Open Access Journals (Sweden)

    Marja Broersma

    2016-01-01

    Conclusions: Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

  1. Anomalous cerebellar anatomy in Chinese children with dyslexia

    Directory of Open Access Journals (Sweden)

    Ying-Hui eYang

    2016-03-01

    Full Text Available The cerebellar deficit hypothesis for developmental dyslexia (DD claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia.

  2. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  3. Cerebellar infarct patterns: The SMART-Medea study

    Directory of Open Access Journals (Sweden)

    Laurens J.L. De Cocker, MD

    2015-01-01

    Conclusions: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

  4. Late Onset of Cerebellar Abiotrophy in a Boxer Dog

    Directory of Open Access Journals (Sweden)

    Sanjeev Gumber

    2010-01-01

    Full Text Available Cerebellar abiotrophy is a degenerative disorder of the central nervous system and has been reported in humans and animals. This case report documents clinical, histopathological, and immunohistochemical findings of cerebellar abiotrophy in an adult Boxer dog. A 3.5-year-old, female, tan Boxer dog presented with a six-week history of left-sided head tilt. Neurological examination and additional diagnostics during her three subsequent visits over 4.5 months revealed worsening of neurological signs including marked head pressing, severe proprioceptive deficits in all the four limbs, loss of menace response and palpebral reflex in the left eye, and a gradual seizure lasting one hour at her last visit. Based on the immunohistochemical staining for glial fibrillary acidic protein and histopathological examination of cerebellum, cerebellar cortical abiotrophy was diagnosed. This is the first reported case of cerebellar abiotrophy in a Boxer dog to our knowledge.

  5. Bilateral cerebellar activation in unilaterally challenged essential tremor

    NARCIS (Netherlands)

    Broersma, Marja; van der Stouwe, Anna M. M.; Buijink, Arthur W. G.; de Jong, Bauke M.; Groot, Paul F. C.; Speelman, Johannes D.; Tijssen, Marina A. J.; van Rootselaar, Anne-Fleur; Maurits, Natasha M.

    2016-01-01

    Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging

  6. Cerebellar blood flow in methylmercury poisoning (Minamata disease)

    International Nuclear Information System (INIS)

    Itoh, K.; Korogi, Y.; Tomiguchi, S.; Takahashi, M.; Okajima, T.; Sato, H.

    2001-01-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99 m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part. (orig.)

  7. Liver Growth Factor (LGF Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2016-12-01

    Full Text Available Friedreich’s ataxia (FA is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF, which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXNYG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold and heart (1.2-fold. LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

  8. Diabetes mellitus in Friedreich Ataxia: A case series of 19 patients from the German-Austrian diabetes mellitus registry.

    Science.gov (United States)

    Pappa, Angeliki; Häusler, Martin G; Veigel, Andreas; Tzamouranis, Konstantina; Pfeifer, Martin W; Schmidt, Andreas; Bökamp, Martin; Haberland, Holger; Wagner, Siegfried; Brückel, Joachim; de Sousa, Gideon; Hackl, Lukas; Bollow, Esther; Holl, Reinhard W

    2018-05-12

    Friedreich ataxia (FRDA) is a multisystem autosomal recessive disease with progressive clinical course involving the neuromuscular and endocrine system. Diabetes mellitus (DM) is one typical non-neurological manifestation, caused by beta cell failure and insulin resistance. Because of its rarity, knowledge on DM in FRDA is limited. Based on data from 200 301 patients with DM of the German-Austrian diabetes registry (DPV) and two exemplary patient reports, characteristics of patients with DM and FRDA are compared with classical type 1 or type 2 diabetes. Diabetes phenotype in FRDA is intermediate between type 1 and type 2 diabetes with ketoacidosis being frequent at presentation and blood glucose levels similar to T1Dm but higher than in T2Dm (356 ±165 and 384± 203 mg/dl). 63.2% of FRDA patients received insulin monotherapy, 21% insulin plus oral antidiabetics and 15.8% lifestyle change only, applying similar doses of insulin in all three groups. FRDA patients did not show overweight and HbA1c levels were even lower than in T1Dm or T2Dm patients, respectively, indicating good overall diabetes control. FRDADm can be controlled by individualized treatment regimen with insulin or oral antidiabetics. Patients with DM in FRDA may show a relevant risk to ketoacidotic complications, which should be avoided. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

    Science.gov (United States)

    Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

    2018-01-01

    Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications

  10. Aberrant cerebellar connectivity in bipolar disorder with psychosis.

    Science.gov (United States)

    Shinn, Ann K; Roh, Youkyung S; Ravichandran, Caitlin T; Baker, Justin T; Öngür, Dost; Cohen, Bruce M

