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Sample records for ataxia patients cellular

  1. The patient with ataxia.

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    Maggs, F G

    2014-01-01

    In this article we look at the causes of ataxia, and how the patient presenting with ataxia should be managed. One of the difficulties in managing the patient with ataxia is that acute ataxia has many causes, but usually these can be teased out by means of a careful history and examination. Investigations can then be targeted at confirming or disproving the differential diagnosis. Some patients with ataxia need to be managed in hospital, but many can be investigated, and receive therapy, as an outpatient.

  2. The clinical characteristics of spinocerebellar ataxia 36: a study of 2121 Japanese ataxia patients.

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    Sugihara, Katsunobu; Maruyama, Hirofumi; Morino, Hiroyuki; Miyamoto, Ryosuke; Ueno, Hiroki; Matsumoto, Masayasu; Kaji, Ryuji; Kitaguchi, Hiroshi; Yukitake, Motohiro; Higashi, Yasuto; Nishinaka, Kazuto; Oda, Masaya; Izumi, Yuishin; Kawakami, Hideshi

    2012-08-01

    Spinocerebellar ataxia 36 is caused by the expansion of the intronic GGCCTG hexanucleotide repeat in NOP56. The original article describing this condition demonstrated that patients with spinocerebellar ataxia 36 present with tongue atrophy, a finding that had not been seen in previous types of spinocerebellar ataxias. A total of 2121 patients with clinically diagnosed spinocerebellar ataxia participated in the study. We screened our patient samples for spinocerebellar ataxia 36 using the repeat-primed polymerase chain reaction method and also determined the clinical features of spinocerebellar ataxia 36. Of the ataxia cases examined, 12 were identified as spinocerebellar ataxia 36. Of these, 7 cases (6 families) were autosomal dominant, 4 cases (three families) had a positive family history but were not autosomal dominant, and 1 case was sporadic. The average age of onset was 51.7 years, and disease progression was slow. The main symptoms and signs of disease included ataxia, dysarthria, and hyperreflexia. Approximately half the affected patients demonstrated nystagmus, bulging eyes, and a positive pathological reflex, although dysphagia, tongue atrophy, and hearing loss were rare. Moreover, the observed atrophy of the cerebellum and brain stem was not severe. The patients identified in this study were concentrated in western Japan. The frequency of spinocerebellar ataxia 36 was approximately 1.2% in the autosomal dominant group, and the age of onset for this condition was later in comparison with other spinocerebellar ataxia subtypes.

  3. Ataxia.

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    Akbar, Umar; Ashizawa, Tetsuo

    2015-02-01

    Ataxia is a disorder of balance and coordination resulted from dysfunctions involving cerebellum and its afferent and efferent connections. While a variety of disorders can cause secondary ataxias, the list of genetic causes of ataxias is growing longer. Genetic abnormalities may involve mitochondrial dysfunction, oxidative stress, abnormal mechanisms of DNA repair, possible protein misfolding, and abnormalities in cytoskeletal proteins. Few ataxias are fully treatable while hope for efficacious gene therapy and pharmacotherapy is emerging. A discussion of the ataxias is presented here with brief mention of acquired ataxias, and a greater focus on inherited ataxias.

  4. Substantia nigra echogenicity in Friedreich's ataxia patients.

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    Sierra, María; Infante, Jon; Berciano, José

    2013-08-01

    The aim of this study is to assess the presence of substantia nigra (SN) hypoechogenicity in a cohort of Friedreich's ataxia (FRDA) patients and its possible association with restless syndrome (RLS). Fourteen genetically confirmed FRDA patients and 14 sex- and age-matched healthy controls underwent transcranial sonography examination to evaluate the area of echogenicity of the SN. Both groups were clinically assessed with the essential and additional diagnostic criteria for RLS established by the International RLS Study Group. Ataxia was evaluated using the Scale for the Assessment and Rating of Ataxia. We did not find significant differences between the mean sum area of SN echogenicity in FRDA patients and in controls. Only one patient in the FDRA group and two control subjects showed SN hypoechogenicity. Two out of the 14 FDRA patients and one of the controls fulfilled diagnostic criteria for RLS. The areas of SN echogenicity in the two FRDA patients with RLS were the lowest found in this group. We conclude that our data do not support the notion that SN hypoechogenicity is related to FRDA itself, although it might be associated with RLS.

  5. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

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    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications.

  6. Sudden stopping in patients with cerebellar ataxia.

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    Serrao, Mariano; Conte, Carmela; Casali, Carlo; Ranavolo, Alberto; Mari, Silvia; Di Fabio, Roberto; Perrotta, Armando; Coppola, Gianluca; Padua, Luca; Monamì, Stefano; Sandrini, Giorgio; Pierelli, Francesco

    2013-10-01

    Stopping during walking, a dynamic motor task frequent in everyday life, is very challenging for ataxic patients, as it reduces their gait stability and increases the incidence of falls. This study was conducted to analyse the biomechanical characteristics of upper and lower body segments during abrupt stopping in ataxic patients in order to identify possible strategies used to counteract the instability in the sagittal and frontal plane. Twelve patients with primary degenerative cerebellar ataxia and 12 age- and sex-matched healthy subjects were studied. Time-distance parameters, dynamic stability of the centre of mass, upper body measures and lower joint kinematic and kinetic parameters were analysed. The results indicate that ataxic patients have a great difficulty in stopping abruptly during walking and adopt a multi-step stopping strategy, occasionally with feet parallel, to compensate for their inability to coordinate the upper body and to generate a well-coordinated lower limb joint flexor-extensor pattern and appropriate braking forces for progressively decelerating the progression of the body in the sagittal plane. A specific rehabilitation treatment designed to improve the ability of ataxic patients to transform unplanned stopping into planned stopping, to coordinate upper body and to execute an effective flexion-extension pattern of the hip and knee joints may be useful in these patients in order to improve their stopping performance and prevent falls.

  7. Analysis of spinocerebellar ataxias due to expanded triplet repeats in Greek patients with cerebellar ataxia.

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    Koutsis, Georgios; Pemble, Sally; Sweeney, Mary G; Paudel, Reema; Wood, Nicholas W; Panas, Marios; Kladi, Athina; Houlden, Henry

    2012-07-15

    The relative frequency of different autosomal dominant cerebellar ataxias, commonly referred to as spinocerebellar ataxias (SCAs), varies considerably among populations of different ethnic origin. No data exist at present on the frequency of different SCAs in the Greek population. In the present study we investigated the presence of triplet repeat expansion SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17 and DRPLA) in a cohort of 83 Greek patients with slowly progressive cerebellar ataxia. Twenty patients came from autosomal dominant (AD) pedigrees, seven displayed recessive or unclear inheritance and 56 were sporadic. We found four patients with pathological SCA expansions, all from AD pedigrees. Two patients had SCA1, one SCA2 and one SCA7 (10.0, 5.0 and 5.0% of the AD group, respectively). The clinical features of these patients were within the expected spectrum. In total, a pathological expansion was detected in 20% of patients from AD pedigrees. Interestingly, no cases of SCA3 or SCA6 were detected in the AD group. No expansions were found in other familial cases or in sporadic patients. Overall, no cases of SCA3, SCA6, SCA12, SCA17 or DRPLA were identified in the Greek population. In conclusion, SCA1, SCA2 and SCA7 are present in Greek patients with AD cerebellar ataxia in frequencies similar to those observed in other populations. SCA3 and SCA6 appear however to be rare in Greece. The genetic cause for the majority of AD ataxias remains to be identified.

  8. Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3)

    NARCIS (Netherlands)

    Seidel, K.; Meister, M.; Dugbartey, G. J.; Zijlstra, M. P.; Vinet, J.; Brunt, E. R. P.; van Leeuwen, F. W.; Rueb, U.; Kampinga, H. H.; den Dunnen, W. F. A.

    2012-01-01

    K. Seidel, M. Meister, G. J. Dugbartey, M. P. Zijlstra, J. Vinet, E. R. P. Brunt, F. W. van Leeuwen, U. Rub, H. H. Kampinga and W. F. A. den Dunnen (2012) Neuropathology and Applied Neurobiology38, 548558 Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type

  9. Ataxia in patients with brain infarcts and hemorrhages.

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    Caplan, Louis R

    2012-01-01

    Gait and limb incoordination and ataxia are most often found in patients with brainstem and cerebellar infarcts and hemorrhages. Lesions involving the thalamus and the deep portions of the cerebral hemispheres also may cause ataxia accompanied by weakness and sensory symptoms. Patients who have lesions in the lateral medulla and inferior cerebellum often topple, lean, or veer when attempting to sit, stand, or walk. They list to the side or abruptly veer when walking. The affected limbs are often hypotonic. In pontine lesions, ataxia is accompanied by weakness and pyramidal tract signs as part of an ataxic hemiparesis syndrome. In lesions affecting the superior cerebellum and the brachium conjunctivum, limb dysmetria and overshoot and dysarthria predominate and gait ataxia is absent or slight and transient. Infarcts affecting the thalamus can cause gait instability and astasia with ataxia. Lateral thalamic lesions are characterized by hemisensory symptoms, extrapyramidal limb postures and dysfunction, and gait ataxia. Lesions that affect the posterior limb of the internal capsule and its afferent and efferent projections may also cause an ataxic hemiparesis syndrome, often with accompanying hemisensory abnormalities.

  10. Spinocerebellar ataxia type 1 and Machado-Joseph disease: Incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia

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    Ranum, L.P.W.; Gomez, C.; Orr, H.T. [Univ. of Minnesota, Minneapolis, MN (United States)] [and others

    1995-09-01

    The ataxias are a complex group of diseases with both environmental and genetic causes. Among the autosomal dominant forms of ataxia the genes for two, spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD), have been isolated. In both of these disorders the molecular basis of disease is the expansion of an unstable CAG trinucleotide repeat. To assess the frequency of the SCA1 and MJD trinucleotide repeat expansions among individuals diagnosed with ataxia, we have collected DNA from individuals representing 311 families with adult-onset ataxia of unknown etiology and screened these samples for trinucleotide repeat expansions within the SCA1 and MJD genes. Within this group there are 149 families with dominantly inherited ataxia. Of these, 3% have SCA1 trinucleotide repeat expansions, whereas 21% were positive for the MJD trinucleotide expansion. Thus, together SCA1 and MJD represent 24% of the autosomal dominant ataxias in our group, and the frequency of MJD is substantially greater than that of SCA1. For the 57 patients with MJD trinucleotide repeat expansions, a strong inverse correlation between CAG repeat size and age at onset was observed (r = -.838). Among the MJD patients, the normal and affected ranges of CAG repeat size are 14-40 and 68-82 repeats, respectively. For SCA1 the normal and affected ranges are much closer, containing 19-38 and 40-81 CAG repeats, respectively. 30 refs., 1 fig., 3 tabs.

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

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    Satoh, J.I.; Tokumoto, H.; Yukitake, M.; Matsui, M.; Kuroda, Y. [Division of Neurology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849 (Japan); Matsuyama, Z.; Kawakami, H.; Nakamura, S. [Third Department of Internal Medicine, Hiroshima University School of Medicine Hiroshima (Japan)

    1998-04-01

    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 {alpha}{sub 1A} voltage-dependent P/Q-type Ca{sup 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.) With 3 figs., 1 tab., 23 refs.

  12. Visual System Involvement in Patients with Friedreich's Ataxia

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    Fortuna, Filippo; Barboni, Piero; Liguori, Rocco; Valentino, Maria Lucia; Savini, Giacomo; Gellera, Cinzia; Mariotti, Caterina; Rizzo, Giovanni; Tonon, Caterina; Manners, David; Lodi, Raffaele; Sadun, Alfredo A.; Carelli, Valerio

    2009-01-01

    Optic neuropathy is common in mitochondrial disorders, but poorly characterized in Friedreich's ataxia (FRDA), a recessive condition caused by lack of the mitochondrial protein frataxin. We investigated 26 molecularly confirmed FRDA patients by studying both anterior and posterior sections of the visual pathway using a new, integrated approach.…

  13. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

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    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

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

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    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.

  15. Urinary Symptoms and Urodynamics Findings in Patients with Friedreich's Ataxia

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    Andre F. A. Musegante

    2013-12-01

    Full Text Available Purpose To assess the prevalence of LUTS, urinary tract and urodynamics changes in patients with Friedreich's Ataxia (FA, the most common form of hereditary ataxia. Materials and Methods This study evaluated 258 patients with genetically confirmed diagnoses of FA. Of the patients, 158 responded to a questionnaire which assessed their urinary symptoms. Patients with clinical changes underwent renal function examinations, ultrasound, and urodynamic studies (UDS. Results The sample analyzed showed that 82% of the patients complained of LUTS, although only 22% related the symptoms with quality of life impairment. Twenty eight (18% of them agreed to undergo urodynamic evaluation. Urgency was the most common symptom. The exam was normal in 4 (14% and detrusor underactivity was the most common finding. 14% (4 patients presented with dilatation of the upper urinary tract at ultrasound scans. None of them had creatinine alterations. Conclusions LUTS was found in a large percentage of patients with FA, but only a few related it to their quality of life impairment. Although creatinine levels was normal in this sample, some patients may show upper urinary tract abnormalities, with deserves close observation and proper care.

  16. Unusual and severe disease course in a child with ataxia-telangiectasia.

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    Meyts, I.; Weemaes, C.M.R.; Wolf-Peeters, C. de; Proesmans, M.; Renard, M.; Uyttebroeck, A.; Boeck, K. de

    2003-01-01

    Ataxia-telangiectasia (AT) is an autosomal recessive syndrome of combined immunodeficiency. Hallmarks of the disease comprise progressive cerebellar ataxia, oculocutaneous telangiectasia, cancer susceptibility and variable humoral and cellular immunodeficiency. We describe a patient with AT presenti

  17. Quantitative analysis of upper-limb ataxia in patients with spinocerebellar degeneration.

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    Ueda, Naohisa; Hakii, Yasuhito; Koyano, Shigeru; Higashiyama, Yuichi; Joki, Hideto; Baba, Yasuhisa; Suzuki, Yume; Kuroiwa, Yoshiyuki; Tanaka, Fumiaki

    2014-07-01

    Spinocerebellar degeneration (SCD) is a progressive neurodegenerative disorder in which cerebellar ataxia causes motor disability. There are no widely applicable methods for objective evaluation of ataxia in SCD. An objective system to evaluate ataxia is necessary for use in clinical trials of newly developed medication and rehabilitation. The aim of this study was to develop a simple method to quantify the degree of upper-limb ataxia. Forty-nine patients with SCD participated in this study. Patients were instructed to trace an Archimedean spiral template, and the gap between the template spiral and the drawn spiral (gap area; GA) was measured using Image J software. Ataxia was rated using the Scale for the Assessment and Rating of Ataxia (SARA) and cerebellar volume was evaluated in 37 patients using an axial cross-section of magnetic resonance images that were obtained within 6 months of clinical evaluation. Regression analysis was performed to assess the relation between GA and patient age, disease duration, SARA score, and cerebellar volume. GA was significantly related to total SARA score (r = 0.660, p ataxia, especially upper-limb ataxia, and can be widely adopted in various settings, including clinical trials.

  18. Patients with autosomal dominant spinocerebellar ataxia have more risk of falls, important balance impairment, and decreased ability to function

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    Carolina Yuri P. Aizawa

    2013-08-01

    Full Text Available OBJECTIVES: To assess balance and ability to function in patients with spinocerebellar ataxia. METHODS: A total of 44 patients with different spinocerebellar ataxia types 1, 2, 3, and 6 were evaluated using the Tinetti balance and gait assessment and the functional independence measure. The scale for the assessment and rating of ataxia and the international cooperative ataxia rating scale were used to evaluate disease severity. RESULTS: Most patients showed significant risk of falls. The balance scores were significantly different in spinocerebellar ataxia types. A significant positive correlation between balance and disease severity was found. CONCLUSION: Patients with spinocerebellar ataxia have important balance impairment and risk of falls that influence the ability to function such as self-care, transfers, and locomotion. Furthermore, the more severe ataxia is, the more compromised are postural balance, risk of falls, and ability to function.

  19. Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

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    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.

  20. In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7.

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    Adanyeguh, Isaac M; Henry, Pierre-Gilles; Nguyen, Tra M; Rinaldi, Daisy; Jauffret, Celine; Valabregue, Romain; Emir, Uzay E; Deelchand, Dinesh K; Brice, Alexis; Eberly, Lynn E; Öz, Gülin; Durr, Alexandra; Mochel, Fanny

    2015-04-15

    Spinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum and the pons. Proton magnetic resonance spectroscopy ((1) H MRS) using an optimized semiadiabatic localization by adiabatic selective refocusing (semi-LASER) protocol was performed at 3 T to determine metabolite concentrations in the cerebellar vermis and pons of a cohort of patients with SCA1 (n=16), SCA2 (n=12), SCA3 (n=21), and SCA7 (n=12) and healthy controls (n=33). Compared with controls, patients displayed lower total N-acetylaspartate and, to a lesser extent, lower glutamate, reflecting neuronal loss/dysfunction, whereas the glial marker, myoinositol (myo-Ins), was elevated. Patients also showed higher total creatine as reported in Huntington's disease, another polyglutamine repeat disorder. A strong correlation was found between the Scale for the Assessment and Rating of Ataxia and the neurometabolites in both affected regions of patients. Principal component analyses confirmed that neuronal metabolites (total N-acetylaspartate and glutamate) were inversely correlated in the vermis and the pons to glial (myo-Ins) and energetic (total creatine) metabolites, as well as to disease severity (motor scales). Neurochemical plots with selected metabolites also allowed the separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected in patients underlie cell-specific changes in neuronal and astrocytic compartments that cannot be assessed by other neuroimaging modalities. The inverse correlation between metabolites from these two compartments suggests a metabolic attempt to compensate for neuronal damage in SCAs. Because these biomarkers reflect dynamic aspects of cellular metabolism, they are good candidates for proof-of-concept therapeutic trials. © 2015 International Parkinson and Movement Disorder Society.

  1. Physiotherapy in degenerative cerebellar ataxias: utilisation, patient satisfaction, and professional expertise.

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    Fonteyn, Ella M R; Keus, Samyra H J; Verstappen, Carla C P; van de Warrenburg, Bart P C

    2013-12-01

    Physiotherapy plays an important role in the management of patients with degenerative cerebellar ataxias. However, our insight in the quantity and quality of physiotherapy prescription in this group of patients is incomplete. The purposes of this study were to investigate the utilization of physiotherapy and patient satisfaction in patients with degenerative ataxias in The Netherlands and to examine the level of expertise and needs of physiotherapists treating ataxia patients. Questionnaires were sent to members of the Dutch association for patients with degenerative cerebellar ataxias (n = 532). In addition, 181 questionnaires were sent to the physiotherapists who had recently treated the patients who responded. Eventually, 317 questionnaires from patients (60 %) and 114 questionnaires from physiotherapists (63 %) could be used for further analysis. Sixty-four percent of the patients were currently treated by a physiotherapist. Their median treatment duration was 5 years. Nineteen percent of the patients had never been referred, often despite the presence of limitations in daily activities. On the other hand, some participants without reported limitations had received physiotherapy. In general, participants were satisfied with their physiotherapist. The most reported treatment goals were improvement or maintenance of balance, general physical condition, and mobility. Physiotherapists reported lack of ataxia-specific expertise and expressed the need for education and evidence-based guidelines. Referral to and use of physiotherapy in patients with degenerative cerebellar ataxia in The Netherlands are currently inconsistent and not in agreement with the little scientific evidence available. Referral rates are high, but referrals and actual necessity are discrepant; treatment duration is long; and ataxia-specific expertise among physiotherapists is insufficient. Evidence-based recommendations and specific training of physiotherapists are needed.

  2. Magnetic resonance imaging biomarkers in patients with progressive ataxia: current status and future direction.

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    Currie, Stuart; Hadjivassiliou, Marios; Craven, Ian J; Wilkinson, Iain D; Griffiths, Paul D; Hoggard, Nigel

    2013-04-01

    A diagnostic challenge commonly encountered in neurology is that of an adult patient presenting with ataxia. The differential is vast and clinical assessment alone may not be sufficient due to considerable overlap between different causes of ataxia. Magnetic resonance (MR)-based biomarkers such as voxel-based morphometry, MR spectroscopy, diffusion-weighted and diffusion-tensor imaging and functional MR imaging are gaining great attention for their potential as indicators of disease. A number of studies have reported correlation with clinical severity and underlying pathophysiology, and in some cases, MR imaging has been shown to allow differentiation of conditions causing ataxia. However, despite recent advances, their sensitivity and specificity vary. In addition, questions remain over their validity and reproducibility, especially when applied in routine clinical practice. This article extensively reviews the current literature regarding MR-based biomarkers for the patient with predominantly adult-onset ataxia. Imaging features characteristic of a particular ataxia are provided and features differentiating ataxia groups and subgroups are discussed. Finally, discussion will turn to the feasibility of applying these biomarkers in routine clinical practice.

  3. Spinocerebellar ataxia: patient and health professional perspectives on whether and how patents affect access to clinical genetic testing.

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    Powell, Ashton; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2010-04-01

    Genetic testing for spinocerebellar ataxia is used in diagnosis of rare movement disorders. Such testing generally does not affect treatment, but confirmation of mutations in a known gene can confirm diagnosis and end an often years-long quest for the cause of distressing and disabling symptoms. Through interviews and a web forum hosted by the National Ataxia Foundation, patients and health professionals related their experiences with the effect of patents on access to genetic testing for spinocerebellar ataxia. In the United States, Athena Diagnostics holds either a patent or an exclusive license to a patent in the case of six spinocerebellar ataxia variants (spinocerebellar ataxia 1-3 and 6-8) and two other hereditary ataxias (Friedreich's Ataxia and Early Onset Ataxia). Athena has enforced its exclusive rights to spinocerebellar ataxia-related patents by sending notification letters to multiple laboratories offering genetic testing for inherited neurological conditions, including spinocerebellar ataxia. Roughly half of web forum respondents had decided not to get genetic tests. Price, coverage and reimbursement by insurers and health plans, and fear of genetic discrimination were the main reasons cited for deciding not to get tested. Price was cited as an access concern by the physicians, and as sole US provider, coverage and reimbursement depend on having payment agreements between Athena and payers. In cases in which payers do not reimburse, the patient is responsible for payment, although some patients can apply to the voluntary Athena Access and Patient Protection Plan offered by the company.

  4. Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich’s Ataxia

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    Mohammad Mehdi HEIDARI*

    2014-01-01

    Full Text Available How to Cite This Article: Heidari MM , Khatami M, Pourakrami J. Novel Point Mutations in Frataxin Gene in Iranian Patients withFriedreich’s Ataxia. Iran J Child Neurol. 2014 Winter; 8(1:32-36. ObjectiveFriedreich’s ataxia is the most common form of hereditary ataxia with autosomal recessive pattern. More than 96% of patients are homozygous for GAA repeat extension on both alleles in the first intron of FXN gene and the remainingpatients have been shown to be heterozygous for a GAA extension in one allele and point mutation in other allele.Materials & MethodsIn this study, exons of 1, 2, 3, and 5 of frataxin gene were searched by single strand conformation polymorphism polymerase chain reaction (PCR-SSCP in 5 patients with GAA extension in one allele. For detection of exact mutation,samples with band shifts were sent for DNA sequencing.Results Three novel point mutations were found in patients heterozygous for the GAA repeat expansion, p.S81A, p.Y123D, and p.S192C. ConclusionOur results showed that these point mutations in one allele with GAA extension in another allele are associated with FRDA signs. Thus, these results emphasize the importance of performing molecular genetic analysis for point mutations inFRDA patients. References:Delatycki MB, Williamson R, Forrest SM. Friedreich ataxia: an overview. J Med Genet 2000;37(1:1-8.Harding AE, Zilkha KJ. ‘Pseudo-dominant’ inheritance in Friedreich’s ataxia. J Med Genet 1981;18(4:285-7.Schulz JB, Boesch S, Burk K, Durr A, Giunti P, Mariotti C, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol 2009;5(4:222-34.Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S, et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 1997;6(11:1771-80.Sharma R, De Biase I, Gomez M, Delatycki MB, Ashizawa T, Bidichandani SI. Friedreich ataxia in carriers of unstable borderline

  5. Impact of Dual Task on Parkinson's Disease, Stroke and Ataxia Patients' Gait: A Comparative Analysis

    Directory of Open Access Journals (Sweden)

    Michelly Arjona Maciel

    2014-01-01

    Full Text Available Introduction: Performing dual task for neurological patients is complex and it can be influenced by the localization of the neurological lesion. Objective: Comparing the impact of dual task on gait in patients with Parkinson's disease, stroke and ataxia. Method: Subjects with Parkinson's disease (PD in initial phase, stroke and ataxia, with independent gait, were evaluated while doing simple gait, with cognitive, motor and cognitive-motor gait demand, assessing average speed and number of steps. Results: Ataxia and stroke patients, compared with PD, showed an increase in the number of steps and decrease the average speed on the march with cognitive demand. Subjects with PD performed better on tasks when compared to others. Conclusion: In this study the impact of dual task was lower in Parkinson's disease patients.

  6. Spinocerebellar ataxias Ataxias espinocerebelares

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    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

  7. The effectiveness of allied health care in patients with ataxia: a systematic review

    NARCIS (Netherlands)

    Fonteyn, E.M.R.; Keus, S.H.J.; Verstappen, C.C.P.; Schols, L.; Groot, I.J.M. de; Warrenburg, B.P.C. van de

    2014-01-01

    Many patients with cerebellar ataxia have serious disabilities in daily life, while pharmacological treatment options are absent. Therefore, allied health care is considered to be important in the management of these patients. The goal of this review is to evaluate scientific evidence for allied hea

  8. Physiotherapy in degenerative cerebellar ataxias: utilisation, patient satisfaction, and professional expertise

    NARCIS (Netherlands)

    Fonteyn, E.M.R.; Keus, S.H.J.; Verstappen, C.C.P.; Warrenburg, B.P.C. van de

    2013-01-01

    Physiotherapy plays an important role in the management of patients with degenerative cerebellar ataxias. However, our insight in the quantity and quality of physiotherapy prescription in this group of patients is incomplete. The purposes of this study were to investigate the utilization of physioth

  9. 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.)

  10. Korean Version of the Scale for the Assessment and Rating of Ataxia in Ataxic Stroke Patients

    OpenAIRE

    Kim, Bo-Ram; Lee, Jin-Youn; Kim, Min Jeong; Jung, Heeyoune; Lee, Jongmin

    2014-01-01

    Objective To investigate the intra-rater and inter-rater reliability and usefulness of the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) in ataxic stroke patients. Methods The original SARA was translated into Korean, back translated to English, and compared to the original version. Stroke patients (n=60) with ataxia were evaluated using the K-SARA by one physiatrist and one occupational therapist. All subjects were rated twice. We divided the subjects into 5 gr...

  11. Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

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    Adriana Moro

    2014-09-01

    Full Text Available Spinocerebellar ataxia type 3 (SCA3 involves cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems with strong phenotypic heterogeneity, that lead us to classify the disorder into different clinical subtypes according to the predominantly affected motor systems. Method The series comprises 167 SCA3 patients belonging to 68 pedigrees, studied from 1989-2013. These patients were categorized into seven different subphenotypes. Results SCA3 cases were clustered according to the predominant clinical features. Three most common forms were subphenotype 2, characterized by ataxia and pyramidal symptom was observed in 67.5%, subphenotype 3 with ataxia and peripheral signs in 13.3%, and subphenotype 6 with pure cerebellar syndrome in 7.2%. Conclusion Our study was the first to systematically classify SCA3 into seven subphenotypes. This classification may be particularly useful for determination of a more specific and direct phenotype/genotype correlation in future studies.

  12. Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6

    Institute of Scientific and Technical Information of China (English)

    JIANG Hong; TANG Bei-sha; XU Bo; ZHAO Guo-hua; SHEN Lu; TANG Jian-guang; LI Qing-hua; XIA Kun

    2005-01-01

    Background Dominantly inherited spinocerebellar ataxia (SCA) is a clinically and genetically heterogeneous group of neurodegenerative disorders. This study was to further assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, SCA8, SCA10, SCA12, SCA14, SCA17 and DRPLA (dentatorubro-pallidoluysian atrophy) in mainland Chinese, and to specifically characterize mainland Chinese patients with SCA6 in terms of clinical and molecular features.Methods Using a molecular approach, we investigated SCA in 120 mainland Chinese families with dominantly inherited ataxias and in 60 mainland Chinese patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 13 patients from 4 families. Results SCA3/MJD was the most common type of autosomal dominant SCA in mainland Chinese, accounting for 83 patients from 59 families (49.2%), followed by SCA2[8(6.7%)], SCA1[7(5.8%)], SCA6[4(3.3%)], SCA7[1(0.8%)], SCA8(0%), SCA10(0%), SCA12(0%), SCA14(0%), SCA17(0%) and DRPLA(0%). The genes responsible for 41 (34.2%) of dominantly inherited SCA families remain to be determined. Among the 60 patients with sporadic ataxias in the present series, 3 (5.0%) was found to harbor SCA3 mutations while none was found to harbor SCA6 mutations. In the 4 families with SCA6, significant anticipation was found in the absence of genetic instability on transmission.Conclusion A geographic cluster of families with SCA6 subtype was initially identified in a mainland Chinese population.

  13. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency.

    Science.gov (United States)

    El Euch-Fayache, Ghada; Bouhlal, Yosr; Amouri, Rim; Feki, Moncef; Hentati, Fayçal

    2014-02-01

    Ataxia with vitamin E deficiency is an autosomal recessive cerebellar ataxia caused by mutations in the α-tocopherol transfer protein coding gene localized on chromosome 8q, leading to lower levels of serum vitamin E. More than 91 patients diagnosed with ataxia with vitamin E deficiency have been reported worldwide. The majority of cases originated in the Mediterranean region, and the 744delA was the most common mutation among the 22 mutants previously described. We examined the clinical and molecular features of a large cohort of 132 Tunisian patients affected with ataxia with vitamin E deficiency. Of these patients, nerve conduction studies were performed on 45, and nerve biopsy was performed on 13. Serum vitamin E was dramatically reduced for 105 of the patients analysed. Molecular analysis revealed that 91.7% of the patients (n = 121) were homozygous for the 744delA mutation. Three other mutations were detected among the remaining patients (8.3%, n = 11) in the homozygous state. Two were previously reported (400C>T and 205-1G>T), and one was novel (553+1T>A). Age of onset was 13.2 ± 5.9 years, with extremes of 2 and 37 years. All described patients exhibited persistent progressive cerebellar ataxia with generally absent tendon reflexes. Deep sensory disturbances, pyramidal syndrome and skeletal deformities were frequent. Head tremor was present in 40% of the patients. Absence of neuropathy or mild peripheral neuropathy was noted in more than half of the cohort. This is the largest study of the genetic, clinical and peripheral neuropathic characteristics in patients with ataxia and vitamin E deficiency. The 744delA mutation represents the most common pathological mutation in Tunisia and worldwide, likely because of a Mediterranean founder effect. Our study led us to suggest that any patient displaying an autosomal recessive cerebellar ataxia phenotype with absent tendon reflexes and minor nerve abnormalities should first be screened for the 744delA mutation

  14. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study

    Directory of Open Access Journals (Sweden)

    Ishani Sahama

    2015-01-01

    Conclusions: Whole tract analysis of the corticomotor, corticospinal and somatosensory pathways in ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia–telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.

  15. The humanδ2 glutamate receptor gene is not mutated in patients with spinocerebellar ataxia

    Institute of Scientific and Technical Information of China (English)

    Jinxiang Huang; Aiyu Lin; Haiyan Dong; Chaodong Wang

    2014-01-01

    The human glutamate receptor delta 2 gene (GRID2) shares 90%homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and sponta-neous mutation of Grid2 leads to a spinocerebellar ataxia-like phenotype. To investigate whether such mutations occur in humans, we screened for mutations in the coding sequence of GRID2 in 24 patients with familial or sporadic spinocerebellar ataxia and in 52 normal controls. We de-tected no point mutations or insertion/deletion mutations in the 16 exons of GRID2. However, a polymorphic 4 nucleotide deletion (IVS5-121_-118 GAGT) and two single nucleotide polymor-phisms (c.1251G>T and IVS14-63C>G) were identiifed. The frequency of these polymorphisms was similar between spinocerebellar ataxia patients and normal controls. These data indicate that spontaneous mutations do not occur in GRID2 and that the incidence of spinocerebellar ataxia in humans is not associated with GRID2 mutation or polymorphisms.

  16. Mutation analysis of the TATA box-binding protein (TBP) gene in Chinese Han patients with spinocerebellar ataxia.

    Science.gov (United States)

    Xu, Q; Li, X H; Wang, J L; Jiang, H; Zhang, S; Lei, L F; Shen, L; Xia, K; Pan, Q; Long, Z G; Tang, B S

    2009-10-01

    Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant progressive neurodegenerative disease caused by the CAG/CAA expansion in the TATA box-binding protein (TBP) gene. This study aimed to assess the frequency of SCA17 in patients from mainland China. Analysis of CAG/CAA expansion in this gene was performed in 263 patients consisting of 100 probands with dominantly inherited ataxias and 163 patients with sporadic ataxias. Abnormal expansion of CAG/CAA repeats in the SCA17 locus was found in a proband and her younger sister. To our knowledge, we are providing the first kindred analysis of SCA17 in mainland China.

  17. Can Latent Class Analysis Be Used to Improve the Diagnostic Process in Pediatric Patients with Chronic Ataxia?

    Science.gov (United States)

    Klassen, Samantha; Dufault, Brenden; Salman, Michael S

    2017-04-01

    Chronic ataxia is a relatively common symptom in children. There are numerous causes of chronic ataxia, making it difficult to derive a diagnosis in a timely manner. We hypothesized that the efficiency of the diagnostic process can be improved with systematic analysis of clinical features in pediatric patients with chronic ataxia. Our aim was to improve the efficiency of the diagnostic process in pediatric patients with chronic ataxia. A cohort of 184 patients, aged 0-16 years with chronic ataxia who received medical care at Winnipeg Children's Hospital during 1991-2008, was ascertained retrospectively from several hospital databases. Clinical details were extracted from hospital charts. The data were compared among the more common diseases using univariate analysis to identify pertinent clinical features that could potentially improve the efficiency of the diagnostic process. Latent class analysis was then conducted to detect unique patterns of clinical features and to determine whether these patterns could be associated with chronic ataxia diagnoses. Two models each with three classes were chosen based on statistical criteria and clinical knowledge for best fit. Each class represented a specific pattern of presenting symptoms or other clinical features. The three classes corresponded to a plausible and shorter list of possible diagnoses. For example, developmental delay and hypotonia correlated best with Angelman syndrome. Specific patterns of presenting symptoms or other clinical features can potentially aid in the initial assessment and diagnosis of pediatric patients with chronic ataxia. This will likely improve the efficiency of the diagnostic process.

  18. Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich’s Ataxia

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi HEIDARI*

    2013-12-01

    Full Text Available Abstract How to Cite This Article: Heidari MM , Khatami M, Pourakrami J. Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich’s Ataxia. Iran J Child Neurol. 2014 Winter; 8(1:32-36. Objective Friedreich’s ataxia is the most common form of hereditary ataxia with autosomal recessive pattern. More than 96% of patients are homozygous for GAA repeat extension on both alleles in the first intron of FXN gene and the remaining patients have been shown to be heterozygous for a GAA extension in one allele and point mutation in other allele. Materials & Methods In this study, exons of 1, 2, 3, and 5 of frataxin gene were searched by single strand conformation polymorphism polymerase chain reaction (PCR-SSCP in 5 patients with GAA extension in one allele. For detection of exact mutation, samples with band shifts were sent for DNA sequencing. Results Three novel point mutations were found in patients heterozygous for the GAA repeat expansion, p.S81A, p.Y123D, and p.S192C. Conclusion Our results showed that these point mutations in one allele with GAA extension in another allele are associated with FRDA signs. Thus, these results emphasize the importance of performing molecular genetic analysis for point mutations in FRDA patients.

  19. Ataxia Telangiectasia

    Science.gov (United States)

    ... all related organizations Publications Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Ataxias and Cerebellar/Spinocerebellar Degeneration information sheet compiled by ...

  20. Conjunctival Telangiectasia in a Patient with Ataxia Telangiectasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Özge Pınar Akarsu

    2012-01-01

    Full Text Available The purpose of this paper is to report a 7-year-old patient who developed bilateral conjunctival hyperemia while being under treatment of pneumonia in Pediatric Infectious Diseases Clinic at Sisli Etfal Training and Research Hospital. Ophthalmological examination revealed bilateral conjunctival telangiectasias which were thought to be the ophthalmologic sign of ataxia telangiectasia after considering the other clinical findings, laboratory and imaging results, and family history. (Turk J Oph thal mol 2012; 42: 75-7

  1. Rehabilitation for a Patient with Hemiplegia, Ataxia, and Cognitive Dysfunction Caused by Pontine Hemorrhage

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsunoda

    2015-10-01

    Full Text Available Patients with pontine hemorrhage usually experience severe disturbances of consciousness, pupillary abnormalities, quadriparesis, and respiratory failure. However, little is known regarding cognitive dysfunction in patients with pontine hemorrhage. We report the case of a rehabilitation patient presenting with hemiplegia, ataxia, and cognitive dysfunction caused by a pontine hemorrhage. A 55-year-old, right-handed male suffered sudden onset of vertigo, dysarthria, and hemiplegia on the right side. He was diagnosed with brain stem hemorrhage, and conservative treatment was administered. The vertigo improved, but dysarthria, ataxia, hemiplegia, and gait disorder persisted. He was disoriented with respect to time and place and showed a poor attention span, impaired executive function, and reduced volition. A computed tomography revealed hematomas across the pons on both sides, but no lesions were obvious in the cerebellum and cerebrum. Single-photon emission tomography showed decreased perfusion in the brain stem, bilateral basal ganglia, and frontal and parietal lobes in the left hemisphere. The patient received exercise therapy and cognitive rehabilitation, and home modifications were performed to allow him to continue living at home under the supervision of his family. His symptoms improved, along with enhanced regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that the pontine hemorrhage caused diaschisis resulting in secondary reduction of activity in the cerebral hemisphere and the occurrence of cortical symptoms. Therefore, rehabilitation is necessary, along with active instructions for the family members of patients with severe neurological deficits.

  2. Ataxia and tremor due to lesions involving cerebellar projection pathways: a DTI tractographic study in six patients.

    Science.gov (United States)

    Marek, M; Paus, S; Allert, N; Mädler, B; Klockgether, T; Urbach, H; Coenen, V A

    2015-01-01

    Focal lesions of brainstem, thalamus, and subcortical white matter may cause movement disorders that are clinically indistinguishable from cerebellar symptoms. It is suspected that ataxia in these cases is due to damage of efferent or afferent pathways of the cerebellum. However, the precise anatomical correlate often remains undefined. We used deterministic diffusion tensor magnetic resonance imaging (DTI) tractography to study the anatomical relationship between lesions causing ataxia and efferent cerebellar pathways. Study subjects were six male patients with focal lesions of different etiology (demyelination, hemorrhage, ischemia, neoplasm) outside the cerebellum. Five patients had cerebellar-like ataxia with prominent contralateral upper limb involvement. One patient with an almost midline mesencephalic lesion had a symmetrical ataxic syndrome. We used 3T MRI (Intera, Philips Medical Systems, Best, Netherlands) and DTI tractography (32 directions, StealthViz DTI, Medtronic Navigation, Louisville, USA) to delineate the dentato-rubro-thalamo-cortical tract (DRT). In all patients, tractography demonstrated focal lesions affecting the DRT in different locations. We conclude that in vivo mapping of cerebral pathways using DTI tractography in patients with focal extracerebellar brain lesions may provide direct evidence of circumscribed damage to the DRT, causing unilateral cerebellar-like ataxia. Also, a unilateral mesencephalic lesion at the level of the crossing of the DRT may cause bilateral ataxia.

  3. Chemo- and radiosensitivity testing in a patient with ataxia telangiectasia and Hodgkin disease.

    Science.gov (United States)

    Tamminga, R Y J; Dolsma, W V; Leeuw, J A; Kampinga, H H

    2002-01-01

    Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or, rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT She was treated with a tailored combined modality approach. No unacceptable toxicity was found, but the girl died of a relapse outside the irradiation field. In comparison with fibroblasts of non-AT patients, the fibroblasts of the patient were 3 times as sensitive for radiotherapy but just 1.2 times as sensitive for doxorubicin. A good correlation was shown between in vitro radio- and chemosensitivity testing and the observed clinical toxicity. The authors suggest, therefore, treating AT patients as much as possible according to standard protocols by adjusting the radiotherapy delivery and the chemotherapy regimen to individual doses derived from in vitro radio- and chemosensitivity testing.

  4. Ataxia Telangiectasia

    Science.gov (United States)

    Ataxia-telangiectasia (A-T) is a rare, inherited disease. It affects the nervous system, immune system, and ... young children, usually before age 5. They include Ataxia - trouble coordinating movements Poor balance Slurred speech Tiny, ...

  5. Ataxia - telangiectasia

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001394.htm Ataxia - telangiectasia To use the sharing features on this page, please enable JavaScript. Ataxia-telangiectasia is a rare childhood disease. It affects ...

  6. Friedreich's Ataxia

    Science.gov (United States)

    Friedreich's ataxia is an inherited disease that damages your nervous system. The damage affects your spinal cord and the ... of 5 and 15. The main symptom is ataxia, which means trouble coordinating movements. Specific symptoms include ...

  7. Diagnosis of Ataxia

    Science.gov (United States)

    ... Donate to the National Ataxia Foundation Diagnosis of Ataxia Being diagnosed with Ataxia can be overwhelming. Below ... help you to understand ataxia better. What is Ataxia? The word "ataxia", comes from the Greek word, " ...

  8. White matter changes in patients with Friedreich ataxia after treatment with erythropoietin

    Science.gov (United States)

    Egger, Karl; Clemm von Hohenberg, Christian; Schocke, Michael F; Guttmann, Charles RG; Wassermann, Demian; Wigand, Marlene C; Nachbauer, Wolfgang; Kremser, Christian; Sturm, Brigitte; Scheiber-Mojdehkar, Barbara; Kubicki, Marek; Shenton, Martha E; Boesch, Sylvia

    2013-01-01

    Background and Purpose Erythropoietin (EPO) has received growing attention because of its neuro-regenerative properties. Preclinical and clinical evidence supports its therapeutic potential in brain conditions like stroke, multiple sclerosis and schizophrenia. Also in Friedreich ataxia, clinical improvement after EPO therapy was shown. The aim of the present study was to assess possible therapy-associated brain white-matter changes in these patients. Methods Nine patients with Friedreich ataxia underwent Diffusion Tensor Imaging (DTI) before and after EPO treatment. Tract-based spatial statistics (TBSS) was used for longitudinal comparison. Results We detected widespread longitudinal increase in fractional anisotropy (FA) and axial diffusivity (D||) in cerebral hemispheres bilaterally (p<0.05, corrected), while no changes were observed within the cerebellum, medulla oblongata and pons. Conclusions To the best of our knowledge, this is the first DTI study to investigate the effects of erythropoietin in a neurodegenerative disease. Anatomically, the diffusivity changes appear disease-unspecific, and their biological underpinnings deserve further study. PMID:24015771

  9. Acetazolamide-responsive ataxia.

    Science.gov (United States)

    Kotagal, Vikas

    2012-11-01

    Acetazolamide-responsive ataxia represents a unique collection of genetically distinct episodic ataxia (EA) disorders associated with paroxysmal cerebellar symptoms many of which are responsive to medical treatment with acetazolamide, a carbonic anhydrase inhibitor. Among all of the subtypes of episodic ataxia, types 2 (EA2), 3 (EA3), and 5 (EA5) are thought be the most medication responsive. Some patients with episodic ataxia type 1 (EA1) will also describe improvement with acetazolamide. Each of these individual genetic syndromes is characterized by its own unique mechanism and clinical presentation. In this review, the author provides an overview of the pathophysiology of acetazolamide-responsive ataxia, its natural history, and its clinical management.

  10. POINT MUTATIONS ON MITOCHONDRIAL DNA IN IRANIAN PATIENTS WITH FRIEDREICH’S ATAXIA

    Directory of Open Access Journals (Sweden)

    S. Etemad Ahari

    2007-11-01

    Full Text Available ObjectiveMitochondrial DNA (mtDNA is considered a candidate modifier factor for neuro-degenerative disorders. The most common type of ataxia is Friedreich’s ataxia (FA. The aim of this study was to investigate different parts of mtDNA in 20 Iranian FA patients and 80 age-matched controls by polymerase chain reaction (PCR and automated DNA sequencing methods to find any probable point mutations involved in the pathogenesis of FA. Materials and MethodsWe identified 13 nucleotide substitutions including A3505G, T3335C, G3421A, G8251A, A8563G, A8563G, G8584A, T8614C, T8598C, C8684T, A8701G, G8994A and A9024G. ResultsTwelve of 13 nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A9024G had not been reported before. The A9024G nucleotide substitution does not change its amino acid. The controls were also investigated for this polymorphism which was found in two of them (2.5%. ConclusionNone of the mutations found in this study can affect the clinical manifestations of FA. This survey also provides evidence that the mtDNA A9024G allele is a new nonpathogenic polymorphism. We suggest follow-up studies for this polymorphism in different populations.

  11. Temporal retinal nerve fiber loss in patients with spinocerebellar ataxia type 1.

    Directory of Open Access Journals (Sweden)

    Sarah Stricker

    Full Text Available BACKGROUND: Autosomal dominant spinocerebellar ataxia type 1 is an adult onset progressive disorder with well characterized neurodegeneration in the cerebellum and brainstem. Beyond brain atrophy, few data exist concerning retinal and optic nerve involvement. OBJECTIVE: To evaluate retinal changes in SCA1 patients compared to age and gender matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Nine patients with SCA1 were prospectively recruited from the ataxia clinic and were compared to nine age and gender matched healthy controls. Both cohorts received assessment of visually evoked potentials and eye examination by optical coherence tomography to determine retinal nerve fiber layer thickness and total macular volume. While no differences were found in visually evoked potentials, SCA1 patients showed a significant reduction of mean retinal nerve fiber layer thickness (RNFLT compared to healthy controls (84±13 µm vs. 97±8 µm, p = 0.004. Temporal areas showed the most prominent RNFLT reduction with high statistical significances (temporal-inferior: p<0.001, temporal: p<0.001, temporal-superior: p = 0.005 whereas RNFLT in nasal areas was in the range of the control group. From six SCA1 patients an additional macular scan was obtained. The comparison to the corresponding healthy control showed a slight but not significant reduction in TMV (8.22±0.68 mm(3 vs. 8.61±0.41 mm(3, p = 0.15. CONCLUSION: In SCA1 patients, we found evidence for degeneration of retinal nerve fibers. The temporal focus of the observed retinal nerve fiber layer reduction suggests an involvement of the papillo-macular bundle which resembles pathology found in toxic or mitochondrial optic nerve disease such as Leber's hereditary optic neuropathy (LHON or dominant optic atrophy (DOA.

  12. Diet for Ataxia

    Science.gov (United States)

    ... citrus fruits and their juices - as well as bananas or foods with banans as ingredients. Foods with ... his contributions in the production of this fact sheet. WHAT IS GLUTEN ATAXIA? Patients with celiac disease ...

  13. Bladder Wall Telangiectasia in a Patient with Ataxia-Telangiectasia and How to Manage?

    Directory of Open Access Journals (Sweden)

    Fatma Deniz Aygün

    2015-01-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare neurodegenerative, inherited disease causing severe morbidity. Oculocutaneous telangiectasias are almost constant findings among the affected cases as telangiectasia is considered the main clinical finding for diagnosis. Vascular abnormalities in organs have been reported infrequently but bladder wall telangiectasias are extremely rare. We aimed to report recurrent hemorrhage from bladder wall telangiectasia in a 9-year-old boy with A-T who had received intravenous cyclophosphamide for non-Hodgkin’s lymphoma. Since A-T patients are known to be more susceptible to chemical agents, we suggested that possibly cyclophosphamide was the drug which induced bladder wall injury in this patient.

  14. Mutational screening of 320 Brazilian patients with autosomal dominant spinocerebellar ataxia.

    Science.gov (United States)

    Cintra, Vívian Pedigone; Lourenço, Charles Marques; Marques, Sandra Elisabete; de Oliveira, Luana Michelli; Tumas, Vitor; Marques, Wilson

    2014-12-15

    Autosomal dominant spinocerebellar ataxias (SCAs) are a clinical and genetically heterogeneous group of debilitating neurodegenerative diseases that are related to at least 36 different genetic loci; they are clinically characterized by progressive cerebellar ataxia and are frequently accompanied by other neurological and non-neurological manifestations. The relative frequency of SCA varies greatly among different regions, presumably because of a founder effect or local ethnicities. Between July 1998 and May 2012, we investigated 320 Brazilian patients with an SCA phenotype who belonged to 150 unrelated families with an autosomal dominant inheritance pattern and 23 sporadic patients from 13 Brazilian states. A total of 265 patients (82.8%) belonging to 131 unrelated families (87.3%) were found to have a definite mutation, and SCA3 accounted for most of the familial cases (70.7%), followed by SCA7 (6%), SCA1 (5.3%), SCA2 (2.7%), SCA6 (1.3%), SCA8 (0.7%) and SCA10 (0.7%). In the Ribeirão Preto mesoregion, which is located in the northeast part of São Paulo State, the prevalence of SCA3 was approximately 5 per 100,000 inhabitants, which is the highest prevalence found in Brazil. No mutation was found in the SCA12, SCA17 and DRPLA genes, and all the sporadic cases remained without a molecular diagnosis. This study further characterizes the spectrum of SCA mutations found in Brazilian patients, which suggests the existence of regional differences and demonstrates the expansion of the SCA8 locus in Brazilian families.

  15. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.B11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by an expansion of the CAG-repeat in ATXN3. In this study, induced pluripotent stem cells (iPSCs) were generated from SCA3 patient dermal fibroblasts by electroporation with episomal plasmids encoding L...

  16. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs) from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28...

  17. [THE ANALYSIS OF LIFE SPAN AND MORTALITY OF PATIENTS WITH SPINOCEREBELLAR ATAXIA TYPE I].

    Science.gov (United States)

    Tikhonov, D G; Goldfarb, L G; Neustroeva, T S; Yakovleva, N V; Timofeev, L F; Luckan, I P; Platonov, F A

    2015-01-01

    The article presents results of investigation of certain unclear aspects of mortality of patients with spinocerebellar ataxia type I including patients with the same number of CAG-repetitions. The analysis of mortality of patients observed from 1993 to nowadays was implemented. Sampling included 112 patients during that period 53 patients died. The comparative analysis was implemented concerning received data and results of analysis of mortality of patients died prior to 1980. According received data, average value of CAG-repetitions of normal allele was equal to 30.2, and ofpathologic allele--48.7. The average life span made up to 52.8 years, average age of disease onset--38 years and natural duration of disease--14.8 years. The analysis of life span of patients with equal length of repetitions demonstrated that range of life span of patients makes up to from 8 to 23 years. It is established that life of patients becomes shorter because of accidents, cancer and concomitant diseases of cardiovascular system. The presence of such concomitant disease as tuberculosis of lungs results in no shortening of life of patients. The comparative analysis of mortality during the period over 34 years demonstrated that age of disease onset turned out to be more conservative and stable indicator of morbidity. Despite of lacking of effective methods of treatment of disease, the natural duration of disease increased statistically reliable up to 1.8 times during period of observation. The analysis of life span ofpatients with spinocerebellar ataxia type I demonstrated that their life span except length of CAG-expansion depends on a number of factors accelerating and retarding development of disease. At that, life span of patients with the same number of CAG-repetitions can significantly differ The malignant neoplasms, diseases of cardiovascular system and external causes are to be referred to factors accelerating and retarding development of main disease. The addition oftuberculosis

  18. Misclassification of Patients with Spinocerebellar Ataxia as having Psychogenic Postural Instability based on Computerized Dynamic Posturography

    Directory of Open Access Journals (Sweden)

    Susan J Herdman

    2011-04-01

    Full Text Available Specific criteria have been developed based on computerized dynamic posturography (CDP to assist clinicians in identifying patients with psychogenic balance problems1-4. Patients with known Spinocerebellar Ataxia (SCA meet several of the criteria for psychogenic balance problem and risk being misclassified as having imbalance of psychogenic origin. However, our research shows that patients with SCA may be distinguished from patients with psychogenic balance problems in several ways. We compared test performance on CDP and the observation of specific behaviors that are associated with psychogenic balance problems in patients with SCA (n = 43 and patients with known psychogenic balance problems (n = 40. Chi square analysis was used to determine if there were significant differences between the groups for the frequency of each criterion for psychogenic CDP and Observed Behaviors. Level of significance was Bonferroni corrected for multiple comparisons. Sensitivity, specificity, and positive likelihood ratios were calculated for each criterion. Hierarchical cluster analysis was used to examine whether the two patient groups demonstrated similar groupings of criteria. Comparison of the results of these analyses identified two criteria that were significantly more frequent in the Psychogenic group than in the SCA group: Regular Periodicity of sway and Circular Sway. Sensitivity, specificity and positive likelihood ratios identified two additional criteria, Inconsistent Motor Responses and Large lateral Sway that also seem to suggest a psychogenic component to a person’s imbalance. Prospective studies are needed to validate the usefulness of these findings.

  19. 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.

  20. Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2012-01-01

    Full Text Available OBJECTIVE: Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias. METHODS: We studied 150 patients from 104 families with spinocerebellar ataxias who had received molecular genetic testing for spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17, and dentatorubral-pallidoluysian atrophy. A statistical analysis of the results was performed using basic descriptive statistics and the correlation coefficient (r, Student's t-test, chi-square test, and Yates' correction. The statistical significance level was established for p-values <0.05. RESULTS: The results show that the most common subtype was spinocerebellar ataxia 3, which was followed by spinocerebellar ataxia 10. Moreover, the comparison between patients with spinocerebellar ataxia 3, spinocerebellar ataxia 10, and other types of spinocerebellar ataxia revealed distinct clinical features for each type. In patients with spinocerebellar ataxia 3, the phenotype was highly pleomorphic, although the most common signs of disease included cerebellar ataxia (CA, ophthalmoplegia, diplopia, eyelid retraction, facial fasciculation, pyramidal signs, and peripheral neuropathy. In patients with spinocerebellar ataxia 10, the phenotype was also rather distinct and consisted of pure cerebellar ataxia and abnormal saccadic eye movement as well as ocular dysmetria. Patients with spinocerebellar ataxias 2 and 7 presented highly suggestive features of cerebellar ataxia, including slow saccadic ocular movements and areflexia in spinocerebellar ataxia 2 and visual loss in spinocerebellar ataxia 7. CONCLUSIONS: Spinocerebellar ataxia 3 was the most common subtype examined, followed by spinocerebellar ataxia 10. Patients with spinocerebellar

  1. Causes of Ataxia

    Science.gov (United States)

    ... Donate to the National Ataxia Foundation Causes of Ataxia The hereditary ataxias are genetic, which means they ... the disease is inherited as a recessive gene. Ataxia Gene Identified in 1993 The first ataxia gene ...

  2. A distinctive pattern of cortical excitability in patients with the syndrome of dystonia and cerebellar ataxia

    NARCIS (Netherlands)

    Talelli, P.; Hoffland, B.S.; Schneider, S.A.; Edwards, M.; Bhatia, K.P.; Warrenburg, B.P.C. van de; Rothwell, J.C.

    2011-01-01

    OBJECTIVE: The syndrome of dystonia and cerebellar ataxia (DYTCA) is a recently described condition where cervical dystonia and mild cerebellar ataxia are the major clinical features. Here we attempted to explore the pathophysiology of this condition by comparing measurements of cortical excitabilit

  3. 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.

  4. Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2.

    Science.gov (United States)

    Fogel, Brent L; Cho, Ellen; Wahnich, Amanda; Gao, Fuying; Becherel, Olivier J; Wang, Xizhe; Fike, Francesca; Chen, Leslie; Criscuolo, Chiara; De Michele, Giuseppe; Filla, Alessandro; Collins, Abigail; Hahn, Angelika F; Gatti, Richard A; Konopka, Genevieve; Perlman, Susan; Lavin, Martin F; Geschwind, Daniel H; Coppola, Giovanni

    2014-09-15

    Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4.

  5. Spinocerebellar ataxia 13 and 25.

    Science.gov (United States)

    Stevanin, Giovanni; Dürr, Alexandra

    2012-01-01

    Spinocerebellar ataxia (SCA) types 13 and 25 are two genetic entities among the autosomal dominant cerebellar ataxias, initially mapped in two French families to chromosomes 19q and 2p, respectively. The SCA13 locus was confirmed by the identification of a second kindred of Filipino ancestry. SCA13 patients have cerebellar ataxia of adult onset, or of early onset when associated with mental impairment. SCA25 patients present with cerebellar ataxia with sensory neuropathy and frequent gastrointestinal features. While the gene responsible for SCA25 is still unknown, missense mutations affecting the potassium channel KCNC3 function have been identified.

  6. Chromosome instability and oxidative stress markers in patients with ataxia telangiectasia and their parents.

    Science.gov (United States)

    Ludwig, Luciane Bitelo; Valiati, Victor Hugo; Palazzo, Roberta Passos; Jardim, Laura Bannach; da Rosa, Darlan Pase; Bona, Silvia; Rodrigues, Graziela; Marroni, Norma Possa; Prá, Daniel; Maluf, Sharbel Weidner

    2013-01-01

    Ataxia telangiectasia (AT) is a rare neurodegenerative disorder, inherited in an autosomal recessive manner. Total blood samples were collected from 20 patients with AT, 13 parents of patients, and 17 healthy volunteers. This study aimed at evaluating the frequency of chromosomal breaks in spontaneous cultures, induced by bleomycin and ionizing radiation, and further evaluated the rates of oxidative stress in AT patients and in their parents, compared to a control group. Three cell cultures were performed to each individual: the first culture did not receive induction to chromosomal instability, the second was exposed to bleomycin, and the last culture was exposed to ionizing radiation. To evaluate the rates of oxidative stress, the markers superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid (TBARS) were utilized. Significant differences were observed between the three kinds of culture treatments (spontaneous, bleomycin, and radiation induced) and the breaks and chromosomal aberrations in the different groups. The oxidative stress showed no significant differences between the markers. This study showed that techniques of chromosomal instability after the induction of ionizing radiation and bleomycin are efficient in the identification of syndrome patients, with the ionizing radiation being the most effective.

  7. Falls in degenerative cerebellar ataxias

    NARCIS (Netherlands)

    van de Warrenburg, Bart P C; Steijns, Janneke A G; Munneke, Marten; Kremer, Berry P H; Bloem, Bastiaan R

    2005-01-01

    We retrospectively and prospectively assessed the frequency and characteristics of falls in patients with degenerative cerebellar ataxias. The results show that falls occur very frequently in patients with degenerative cerebellar ataxias and that these falls are serious and often lead to injuries or

  8. Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia.

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Goulding, Niamh; Palma, Jose-Alberto; Fuente Mora, Cristina; Kaufmann, Horacio

    2016-02-01

    Hereditary sensory and autonomic neuropathy type III (HSAN III) features disturbed proprioception and a marked ataxic gait. We recently showed that joint angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers and the absolute error, gradient, and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle matching test [mean matching error 8.0 ± 0.8° (±SE); controls 3.0 ± 0.3°]. Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

  9. 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.

  10. Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs

    Directory of Open Access Journals (Sweden)

    Yoshihito Ishida

    2016-11-01

    Full Text Available Spinocerebellar ataxia type 6 (SCA6 is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies. Patient-derived Purkinje cells exhibit increased levels of full-length Cav2.1 protein but decreased levels of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. We further demonstrate that SCA6 Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus, we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model may be useful for pathogenic investigation and drug screening.

  11. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  12. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.B11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich;

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by an expansion of the CAG-repeat in ATXN3. In this study, induced pluripotent stem cells (iPSCs) were generated from SCA3 patient dermal fibroblasts by electroporation with episomal plasmids encoding L......PSC line could be a useful tool for the investigation of SCA3 disease mechanisms....

  13. Friedreich ataxia

    Science.gov (United States)

    ... for Friedreich ataxia includes: Counseling Speech therapy Physical therapy Walking aids or wheelchairs Orthopedic devices (braces) may be needed for scoliosis and foot problems. Treating heart disease and diabetes help people ...

  14. Social and Cultural Elements Associated with Neurocognitive Dysfunctions in Spinocerebellar Ataxia Type 2 Patients

    Science.gov (United States)

    Mercadillo, Roberto Emmanuele; Galvez, Víctor; Díaz, Rosalinda; Paredes, Lorena; Velázquez-Moctezuma, Javier; Hernandez-Castillo, Carlos R.; Fernandez-Ruiz, Juan

    2015-01-01

    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 medical approach to

  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. Acute cerebellar ataxia

    Science.gov (United States)

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  17. Friedreich's Ataxia Research Alliance

    Science.gov (United States)

    ... Tools Raising Awareness Advocacy Memorials What is Friedreich's Ataxia? About FARA Mission & Organization Financials Leadership & Staff Scientific ... Tools Raising Awareness Advocacy Memorials What is Friedreich's Ataxia? FARA News / Blogs Ride Ataxia rideATAXIA Chicago 2016 ...

  18. Atypical Friedreich ataxia in patients with FXN p.R165P point mutation or comorbid hemochromatosis

    DEFF Research Database (Denmark)

    Ygland, Emil; Taroni, Franco; Gellera, Cinzia

    2014-01-01

    BACKGROUND: Compound heterozygosity for a trinucleotide repeat expansion and a point mutation in the FXN gene is a rare cause of Friedreich ataxia (FRDA). METHODS: We identified three Swedish FRDA patients with an FXN p.R165P missense mutation and compared their clinical features with six......, and were more independent in activities of daily living. One p.R165P mutation carrier developed psychosis. Frataxin levels were higher than in homozygous trinucleotide expansion patients. One patient with homozygous trinucleotide repeat expansions and comorbid hemochromatosis had more severe FRDA symptoms...

  19. Genetic testing for spinocerebellar ataxias in patients diagnosed as Parkinson's disease in Bangladesh.

    Science.gov (United States)

    Rahman, M S; Sarkar, M A; Rahman, M F; Paul, S K; Nagai, S Y; Uddin, M J; Toda, T

    2015-01-01

    This study was conducted to find out Spinocerebellar Ataxias (SCA) by genetic analysis from those patients presenting with Parkinsonism in the Neurology department of Mymensingh Medical College Hospital, Bangladesh. A sample of about 5ml blood was collected by venipuncture in EDTA tube after having informed consent from each patients and healthy individual, with due Institutional Ethical committee approval for genetic study of 7 healthy people and 9 patients. The neurological disorder along with a complete physical and/or psychological, as well as family history and demographic data was recorded with a prescribed questionnaire by the neurologists of Mymensingh Medical College Hospital. Extraction of genomic DNA from the venous blood using Flexi Gene DNA kit (Qiagen, Japan) was performed in Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh. The extracted DNA was stored, accumulated and then were sent to Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan for PCR and further analysis. PCR amplification of the CAG repeat was performed for the SCA1, SCA2, SCA3, SCA6 loci using primers SCA1N-F1 and SCA1N-R1, SCA2-F1 and SCA2-R1, MJDF1 and MJDR1, SCA6-F1 and SCA6-R1, respectively. SCA1 PCR of both healthy individual and suspected Parkinsons Disease (PD) patients DNA was found 250 bp (no. of CAG repeats=36). SCA2 PCR products reveal the DNA products of about 150 bp (no. of CAG repeats=23) except one patient that was suspected and it was sequenced and revealed 175bp (no. of CAG repeats=30). SCA3 PCR product size of both healthy individual and patient DNA was within 250 (no. of CAG repeats=11) to 300 bp (no. of CAG repeats=28) except one patient which was about 320 bp and its CAG repeats was about 34. SCA6 PCR product size of both healthy individual and patient DNA was about 150 bp (no. of CAG repeats=16).

  20. 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

  1. A novel frameshift mutation in the AFG3L2 gene in a patient with spinocerebellar ataxia.

    Science.gov (United States)

    Musova, Zuzana; Kaiserova, Michaela; Kriegova, Eva; Fillerova, Regina; Vasovcak, Peter; Santava, Alena; Mensikova, Katerina; Zumrova, Alena; Krepelova, Anna; Sedlacek, Zdenek; Kanovsky, Petr

    2014-06-01

    Spinocerebellar ataxia type 28 (SCA28) is an autosomal dominant neurodegenerative disorder caused by missense AFG3L2 mutations. To examine the occurrence of SCA28 in the Czech Republic, we screened 288 unrelated ataxic patients with hereditary (N = 49) and sporadic or unknown (N = 239) form of ataxia for mutations in exons 15 and 16, the AFG3L2 mutation hotspots. A single significant variant, frameshift mutation c.1958dupT leading to a premature termination codon, was identified in a patient with slowly progressive speech and gait problems starting at the age of 68 years. Neurological examination showed cerebellar ataxia, mild Parkinsonian features with predominant bradykinesia, polyneuropathy of the lower limbs, and cognitive decline. However, other common SCA28 features like pyramidal tract signs (lower limb hyperreflexia, positive Babinski sign), ophthalmoparesis or ptosis were absent. The mutation was also found in a patient's unaffected daughter in whom a targeted examination at 53 years of age revealed mild imbalance signs. RNA analysis showed a decreased ratio of the transcript from the mutated AFG3L2 allele relative to the normal transcript in the peripheral lymphocytes of both patients. The ratio was increased by puromycin treatment, indicating that the mutated transcript can be degraded via nonsense-mediated RNA decay. The causal link between the mutation and the phenotype of the patient is currently unclear but a pathogenic mechanism based on AFG3L2 haploinsufficiency rather than the usual dominant-negative effect of missense AFG3L2 mutations reported in SCA28, cannot be excluded.

  2. Generation of spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. Here, we demonstrate the generation of an induced pluripotent stem cell...

  3. Generation of spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Tubsuwan, Alisa; Schmid, Benjamin

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. Here, we demonstrate the generation of an induced pluripotent stem cell...

  4. Generation of spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. Here, we demonstrate the generation of an induced pluripotent stem cell...

  5. Different subregional metabolism patterns in patients with cerebellar ataxia by 18F-fluorodeoxyglucose positron emission tomography

    Science.gov (United States)

    Kim, Jae Seung; Oh, Jungsu S.; Lee, Chong Sik; Chung, Sun Ju

    2017-01-01

    We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p MSA-C exhibited more asymmetric hypometabolism in the posterior lobe. PMID:28319124

  6. Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and a spinocerebellar ataxia type 3 (SCA3) patient, and its clinical relevance

    NARCIS (Netherlands)

    Rub, U; Del Turco, D; Del Tredici, K; de Vos, RAI; Brunt, ER; Reifenberger, G; Seifried, C; Schultz, C; Auburger, G; Braak, H

    2003-01-01

    In spite of the considerable progress in clinical and molecular research, knowledge regarding brain damage in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) still is limited and the extent to which the thalamus is involved in both diseases is uncertain. Accordingly, we performed a pathoanato

  7. Expansion of the Spinocerebellar ataxia type 10 (SCA10 repeat in a patient with Sioux Native American ancestry.

    Directory of Open Access Journals (Sweden)

    Khalaf Bushara

    Full Text Available Spinocerebellar ataxia type 10 (SCA10, an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described "SCA10 haplotype". This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.

  8. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich;

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs) from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28......, SOX2, KLF4, OCT4 and short hairpin RNA targeting P53. The resulting iPSCs had normal karyotype, were free of genomically integrated episomal plasmids, expressed pluripotency markers, could differentiate into the three germ layers in vitro and retained the disease-causing ATXN3 mutation. This iPSC line...

  9. Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias.

    Science.gov (United States)

    Kasumu, Adebimpe; Bezprozvanny, Ilya

    2012-09-01

    Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. It is not currently understood how mutations in these 17 proteins lead to the cerebellar atrophy and ataxia. Several pathogenic mechanisms have been studied in SCAs but there is yet to be a promising target for successful treatment of SCAs. Emerging research suggests that a fundamental cellular signaling pathway is disrupted by a majority of these mutated genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. We propose that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients.

  10. Trial in Adult Subjects With Spinocerebellar Ataxia

    Science.gov (United States)

    2017-03-08

    Spinocerebellar Ataxias; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 8; Spinocerebellar Ataxia Type 10

  11. Different subregional metabolism patterns in patients with cerebellar ataxia by 18F-fluorodeoxyglucose positron emission tomography.

    Science.gov (United States)

    Oh, Minyoung; Kim, Jae Seung; Oh, Jungsu S; Lee, Chong Sik; Chung, Sun Ju

    2017-01-01

    We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p < 0.001). SCA type 6 showed lower metabolic ratios in almost all cerebellar subregions (ANT, 0.57 ± 0.06, p < 0.001) except INFV. Anterior-posterior lobe ratio measurements revealed that SCA type 2 (Right, 0.81 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.83 ± 0.05 vs. 0.88 ± 0.04, p = 0.003) and SCA type 6 (Right, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001) showed preferential hypometabolism in the anterior lobe compared to normal controls, which was not observed in CCD and MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p < 0.001), whereas such differences were not found in SCA types 2 and 6. In summary, quantitative analysis of cerebellar subregional metabolism ratios revealed preferential involvement of the anterior lobe, corresponding to the spinocerebellum, in patients with cerebellar ataxia, whereas patients with CCD and MSA-C exhibited more asymmetric hypometabolism in the posterior lobe.

  12. The scale for the assessment and rating of ataxia correlates with dysarthria assessment in Friedreich's ataxia.

    Science.gov (United States)

    Eigentler, Andreas; Rhomberg, Johanna; Nachbauer, Wolfgang; Ritzer, Irmgard; Poewe, Werner; Boesch, Sylvia

    2012-03-01

    Dysarthria is an acquired neurogenic sensorimotor speech symptom and an integral part within the clinical spectrum of ataxia syndromes. Ataxia measurements and disability scores generally focus on the assessment of motor functions. Since comprehensive investigations of dysarthria in ataxias are sparse, we assessed dysarthria in ataxia patients using the Frenchay Dysarthria Assessment. The Frenchay Dysarthria Assessment is a ten-item validated test in which eight items focus on the observation of oral structures and speech functions. Fifteen Friedreich's ataxia patients and 15 healthy control individuals were analyzed using clinical and logopedic methodology. All patients underwent neurological assessment applying the Scale for the Assessment and Rating of Ataxia. In Friedreich's ataxia patients, the Frenchay sub-item voice showed to be most affected compared to healthy individuals followed by items such as reflexes, palate, tongue, and intelligibility. Scoring of lips, jaw, and respiration appeared to be mildly affected. Ataxia severity in Friedreich's ataxia patients revealed a significant correlation with the Frenchay dysarthria sum score. The introduction of a binary Adapted Dysarthria Score additionally allowed allocation to distinct dysarthria pattern in ataxias. The Frenchay Dysarthria Assessment proved to be a valid dysarthria measure in Friedreich's ataxia. Its availability in several languages provides a major advantage regarding the applicability in international clinical studies. Shortcomings of the Frenchay test are the multiplicity of items tested and its alphabetic coding. Numerical scoring and condensation of assessments in a modified version may, however, provide an excellent clinical tool for the measurement and scoring of dysarthria in ataxic speech disorders.

  13. National Ataxia Foundation

    Science.gov (United States)

    ... Facebook Page - Twitter - YouTube Giving a talk on Ataxia? - Ataxia Presentation Thank You To Our Partners Get ... new NAF App today The new NAF Store - Ataxia Awareness Merchandise & More... Shop NAF Today! Donate Now! ...

  14. Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia Telangiectasia Patients: A Precision Medicine Perspective.

    Directory of Open Access Journals (Sweden)

    Zhao Chen

    Full Text Available Ataxia telangiectasia (AT is an autosomal recessive disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and immunodeficiency due to mutations in the ATM gene. We performed targeted next-generation sequencing (NGS on three unrelated patients and identified five disease-causing variants in three probands, including two pairs of heterozygous variants (FAT-1:c.4396C>T/p.R1466X, c.1608-2A>G; FAT-2:c.4412_4413insT/p.L1472Ffs*19, c.8824C>T/p.Q2942X and one pair of homozygous variants (FAT-3: c.8110T>G/p.C2704G, Hom. With regard to precision medicine for rare genetic diseases, targeted NGS currently enables the rapid and cost-effective identification of causative mutations and is an updated molecular diagnostic tool that merits further optimization. This high-throughput data-based strategy would propel the development of precision diagnostic methods and establish a foundation for precision medicine.

  15. Occupational therapy intervention to inspire self-efficacy in a patient with spinal ataxia and visual disturbance.

    Science.gov (United States)

    Tohyama, Satsuki; Usuki, Fusako

    2015-02-09

    We report a case of a patient with severe ataxia and visual disturbance due to vitamin E deficiency, whose self-efficacy was inspired by intervention with an appropriate occupational therapy activity. Before the handloom intervention, her severe neurological deficits decreased her activities of daily living (ADL) ability, which made her feel pessimistic and depressed. The use of a handloom, however, inspired her sense of accomplishment because she could perform the weft movement by using her residual physical function, thereby relieving her pessimistic attitude. This perception of capability motivated her to participate in further rehabilitation. Finally, her eager practice enhanced her ADL ability and quality of life (QOL). The result suggests that it is important to provide an appropriate occupational therapy activity that can inspire self-efficacy in patients with chronic refractory neurological disorders because the perception of capability can enhance the motivation to improve performance in general activities, ADL ability and QOL.

  16. Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, N.G.; Taalman, R.D.; Baan, C.

    1988-01-01

    Fibroblast cultures from six unrelated patients having a familial type of immunodeficiency combined with microcephaly, developmental delay, and chromosomal instability were studied with respect to their response to ionizing radiation. The cells from five of them resembled those from individuals with ataxia telangiectasia (AT) in that they were two to three times more radiosensitive on the basis of clonogenic cell survival. In addition, after exposure to either X-rays or bleomycin, they showed an inhibition of DNA replication that was less pronounced than that in normal cells and characteristic of AT fibroblasts. However, the patients are clinically very different from AT patients, not showing any signs of neurocutaneous symptoms. Genetic complementation studies in fused cells, with the radioresistant DNA synthesis used as a marker, showed that the patients' cells could complement representatives of all presently known AT complementation groups. Furthermore, they were shown to constitute a genetically heterogeneous group as well. It is concluded that these patients are similar to AT patients with respect to cytological parameters. The clinical differences between these patients and AT patients are a reflection of genetic heterogeneity. The data indicate that the patients suffer from a chromosome-instability syndrome that is distinct from AT.

  17. Paroxysmal ataxia and dysarthria in multiple sclerosis.

    Science.gov (United States)

    Iorio, R; Capone, F; Plantone, D; Batocchi, A P

    2014-01-01

    Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.

  18. Association between proton magnetic resonance spectroscopy measurements and CAG repeat number in patients with spinocerebellar ataxias 2, 3, or 6.

    Directory of Open Access Journals (Sweden)

    Po-Shan Wang

    Full Text Available The aim of this study was to correlate magnetic resonance spectroscopy (MRS measurements, including that for the N-acetyl aspartate (NAA/creatine (Cr ratio in the vermis (denoted V-NAA, right cerebellar hemisphere (R-NAA, and left (L-NAA cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA score for patients with spinocerebellar ataxia (SCA types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

  19. Association between proton magnetic resonance spectroscopy measurements and CAG repeat number in patients with spinocerebellar ataxias 2, 3, or 6.

    Science.gov (United States)

    Wang, Po-Shan; Chen, Hung-Chieh; Wu, Hsiu-Mei; Lirng, Jiing-Feng; Wu, Yu-Te; Soong, Bing-Wen

    2012-01-01

    The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

  20. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

    Directory of Open Access Journals (Sweden)

    Susanne K. Hansen

    2016-05-01

    Full Text Available Spinocerebellar ataxia type 3 (SCA3 is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28, SOX2, KLF4, OCT4 and short hairpin RNA targeting P53. The resulting iPSCs had normal karyotype, were free of genomically integrated episomal plasmids, expressed pluripotency markers, could differentiate into the three germ layers in vitro and retained the disease-causing ATXN3 mutation. This iPSC line could be useful for the investigation of SCA3 disease mechanisms.

  1. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.B11

    Directory of Open Access Journals (Sweden)

    Susanne K. Hansen

    2016-05-01

    Full Text Available Spinocerebellar ataxia type 3 (SCA3 is a dominantly inherited neurodegenerative disease caused by an expansion of the CAG-repeat in ATXN3. In this study, induced pluripotent stem cells (iPSCs were generated from SCA3 patient dermal fibroblasts by electroporation with episomal plasmids encoding L-MYC, LIN28, SOX2, KLF4, OCT4 and short hairpin RNA targeting P53. The resulting iPSCs had normal karyotype, were free of integrated episomal plasmids, expressed pluripotency markers, could differentiate into the three germ layers in vitro and retained the disease-causing ATXN3 mutation. Potentially, this iPSC line could be a useful tool for the investigation of SCA3 disease mechanisms.

  2. 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.

  3. 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.

    2014-01-01

    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

  4. Differences in saccade dynamics between spinocerebellar ataxia 2 and late-onset cerebellar ataxias.

    Science.gov (United States)

    Federighi, Pamela; Cevenini, Gabriele; Dotti, Maria T; Rosini, Francesca; Pretegiani, Elena; Federico, Antonio; Rufa, Alessandra

    2011-03-01

    The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the neural substrate underlying saccadic motor control. We investigated the different extent of saccade dynamic abnormalities in spinocerebellar ataxia type 2 and late-onset cerebellar ataxias, genetically undefined and with prevalent cerebellar atrophy. Reflexive and voluntary saccades of different amplitude (10°-18°) were studied in seven patients with spinocerebellar ataxia 2, eight patients with late-onset cerebellar ataxia and 25 healthy controls. Quantitative analysis of saccade parameters and measures of saccade accuracy were performed. Detailed neurological, neurophysiological and magnetic resonance imaging assessment was obtained for each patient. Genetic and laboratory screening for spinocerebellar ataxias and other forms of late-onset cerebellar ataxias were also performed. A lower peak saccade velocity and longer duration was observed in patients with spinocerebellar ataxia 2 with respect to those with late-onset cerebellar ataxia and controls. Unlike subjects with spinocerebellar ataxia 2, patients with late-onset cerebellar ataxia showed main sequence relationships to similar saccades made by normal subjects. Saccades were significantly more inaccurate, namely hypometric, in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and inaccuracy increased with saccade amplitude. The percentage of hypometric primary saccades and of larger secondary corrective saccades were consistently higher in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and controls. No other significant differences were found between groups. Two different mechanisms were adopted to redirect the fovea as fast

  5. Brain pathology of spinocerebellar ataxias.

    Science.gov (United States)

    Seidel, Kay; Siswanto, Sonny; Brunt, Ewout R P; den Dunnen, Wilfred; Korf, Horst-Werner; Rüb, Udo

    2012-07-01

    The autosomal dominant cerebellar ataxias (ADCAs) represent a heterogeneous group of neurodegenerative diseases with progressive ataxia and cerebellar degeneration. The current classification of this disease group is based on the underlying genetic defects and their typical disease courses. According to this categorization, ADCAs are divided into the spinocerebellar ataxias (SCAs) with a progressive disease course, and the episodic ataxias (EA) with episodic occurrences of ataxia. The prominent disease symptoms of the currently known and genetically defined 31 SCA types result from damage to the cerebellum and interconnected brain grays and are often accompanied by more specific extra-cerebellar symptoms. In the present review, we report the genetic and clinical background of the known SCAs and present the state of neuropathological investigations of brain tissue from SCA patients in the final disease stages. Recent findings show that the brain is commonly seriously affected in the polyglutamine SCAs (i.e. SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) and that the patterns of brain damage in these diseases overlap considerably in patients suffering from advanced disease stages. In the more rarely occurring non-polyglutamine SCAs, post-mortem neuropathological data currently are scanty and investigations have been primarily performed in vivo by means of MRI brain imaging. Only a minority of SCAs exhibit symptoms and degenerative patterns allowing for a clear and unambiguous diagnosis of the disease, e.g. retinal degeneration in SCA7, tau aggregation in SCA11, dentate calcification in SCA20, protein depositions in the Purkinje cell layer in SCA31, azoospermia in SCA32, and neurocutaneous phenotype in SCA34. The disease proteins of polyglutamine ataxias and some non-polyglutamine ataxias aggregate as cytoplasmic or intranuclear inclusions and serve as morphological markers. Although inclusions may impair axonal transport, bind transcription factors, and block protein

  6. Antigliadin antibody in sporadic adult ataxia

    Directory of Open Access Journals (Sweden)

    Mahdi Aloosh

    2012-09-01

    Full Text Available Background: The most common neurologic manifestationof gluten sensitivity is ataxia, which accounts for up to 40%of idiopathic sporadic ataxia. Timing of diagnosis of glutenataxia is vital as it is one of the very few treatable causes ofsporadic ataxia and causes irreversible loss of Purkinje cells.Antigliadin antibody (AGA of the IgG type is the bestmarker for neurological manifestations of gluten sensitivity.This study was conducted to measure the prevalence ofgluten ataxia in a group of Iranian patients with idiopathicataxia.Methods: For 30 patients with idiopathic cerebellar ataxia, aquestionnaire about clinical and demographic data wascompleted. Serum AGA (IgA and IgG and antiendomysialantibody (AEA were assessed. Gluten ataxic patientsunderwent duodenal biopsy. Magnetic resonanceimaging was done for all patients to see if cerebellaratrophy is present.Results: Only 2 patients had a positive IgG AGA (6.7%who both had a positive AEA while none of themshowed changes of celiac disease in their duodenalbiopsies. Only presence of gastrointestinal symptomsand pursuit eye movement disorders were higher inpatients with gluten ataxia.Conclusion: Prevalence of gluten ataxia in Iranianpatients with idiopathic ataxia seems to be lower thanmost of other regions. This could be explained by smallsample size, differences in genetics and nutritionalhabits and also effect of serologic tests in clinical versusresearch setting. Further researches with larger samplesize are recommended.

  7. [Friedrich's ataxia: clinical difficulties and genetic possibilities

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Knoers, N.V.A.M.; Kremer, H.P.H.

    2002-01-01

    Atypical Friedreich's ataxia was diagnosed by DNA-analysis in 4 patients, 2 men aged 70 and 67 and 2 women aged 32 and 37, who had features that included an onset of ataxia after the age of 25, retained tendon reflexes or hyperreflexia, absence of Babinski's sign, and/or a slowly progressive course.