    2017-07-01

    The cerebellum, which modulates affect and cognition in addition to motor functions, may contribute substantially to the pathophysiology of mood and psychotic disorders, such as bipolar disorder. A growing literature points to cerebellar abnormalities in bipolar disorder. However, no studies have investigated the topographic representations of resting state cerebellar networks in bipolar disorder, specifically their functional connectivity to cerebral cortical networks. Using a well-defined cerebral cortical parcellation scheme as functional connectivity seeds, we compared ten cerebellar resting state networks in 49 patients with bipolar disorder and a lifetime history of psychotic features and 55 healthy control participants matched for age, sex, and image signal-to-noise ratio. Patients with psychotic bipolar disorder showed reduced cerebro-cerebellar functional connectivity in somatomotor A, ventral attention, salience, and frontoparietal control A and B networks relative to healthy control participants. These findings were not significantly correlated with current symptoms. Patients with psychotic bipolar disorder showed evidence of cerebro-cerebellar dysconnectivity in selective networks. These disease-related changes were substantial and not explained by medication exposure or substance use. Therefore, they may be mechanistically relevant to the underlying susceptibility to mood dysregulation and psychosis. Cerebellar mechanisms deserve further exploration in psychiatric conditions, and this study's findings may have value in guiding future studies on pathophysiology and treatment of mood and psychotic disorders, in particular.

  11. Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions

    International Nuclear Information System (INIS)

    Soenmezoglu, K.; Sperling, B.; Lassen, N.A.; Henriksen, T.; Tfelt-Hansen, P.

    1993-01-01

    Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using 99m Tc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduction (average 10%) in contralateral hemispheric cortex. In all four cases clinical signs of unilateral cerebellar dysfunction were still present when rescanned 1 to 4 months later and the relative CBF decrease in the contralateral cortex of the forebrain also remained. The basal ganglia contralateral to the cerebellar lesion CBF showed variable alterations. A relative CBF decrease was seen in upper part of basal ganglia in all four cases, but it was not a constant phenomenon. A relative CBF increase in both early and late SPECT scans was seen at low levels of neostriatum in two cases. The remote CBF changes in cerebellar stroke seen in the forebrain are probably caused by reduced or abolished cerebellar output. The term ''Crossed Cerebral Diaschisis'' may be used to describe these CBF changes that would appear to reflect both decreased and increased neuronal activity. (au)

  12. Verbal Memory Impairments in Children after Cerebellar Tumor Resection

    Directory of Open Access Journals (Sweden)

    Matthew P. Kirschen

    2008-01-01

    Full Text Available This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to quantify the extent of cerebellar lobular damage from each patient's resection. Patients exhibited significantly reduced digit span for auditory but not visual stimuli, relative to controls, and damage to left hemispheral lobule VIII was significantly correlated with this deficit. Patients also showed reduced effects of articulatory suppression and this was correlated with damage to the vermis and hemispheral lobule IV/V bilaterally. Phonological similarity and recency effects did not differ overall between patients and controls, but outlier patients with abnormal phonological similarity effects to either auditory or visual stimuli were found to have damage to hemispheral lobule VIII/VIIB on the left and right, respectively. We postulate that damage to left hemispheral lobule VIII may interfere with encoding of auditory stimuli into the phonological store. These data corroborate neuroimaging studies showing focal cerebellar activation during VWM paradigms, and thereby allow us to predict with greater accuracy which specific neurocognitive processes will be affected by a cerebellar tumor resection.

  13. Factors associated with the misdiagnosis of cerebellar infarction.

    Science.gov (United States)

    Masuda, Yoko; Tei, Hideaki; Shimizu, Satoru; Uchiyama, Shinichiro

    2013-10-01

    Cerebellar infarction is easily misdiagnosed or underdiagnosed. In this study, we investigated factors leading to misdiagnosis of cerebellar infarction in patients with acute ischemic stroke. Data on neurological and radiological findings from 114 consecutive patients with acute cerebellar infarction were analyzed. We investigated factors associated with misdiagnosis from the data on clinical findings. Thirty-two (28%) patients were misdiagnosed on admission. Misdiagnosis was significantly more frequent in patients below 60 years of age and in patients with vertebral artery dissection, and significantly less frequent in patients with dysarthria. It tended to be more frequent in patients with the medial branch of posterior inferior cerebellar artery territory infarction, and infrequent in patients with the medial branch of the superior cerebellar artery territory infarction. Thirty out of 32 (94%) misdiagnosed patients were seen by physicians that were not neurologists at the first visit. Twenty-four of 32 (75%) misdiagnosed patients were screened only by brain CT. However, patients were not checked by brain MRI or follow-up CT until their conditions worsened. Patients below 60 years of age and patients with vertebral artery dissection are more likely to have a cerebellar infarction misdiagnosed by physicians other than neurologists. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Semiconductor structure and recess formation etch technique

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Bin; Sun, Min; Palacios, Tomas Apostol

    2017-02-14

    A semiconductor structure has a first layer that includes a first semiconductor material and a second layer that includes a second semiconductor material. The first semiconductor material is selectively etchable over the second semiconductor material using a first etching process. The first layer is disposed over the second layer. A recess is disposed at least in the first layer. Also described is a method of forming a semiconductor structure that includes a recess. The method includes etching a region in a first layer using a first etching process. The first layer includes a first semiconductor material. The first etching process stops at a second layer beneath the first layer. The second layer includes a second semiconductor material.

  15. An uncommon manifestation of paraneoplastic cerebellar degeneration in a patient with high grade urothelial, carcinoma with squamous differentiation: A case report and literature review

    International Nuclear Information System (INIS)

    Zhu, Yaofeng; Chen, Shouzhen; Chen, Songyu; Song, Jing; Chen, Fan; Guo, Hu; Shang, Zhenhua; Wang, Yong; Zhou, Changkuo; Shi, Benkang

    2016-01-01

    Paraneoplastic neurological syndromes (PNS) are rare disorders associated with malignant tumours, which are triggered by autoimmune reactions. Paraneoplastic cerebellar degeneration (PCD) is the PNS type most commonly associated with ovarian and breast cancer. Two bladder cancers manifesting in PCD were previously reported. However, the cancers in these cases had poor outcomes. Here, we present a 68-year old man with history of high-grade papillary urothelial carcinoma of the bladder. The patient suffered from persistent cerebellar ataxia accompanied by bladder cancer recurrence five months after transurethral resection of the bladder tumour (TURBt). Laboratory screening for the specific antibodies of paraneoplastic neurological syndromes revealed no positive results. Symptoms were not remitted after a 7-day-course of high-dose glucocorticoid therapy. To our surprise, the patient recovered fully after laparoscopic radical cystectomy. Postoperative pathology revealed that surgical specimens were urothelial carcinoma in situ (CIS) and squamous cell carcinoma of the bladder. The patient remained asymptomatic and there was no evidence of recurrence after the followup period of 11 months. To our knowledge, this is the third report of PCD in a patient with bladder cancer. This case showed that tumour resection cured the PCD. To assist clinical evaluation and management, literature regarding basic PNS characteristics and bladder cancers was reviewed

  16. Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

    Science.gov (United States)

    Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

    2012-01-01

    Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

  17. POSSIBLE RECESSION CURVE APPLICATIONS FOR RETENTION EVALUATION

    Directory of Open Access Journals (Sweden)

    Daniel Liberacki

    2015-11-01

    Full Text Available The objective of the article was to present possible applications of recession flow curve in a small lowland watershed retention discharge size evaluation. The examined woodland micro catchment area of 0.52 sq km is located in Puszcza Zielonka in central Wielkopolska. The Hutka catchment is typically woody with high retention abilities. The catchment of the Hutka watercourse is forested in 89%, the other 11% is covered by swamps and wasteland. The predominant sites are fresh mixed coniferous forest (BMśw, fresh coniferous forest (Bśw and alder carr forest (Ol. Landscape in catchment is characterized by a large number of interior depressions, filled partly with rainwater or peatbogs, with poorly developed natural drainage. The watercourses do not exceed 1 km in length, the mean width is approx. 0.5 m, while mean depth ranges from 0.2 to 0.3 m. During hydrological research conducted in 1997/1998–1999/2000, 35 major (characteristic raised water stages were observed in Hutka after substantial precipitation. The recession curve dating from 18–24 September 2000 has the α and n rates nearest to average. Comparing the model curve and the curve created by observing watercourse flow, one can notice their resemblance and that they have similar ordinate values as well as shape. In the case of other recession curves, the maximum differences of ordinate values are also about 0.1–0.2 l/s/km2. The measuured α and n rates do not reveal any regularities. There are no significant statistical Horton model parameter (for recession flow curves dependencies between α and n and e.g. initial flows (Qo or the whole period of high water waves (Qp. Consequently, calculated relation between these parameters is only an approximation for the general evaluation of the retention discharge in the catchment area towards retention with flow function.

  18. Clinical phenotype and genetic mutation of one case with head tremor and cerebellar atrophy

    Directory of Open Access Journals (Sweden)

    Kun-ming XIE

    2017-07-01

    Full Text Available Objective To make the diagnosis for a patient presented with head tremor and cerebellar atrophy by integrating clinical features and accessory examination with genetic testing and to explore the interpretation of genetic testing results.  Methods A 30-year-old male patient's medical information, clinical pheontype, family history and accessory examinations were collected. The next?generation sequencing (NGS of exons in 3994 causative genes of Mendelian inheritance diseases and the family tree verification were carried out. China Human Phenotype Ontology (CHPO, Phenomizer, Ensembl and Online Mendelian Inheritance in Man (OMIM database were used to interpret the genetic test results.  Results The patient carried heterozygous mutation of spinocerebellar ataxia type 19 (SCA19 related KCND3 gene c.1057A > G (p. Ser353Gly, but his parents did not carry this mutation. The patient also carried heterozygous mutation of parkinsonism type 20 (PARK20 related SYNJ1 gene c.4436C > T (p.Thr1479Ile which was also seen in his mother. Phenotypic similarity analysis showed the patient's phenotype was correspond with the phenotype of SCA19, and the variation locus of KCND3 gene c.1057A > G was highly conservative with homologous gene in different species.  Conclusions By means of the integration of clinical phenotype with the result of genetic test, KCND3 gene c.1057A > G (p.Ser353Gly carried in the patient is the pathogenic mutation. DOI: 10.3969/j.issn.1672-6731.2017.07.007