  8. The evaluation of swallowing in patients with spinocerebellar ataxia and oropharyngeal dysphagia: A comparison study of videofluoroscopic and sonar doppler

    Directory of Open Access Journals (Sweden)

    Abdulmassih, Edna Márcia da Silva

    2013-01-01

    Full Text Available Introduction: Spinocerebellar ataxia (SCA is a degenerative disease that can cause loss of coordination of voluntary muscle movement such as that required for swallowing. Aims: The purposes of this cross-sectional and comparative case study were: (1 to assess the severity of dysphagia through a videofluoroscopic swallow study, and (2 to compare differences in frequency, intensity, and duration of sound waves produced during swallowing in normal and SCA patients by using sonar Doppler. Method: During swallow evaluation using videofluoroscopy, a sonar Doppler transducer was placed on the right side of the neck, at the lateral edge of the trachea, just below the cricoid cartilage to capture the sounds of swallowing in 30 SCA patients and 30 controls. Result: The prevalence in the dynamic evaluation of swallowing videofluoroscopy was by changes in the oral phase of swallowing. The analysis of variance of the averages found in each variable - frequency, intensity and duration of swallowing - shows there was a significant correlation when compared to the healthy individual curve. Conclusion: The study demonstrates the prevalence of oral dysphagia observed in dynamic videofluoroscopic swallow evaluation. In patients with SCA, the mean initial frequency (IF, initial intensity (II, and final intensity (FI were higher and the time (T and peak frequency (PF were lower, demonstrating a pattern of cricopharyngeal opening very close to that found in normal populations.

  9. Detection of aneuploidy in sperm of an ataxia telangiectasia patient using three-chromosome fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, X.R.; Baulch, J.E. [Lawrence Livermore National Lab., CA (United States); Arnheim, N. [USC, Los Angeles, CA (United States)] [and others

    1994-09-01

    Ataxia telangiectasia (A-T) is an inherited, recessive, cancer-prone disorder. Fluorescence in situ hybridization (FISH) with DNA probes specific for three chromosomes was applied to sperm of an A-T patient to determine if there may be an increased germinal risk for aneuploidy. Air-dried sperm smears were treated with proteinase K and were decondensed with DTT and LIS. The slides were then hybridized with fluorescently labeled repetitive DNA probes specific for chromosomes X, Y and 8, and a total of 11,825 sperm cells were scored. The ratio of sperm bearing X-8 and Y-8 was 1:1, as predicted. The frequencies of hyperhaploidy were 3.9, 1.0, 17.6 and 7.8 per 10,000 cells for categories X-X-8, Y-Y-8, X-Y-8 and 8-8-(X or Y), respectively, In addition, the frequency of diploidy (X-Y-8-8) was 18.6 and auto-diploidies (X-X-8-8 and Y-Y-8-8) were 1.0 and 2.0, respectively. These frequencies were not significantly different when compared with levels in healthy men (p > 0.1). Our finding suggests that chromosome X, Y and 8 aneuploidies are not elevated in the sperm of A-T patients, but studies with additional patients and chromosomes are needed.

  10. Truncal ataxia from infarction involving the inferior olivary nucleus.

    Science.gov (United States)

    Park, Jae Hyun; Ryoo, Sookyung; Moon, So Young; Seo, Sand Won; Na, Duk L

    2012-08-01

    Truncal ataxia in medullary infarction may be caused by involvement of the lateral part of the medulla; however, truncal ataxia in infarction involving the inferior olivary nucleus (ION) has received comparatively little attention. We report a patient with truncal ataxia due to medial medullary infarction located in the ION. A lesion in the ION could produce a contralateral truncal ataxia due to increased inhibitory input to the contralesional vestibular nucleus from the contralesional flocculus.

  11. 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.

  12. Clinical challenges in the ataxias

    Institute of Scientific and Technical Information of China (English)

    S.H. Subramony

    2011-01-01

    Ataxias are rare diseases and the etiologic heterogeneity make individual entities even rarer. There are still substantial numbers of patients who are still poorly understood. Available assessment techniques still point to large numbers of patients needed for clinical trials and the need for cooperative efforts, better assessment tools and novel trial designs. Better understanding of neural circuitry abnormalities may lead to more effective symptomatic therapy. Opportunities exist for targeting at risk individuals for effective therapies but how this can be done is not clear. Preventive strategies may become feasible in many ataxias.

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

    OpenAIRE

    2016-01-01

    Background The autosomal recessive ataxias are a heterogeneous group of disorders that are characterized by complex neurological features in addition to progressive ataxia. Hyperkinetic movement disorders occur in a significant proportion of patients, and may sometimes be the presenting motor symptom. Presentations with involuntary movements rather than ataxia are diagnostically challenging, and are likely under-recognized. Methods A PubMed literature search was performed in October 2015 util...

  14. Neuromuscular electrical stimulation of the median nerve facilitates low motor cortex excitability in patients with spinocerebellar ataxia.

    Science.gov (United States)

    Chen, Chih-Chung; Chuang, Yu-Fen; Yang, Hsiao-Chu; Hsu, Miao-Ju; Huang, Ying-Zu; Chang, Ya-Ju

    2015-02-01

    The neuromodulation of motor excitability has been shown to improve functional movement in people with central nervous system damage. This study aimed to investigate the mechanism of peripheral neuromuscular electrical stimulation (NMES) in motor excitability and its effects in people with spinocerebellar ataxia (SCA). This single-blind case-control study was conducted on young control (n=9), age-matched control (n=9), and SCA participants (n=9; 7 SCAIII and 2 sporadic). All participants received an accumulated 30 min of NMES (25 Hz, 800 ms on/800 ms off) of the median nerve. The central motor excitability, measured by motor evoked potential (MEP) and silent period, and the peripheral motor excitability, measured by the H-reflex and M-wave, were recorded in flexor carpi radialis (FCR) muscle before, during, and after the NMES was applied. The results showed that NMES significantly enhanced the MEP in all 3 groups. The silent period, H-reflex and maximum M-wave were not changed by NMES. We conclude that NMES enhances low motor excitability in patients with SCA and that the mechanism of the neuromodulation was supra-segmental. These findings are potentially relevant to the utilization of NMES for preparation of motor excitability. The protocol was registered at Clinicaltrials.gov (NCT02103075).

  15. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F; Kuiper, Marieke J; Lunsing, Roelineke J; Burger, Huibert; Sival, Deborah A

    2016-01-01

    AIM: To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD: In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation c

  16. Burden of Friedreich’s Ataxia to the Patients and Healthcare Systems in the United States and Canada

    Directory of Open Access Journals (Sweden)

    Barbara ePolek

    2013-05-01

    Full Text Available Objective: The study intended to substantiate healthcare resource utilization, costs and funding patterns of US and Canadian Friedreich's Ataxia (FRDA populations, to assess compliance with treatment guidance and to identify areas where novel healthcare measures or improved access to existing care may improve patients’ functional and social capabilities and reduce the financial impact on the healthcare systems. Methods: Healthcare resource utilization and costs were collected in a cross sectional study in the US (N=197 and Canada (N=43 and analyzed across severity of disease categories. Descriptive statistics, correlation analysis and hypothesis testing were applied.Results: In the US, healthcare costs of FRDA patients were higher than those of ‘adults with two and more chronic conditions’. Significantly higher costs were incurred in advanced stages of the disease, with paid homecare being the main driver. This pattern was also observed in Canada. Compliance with the recommended annual neurological and cardiological follow-up was high, but was low for the recommended regular speech therapy. In the US public and private funding ratios were similar for the FRDA and the general populations. In Canada the private funding ratio for FRDA was higher than average. Conclusions: The variety of healthcare measures addressing the broad range of symptoms of FRDA, and the increasing use of paid home care as disease progresses made total US healthcare costs of FRDA exceed the costs of US adults with two and more chronic conditions. Therefore, measures delaying disease progression will allow patients to maintain their independence longer and may reduce costs to the healthcare system. Novel measures to address dysarthria and to ensure access to them should be further investigated. The higher than average private funding ratio in Canada was due to the relatively high cost of the pharmacological treatment of FRDA.

  17. Inherited ataxia with slow saccades

    Directory of Open Access Journals (Sweden)

    R T Chakor

    2012-01-01

    Full Text Available Ataxia is a symptom of cerebellar dysfunction. Slowly progressive ataxia, dysarthria in an adult with a positive family history suggests an inherited cerebellar ataxia. We present an adult with gradually progressive ataxia and slow saccades. There was history of similar illness in his son. Genetic testing for spinocerebellar ataxia 2 was positive. We discuss the various inherited ataxias, causes of acute, progressive ataxia syndromes, episodic ataxias and ataxia associated with other neurological signs like peripheral neuropathy, pyramidal features, movement disorders and cognitive decline.

  18. 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.

  19. GENETICS OF SPINOCEREBELLAR ATAXIAS

    OpenAIRE

    Hirano, Makito; Ueno, Satoshi

    2004-01-01

    Over the last decade, more than 25 genes responsible for spinocerebellar ataxias (SCAs) have been isolated. This review classifies hereditary SCAs into two groups: autosomal dominant and recessive ataxias, and sunmiarizes the genetic features of these diseases with some clinical characteristics. The unraveling of the molecular cause of a growing number of ataxia has revealed that these diseases are the consequences of a large variety of different mechanisms, even involving novel, unsuspected ...

  20. Concordance of ATM (ataxia telangiectasia mutated) immunohistochemistry between biopsy or metastatic tumor samples and primary tumors in gastric cancer patients.

    Science.gov (United States)

    Kim, Hee Sung; Kim, Min A; Hodgson, Darren; Harbron, Christopher; Wellings, Robert; O'Connor, Mark J; Womack, Christopher; Yin, Xiaolu; Bang, Yung-Jue; Im, Seok-Ah; Lee, Byung Lan; Kim, Woo Ho

    2013-01-01

    ATM (ataxia telangiectasia mutated) is one of several DNA repair proteins that are suggested to sensitize tumor cells to the poly(ADP-ribose) polymerase inhibitor olaparib when deficient. The aim of this study was to assess the spatiotemporal concordance of ATM immunohistochemistry (IHC) in gastric cancer in order to determine if measurements made at the level of various sample types and times could be inferred as having the potential to be relevant to treatment decisions made at the patient level. Two independent cohorts composed of 591 gastric cancer patients divided into a gastrectomy cohort (n = 450) and a metastasis cohort (n = 141) were used in this study. A total of 2,705 ATM IHC samples were examined, including 450 whole tissue, 3 sets of 450 tissue microarray (TMA), 301 biopsy, 222 metastatic tumor and 2 additional whole tissue samples of 50 cases from the gastrectomy cohort, and 141 pairs of primary and metastatic tumors from the metastasis cohort. The prevalence of ATM negativity was 13.1% in biopsies, 13.9, 15.1, and 16.0% in TMAs and 15.9% in whole tissue samples of the gastrectomy cohort, and 21.4% in primary tumor and 21.5% in metastatic tumor samples of the metastasis cohort. coefficients were 0.341 for biopsy, 0.572 as the average of 3 TMAs and 0.415 for the largely synchronous metastatic tumors of the gastrectomy cohort, and 0.153 for the largely asynchronous metastatic tumors of the metastasis cohort. Using whole tissue sections from tumor resections or primary tumor, respectively, as the reference standards, specificity and sensitivity were 91.6 and 41.0% for biopsy, 93.9 and 61.9% as the average of 3 TMAs, and 86.6 and 58.8% for metastatic tumors of the gastrectomy cohort and 81.7 and 33.3% for metastatic tumors of the metastasis cohort, respectively. Although we have demonstrated that the IHC assay for ATM was robust and reproducible in gastric tumor samples, we have also found that measurements were subject to significant discordance across

  1. What Is Ataxia-Telangiectasia?

    Science.gov (United States)

    ... About A-T Research Fundraising About Us About Ataxia-telangiectasia About A-T » WHAT IS A- ... develop slurred or distorted speech, and swallowing problems. Ataxia... The onset of this ataxia marks the beginning ...

  2. Genetics Home Reference: Friedreich ataxia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions Friedreich ataxia Friedreich ataxia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Friedreich ataxia is a genetic condition that affects the nervous ...

  3. Genetics Home Reference: episodic ataxia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions episodic ataxia episodic ataxia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Episodic ataxia is a group of related conditions that affect ...

  4. [Chronic ataxia in childhood].

    Science.gov (United States)

    Erazo Torricelli, Ricardo

    2013-01-01

    Chronic ataxias are an heterogeneous group of disorders that affect the child at different ages. Thus, the congenital forms, generally non progressive are observed from first months of life and are expressed by hypotonia and motor delay long before the ataxia became evident. The cerebral magnetic resonance images (MRI) may be diagnostic in some pictures like Joubert syndrome. The group of progressive hereditary ataxias, usually begin after the infant period. The clinical signs are gait instability and ocular apraxia that can be associated with oculocutaneous telangiectasias (ataxia-telangiesctasia) or with sensory neuropathy (Friedreich ataxia). In this review are briefly described congenital ataxias and in more detailed form the progressive hereditary ataxias autosomal recessive, autosomal dominants and mitochondrials. The importance of genetic study is emphasized, because it is the key to obtain the diagnosis in the majority of these diseases. Although now there are no treatments for the majority of progressive hereditary ataxias, some they have like Refsum disease, vitamine E deficiency, Coenzyme Q10 deficiency and others, thus the diagnosis in these cases is even more important. At present the diagnosis of childhood hereditary ataxia not yet treatable is fundamental to obtain suitable handling, determine a precise outcome and to give to the family an opportune genetic counseling.

  5. [Acute benign ataxia in childhood].

    Science.gov (United States)

    Grippo, J; Arroyo, H A; Rocco, R D; Iraola, J

    1979-01-01

    The patogenesis and etiology of acute ataxia in childhood is not well known. It may occur without previous symptoms or may be the expression of specific infectious diseases. Forty patients hospitalized at the Hospital de Niños de Buenos Aires en 1972-1978, were studied. The neurological manifestations showed an acute onset, being ataxia the main sign, associate to tremor, nystagmus, dysartria, oculo-motor paresia, muscular weakness, and hyporeflexia. Most of the patients (82%) became cured within the first four weeks. It is advisable to establish a follow-up with periodic controls, mainly in those patients in whom an association with previous infectious diseases did not exist to be able to detect an association with degenerative or desmyelinizing diseases.

  6. SPECIFIC IMMUNOTHERAPY AND CELLULAR IMMUNITY IN PATIENTS WITH CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    D. K. Kenbaeva

    2013-01-01

    Full Text Available Cellular mechanisms are quite important immunological components of tumor surveillance, being, however, most vulnerable to influence of different adverse factors, including surgery-associated stress and ionizing radiation. Our study was aimed for assessing specific effects of immunotherapy upon indices of cellular immunity in patients with cervical cancer. Eighty-eight patients with cervical cancer (clinical stage I-IIA, Т1аN0M0-T2aN0M0, who underwent appropriate surgery (for IA stage, or a combined treatment, including surgery gamma-ray teletherapy (IB, IIA stages are under study. The patients were distributed in two groups, depending on the therapy applied. Group 1 included patients subjected to surgical treatment plus and radiation therapy, Group 2 included those patients who were treated according to this protocol, with addition of a specific immunotherapy. Contents of T cells and various CD subpopulations of T-lymphocytes were identified by immunofluorescence techniques. Among patients with cervical cancer at clinical stages IA, IB, IIA, a reliable decrease in cellular immunity indices was registered, both after surgery, and during combined treatment. Introduction of specific immunotherapy to the conventional treatment schedule was associated with increase of cellular immune indices, and, in first line, the antineoplastic mechanisms (e.g., NK’s and NKT cell contents. One should point to a relatively low efficiency of this immunotherapy in combined treatment of patients with cervical cancer at IIA stage.

  7. Spinocerebellar Ataxia Type 10 (SCA10)

    Science.gov (United States)

    NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT ... Spinocerebellar Ataxia Type 10 (SCA10) What is spinocerebellar ataxia type 10? Spinocerebellar ataxia type 10 (SCA10) is one specific type of ataxia among a group ...

  8. Spinocerebellar Ataxia Type 5 (SCA5)

    Science.gov (United States)

    NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT ... Spinocerebellar Ataxia Type 5 (SCA5) What is spinocerebellar ataxia type 5? Spinocerebellar ataxia type 5 is one specific type of ataxia among a group of ...

  9. Writer's cramp in spinocerebellar ataxia Type 1

    Science.gov (United States)

    Khwaja, Geeta Anjum; Srivastava, Abhilekh; Ghuge, Vijay Vishwanath; Chaudhry, Neera

    2016-01-01

    Dystonia can be encountered in a small subset of patients with spinocerebellar ataxia (SCA), but task specific dystonia is extremely rare. We report a case of a 48-year-old male with confirmed SCA Type 1 (SCA1) with mild progressive cerebellar ataxia and a prominent and disabling Writer's cramp. This case highlights the ever-expanding phenotypic heterogeneity of the SCA's in general and SCA1 in particular. PMID:27695243

  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. Optic ataxia as a model to investigate the role of the posterior parietal cortex in visually guided action: Evidence from studies of patient M.H.

    Directory of Open Access Journals (Sweden)

    Cristiana eCavina-Pratesi

    2013-07-01

    Full Text Available Optic ataxia is a neuropsychological disorder that affects the ability to interact with objects presented in the visual modality following either unilateral or bilateral lesions of the posterior parietal cortex (PPC. Patients with optic ataxia fail to reach accurately for objects, particularly when they are presented in peripheral vision. The present review will focus on a series of experiments performed on patient M.H. Following a lesion restricted largely to the left PPC, he developed mis-reaching behaviour when using his contralesional right arm for movements directed toward the contralesional (right visual half-field. Given the clear-cut specificity of this patient’s deficit, whereby reaching actions are essentially spared when executed toward his ipsilateral space or when using his left arm, M.H. provides a valuable experiment of nature for investigating the role of the PPC in performing different visually guided actions. In order to address this, we used kinematic measurement techniques to investigate M.H.’s reaching and grasping behaviour in various tasks. Our experiments support the idea that optic ataxia is highly function-specific: it affects a specific sub-category of visually guided actions (reaching but not grasping, regardless of their specific end goal (both reaching toward an object and reaching to avoid an obstacle; and finally, is independent of the limb used to perform the action (whether the arm or the leg. Critically, these results are congruent with recent functional MRI experiments in neurologically intact subjects which suggest that the PPC is organized in a function-specific, rather than effector-specific, manner with different sub-portions of its mantle devoted to guiding actions according to their specific end-goal (reaching, grasping or looking, rather than according to the effector used to perform them (leg, arm, hand or eyes.

  12. A Precocious Cerebellar Ataxia and Frequent Fever Episodes in a 16-Month-Old Infant Revealing Ataxia-Telangiectasia Syndrome

    Directory of Open Access Journals (Sweden)

    Luigi Nespoli

    2013-01-01

    Full Text Available Ataxia-telangiectasia (AT is the most frequent progressive cerebellar ataxia in infancy and childhood. Immunodeficiency which includes both cellular and humoral arms has variable severity. Since the clinical presentation is extremely variable, a high clinical suspicion will allow an early diagnosis. Serum alpha-fetoprotein is elevated in 80–85% of patients and therefore could be used as a screening tool. Here, we present a case of a 5-year-old female infant who was admitted to our department at the age of 16 months because of gait disorders and febrile episodes that had begun at 5 months after the cessation of breastfeeding. Serum alfa-fetoprotein level was elevated. Other investigations showed leukocytopenia with lymphopenia, reduced IgG2 and IgA levels, and low titers of specific postimmunization antibodies against tetanus toxoid and Haemophilus B polysaccharide. Peripheral lymphocytes subsets showed reduction of T cells with a marked predominance of T cells with a memory phenotype and a corresponding reduction of naïve T cells; NK cells were very increased (41% with normal activity. The characterization of the ATM gene mutations revealed 2 specific mutations (c.5692C > T/c.7630-2A > C compatible with AT diagnosis. It was concluded that AT syndrome should be considered in children with precocious signs of cerebellar ataxia and recurrent fever episodes.

  13. Gluten-related disorders: gluten ataxia.

    Science.gov (United States)

    Hadjivassiliou, Marios; Sanders, David D; Aeschlimann, Daniel P

    2015-01-01

    The term gluten-related disorders (GRD) refers to a spectrum of diverse clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals. They include both intestinal and extraintestinal manifestations. Gluten ataxia (GA) is one of the commonest neurological manifestations of GRD. It was originally defined as otherwise idiopathic sporadic ataxia in the presence of circulating antigliadin antibodies of IgA and/or IgG type. Newer more specific serological markers have been identified but are not as yet readily available. GA has a prevalence of 15% amongst all ataxias and 40% of all idiopathic sporadic ataxias. It usually presents with gait and lower limb ataxia. It is of insidious onset with a mean age at onset of 53 years. Up to 40% of patients have evidence of enteropathy on duodenal biopsy. Gastrointestinal symptoms are seldom prominent and are not a reliable indicator for the presence of enteropathy. Furthermore, the presence of enteropathy does not influence the response to a gluten-free diet. Most patients will stabilise or improve with strict adherence to gluten-free diet depending on the duration of the ataxia prior to the treatment. Up to 60% of patients with GA have evidence of cerebellar atrophy on MR imaging, but all patients have spectroscopic abnormalities primarily affecting the vermis. Recent evidence suggests that patients with newly diagnosed coeliac disease presenting to the gastroenterologists have abnormal MR spectroscopy at presentation associated with clinical evidence of subtle cerebellar dysfunction. The advantage of early diagnosis and treatment (mean age 42 years in patients presenting with gastrointestinal symptoms vs. 53 years in patients presenting with ataxia) may protect the first group from the development and/or progression of neurological dysfunction.

  14. 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.

  15. Retinitis pigmentosa and macular degeneration in a patient with ataxia with isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.

    Science.gov (United States)

    Iwasa, Kazuo; Shima, Keisuke; Komai, Kiyonobu; Nishida, Yoichiro; Yokota, Takanori; Yamada, Masahito

    2014-10-15

    Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease caused by a mutation in the α-tocopherol transfer protein gene (TTPA). The clinical features of the disease resemble Friedreich's ataxia. However, AVED is associated with low plasma vitamin E levels, which results in compromised antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin plays a major role in the neurodegeneration observed in AVED. Some AVED patients experience decreased visual acuity. Retinitis pigmentosa is thought to be the main cause of this visual impairment. Although antioxidant levels are important for the prevention of macular degeneration, there have been no reports of macular degeneration in AVED. Here, we describe a patient with AVED with progressive macular degeneration, who carried a novel truncating mutation-c.717 del C (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly identified mutation results in severely low serum vitamin E levels, which may be associated with the development of retinitis pigmentosa and macular degeneration.

  16. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition

    Directory of Open Access Journals (Sweden)

    Wladimir Bocca Vieira de Rezende Pinto

    2015-01-01

    Full Text Available Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  17. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition

    Directory of Open Access Journals (Sweden)

    Wladimir Bocca Vieira de Rezende Pinto

    2015-10-01

    Full Text Available Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  18. Spinocerebellar ataxias – genotype-phenotype correlations in 104 Brazilian families

    OpenAIRE

    Teive,Hélio A. G.; Munhoz, Renato P.; Arruda,Walter O.; Iscia Lopes-Cendes; Salmo Raskin; Lineu C.Werneck; Tetsuo Ashizawa

    2012-01-01

    OBJECTIVE: Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias. METHODS: We studied 150 patients from 104 families with spinocerebellar ataxias who had received molecular genetic testing for spinocerebellar ataxia types 1, 2,...

  19. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    Science.gov (United States)

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

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

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    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.

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

    Science.gov (United States)

    Albuquerque, Marcus Vinicius Cristino de; Pedroso, José Luiz; Braga Neto, Pedro; Barsottini, Orlando Graziani Povoas

    2015-01-01

    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.

  2. 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.

  3. Scale for the assessment and rating of ataxia: development of a new clinical scale.

    NARCIS (Netherlands)

    Schmitz-Hubsch, T.; Montcel, S.T. du; Baliko, L.; Berciano, J.; Boesch, S.; Depondt, C.; Giunti, P.; Globas, C.; Infante, J.; Kang, J.S.; Kremer, H.P.H.; Mariotti, C.; Melegh, B.; Pandolfo, M.; Rakowicz, M.; Ribai, P.; Rola, R.; Schols, L.; Szymanski, S.; Warrenburg, B.P.C. van de; Durr, A.; Klockgether, T.; Fancellu, R.

    2006-01-01

    OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA

  4. Gly118Asp is a SCA14 founder mutation in the Dutch ataxia population

    NARCIS (Netherlands)

    Verbeek, DS; van de Warrenburg, BPC; Hennekam, FAM; Dooijes, D; Ippel, PF; Verschuuren-Bemelmans, CC; Kremer, HPH; Sinke, RJ

    2005-01-01

    Missense mutations in the PRKCG gene have recently been identified in spinocerebellar ataxia 14 (SCA14) patients; these include the Gly118Asp mutation that we found in a large Dutch autosomal dominant cerebellar ataxia (ADCA) family. We subsequently screened the current Dutch ataxia cohort (approxim

  5. Neuropathology in classical and variant ataxia-telangiectasia.

    NARCIS (Netherlands)

    Verhagen, M.M.M.; Martin, J.J.; Deuren, M. van; Ceuterick-de Groote, C.; Weemaes, C.M.R.; Kremer, B.; Taylor, M.A.; Willemsen, M.A.A.P.; Lammens, M.M.Y.

    2012-01-01

    Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated alpha-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms

  6. Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

    Directory of Open Access Journals (Sweden)

    Wolfgang Nachbauer

    Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

  7. Spinocerebellar ataxia type 7 (SCA7): First report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat

    NARCIS (Netherlands)

    Rub, U.; Brunt, E.R.; Gierga, K.; Seidel, K.; Schultz, C.; Schols, L.; Auburger, G.; Heinsen, H.; Ippel, P.F.; Glimmerveen, W.F.; Wittebol-Post, D.; Arai, K.; Deller, T.; Rai, D.

    2005-01-01

    Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic stu

  8. Spinocerebellar ataxia type 7 (SCA7) : First report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat

    NARCIS (Netherlands)

    Rub, U; Brunt, ER; Gierga, K; Seidel, K; Schultz, C; Schols, L; Auburger, G; Heinsen, H; Ippel, PF; Glimmerveen, WF; Wittebol-Post, D; Arai, K; Deller, T; Rai, D

    2005-01-01

    Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic stu

  9. Spinocerebellar ataxia type 6.

    Science.gov (United States)

    Solodkin, Ana; Gomez, Christopher M

    2012-01-01

    The autosomal dominant spinocerebellar ataxias (SCA) are a genetically heterogeneous group of neurodegenerative disorders characterized by progressive motor incoordination, in some cases with ataxia alone and in others in association with additional progressive neurological deficits. Spinocerebellar ataxia type 6 (SCA6) is the prototype of a pure cerebellar ataxia, associated with a severe form of progressive ataxia and cerebellar dysfunction. SCA6, originally classified as such by Zhuchenko et al. (1997), is caused by a CAG repeat expansion in the CACNA1A gene which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel. SCA6 is one of ten polyglutamine-encoding CAG nucleotide repeat expansion disorders comprising other neurodegenerative disorders such as Huntington's disease. The present review describes clinical, genetic, and pathological manifestations associated with this illness. Currently, there is no treatment for this neurodegenerative disease. Successful therapeutic strategies must target a valid pathological mechanism; thus, understanding the underlying mechanisms of disease is crucial to finding a proper treatment. Hence, this chapter will discuss as well the molecular mechanisms possibly associated with SCA6 pathology and their implication for the development of future treatment.

  10. Overview of Cellular Immunotherapy for Patients with Glioblastoma

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    Elodie Vauleon

    2010-01-01

    Full Text Available High grade gliomas (HGG including glioblastomas (GBM are the most common and devastating primary brain tumours. Despite important progresses in GBM treatment that currently includes surgery combined to radio- and chemotherapy, GBM patients' prognosis remains very poor. Immunotherapy is one of the new promising therapeutic approaches that can specifically target tumour cells. Such an approach could also maintain long term antitumour responses without inducing neurologic defects. Since the past 25 years, adoptive and active immunotherapies using lymphokine-activated killer cells, cytotoxic T cells, tumour-infiltrating lymphocytes, autologous tumour cells, and dendritic cells have been tested in phase I/II clinical trials with HGG patients. This paper inventories these cellular immunotherapeutic strategies and discusses their efficacy, limits, and future perspectives for optimizing the treatment to achieve clinical benefits for GBM patients.

  11. Brain pathology of spinocerebellar ataxias

    NARCIS (Netherlands)

    Seidel, Kay; Siswanto, Sonny; Brunt, Ewout R. P.; den Dunnen, Wilfred; Korf, Horst-Werner; Rueb, Udo

    2012-01-01

    The autosomal dominant cerebellar ataxias (ADCAs) represent a heterogeneous group of neurodegenerative diseases with progressive ataxia and cerebellar degeneration. The current classification of this disease group is based on the underlying genetic defects and their typical disease courses. Accordin

  12. Ataxia with Vitamin E Deficiency in Norway

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    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.

  13. 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.

  14. Uterine tumors in ataxia-telangiectasia.

    Science.gov (United States)

    Gatti, R A; Nieberg, R; Boder, E

    1989-02-01

    Roughly one-third of patients with ataxia-telangiectasia (AT) develop malignant tumors, usually of lymphoid origin. AT patients also exhibit progeric changes. We describe three patients, between the ages of 27 and 32 years, with uterine tumors: one with a frank leiomyosarcoma and chronic T-cell leukemia, one with a multilobulated leiomyoma of uncertain malignant potential, and one with an unremarkable leiomyoma. Thus, the spectrum of tumors in AT patients beyond adolescence includes nonlymphoid malignancies and precocious, benign leiomyomas.

  15. Specific cerebellar and cortical degeneration correlates with ataxia severity in spinocerebellar ataxia type 7.

    Science.gov (United States)

    Hernandez-Castillo, Carlos R; Galvez, Victor; Diaz, Rosalinda; Fernandez-Ruiz, Juan

    2016-03-01

    Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder that is accompanied by loss of motor control and macular degeneration. Previous studies have shown cerebellar and pons atrophy as well as functional connectivity changes across the whole brain. Although different MRI modalities have been used to study the degenerative process, little is known about the relationship between the motor symptoms and cerebral atrophy. Twenty-four patients with molecular diagnosis of SCA7 where invited to participate in this study. Ataxia severity was evaluated using the scale for the assessment and rating of ataxia (SARA). Structural magnetic resonance imaging (MRI) brain images were used to obtain the grey matter volume of each participant. As expected, we found a significant negative correlation between the SARA score and the grey matter volume in distinct regions of the cerebellum in the patient group. Additionally, we found significant correlations between the ataxia degree and the degeneration of specific cortical areas in these patients. These findings provide a better understanding of the relationship between gray matter atrophy and ataxia related symptoms that result from the SCA7 mutation.

  16. Epilepsy and Spinocerebellar Ataxia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-07-01

    Full Text Available A large consanguinous family from Saudi Arabia with 4 affected children presenting with an autosomal recessive ataxia, generalized tonic-clonic epilepsy and mental retardation is reported from the Institut de Genetique, Universite Louis Pasteur, Illkirch, France; Division of Pediatric Neurology, King Saud University, Riyadh, Saudi Arabia; and other centers.

  17. Quantitative evaluation of gait ataxia by accelerometers.

    Science.gov (United States)

    Shirai, Shinichi; Yabe, Ichiro; Matsushima, Masaaki; Ito, Yoichi M; Yoneyama, Mitsuru; Sasaki, Hidenao

    2015-11-15

    An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia.

  18. Partial correction of sensitivity to oxidant stress in Friedreich ataxia patient fibroblasts by frataxin-encoding adeno-associated virus and lentivirus vectors.

    Science.gov (United States)

    Fleming, Jane; Spinoulas, Afroditi; Zheng, Maolin; Cunningham, Sharon C; Ginn, Samantha L; McQuilty, Robert C; Rowe, Peter B; Alexander, Ian E

    2005-08-01

    Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of a number of debilitating inherited and acquired neurological conditions. The lack of effective treatments for many such conditions provides a strong rationale for exploring novel therapeutic approaches, including gene therapy. Friedreich ataxia (FRDA), a sensory neuropathy, is a progressive neurodegenerative disease associated with a loss of large sensory neurons from the dorsal root ganglia. Because a mouse model for this well-characterized disease has been generated, we elected to use FRDA as a model disease. In previous studies we achieved efficient and sustained delivery of a reporter gene to PNS sensory neurons, using recombinant adeno-associated viral (AAV) and lentiviral (LV) vectors. In the current study, AAV and LV vectors encoding the human frataxin cDNA were constructed and assessed for frataxin expression and function in primary FRDA patient fibroblast cell lines. FRDA fibroblasts have been shown to exhibit subtle biochemical changes, including increased mitochondrial iron and sensitivity to oxidant stress. Despite the inherent difficulty in working with primary cells, transduction of patient fibroblasts with either vector resulted in the expression of appropriately localized frataxin and partial reversal of phenotype.

  19. Eye movements in ataxia-telangiectasia.

    Science.gov (United States)

    Baloh, R W; Yee, R D; Boder, E

    1978-11-01

    The spectrum of eye movement disorders in six patients with ataxia-telangiectasia at different stages of progression was assessed quantitatively by electrooculography. All patients demonstrated abnormalities of voluntary and involuntary saccades. The youngest and least involved patient had significantly increased reaction times of voluntary saccades, but normal accuracy and velocity. The other patients demonstrated increased reaction times and marked hypometria of horizontal and vertical voluntary saccades. Saccade velocity remained normal. Vestibular and optokinetic fast components (involuntary saccades) had normal amplitude and velocity but the eyes deviated tonically in the direction of the slow component. We conclude that patients with ataxia-telangiectasia have a defect in the initiation of voluntary and involuntary saccades in the earliest stages. These findings are distinctly different from those in other familial cerebellar atrophy syndromes.

  20. Molecular basis of ataxia telangiectasia and related diseases

    Institute of Scientific and Technical Information of China (English)

    Lindsay G BALL; Wei XIAO

    2005-01-01

    Ataxia telangiectasia (AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer, with a hallmark of onset in early childhood. Several human diseases also share similar symptoms with AT albeit with different degrees of severity and different associated disorders. While all AT patients contain mutations in the AT-mutated gene (ATM), most other ATlike disorders are defective in genes encoding an MRN protein complex consisting of Mre11, Rad50 and Nbs1. Both ATM and MRN function as cellular sensors to DNA double-strand breaks, which lead to the recruitment and phosphorylation of an array of substrate proteins involved in DNA repair, apoptosis and cell-cycle checkpoints, as well as gene regulation, translation initiation and telomere maintenance. ATM is a member of the family of phosphatidylinositol 3-kinase-like protein kinases (PIKK), and the discovery of many ATM substrates provides the underlying mechanisms of heterologous symptoms among AT patients. This review article focuses on recent findings related to the initial recognition of doublestrand breaks by ATM and MRN, as well as a DNA-dependent protein kinase complex consisting of the heterodimer Ku70/Ku80 and its catalytic subunit DNAPKcs, another member of PIKK. This possible interaction suggests that a much greater complex is involved in sensing, transducing and co-ordinating cellular events in response to genome instability.

  1. Spinocerebellar Ataxia Type 2

    OpenAIRE

    Velázquez-Pérez, Luis; Rodríguez-Labrada, Roberto; Freund, Hans-Joachim; Auburger, Georg

    2012-01-01

    1. Introduction: The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections. The degenerative process may additionally involves the ponto- medullar systems, pyramidal tracts, basal ganglia, cerebral cortex, peripheral nerves (ADCA I) and the retina (ADCA II), or can be limited to the cerebellum (ADCA III) (Harding et al., 1993...

  2. Friedreich ataxia: dysarthria profile and clinical data.

    Science.gov (United States)

    Brendel, Bettina; Ackermann, Hermann; Berg, Daniela; Lindig, Tobias; Schölderle, Theresa; Schöls, Ludger; Synofzik, Matthis; Ziegler, Wolfram

    2013-08-01

    Friedreich ataxia (FRDA) is the most frequent recessive ataxia in the Western world. Dysarthria is a cardinal feature of FRDA, often leading to severe impairments in daily functioning, but its exact characteristics are only poorly understood so far. We performed a comprehensive evaluation of dysarthria severity and the profile of speech motor deficits in 20 patients with a genetic diagnosis of FRDA based on a carefully selected battery of speaking tasks and two widely used paraspeech tasks, i.e., oral diadochokinesis and sustained vowel productions. Perceptual ratings of the speech samples identified respiration, voice quality, voice instability, articulation, and tempo as the most affected speech dimensions. Whereas vocal instability predicted ataxia severity, tempo turned out as a significant correlate of disease duration. Furthermore, articulation predicted the overall intelligibility score as determined by a systematic speech pathology assessment tool. In contrast, neurologists' ratings of intelligibility--a component of the "Scale for the Assessment and Rating of Ataxia"--were found to be related to perceived speech tempo. Obviously, clinicians are more sensitive to slowness of speech than to any other feature of spoken language during dysarthria evaluation. Our results suggest that different components of speech production and trunk/limb motor functions are differentially susceptible to FRDA pathology. Furthermore, evidence emerged that paraspeech tasks do not allow for an adequate scaling of speech deficits in FRDA.

  3. Genetics Home Reference: ataxia-telangiectasia

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions ataxia-telangiectasia ataxia-telangiectasia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Ataxia-telangiectasia is a rare inherited disorder that affects ...

  4. Genetics Home Reference: ataxia neuropathy spectrum

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions ataxia neuropathy spectrum ataxia neuropathy spectrum Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Ataxia neuropathy spectrum is part of a group of ...

  5. 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.

  6. Distinct neurochemical profiles of spinocerebellar ataxias 1, 2, 6, and cerebellar multiple system atrophy.

    Science.gov (United States)

    Oz, Gülin; Iltis, Isabelle; Hutter, Diane; Thomas, William; Bushara, Khalaf O; Gomez, Christopher M

    2011-06-01

    Hereditary and sporadic neurodegenerative ataxias are movement disorders that affect the cerebellum. Robust and objective biomarkers are critical for treatment trials of ataxias. In addition, such biomarkers may help discriminate between ataxia subtypes because these diseases display substantial overlap in clinical presentation and conventional MRI. Profiles of 10-13 neurochemical concentrations obtained in vivo by high field proton magnetic resonance spectroscopy ((1)H MRS) can potentially provide ataxia-type specific biomarkers. We compared cerebellar and brainstem neurochemical profiles measured at 4 T from 26 patients with spinocerebellar ataxias (SCA1, N = 9; SCA2, N = 7; SCA6, N = 5) or cerebellar multiple system atrophy (MSA-C, N = 5) and 15 age-matched healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA) was used to assess disease severity. The patterns of neurochemical alterations relative to controls differed between ataxia types. Myo-inositol levels in the vermis, myo-inositol, total N-acetylaspartate, total creatine, glutamate, glutamine in the cerebellar hemispheres and myo-inositol, total N-acetylaspartate, glutamate in the pons were significantly different between patient groups (Bonferroni corrected p ataxia types. Studies with higher numbers of patients and other ataxias are warranted to further investigate the clinical utility of neurochemical levels as measured by high-field MRS as ataxia biomarkers.

  7. High-dose thiamine improves the symptoms of Friedreich's ataxia.

    Science.gov (United States)

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-05-22

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3-5 days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease.

  8. Ocular motor characteristics of different subtypes of spinocerebellar ataxia: distinguishing features.

    Science.gov (United States)

    Kim, Ji Sun; Kim, Ji Soo; Youn, Jinyoung; Seo, Dae-Won; Jeong, Yuri; Kang, Ji-Hoon; Park, Jeong Ho; Cho, Jin Whan

    2013-08-01

    Because of frequent involvement of the cerebellum and brainstem, ocular motor abnormalities are key features of spinocerebellar ataxias and may aid in differential diagnosis. Our objective for this study was to distinguish the subtypes by ophthalmologic features after head-shaking and positional maneuvers, which are not yet recognized as differential diagnostic tools in most common forms of spinocerebellar ataxias. Of the 302 patients with a diagnosis of cerebellar ataxia in 3 Korean University Hospitals from June 2011 to June 2012, 48 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, or 8 or with undetermined spinocerebellar ataxias were enrolled. All patients underwent a video-oculographic recording of fixation abnormalities, gaze-evoked nystagmus, positional and head-shaking nystagmus, and dysmetric saccades. Logistic regression analysis controlling for disease duration revealed that spontaneous and positional downbeat nystagmus and perverted head-shaking nystagmus were strong predictors for spinocerebellar ataxia 6, whereas saccadic intrusions and oscillations were identified as positive indicators of spinocerebellar ataxia 3. In contrast, the presence of gaze-evoked nystagmus and dysmetric saccades was a negative predictor of spinocerebellar ataxia 2. Positional maneuvers and horizontal head shaking occasionally induced or augmented saccadic intrusions/oscillations in patients with spinocerebellar ataxia types 1, 2, and 3 and undetermined spinocerebellar ataxia. The results indicated that perverted head-shaking nystagmus may be the most sensitive parameter for SCA6, whereas saccadic intrusions/oscillations are the most sensitive for spinocerebellar ataxia 3. In contrast, a paucity of gaze-evoked nystagmus and dysmetric saccades is more indicative of spinocerebellar ataxia 2. Head-shaking and positional maneuvers aid in defining ocular motor characteristics in spinocerebellar ataxias. © 2013 Movement Disorder Society.