  19. Financialisation, oil and the Great Recession

    International Nuclear Information System (INIS)

    Gkanoutas-Leventis, Angelos; Nesvetailova, Anastasia

    2015-01-01

    This article addresses the role of world oil price hike of 2007–08 in serving to transform the financial and banking crisis into what is commonly referred to the Great Recession. Existing literature on the global crisis of 2007–09 tends to view it as a financial or banking phenomenon, with analyses focusing mainly on state policies, governance mechanisms and market dynamics in transforming the banking crisis of 2007–08 into the economic recession of 2008-12/13 Although often attributing the global meltdown to wider phenomenon of financialisation, rarely do existing perspectives delve into the role of the commodity sector in the global credit crunch. In this paper, we aim to fill this gap, by inquiring into the role played by oil as a financial asset class in the political economy of the global crisis. - Highlights: • We study the oil price and its effects on the Great Recession. • We approach oil as a financial asset class. • We observe the transformation of oil through deregulation.

  20. [Spinocerebellar ataxia type 8: the case of a Spanish family].

    Science.gov (United States)

    Mayo-Cabrero, D; Sánchez-Migallón, M; Cantarero, S; García-Ruiz Espiga, P J; Giménez-Pardo, A; Trujillo-Tiebas, M; Ayuso-García, C

    Dominant autosomic ataxias include a group of neurodegenerative diseases characterized by the abnormal expansion of triplets. Male aged 33, with expansion of the SCA 8 gene (100 repetitions), who presented a clinical picture compatible with a pancerebellar syndrome. The patient had been diagnosed 11 years earlier as suffering from previously of histiocytosis X. A clinico genetic study was conducted on the patient and several members of his family (parents and two sisters). Both sisters and the father were found to be carriers of the expansion (110 and 150 repetitions, respectively), and are currently asymptomatic. There is no relation between the number of repetitions and the age of onset of the disease. The normal interval in our population oscillates between 16 37 repetitions, and the pathological interval has not been well determined. There may be a relation between the SCA 8 form and histiocytosis X.

  1. Vitamin B12 deficiency presenting as acute ataxia.

    Science.gov (United States)

    Crawford, John Ross; Say, Daphne

    2013-03-26

    A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.

  2. ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

    Directory of Open Access Journals (Sweden)

    Jayesh M. Bhatt

    2015-12-01

    Full Text Available Ataxia telangiectasia (A-T is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

  3. Electrophysiological mapping of novel prefrontal - cerebellar pathways

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2009-08-01

    Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  4. DNA strand breakage repair in ataxia telangiectasia fibroblast-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, Jr, R A; Sheridan, III, R B; Huang, P C [Johns Hopkins Univ., Baltimore, Md. (USA). Dept. of Environmental and Biophysical Sciences

    1975-12-01

    Human diploid fibroblast-like cells derived from four patients with the genetic disease ataxia telangiectasia and from two non-mutant donors were examined for the repair of x-ray induced strand breaks in DNA. The ataxia telangiectasia cultures showed no significant differences from the non-mutant cultures in the kinetics and extent of strand repair. This suggests that the increased spontaneous and x-ray induced chromatid aberrations observed in ataxia telangiectasia cells are not caused by a defect in the repair of single strand breaks as might be suspected from a general model of aberration production.

  5. Deep Brain Stimulation for the Treatment of Tremor and Ataxia Associated with Abetalipoproteinemia

    Directory of Open Access Journals (Sweden)

    Antonios Mammis

    2012-07-01

    Full Text Available Background: Abetalipoproteinemia is a rare disorder of fat absorption, characterized by vitamin deficiency, acanthocytosis, and neurologic symptoms including ataxia and tremor.Case Report: A 41-year-old male with abetalipoproteinemia is presented. He underwent staged bilateral thalamic deep brain stimulation (DBS for the treatment of his tremors. After DBS, the patient achieved significant improvements in his tremors, ataxia, and quality of life.Discussion: Thalamic DBS proved to be both safe and efficacious in the management of ataxia and tremors in a patient with abetalipoproteinemia. This is the first report of DBS in abetalipoproteinemia in the literature. 

  6. A cerebellar neuroprosthetic system: computational architecture and in vivo experiments

    Directory of Open Access Journals (Sweden)

    Ivan eHerreros Alonso

    2014-05-01

    Full Text Available Emulating the input-output functions performed by a brain structure opens the possibility for developing neuro-prosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuro-prosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step towards replacing lost functions of the central nervous system via neuro-prosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuro-prosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step towards the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term

  7. Microvascular anatomy of the cerebellar parafloccular perforating space.

    Science.gov (United States)

    Sosa, Pablo; Dujovny, Manuel; Onyekachi, Ibe; Sockwell, Noressia; Cremaschi, Fabián; Savastano, Luis E