  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. Acute cerebellar ataxia: A neurological manifestation in malaria

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    Peddametla Shravan Kumar

    2014-01-01

    Full Text Available Malaria is a vector-borne disease transmitted by the bite of an infected female anopheles mosquito presents with varied clinical manifestations. Neurological manifestations include headaches, confusion, convulsions, hemiplegia, ataxia, cerebral palsy, cortical blindness, and Guillain-Barre syndrome (GBS. We are presenting a case report of acute cerebellar ataxia in a 20-year-old male patient who presented with fever and positive for Plasmodium vivax and Plasmodium falciparum malaria antibodies.

  11. Genetics of the dominant ataxias

    NARCIS (Netherlands)

    Verbeek, Dineke S.; van de Warrenburg, Bart P. C.

    2011-01-01

    The relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar comp

  12. Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA in a large group of Brazilian patients Freqüência das mutações que causam ataxia espinocerebelar (SCA1, SCA2, MJD/SCA3 e DRPLA em um grupo numeroso de pacientes Brasileiros

    Directory of Open Access Journals (Sweden)

    Iscia Lopes-Cendesi

    1997-09-01

    Full Text Available Spinocerebellar ataxia type 1 (SCA1, spinocerebellar ataxia type 2 (SCA2 and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3 are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%, 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6 % in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30 % of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.Ataxia espinocerebelar tipo 1 (SCA1, ataxia espinocerebelar tipo 2 (SCA2 e doença de Machado-Joseph ou ataxia espinocerebelar tipo 3 (MJD/SCA3 são três formas de ataxia espinocerebelar (SCA que apresentam herança genética autossômica dominante. Nessas três doenças foi encontrada uma expansão instável de trinucleotídeo CAG localizada na região codificadora dos

  13. Ataxia-telangiectasia

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    Nelson Pires Ferreira

    1966-09-01

    Full Text Available São apresentados os casos de dois irmãos com ataxia-telangiectasia, estudados sob os pontos de vista clínico, eletrencefalográfico, liquórico e encefalográfico. O autor resume os achados de diversos autores e chama a atenção para a regressão parcial da síndrome cerebelar em ambos os pacientes, fato ainda não referido na literatura.

  14. Ornidazole-induced ataxia in an Indian woman: A case report

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    Kango Gopal Gopinath

    2015-12-01

    Full Text Available The nitroimidazole group of antibiotics like metronidazole have been reported to cause cerebellar ataxia as a rare side effect. Ornidazole, the newest derivative of this class, has a long half life and is very rarely known to cause cerebellar ataxia. Here, we report a 61-year-old patient who developed ataxia due to ornidazole to highlight an unusual adverse event that improved rapidly after discontinuation of the offending drug.

  15. Ornidazole-induced ataxia in an Indian woman: A case report.

    Science.gov (United States)

    Gopinath, Kango Gopal; Wilson, Benny Paul; Viggeswarpu, Surekha; Mathews, Prasad K; Mani, Sunithi

    2015-01-01

    The nitroimidazole group of antibiotics like metronidazole have been reported to cause cerebellar ataxia as a rare side effect. Ornidazole, the newest derivative of this class, has a long half life and is very rarely known to cause cerebellar ataxia. Here, we report a 61-year-old patient who developed ataxia due to ornidazole to highlight an unusual adverse event that improved rapidly after discontinuation of the offending drug.

  16. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cel...

  17. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cel...

  18. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Tubsuwan, Alisa; Schmid, Benjamin

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cel...

  19. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele G; Schmid, Benjamin; Tubsuwan, Alisa;

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  20. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele G; Schmid, Benjamin; Tubsuwan, Alisa;

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  1. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele G; Tubsuwan, Alisa; Schmid, Benjamin;

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  2. Therapeutic effect of allogeneic cord blood stem cells transplantation on ataxia patients%异体脐血干细胞移植治疗共济失调患者疗效观察

    Institute of Scientific and Technical Information of China (English)

    周艳辉; 王琦; 余丹; 林珍

    2012-01-01

    Objective To observe the effect of allogeneic cord blood stem cells transplantation on ataxia patients. Methods A retrospective analysis of the effect of allogeneic cord blood stem cells transplantation on 3 ataxia patients,using ICARS and Berg Balance Scale.ReSUltS The ICARS score of 3 patients' after treatment dropped by 2.30El?.65,and Berg Balance Scale score rised about 9.00 ?3.00, showing significant difference (P<0.05 = . Conclusion The stem cells transplantation is effective in treatment of ataxia patients, while a followup of long - term effect and side effects is indicated.%目的 探讨异体脐血干细胞移植治疗共济失调患者的疗效.方法 回顾性分析3例共济失调患者经异体脐血干细胞移植治疗后的疗效,使用世界神经病联合会国际合作共济失调量表(ICARS)及Berg平衡量表评分.结果 3例患者治疗后ICARS评分下降2.30E1±2.65,Berg平衡量表评分升高9.00±3.00,P< 0.05.结论 异体脐血干细胞移植治疗共济失调疗效明确,但长期疗效及副作用尚需继续观察.

  3. Early-Onset Friedreich's Ataxia With Oculomotor Apraxia

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    Amene Saghazadeh

    2017-02-01

    Full Text Available Friedreich’s ataxia (FRDA is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1 is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Here we describe two siblings (13- and 10-year-old display overlapping clinical features of both early-onset FRDA and AOA1. Almost all of laboratory test (including urinary analysis/culture, biochemistry, peripheral blood smear, C-reactive protein level, erythrocyte sedimentation rate-1h results were within the normal range for both patients. Due to the normal laboratory test results; we concluded that the diagnosis was more likely to be FRDA than AOA1. Therefore, neurologists should bear in mind that clinical presentations of FRDA may vary widely from the classical phenotype of gait and limb ataxia to atypical manifestations such as oculomotor apraxia.

  4. Parkinsonism in spinocerebellar ataxia.

    Science.gov (United States)

    Park, Hyeyoung; Kim, Han-Joon; Jeon, Beom S

    2015-01-01

    Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive Parkinson disease (PD) like phenotype and atypical parkinsonism have been described especially in SCA2, SCA3, and SCA17 with geographic differences in prevalence. SCA2 is the most frequently reported subtype of SCA related to parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable in Asian populations especially in Korea. In addition, an unclear cutoff of the pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and pathologic features of parkinsonism in SCAs.

  5. A comprehensive clinical and genetic study of a large Mexican population with spinocerebellar ataxia type 7.

    Science.gov (United States)

    Velázquez-Pérez, L; Cerecedo-Zapata, C M; Hernández-Hernández, O; Martínez-Cruz, E; Tapia-Guerrero, Y S; González-Piña, R; Salas-Vargas, J; Rodríguez-Labrada, R; Gurrola-Betancourth, R; Leyva-García, N; Cisneros, B; Magaña, J J

    2015-01-01

    Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration. We recently described one of the largest series of patients with SCA7 that originated from a founder effect in a Mexican population, which allowed us to perform herein the first comprehensive clinical, neurophysiological, and genetic characterization of Mexican patients with SCA7. In this study, 50 patients, categorized into adult or early phenotype, were clinically assessed using standard neurological exams and genotyped using fluorescent PCR and capillary electrophoresis. Patients with SCA7 exhibited the classical phenotype of the disease characterized by cerebellar ataxia and visual loss; however, we reported, for the first time, frontal-executive disorders and altered sensory-motor peripheral neuropathy in these patients. Semiquantitative analysis of ataxia-associated symptoms was performed using Scale for the Assessment and Rating of Ataxia (SARA) and the Brief Ataxia Rating Scale (BARS) scores, while extracerebellar features were measured employing the Inventory of Non-ataxia Symptoms (INAS) scale. Ataxia rating scales confirmed the critical role size of cytosine-adenine-guanine (CAG) repeat size on age at onset and disease severity, while analysis of CAG repeat instability showed that paternal rather than maternal transmission led to greater instability.

  6. Coenzyme Q10 and spinocerebellar ataxias.

    Science.gov (United States)

    Lo, Raymond Y; Figueroa, Karla P; Pulst, Stefan M; Lin, Chi-Ying; Perlman, Susan; Wilmot, George; Gomez, Christopher; Schmahmann, Jeremy; Paulson, Henry; Shakkottai, Vikram G; Ying, Sarah; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael; Xia, Guangbin; Subramony, S H; Ashizawa, Tetsuo; Kuo, Sheng-Han

    2015-02-01

    The aim of this study was to investigate the association between drug exposure and disease severity in SCA types 1, 2, 3 and 6. The Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) enrolled 319 participants with SCA1, 2, 3, and 6 from 12 medical centers in the United States and repeatedly measured clinical severity by the Scale for Assessment and Rating of Ataxia (SARA), the Unified Huntington's Disease Rating Scale part IV (UHDRS-IV), and the 9-item Patient Health Questionnaire during July 2009 to May 2012. We employed generalized estimating equations in regression models to study the longitudinal effects of coenzyme Q10 (CoQ10), statin, and vitamin E on clinical severity of ataxia after adjusting for age, sex, and pathological CAG repeat number. Cross-sectionally, exposure to CoQ10 was associated with lower SARA and higher UHDRS-IV scores in SCA1 and 3. No association was found between statins, vitamin E, and clinical outcome. Longitudinally, CoQ10, statins, and vitamin E did not change the rates of clinical deterioration indexed by SARA and UHDRS-IV scores within 2 years. CoQ10 is associated with better clinical outcome in SCA1 and 3. These drug exposures did not appear to influence clinical progression within 2 years. Further studies are warranted to confirm the association.

  7. Ataxia, acute mountain sickness, and high altitude cerebral edema

    Institute of Scientific and Technical Information of China (English)

    Wu Tianyi; Ma Siqing; Bian Huiping; Zhang Minming

    2013-01-01

    Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE).The aim of this study was to investigate the diagnostic role of ataxia in acute mountain sickness (AMS) and HACE among mountain rescuers on the quake areas,and in approaching the relation between AMS and HACE.After the earthquake on April 14,2010,approximately 24080 lowland rescuers were rapidly transported from sea level or lowlands to the mountainous rescue sites at 3750 ~ 4568 m,and extremely hardly worked for an emergency treatment after arrival.Assessments of acute altitude illness on the quake areas were using the Lake Louise Scoring System.73 % of the rescuers were found to be developed AMS.The incidence of high altitude pulmonary edema(HAPE) and HACE was 0.73 % and 0.26 %,respectively,on the second to third day at altitude.Ataxia sign was measured by simple tests of coordination including a modified Romberg test.The clinical features of 62 patients with HACE were analyzed.It was found that the most frequent,serious neurological symptoms and signs were altered mental status(50/62,80.6 %)and truncal ataxia (47/62,75.8 %).Mental status change was rated slightly higher than ataxia,but ataxia occurred earlier than mental status change and other symptoms.The earliest sign of ataxia was a vague unsteadiness of gait,which may be present alone in association with or without AMS.Advanced ataxia was correlated with the AMS scores,but mild ataxia did not correlate with AMS scores at altitudes of 3750~4568 m.Of them,14 patients were further examined by computerized tomographic scanning of the brain and cerebral magnetic resonance imagines were examined in another 15 cases.These imaging studies indicated that the presence of the cerebral edema was in 97 % of cases who were clinically diagnosed as HACE (28/29).Ataxia seems to be a reliable sign of advanced AMS or HACE,so does altered mental status.

  8. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.

    2012-01-01

    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  9. Cardiac transplantation in Friedreich ataxia.

    Science.gov (United States)

    Yoon, Grace; Soman, Teesta; Wilson, Judith; George, Kristen; Mital, Seema; Dipchand, Anne I; McCabe, Jane; Logan, William; Kantor, Paul

    2012-09-01

    In this article, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurological disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac transplantation.

  10. Cardiac Transplantation in Friedreich Ataxia

    OpenAIRE

    Yoon, Grace; Soman, Teesta; Wilson, Judith; George, Kristen; Mital, Seema; Dipchand, Anne I; McCabe, Jane; Logan, William; Kantor, Paul

    2012-01-01

    In this paper, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurologic disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac ...

  11. An unusual cause of adult onset cerebellar ataxia with hypogonadism

    Directory of Open Access Journals (Sweden)

    Menon Ramshekhar

    2009-01-01

    Full Text Available We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.

  12. Neurodegeneration in ataxia-telangiectasia is caused by horror autotoxicus.

    Science.gov (United States)

    Kuljis, R O; Aguila, M C

    1999-05-01

    Ataxia-telangiectasia (A-T) is a pleiotropic, multi-system disorder with manifestations that include immune deficiency, sensitivity to ionizing radiation and neoplasms. Many of these manifestations are understood in principle since the identification in A-T patients of mutations in a gene encoding a protein kinase that plays a key role in signaling and repair of DNA damage. However, the cause of the neurodegeneration that afflicts patients with A-T for at least a decade before they succumb to overwhelming infections or malignancy remains mysterious. Based on our work in a mouse model of A-T and previous evidence of extra-neural autoimmune disorders in A-T, we postulate that the neurodegenerative process in A-T is not due to a function for A-T mutated (ATM) essential for the postnatal brain, but to an autoimmune process (hence 'horror autotoxicus', Paul Ehrlich's term for autoimmune disorder). This hypothetical mechanism may be analogous to that in the so-called 'paraneoplastic' neurodegenerative syndromes in patients with various malignancies. Thus, alterations in the balance between cellular and humoral immunity in A-T probably result in autoantibodies to cerebral epitopes shared with cells of the immune system. This hypothesis has important implications for the understanding and development of effective palliative and even preventative strategies for A-T, and probably for other so far relentlessly progressive neurodegenerative disorders.

  13. Ramsay Hunt Syndrome : Clinical Characterization of Progressive Myoclonus Ataxia Caused by GOSR2 Mutation

    NARCIS (Netherlands)

    van Egmond, Martje E.; Verschuuren - Bemelmans, Cornelia; Nibbeling, Esther A.; Elting, Jan Willem J.; Sival, Deborah A.; Brouwer, Oebele F.; de Vries, Jeroen J.; Kremer, Hubertus P.; Sinke, Richard J.; Tijssen, Marina A.; de Koning, Tom J.

    2014-01-01

    BACKGROUND: Ramsay Hunt syndrome (progressive myoclonus ataxia) is a descriptive diagnosis characterized by myoclonus, ataxia, and infrequent seizures. Often the etiology cannot be determined. Recently, a mutation in the GOSR2 gene (c.430G>T, p.Gly144Trp) was reported in 6 patients with childhood-on

  14. Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia.

    NARCIS (Netherlands)

    Hiel, J.A.P.; Engelen, B.G.M. van; Weemaes, C.M.R.; Broeks, A.; Verrips, A.; Laak, H.J. ter; Vingerhoets, H.M.; Heuvel, L.P.W.J. van den; Lammens, M.M.Y.; Gabreëls, F.J.M.; Last, J.I.; Taylor, A.M.R.

    2006-01-01

    The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy. AT was proven by genetic studies showing ATM mutations and a reduced level of ATM. ATM activity, as measured by phosph

  15. Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2)

    NARCIS (Netherlands)

    Rueb, U.; Farrag, K.; Seidel, K.; Brunt, E. R.; Heinsen, H.; Buerk, K.; Melegh, B.; von Gall, C.; Auburger, G.; Bohl, J.; Korf, H. W.; Hoche, F.; den Dunnen, W.

    2013-01-01

    Aims: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of att

  16. 共济失调患者手运动时脑激活区域的定量分析%Quantitative analysis of the hand motor cortex in ataxia patients using blood oxygen level dependent functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    元小冬; 王小洁; 王德; 赵丽君; 王守红

    2010-01-01

    Objective To study the characteristics of the hand motor cortex in ataxia patients during active and passive finger-to-thumb opposition movements using bold oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Methods Ten right-handed healthy volunteers and 16 ataxia patients with motor cortex lesions were selected, and whole-brain BOLD-fMRI examinations were made while the subjects were performing the active and passive movements. Activated volume and intensity were recorded from the corresponding motor cortex and analyzed quantitatively. Meanwhile, the patients' coordination was evaluated using the international cooperative ataxia rating scale (ICARS). Results During passive movement of the ataxia patient's affected hands, the ipsilateral supplementary motor area (SMA) activated volume was larger than that during normal ipsilateral hand movement, and the activation intensity was also higher than that in the healthy controls. The ipsilateral cerebellum activated volume and intensity were significantly lower than those in the control group, and the frequency of appearance of the cerebellum was also less. The patients' activated volume and intensity in the ipsilateral cerebellum showed no correlation with ICARS scores. Conclusions When the ataxia patients' affected side cerebellum was dysfunctional, the ipsilateral SMA could compensate for the weak cerebellum function. The ICARS does not reflect cerebellum function.%目的 利用血氧水平依赖性功能性磁共振成像(BOLD-fMRI)技术,探讨共济失调患者在主动与被动复杂对指运动模式下关键脑功能区激活体积和强度的变化.方法 选取共济失调患者16例作为病例组,另选10名健康志愿者作为正常组.入选者均进行主动与被动复杂对指运动,在这两种运动模式下进行BOLD-fMRl检查,记录相应脑运动功能区的激活体积和强度并进行定量分析.采用共济失调量表(ICARS)对共济失调患者的

  17. Comparing speech characteristics in spinocerebellar ataxias type 3 and type 6 with Friedreich ataxia.

    Science.gov (United States)

    Brendel, Bettina; Synofzik, Matthis; Ackermann, Hermann; Lindig, Tobias; Schölderle, Theresa; Schöls, Ludger; Ziegler, Wolfram

    2015-01-01

    Patterns of dysarthria in spinocerebellar ataxias (SCAs) and their discriminative features still remain elusive. Here we aimed to compare dysarthria profiles of patients with (SCA3 and SCA6 vs. Friedreich ataxia (FRDA), focussing on three particularly vulnerable speech parameters (speaking rate, prosodic modulation, and intelligibility) in ataxic dysarthria as well as on a specific oral non-speech variable of ataxic impairment, i.e., the irregularity of oral motor diadochokinesis (DDK). 30 Patients with SCA3, SCA6, and FRDA, matched for group size (n = 10 each), disease severity, and disease duration produced various speech samples and DDK tasks. A discriminant analysis was used to differentiate speech and non-speech parameters between groups. Regularity of DDK was specifically impaired in SCA3, whereas impairments of speech parameters, i.e., rate and modulation were stronger affected in SCA6. Speech parameters are particularly vulnerable in SCA6, while non-speech oral motor features are notably impaired in SCA3.

  18. Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings.

    Science.gov (United States)

    Jacobi, Heike; Hauser, Till-Karsten; Giunti, Paola; Globas, Christoph; Bauer, Peter; Schmitz-Hübsch, Tanja; Baliko, László; Filla, Alessandro; Mariotti, Caterina; Rakowicz, Maria; Charles, Perine; Ribai, Pascale; Szymanski, Sandra; Infante, Jon; van de Warrenburg, Bart P C; Dürr, Alexandra; Timmann, Dagmar; Boesch, Sylvia; Fancellu, Roberto; Rola, Rafal; Depondt, Chantal; Schöls, Ludger; Zdzienicka, Elzbieta; Kang, Jun-Suk; Ratzka, Susanne; Kremer, Berry; Stephenson, Dennis A; Melegh, Béla; Pandolfo, Massimo; Tezenas du Montcel, Sophie; Borkert, Johannes; Schulz, Jörg B; Klockgether, Thomas

    2012-03-01

    To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS). In a subgroup of patients, in which magnetic resonance images (MRIs) were available, we correlated MRI morphometric measures with clinical signs on an exploratory basis. The SARA subscores posture and gait (items 1-3), speech (item 4) and the limb kinetic subscore (items 5-8) did not differ between the genotypes. The scores of SARA item 3 (sitting), 5 (finger chase) and 6 (nose-finger test) differed between the subtypes whereas the scores of the remaining items were not different. In SCA1, ataxia symptoms were correlated with brainstem atrophy and in SCA3 with both brainstem and cerebellar atrophy. Cerebellar oculomotor deficits were most frequent in SCA6 followed by SCA3, whereas these abnormalities were less frequent in SCA1 and SCA2. Our data suggest that vestibulocerebellar, spinocerebellar and pontocerebellar circuits in SCA1, SCA2, SCA3 and SCA6 are functionally impaired to almost the same degree, but at different anatomical levels. The seemingly low prevalence of cerebellar oculomotor deficits in SCA1 and SCA2 is most probably related to the defective saccadic system in these disorders.

  19. Neuropathology in classical and variant ataxia-telangiectasia

    NARCIS (Netherlands)

    Verhagen, Mijke M. M.; Martin, Jean-Jacques; van Deuren, Marcel; Groote, Chantal Ceuterick-de; Weemaes, Corry M. R.; Kremer, Berry H. P. H.; Taylor, Malcolm A. R.; Willemsen, Michel A. A. P.; Lammens, Martin

    2012-01-01

    Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated a-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms, in

  20. Recessive spinocerebellar ataxia with paroxysmal cough attacks: a report of five cases.

    Science.gov (United States)

    Velázquez-Pérez, Luis; González-Piña, Rigoberto; Rodríguez-Labrada, Roberto; Aguilera-Rodríguez, Raul; Galicia-Polo, Lourdes; Vázquez-Mojena, Yaimeé; Cortés-Rubio, Ana M; Trujillo-Bracamontes, Marla R; Cerecedo-Zapata, Cesar M; Hernández-Hernández, Oscar; Cisneros, Bulmaro; Magaña, Jonathan J

    2014-04-01

    Hereditary ataxias are a heterogeneous group of neurological diseases characterized by progressive cerebellar syndrome and numerous other features, which result in great diversity of ataxia subtypes. Despite the characterization of a number of both autosomal dominant and autosomal recessive ataxias, it is thought that a large group of these conditions remains to be identified. In this study, we report the characterization of five patients (three Mexicans and two Italians) who exhibit a peculiar form of recessive ataxia associated with coughing. The main clinical and neurophysiological features of these patients include cerebellar ataxia, paroxysmal cough, restless legs syndrome (RLS), choreic movements, atrophy of distal muscles, and oculomotor disorders. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy, while video polysomnography (VPSG) studies showed a severe pattern of breathing-related sleep disorder, including sleep apnea, snoring, and significant oxygen saturation in the absence of risk factors. All patients share clinical features in the peripheral nervous system, including reduction of amplitude and prolonged latency of sensory potentials in median and sural nerves. Altogether, clinical criteria as well as molecular genetic testing that was negative for different autosomal dominant and autosomal recessive ataxias suggest the presence of a new form of recessive ataxia. This ataxia, in which cerebellar signs are preceded by paroxysmal cough, affects not only the cerebellum and its fiber connections, but also the sensory peripheral nervous system and extracerebellar central pathways.

  1. Genetics Home Reference: spinocerebellar ataxia type 3

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions SCA3 spinocerebellar ataxia type 3 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Spinocerebellar ataxia type 3 ( SCA3 ) is a condition characterized by ...

  2. Genetics Home Reference: spinocerebellar ataxia type 2

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions SCA2 spinocerebellar ataxia type 2 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Spinocerebellar ataxia type 2 ( SCA2 ) is a condition characterized by ...

  3. Genetics Home Reference: spinocerebellar ataxia type 6

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions SCA6 spinocerebellar ataxia type 6 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Spinocerebellar ataxia type 6 ( SCA6 ) is a condition characterized by ...

  4. Genetics Home Reference: spinocerebellar ataxia type 1

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions SCA1 spinocerebellar ataxia type 1 Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Spinocerebellar ataxia type 1 ( SCA1 ) is a condition characterized by ...

  5. 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...

  6. Ataxias and Cerebellar or Spinocerebellar Degeneration

    Science.gov (United States)

    ... Disorders Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Ataxia often occurs when parts of the nervous system that control movement are damaged. People with ataxia experience a failure of muscle control in their arms ...

  7. SUBCLINICAL HEPATIC ENCEPHALOPATHY DETECTED THROUGH PSYCHOMETRIC TESTS IN PATIENTS WITH HEPATIC CELLULAR CARCINOMA AND CIRRHOSIS

    Institute of Scientific and Technical Information of China (English)

    李薇; 吴积坰; 李惠芳; 顾海蔚; 范晓方

    2002-01-01

    Objective To study subclinical hepatic encephalopathy (SHE) in patients with hepatic cellular carcinoma by using psychometric tests.Methods 112 cases of hepatic cellular carcinoma complicated with cirrhosis and 65 controls were detected with number connection test (NCT), digital span test (DSP) and digital symbol test (DSY).Results The abnormal rate of NCT, DSY and DSP in patients was 23.2% (26/112), 14.3% (16/112) and 11.6%(13/112) respectively. Patients in the Child-Pugh B group had a significantly higher abnormal rate than that in the Child-Pugh A group.Conclusion SHE has an incidence of 25.0% (28/112) in patients with hepatic cellular carcinoma and cirrhosis in this study population; its occurrence is associated with the severity of liver impairment.

  8. [The genetics of spinocerebellar ataxias].

    Science.gov (United States)

    Jacobi, H; Minnerop, M; Klockgether, T

    2013-02-01

    Spinocerebellar ataxias are genetically heterogeneous autosomal dominant ataxia disorders. To date more than 30 different subtypes are known. In Germany particularly SCA1, SCA2, SCA3 and SCA6 are prevalent, as well as the less frequent subtypes SCA5, SCA14, SCA15, SCA17 and SCA28. Genetic causes range from coding repeat expansions (polyglutamine diseases), to non-coding expansions as well as conventional mutations. In some subtypes the genetic background is currently unknown. Age of onset, typical clinical findings and geographic distribution may help to reach a correct diagnosis; however a definitive diagnosis requires molecular genetic testing.

  9. Characteristics of Individuals at Risk for Spinocerebellar Ataxia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-08-01

    Full Text Available Investigators at University Hospital of Bonn and 13 other centers in Germany, France, and Italy conducted a prospective, longitudinal observational study (2008-2011 of offspring or siblings of patients with spinocerebellar ataxias (SCA-1, 2, 3, and 6.

  10. Clinical spectrum of ataxia-telangiectasia in adulthood.

    NARCIS (Netherlands)

    Verhagen, M.M.; Abdo, W.; Willemsen, M.A.A.P.; Hogervorst, F.B.L.; Smeets, D.F.C.M.; Hiel, J.A.P.; Brunt, E.R.; Rijn, M.A. van; Majoor Krakauer, D.; Oldenburg, R.A.; Broeks, A.; Last, J.I.; Veer, L.J. van 't; Tijssen, M.A.; Dubois, A.M.; Kremer, H.P.H.; Weemaes, C.M.R.; Taylor, A.M.; Deuren, M. van

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  11. Clinical spectrum of ataxia-telangiectasia in adulthood

    NARCIS (Netherlands)

    Verhagen, M M M; Abdo, W F; Willemsen, M A A P; Hogervorst, F B L; Smeets, D F C M; Hiel, J A P; Brunt, E R; van Rijn, M A; Majoor Krakauer, D; Oldenburg, R A; Broeks, A; Last, J I; van't Veer, L J; Tijssen, M A J; Dubois, A M I; Kremer, H P H; Weemaes, C M R; Taylor, A M R; van Deuren, M

    2009-01-01

    OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the

  12. [Autosomal dominant cerebellar ataxias in the Netherlands: a national inventory

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de

    2001-01-01

    OBJECTIVE: To provide a comprehensive estimate of the number of Dutch autosomal dominant cerebellar ataxias (ADCA) families and patients and thus estimate the minimal prevalence of ADCA in the Netherlands. Furthermore, to observe the relative frequency of SCA mutations and to study genotype-phenotyp

  13. 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.

  14. Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases.

    Science.gov (United States)

    Singh, Ankur; Faruq, Mohammed; Mukerji, Mitali; Dwivedi, Manish Kumar; Pruthi, Sumit; Kapoor, Seema

    2014-01-01

    Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

  15. DNA triplex structures in neurodegenerative disorder, Friedreich's ataxia

    Indian Academy of Sciences (India)

    Moganty R Rajeswari

    2012-07-01

    It is now established that a small fraction of genomic DNA does adopt the non-canonical B-DNA structure or ‘unusual’ DNA structure. The unusual DNA structures like DNA-hairpin, cruciform, Z-DNA, triplex and tetraplex are represented as hotspots of chromosomal breaks, homologous recombination and gross chromosomal rearrangements since they are prone to the structural alterations. Friedreich’s ataxia (FRDA), the autosomal recessive degenerative disorder of nervous and muscles tissue, is caused by the massive expansion of (GAA) repeats that occur in the first intron of Frataxin gene X25 on chromosome 9q13-q21.1. The purine strand of the DNA in the expanded (GAA) repeat region folds back to form the (R∙R*Y) type of triplex, which further inhibits the frataxin gene expression, and this clearly suggests that the shape of DNA is the determining factor in the cellular function. FRDA is the only disease known so far to be associated with DNA triplex. Structural characterization of GAA-containing DNA triplexes using some simple biophysical methods like UV melting, UV absorption, circular dichroic spectroscopy and electrophoretic mobility shift assay are discussed. Further, the clinical aspects and genetic analysis of FRDA patients who carry (GAA) repeat expansions are presented. The potential of some small molecules that do not favour the DNA triplex formation as therapeutics for FRDA are also briefly discussed.

  16. 脊髓小脑共济失调12型患者认知功能障碍的研究%Study on cognitive impairment in patients with spinocerebellar ataxia type 12

    Institute of Scientific and Technical Information of China (English)

    武传佳; 李海涛; 雷晶; 马建华; 关玉华; 张小宁

    2012-01-01

    Objective To study whether the cognitive impairment exists in patients with spinocerebellar ataxia type 12 (SCA12), and its influential factors. Methods The cognitive function in 5 SCA12 paitients (SCA12 group) and 13 health controls (normal control group) were examined by Montreal cognitive assessment scale (MoCA) and mini mental state examination scale ( MMSE). The degree of ataxia was assessed by international cooperative ataxia rating scale (ICARS). Results The MoCA score showed that there were 5 cases (100% ) with cognitive impairment in SCA12 group and 10 cases (77% ) with cognitive impairment in normal control group. The MMSE score showed that there were 2 cases (40% ) with cognitive impairment in SCA12 group and 1 case (7.7% ) with cognitive impairment in normal control group. The scores of MoCA and MMSE in SCA12 group were significantly lower than that in the normal control group (all P <0. 05). The score of ICARS in SCA12 group was 23-75, and the average score was (42.6 ±21.0). There was no ataxia in normal control group. Spearmans correlation analysis showed that the score of MMSE was negatively correlated with disease duration of SCA12 patients (r= -0. 894, P = 0.041); the score of abstraction in MoCA was negatively correlated with disease duration of SCA12 patients (r = -0.884,P= 0.047). Conclusion SCA12 patients can complicate with cognitive impairment, which may becorrelated with its long duration of disease.%目的 探讨脊髓小脑共济失凋(SCA)12型患者是否存在认知功能障碍及其影响因素.方法 采用蒙特利尔认知评估量表(MoCA)、简易精神状态检查量表(MMSE)对5例SCA12型患者(SCA12型组)及13名健康体检者(正常对照组)进行认知功能评估;采用国际协作共济失调评估量表(ICARS)进行共济失调严重程度评分.结果 MoCA评分结果显示,SCA12型组存在认知功能障碍5例(100%),正常对照组存在认知功能障碍10例(77%).MMSE评分结果显示,SCA12

  17. Movement disorders in spinocerebellar ataxias

    NARCIS (Netherlands)

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

    2011-01-01

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

  18. Hereditary Cerebellar Ataxias: A Korean Perspective

    Directory of Open Access Journals (Sweden)

    Ji Sun Kim

    2015-05-01

    Full Text Available Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes.

  19. The cellular and humoral immunity assay in patients with complicated urolithiasis

    Science.gov (United States)

    Ceban, E; Banov, P; Galescu, A; Tanase, D

    2017-01-01

    Especially complicated, renal lithiasis contributes to the general inflammatory syndrome development that interferes with nonspecific, humoral and cellular immune system. The surgical treatment of nephrolithiasis is closely related to drug therapy of urinary infection, one of the reasons being the reduction of the immune status. The work is performed by evaluating the immunological status preoperatively in 58 patients with complicated lithiasis. The analysis of the status in these patients demonstrated that complicated urolithiasis results in significant changes in the immune system, these changes being expressed at the cellular and humoral level of immunity. PMID:28255384

  20. Memory loss and ataxia after hyperemesis gravidarum: a case of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Accetta, Solange G; Abeche, Alberto M; Buchabqui, Jorge A; Hammes, Luciano; Pratti, Raquel; Afler, Taciana; Capp, Edison

    2002-04-10

    Hyperemesis gravidarum can induce Wernicke-Korsakoff syndrome (WKS), a thiamin deficiency disorder characterized by ocular abnormalities, ataxia and disturbance of consciousness. This should be considered in the differential diagnosis of pregnant patients with persisting vomiting and neurological alterations.

  1. Telemedicine system using a cellular telephone for continuous ambulatory peritoneal dialysis patients.

    Science.gov (United States)

    Nakamoto, Hidetomo; Kawamoto, Atsushi; Tanabe, Yoshimasa; Nakagawa, Yoshinori; Nishida, Eiichi; Akiba, Takashi; Suzuki, Hiromichi

    2003-01-01

    We developed a new telemedicine system to monitor the condition of continuous ambulatory peritoneal dialysis (CAPD) patients by using a cellular telephone and an Internet Web site. All data for the CAPD patients--blood pressure, heart rate, body weight, ultrafiltration volume, and urine volume--are collected and sent directly by cellular telephone to a data server that was constructed at the NTT DoCoMo Company data center. The system is directly connected to Internet by application service provider (ASP) technology. Anywhere, at any time, each patient can confirm changes in their data in graph form by using a cellular telephone or a computer connection to an Internet Web site. The average of each type of data is calculated and shown at the Web site. All data collected by cellular telephone are calculated and, in real time, sent directly to the treating physician's office over the Internet. Abnormal data are sent directly to the treating physician's office and shown in the host computer with an emergency signal (emergency alarm system). In addition, CAPD patients can easily contact the medical staff in the Kidney and Dialysis Center of Saitama Medical School (main hospital) using the same telemedicine system. We are using this telemedicine system for 46 CAPD patients being treated by Saitama Medical School. The cost of using the system is just US$3.00 or less per month for each patient. This newly developed system has great advantages for CAPD patients, especially elderly and handicapped patients. The system can be expanded into a network that serves all CAPD patients and all hospitals in Japan.

  2. Paroxysmal dysarthria-ataxia in remitting-relapsing Bickerstaff's-like encephalitis.

    Science.gov (United States)

    Piffer, Silvio; Turri, Giulia; Acler, Michele; Richelli, Silvia; Cerini, Roberto; Fiaschi, Antonio; Monaco, Salvatore; Bonetti, Bruno

    2014-06-15

    Paroxysmal dysarthria-ataxia is a rare neurological condition due to ephaptic transmission, generally appearing in multiple sclerosis patients characterized by stereotyped attacks of slurred speech usually accompanied by ataxia, appearing many times a day. Here we describe a patient with an unusual remitting-relapsing form of Bickerstaff's-like brainstem encephalitis who manifested PDA after a relapse with the involvement of a peculiar region below the red nuclei and benefited from lamotrigine.

  3. Clinical and neurophysiological profile of four German families with spinocerebellar ataxia type 14.

    Science.gov (United States)

    Ganos, Christos; Zittel, Simone; Minnerop, Martina; Schunke, Odette; Heinbokel, Christina; Gerloff, Christian; Zühlke, Christine; Bauer, Peter; Klockgether, Thomas; Münchau, Alexander; Bäumer, Tobias

    2014-02-01

    Spinocerebellar ataxia type 14 (SCA14) is an autosomal-dominant ataxia caused by point mutations of the Protein Kinase C Gamma gene. In addition to slowly progressive cerebellar ataxia, it is characterised by dystonia and myoclonus. With scant neuropathological data and no detailed neurophysiological examinations little is known on extracerebellar consequences of SCA14 related cerebellar pathology. To this end, we here delineate clinical phenomenology and neurophysiology of four German SCA14 families. Detailed clinical examination including ataxia severity evaluation by means of the Scale for the Assessment and Rating of Ataxia (SARA) was carried out in 9 affected family members (mean age 49.8 years ± 14.4 SD). Motor thresholds (MT), the contralateral silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), interhemispheric inhibition (IHI) and short afferent inhibition (SAI) were determined using transcranial magnetic stimulation (TMS). Somatosensory evoked potentials (SEP) of the median nerve, and acoustic and visual evoked potentials (AEP, VEP) were also performed. Most patients reported symptoms since early childhood. There was a positive correlation between age and SARA scores (r = .721, P ataxia, mild dystonia (focal, task-specific or segmental), subtle pyramidal signs and myoclonus. SICI increased with increasing conditioning pulse intensities in healthy controls but not in patients. Other neurophysiological parameters did not differ between groups. SCA14 is a slowly progressive ataxia associated with mild dystonia and myoclonus. Reduced SICI reflects abnormalities of intracortical inhibitory circuits.

  4. Rapid touchdown PCR assay for the molecular diagnosis of spinocerebellar ataxia type 2.

    Science.gov (United States)

    Condorelli, D F; Trovato-Salinaro, A; Spinella, F; Valvo, S; Saponara, R; Giuffrida, S

    1998-01-01

    Seven different chromosomal loci, designated SCA1 to SCA7 (spinocerebellar ataxias), have been identified as responsible for autosomal dominant cerebellar ataxias. Five genes (SCA1, 2, 3, 6, 7) have been cloned to date and show a single type of mutation, an unstable expansion of a CAG repeat coding for a polyglutamine stretch in the corresponding protein. We describe an improved polymerase chain reaction assay, based on a touchdown protocol, for the diagnosis of spinocerebellar ataxia type 2. This method produces an efficient amplification of both normal and pathological alleles and no radioactive labelling is necessary to observe the amplification products. The pathological alleles are identified by a simple non-denaturing polyacrylamide electrophoretic separation followed by ethidium bromide staining. A comparison of this technique with previously reported methods confirmed its utility for the rapid molecular diagnosis of spinocerebellar ataxia type 2. We found that the spinocerebellar ataxia type 2 mutation is responsible for 88% of the examined autosomal dominant cerebellar ataxia type 1 families in our territory (eastern Sicily). With the rapid touchdown polymerase chain reaction method, the trinucleotide expansion was also observed in 2 ataxic patients without family history of the disease, suggesting the necessity for analysis of spinocerebellar ataxia type 2 expansion even in sporadic patients.

  5. 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.

  6. Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patients.

    Science.gov (United States)

    Geiger, Stefan M; Massara, Cristiano L; Bethony, Jeffrey; Soboslay, Peter T; Carvalho, Omar S; Corrêa-Oliveira, Rodrigo

    2002-01-01

    The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

  7. Spinocerebellar ataxia type 7 (SCA7) : widespread brain damage in an adult-onset patient with progressive visual impairments in comparison with an adult-onset patient without visual impairments

    NARCIS (Netherlands)

    Rueb, U.; Brunt, E. R.; Seidel, K.; Gierga, K.; Mooy, C. M.; Kettner, M.; Van Broeckhoven, C.; Bechmann, I.; La Spada, A. R.; Schoels, L.; den Dunnen, W.; de Vos, R. A. I.; Deller, T.

    2008-01-01

    Spinocerebellar ataxia type 7 (SCA7) represents a rare and severe autosomal dominantly inherited ataxic disorder and is among the known CAG-repeat, or polyglutamine, diseases. In contrast to other currently known autosomal dominantly inherited ataxic disorders, SCA7 may manifest itself with differen

  8. Cognitive dysfunction in spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Helio Afonso Ghizoni Teive

    Full Text Available Abstract Spinocerebellar ataxias (SCAs comprise a heterogeneous group of complex neurodegenerative diseases, characterized by the presence of progressive cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs, extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. Objective: To verify the presence of cognitive dysfunction among the main types of SCA described in the literature. Methods: the review was conducted using the search system of the PUBMED and OMIM databases. Results: Cognitive dysfunction occurs in a considerable proportion of SCA, particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA. Mental retardation is a specific clinical feature of SCA 13. Conclusions: The role of the cerebellum in cognitive functions has been observed in different types of SCAs which can manifest varying degrees of cognitive dysfunction, dementia and mental retardation.

  9. Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

    Science.gov (United States)

    Cantarutti, Nicoletta; Claps, Alessia; Angelino, Giulia; Chessa, Luciana; Callea, Francesco; El Hachem, May; Diociaiuti, Andrea; Finocchi, Andrea

    2015-03-28

    Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

  10. Huntington’s disease masquerading as spinocerebellar ataxia

    OpenAIRE

    Rodríguez-Quiroga, Sergio Alejandro; Gonzalez-Morón, Dolores; Garretto, Nelida; Kauffman, Marcelo Andres

    2013-01-01

    Huntington’s disease (HD) is a neurodegenerative disorder of the central nervous system characterised by the presence of choreic abnormal movements, behavioural or psychiatric disturbances and dementia. Noteworthy, despite atypical motor symptoms other than chorea have been reported as initial presentation in some patients, a very few number of HD patients, presenting at onset mostly cerebellar dysfunction masquerading dominant spinocerebellar ataxias (SCA), were occasionally reported. We rep...