    2016-02-01

    The cerebellopontine angle is a common site for tumor growth and vascular pathologies requiring surgical manipulations that jeopardize cranial nerve integrity and cerebellar and brainstem perfusion. To date, a detailed study of vessels perforating the cisternal surface of the middle cerebellar peduncle-namely, the paraflocculus or parafloccular perforating space-has yet to be published. In this report, the perforating vessels of the anterior inferior cerebellar artery (AICA) in the parafloccular space, or on the cisternal surface of the middle cerebellar peduncle, are described to elucidate their relevance pertaining to microsurgery and the different pathologies that occur at the cerebellopontine angle. Fourteen cadaveric cerebellopontine cisterns (CPCs) were studied. Anatomical dissections and analysis of the perforating arteries of the AICA and posterior inferior cerebellar artery at the parafloccular space were recorded using direct visualization by surgical microscope, optical histology, and scanning electron microscope. A comprehensive review of the English-language and Spanish-language literature was also performed, and findings related to anatomy, histology, physiology, neurology, neuroradiology, microsurgery, and endovascular surgery pertaining to the cerebellar flocculus or parafloccular spaces are summarized. A total of 298 perforating arteries were found in the dissected specimens, with a minimum of 15 to a maximum of 26 vessels per parafloccular perforating space. The average outer diameter of the cisternal portion of the perforating arteries was 0.11 ± 0.042 mm (mean ± SD) and the average length was 2.84 ± 1.2 mm. Detailed schematics and the surgical anatomy of the perforating vessels at the CPC and their clinical relevance are reported. The parafloccular space is a key entry point for many perforating vessels toward the middle cerebellar peduncle and lateral brainstem, and it must be respected and protected during surgical approaches to the

  8. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

    International Nuclear Information System (INIS)

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H.; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F. M. J.

    2014-01-01

    Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

  9. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

    Energy Technology Data Exchange (ETDEWEB)

    Herreros, Ivan; Giovannucci, Andrea [Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra, Barcelona (Spain); Taub, Aryeh H.; Hogri, Roni; Magal, Ari [Psychobiology Research Unit, Tel Aviv University, Tel Aviv (Israel); Bamford, Sim [Physics Laboratory, Istituto Superiore di Sanità, Rome (Italy); Prueckl, Robert [Guger Technologies OG, Graz (Austria); Verschure, Paul F. M. J., E-mail: paul.verschure@upf.edu [Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra, Barcelona (Spain); Institució Catalana de Recerca i Estudis Avançats, Barcelona (Spain)

    2014-05-21

    Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

  10. Reduced cardiac {sup 123}I-metaiodobenzylguanidine uptake in patients with spinocerebellar ataxia type 2: a comparative study with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    De Rosa, Anna; De Leva, Maria Fulvia; Maddaluno, Gennaro; Filla, Alessandro; De Michele, Giuseppe [University Federico II, Department of Neurosciences and Reproductive and Odontostomatologic Sciences, Naples (Italy); Pappata, Sabina; Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Fiumara, Giovanni [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Carotenuto, Raffaella; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy)

    2013-12-15

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia, supranuclear ophthalmoplegia, and peripheral neuropathy. Autonomic nervous system dysfunction is often present. This study evaluated the cardiac sympathetic function in patients with SCA2 using {sup 123}I-metaiodobenzylguanidine (MIBG) in comparison with patients with Parkinson's disease (PD) and control subjects. Nine patients with SCA2, nine patients with PD, and nine control subjects underwent {sup 123}I-MIBG imaging studies from which early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates were calculated. Early (F = 12.3, p < 0.0001) and late (F = 16.8, p < 0.0001) H/M ratios were significantly different among groups. In controls, early and late H/M ratios (2.2 {+-} 0.12 and 2.1 {+-} 0.20) were significantly higher than in patients with SCA2 (1.9 {+-} 0.23 and 1.8 {+-} 0.20, both p < 0.05) and with patients with PD (1.7 {+-} 0.29 and 1.4 {+-} 0.35, both p < 0.001). There was also a significant difference in washout rates among groups (F = 11.7, p < 0.0001). In controls the washout rate (19.9 {+-} 9.6 %) was significantly lower (p < 0.005) than in patients with PD (51.0 {+-} 23.7 %), but not different from that in SCA2 patients (19.5 {+-} 9.4 %). In SCA2 patients, in a multivariable linear regression analysis only the Scale for the Assessment and Rating of Ataxia score was independently associated with early H/M ratio ({beta} = -0.12, p < 0.05). {sup 123}I-MIBG myocardial scintigraphy demonstrated an impairment of cardiac sympathetic function in patients with SCA2, which was less marked than in PD patients. These results suggest that {sup 123}I-MIBG cardiac imaging could become a useful tool for analysing the pathophysiology of SCA2. (orig.)

  11. Challenges in sleep stage R scoring in patients with autosomal dominant spinocerebellar ataxias (SCA1, SCA2 and SCA3) and oculomotor abnormalities: a whole night polysomnographic evaluation.