  11. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ke-Xia Wang; Li-Hua Zhang; Jiang-Long Peng; Yong Liang; Xue-Feng Wang; Hui Zhi; Xiang-Xia Wang; Huan-Xiong Geng

    2005-01-01

    AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.METHODS: The levels of T lymphocyte subsets and mlL-2R in peripheral blood mononuclear cells (PBMCs)were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole.RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole.CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

  12. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Home Health Conditions ataxia with vitamin E deficiency ataxia with vitamin E deficiency Enable Javascript to view ... boxes. Download PDF Open All Close All Description Ataxia with vitamin E deficiency is a disorder that ...

  13. Autosomal recessive cerebellar ataxias : the current state of affairs

    NARCIS (Netherlands)

    Vermeer, S.; van de Warrenburg, B. P. C.; Willemsen, M. A. A. P.; Cluitmans, M.; Scheffer, H.; Kremer, B. P.; Knoers, N. V. A. M.

    2011-01-01

    Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, an

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

    Science.gov (United States)

    ... linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Enable Javascript to view the expand/ ... Open All Close All Description X-linked sideroblastic anemia and ataxia is a rare condition characterized by ...

  15. 脊髓小脑性共济失调12型MRI表现及其相关因素分析%MRI Features of Spinocerebellar Ataxia Type 12 from Uygur Nationality Patients and Analysis of Related Factors

    Institute of Scientific and Technical Information of China (English)

    李海涛; 马建华; 雷晶; 张小宁

    2012-01-01

    目的:评价脊髓小脑性共济失调12型维吾尔族患者的MRI表现对此类疾病的诊断价值.方法:回顾分析了7例SCA12型患者的MRI表现.结果:SCA12型患者MRI特点以大脑皮质、小脑皮质和蚓部萎缩为主.结论:国内首次报道维吾尔族SCA12型神经影像学特点,其对临床诊断有提示作用,并且可以帮助鉴别诊断.%Purpose: To assess the value of MRI features in diagnosis of spinocerebellar ataxia type 12 (SCA12) from Uygur nationality patients. Methods: MRI features of seven SCA12 patients were retrospectively analyzed. Results: The main characteristics of SCA12 patients were atrophy of the cerebral cortex, cerebellar cortex and vermis. Conclusion: In domestic, we firstly reported the neuroimaging characteristics of SCA12 from Uygur nationality. MRI features can be the hint for clinical diagnosis and can provide an effective way for differential diagnosis.

  16. The effect of strength training on muscle cellular stress in prostate cancer patients on ADT

    Directory of Open Access Journals (Sweden)

    T S Nilsen

    2016-05-01

    Full Text Available Background Androgen deprivation therapy (ADT for prostate cancer (PCa is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. Methods Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG (n=16 or a control group (CG (n=15 for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV, HSP60 and indicators of muscle cellular stress (heat shock protein (HSP 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins using Western blot and ELISA. Results No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. Conclusion Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

  17. Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

    OpenAIRE

    Luis Velázquez-Perez; Rosalinda Díaz; Ruth Pérez-González; Nalia Canales; Roberto Rodríguez-Labrada; Jacquelín Medrano; Gilberto Sánchez; Luis Almaguer-Mederos; Cira Torres; Juan Fernandez-Ruiz

    2009-01-01

    BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and...

  18. Falls in spinocerebellar ataxias: Results of the EuroSCA Fall Study.

    Science.gov (United States)

    Fonteyn, Ella M R; Schmitz-Hübsch, Tanja; Verstappen, Carla C; Baliko, Laslo; Bloem, Bastiaan R; Boesch, Silvia; Bunn, Lisa; Charles, Perrine; Dürr, Alexandra; Filla, Allesandro; Giunti, Paola; Globas, Christoph; Klockgether, Thomas; Melegh, Bela; Pandolfo, Massimo; De Rosa, Anna; Schöls, Ludger; Timmann, Dagmar; Munneke, Marten; Kremer, Berry P H; van de Warrenburg, Bart P C

    2010-06-01

    To investigate the frequency, details, and consequences of falls in patients with autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease-related risk factors that are associated with an increased fall frequency. Two hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the EuroSCA natural history study, completed a fall questionnaire that assessed the frequency, consequences, and several details of falls in the previous 12 months. Relevant disease characteristics were retrieved from the EuroSCA registry. The database of the natural history study provided the ataxia severity scores as well as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at least one fall in the preceding 12 months. There was a high rate of fall-related injuries (74%). Factors that were associated with a higher fall frequency included: disease duration, severity of ataxia, the presence of pyramidal symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors associated with a lower fall frequency were: the presence of extrapyramidal symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2. The total number of non-ataxia symptoms and longer disease duration were independently associated with a higher fall frequency in a logistic regression analysis, while the presence of extrapyramidal symptoms was independently associated with a lower fall frequency. Our findings indicate that, in addition to more obvious factors that are associated with frequent falls, such as disease duration and ataxia severity, non-ataxia manifestations in SCA play a major role in the fall etiology of these patients.

  19. Complementation analysis of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. The clinical study of patients with spinocerebellar ataxia type 1 in Anhui region%安徽地区遗传性脊髓小脑性共济失调1型患者的临床研究

    Institute of Scientific and Technical Information of China (English)

    赵静; 程楠; 王训; 韩咏竹; 杨任民; 胡纪源

    2012-01-01

    Objective To study the clinical features of the patients with hereditary spinocerebellar ataxia type 1 (SCA1) in Anhui region. Methods The clinical data and the genomic DNA samples of these SCA patients and their family members from Anhui region were collected, their genotypes were analyzed by PCR-denaturing polyacrylamide gel electrophoresis and cloning sequencing, and their clinical features were also analyzed. Results There were 59 patients from Anhui region who were diagnosed as SCA in the study, of which 39 cases came from 15 families and 20 cases were sporadic. 7 SCA1 patients were detected and confirmed by gene diagnosis, who showed symptoms and signs such as cerebellar ataxia, dysarthria, tendon hyperreflexia, Romberg's signs and so on. 4 cases (4/7) had mental retardation and 2 cases (2/7) had peripheral sensory loss. None of them had symptoms and signs such as vision loss chorea and so on. The results of cranial MRI scan of these 7 patients showed cerebellar sulci widened, vermis atrophy, the pool around the brain stem expanded and cerebral cortex atrophy. 2 cases were with abnormal BAEP by evoked potential and 1 case was with neurogenic lesions by EMG. All patients were with normal liver function, blood lipids, serum copper, copper oxidase and ceruloplasmin. Conclusion Except for the common symptoms and signs for all patients with cerebellar ataxia, mental retardation, brain stem and cerebral cortex atrophy are the clinical features for patients with SCA1, which provides the basis for the patients diagnosed with cerebellar ataxia to be screened for SCA1 gene subtype.%目的 了解安徽地区遗传性脊髓小脑性共济失调1型(SCA1)患者的临床特征.方法收集安徽地区SCA患者及其家系成员的临床资料及基因组DNA标本,应用PCR-变性聚丙烯酰胺凝胶电泳结合克隆测序等技术检测其基因型,分析SCA1基因型的临床特征.结果经基因诊断证实,在临床诊断的59例安徽地区SCA患者(15个家系39

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

    Directory of Open Access Journals (Sweden)

    Aasef G Shaikh

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

  2. Reliability and validity of the Chinese version of the Scale for Assessment and Rating of Ataxia

    Institute of Scientific and Technical Information of China (English)

    TAN Song; NIU Hui-xia; ZHAO Lu; GAO Yuan; LU Jia-meng; SHI Chang-he; Chandra Avinash

    2013-01-01

    Background The Scale for the Assessment and Rating of Ataxia (SARA) was shown to be a reliable and valid measurement for patients with spinocerebellar ataxia (SCA).The Brazilian version and the Japanese version of SARAwere favorable for good reliability and validity.This study aimed to translate SARA into Chinese and test its reliability and validity in measurement of cerebellar ataxia.Methods SARA was translated into Chinese.A total 39 patients with degeneration cerebellar ataxia were evaluated independently by two neurologists with the Chinese version of SARA.Then the patients were evaluated by one of above neurologists with International Cooperative Ataxia Rating Scale (ICARS).The statistical analyses were performed using SPSS 17.0 for Windows.Results The Cronbach's alpha coefficient of the Chinese version of SARA was 0.78,which represents a good internal consistence.The correlation coefficient of the Chinese version of SARA scores between the two evaluators was 0.86,illustrating that the inter-rater reliability of Chinese version of SARA was good.The correlation coefficient between the Chinese version of SARA and ICARS was 0.91,illustrating that the criterion validity of Chinese version of SARA was not bad.Conclusions The Chinese version of SARA is reliable and effective for the assessment of degeneration cerebellar ataxia.Compared with ICARS,the evaluation of Chinese version of SARA is more objective,the assessment time is shortened,and the maneuverability is better.

  3. Downward Vertical Gaze Palsy As A Prominent Manifestation Of Episodic Ataxia Type 2: A Case Report

    Directory of Open Access Journals (Sweden)

    Reza SHERVIN BADV

    2013-11-01

    Full Text Available How to Cite This Article: Shervin Badv R, Niksirat A. Downward Vertical Gaze Palsy As A Prominent Manifestation Of Episodic Ataxia Type 2: A Case Report. Iran J Child Neurol. 2013 Autumn; 7(4:58- 60. ObjectiveEpisodic ataxia type 2 (EA2 is an inherited autosomal dominant disorder characterized by intermittent ataxia, nausea, vomiting, dysarthria, or nystagmus.We report a case of EA2, which downward gaze palsy exists as a common sign in all her attacks. Responsiveness of EA2 to acetazolamide was observed in this patient. ReferencesOuvrier R, Aicardi J. Disorders of the peripheral nerves. In: Aicardi J, Bax M, Gillberg C, editors.Diseases of the nervous system in Childhood. 3rd ed. London: Mackeith Press; 2009.Swaiman KF, Ashwal S, Ferriero DM, Schor NF. Pediatric neurology: principles & practice. 5th ed. London: Elsevier Saunders; 2012.National Ataxia Foundation. Minneapolis: National Ataxia Foundation; 2007 (cited 2007 Feb. Available from: URL: http://www.ataxia.org.Subramony SH, Schott K, Raike RS, Callahan J, Langford LR, Christova PS, et al. Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits. Ann Neurol. 2003;54(6:725-31.Brunt ER, van Weerden TW. Familial paroxysmal kinesigenic ataxia and continuous myokymia. Brain 1990;113(5:1361-82.Jen J. Familial Episodic Ataxias and Related Ion Channel Disorders. Curr Treat Options Neurol 2000;2(5:429-31.Fenichel M. Clinical Pediatric Neurology: A Signs and Symptoms Approach. 6th ed. Philadelphia: Elsevier Saunders; 2009. P.227-247.Griggs RC, Moxley RT 3rd, Lafrance RA, McQuillen J. Hereditary paroxysmal ataxia: response to Acetazolamide. Neurology 1978;28(12:1259-64.Scoggan KA, Friedman JH, Bulman DE. CACNA1A mutation in a EA-2 patient responsive to acetazolamide and valproic acid. Can J Neurol Sci 2006;33(1:68-72.Kim JM, Kim JS, Ki CS, Jeon BS. Episodic Ataxia Type 2 due to a Deletion Mutation in the CACNA1A Gene in a Korean Family. J Clin Neurol 2006

  4. Spinocerebellar ataxia type 23 : a genetic update

    NARCIS (Netherlands)

    Verbeek, Dineke S.

    2009-01-01

    The spinocerebellar ataxia type 23 locus was identified in 2004 based on linkage analysis in a large, two-generation Dutch family. The age of onset ranged 43-56 years and the phenotype was characterized by a slowly progressive, isolated ataxia. Neuropathological examination revealed neuronal loss in

  5. Ataxia-Telangiectasia (A-T)

    Science.gov (United States)

    Ataxia-Telangiectasia (A-T) What is ataxia-telangiectasia (A-T)? A-T is a hereditary progressive neurodegenerative disorder that begins in early childhood. ... nervous system. What are the symptoms of A-T? An affected child usually begins to show signs ...

  6. Genes and genetic testing in hereditary ataxias.

    Science.gov (United States)

    Sandford, Erin; Burmeister, Margit

    2014-07-22

    Ataxia is a neurological cerebellar disorder characterized by loss of coordination during muscle movements affecting walking, vision, and speech. Genetic ataxias are very heterogeneous, with causative variants reported in over 50 genes, which can be inherited in classical dominant, recessive, X-linked, or mitochondrial fashion. A common mechanism of dominant ataxias is repeat expansions, where increasing lengths of repeated DNA sequences result in non-functional proteins that accumulate in the body causing disease. Greater understanding of all ataxia genes has helped identify several different pathways, such as DNA repair, ubiquitination, and ion transport, which can be used to help further identify new genes and potential treatments. Testing for the most common mutations in these genes is now clinically routine to help with prognosis and treatment decisions, but next generation sequencing will revolutionize how genetic testing will be done. Despite the large number of known ataxia causing genes, however, many individuals with ataxia are unable to obtain a genetic diagnosis, suggesting that more genes need to be discovered. Utilization of next generation sequencing technologies, expression studies, and increased knowledge of ataxia pathways will aid in the identification of new ataxia genes.

  7. Machado-Joseph disease is genetically different from Holguin dominant ataxia (SCA2)

    Energy Technology Data Exchange (ETDEWEB)

    Silveria, I.; Manaia, A. (Univ. Porto (Portugal) Hopital Necker-Enfants Malades, Paris (France)); Melki, J.; Burlet, P.; Rozet, J.M.; Munnich, A. (Hopital Necker-Enfants Malades, Paris (France)); Magarino, C.; Gispert, S. (Univ. Porto (Portugal) Centro Nacional Genetica Medica, Havana (Cuba)); Lunkes, A.; Auburger, G. (Univ. Hospital, Duesseldorf (Germany))

    1993-09-01

    Machado-Joseph disease (MJD) and Holguin ataxia (SCA2) are autosomal dominant multisystem degenerations with spinocerebellar involvement that are predominant among people of Portuguese-Azorean and of Cuban descent, respectively. Their clinical distinction may at times be difficult to make in individual patients, due to significant phenotypic overlapping (similar overall age-of-onset and duration of cerebellar ataxia, eye movement, and, often, other common problems). The recent mapping of SCA2 to chromosome 12q provided another candidate region for linkage studies of MJD. Original data on 10 families with Holguin ataxia show that the locus of phenylalanine hydroxylase (PAH) on chromosome 12q is linked to SCA2 at 4 cM and is thus far its closest marker. The exclusion of linkage 15 cM on each side of PAH in 16 families with MJD shows that these two forms of dominant ataxia are genetically distinct and at different chromosomal locations (nonallelic). 20 refs., 2 tabs.

  8. 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.

  9. Cognitive Functions in Ataxia with Oculomotor Apraxia Type 2

    OpenAIRE

    Péter eKlivényi; Dezso eNemeth; Tamás eSefcsik; Karolina eJanacsek; Ildiko eHoffmann; Gábor Péter Háden; Zsuzsa eLonde; László eVécsei

    2012-01-01

    Background: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by cerebellar atrophy, peripheral neuropathy, oculomotor apraxia, and elevated serum alpha-fetoprotein (AFP) 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 ...

  10. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Lihua [Department of Radiation Oncology, The First Hospital of Jilin University, Changchun (China); Cui, Jingkun [Department of Internal Medicine, Nanling School District Hospital of Jilin University, Changchun (China); Tang, Fengjiao; Cong, Xiaofeng [Cancer Center, The First Hospital of Jilin University, Changchun (China); Han, Fujun, E-mail: fujun_han@aliyun.com [Cancer Center, The First Hospital of Jilin University, Changchun (China)

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  11. An update on Spino-cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Banashree Mondal

    2013-01-01

    Full Text Available The dominantly inherited ataxias, also known as Spino-cerebellar ataxias (SCAs, are rapidly expanding entities. New mutations are being identified at remarkable regularity. Recent awareness of molecular abnormalities in SCAs has addressed some of the long sought questions, but gaps in knowledge still exist. Three major categories of SCAs, according to molecular mechanisms, have evolved over recent few years: Polyglutamate expansion ataxia, non-coding zone repeat ataxia, and ataxia due to conventional mutation. Using the fulcrum of these mechanisms, the article provides an update of SCAs. Shared and specific clinical features, genetic abnormalities, and possible links between molecular abnormalities and cerebellar degeneration have been discussed. Emphasis has been placed on the mechanisms of polyglutamate toxicity.

  12. Influence of D-net (European GSM-Standard) cellular phones on pacemaker function in 50 patients with permanent pacemakers.

    Science.gov (United States)

    Wilke, A; Grimm, W; Funck, R; Maisch, B

    1996-10-01

    The widespread use of cellular phones in the last years has prompted some recent studies to suggest an interference of pacemaker function by cellular phone usage. To determine the risk of pacemaker patients using D-net cellular phones, we tested 50 patients with permanent pacemakers after routine pacemaker check by short phone calls using a cellular phone (Ericsson, D-net, frequency 890-915 MHz, digital information coding, equivalent to the European Groupe Systemes Mobiles standard). A six-channel surface ECG was continuously recorded from each patient to detect any interactions between pacemakers and cellular phones. Phone calls were repeated during the following pacemaker settings: (1) preexisting setting; (2) minimum ventricular rate of 90 beats/min and preexisting sensitivity; and (3) minimum ventricular rate of 90 beats/min and maximum sensitivity without T wave oversensing. Only 2 (4%) of 50 patients repeatedly showed intermittent pacemaker inhibition during calls with the cellular phone. Both pacemakers had unipolar sensing. Therefore, although interactions between cellular phone use and pacemaker function appear to be rare in our study, pacemaker dependent patients in particular should avoid the use of cellular phones.

  13. Friedreich's ataxia 1979: an overview.

    Science.gov (United States)

    Barbeau, A

    1979-05-01

    This overview summarizes the investigations carried out during the second part of Phase Two of the Quebec Cooperative Study of Friedreich's Ataxia. These investigations outline in more details the fundamental role played by an abnormality in the fatty acid composition (deficient linoleic acid, 18:2) of the cholesterol esters of high density lipoproteins (HDL) in the phenotypic expression of the disease. They postulate a defective incorporation of linoleic acid to surface phosphatidylcholine of chylomicrons and consequent relative and absolute decreases in lipoprotein protein components because of overpacking with defective cholesteryl esters. Secondarily to these changes, the postulated lack of activation of the lipoamide dehydrogenase (LAD) of the pyruvate dehydrogenase (PDH) complex could result in slow pyruvate oxidation, glucose intolerance, deficient synthesis of acetylcholine, and depletion of glutamic and aspartic acid pools. In parallel, abnormal phosphatidyl-choline molecules could be incorporated to membranes, resulting in specific defects in some functions of these membranes, including transport of calcium and/or taurine and myelinization. The framework of an understanding of Friedreich's ataxia is now available, but much fundamental and clinical work remains to be done to fill in and prove each one of these postulated steps.

  14. Evaluation of Severe Combined Immunodeficiency and Combined Immunodeficiency Pediatric Patients on the Basis of Cellular Radiosensitivity

    Science.gov (United States)

    Lobachevsky, Pavel; Woodbine, Lisa; Hsiao, Kuang-Chih; Choo, Sharon; Fraser, Chris; Gray, Paul; Smith, Jai; Best, Nickala; Munforte, Laura; Korneeva, Elena; Martin, Roger F.; Jeggo, Penny A.; Martin, Olga A.

    2016-01-01

    Pediatric patients with severe or nonsevere combined immunodeficiency have increased susceptibility to severe, life-threatening infections and, without hematopoietic stem cell transplantation, may fail to thrive. A subset of these patients have the radiosensitive (RS) phenotype, which may necessitate conditioning before hematopoietic stem cell transplantation, and this conditioning includes radiomimetic drugs, which may significantly affect treatment response. To provide statistical criteria for classifying cellular response to ionizing radiation as the measure of functional RS screening, we analyzed the repair capacity and survival of ex vivo irradiated primary skin fibroblasts from five dysmorphic and/or developmentally delayed pediatric patients with severe combined immunodeficiency and combined immunodeficiency. We developed a mathematical framework for the analysis of γ histone 2A isoform X foci kinetics to quantitate DNA-repair capacity, thus establishing crucial criteria for identifying RS. The results, presented in a diagram showing each patient as a point in a 2D RS map, were in agreement with findings from the assessment of cellular RS by clonogenic survival and from the genetic analysis of factors involved in the nonhomologous end-joining repair pathway. We provide recommendations for incorporating into clinical practice the functional assays and genetic analysis used for establishing RS status before conditioning. This knowledge would enable the selection of the most appropriate treatment regimen, reducing the risk for severe therapy-related adverse effects. PMID:26151233

  15. Evaluation of Severe Combined Immunodeficiency and Combined Immunodeficiency Pediatric Patients on the Basis of Cellular Radiosensitivity.

    Science.gov (United States)

    Lobachevsky, Pavel; Woodbine, Lisa; Hsiao, Kuang-Chih; Choo, Sharon; Fraser, Chris; Gray, Paul; Smith, Jai; Best, Nickala; Munforte, Laura; Korneeva, Elena; Martin, Roger F; Jeggo, Penny A; Martin, Olga A

    2015-09-01

    Pediatric patients with severe or nonsevere combined immunodeficiency have increased susceptibility to severe, life-threatening infections and, without hematopoietic stem cell transplantation, may fail to thrive. A subset of these patients have the radiosensitive (RS) phenotype, which may necessitate conditioning before hematopoietic stem cell transplantation, and this conditioning includes radiomimetic drugs, which may significantly affect treatment response. To provide statistical criteria for classifying cellular response to ionizing radiation as the measure of functional RS screening, we analyzed the repair capacity and survival of ex vivo irradiated primary skin fibroblasts from five dysmorphic and/or developmentally delayed pediatric patients with severe combined immunodeficiency and combined immunodeficiency. We developed a mathematical framework for the analysis of γ histone 2A isoform X foci kinetics to quantitate DNA-repair capacity, thus establishing crucial criteria for identifying RS. The results, presented in a diagram showing each patient as a point in a 2D RS map, were in agreement with findings from the assessment of cellular RS by clonogenic survival and from the genetic analysis of factors involved in the nonhomologous end-joining repair pathway. We provide recommendations for incorporating into clinical practice the functional assays and genetic analysis used for establishing RS status before conditioning. This knowledge would enable the selection of the most appropriate treatment regimen, reducing the risk for severe therapy-related adverse effects.

  16. ANO10 mutations cause ataxia and coenzyme Q₁₀ deficiency.

    Science.gov (United States)

    Balreira, Andrea; Boczonadi, Veronika; Barca, Emanuele; Pyle, Angela; Bansagi, Boglarka; Appleton, Marie; Graham, Claire; Hargreaves, Iain P; Rasic, Vedrana Milic; Lochmüller, Hanns; Griffin, Helen; Taylor, Robert W; Naini, Ali; Chinnery, Patrick F; Hirano, Michio; Quinzii, Catarina M; Horvath, Rita

    2014-11-01

    Inherited ataxias are heterogeneous disorders affecting both children and adults, with over 40 different causative genes, making molecular genetic diagnosis challenging. Although recent advances in next-generation sequencing have significantly improved mutation detection, few treatments exist for patients with inherited ataxia. In two patients with adult-onset cerebellar ataxia and coenzyme Q10 (CoQ10) deficiency in muscle, whole exome sequencing revealed mutations in ANO10, which encodes anoctamin 10, a member of a family of putative calcium-activated chloride channels, and the causative gene for autosomal recessive spinocerebellar ataxia-10 (SCAR10). Both patients presented with slowly progressive ataxia and dysarthria leading to severe disability in the sixth decade. Epilepsy and learning difficulties were also present in one patient, while retinal degeneration and cataract were present in the other. The detection of mutations in ANO10 in our patients indicate that ANO10 defects cause secondary low CoQ10 and SCAR10 patients may benefit from CoQ10 supplementation.

  17. RELATIONSHIP BETWEEN PROPRIOCEPTION AT THE KNEE JOINT AND GAIT ATAXIA IN HSAN III

    Science.gov (United States)

    Macefield, Vaughan G.; Norcliffe-Kaufmann, Lucy J.; Axelrod, Felicia B.; Kaufmann, Horacio

    2013-01-01

    Hereditary sensory and autonomic neuropathy type III features a marked ataxic gait that progressively worsens over time. We assessed whether proprioceptive disturbances can explain the ataxia. Proprioception at the knee joint was assessed using passive joint angle matching in 18 patients and 14 age-matched controls; 5 patients with cerebellar ataxia were also studied. Ataxia was quantified using the Brief Ataxia Rating Score, which ranged from 7 to 26/30. Neuropathy patients performed poorly in judging joint position: mean absolute error was 8.7±1.0° and the range was very wide (2.8–18.1°); conversely, absolute error was only 2.7±0.3° (1.6–5.5°) in the controls and 3.0±0.2° (2.1–3.4°) in the cerebellar patients. This error was positively correlated to the degree of ataxia in the neuropathy patients but not the cerebellar patients, suggesting that poor proprioceptive acuity at the knee joint is a major contributor to the ataxic gait associated with hereditary sensory and autonomic neuropathy type III. PMID:23681701

  18. Expression Analysis of Cellular Mir-29a and mir-29b in HIV Positive Patients

    Directory of Open Access Journals (Sweden)

    Hasan Kaleji (MSc

    2016-01-01

    Full Text Available Background and Objective: Various cellular factors affect the process of HIV activity. One of these cellular factors are structures known as microRN that are expected to be involved in controlling HIV replication and infectivity. The expression of one or a set of them may represent the patient's clinical conditions. In this study, the expression of miR-29a and miR-29b involved in regulating viral genes’ expression was evaluated in three HIV-positive groups and a healthy control group. Later, the expression level of these microRNAs was compared between the cases and controls. Methods: Total RNA extraction was performed on the collected samples using RNx-plus kit and then the microRNA expression levels were evaluated using Relative Real-time PCR. The obtained data was entered into SPSS 22 and Graphpad softwares and analyzed using Kruskal-Wallis and Man-Whitney tests. P-value of less than 0.05 was considered as statistical significance level. Results: The expression level of miR-29a was reduced in patients under treatment and drug-resistant patients ( P ≤ 0.05 . All three HIV-positive groups including people without drug treatment, patients under treatment and drug-resistant patients showed reduced miR-29b expression level compared to control group (P ≤ 0.05. Conclusion: the decreased expression of miR-29a and miR-29b in patients under treatment and drug-resistant patients indicates an increased viral replication and reduced CD4 cell count. It may be possible to predict the progression of the disease by miRNA measurement or control viral replication using these mir-RNAs that requires further studies.

  19. Reviewing the genetic causes of spastic-ataxias

    NARCIS (Netherlands)

    de Bot, Susanne T.; Willemsen, Michel A. A. P.; Vermeer, Sascha; Kremer, Hubertus P. H.; van de Warrenburg, Bart P. C.

    2012-01-01

    Although the combined presence of ataxia and pyramidal features has a long differential, the presence of a true spastic-ataxia as the predominant clinical syndrome has a rather limited differential diagnosis. Autosomal recessive ataxia of Charlevoix-Saguenay, late-onset Friedreich ataxia, and heredi

  20. Cytotoxic CD8+ T cells and CD138+ plasma cells prevail in cerebrospinal fluid in non-paraneoplastic cerebellar ataxia with contactin-associated protein-2 antibodies

    Directory of Open Access Journals (Sweden)

    Melzer Nico

    2012-07-01

    Full Text Available Abstract Objective The purpose of this paper is to report a patient with otherwise unexplained cerebellar ataxia with serum antibodies against contactin-associated protein-2 (CASPR-2 and provide a detailed description of the composition of cellular infiltrates in the cerebrospinal fluid (CSF compared to the peripheral blood (PB. CASPR-2 antibodies strongly labeling axons of cerebellar granule neurons have recently been identified in sera from nine patients with otherwise unexplained progressive cerebellar ataxia with mild to severe cerebellar atrophy. Design This is a report of a single case. Methods The study methods used were neurologic examination, magnetic resonance imaging, fluorodeoxyglucose positron emisson tomography, lumbar puncture and multicolor flow-cytometry. Results A 23-year-old Caucasian male presented with a two-year history of a progressive cerebellar and brainstem syndrome. Magnetic resonance imaging (MRI showed pronounced cerebellar atrophy, especially of the medial parts of the hemispheres and the vermis. Cerebral fluorodeoxyglucose positron emission tomography (FDG-PET showed pronounced hypometabolism of the whole cerebellum. CASPR-2 antibodies were detected in the serum but not the CSF, and none of the staging and laboratory assessments revealed other causes of progressive cerebellar degeneration. Interestingly, flow-cytometry of the CSF as compared to the PB showed increased fractions of CD138+ plasma cells as well as human leukocyte antigen (HLA-DR+ CD8+ T cells suggesting that both B cells and CD8+ T cells were preferentially recruited to and activated within the CSF- (and putatively central nervous system (CNS- compartment. Conclusion We confirm the association of CASPR-2 serum antibodies with cerebellar ataxia and provide the first evidence for a combined humoral and cellular immune response in this novel antibody-associated inflammatory CNS disease.

  1. Paroxysmal dysarthria and ataxia in multiple sclerosis and corresponding magnetic resonance imaging findings.

    Science.gov (United States)

    Li, Yongmei; Zeng, Chun; Luo, Tianyou

    2011-02-01

    Paroxysmal dysarthria (PD) and paroxysmal dysarthria-ataxia (PDA) syndromes are uncommon symptoms of the neurological dysfunction in multiple sclerosis (MS). We describe two patients who had clinically definite MS presented with symptomatic PD and PDA syndromes, respectively, related to demyelinating lesions. In one patient, the PD symptom was the initial manifestation of an acute episode. In the other patient, the episode of dysarthria was accompanied by ataxia disorders. Both patients had midbrain lesions at or below the level of the right red nucleus on magnetic resonance imaging (MRI), confirming that this area is critically involved. Both responded well to carbamazepine (CBZ).

  2. 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.

  3. [Hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada].

    Science.gov (United States)

    Dupré, N; Chrestian, N; Thiffault, I; Brais, B; Rouleau, G A; Bouchard, J-P

    2008-01-01

    It has been demonstrated, for many inherited diseases, that historical events have shaped the various regional gene pools of Eastern Canada. In so doing, it has given rise to the increased prevalence of some rare diseases due, to founder effects. The following neurogenetic disorders were first identified in patients from Eastern Canada: AOA-2, Arsacs, HSN-2, Arca-1, HMSN/ACC and Arsal. The population of Eastern Canada, we are convinced, will still allow the identification of new rare forms of hereditary ataxias, spastic parapareses and neuropathies as well as contribute to the uncovering of their mutated genes. We have summarized our current knowledge of the various hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada. The study of the more common and homogenous features of these diseases has been largely completed.

  4. The ataxia (axJ mutation causes abnormal GABAA receptor turnover in mice.

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    Corinna Lappe-Siefke

    2009-09-01

    Full Text Available Ataxia represents a pathological coordination failure that often involves functional disturbances in cerebellar circuits. Purkinje cells (PCs characterize the only output neurons of the cerebellar cortex and critically participate in regulating motor coordination. Although different genetic mutations are known that cause ataxia, little is known about the underlying cellular mechanisms. Here we show that a mutated ax(J gene locus, encoding the ubiquitin-specific protease 14 (Usp14, negatively influences synaptic receptor turnover. Ax(J mouse mutants, characterized by cerebellar ataxia, display both increased GABA(A receptor (GABA(AR levels at PC surface membranes accompanied by enlarged IPSCs. Accordingly, we identify physical interaction of Usp14 and the GABA(AR alpha1 subunit. Although other currently unknown changes might be involved, our data show that ubiquitin-dependent GABA(AR turnover at cerebellar synapses contributes to ax(J-mediated behavioural impairment.

  5. 安徽脊髓小脑性共济失调患者基因型与中医证型相关性%Relationship between Genotypes and Traditional Chinese Medicine Syndromes in Spinocerebellar Ataxia Patients from Anhui Province

    Institute of Scientific and Technical Information of China (English)

    程楠; 赵静; 王训; 喻绪恩; 胡纪源; 韩咏竹; 杨任民

    2012-01-01

    目的 通过探讨脊髓小脑性共济失调(spinocerebellar ataxia,SCA)患者基因型与中医证型的关系,为SCA的辨证客观化提供依据.方法 检测59例来自安徽地区的家族性或散发性SCA患者的基因型,以30例无血缘关系的健康人为对照.对这些SCA患者进行辨证分型,分析其基因型与中医证型的相关性.结果 本组59例SCA患者有17例检出SCA3基因亚型,有7例检出SCA1基因亚型.上述患者中医证型表现为肾精亏虚型、脾肾两虚型、肝肾阴虚型、肾虚血瘀型4种,且以肾精亏虚型和脾肾两虚型为主.其中SCA3基因亚型患者与脾肾两虚型相关,而SCA1基因亚型患者与上述证型均无相关性.结论 研究初步证实,不同基因亚型的SCA患者与中医证型可能存在相关性,SCA患者不同的中医证型应有其相应的分子基础.%Objective To provide a basis for the objectification of syndrome-differentiation in spinocerebellar ataxia (SCA) patients, via studying the relationship between genotypes of SCA and traditional Chinese medicine (TCM) syndromes. Methods A total of 59 familial or sporadic SCA patients from Anhui province were collected according to inclusion criteria, and their SCA genotypes were detected, and other 30 unrelated healthy people served as controls. Their TCM syndrome types were differentiated, and the relationship between SCA genotypes and TCM syndrome types were analyzed. Results Of 59 SCA patients,17 were diagnosed as SCA3 genotype, and 7 as SCA1 genotype. Four TCM syndrome types were found among these patients, including kidney essence deficiency, asthenia of both spleen and kidney, asthenia of both kidney-yin and liver-yin, and kidney deficiency complicated with blood stasis, with kidney essence deficiency and asthenia of both spleen and kidney being the most common types. The SCA3 genotype was significantly related to asthenia of both spleen and kidney, while SCA1 genotype did not correlate with any of the four TCM

  6. Effect of Astragalus Injection on Serious Abdominal Traumatic Patients' Cellular Immunity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the change of serious abdominal traumatic patients' cellular immunity and the effect of Astragalus Injection (Al) on it. Methods: Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with Al 20 mi was added into 250 mi of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored.Results: On the first day, in the conventional group and treated group, the levels of CD3 + , CD4 + , CD4 +/CD8 + ,CD16+ , CD69 + and CD3 +/homologous leucocytic antigen-DR (HLA-DR+) were apparently lower than those in the healthy group (P<0.05), while the CD8 + was significantly higher than that in the healthy group ( P<0.05), and there was no significant difference between the conventional group and the treated group (P>0.05) ; on the 14th days, the levels of CD3+, CD4+, CD4+/CD8+, CD16+, CD69+ and CD3+/HLA-DR+ of the treated group gotclosed to healthy subject value, and got even higher than those of conventional group (P<0.05); CD8 + got close to that of healthy subjects, while obviously lower than that of conventional group (P<0.05). Conclusion: After serious abdominal trauma, cellular immunity lowered, auxiliary use of Al was beneficial to the restoration of cellular immunity.

  7. 100 CHILDREN WITH ACUTE ATAXIA; A SURVEY IN MOFID CHILDREN'S HOSPITAL

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    P. Karimzadeh

    2006-10-01

    Full Text Available Objective:The term "Ataxia" refers to disturbances of body posture and movementthat are normally controlled by the cerebellum, frontal lobes and theposterior columns of the spinal cord. The primary symptom and themost prominent feature of ataxia is abnormal gait which is characterizedby lurching and wide base walking.Ataxia was considered acute, if it had occurred within the two precedingweeks. Knowing how frightening acute-onset Ataxia is for the familyis not surprising that the condition prompts an immediate visit to thephysician.Material & Methods:In view of the lack of information in our country, on the etiology ofsudden-onset Ataxia, the authors enrolled 100 children with the chiefcomplaint of acute loss of equilibrium, who came to the attention ofthe Pediatric Neurology Department over a two year duration(Sept.2001-Sept 2003; they were admitted to the Mofid Childrens'Hospital and all necessary investigations were carried out.Results & Conclusion:The results revealed that Acute Cerebellar Ataxia was the most commoncause of the problem, the second most frequent being drug intoxication,which most commonly occurred in patients, 2-4years old. The remainingcausative factors in order of descending frequency consisted ofinfectious polyneuropathy, migraine, opsoclonus-myoclonus, braintumor, acute disseminated encephalomyelitis, multiple sclerosis, andepilepsy.

  8. Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation.

    Science.gov (United States)

    Graves, Tracey D; Cha, Yoon-Hee; Hahn, Angelika F; Barohn, Richard; Salajegheh, Mohammed K; Griggs, Robert C; Bundy, Brian N; Jen, Joanna C; Baloh, Robert W; Hanna, Michael G

    2014-04-01

    Episodic ataxia type 1 is considered a rare neuronal ion channel disorder characterized by brief attacks of unsteadiness and dizziness with persistent myokymia. To characterize the natural history, develop outcome measures for future clinical trials, and correlate genotype with phenotype, we undertook an international, prospective, cross-sectional study. Thirty-nine individuals (51% male) were enrolled: median age 37 years (range 15-65 years). We identified 10 different pathogenic point mutations in KCNA1 that accounted for the genetic basis of 85% of the cohort. Participants with KCNA1 mutations were more likely to have a positive family history. Analysis of the total cohort showed that the first episode of ataxia occurred before age 20 in all but one patient, with an average age of onset of 7.9 years. Physical exertion, emotional stress and environmental temperature were the most common triggers for attacks. Attack frequency ranged from daily to monthly, even with the same KCNA1 genotype. Average attack duration was in the order of minutes. Ten participants (26%) developed permanent cerebellar signs, which were related to disease duration. The average Scale for the Assessment and Rating of Ataxia score (SARA, a standardized measure of cerebellar dysfunction on clinical examination, scores range from 0-40) was an average of 3.15 for all participants (range 0-14), but was only 2 in those with isolated episodic ataxia compared with 7.7 in those with progressive cerebellar ataxia in addition to episodic ataxia. Thirty-seven participants completed the SF-36, a quality of life survey; all eight domain norm-based average scores (mean=50) were below normal with mental health being the lowest (41.3) in those with mutation positive episodic ataxia type 1. Scores on SF-36 correlated negatively with attack frequency. Of the 39 participants in the study, 33 harboured mutations in KCNA1 whereas the remaining six had no mutation identified. Episodic ataxia type 1 phenocopies

  9. [Peripheral neuropathies associated with hereditary cerebellar ataxias].

    Science.gov (United States)

    Anheim, M; Tranchant, C

    2011-01-01

    Inherited cerebellar ataxias constitute a complicated and heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or spinocerebellar tract, spinal cord and peripheral nerves. A peripheral neuropathy is frequently seen in inherited cerebellar ataxias although it rarely reveals the disease. Moreover, the peripheral neuropathy is helpful for the diagnostic procedure and contributes to the functional prognosis of the disease. Thus, electroneuromyography is essential in the algorithm for the diagnosis of inherited cerebellar ataxias, as well as brain MRI (looking especially for cerebellar atrophy) and the assessment of several biomarkers (alpha-foetoprotein, vitamin E, albumin, LDL cholesterol, lactic acid, phytanic acid).

  10. 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.

  11. Cellular and humoral immune responses to Borrelia burgdorferi antigens in patients with culture-positive early Lyme disease.

    Science.gov (United States)

    Vaz, A; Glickstein, L; Field, J A; McHugh, G; Sikand, V K; Damle, N; Steere, A C

    2001-12-01

    We determined cellular and humoral immune responses to Borrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

  12. EFFECT OF ACUPUNCTURE TREATMENT ON CELLULAR HEMORHEOLOGY,CHOLESTEROL AND TRIGLYCERIDE OF SIMPLE OBESITY PATIENTS

    Institute of Scientific and Technical Information of China (English)

    赵宁侠; 郭瑞林; 任秦有; 张周良; 史恒军

    2004-01-01

    Objective: To observe the effect of acupuncture on simple obesity and cellular hemorheology. Methods: Thirty-two cases of simple obesity patients were enrolled into this study. Acupoints of the Stomach Meridian and Spleen Meridian as Zhongwan (中脘CV 12), Liangmen (梁门ST 21), Tianshu (天枢ST 25), Guanyuan (关元CV 4), etc. were punctured, once daily in the first 5 days, and once every other day afterwards, with 10 sessions being a therapeutic course. Before treatment and after 3 courses of treatment, the body weight, waistline, weight index, serum cholesterol (CH), triglyceride and aggregation index of red blood cell (RBC) were detected. Results: After acupuncture treatment, all the indexes of body weight, waistline, weight index, serum CH, triglyceride and aggregation index of RBC decreased significantly in comparison with those of pre-treatment (P<0.05). Conclusion: Acupuncture can apparently improve cellular hemorheology, reduce body weight, serum cholesterol and TG levels in simple obesity patients.

  13. Genetics Home Reference: ataxia with oculomotor apraxia

    Science.gov (United States)

    ... high amounts of a protein called alpha-fetoprotein (AFP) in their blood. (An increase in the level ... tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor ...

  14. [Pathophysiology of Ataxia in Fisher Syndrome].