    Science.gov (United States)

    Seshagiri, Doniparthi Venkata; Sasidharan, Arun; Kumar, Gulshan; Pal, Pramod Kumar; Jain, Sanjeev; Kutty, Bindu M; Yadav, Ravi

    2018-02-01

    Spinocerebellar ataxias are progressive neurodegenerative disorders characterized by progressive cerebellar features with additional neuro-axis involvement. Oculomotor abnormality is one of the most frequent manifestations. This study was done to assess the polysomnographic abnormalities in patients with Spinocerebellar ataxia (SCA1, SCA2 and SCA3) and also to evaluate whether oculomotor abnormalities interfere with sleep stage R scoring. The study was carried out using 36 genetically positive SCA patients. All patients underwent neurological examination with special focus on oculomotor function (optokinetic nystagmus-OKN and extraocular movement restriction-EOM). The sleep quality was measured with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Disease severity was assessed with International Cooperative Ataxia Rating Scale (ICARS). All the patients underwent over-night video-polysomnography (VPSG). Out of 36 patients studied, the data of 34 patients [SCA1 (n = 12), SCA2 (n = 13), SCA3 (n = 9)] were used for final analysis. Patients from SCA1, SCA2, and SCA3 category did not show significant differences in age and diseases severity (ICARS). All patients had vertical OKN impairment. Oculomotor impairment was higher in SCA2 patients. Sleep macro-architecture analysis showed absent stage R sleep, predominantly in SCA2 (69%) followed by SCA3 (44%) and SCA1 (8%). Patients showed a strong negative correlation of stage R sleep percentage with disease severity and oculomotor dysfunction. Voluntary saccadic eye movement velocity and rapid eye movements (REMs) in sleep are strongly correlated. The more severe the saccadic velocity impairment, the less likely was it to generate REMs (rapid eye movements) during stage R. Accordingly 69% of SCA2 patients with severe occulomotor impairments showed absent stage R as per the AASM sleep scoring. We presume that the impaired REMs generation in sleep could be due to oculomotor abnormality and has

  12. Distributed Cerebellar Motor Learning; a Spike-Timing-Dependent Plasticity Model

    Directory of Open Access Journals (Sweden)

    Niceto Rafael Luque

    2016-03-01

    Full Text Available Deep cerebellar nuclei neurons receive both inhibitory (GABAergic synaptic currents from Purkinje cells (within the cerebellar cortex and excitatory (glutamatergic synaptic currents from mossy fibres. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP located at different cerebellar sites (parallel fibres to Purkinje cells, mossy fibres to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibres to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP and inhibitory (i-STDP mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibres to Purkinje cells synapses and then transferred to mossy fibres to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation towards optimising its working range.

  13. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  14. Does cerebellar neuronal integrity relate to cognitive ability?

    International Nuclear Information System (INIS)

    Rae, C.; Lee, M.; Dixon, R.M.; Blamire, A.; Thompson, C.; Styles, P.; Radda, G.K.; University of Sydney, NSW; Karmiloff-Smith, A.; Grant, J.

    1998-01-01

    Full text: Magnetic resonance spectroscopy (MRS) allows the non-invasive measurement of metabolite levels in the brain. One of these is N-acetylaspartate (NA), a molecule found solely in neurones, synthesised there by mitochondria. This compound can be considered as a marker of 1) neuronal density and 2) neuronal mitochondria function. We recently completed a joint MRS and neuropsychological investigation of Williams-Beuren syndrome (WBS), a rare (1/20,000) autosomal dominant disorder caused by a deletion which includes the elastin locus and LIM-kinase. The syndrome has an associated behavioural and cognitive profile which includes hyperactivity, hyperacusis and excessive sociability. Spatial skills are severely affected, while verbal skills are left relatively intact Our investigation showed loss of NA from the cerebellum in WBS compared with normal controls, with the subject population as a whole displaying a continuum of cerebellar NA concentration. Ability at cognitive tests, including the Weschler IQ scale and various verbal and spatial tests, was shown to correlate significantly and positively with the concentration of NA in the cerebellum. This finding can be interpreted in one of two ways: 1. Our sampling of cerebellar metabolite levels represents a 'global' sampling of total brain neuronal density and, as such, is independent of cerebellar integrity. 2. Cerebellar neuronal integrity is associated with performance at cognitive tests. If the latter interpretation is shown to be the case, it will have important implications for our current understanding of cerebellar function. Copyright (1998) Australian Neuroscience Society

  15. CT and MR imaging of splenic leiomyoma in a child with ataxia telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Coskun, M. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey); Aydingoez, Ue. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey); Tacal, T. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey); Ariyuerek, M. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey); Demirkazik, F. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey); Oguzkurt, L. [Dept. of Radiology, Hacettepe University Hospital, Ankara (Turkey)

    1995-02-01

    Computed tomographic and magnetic resonance imaging findings of a splenic leiomyoma in an 8-year-old boy with ataxia telangiectasia are presented. This is the first reported case of a splenic leiomyoma in the literature. (orig.)

  16. CT and MR imaging of splenic leiomyoma in a child with ataxia telangiectasia

    International Nuclear Information System (INIS)

    Coskun, M.; Aydingoez, Ue.; Tacal, T.; Ariyuerek, M.; Demirkazik, F.; Oguzkurt, L.

    1995-01-01

    Computed tomographic and magnetic resonance imaging findings of a splenic leiomyoma in an 8-year-old boy with ataxia telangiectasia are presented. This is the first reported case of a splenic leiomyoma in the literature. (orig.)

  17. Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia.

    Science.gov (United States)

    Ejaz, Resham; Chen, Shiyi; Isaacs, Charles J; Carnevale, Amanda; Wilson, Judith; George, Kristen; Delatycki, Martin B; Perlman, Susan L; Mathews, Katherine D; Wilmot, George R; Hoyle, J Chad; Subramony, Sub H; Zesiewicz, Theresa; Farmer, Jennifer M; Lynch, David R; Yoon, Grace

    2018-05-01

    To determine how mobility device use impacts quality of life in children with Friedreich ataxia. Data from 111 pediatric patients with genetically confirmed Friedreich ataxia were collected from a prospective natural history study utilizing standardized clinical evaluations, including health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Module. Mobility device use was associated with worse mean PedsQL total, physical, emotional, social, and academic subscores, after adjusting for gender, age of disease onset, and Friedreich Ataxia Rating Scale score. The magnitude of the difference was greatest for the physical subscore (-19.5 points, 95% CI = -30.00, -8.99, P mobility devices trended toward worse physical subscore (-16.20 points, 95% CI = -32.07, -0.33, P = .05). Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia.

  18. Deep Brain Stimulation for Tremor Associated with Underlying Ataxia Syndromes: A Case Series and Discussion of Issues

    Directory of Open Access Journals (Sweden)

    Genko Oyama

    2014-07-01

    Full Text Available Background: Deep brain stimulation (DBS has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy.Methods: A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2, fragile X associated tremor ataxia syndrome (FXTAS, a case of idiopathic ataxia (ataxia not otherwise specified [NOS], spinocerebellar ataxia type 17 (SCA17, and a senataxin mutation (SETX.Results: DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia‐related symptoms.Discussion: DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened.Erratum published on July 27, 2016

  19. The Great Recession, unemployment and suicide.

    Science.gov (United States)

    Norström, Thor; Grönqvist, Hans

    2015-02-01

    How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960-2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Avances en el tratamiento de las ataxias crónicas

    Directory of Open Access Journals (Sweden)

    María Celeste Buompadre

    2013-09-01

    Full Text Available Las ataxias crónicas cerebelosas autosómicas recesivas constituyen el grupo más amplio de ataxias hereditarias, con presentación principalmente en la edad pediátrica, se caracterizan por degeneración o desarrollo anormal del cerebelo y de la médula espinal. Hasta el momento el tratamiento etiológico está disponible sólo para algunas formas: aquellas con defecto metabólico conocido como la abetalipoproteinemia, la ataxia con deficiencia de vitamina E y la xantomatosis cerebrotendinosa. En estas entidades la modificación de la dieta, el suplemento con vitaminas E y A principalmente y la administración de ácido quenodexocicólico pueden cambiar el curso de la enfermedad. En la mayoría de los otros tipos de ataxia el tratamiento es solo de soporte, como por ejemplo el uso de antioxidantes y quelantes del hierro en la ataxia de Friederich con el objetivo de disminuir los depósitos de hierro mitocondriales, de corticoides en la ataxia telangiectasia y de ubiquinona /coenzima Q10 en la ataxia por deficiencia de coenzima Q-10. Si bien hasta el momento ningún tratamiento es curativo para la mayoría de las ataxias crónicas autosómico recesivas, el diagnóstico precoz de estas entidades se asocia con una mejor respuesta a las diferentes drogas.

  1. Autosomal recessive Charcot-Marie-Tooth neuropathy.

    Science.gov (United States)

    Espinós, Carmen; Calpena, Eduardo; Martínez-Rubio, Dolores; Lupo, Vincenzo

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy that comprises a complex group of more than 50 diseases, is the most common inherited neuropathy. CMT is generally divided into demyelinating forms, axonal forms and intermediate forms. CMT is also characterized by a wide genetic heterogeneity with 29 genes and more than 30 loci involved. The most common pattern of inheritance is autosomal dominant (AD), although autosomal recessive (AR) forms are more frequent in Mediterranean countries. In this chapter we give an overview of the associated genes, mechanisms and epidemiology of AR-CMT forms and their associated phenotypes.

  2. Impact of recession on Swiss pension program.

    Science.gov (United States)

    McArdle, F B

    1978-04-01

    Legislation drafted in Switzerland in 1975--77 aims at countering the effects of inflation and recession by bringing increased revenues into the system, reducing expenditures, devising a mechanism to adjust pensions automatically, and improving income maintenance for the unemployed. The proposed legislation to place the social security system on a sound financial basis now needs voter approval in a referendum. Swiss voters meanwhile rejected (in mid-1977) a government-proposed value-added tax designed to finance increasing government contributions during 1978-82. Still to be resolved, therefore, is the problem of how the government will finance higher contributions and still achieve its staged goal of a balanced budget.