    Science.gov (United States)

    Kuwabara, Satoshi

    2016-12-01

    Fisher syndrome is regarded as a peculiar inflammatory neuropathy associated with ophthalmoplegia, ataxia, and areflexia. The disorder is associated with preceding infection, cerebrospinal fluid albumino-cytological dissociation, and spontaneous recovery, and regarded as a variant of Guillain-Barré syndrome. The discovery of anti-GQ1b IgG antibodies led to dramatic advances in understanding the pathophysiology of Fisher syndrome. The lesions in Fisher syndrome are determined by expression of ganglioside GQ1b in the human nervous system. This review article focuses on the pathophysiology of ataxia in Fisher syndrome. Current evidence suggests that antibody attack on Group Ia neurons in the dorsal root ganglia is mainly responsible for the sensory ataxia. Involvement of the muscle spindles might also contribute to the development of ataxia.

  15. Cerebellar Involvement in Ataxia and Generalized Epilepsy

    NARCIS (Netherlands)

    L. Kros (Lieke)

    2015-01-01

    markdownabstract__Abstract__ The work described in this thesis was performed in order to elucidate the role of different cerebellar modules in ataxia and generalized epilepsy using various techniques including in vivo electrophysiology, optogenetics, pharmacological interventions, immunohistology a

  16. Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.

    Science.gov (United States)

    Roque-Cuéllar, M C; Sánchez, B; García-Lozano, J R; Praena-Fernández, J M; Núñez-Roldán, A; Aguilar-Reina, J

    2011-10-01

    It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.

  17. Genetic and molecular aspects of spinocerebellar ataxias

    OpenAIRE

    Honti, Viktor; Vécsei, László

    2005-01-01

    The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to aggregate and form inclusions. In some cases, protein–protein interaction...

  18. 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...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  19. Guidelines and quality measures for the diagnosis of optic ataxia

    Directory of Open Access Journals (Sweden)

    Svenja eBorchers

    2013-07-01

    Full Text Available Since the first description of a systematic mis-reaching by Bálint in 1909, a reasonable number of patients showing a similar phenomenology, later termed optic ataxia (OA, has been described. However, there is surprising inconsistency regarding the behavioral measures that are used to detect OA in experimental and clinical reports, if the respective measures are reported at all. A typical screening method, that was presumably used by most researchers and clinicians, reaching for a target object in the peripheral visual space, has never been evaluated. We developed a set of instructions and evaluation criteria for the scoring of a semi-standardized version of this reaching task. We tested 36 healthy participants, a group of 52 acute and chronic stroke patients, and 24 patients suffering from cerebellar ataxia. We found a high interrater reliability and a moderate test-retest reliability comparable to other clinical instruments in the stroke sample. The calculation of cut-off thresholds based on healthy control and cerebellar patient data showed an unexpected high number of false positives in these samples due to individual outliers that made a considerable number of errors in peripheral reaching. This study provides first empirical data from large control and patient groups for a screening procedure that seems to be widely used but rarely explicity reported and prepares the grounds for its use as a standard tool for the description of patients who are included in single case or group studies addressing optic ataxia similar to the use of neglect, extinction, or apraxia screening tools.

  20. Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Yugoslavia.

    Science.gov (United States)

    Topisirovic, I; Dragasevic, N; Savic, D; Ristic, A; Keckarevic, M; Keckarevic, D; Culjkovic, B; Petrovic, I; Romac, S; Kostic, V S

    2002-10-01

    Spinocerebellar ataxia type 8 (SCA8) is a slowly progressive ataxia causally associated with untranslated CTG repeat expansion on chromosome 13q21. However, the role of the CTG repeat in SCA8 pathology is not yet well understood. Therefore, we studied the length of the SCA8 CTA/CTG expansions (combined repeats, CRs) in 115 patients with ataxia, 64 unrelated individuals with non-triplet neuromuscular diseases, 70 unrelated patients with schizophrenia, and 125 healthy controls. Only one patient with apparently sporadic ataxia was identified with an expansion of 100 CRs. He had inherited the expansion from his asymptomatic father (140 CRs) and transmitted the mutation to his son (92 CRs). Paternal transmission in this family produced contractions of 40 and 8 CRs, respectively. None of the subjects from other studied groups had an expansion at the SCA8 locus. In the control group the number of CRs at the SCA8 locus ranged from 14 to 34. Our findings support the notion that allelic variants of the expansion mutation at the SCA8 locus can predispose to ataxia.

  1. Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne;

    2010-01-01

    The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine...... with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats......-like phenotypes and ataxia syndromes, also in isolated cases....

  2. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients.

    Science.gov (United States)

    Lee, C; Longo, V D

    2011-07-28

    The dietary recommendation for cancer patients receiving chemotherapy, as described by the American Cancer Society, is to increase calorie and protein intake. Yet, in simple organisms, mice, and humans, fasting--no calorie intake--induces a wide range of changes associated with cellular protection, which would be difficult to achieve even with a cocktail of potent drugs. In mammals, the protective effect of fasting is mediated, in part, by an over 50% reduction in glucose and insulin-like growth factor 1 (IGF-I) levels. Because proto-oncogenes function as key negative regulators of the protective changes induced by fasting, cells expressing oncogenes, and therefore the great majority of cancer cells, should not respond to the protective signals generated by fasting, promoting the differential protection (differential stress resistance) of normal and cancer cells. Preliminary reports indicate that fasting for up to 5 days followed by a normal diet, may also protect patients against chemotherapy without causing chronic weight loss. By contrast, the long-term 20 to 40% restriction in calorie intake (dietary restriction, DR), whose effects on cancer progression have been studied extensively for decades, requires weeks-months to be effective, causes much more modest changes in glucose and/or IGF-I levels, and promotes chronic weight loss in both rodents and humans. In this study, we review the basic as well as clinical studies on fasting, cellular protection and chemotherapy resistance, and compare them to those on DR and cancer treatment. Although additional pre-clinical and clinical studies are necessary, fasting has the potential to be translated into effective clinical interventions for the protection of patients and the improvement of therapeutic index.

  3. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, R.; Lawerman, T. F.; Kuiper, M. J.; Geffen, van Joke; Lunsing, I. J.; Burger, H.; de Koning, T. J.; de Vries, J. J.; de Koning-Tijssen, M. A. J.; Sival, D. A.

    2015-01-01

    Objective: To determine observer-agreement and discriminantvalidity of ataxia rating scales.Background: In children and young adults, Early Onset Ataxia(EOA) is frequently concurrent with other Movement Disorders,resulting in moderate inter-observer agreement among MovementDisorder professionals. To

  4. Cerebellar ataxia and functional genomics : Identifying the routes to cerebellar neurodegeneration

    NARCIS (Netherlands)

    Smeets, C J L M; Verbeek, D S

    2014-01-01

    Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include among others, the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Fried

  5. 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…

  6. Age at onset variance analysis in spinocerebellar ataxias : a study in a Dutch-French cohort

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Hendriks, H.; Durr, A.; Zuijlen, M.C.A. van; Stevanin, G.; Camuzat, A.; Sinke, R.J.; Brice, A.; Kremer, H.P.H.

    2005-01-01

    In dominant spinocerebellar ataxias (SCAs), the issue of whether non-CAG dependent factors contribute to onset age remains unsettled. Data on SCA genotype, onset age, normal/expanded CAG repeat length, sex of the patient and transmitting parent, and family details were available from 802 patients. B

  7. 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.

  8. Maximum entropy, fractal dimension and lacunarity in quantification of cellular rejection in myocardial biopsy of patients submitted to heart transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Neves, L A [Universidade Estadual Paulista, IGCE, DEMAC, Rio Claro, SP (Brazil); Oliveira, F R; Peres, F A [Faculdade de Tecnologia de Sao Jose do Rio Preto, Sao Jose do Rio Preto, SP (Brazil); Moreira, R D; Moriel, A R; De Godoy, M F [Faculdade de Medicina de Sao Jose do Rio Preto, FAMERP, Sao Jose do Rio Preto, SP (Brazil); Murta Junior, L O, E-mail: laneves@rc.unesp.br [Universidade de Sao Paulo, FFCLRP, Depto Computacao e Matematica, Ribeirao Preto (Brazil)

    2011-03-01

    This paper presents a method for the quantification of cellular rejection in endomyocardial biopsies of patients submitted to heart transplant. The model is based on automatic multilevel thresholding, which employs histogram quantification techniques, histogram slope percentage analysis and the calculation of maximum entropy. The structures were quantified with the aid of the multi-scale fractal dimension and lacunarity for the identification of behavior patterns in myocardial cellular rejection in order to determine the most adequate treatment for each case.

  9. Clinical characteristics of combined cases of spinocerebellar ataxia types 6 and 31.

    Science.gov (United States)

    Ohmori, Hiroyuki; Hara, Akio; Ishikawa, Kinya; Mizusawa, Hidehiro; Ando, Yukio

    2015-01-01

    This study reports the first family in which spinocerebellar ataxia type 6 (SCA6) and spinocerebellar ataxia type 31 (SCA31) mutations were seen. An index patient first presented to our hospital due to gait and speech disturbances. Subsequent clinical investigation of this patient and her family members revealed consistent pure cerebellar ataxia transmitted in an autosomal-dominant manner. Genetic examination unexpectedly demonstrated that two of the five affected individuals had expansions of SCA6 and SCA31, while two others had SCA31 alone and the remaining had SCA6. Clinical manifestations were more severe in individuals with combined mutations relative to those with single mutation, suggesting that the SCA6 and SCA31 mutations have a cumulative pathogenic effect.

  10. The genetics of ataxia: through the labyrinth of the Minotaur, looking for Ariadne's thread.

    Science.gov (United States)

    Mancuso, M; Orsucci, D; Siciliano, G; Bonuccelli, U

    2014-09-01

    Among the hereditary cerebellar ataxias (CAs), there are at least 36 different forms of autosomal dominant cerebellar ataxia (ADCAs), 20 autosomal recessive cerebellar ataxias (ARCAs), two X-linked ataxias, and several forms of ataxia associated with mitochondrial defects. Despite the steady increase in the number of newly discovered CA genes, patients, especially those with putative ARCAs, cannot yet be genotyped. Moreover, in daily clinical practice, ataxia may present as an isolated cerebellar syndrome or, more often, it is associated with a broad spectrum of neurological manifestations including pyramidal, extrapyramidal, sensory, and cognitive dysfunction. Furthermore, non-neurological symptoms may also coexist. A close integration between clinical records, neurophysiological, neuroradiological and, in some instances, biochemical findings will help physicians in the diagnostic work-up (including selection of the correct genetic tests) and may lead to timely therapy. Some inherited CAs are in fact potentially treatable, and the efficacy of the therapy is directly related to the severity of the cerebellar atrophy and to the time of onset of the disease. Most cases of CA are sporadic, and the diagnostic work-up remains a challenge. Detailed anamnesis and deep investigation of the family pedigree are usually enough to discriminate between acquired and genetic conditions. In the case of ADCA, molecular testing should be guided by taking into account the main associated symptoms. In sporadic cases, a multi-disciplinary approach is needed and should consider the following points: (1) onset and clinical course; (2) associated features; (3) neurophysiological parameters, with special attention to the occurrence of peripheral neuropathy; (4) neuroimaging results; and (5) laboratory findings. A late-onset sporadic ataxia, in which other possible causes have been excluded by following the proposed steps, might be attributable to metabolic disorders, which in some

  11. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing.

    Science.gov (United States)

    Wang, Jun Ling; Yang, Xu; Xia, Kun; Hu, Zheng Mao; Weng, Ling; Jin, Xin; Jiang, Hong; Zhang, Peng; Shen, Lu; Guo, Ji Feng; Li, Nan; Li, Ying Rui; Lei, Li Fang; Zhou, Jie; Du, Juan; Zhou, Ya Fang; Pan, Qian; Wang, Jian; Wang, Jun; Li, Rui Qiang; Tang, Bei Sha

    2010-12-01

    Autosomal-dominant spinocerebellar ataxias constitute a large, heterogeneous group of progressive neurodegenerative diseases with multiple types. To date, classical genetic studies have revealed 31 distinct genetic forms of spinocerebellar ataxias and identified 19 causative genes. Traditional positional cloning strategies, however, have limitations for finding causative genes of rare Mendelian disorders. Here, we used a combined strategy of exome sequencing and linkage analysis to identify a novel spinocerebellar ataxia causative gene, TGM6. We sequenced the whole exome of four patients in a Chinese four-generation spinocerebellar ataxia family and identified a missense mutation, c.1550T-G transition (L517W), in exon 10 of TGM6. This change is at a highly conserved position, is predicted to have a functional impact, and completely cosegregated with the phenotype. The exome results were validated using linkage analysis. The mutation we identified using exome sequencing was located in the same region (20p13-12.2) as that identified by linkage analysis, which cross-validated TGM6 as the causative spinocerebellar ataxia gene in this family. We also showed that the causative gene could be mapped by a combined method of linkage analysis and sequencing of one sample from the family. We further confirmed our finding by identifying another missense mutation c.980A-G transition (D327G) in exon seven of TGM6 in an additional spinocerebellar ataxia family, which also cosegregated with the phenotype. Both mutations were absent in 500 normal unaffected individuals of matched geographical ancestry. The finding of TGM6 as a novel causative gene of spinocerebellar ataxia illustrates whole-exome sequencing of affected individuals from one family as an effective and cost efficient method for mapping genes of rare Mendelian disorders and the use of linkage analysis and exome sequencing for further improving efficiency.

  12. A gene for nystagmus-associated episodic ataxia maps to chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, P.L.; Root, D.; Gancher, S. [and others

    1994-09-01

    Episodic ataxia (EA) is a rare, autosomal dominant disorder, characterized by attacks of generalized ataxia and relatively normal neurological function between attacks. Onset occurs in childhood or adolescence and persists through adulthood. Penetrance is nearly complete. EA is clinically heterogeneous, including at least two distinct entities: (1) episodes of ataxia and dysarthria lasting hours to days, generally with interictal nystagmus (MIM 108500); (2) episodes of ataxia and dysarthria lasting only minutes, with interictal myokymia (MMM 160120). The EA/nystagmus patients sometimes develop persistent ataxia and cerebellar atrophy. Previously we reported linkage in four EA/myokymia families to a K{sup +} channel gene on chromosome 12p. We excluded this region in a large family with EA/nystagmus. We now report evidence for linkage to chromosome 19p in this and in one other EA/nystagmus family, based on eight microsatellite markers which span approximately 30 cM. The region is flanked distally by D19S209 and proximally by D19S226. All six markers within this region gave positive evidence for linkage; the highest total two-point lod scores occurred wtih D19S221 (3.98 at theta = 0.10) and D19S413 (3.37 at theta = 0.05). Interestingly, Joutel et al. (1993) mapped a gene for familial hemiplegic migraine (FHM) to the region around D19S221. Some individuals in these families have ataxia, cerebellar atrophy and interictal nystagmus, but no episodic ataxia. These results demonstrate that the clinical heterogeneity in EA reflects underlying genetic hetreogeneity. In addition, they suggest that EA/nystagmus and some FHM may represent different mutations in the same gene locus on chromosome 19p.

  13. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    Science.gov (United States)

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

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

    Science.gov (United States)

    ... Genetics Home Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by ...

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

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions NARP neuropathy, ataxia, and retinitis pigmentosa Enable Javascript to view the ... Download PDF Open All Close All Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that ...

  16. Fragile X-Associated Tremor and Ataxia Syndrome (FXTAS)

    Science.gov (United States)

    ... Resources and Publications Fragile X-Associated Tremor and Ataxia Syndrome (FXTAS): Overview Skip sharing on social media ... this: Page Content Fragile X-associated tremor and ataxia syndrome (FXTAS) is a late-onset condition (occurs ...

  17. Genetics Home Reference: myoclonic epilepsy myopathy sensory ataxia

    Science.gov (United States)

    ... Home Health Conditions MEMSA myoclonic epilepsy myopathy sensory ataxia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Myoclonic epilepsy myopathy sensory ataxia , commonly called MEMSA , is part of a group ...

  18. Genetics Home Reference: infantile-onset spinocerebellar ataxia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions IOSCA infantile-onset spinocerebellar ataxia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Infantile-onset spinocerebellar ataxia ( IOSCA ) is a progressive disorder that affects the ...

  19. Gradually Progressive Spastic Ataxia in a Young Man: Steadily Unsteady.

    Science.gov (United States)

    Dubey, Divyanshu; Khemani, Pravin; Remster, Eric; Elliott, Jeffrey L

    2017-02-01

    A 26-year-old right-handed man presented with progressive gait imbalance over 6 years. His examination was consistent with cerebellar and upper motor neuronal dysfunction. He had no significant family history. Most of the serum and cerebrospinal fluid studies were unremarkable. Neuroimaging was remarkable for mild cerebellar and noticeable thoracic spinal cord atrophy. The initial differential diagnosis for the patient's presentation was broad, but because of certain clinical characteristics, it was later focused on hereditary ataxias. Detailed analysis of the clinical features in the history, neurologic examination, and neuroimaging studies led to the diagnosis.

  20. Cerebellar Ataxia and Glutamic Acid Decarboxylase Antibodies

    Science.gov (United States)

    Ariño, Helena; Gresa-Arribas, Nuria; Blanco, Yolanda; Martínez-Hernández, Eugenia; Sabater, Lidia; Petit-Pedrol, Mar; Rouco, Idoia; Bataller, Luis; Dalmau, Josep O.; Saiz, Albert; Graus, Francesc

    2016-01-01

    IMPORTANCE Current clinical and immunologic knowledge on cerebellar ataxia (CA) with glutamic acid decarboxylase 65 antibodies (GAD65-Abs) is based on case reports and small series with short-term follow-up data. OBJECTIVE To report the symptoms, additional antibodies, prognostic factors, and long-term outcomes in a cohort of patients with CA and GAD65-Abs. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study and laboratory investigations at a center for autoimmune neurologic disorders among 34 patients with CA and GAD65-Abs, including 25 with long-term follow-up data (median, 5.4 years; interquartile range, 3.1-10.3 years). MAIN OUTCOMES AND MEASURES Analysis of clinicoimmunologic features and predictors of response to immunotherapy. Immunochemistry on rat brain, cultured neurons, and human embryonic kidney cells expressing GAD65, GAD67, α1-subunit of the glycine receptor, and a repertoire of known cell surface autoantigens were used to identify additional antibodies. Twenty-eight patients with stiff person syndrome and GAD65-Abs served as controls. RESULTS The median age of patients was 58 years (range, 33-80 years); 28 of 34 patients (82%) were women. Nine patients (26%) reported episodes of brainstem and cerebellar dysfunction or persistent vertigo several months before developing CA. The clinical presentation was subacute during a period of weeks in 13 patients (38%). Nine patients (26%) had coexisting stiff person syndrome symptoms. Systemic organ-specific autoimmunities (type 1 diabetes mellitus and others) were present in 29 patients (85%). Twenty of 25 patients with long-term follow-up data received immunotherapy (intravenous immunoglobulin in 10 and corticosteroids and intravenous immunoglobulin or other immunosuppressors in 10), and 7 of them (35%) improved. Predictors of clinical response included subacute onset of CA (odds ratio [OR], 0.50; 95% CI, 0.25-0.99; P = .047) and prompt immunotherapy (OR, 0.98; 95% CI, 0.96-0.99; P = .01). Similar

  1. Optic ataxia affects the lower limbs: evidence from a single case study.

    Science.gov (United States)

    Evans, Carys; Milner, A David; Humphreys, Glyn W; Cavina-Pratesi, Cristiana

    2013-05-01

    Optic ataxia represents a spatial impairment of visually guided reaching following bilateral or unilateral damage to the posterior parietal cortex that is independent of purely motor or visual deficits. Research to date has focused on reaching actions performed with the upper limbs but has neglected to explore whether or not optic ataxia affects the lower limbs, that is, whether it is effector-specific. We asked patient M.H., who suffers from unilateral optic ataxia from left hemispheric damage, and eight age-matched controls, to perform leg movements by stepping down from a wooden block towards a visually presented target. Steps were performed using the left or the right leg, in conditions of central fixation or free viewing. Patient M.H. performed significantly worse than controls. His errors in step accuracy were most pronounced when stepping into the visual periphery (during central fixation), particularly while using the contralesional right foot towards the contralesional right hemispace. This behaviour is consistent with M.H.'s impairments in optic ataxia previously recorded for reaching and grasping actions with the upper limbs. The lesion affecting M.H.'s brain is quite large, encompassing functional areas associated with visuomotor transformations performed with different effectors such as arm and eye (superior parietal-occipital cortex and medial intraparietal sulcus). Our data suggest that optic ataxia is not completely effector-specific, and that neurons encoding visuomotor transformations for both arm and leg are probably both affected by the damage. Our results support the notion that lesions affecting the medial portion of the left posterior parietal cortex similarly affect different effectors (arm and leg) when visually guided actions are directed towards the same contralesional hemispace. In addition they may help explain why patients with optic ataxia have been reported to have difficulties in certain aspects of visually guided locomotion.

  2. The electrophysiology of spinocerebellar ataxias.

    Science.gov (United States)

    Liang, Lipin; Chen, Tao; Wu, Yan

    2016-02-01

    Spinocerebellar Ataxias (SCAs) are a group of autosomal dominantly inherited neurodegenerative diseases, involving the cerebellum and the brainstem. Genetic testing is the most important method of diagnosis. Nowadays, nearly 40 types of SCAs have been identified by genetic analysis. Peripheral nerve impairment is common in SCAs: electrophysiological examination of SCA1, SCA2 and SCA3 usually shows sensorimotor and sensory neuropathy, while pure motor neuropathy is more rare, being seen only in SCA2. The abnormal VEP of SCA1, SCA2 and SCA3 include prolonged P100 latencies and reduced P100 amplitudes. Abnormal BAEP involves prolonged interpeak latency of I-III and III-V. Abnormal SEP usually show absent P40 wave and prolonged P40 latency. The abnormal MEP usually shows prolonged central motor conduction time or absent responses. SCA2 is not associated with gaze-evoked nystagmus and dysmetric saccades. SCA3 usually presents as saccadic intrusions and oscillations. Whether peripheral nerves are involved in SCA6 is uncertain; although abnormal electrophysiology has been reported, neuropathological examinations have not found degenerative changes or reductions in the number of neurons in the anterior horns and/or dorsal root ganglia in SCA6. It is therefore hypothesized that this might be a displayed feature of axonopathy. The clinical presentation of most cases of SCA6 includes spontaneous and positional downbeat nystagmus, and perverted head-shaking nystagmus. Opinion about peripheral nerve involvement in SCA7 varies between authors. Losing P100 is a predominant feature of SCA7, while III and IV/V wave absence is common in SCA17. Electrophysiological study of other types is currently limited, requiring large-scale studies for confirmation. Similar and overlapping clinical features make it difficult to differentiate each type. Electrophysiological testing can therefore play an important role in helping to identify the common phenotypes of SCAs, and determine the extent

  3. 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...... 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...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  4. [Clinical features and MRI findings in spinocerebellar ataxia type 31 (SCA31) comparing with spinocerebellar ataxia type 6 (SCA6)].

    Science.gov (United States)

    Sakakibara, Satoko; Aiba, Ikuko; Saito, Yufuko; Inukai, Akira; Ishikawa, Kinya; Mizusawa, Hidehiro

    2014-01-01

    Since the discovery of spinocerebellar ataxia type 31 (SCA31) gene, we identified 6 patients whose SCA type had been unkown for a long period of time as having SCA31 in our hospital and realized that SCA31 is not a rare type of autosomal dominant spinocerebellar ataxia in this region. We examined and compared the clinical details of these six SCA31 patients and the same number of SCA6 patients, finding that some SCA31 patients had hearing loss in common while there are more wide range and complicated signs of extra cerebellum in SCA6 such as pyramidal signs, extrapyramidal signs, dizzy sensations or psychotic, mental problems. There is a significant difference in the number of extracerebellar symptoms between SCA31 and SCA6. There are differences also in MRI findings. Cerebellar atrophy starts from the upper vermis in SCA31, as well as some SCA types, whereas the 4th ventricule becomes enlarged in SCA6 even in the early stage of disease. We suggest that these differences in clinical and MRI findings can be clues for accurate diagnosis before gene analysis.

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

    OpenAIRE

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

    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 t...

  6. Childhood Ataxia with Cerebral Hypomyelination (CACH syndrome: A study of three siblings

    Directory of Open Access Journals (Sweden)

    Vaidya Sachin

    2004-07-01

    Full Text Available We report a family of three siblings with Childhood Ataxia with Cerebral Hypomyelination. All the siblings presented with early onset cerebellar ataxia beginning around five years of age with mild mental retardation. MRI showed diffuse white matter signal changes in all three patients with cerebellar atrophy while the spectroscopy was abnormal only in the eldest who was the most severely affected. The cases are reported for their rarity as well as for an opportunity of observing this uncommon disease in its stages of evolution in three siblings.

  7. Spinocerebellar ataxia-10 with paranoid schizophrenia

    OpenAIRE

    Bhavesh Trikamji; Parampreet Singh; Shrikant Mishra

    2015-01-01

    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 ataxi...

  8. Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Stummann, Tina C.; Madsen, Helena Borland

    2016-01-01

    The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method...

  9. Cognitive and speech-language performance in children with ataxia telangiectasia

    NARCIS (Netherlands)

    Vinck, Anja; Verhagen, Mijke M. M.; van Gerven, Marjo; de Groot, Imelda J. M.; Weemaes, Corry M. R.; Maassen, Ben A. M.; Willemsen, Michel A. A. P.

    2011-01-01

    Objective: To describe cognitive and speech-language functioning of patients with ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor function. Design: Observational case series. Methods: Cognitive functioning, language, speech and oral-motor functioning were examined in eigh

  10. Cognitive and speech-language performance in children with ataxia telangiectasia

    NARCIS (Netherlands)

    Vinck, A.; Verhagen, M.M.; Gerven, M.; Groot, I.J.M. de; Weemaes, C.M.R.; Maassen, B.A.M.; Willemsen, M.A.A.P.

    2011-01-01

    OBJECTIVE: To describe cognitive and speech-language functioning of patients with ataxia-telangiectasia (A-T) in relation to their deteriorating (oculo)motor function. DESIGN: Observational case series. METHODS: Cognitive functioning, language, speech and oral-motor functioning were examined in eigh

  11. Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy

    NARCIS (Netherlands)

    E. Aronica; J.A. Gorter; M. Ramkema; S. Redeker; F. Ozbas-Gercer; E.A. van Vliet; G.L. Scheffer; R.J. Scheper; P. van der Valk; J.C. Baayen; D. Troost

    2004-01-01

    Purpose: This study investigated the cellular distribution of different multidrug resistance (MDR)-related proteins such as P-glycoprotein (P-gp), the multidrug resistance-associated proteins (MRP) 1 and 2, and the major vault protein (MVP) in normal and sclerotic hippocampus of patients with medica

  12. Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3.

    Science.gov (United States)

    Paulson, Henry L

    2007-04-01

    To date, nearly 30 distinct genetic forms of dominantly inherited ataxia are known to exist. Of these, Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is perhaps the most common in many regions of the world including the United States. This article discusses MJD/SCA3 as a paradigm example of the dominant ataxias, which are collectively known as the spinocerebellar ataxias. Using MJD/SCA3 as a starting point, the article reviews common clinical and genetic features of the SCAs and highlights new insights into molecular mechanisms, especially of the SCAs caused by polyglutamine expansion. Also discussed are current and future therapeutic opportunities for MJD/SCA3 in particular, many of which have relevance to other SCAs.

  13. Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies

    Science.gov (United States)

    Lombardi, Sara; Fuoco, Ilenia; di Fluri, Giorgia; Costa, Francesco; Ricchiuti, Angelo; Biondi, Graziano; Nardini, Vincenzo; Scarpato, Roberto

    2015-01-01

    Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal biopsies and peripheral blood lymphocytes of patients with IBD, polyps and CRC, we evaluated 1) genomic instability using the γH2AX assay as marker of DSB and micronuclei in mononuclear lymphocytes kept under cytodieresis inhibition, and 2) cellular stress through expression and cellular localization of glutathione-S-transferase omega 1 (GSTO1). Colon biopsies showed γH2AX increase starting from polyps, while lymphocytes already from IBD. Micronuclei frequency began to rise in lymphocytes of subjects with polyps, suggesting a systemic genomic instability condition. Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression. Lymphocytes did not change GSTO1 expression and localization until CRC formation, where enzyme expression was increased. We propose that the growing genomic instability found in our patients is connected with the alteration of cellular environment. Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC. PMID:26046795

  14. The dynamic regulation of cortical excitability is altered in episodic ataxia type 2.

    Science.gov (United States)

    Helmich, Rick C; Siebner, Hartwig R; Giffin, Nicola; Bestmann, Sven; Rothwell, John C; Bloem, Bastiaan R

    2010-12-01

    Episodic ataxia type 2 and familial hemiplegic migraine are two rare hereditary disorders that are linked to dysfunctional ion channels and are characterized clinically by paroxysmal neurological symptoms. Impaired regulation of cerebral excitability is thought to play a role in the occurrence of these paroxysms, but the underlying mechanisms are poorly understood. Normal ion channels are crucial for coordinating neuronal firing in response to facilitatory input. Thus, we hypothesized that channel dysfunction in episodic ataxia type 2 and familial hemiplegic migraine may impair the ability to adjust cerebral excitability after facilitatory events. We tested this hypothesis in patients with episodic ataxia type 2 (n = 6), patients with familial hemiplegic migraine (n = 7) and healthy controls (n = 13). All subjects received a high-frequency burst (10 pulses at 20 Hz) of transcranial magnetic stimulation to transiently increase the excitability of the motor cortex. Acute burst-induced excitability changes were probed at 50, 250, 500 and 1000 ms after the end of the burst. This was done using single-pulse transcranial magnetic stimulation to assess corticospinal excitability, and paired-pulse transcranial magnetic stimulation at an interstimulus interval of 2 and 10 ms to assess intracortical inhibition and facilitation, respectively. The time course of burst-induced excitability changes differed between groups. Healthy controls showed a short-lived increase in excitability that was only present 50 ms after the burst. In contrast, patients with episodic ataxia type 2 showed an abnormally prolonged increase in corticospinal excitability that was still present 250 ms after the transcranial magnetic stimulation burst. Furthermore, while controls showed a decrease in intracortical facilitation during the 1 s period following the transcranial magnetic stimulation burst, patients with episodic ataxia type 2 had increased intracortical facilitation 1000 ms after the burst

  15. Clinical and neuroimaging study of spinocerebellar ataxia type 2

    Directory of Open Access Journals (Sweden)

    JIN Miao

    2013-06-01

    Full Text Available Background Spinocerebellar ataxia type 2 (SCA2 is an autosomal dominant genetic disease characterized by cerebellar ataxia, ophthalmoplegia, slow saccade, hyporeflexia, action tremor, cognitive decline and peripheral neuropathy. The brain MRI shows obvious atrophy of cerebellum and brainstem, indicating typical change of olivopontocerebellar atrophy. SCA2 is caused by an expanded cytosine-adenine-guanine (CAG trinucleotide repeat in the encoding region of ATXN2. The normal CAG repeats range from 13 to 31, and ataxic phenotype occurs when the repeats are more than 34. This study focused on the clinical and imaging features of 5 SCA2 families confirmed by genetic testing. The correlation between phenotype and genotype was analyzed. Methods The pathological CAG triplet repeat expansions of SCA1-3, 6, 7, 17 and dentatorubral-pallidoluysian atrophy (DRPLA genes were analyzed in the probands of 708 autosomal dominant SCA families and 119 sporadic SCA cases. The CAG repeat of ATXN2 gene was amplified by polymerase chain reaction (PCR and agarose gel electrophoresis. Fragment analysis based on CEQ8000 sequencer were applied to analyze expanded alleles. Results Expanded CAG repeats of ATXN2 gene were detected in 45 probands of SCA2 families. Most of the patients manifested with the typical clinical features of SCA2 such as cerebellar ataxia, ophthalmoplegia, slow saccade and hyporeflexia. Some of them also associated with action tremor. The brain MRI showed obvious atrophy of cerebellum and brainstem. The correlation between clinical features and CAG repeat of ATXN2 gene was studied carefully in 5 families. Conclusion Genetic analysis provides the basis for the diagnosis of SCA2. Clinical and neuroimaging features are very helpful in the diagnosis and differential diagnosis of this disease. For the identification of cases carrying intermediate allele, it is important to combine clinical, imaging features with dynamic mutation analysis in the affected

  16. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Ashley M. Brouillette

    2015-01-01

    Full Text Available Neurodegenerative diseases, including the spinocerebellar ataxias (SCA, would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP, proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C, compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA. Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that α-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C.

  17. The preclinical stage of spinocerebellar ataxias.

    Science.gov (United States)

    Maas, Roderick P P W M; van Gaalen, Judith; Klockgether, Thomas; van de Warrenburg, Bart P C

    2015-07-07

    The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of degenerative diseases of the cerebellum and connected regions. The discovery of various SCA genes and the subsequent possibility of predictive testing currently allow a genetic diagnosis to be established years or even decades before the actual appearance of ataxia symptoms. A growing body of evidence, however, indicates that this preclinical stage is subject to the earliest pathophysiologic changes. This review article comprehensively summarizes the studies conducted in preclinical carriers of a mutation in one of the SCA genes. From these data, it can indeed be concluded that the preclinical phase in SCA is already characterized by detectable central and peripheral nervous system changes, which are reflected by subtle abnormalities during a careful clinical examination, changes in structural and functional brain imaging, abnormal neurophysiologic measurements, and/or altered motor learning paradigms. As these may be compensated for a long time, ataxia symptoms probably only appear after a certain threshold of dysfunction or degeneration has been exceeded. Detailed knowledge of this disease stage is of particular relevance for a better understanding of the pathogenesis of SCAs, will allow us to determine the optimal point in time for interventions in future therapeutic trials, and points to objective, valid biomarkers to assess disease progression. Further studies will benefit from a consensus-based definition of the preclinical stage, from using one and the same validated ataxia rating scale with one fixed cutoff value, and from applying similar mathematical models to calculate time to predicted disease onset.

  18. Recent advances in hereditary spinocerebellar ataxias.

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Sinke, R.J.; Kremer, H.P.H.

    2005-01-01

    In recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinicia

  19. Recent advances in hereditary spinocerebellar ataxias

    NARCIS (Netherlands)

    van de Warrenburg, Bart P C; Sinke, Richard J; Kremer, Berry

    2005-01-01

    In recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinicia

  20. Peripheral nerve involvement in spinocerebellar ataxias

    NARCIS (Netherlands)

    van de Warrenburg, Bart P C; Notermans, Nicolette C; Schelhaas, Helenius J; van Alfen, Nens; Sinke, Richard J; Knoers, Nine V A M; Zwarts, Machiel J; Kremer, Berry P H

    2004-01-01

    BACKGROUND: In autosomal dominant cerebellar ataxias (ADCAs), it is unclear whether the associated peripheral nerve involvement is always a typical length-dependent axonopathy rather than primary neuronopathy due to neuronal degeneration in the spinal anterior horns and/or dorsal root ganglia. OBJEC

  1. Spinocerebellar ataxia-10 with paranoid schizophrenia.

    Science.gov (United States)

    Trikamji, Bhavesh; Singh, Parampreet; Mishra, Shrikant

    2015-01-01

    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.

  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. The gene for the ataxia-telagiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21

    Energy Technology Data Exchange (ETDEWEB)

    Saar, K.; Stumm, M.; Wegner, R.D. [Humboldt Univ. (Germany)] [and others

    1997-03-01

    Nijmegen breakage syndrome (NBS; Seemanova II syndrome) and Berlin breakage syndrome (BBS), also known as ataxia-telangiectasia variants, are two clinically indistinguishable autosomal recessive familial cancer syndromes that share with ataxia-telangiectasia similar cellular, immunological, and chromosomal but not clinical findings. Classification in NBS and BBS was based on complementation of their hypersensitivity to ionizing radiation in cell-fusion experiments. Recent investigations have questioned the former classification into two different disease entities, suggesting that NBS/BBS is caused by mutations in a single radiosensitivity gene. We now have performed a whole-genome screen in 14 NBS/BBS families and have localized the gene for NBS/BBS to a 1-cM interval on chromosome 8q21, between markers D8S271 and D8S270, with a peak LOD score of 6.86 at D8S1811. This marker also shows strong allelic association to both Slavic NBS and German BBS patients, suggesting the existence of one major mutation of Slavic origin. Since the same allele is seen in both former complementation groups, genetic homogeneity of NBS/BBS can be considered as proved. 21 refs., 2 figs., 2 tabs.

  4. Indistinguishable cellular changes in gastric mucosa between helicobacter pylori infected asymptomatic tribal and duodenal ulcer patients

    Institute of Scientific and Technical Information of China (English)

    Dhira Rani Saha; Simanti Datta; Santanu Chattopadhyay; Rajashree Patra; Ronita De; Krishnan Rajendran; Abhijit Chowdhury; Thandavaryan Ramamurthy; Asish Kumar Mukhopadhyay

    2009-01-01

    cells among asymptomatic tribals and DU Bengali patients. Interestingly, the tribal population are free from any clinical symptoms despite evidence of active histologic gastritis and infection with Hpylori strains carrying similar virulence markers as of strains isolated from patients with DU.There was an increased cellular response, especially in terms of neutrophil infiltration, but much lower risk of developing atrophy and metaplastic changes among the tribal population.

  5. Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology.

    Science.gov (United States)

    Horton, Laura C; Frosch, Matthew P; Vangel, Mark G; Weigel-DiFranco, Carol; Berson, Eliot L; Schmahmann, Jeremy D

    2013-04-01

    Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = -0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.

  6. Electronystagmography findings in spinocerebellar ataxia type 3 (SCA3) and type 2 (SCA2)

    OpenAIRE

    Bianca Simone Zeigelboim; Hélio A.G. Teive; Rosane Sampaio; Ari Leon Jurkiewicz; Liberalesso,Paulo B.N.

    2011-01-01

    OBJECTIVE: To describe the alterations observed in electronystagmography (ENG) of patients with spinocerebellar ataxia (SCA) types 2 and 3. METHOD: Sixteen patients were studied and the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluations. RESULTS: The clinical findings in the entire group of patients were: gait disturbances (93.75%), dysarthria (43.75%), headache (43.75%), dizziness (37.50%) and dysphagia (37.50%). In the vestibular exam, the ro...

  7. Clinical and molecular studies in five Brazilian cases of Friedreich ataxia Avaliação clínica e molecular de cinco pacientes brasileiros com ataxia de Friedreich

    Directory of Open Access Journals (Sweden)

    IDA V.D. SCHWARTZ

    1999-03-01

    Full Text Available Friedreich ataxia (FRDA, the most common autosomal recessive ataxia, is caused in 94% of cases by homozygous expansions of an unstable GAA repeat localised in intron 1 of the X25 gene. We have investigated this mutation in five Brazilian patients: four with typical FRDA findings and one patient with atypical manifestations, who was considered to have some other form of cerebellar ataxia with retained reflexes. The GAA expansion was detected in all these patients. The confirmation of FRDA diagnosis in the atypical case may be pointing out, as in other reports, that clinical spectrum of Friedreich's ataxia is broader than previously recognised and includes cases with intact tendon reflexes.A ataxia de Friedreich (FRDA é a mais frequente das ataxias com herança autossômica recessiva. Em 94 % dos casos, é causada por uma expansão homozigota instável da repetição de trinucleotídeos GAA, localizada no primeiro íntron do gene X25. Esta mutação foi investigada em cinco pacientes brasileiros: quatro com quadro clínico típico de FRDA e um paciente com manifestações atípicas, cujo diagnóstico prévio era o de alguma outra forma de ataxia cerebelar com preservação de reflexos. A investigação foi positiva nos cinco casos. A confirmação do diagnóstico de FRDA no paciente com quadro atípico, assim como em outros casos semelhantes já relatados na literatura, sugere que o espectro de manifestações clínicas da FRDA seja mais amplo do que o classicamente reconhecido, incluindo casos com preservação de reflexos.

  8. 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.

  9. Altered lipid metabolism in a Drosophila model of Friedreich's ataxia.

    Science.gov (United States)

    Navarro, Juan A; Ohmann, Elisabeth; Sanchez, Diego; Botella, José A; Liebisch, Gerhard; Moltó, María D; Ganfornina, María D; Schmitz, Gerd; Schneuwly, Stephan

    2010-07-15

    Friedreich's ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in the mitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellular model has yet been developed to study the involvement of glial cells in FRDA. Using the recently established RNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects of general versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay between lowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on the sensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increase in fatty acids catalyzing an enhancement of lipid peroxidation levels, elevating the intracellular toxic potential. Specific loss of frataxin in glial cells triggers a similar phenotype which can be visualized by accumulating lipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivity to oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptoms fit very well with our observation of an increase in intracellular toxicity by lipid peroxides. Interestingly, co-expression of a Drosophila apolipoprotein D ortholog (glial lazarillo) has a strong protective effect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly support a strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.

  10. Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.

    Science.gov (United States)

    Falcon, M I; Gomez, C M; Chen, E E; Shereen, A; Solodkin, A

    2016-07-01

    Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.

  11. 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.

  12. Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report

    Directory of Open Access Journals (Sweden)

    Antoccia Antonio

    2010-04-01

    Full Text Available Abstract Ataxia-telangiectasia (A-T is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T. A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.

  13. Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Stamatopoulos, Basile; Van Damme, Michaël; Crompot, Emerence; Dessars, Barbara; Housni, Hakim El; Mineur, Philippe; Meuleman, Nathalie; Bron, Dominique; Lagneaux, Laurence

    2015-01-09

    MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL) physiopathology and prognosis. In addition, circulating microRNAs in body fluids have been proposed as new biomarkers. We investigated the expression of matched cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR) from purified CD19(+) cells or from CLL serums obtained at diagnosis in a cohort of 273/252 CLL patients with a median follow-up of 78 months (range 7-380) and correlated it to other biological or clinical parameters. We showed that miR-150 was significantly overexpressed in CLL cells/serums compared with healthy subjects (P disease aggressiveness and poor prognostic factors. In contrast, a high level of serum miR-150 was associated with tumor burden markers and some markers of poor prognosis. Similarly, cellular and serum miR-150 also predicted treatment-free survival (TFS) and overall survival (OS) in an opposite manner: patients with low cellular/serum miR-150 levels have median TFS of 40/111 months compared with high-level patients who have a median TFS of 122/60 months (P disease progression and that cellular miR-150 could be regulated by its release into the extracellular space. Cellular and serum levels of miR-150 are associated with opposite clinical prognoses and could be used to molecularly monitor disease evolution as a new prognostic factor in CLL.

  14. 'Costa da Morte' ataxia is spinocerebellar ataxia 36: clinical and genetic characterization.

    Science.gov (United States)

    García-Murias, María; Quintáns, Beatriz; Arias, Manuel; Seixas, Ana I; Cacheiro, Pilar; Tarrío, Rosa; Pardo, Julio; Millán, María J; Arias-Rivas, Susana; Blanco-Arias, Patricia; Dapena, Dolores; Moreira, Ramón; Rodríguez-Trelles, Francisco; Sequeiros, Jorge; Carracedo, Angel; Silveira, Isabel; Sobrido, María J

    2012-05-01

    Spinocerebellar ataxia 36 has been recently described in Japanese families as a new type of spinocerebellar ataxia with motor neuron signs. It is caused by a GGCCTG repeat expansion in intron 1 of NOP56. Family interview and document research allowed us to reconstruct two extensive, multigenerational kindreds stemming from the same village (Costa da Morte in Galicia, Spain), in the 17th century. We found the presence of the spinocerebellar ataxia 36 mutation co-segregating with disease in these families in whom we had previously identified an ~0.8 Mb linkage region to chromosome 20 p. Subsequent screening revealed the NOP56 expansion in eight additional Galician ataxia kindreds. While normal alleles contain 5-14 hexanucleotide repeats, expanded alleles range from ~650 to 2500 repeats, within a shared haplotype. Further expansion of repeat size was frequent, especially upon paternal transmission, while instances of allele contraction were observed in maternal transmissions. We found a total of 63 individuals carrying the mutation, 44 of whom were confirmed to be clinically affected; over 400 people are at risk. We describe here the detailed clinical picture, consisting of a late-onset, slowly progressive cerebellar syndrome with variable eye movement abnormalities and sensorineural hearing loss. There were signs of denervation in the tongue, as well as mild pyramidal signs, but otherwise no signs of classical amyotrophic lateral sclerosis. Magnetic resonance imaging findings were consistent with the clinical course, showing atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivo-ponto-cerebellar atrophy. We estimated the origin of the founder mutation in Galicia to have occurred ~1275 years ago. Out of 160 Galician families with spinocerebellar ataxia, 10 (6.3%) were found to have spinocerebellar ataxia 36, while 15 (9.4%) showed other of the routinely tested dominant spinocerebellar ataxia types. Spinocerebellar ataxia 36 is

  15. ‘Costa da Morte’ ataxia is spinocerebellar ataxia 36: clinical and genetic characterization

    Science.gov (United States)

    García-Murias, María; Quintáns, Beatriz; Arias, Manuel; Seixas, Ana I.; Cacheiro, Pilar; Tarrío, Rosa; Pardo, Julio; Millán, María J.; Arias-Rivas, Susana; Blanco-Arias, Patricia; Dapena, Dolores; Moreira, Ramón; Rodríguez-Trelles, Francisco; Sequeiros, Jorge; Carracedo, Ángel; Silveira, Isabel

    2012-01-01

    Spinocerebellar ataxia 36 has been recently described in Japanese families as a new type of spinocerebellar ataxia with motor neuron signs. It is caused by a GGCCTG repeat expansion in intron 1 of NOP56. Family interview and document research allowed us to reconstruct two extensive, multigenerational kindreds stemming from the same village (Costa da Morte in Galicia, Spain), in the 17th century. We found the presence of the spinocerebellar ataxia 36 mutation co-segregating with disease in these families in whom we had previously identified an ∼0.8 Mb linkage region to chromosome 20 p. Subsequent screening revealed the NOP56 expansion in eight additional Galician ataxia kindreds. While normal alleles contain 5–14 hexanucleotide repeats, expanded alleles range from ∼650 to 2500 repeats, within a shared haplotype. Further expansion of repeat size was frequent, especially upon paternal transmission, while instances of allele contraction were observed in maternal transmissions. We found a total of 63 individuals carrying the mutation, 44 of whom were confirmed to be clinically affected; over 400 people are at risk. We describe here the detailed clinical picture, consisting of a late-onset, slowly progressive cerebellar syndrome with variable eye movement abnormalities and sensorineural hearing loss. There were signs of denervation in the tongue, as well as mild pyramidal signs, but otherwise no signs of classical amyotrophic lateral sclerosis. Magnetic resonance imaging findings were consistent with the clinical course, showing atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivo-ponto-cerebellar atrophy. We estimated the origin of the founder mutation in Galicia to have occurred ∼1275 years ago. Out of 160 Galician families with spinocerebellar ataxia, 10 (6.3%) were found to have spinocerebellar ataxia 36, while 15 (9.4%) showed other of the routinely tested dominant spinocerebellar ataxia types. Spinocerebellar ataxia

  16. Machado-Joseph disease and other rare spinocerebellar ataxias.

    Science.gov (United States)

    Matilla-Dueñas, Antoni

    2012-01-01

    The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterised by progressive lack of motor coordination leading to major disability. SCAs show high clinical, genetic, molecular and epidemiological variability. In the last one decade, the intensive scientific research devoted to the SCAs is resulting in clear advances and a better understanding on the genetic and nongenetic factors contributing to their pathogenesis which are facilitating the diagnosis, prognosis and development of new therapies. The scope of this chapter is to provide an updated information on Machado-Joseph disease (MJD), the most frequent SCA subtype worldwide and other rare spinocerebellar ataxias including dentatorubral-pallidoluysian atrophy (DRPLA), the X-linked fragile X tremor and ataxia syndrome (FXTAS) and the nonprogressive episodic forms of inherited ataxias (EAs). Furthermore, the different therapeutic strategies that are currently being investigated to treat the ataxia and non-ataxia symptoms in SCAs are also described.

  17. Case of infantile onset spinocerebellar ataxia type 5.

    Science.gov (United States)

    Jacob, Francois-Dominique; Ho, Eugenia S; Martinez-Ojeda, Mayra; Darras, Basil T; Khwaja, Omar S

    2013-10-01

    Dominant spinocerebellar ataxias are a rare clinically and genetically heterogeneous group of neurodegenerative disorders. They are characterized by progressive cerebellar ataxia resulting in unsteady gait, clumsiness, dysarthria, and swallowing difficulty. The onset of symptoms is usually in the third or fourth decade of life; however, more subtle clinical manifestations can start in early childhood. Spinocerebellar ataxia type 5, a dominant spinocerebellar ataxia associated with mutations involving β-III spectrin (SPTBN2), has been described in 3 families. It typically consists of a slowly progressive spinocerebellar ataxia with onset in the third decade. The authors present the first case of infantile-onset spinocerebellar ataxia associated with a novel SPTBN2 mutation (transition C>T at nucleotide position 1438), the proband having a much more severe phenotype with global developmental delay, hypotonia, tremor, nystagmus, and facial myokymia.

  18. Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

    OpenAIRE

    Adriana Moro; Renato Puppi Munhoz; Walter Oleschko Arruda; Salmo Raskin; Hélio Afonso Ghizoni Teive

    2013-01-01

    Objective To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. Methods Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 ...

  19. The ever expanding spinocerebellar ataxias. Editorial.

    Science.gov (United States)

    Matilla-Dueñas, Antoni

    2012-12-01

    The spinocerebellar ataxias (SCAs) are a clinically, genetically, and neuropathologically heterogeneous group of neurological disorders defined by variable degrees of cerebellar ataxia often accompanied by additional cerebellar and non-cerebellar symptoms that, in many cases,defy differentiation based on clinical characterisation alone. The clinical symptoms are triggered by neurodegeneration of the cerebellum and its relay connexions. The current identification of at least 43 SCA subtypes and the causative molecular defects in 27 of them refine the clinical diagnosis,provide molecular testing of at risk, a/pre-symptomatic, prenatal or pre-implantation and facilitate genetic counselling. The recent discovery of new causative SCA genes along with the respective scientific advances is uncovering high complexity and altered molecular pathways involved in the mechanisms by which the mutant gene products cause pathogenesis. Fortunately, the intensive ongoing clinical and neurogenetic research together with the applied molecular approaches is sure to yield scientific advances that will be translated into developing effective treatments for the spinocerebellar ataxias and other similar neurological conditions.

  20. Clinical variability in ataxia-telangiectasia.

    Science.gov (United States)

    Lohmann, Ebba; Krüger, Stefanie; Hauser, Ann-Kathrin; Hanagasi, Hasmet; Guven, Gamze; Erginel-Unaltuna, Nihan; Biskup, Saskia; Gasser, Thomas

    2015-07-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive inherited disease characterized by progressive childhood-onset cerebellar ataxia, oculomotor apraxia, choreoathetosis and telangiectasias of the conjunctivae. Further symptoms may be immunodeficiency and frequent infections, and an increased risk of malignancy. As well as this classic manifestation, several other non-classic forms exist, including milder or incomplete A-T phenotypes caused by homozygous or compound heterozygous mutations in the ATM gene. Recently, ATM mutations have been found in 13 Canadian Mennonites with early-onset, isolated, predominantly cervical dystonia, in a French family with generalized dystonia and in an Indian family with dopa-responsive cervical dystonia. In this article, we will describe a Turkish family with three affected sibs. Their phenotypes range from pure cervical dystonia associated with hand tremor to truncal and more generalized dystonic postures. Exome sequencing has revealed the potentially pathogenic compound heterozygous variants p.V2716A and p.G301VfsX19 in the ATM gene. The variants segregated perfectly with the phenotypes within the family. Both mutations detected in ATM have been shown to be pathogenic, and the α-fetoprotein, a marker of ataxia telangiectasia, was found to be increased. This report supports recent literature showing that ATM mutations are not exclusively associated with A-T but may also cause a more, even intra-familial variable phenotype in particular in association with dystonia.

  1. Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory.

    Science.gov (United States)

    Mehdipour, P; Karami, F; Javan, Firouzeh; Mehrazin, M

    2015-08-01

    Ataxia telangiectasia mutated (ATM) is a key gene in DNA double-strand break (DSB), and therefore, most of its disabling genetic alterations play an important initiative role in many types of cancer. However, the exact role of ATM gene and its epigenetic alterations, especially promoter methylation in different grades of brain tumors, remains elusive. The current study was conducted to query possible correlations among methylation statue of ATM gene, ATM/ retinoblastoma (RB) protein expression, D1853N ATM polymorphism, telomere length (TL), and clinicopathological characteristics of various types of brain tumors. Isolated DNA from 30 fresh tissues was extracted from different types of brain tumors and two brain tissues from deceased normal healthy individuals. DNAs were treated with bisulfate sodium using DNA modification kit (Qiagen). Methylation-specific polymerase chain reaction (MSP-PCR) was implicated to determine the methylation status of treated DNA templates confirmed by promoter sequencing. Besides, the ATM and RB protein levels were determined by immunofluorescence (IF) assay using monoclonal mouse antihuman against ATM, P53, and RB proteins. To achieve an interactive correlation, the methylation data were statistically analyzed by considering TL and D1853N ATM polymorphism. More than 73% of the brain tumors were methylated in ATM gene promoter. There was strong correlation between ATM promoter methylation and its protein expression (p ATM promoter and ATM protein expression with D1853N ATM polymorphism (p = 0.01). ATM protein expression was not in line with RB protein expression while it was found to be significantly correlated with ATM promoter methylation (p = 0.01). There was significant correlation between TL neither with ATM promoter methylation nor with ATM protein expression nor with D1853N polymorphism. However, TL has shown strong correlation with patient's age and tumor grade (p = 0.01). Given the important role of cell cycle checkpoint

  2. CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

    OpenAIRE

    Huang, Shang-Ran; Wu, Yu-Te; Jao, Chii-Wen; Soong, Bing-wen; Lirng, Jiing-Feng; Wu, Hsiu-Mei; Wang, Po-Shan

    2016-01-01

    This cross-sectional study investigated the correlation between the CAG repeat length and the degeneration of cerebellum in spinocerebellar ataxia type 3 (SCA3) patients based on neuroimaging approaches. Forty SCA3 patients were recruited and classified into two subgroups according to their CAG repeat lengths (≥ 74 and

  3. Hodgkin Lymphoma in a patient with mycosis fungoides: molecular evidence for separate cellular origins.

    Science.gov (United States)

    Sidwell, R U; McLaughlin, J E; Jones, A; Whittaker, S J

    2003-04-01

    We report the case of a man with mycosis fungoides (MF), who, 11 years after diagnosis, developed Hodgkin's disease. Although MF is associated with a higher than expected prevalence of other malignancies, including Hodgkin lymphoma, analysis of cells from the skin and lymph nodes showed findings that suggest a separate cellular origin for the two diseases.

  4. Genetics Home Reference: PRICKLE1-related progressive myoclonus epilepsy with ataxia

    Science.gov (United States)

    ... with ataxia PRICKLE1-related progressive myoclonus epilepsy with ataxia Enable Javascript to view the expand/collapse boxes. ... All Description PRICKLE1 -related progressive myoclonus epilepsy with ataxia is a rare inherited condition characterized by recurrent ...

  5. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.

    Science.gov (United States)

    Wolf, Nicole I; Koenig, Michel

    2013-01-01

    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  6. DNA synthesis in ataxia telangiectasia

    NARCIS (Netherlands)

    N.G.J. Jaspers (Nicolaas)

    1985-01-01

    textabstractAfter the discovery that cultured cells from AT patients are hypersensitive to ionizing radiation the suggestion was made that AT-could be the 1 X-ray-analogue 1 of xeroderma pigmentosum. The latter syndrome (XP) is characterized by hypersensitivity to short-wave UV-radiation, caused by

  7. Mesenchymal stem cells restore frataxin expression and increase hydrogen peroxide scavenging enzymes in Friedreich ataxia fibroblasts.

    Directory of Open Access Journals (Sweden)

    Kevin Kemp

    Full Text Available Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA--a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin--have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions that restore frataxin expression are attractive therapeutic approaches, as, in theory, it may be possible to re-establish normal function in frataxin deficient cells if frataxin levels are increased above a specific threshold. With this in mind several drugs and cytokines have been tested for their ability to increase frataxin levels. Cell transplantation strategies may provide an alternative approach to this therapeutic aim, and may also offer more widespread cellular protective roles in FRDA. Here we show a direct link between frataxin expression in fibroblasts derived from FRDA patients with both decreased expression of hydrogen peroxide scavenging enzymes and increased sensitivity to hydrogen peroxide-mediated toxicity. We demonstrate that normal human mesenchymal stem cells (MSCs induce both an increase in frataxin gene and protein expression in FRDA fibroblasts via secretion of soluble factors. Finally, we show that exposure to factors produced by human MSCs increases resistance to hydrogen peroxide-mediated toxicity in FRDA fibroblasts through, at least in part, restoring the expression of the hydrogen peroxide scavenging enzymes catalase and glutathione peroxidase 1. These findings suggest, for the first time, that stem cells may increase frataxin levels in FRDA and transplantation of MSCs may offer an effective treatment for these patients.

  8. Serum cortisol level in cerebral infarction patients with infection and its correlation with nerve function, humoral immunity and cellular immunity

    Institute of Scientific and Technical Information of China (English)

    Jie-Min Zhai; Hui-Qi Li; Jian-Bo He; Hai-Guo Wang

    2016-01-01

    Objective:To analyze the serum cortisol level in cerebral infarction patients with infection and its correlation with nerve function, humoral immunity and cellular immunity.Methods:A total of 86 patients with cerebral infarction were divided into observation group (cerebral infarction combined with infection) (n=40) and control group (cerebral infarction alone) (n=46) according to the combination of infection. Serum content of cortisol, nerve function-related indexes and humoral immunity indexes as well as peripheral blood levels of cellular immunity indexes of two groups of patients were determined on admission, and the correlation between serum cortisol level and the above illness-related indexes in cerebral infarction patients with infection was further analyzed.Results: Serum cortisol content of observation group was significantly higher than that of control group; serum nerve function indexes S100β, GFAP, Hcy and HO1 content were significantly higher than those of control group while IGF-1 content was significantly lower than that of control group; humoral immunity indexes IgA, IgM, IgG, C3 and C4 content in serum were significantly lower than those of control group; cellular immunity indexes CD3+, CD4+ and CD54+T lymphocyte content in peripheral blood were significantly lower than those of control group while CD19+T lymphocyte content and CD4+/CD8+ level were significantly higher than those of control group; hemodynamic indexes rCBF and rCBV levels were significantly lower than those of control group while MTT, TTP and DLY levels were significantly higher than those of control group. Serum cortisol level in cerebral infarction patients with infection was directly correlated with the levels of nerve function, humoral immunity, cellular immunity and other illness-related indexes. Conclusions:The high cortisol state in cerebral infarction patients with infection is the visual sign of severe nerve function damage and suppressed immune function, and it can be a

  9. Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination

    DEFF Research Database (Denmark)

    Margolin, David H.; Kousi, Maria; Chan, Yee-Ming

    2013-01-01

    affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase...... in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia...... can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil...

  10. 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.

  11. Ataxia-telangiectasia: an overview.

    Science.gov (United States)

    Boder, E

    1985-01-01

    The more subtle clinical findings that facilitate early diagnosis and the most provocative long-term clinical observations in our series of patients are emphasized. The most striking pathological findings in our own series of 11 complete autopsies are reviewed in relation to new findings from 57 autopsy reports in the recent literature. Clinical and pathological findings in our oldest patient, who died at age 32, are systematically compared with those of her sister, who died 20 years earlier at age 10 1/2 and who was the subject of the first autopsy in AT, thus providing a rare comparison of the early and late stages of the disease. The clinical and pathological findings, including the gliovascular malformations in the CNS described recently in autopsies on older patients, reveal that AT is characterized throughout its course by multisystemic progeric changes. It is proposed, therefore, that AT can serve as a model for the study of premature aging. Clinical diagnosis, laboratory markers, and special diagnostic procedures, along with general management, immunotherapy, and rehabilitative measures, are reviewed in Part II.

  12. 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.

  13. Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13.

    Directory of Open Access Journals (Sweden)

    Karla P Figueroa

    Full Text Available BACKGROUND: Gain-of function or dominant-negative mutations in the voltage-gated potassium channel KCNC3 (Kv3.3 were recently identified as a cause of autosomal dominant spinocerebellar ataxia. Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers. METHODOLOGY: DNA sequence analysis of the coding region of the KCNC3 gene was performed in 327 index cases with ataxia. Analysis of channel function was performed by expression of DNA variants in Xenopus oocytes. PRINCIPAL FINDINGS: Sequence analysis revealed two non-synonymous substitutions in exon 2 and five intronic changes, which were not predicted to alter splicing. We identified another pedigree with the p.Arg423His mutation in the highly conserved S4 domain of this channel. This family had an early-onset of disease and associated seizures in one individual. The second coding change, p.Gly263Asp, subtly altered biophysical properties of the channel, but was unlikely to be disease-associated as it occurred in an individual with an expansion of the CAG repeat in the CACNA1A calcium channel. CONCLUSIONS: Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. The p.Arg423His mutation is recurrent in different populations and associated with early onset. In contrast to previous p.Arg423His mutation carriers, we now observed seizures and mild mental retardation in one individual. This study confirms the wide phenotypic spectrum in SCA13.

  14. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

    DEFF Research Database (Denmark)

    Gatei, Magtouf; Sloper, Katie; Sørensen, Claus Storgaard

    2003-01-01

    In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2...

  15. DNA synthesis in ataxia telangiectasia

    OpenAIRE

    Jaspers, Nicolaas

    1985-01-01

    textabstractAfter the discovery that cultured cells from AT patients are hypersensitive to ionizing radiation the suggestion was made that AT-could be the 1 X-ray-analogue 1 of xeroderma pigmentosum. The latter syndrome (XP) is characterized by hypersensitivity to short-wave UV-radiation, caused by a reduced ability to properly remove UV-induced DNA damage. The evidence for a DNA repair defect in AT cells is not as strong as in the case of XP (see section 2.2.5 of this thesis). Different XP p...

  16. Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

    Directory of Open Access Journals (Sweden)

    Taysa Ribeiro Schalcher

    2013-09-01

    Full Text Available Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

  17. Ataxia, ophthalmoplegia, and impairment of consciousness in a 19-month-old American boy.

    Science.gov (United States)

    Gliebus, Gediminas; Faerber, Eric N; Valencia, Ignacio; Khurana, Divya S; Singh, Sabina B; Legido, Agustín

    2014-06-01

    A 19-month-old, white, Pennsylvanian boy, with an unremarkable medical history, presented to our hospital with a 3-week history of nonbloody, nonbilious emesis up to 5 times a day and nonbloody diarrhea. Ten days before admission, his gait became progressively unsteady, until he finally refused to walk. A day before admission, he found it difficult to move his eyes. The patient was hypoactive. History, physical and neurologic examination, blood and cerebrospinal (CSF) fluid studies, and neuroimaging studies ruled out the most frequent causes of acute ataxia. The etiology of bilateral, complete ophthalmoplegia was also taken into consideration. Magnetic resonance imaging (MRI) findings of bilateral thalami and mammillary bodies provided diagnostic clues. Additional history and specific tests established the final diagnosis and treatment plan. The patient improved to a normal neurologic state. This case provides important practical information about an unusual malnutrition cause of acute ataxia, particularly in young children of developing countries.

  18. Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin of the disease.

    Science.gov (United States)

    Leonardi, Luca; Marcotulli, Christian; McFarland, Karen N; Tessa, Alessandra; DiFabio, Roberto; Santorelli, Filippo M; Pierelli, Francesco; Ashizawa, Tetsuo; Casali, Carlo

    2014-09-01

    Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder manifested by ataxia with a variable presentation of epileptic seizures, which is caused by a large expansion of an intronic ATTCT pentanucleotide repeat in ATXN10 on 22q13.3. Herein, we report the first description of SCA10 in a Peruvian family, supporting the Amerindian origin of SCA10 and the Panamerican geographical distribution of the disease in North, Central and South America. Moreover, the presence of an interruption motif in the SCA10 expansion along with epileptic seizures in this family supports the correlation between the two, as seen in other families. Finally, this is the first SCA10 patient ever observed outside of America, specifically in Italy. Since this patient is a Peruvian immigrant of Amerindian ancestry, our case report highlights the growing need for awareness amongst clinicians of seemingly geographically restricted rare diseases.

  19. The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes suggest pervasive Purkinje cell vulnerability.

    Science.gov (United States)

    Hekman, Katherine E; Gomez, Christopher M

    2015-05-01

    The spinocerebellar ataxias are a genetically heterogeneous group of disorders with clinically overlapping phenotypes arising from Purkinje cell degeneration, cerebellar atrophy and varying degrees of degeneration of other grey matter regions. For 22 of the 32 subtypes, a genetic cause has been identified. While recurring themes are emerging, there is no clear correlation between the clinical phenotype or penetrance, the type of genetic defect or the category of the disease mechanism, or the neuronal types involved beyond Purkinje cells. These phenomena suggest that cerebellar Purkinje cells may be a uniquely vulnerable neuronal cell type, more susceptible to a wider variety of genetic/cellular insults than most other neuron types.

  20. Drug-induced cerebellar ataxia: a systematic review

    NARCIS (Netherlands)

    Gaalen, J. van; Kerstens, F.G.; Maas, R.P.P.W.M.; Harmark, L.; Warrenburg, B.P.C. van de

    2014-01-01

    BACKGROUND AND OBJECTIVES: Cerebellar ataxia can be induced by a large number of drugs. We here conducted a systemic review of the drugs that can lead to cerebellar ataxia as an adverse drug reaction (ADR). METHODS: We performed a systematic literature search in Pubmed (1966 to January 2014) and EMB

  1. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

    Science.gov (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

    2010-01-01

    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  2. Meningococcal meningitis presenting with bilateral deafness and ataxia.

    OpenAIRE

    Sandyk, R; Brennan, M J

    1984-01-01

    A 50-year-old man presented with bilateral deafness and ataxia of sudden onset and without constitutional symptoms or signs of meningeal irritation. He was subsequently proved to have meningococcal meningitis, and the deafness and ataxia resolved following appropriate antibiotic therapy.

  3. Dysarthria and Friedreich's Ataxia: What Can Intelligibility Assessment Tell Us?

    Science.gov (United States)

    Blaney, Bronagh; Hewlett, Nigel

    2007-01-01

    Background: Friedreich's ataxia is one of the most common hereditary disorders of the nervous system. Dysarthria is a pervasive symptom of Friedreich's ataxia, yet the clinical presentation of speech symptoms remains poorly understood, leaving clinicians without the evidence required to develop therapy interventions. Aims: The research reported…

  4. 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.

    2014-01-01

    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

  5. A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, N.; Katayama, T.; Makita, Y.; Kuroda, K.; Aizawa, H.; Kikuchi, K. [First Dept. of Internal Medicine, Asahikawa Medical Coll. (Japan)

    1999-07-01

    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum. (orig.)

  6. Friedreich's ataxia--a case of aberrant transcription termination?

    Science.gov (United States)

    Butler, Jill Sergesketter; Napierala, Marek

    2015-01-01

    Reduced expression of the mitochondrial protein Frataxin (FXN) is the underlying cause of Friedreich's ataxia. We propose a model of premature termination of FXN transcription induced by pathogenic expanded GAA repeats that links R-loop structures, antisense transcription, and heterochromatin formation as a novel mechanism of transcriptional repression in Friedreich's ataxia.

  7. Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model.

    Science.gov (United States)

    Németh, Andrea H; Kwasniewska, Alexandra C; Lise, Stefano; Parolin Schnekenberg, Ricardo; Becker, Esther B E; Bera, Katarzyna D; Shanks, Morag E; Gregory, Lorna; Buck, David; Zameel Cader, M; Talbot, Kevin; de Silva, Rajith; Fletcher, Nicholas; Hastings, Rob; Jayawant, Sandeep; Morrison, Patrick J; Worth, Paul; Taylor, Malcolm; Tolmie, John; O'Regan, Mary; Valentine, Ruth; Packham, Emily; Evans, Julie; Seller, Anneke; Ragoussis, Jiannis

    2013-10-01

    Many neurological conditions are caused by immensely heterogeneous gene mutations. The diagnostic process is often long and complex with most patients undergoing multiple invasive and costly investigations without ever reaching a conclusive molecular diagnosis. The advent of massively parallel, next-generation sequencing promises to revolutionize genetic testing and shorten the 'diagnostic odyssey' for many of these patients. We performed a pilot study using heterogeneous ataxias as a model neurogenetic disorder to assess the introduction of next-generation sequencing into clinical practice. We captured 58 known human ataxia genes followed by Illumina Next-Generation Sequencing in 50 highly heterogeneous patients with ataxia who had been extensively investigated and were refractory to diagnosis. All cases had been tested for spinocerebellar ataxia 1-3, 6, 7 and Friedrich's ataxia and had multiple other biochemical, genetic and invasive tests. In those cases where we identified the genetic mutation, we determined the time to diagnosis. Pathogenicity was assessed using a bioinformatics pipeline and novel variants were validated using functional experiments. The overall detection rate in our heterogeneous cohort was 18% and varied from 8.3% in those with an adult onset progressive disorder to 40% in those with a childhood or adolescent onset progressive disorder. The highest detection rate was in those with an adolescent onset and a family history (75%). The majority of cases with detectable mutations had a childhood onset but most are now adults, reflecting the long delay in diagnosis. The delays were primarily related to lack of easily available clinical testing, but other factors included the presence of atypical phenotypes and the use of indirect testing. In the cases where we made an eventual diagnosis, the delay was 3-35 years (mean 18.1 years). Alignment and coverage metrics indicated that the capture and sequencing was highly efficient and the consumable cost

  8. Unusual cerebral white matter change in a Chinese family with Spinocerebellar ataxia type 12.

    Science.gov (United States)

    Hu, Tao; Zhao, Bi; Wei, Qian-qian; Shang, Huifang

    2015-02-15

    In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2, regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the first report on patients with SCA12 presenting with prominent cerebral white matter change besides cerebral and/or cerebellar atrophy.

  9. The contribution of the cerebellum to cognition in Spinocerebellar Ataxia Type 6

    OpenAIRE

    Cooper, Freya E.; Manon Grube; Elsegood, Kelly J.; Welch, John L.; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2010-01-01

    This study sought evidence for a specific cerebellar contribution to cognition by characterising the cognitive phenotype of Spinocerebellar Ataxia Type 6 (SCA-6); an autosomal dominant genetic disease which causes a highly specific late-onset cerebellar degeneration. A comprehensive neuropsychological assessment was administered to 27 patients with genetically confirmed SCA-6. General intellectual ability, memory and executive function were examined using internationally standardised tests (W...

  10. Approach to acute ataxia in childhood: diagnosis and evaluation.

    Science.gov (United States)

    Sivaswamy, Lalitha

    2014-04-01

    Ataxia refers to motor incoordination that is usually most prominent during movement or when a child is attempting to maintain a sitting posture. The first part of the review focuses on the anatomic localization of ataxia--both within the nervous system and without--using a combination of historical features and physical findings. The remainder of the review discusses etiological considerations that vary depending on the age group under consideration. In infancy, certain specific diseases, such as opsoclonus myoclonus ataxia syndrome, must receive special mention because the underlying disease process may be amenable to surgical intervention. In the toddler- and school-age groups, certain conditions (such as stroke and acute cerebellitis) require immediate recognition and imaging, whereas others (such as post-infectious ataxia and concussion) require close follow-up. Finally, mention must be made of diseases outside of the central nervous system that can present with ataxia, such as Guillain-Barré syndrome.

  11. In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2.

    Science.gov (United States)

    Tomlinson, Susan E; Tan, S Veronica; Burke, David; Labrum, Robyn W; Haworth, Andrea; Gibbons, Vaneesha S; Sweeney, Mary G; Griggs, Robert C; Kullmann, Dimitri M; Bostock, Hugh; Hanna, Michael G

    2016-02-01

    Ion channel dysfunction causes a range of neurological disorders by altering transmembrane ion fluxes, neuronal or muscle excitability, and neurotransmitter release. Genetic neuronal channelopathies affecting peripheral axons provide a unique opportunity to examine the impact of dysfunction of a single channel subtype in detail in vivo. Episodic ataxia type 2 is caused by mutations in CACNA1A, which encodes the pore-forming subunit of the neuronal voltage-gated calcium channel Cav2.1. In peripheral motor axons, this channel is highly expressed at the presynaptic neuromuscular junction where it contributes to action potential-evoked neurotransmitter release, but it is not expressed mid-axon or thought to contribute to action potential generation. Eight patients from five families with genetically confirmed episodic ataxia type 2 underwent neurophysiological assessment to determine whether axonal excitability was normal and, if not, whether changes could be explained by Cav2.1 dysfunction. New mutations in the CACNA1A gene were identified in two families. Nerve conduction studies were normal, but increased jitter in single-fibre EMG studies indicated unstable neuromuscular transmission in two patients. Excitability properties of median motor axons were compared with those in 30 age-matched healthy control subjects. All patients had similar excitability abnormalities, including a high electrical threshold and increased responses to hyperpolarizing (P ataxia type 2 thus has unexpected effects on axon excitability, which may reflect an indirect effect of abnormal calcium current fluxes during development.

  12. The effect of ranitidine on cellular immunity in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Nielsen, H; Moesgaard, F;

    1990-01-01

    Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 af...

  13. Optical quantification of cellular mass, volume and density of circulating tumor cells identified in an ovarian cancer patient

    Directory of Open Access Journals (Sweden)

    Kevin Gregory Phillips

    2012-07-01

    Full Text Available Clinical studies have demonstrated that circulating tumor cells (CTCs are present in the blood of cancer patients with known metastatic disease across the major types of epithelial malignancies. Recent studies have shown that the concentration of CTCs in the blood is prognostic of overall survival in breast, prostate, colorectal and non-small cell lung cancer. This study characterizes CTCs identified using the high-definition (HD-CTC assay in an ovarian cancer patient with stage IIIC disease. We characterized the physical properties of 31 HD-CTCs and 50 normal leukocytes from a single blood draw taken just prior to the initial debulking surgery. We utilized a non-interferometric quantitative phase microscopy technique using brightfield imagery to measure cellular dry mass. Next we used a quantitative differential interference contrast microscopy technique to measure cellular volume. These techniques were combined to determine cellular dry mass density. We found that HD-CTCs were more massive than leukocytes: 33.6 ± 3.2 pg (HD-CTC compared to 18.7 ± 0.6 pg (leukocytes, p < 0.001; had greater volumes: 518.3 ± 24.5 fL (HD-CTC compared to 230.9 ± 78.5 fL (leukocyte, p<0.001; and possessed a decreased dry mass density with respect to leukocytes: 0.065 ± 0.006 pg/fL (HD-CTC compared to 0.085 ± 0.004 pg/fL (leukocyte, p < 0.006. Quantification of HD-CTC dry mass content and volume provide key insights into the fluid dynamics of cancer, and may provide the rationale for strategies to isolate, monitor or target CTCs based on their physical properties. The parameters reported here can also be incorporated into blood cell flow models to better understand metastasis.

  14. Evidence that the Nijmegen breakage syndrome protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia-mutated kinase in a process similar to, but distinct from, cellular DSB repair.

    Science.gov (United States)

    Smith, Johanna A; Wang, Feng-Xiang; Zhang, Hui; Wu, Kou-Juey; Williams, Kevin Jon; Daniel, René

    2008-01-22

    Retroviral transduction involves integrase-dependent linkage of viral and host DNA that leaves an intermediate that requires post-integration repair (PIR). We and others proposed that PIR hijacks the host cell double-strand DNA break (DSB) repair pathways. Nevertheless, the geometry of retroviral DNA integration differs considerably from that of DSB repair and so the precise role of host-cell mechanisms in PIR remains unclear. In the current study, we found that the Nijmegen breakage syndrome 1 protein (NBS1), an early sensor of DSBs, associates with HIV-1 DNA, recruits the ataxia telangiectasia-mutated (ATM) kinase, promotes stable retroviral transduction, mediates efficient integration of viral DNA and blocks integrase-dependent apoptosis that can arise from unrepaired viral-host DNA linkages. Moreover, we demonstrate that the ATM kinase, recruited by NBS1, is itself required for efficient retroviral transduction. Surprisingly, recruitment of the ATR kinase, which in the context of DSB requires both NBS1 and ATM, proceeds independently of these two proteins. A model is proposed emphasizing similarities and differences between PIR and DSB repair. Differences between the pathways may eventually allow strategies to block PIR while still allowing DSB repair.

  15. A novel mitochondrial mutation m.8989G>C associated with neuropathy, ataxia, retinitis pigmentosa - the NARP syndrome

    DEFF Research Database (Denmark)

    Duno, Morten; Wibrand, Flemming; Baggesen, Kirsten

    2013-01-01

    mitochondrial point mutation, m.8989G>C, in a patient presenting with neuropathy, ataxia and retinitis pigmentosa constituting the classical NARP phenotype. This mutation alters the amino acid right next to canonical NARP mutation. We suggest that classic NARP syndrome relates to a defined dysfunction of p...

  16. Síndrome de Ataxia-Telangiectasia

    Directory of Open Access Journals (Sweden)

    Amauri Batista da Silva

    1971-06-01

    Full Text Available A ataxia-telangiectasia, doença de Mme. Louis-Bar, é caracterizada pela associação de ataxia cerebelar progressiva, em geral com início na primeira infância, telangiectasas óculo-cutâneas, movimentos coreoatetósicos, tendência a infecções repetidas do sistema respiratório, retardo estaturo-ponderal, demenciação. São mais ou menos freqüentes os tumores do sistema reticuloendotelial. A doença é geralmente familiar, transmitida por genes recessivos, autossômicos, não ligados ao sexo. A alteração bioquímica mais encontrada consiste na diminuição ou ausência completa da fração A das gamaglobulinas, bem como na perturbação das reações de hipersensibilidade retardada. Os AA. relatam o estudo clínico, biológico e pneumencefalográfico de uma criança de 3 anos de idade, apresentando essa enfermidade desde os 18 meses de vida, sem antecedentes familiares.

  17. Administrative and research policies required to bring cellular therapies from the research laboratory to the patient's bedside.

    Science.gov (United States)

    Yim, Robyn

    2005-10-01

    presidential administrations on cellular therapy, variations in individual state laws, and states becoming involved in research funding, such as California's Proposition 71. Legal concerns include expanding private litigation with diversity of lawsuits, expanding lists of defendants, and the use of class-action lawsuits in research cases. Ownership issues also arise in terms of intellectual property, patents, and ownership of stem cells collected from minors, as in umbilical cord blood donations. Situations that challenge the regulatory processes established to ensure participant safety include differences in reporting requirements for private- and public-funded research and the lack of adequate funding and resources to implement and support the institutional review board (IRB) process. Financial considerations influence the development of clinical protocols, because funding is often limited. Financial incentives, personal investment in companies funding research activities, and fundraising pressures may present potential conflicts. In addition, the increasing role of emerging biotechnology start-up companies and pharmaceutical companies in clinical research introduces additional financial considerations. Administrative policies are needed to address these possible conflicts and ensure research participant safety as cellular therapies progress from the research laboratories to the patient's bedside. Administrative policies to ensure minimum standards of quality for emerging products before human clinical trials, policies to enforce consistent reporting requirements for private and public cellular research, policies to minimize financial conflicts of interest, policies to strengthen implementation of the existing IRB process and to structure into the process a consistent, systematic review of these identified conflicts, and policies to limit private litigation will help to preserve the objectivity of the review process and ultimately increase participant safety.

  18. Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort

    Directory of Open Access Journals (Sweden)

    Rufei Lu

    2012-01-01

    Full Text Available Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.

  19. 中国大陆遗传性脊髓小脑型共济失调患者PURATROPHIN-1基因c.-16C>T突变研究%Study on the single-nucleotide substitution (c.-16C>T)of the PURATROPHIN-1 gene on Chinese patients with spinocerebellar ataxia

    Institute of Scientific and Technical Information of China (English)

    周亚芳; 宋兴旺; 易继平; 江泓; 王俊岭; 廖书胜; 唐北沙

    2008-01-01

    目的 研究中国大陆遗传性脊髓小脑型共济失调(spinocerebellar ataxia,scA)患者PURATROPHIN-1 c.-16C>T突变分布.方法 应用聚合酶链反应.限制性片段长度多态技术,对已经排除了SCA1、SCA2、SCA3、SCA6、SCA7、SCA17和齿状核.红核.苍白球路易体萎缩的68个常染色体显性遗传SCA家系的先证者及119例散发SCA患者进行PURATROPHIN-1基因c.-16C>T突变检测.结果 未发现PUPURATROPHIN-1基因c.-16C>T突变.结论 PURATROPHIN-1基因c.-16C>T突变在中国大陆SCA人群中罕见.%Objective To study the single-nucleotide substitution (c.-16C>T) of the PURATROPHIN-1 gene in spinocerebellar ataxia (SCA) patients in China.Methods The single-nucleotide substitution(c.-16 C>T) of the PURATROPHIN-1 gene was detected by PCR,digested with EcoN I,separated on 8% polyacrylamide gel in 68 probands of autosomal dominant SCA families and 119 sporadic SCA patients,who had been excluded for CAG/CAA repeat expansion at the SCA1,2,3,6,7,17 and dentatorubral-pallidolluysian atrophy (DRPLA) loci.The results were confirmed in four patients by direet sequencing.Results The single-nucleotide substitution(c.-16C>T)of the PURATROPHIN-1 gene was not identified in authors' cohort.Conclusion The mutation of c.-16C>T of the PURATROPHIN-1 gene might be rare in SCA patients in China.