  3. Children's Physical Activity Behavior during School Recess

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Andersen, Henriette Bondo; Troelsen, Jens

    2016-01-01

    participated in go-along group interviews, and recess behavior was observed using an ethnographical participant observation approach. All data were analyzed separated systematically answering the Five W Questions. Children were categorized into Low, Middle and High physical activity groups and these groups...... quantitative GPS and accelerometer measurements with qualitative go-along group interviews and participant observations. Data were collected during three weekdays in a public school in Denmark. Eighty-one children (47 girls) wore an accelerometer (ActiGraph GT3X) and GPS (QStarz BT-Q1000xt), sixteen children...

  4. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  5. Early childhood obesity is associated with compromised cerebellar development.

    Science.gov (United States)

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  6. Distal anterior inferior cerebellar artery syndrome after acoustic neuroma surgery.

    Science.gov (United States)

    Hegarty, Joseph L; Jackler, Robert K; Rigby, Peter L; Pitts, Lawrence H; Cheung, Steven W

    2002-07-01

    To define a clinicopathologic syndrome associated with persistent cerebellar dysfunction after acoustic neuroma (AN) excision. Case series derived from radiographic and clinical chart review. Tertiary referral center. In 12 patients with AN, persistent cerebellar dysfunction developed after AN removal. Each case demonstrated abnormality in the ipsilateral cerebellar peduncle on postoperative magnetic resonance imaging. Cerebellar function and ambulatory status over the first postoperative year. On magnetic resonance imaging scans, the extent of cerebellar peduncle infarcts was variable. It ranged from focal brain injury (2 cm) spanning the full thickness of the peduncle. Peduncular infarcts were associated with large tumor size (average 3.8 cm, range 2.0-5.5 cm diameter). The long-term functional outcomes (>1 yr) varied. Dysmetria was unchanged or improved in over half of the patients (6 of 11 patients). Gait recovered to normal or to preoperative levels in 5 patients. In the 6 patients with persistent impaired mobility, 2 had mild gait disturbance, 3 required regular use of a cane, and 1 has been dependent on a walker. One patient had sustained mild motor weakness. Three of 11 patients remained dependent on others for activities of daily living. Peduncle injury most likely stems from interruption of distal branches of the anterior inferior cerebellar artery (AICA). These small vessels are intimately related to the capsule of the tumor and may supply both the neoplasm and the brain parenchyma. It has long been recognized that interruption of the proximal segment of the AICA results in severe injury to the pons, with devastating neurologic sequelae. A limited AICA syndrome caused by loss of its distal ramifications seems a more plausible explanation for peduncular infarction than either venous insufficiency or direct surgical trauma.

  7. State Government Revenue Recovery from the Great Recession

    OpenAIRE

    James Alm; David L. Sjoquist

    2014-01-01

    The "Great Recession" lasted from December 2007 to June 2009, and it wreaked havoc on the revenues of state (and local) governments. While the U.S. economy has improved since the end of the Great Recession, state government revenues have in most cases still not completely recovered. We use various indicators to measure how different states have -- or have not -- recovered in the aftermath of the Great Recession, and we also attempt to explain why these different patterns of recovery have emer...

  8. Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

    Science.gov (United States)

    Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

    2014-05-01

    To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and

  9. CT EVALUATION OF AZYGOESOPHAGEAL RECESS IN ADULTS

    Directory of Open Access Journals (Sweden)

    Kulamani Sahoo

    2015-02-01

    Full Text Available Azygoesophageal recess (AER is right posterior mediastinal recess . Knowledge of normal radiologic appearance and manifestations of disease in AER can facilitate the detection and diagnosis of many intrathoracic diseases ranging from infective processes to tumors involving mediastinum, lung/pleura, lymphatic system, upper gastrointestinal system (esophagus & stomach & cardio - vascular system. Aim of this study was to investigate various intrathoracic pathologies, altering the configuration of AER on CT in adults & to find out any significance with various disease processes. This study was carried out in CT center, Department of Radiodiagnosis, Krishna Institute of medical sciences, Karad from October 2012 - September 2014. CT thorax of 156 patients was studied for configuration of AER irrespective of pathology. In this study , configuration of AER was altered in descending order with pathologies belonging to following systems: Respiratory system (Lung parenchyma pathologies causing volume loss of right lower lobe particularly Koch’s , UIP , Malignancy , Pleural pathologies (Secondary more common than Primary >Lymphatic system(secondary subcarinal lymph node more common than Primary Lymphoma >Cardio - vascular system(Cardiomegaly particularly Left atrial enlargement >Gastrointestinal system ( hiatus herni a & esophageal Cancer > Mediastinum ( Koch’s of dorsal spine with paraspinal abscess.

  10. Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

    Science.gov (United States)

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-12-01

    Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

  11. A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

    Science.gov (United States)

    McBride, Devin W; Nowrangi, Derek; Kaur, Harpreet; Wu, Guangyong; Huang, Lei; Lekic, Tim; Tang, Jiping; Zhang, John H

    2018-03-01

    Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

  12. File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.50.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  13. File list: Pol.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  14. File list: Pol.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  15. File list: Unc.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  16. File list: His.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  17. File list: His.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  18. File list: His.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  19. File list: Oth.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  20. File list: Pol.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...