  20. 中国南方汉族遗传性脊髓小脑型共济失调患者蛋白激酶Cγ基因突变分析%Mutation analysis of protein kinase Cγ gene in hereditary spinocerebellar ataxia patients in southern Chinese Han nationality

    Institute of Scientific and Technical Information of China (English)

    易继平; 唐北沙; 江泓; 周亚芳; 王俊岭; 徐倩; 李晓辉; 沈璐; 潘乾; 夏昆

    2009-01-01

    目的 探讨中国南方汉族遗传性脊髓小脑型共济失调(SCA)患者蛋白激酶Cγ(PRKCG)基因突变特点.方法 应用聚合酶链反应结合变性高效液相色谱法(denaturing high performance liquid chromatography,DHPLC),对已经排除SCA1、2、3、6、7、8 10、12、17和齿状核-红核-苍白球-路易体萎缩的67例常染色体显性遗传SCA家系先证者进行PRKCG基因全编码区18个外显子及外显子-内含子交界区突变检测.结果 本组SCA患者未检测到PRKCG基凶致病突变,共发现4个单核苷酸多态(c.507A>G,IVS15-41T>C,纯合、杂合c.1941C>T),其中c.507A>G为新发现的罕见多念.结论 PRKCG基因突变在中国大陆汉族SCA患者中可能罕见.%Objective To investigate the mutation characteristics of protein kinase Cγ (PRKCG)gene in hereditary spinocerebellar ataxia (SCA) patients in southern Chinese Han nationality.Methods The mutation analysis of all 18 exons including exon-intron junctions of PRKCG gene was carried out by polymerase chain reaction combined with denaturing high performance liquid chromatography (DHPLC) in 67 indexs of autosomal dominant cerebellar ataxia families.All patients were excluded for SCA1,2,3,6,7,8,10,12,17 and dentatorubral pallidoluysian atrophy.Results No pathogenic mutation in PRKCG gene was identified in this group of SCA patients.However four nucleotide polymorphisms were found (c.507A>G,IVS15-41T > C and c.1941C > T) and one of them (c.507A > G) was not reported previously.Conclusions Mutation of PRKCG gene may be rare in mainland Chinese SCA patients.

  1. Use of cellular biotechnologies in treatment metastatic pericarditis at patients with tumors of female reproductive system

    Directory of Open Access Journals (Sweden)

    K. S. Titov

    2013-01-01

    Full Text Available Malignant pericardial effusions often arise in patients with breаst cancer and ovarian cancer. Sistem antitumor therapy is uneffective in gen- erally and causes side effects. Here we show that intrapericardial interleukin-2 with allogenеc lymphokine-activated killers and interleukin-2 immunotherapy demonstrated the high efficacy in threatment of breаst and ovarian cancer patients with malignant pericardial effusions. The objective effect was 92.3 % аnd 90.0 % accordingly. These results indicates that intrapericardial immunotherapy might be one of the stages of combined treatment of such group of patients. The suggested type of biotherapy increases the survival and life quality of patients.

  2. [The cellular immunity indices of patients with a rheumatic heart defect].

    Science.gov (United States)

    Manev, V; Grigorov, M; Penkova, K; Chaushev, A; Ramshev, K; Topalov, I; Leseva, N; Ivanov, G; Ivanova, I; Nedialkova, V

    1990-01-01

    In 29 patients with clinical diagnosis of rheumatic valvular disease the quantitative values of active rosettes and the specific sensitization to human heart myosin were examined. The specific sensitization to human heart myosin was examined by two methods concurrently: method of inhibiting leucocyte migration in agarose and method for direct specific lymphocytolysis with myosin. The results were compared with those of 44 clinically healthy controls. In the patients with rheumatic valvular disease (RVD) the values of the active rosettes are significantly lower (p less than 0.01) than in the healthy controls. With the method of direct specific lymphocytolysis with myosin statistically significant sensibilization of the lymphocytes to myosin was found in the patients with RVD (p less than 0.001). In 5 patients examined before and after operation it was established that 2-4 weeks after a successful correction of the hemodynamics the specific sensibilization of the lymphocytes to myosin was no more present.

  3. Assessment of speech in early-onset ataxia : a pilot study

    NARCIS (Netherlands)

    Kuiper, Marieke J.; Brandsma, Rick; Lawerman, T.F.; Lunsing, Roelineke J.; Keegstra, Anne L.; Burger, Huibert; De Koning, Tom J.; Tijssen, Marina A. J.; Sival, Deborah A.

    2014-01-01

    AIM: The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia (EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement, includ

  4. Association of Angiotensin-Converting Enzyme (ACE Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

    Directory of Open Access Journals (Sweden)

    Laila Rashed

    Full Text Available Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D polymorphism of the ACE gene was reported be associated with the development of vitiligo.Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL-6 and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide in vitiligo patients.This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively.The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026. However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115. There were statistically significant higher VIDA score (P = 0.007, and serum IL-6 (P < 0.001 in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007 when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls.As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

  5. [The clinical features and gene mutation analysis in a pedigree of spinocerebellar ataxia type 7].

    Science.gov (United States)

    Yin, Xin-Zhen; Zhang, Bao-Rong; Wu, Ding-Wen; Tian, Jun; Zhang, Hao

    2007-06-01

    We investigated the clinical features and gene mutation in a pedigree of spinocerebellar ataxia (SCA). A series of clinical tests was performed including visual examination, retinal angiography, visual evoked potential, electroretinogram and magnetic resonance imaging. Genomic DNA of the family members and normal controls was used for amplification of the (CAG)n repeats of SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA genes by PCR. The number of (CAG)n was determined by 8% denaturing polyacrylamide gel electrophoresis and direct sequencing. The main features of 2 patients were ataxia, visual failure, retinal degeneration, cerebellar and pontine atrophy. A mutation in SCA7 gene was detected, while no mutations were found in SCA1, SCA2, SCA3, SCA6, SCA17 or DRPLA gene. Therefore, this is a pedigree of SCA7. Analysis of the CAG trinucleotide repeat expansion at the SCA7 locus can provide valuable insights into SCA7.

  6. The dynamic regulation of cortical excitability is altered in episodic ataxia type 2

    DEFF Research Database (Denmark)

    Helmich, Rick C; Siebner, Hartwig R; Giffin, Nicola

    2010-01-01

    Episodic ataxia type 2 and familial hemiplegic migraine are two rare hereditary disorders that are linked to dysfunctional ion channels and are characterized clinically by paroxysmal neurological symptoms. Impaired regulation of cerebral excitability is thought to play a role in the occurrence......-pulse transcranial magnetic stimulation at an interstimulus interval of 2 and 10 ms to assess intracortical inhibition and facilitation, respectively. The time course of burst-induced excitability changes differed between groups. Healthy controls showed a short-lived increase in excitability that was only present 50...... ms after the burst. In contrast, patients with episodic ataxia type 2 showed an abnormally prolonged increase in corticospinal excitability that was still present 250 ms after the transcranial magnetic stimulation burst. Furthermore, while controls showed a decrease in intracortical facilitation...

  7. 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.

  8. The Pointing Errors in Optic Ataxia Reveal the Role of "Peripheral Magnification" of the PPC.

    Science.gov (United States)

    Vindras, Philippe; Blangero, Annabelle; Ota, Hisaaki; Reilly, Karen T; Rossetti, Yves; Pisella, Laure

    2016-01-01

    Interaction with visual objects in the environment requires an accurate correspondence between visual space and its internal representation within the brain. Many clinical conditions involve some impairment in visuo-motor control and the errors created by the lesion of a specific brain region are neither random nor uninformative. Modern approaches to studying the neuropsychology of action require powerful data-driven analyses and error modeling in order to understand the function of the lesioned areas. In the present paper we carried out mixed-effect analyses of the pointing errors of seven optic ataxia patients and seven control subjects. We found that a small parameter set is sufficient to explain the pointing errors produced by unilateral optic ataxia patients. In particular, the extremely stereotypical errors made when pointing toward the contralesional visual field can be fitted by mathematical models similar to those used to model central magnification in cortical or sub-cortical structure(s). Our interpretation is that visual areas that contain this footprint of central magnification guide pointing movements when the posterior parietal cortex (PPC) is damaged and that the functional role of the PPC is to actively compensate for the under-representation of peripheral vision that accompanies central magnification. Optic ataxia misreaching reveals what would be hand movement accuracy and precision if the human motor system did not include elaborated corrective processes for reaching and grasping to non-foveated targets.

  9. Evaluation of the child with acute ataxia: a systematic review.

    Science.gov (United States)

    Whelan, Harry T; Verma, Sumit; Guo, Yan; Thabet, Farouq; Bozarth, Xiuhua; Nwosu, Michelle; Katyayan, Akshat; Parachuri, Venu; Spangler, Katie; Ruggeri, Barbara E; Srivatsal, Sindhu; Zhang, Guojun; Ashwal, Stephen

    2013-07-01

    Evaluation of acute ataxia in a child poses a dilemma for the clinician in determining the extent and timing of initial screening tests. This article reviews the evidence concerning the diagnostic yield of commonly ordered tests in evaluating the child with acute ataxia. The literature revealed the following frequencies of laboratory screening abnormalities in children with acute ataxia: CT (∼2.5%), MRI (∼5%), lumbar puncture (43%), EEG (42%), and toxicology (49%). In most studies, abnormalities detected by these screening tests were nondiagnostic. There are insufficient data to assess yields of testing for autoimmune disorders or inborn errors of metabolism. A toxicology screen should be considered in all children presenting with acute ataxia. Neuroimaging should be considered in all children with new onset ataxia. Cerebrospinal fluid analysis has limited diagnostic specificity unless clinically indicated. Studies to examine neurophysiology testing did have sufficient evidence to support their use. There is insufficient evidence to establish a role for autoantibody testing or for routine screening for inborn error of metabolism in children presenting with acute ataxia. Finally, in a child presenting with ataxia and opsoclonus myoclonus, urine catecholamine testing for occult neuroblastoma is recommended. Nuclear scan may be considered, however, there is insufficient evidence for additional body imaging.

  10. [A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia].

    Science.gov (United States)

    Saito, Rie; Kikuno, Shota; Maeda, Meiko; Uesaka, Yoshikazu; Ida, Masahiro

    2014-01-01

    We report on the case of a 77-year-old male with genetically proven spinocerebellar ataxia type 31 (SCA31) who had dystonia. He was referred to our hospital for evaluation following a 6-year history of slowly progressive unsteadiness of his left leg during walking and dysarthria at the age of 62 years old. On the basis of his symptoms, we diagnosed him as spinocerebellar degeneration (SCD), and prescribed taltirelin hydrate. However, his symptoms continued to worsen. He required a cane for walking at the age of 63 years, and a wheelchair at the age of 66 years. He was admitted to our hospital following acute cerebral infarction at the age of 77 years. On examination at admission, right hemiparesis and cerebellar ataxia were detected. And left hallux moved involuntarily toward the top surface of the foot at rest, that is dystonia. The dystonia was not associated with cerebral infarction, because it had been several years with dystonia that he got cerebral infarction. Genetic analysis revealed that this patient harbored a heterozygous SCA31 mutation. Previously there have been no reports of SCA31 associated with dystonia. Our case report support clinical heterogeneity of SCA31, and highlight the importance of considering this type in patients with dystonia and ataxia. Patients with the combination of dystonia and ataxia and a family history of a neurodegenerative disorder should be tested for SCA31.

  11. Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy.

    Directory of Open Access Journals (Sweden)

    Jiing-Feng Lirng

    Full Text Available PURPOSE: A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS may help differentiate spinocerebellar ataxias (SCA from multiple systemic atrophy- cerebellar type (MSA-C. MATERIAL AND METHODS: This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA types 1, 2, 3, 6 and 17 (N = 94 and MSA-C (N = 62, and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. RESULTS: When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002. The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005. The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018. The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04. The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005. In the early stages of diseases (SARA score<10, significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017. The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005. Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016. CONCLUSION: By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C. Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.

  12. Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome.

    Science.gov (United States)

    O'Keefe, Joan A; Robertson-Dick, Erin E; Hall, Deborah A; Berry-Kravis, Elizabeth

    2016-08-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" (PM) size CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Cerebellar gait ataxia is the primary feature in some FXTAS patients causing progressive disability. However, no studies have quantitatively characterized gait and mobility deficits in FXTAS. We performed quantitative gait and mobility analysis in seven FMR1 PM carriers with FXTAS and ataxia, six PM carriers without FXTAS, and 18 age-matched controls. We studied four independent gait domains, trunk range of motion (ROM), and movement transitions using an instrumented Timed Up and Go (i-TUG). We correlated these outcome measures with FMR1 molecular variables and clinical severity scales. PM carriers with FXTAS were globally impaired in every gait performance domain except trunk ROM compared to controls. These included total i-TUG duration, stride velocity, gait cycle time, cadence, double-limb support and swing phase times, turn duration, step time before turn, and turn-to-sit duration, and increased gait variability on several measures. Carriers without FXTAS did not differ from controls on any parameters, but double-limb support time was close to significance. Balance and disability scales correlated with multiple gait and movement transition parameters, while the FXTAS Rating Scale did not. This is the first study to quantitatively examine gait and movement transitions in FXTAS patients. Gait characteristics were consistent with those from previous cohorts with cerebellar ataxia. Sensitive measures like the i-TUG may help determine efficacy of interventions, characterize disease progression, and provide early markers of disease in FXTAS.

  13. FXN Promoter Silencing in the Humanized Mouse Model of Friedreich Ataxia.

    Directory of Open Access Journals (Sweden)

    Yogesh K Chutake

    Full Text Available Friedreich ataxia is caused by an expanded GAA triplet-repeat sequence in intron 1 of the FXN gene that results in epigenetic silencing of the FXN promoter. This silencing mechanism is seen in patient-derived lymphoblastoid cells but it remains unknown if it is a widespread phenomenon affecting multiple cell types and tissues.The humanized mouse model of Friedreich ataxia (YG8sR, which carries a single transgenic insert of the human FXN gene with an expanded GAA triplet-repeat in intron 1, is deficient for FXN transcript when compared to an isogenic transgenic mouse lacking the expanded repeat (Y47R. We found that in YG8sR the deficiency of FXN transcript extended both upstream and downstream of the expanded GAA triplet-repeat, suggestive of deficient transcriptional initiation. This pattern of deficiency was seen in all tissues tested, irrespective of whether they are known to be affected or spared in disease pathogenesis, in both neuronal and non-neuronal tissues, and in cultured primary fibroblasts. FXN promoter function was directly measured via metabolic labeling of newly synthesized transcripts in fibroblasts, which revealed that the YG8sR mouse was significantly deficient in transcriptional initiation compared to the Y47R mouse.Deficient transcriptional initiation accounts for FXN transcriptional deficiency in the humanized mouse model of Friedreich ataxia, similar to patient-derived cells, and the mechanism underlying promoter silencing in Friedreich ataxia is widespread across multiple cell types and tissues.

  14. A new Purkinje cell antibody (anti-Ca associated with subacute cerebellar ataxia: immunological characterization

    Directory of Open Access Journals (Sweden)

    Horn Sigrun

    2010-03-01

    Full Text Available Abstract We report on a newly discovered serum and cerebrospinal fluid (CSF reactivity to Purkinje cells (PCs associated with subacute inflammatory cerebellar ataxia. The patient, a previously healthy 33-year-old lady, presented with severe limb and gait ataxia, dysarthria, and diplopia two weeks after she had recovered from a common cold. Immunohistochemical studies on mouse, rat, and monkey brain sections revealed binding of a high-titer (up to 1:10,000 IgG antibody to the cerebellar molecular layer, Purkinje cell (PC layer, and white matter. The antibody is highly specific for PCs and binds to the cytoplasm as well as to the inner side of the membrane of PC somata, dendrites and axons. It is produced by B cell clones within the CNS, belongs to the IgG1 subclass, and activates complement in vitro. Western blotting of primate cerebellum extract revealed binding of CSF and serum IgG to an 80-97 kDa protein. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic antibodies known to be associated with cerebellar ataxia. Screening of >9000 human full length proteins by means of a protein array and additional confirmatory experiments revealed Rho GTPase activating protein 26 (ARHGAP26, GRAF, oligophrenin-1-like protein as the target antigen. Preadsorption of the patient's serum with human ARHGAP26 but not preadsorption with other proteins resulted in complete loss of PC staining. Our findings suggest a role of autoimmunity against ARHGAP26 in the pathogenesis of subacute inflammatory cerebellar ataxia, and extend the panel of diagnostic markers for this devastating disease.

  15. 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.

  16. Molecular genetics of a Chinese family with spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Dan-dan WU

    2015-10-01

    Full Text Available Objective To study the genotype of the members of a Chinese family with spinocerebellar ataxia (SCA. Methods The peripheral blood samples of 6 patients and 40 asymptomatic people belonged to the family were collected. Referring to the clinical manifestations of the proband and second-generation sequencing results, the CAG trinucleotide repeats of the pathogenic gene ATXN2 were amplified by polymerase chain reaction (PCR. The repeated times of the trinucleotide in normally and abnormally amplified alleles were defined by agarose gel electrophoresis and PCR products sequencing. Results Autosomal dominant heredity was the cause of the SCA in this family. Six out of 46 in the fourth-generation were SCA2 patients, 7 were the carriers of pathogenic allele. The repeated times of CAG trinucleotide were within the normal range in one of the two alleles of ATXN2, but they were in abnormal range in the another one. The repeated times of CAG trinucleotide were 40-46 in abnormal alleles of patients. Conclusion Autosomal dominant heredity SCA2 has been diagnosed in this family caused by the dynamic nutation of CAG trinucleotide repeats, and 7 pathogenic allele carriers in this family were confirmed by genetic diagnosis. DOI: 10.11855/j.issn.0577-7402.2015.08.07

  17. Ataxia crónica en pediatría

    OpenAIRE

    Ricardo Erazo Torricelli

    2013-01-01

    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 ...

  18. Localization of the candidate gene d-amino acid oxidase outside the refined 1-cM region of spinocerebellar ataxia 2

    Energy Technology Data Exchange (ETDEWEB)

    Auburger, G.; Gispert, S.; Lunkes, A. [Univ. Hospital, Duesseldorf (Germany)] [and others

    1995-10-01

    Spinocerebellar ataxia 2 (SCA2) is one form of the neurodegenerative autosomal dominant cerebellar ataxias and has been linked to chromosome 12q in 25 previously described and 13 new families from a founder collective of {ge}500 patients in Holguin, Cuba. Although SCA2 in most patients cannot be distinguished from other spinocerebellar ataxias by clinical criteria, in some patients it exhibits a particular phenotype with early neuropathy/late slow saccades and late myoclonus. Autopsy in 11 patients demonstrated olivo-ponto-cerebellar atrophy with a selective sparing of the dentate nucleus. Complete allelic association within the Holguin population was established with the microsatellite D12S105, and the candidate region was determined to be within a 6-cM region distal to the marker D12S84, contrasting previous reports by Pulst and Lopes-Cendes and according to preliminary data between D12S84 and D12S1329. 17 refs., 1 fig., 1 tab.

  19. [Diabetes and alternative medicine: diabetic patients experiences with Ayur-Ved, "clinical ecology" and "cellular nutrition" methods].

    Science.gov (United States)

    Vanelli, M; Chiari, G; Gugliotta, M; Capuano, C; Giacalone, T; Gruppi, L; Condò, M

    2002-04-01

    In the last two years we discovered that three of our patients with type 1 diabetes mellitus (0.8%) suffered an unexpected worsening in their glycemic control due to a reduction of their insulin dosage in favour of some "alternative" diabetes treatments using herbs, vitamins, fantastic diets and trace elements prescribed by non-medical practitioners. The first patient, a 6.6 year old boy, was admitted to hospital because of a severe ketoacidosis with first degree coma as a result of his parents having reduced his insulin dosage by 77% and replacing the insulin with an ayurvedic herbal preparation (Bardana Actium Lapp). The second patient, a 10.4 year old boy, was admitted to hospital after his teachers noticed that he appeared tired, thinner and polyuric. During hospital admission for mild ketoacidosis the mother, reluctant at first, finally confessed that her son was under the care of a "clinical ecologist". Having identified several food allergies this "clinical ecologist" had placed the child on a spartan diet of bread, water and salt, and had reduced his insulin dosage by 68%. The third patient, a 21 year old male, upon transfer to the Adult Diabetic Center, reported that he had been under the care of a pranotherapist for several years. The pranotherapist had prescribed a cellular nutrition preparation (called "Madonna drops"), a meditation program and also a 50% reduction in his insulin dosage. During this period his HbAlc values had increased from 6.4% to 12%. Current orthodox diabetes treatments are considered unsatisfactory by many people and it is thus not surprising that they search for "miracle" cures. It is important, however, that hospital staff do not ridicule the patients or their parents for trying these alternative therapies. Nevertheless, it would be useful for staff to discuss in advance these "therapies" with patients, highlighting their ineffectiveness and strongly discouraging cures that call for a reduction or elimination of the insulin

  20. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis.

    Science.gov (United States)

    León Fernández, Olga Sonia; Viebahn-Haensler, Renate; Cabreja, Gilberto López; Espinosa, Irainis Serrano; Matos, Yanet Hernández; Roche, Liván Delgado; Santos, Beatriz Tamargo; Oru, Gabriel Takon; Polo Vega, Juan Carlos

    2016-10-15

    Medical ozone reduced inflammation, IL-1β, TNF-α mRNA levels and oxidative stress in PG/PS-induced arthritis in rats. The aim of this study was to investigate the medical ozone effects in patients with rheumatoid arthritis treated with methotrexate and methotrexate+ozone, and to compare between them. A randomized clinical study with 60 patients was performed, who were divided into two groups: one (n=30) treated with methotrexate (MTX), folic acid and Ibuprophen (MTX group) and the second group (n=30) received the same as the MTX group+medical ozone by rectal insufflation of the gas (MTX+ozone group). The clinical response of the patients was evaluated by comparing Disease Activity Score 28 (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), Anti-Cyclic Citrullinated (Anti-CCP) levels, reactants of acute phase and biochemical markers of oxidative stress before and after 20 days of treatment. MTX+ozone reduced the activity of the disease while MTX merely showed a tendency to decrease the variables. Reactants of acute phase displayed a similar picture. MTX+ozone reduced Anti-CCP levels as well as increased antioxidant system, and decreased oxidative damage whereas MTX did not change. Glutathione correlated with all clinical variables just after MTX+ozone. MTX+ozone increased the MTX clinical response in patients with rheumatoid arthritis. No side effects were observed. These results suggest that ozone can increase the efficacy of MTX probably because both share common therapeutic targets. Medical ozone treatment is capable of being a complementary therapy in the treatment of rheumatoid arthritis.

  1. 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

  2. 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.

  3. [Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition].

    Science.gov (United States)

    Słotwiński, R; Pertkiewicz, M; Lech, G; Szczygieł, B

    2000-06-01

    The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

  4. Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease.

    Science.gov (United States)

    Calabrese, Vittorio; Sultana, Rukhsana; Scapagnini, Giovanni; Guagliano, Eleonora; Sapienza, Maria; Bella, Rita; Kanski, Jaroslaw; Pennisi, Giovanni; Mancuso, Cesare; Stella, Anna Maria Giuffrida; Butterfield, D A

    2006-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and memory decline, personality changes, and synapse loss. Increasing evidence indicates that factors such as oxidative and nitrosative stress, glutathione depletion, and impaired protein metabolism can interact in a vicious cycle, which is central to AD pathogenesis. In the present study, we demonstrate that brains of AD patients undergo oxidative changes classically associated with a strong induction of the so-called vitagenes, including the heat shock proteins (HSPs) heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase (TRXr). In inferior parietal brain of AD patients, a significant increase in the expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased, compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was decreased in AD patients, compared with the control group, and was associated with a significant increase in oxidative stress markers (i.e., GSSG, hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes, we observed an increased expression of inducible nitric oxide synthase, HO-1, Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1 and TRXr, may represent important targets for novel cytoprotective strategies.

  5. Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.

    Science.gov (United States)

    Deik, A; Johannes, B; Rucker, J C; Sánchez, E; Brodie, S E; Deegan, E; Landy, K; Kajiwara, Y; Scelsa, S; Saunders-Pullman, R; Paisán-Ruiz, C

    2014-12-01

    PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.

  6. Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5

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    O’Brien, Kevin J.; Nicoli, Elena-Raluca; Brooks, Brian P.; Huryn, Laryssa; Titus, Steven A.; Adams, David R.; Chen, Dong; Gahl, William A.; Gochuico, Bernadette R.

    2017-01-01

    Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of genetic disorders typically manifesting with tyrosinase-positive oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis, in some subtypes. Most HPS subtypes are associated with defects in Biogenesis of Lysosome-related Organelle Complexes (BLOCs), which are groups of proteins that function together in the formation and/or trafficking of lysosomal-related endosomal compartments. BLOC-2, for example, consists of the proteins HPS3, HPS5, and HPS6. Here we present an HPS patient with defective BLOC-2 due to a novel intronic mutation in HPS5 that activates a cryptic acceptor splice site. This mutation leads to the insertion of nine nucleotides in-frame and results in a reduced amount of HPS5 at the transcript and protein level. In studies using skin fibroblasts derived from the proband and two other individuals with HPS-5, we found a perinuclear distribution of acidified organelles in patient cells compared to controls. Our results suggest the role of HPS5 in the endo-lysosomal dynamics of skin fibroblasts. PMID:28296950

  7. Analysis of autosomal dominant spinocerebellar ataxia type 1 in an extended family of central India

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    Shashikant Sharma

    2012-01-01

    Full Text Available Background: Spinocerebeller ataxia type 1 (SCA1 is a specific type of ataxia among a group of inherited diseases of the central nervous system. In SCA1, genetic defects lead to impairment of specific nerve fibers carrying messages to and from the brain, resulting in the degeneration of the cerebellum, the coordination center of the brain. We investigated 24 members of an extended family in Gwalior city, India, some of which were earlier clinically diagnosed to be suffering from yet unconfirmed type of SCA neurodegenerative disorder. Materials and Methods: All the family members from each age group were screened clinically and the characteristics of those resembling with ataxia were recorded for diagnosis by MRI. The confirmed patients of the family were genetically tested by PCR based molecular testing to identify the type of SCA (i.e., SCA 1, 2, 3, 4, 6 or 7. Family tree of the disease inheritance was constructed by pedigree based method. Result and Conclusion: We found the clinical (symptoms and MRI and genetic (Pedigree and PCR results to be correlated. The PCR result revealed the disease to be of SCA 1 type being inherited in the family.

  8. Motor decline in clinically presymptomatic spinocerebellar ataxia type 2 gene carriers.

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    Luis Velázquez-Perez

    Full Text Available BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents.

  9. 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.

  10. Neurobehavioral deficits in the KIKO mouse model of Friedreich's ataxia.

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    McMackin, Marissa Z; Henderson, Chelsea K; Cortopassi, Gino A

    2017-01-01

    Friedreich's Ataxia (FA) is a pediatric neurodegenerative disease whose clinical presentation includes ataxia, muscle weakness, and peripheral sensory neuropathy. The KIKO mouse is an animal model of FA with frataxin deficiency first described in 2002, but neurobehavioral deficits have never been described in this model. The identification of robust neurobehavioral deficits in KIKO mice could support the testing of drugs for FA, which currently has no approved therapy. We tested 13 neurobehavioral tasks to identify a robust KIKO phenotype: Open Field, Grip Strength Test(s), Cylinder, Skilled Forelimb Grasp Task(s), Treadmill Endurance, Locotronic Motor Coordination, Inverted Screen, Treadscan, and Von Frey. Of these, Inverted Screen, Treadscan and Von Frey produced significant neurobehavioral deficits at >8 months of age, and relate to the clinically relevant endpoints of muscle strength and endurance, gait ataxia, and peripheral insensitivity. Thus we identify robust phenotypic measures related to Friedreich's ataxia clinical endpoints which could be used to test effectiveness of potential drug therapy.

  11. 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

  12. Spinocerebellar ataxia type 6 in eastern India: Some new observations

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    Kalyan B Bhattacharyya

    2016-01-01

    Full Text Available Introduction: Spinocerebellar ataxias (SCAs are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand. Objective: The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India. Materials and Methods: 83 consecutive patients were recruited for the study of possible SCAs and their clinical features and genotype were investigated. Results: 6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool. Discussion: SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties. Conclusions: Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.

  13. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

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    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  14. Studying of a wave activity condition and cellular metabolism of tissues in patients with perioral dermatitis

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    Grashkin V.A.

    2012-06-01

    Full Text Available

    Perioral dermatitis is a facial skin disease with insuffciently studied ethiology and pathogenetic mechanisms, being one of actual problems of dermatology. It is a chronic relapsing facial skin disease mainly in women of young and middle age (in men and children meets less often. The disease has an independent clinical picture which is different from rosacea, demodecosis, seborrheic dermatitis, etc. The standard diagnostic criterion is a visual estimation of expression of an infammation on the basis of signs of exudative reaction which has a subjective character. Possibilities of a radiometric method for an objective estimation of a facial skin functional condition and indicators of an intracellular metabolism in patients with a perioral dermatitis were frst studied.

  15. The effect of goals and vision on movements: a case study of optic ataxia and limb apraxia.

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    Ambron, Elisabetta; Lingnau, Angelika; Lunardelli, Alberta; Pesavento, Valentina; Rumiati, Raffaella I

    2015-04-01

    Normally we can perform a variety of goal-directed movements effortlessly. However, damage to the parietal cortex may dramatically reduce this ability, giving rise to optic ataxia and limb apraxia. Patients with optic ataxia show clear misreaches towards targets when presented in the peripheral visual field, whereas limb apraxia refers to the inability to use common tools or to imitate simple gestures. In the present paper we describe the case of a left-brain damaged patient, who presented both symptoms. We systematically investigated both spatial and temporal parameters of his movements, when asked to reach and grasp common objects to move (Experiment 1) or to use them (Experiment 2), presented either in the central or peripheral visual field. Different movement parameters changed in relation to the goal of the task (grasp to move vs. grasp to use), reflecting a normal modulation of the movement to accomplish tasks with different goals. On the other hand, grip aperture appeared to be more affected from both task goal and viewing condition, with a specific decrement observed when CF was asked to use objects presented peripherally. On the contrary, a neat effect of the viewing condition was observed in the spatial distribution of the end-points of the movements, and of the horizontal end point in particular, which were shifted towards the fixation point when reaching towards peripheral targets. We hypothesized that optic ataxia and limb apraxia have a differential effect on the patient's performance. The specific presence of optic ataxia would have an effect on the movement trajectory, but both symptoms might interact and influence the grasping component of the movement. As a 'cognitive side of motor control impairment', the presence of limb apraxia may have increased the task demands in grasping to use the objects thus exacerbating optic ataxia.

  16. 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.

  17. Post-Plasmodium vivax malaria cerebellar ataxia and optic neuritis: A new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?

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    Gaurav M Kasundra

    2015-01-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF malaria. Plasmodium vivax (PV rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM.

  18. Climbing fibers in spinocerebellar ataxia: A mechanism for the loss of motor control.

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    Smeets, C J L M; Verbeek, D S

    2016-04-01

    The spinocerebellar ataxias (SCAs) form an ever-growing group of neurodegenerative disorders causing dysfunction of the cerebellum and loss of motor control in patients. Currently, 41 different genetic causes have been identified, with each mutation affecting a different gene. Interestingly, these diverse genetic causes all disrupt cerebellar function and produce similar symptoms in patients. In order to understand the disease better, and define possible therapeutic targets for multiple SCAs, the field has been searching for common ground among the SCAs. In this review, we discuss the physiology of climbing fibers and the possibility that climbing fiber dysfunction is a point of convergence for at least a subset of SCAs.

  19. Cortical blindness and ataxia complicating bronchial artery embolization for severe hemoptysis.

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    Peng, Guoping; Liang, Hui; Ruan, Lingxiang; Luo, Benyan

    2010-01-01

    Complications of bronchial artery embolization (BAE) are uncommon. A 37-year-old patient with pulmonary tuberculosis received bronchial artery embolization because of severe hemoptysis. The bilateral bronchial arteries and left internal mammary artery were embolized using a gelatin sponge, and the patient exhibited occipital blindness and ataxia after the second BAE. The dissolvable gelatin sponge possibly entered the posterior circulation, resulting in the multiple infarctions in the bilateral occipital lobes and cerebellum. Because of the bad prognosis and the difficulty for curability, this kind of complication should be recognized in a timely manner and carefully avoided by the interventional radiologists carrying out the BAE.

  20. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

    Science.gov (United States)

    Miura, Yumako; Devaux, Jérôme J; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi; Yuki, Nobuhiro

    2015-06-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

  1. Trehalose improves human fibroblast deficits in a new CHIP-mutation related ataxia.

    Science.gov (United States)

    Casarejos, Maria Jose; Perucho, Juan; López-Sendón, Jose Luis; García de Yébenes, Justo; Bettencourt, Conceição; Gómez, Ana; Ruiz, Carolina; Heutink, Peter; Rizzu, Patrizia; Mena, Maria Angeles

    2014-01-01

    In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein misfolding and proteostasis were evaluated. Recent studies have revealed that mutations in STUB-1 gene lead to a growing list of molecular defects as deregulation of protein quality, inhibition of proteasome, cell death, decreased autophagy and alteration in CHIP and HSP70 levels. In this CHIP-mutant patient fibroblasts the inhibition of proteasome with epoxomicin induced severe pathophysiological age-associated changes, cell death and protein ubiquitination. Additionally, treatment with epoxomicin produced a dose-dependent increase in the number of cleaved caspase-3 positive cells. However, co-treatment with trehalose, a disaccharide of glucose present in a wide variety of organisms and known as a autophagy enhancer, reduced these pathological events. Trehalose application also increased CHIP and HSP70 expression and GSH free radical levels. Furthermore, trehalose augmented macro and chaperone mediated autophagy (CMA), rising the levels of LC3, LAMP2, CD63 and increasing the expression of Beclin-1 and Atg5-Atg12. Trehalose treatment in addition increased the percentage of immunoreactive cells to HSC70 and LAMP2 and reduced the autophagic substrate, p62. Although this is an individual case based on only one patient and the statistical comparisons are not valid between controls and patient, the low variability among controls and the obvious differences with this patient allow us to conclude that trehalose, through its autophagy activation capacity, anti-aggregation properties, anti-oxidative effects and lack of toxicity, could be very promising for the treatment of CHIP-mutation related ataxia, and possibly a wide spectrum

  2. Occupational therapy in spinocerebellar ataxia type 3: an open-label trial

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    R.C.R. Silva

    2010-06-01

    Full Text Available Occupational therapy (OT is a profession concerned with promoting health and well-being through occupation, by enabling handicapped people to participate in the activities of everyday life. OT is part of the clinical rehabilitation of progressive genetic neurodegenerative diseases such as spinocerebellar ataxias; however, its effects have never been determined in these diseases. Our aim was to investigate the effect of OT on both physical disabilities and depressive symptoms of spinocerebellar ataxia type 3 (SCA3 patients. Genomically diagnosed SCA3 patients older than 18 years were invited to participate in the study. Disability, as evaluated by functional independence measurement and Barthel incapacitation score, Hamilton Rating Scale for Depression, and World Health Organization Quality of Life questionnaire (WHOQOL-BREF, was determined at baseline and after 3 and 6 months of treatment. Twenty-six patients agreed to participate in the study. All were treated because OT prevents blinding of a control group. Fifteen sessions of rehabilitative OT were applied over a period of 6 months. Difficult access to food, clothing, personal hygiene, and leisure were some of the main disabilities focused by these patients. After this treatment, disability scores and quality of life were stable, and the Hamilton scores for depression improved. Since no medication was started up to 6 months before or during OT, this improvement was related to our intervention. No association was found between these endpoints and a CAG tract of the MJD1 gene (CAGn, age, age of onset, or neurological scores at baseline (Spearman test. Although the possibly temporary stabilization of the downhill disabilities as an effect of OT remains to be established, its clear effect on depressive symptoms confirms the recommendation of OT to any patient with SCA3 or spinocerebellar ataxia.

  3. 脊髓小脑性共济失调3型/Machado-Joseph病患者小脑的磁共振波谱分析%Magnetic resonance spectroscopy of the cerebellum in patients with spinocerebellar ataxia type 3/Machado-Joseph disease

    Institute of Scientific and Technical Information of China (English)

    雷立芳; 廖云杰; 廖伟华; 周洁; 袁毅; 王俊岭; 江泓; 沈璐; 唐北沙

    2011-01-01

    Objective To evaluate the metabolite pattern and the severity in patients with spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by 1H magnetic resonance spectroscopy (1H-MRS) on different cerebellar regions, including cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum. Methods Thirty-six SCA3/MJD patients, and 27 sex,age-matched healthy controls were scanned with 1H-MRS for N-acetylaspartate ( NAA ), choline (Cho) and creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar cortex,and dentatum as the region of interests (ROI), and finally got access to NAA/Cr, Cho/Cr, and NAA/Cho ratios. We also examined the CAG repeat numbers of MJDI gene, scored the 36 patients by the scale for the assessment and rating of ataxia ( SARA), analyzed the differences in ratios between SCA3/MJD patients and the control group, and explored whether relevance existed between these ratios and duration of the disease, age of onset, CAG repeat times, and SARA scores respectively. Results The ratio of NAA/Cr in SCA3/MJD patients showed a significant reduction in the cerebellar cortex, dentatum, eerebellar vermis and medipeduncle ( P < 0. 01 ) compared with the controls. The ratio of NAA/Cho also showed significant reduction in the dentatum and cerebellar vermis (P <0. 01 ). A number of correlations were found between the metabolite ratios of 1H-MRS and duration of the disease, age of onset, expanded CAG and SARA score in SCA3/MJD patients.Conclusion 1H-MRS, which shows the neural metabolic changes in the cerebella of SCA3/MJD patients, provides useful information about the severity of SCA3/MJD.%目的:通过研究脊髓小脑共济失调3型(SCA3/MJD)患者小脑蚓部、桥臂、小脑皮质、齿状核的氢质子磁共振波谱(1H-MRS)的特点,探讨1H-MRS评估SCA3型疾病严重程度的价值.方法:对36例SCA3/MJD患者与27例性别、年龄与之匹配的健康对照进行单体素1H-MRS测定,比较2组间小脑上述

  4. Change in the cortical complexity of spinocerebellar ataxia type 3 appears earlier than clinical symptoms.

    Science.gov (United States)

    Wang, Tzu-Yun; Jao, Chii-Wen; Soong, Bing-Wen; Wu, Hsiu-Mei; Shyu, Kuo-Kai; Wang, Po-Shan; Wu, Yu-Te

    2015-01-01

    Patients with spinocerebellar ataxia type 3 (SCA3) have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE) and electroencephalography (EEG), are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD) method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA), the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients' MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.

  5. Change in the cortical complexity of spinocerebellar ataxia type 3 appears earlier than clinical symptoms.

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    Tzu-Yun Wang

    Full Text Available Patients with spinocerebellar ataxia type 3 (SCA3 have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE and electroencephalography (EEG, are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA, the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients' MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.

  6. 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...

  7. 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.

  8. Evidence for a common founder effect amongst South African and Zambian individuals with Spinocerebellar ataxia type 7.

    Science.gov (United States)

    Smith, Danielle C; Atadzhanov, Masharip; Mwaba, Mwila; Greenberg, Leslie Jacqueline

    2015-07-15

    Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by the expansion of a CAG repeat within the ataxin 7 gene, leading to a pathogenic polyglutamine tract within the ataxin 7 protein. SCA7 patients suffer from progressive cerebellar ataxia and macular degeneration. SCA7 is considered to be rare, although founder effects have been reported in South Africa, Scandinavia and Mexico. The South African SCA7-associated haplotype has not been investigated in any other populations, and there have been limited reports of SCA7 patients from other African countries. Here, we describe the first two ethnic Zambian families with confirmed SCA7. Haplotype analysis showed that the South African SCA7 haplotype alleles were significantly associated with the pathogenic expansion in affected Zambian individuals, providing strong evidence for a shared founder effect between South African and Zambian SCA7 patients.

  9. Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers

    Institute of Scientific and Technical Information of China (English)

    Fu-Ling Zhou; Wang-Gang Zhang; Yong-Chang Wei; Kang-Ling Xu; Ling-Yun Hui; Xu-Sheng Wang; Ming-Zhong Li

    2005-01-01

    AIM: A study was performed to investigate the impact of comorbid anxiety and depression (CAD) on quality of life (QOL) and cellular immunity changes in patients with digestive tract cancers.METHODS: One hundred and fifty-six cases of both sexes with cancers of the digestive tract admitted between March 2001 and February 2004 in the Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly enrolled in the study. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-Ⅳ. All adult patients were evaluated with the Hamilton depressive scale (HAMD, the 24-item version), the Hamilton anxiety scale (HAMA, a modified 14-item version), quality of life questionnaire-core 30 (QLQ-C30), social support rating scale (SSRS), simple coping style questionnaire (SCSQ), and other questionnaires, respectively. In terms of HAMD ≥ 20 and HAMA ≥ 14, the patients were categorized, including CAD (n = 31) in group A, anxiety disorder (n = 23) in group B,depressive disorder (n = 37) in group C, and non-disorder (n = 65) in group D. Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared among the four groups.RESULTS: The incidence of CAD was 21.15% in patients with digestive tract cancers. The average scores of social support was 43.67±7.05 for 156 cases, active coping 20.34±7.33, and passive coping 9.55±5.51. Compared with group D, subjective support was enhanced slightly in group A, but social support, objective support, and utilization of support reduced, especially utilization of support with significance (6.16 vs 7.80, P<0.05); total scores of active coping decreased, while passive coping reversed; granulocytes proliferated, monocytes declined,and lymphocytes declined significantly (32.87 vs 34.00,P<0.05); moreover, the percentage of CD3, CD4, CD8and CD56 in T lymphocyte subsets was in lower

  10. Dysarthria in Friedreich's ataxia: a perceptual analysis.

    Science.gov (United States)

    Folker, Joanne; Murdoch, Bruce; Cahill, Louise; Delatycki, Martin; Corben, Louise; Vogel, Adam

    2010-01-01

    The aims of this study were to: (1) evaluate the perceptual speech dimensions, speech intelligibility and dysarthria severity of a group of individuals diagnosed with Friedreich's ataxia (FRDA); (2) determine the presence of subgroups within FRDA dysarthria; (3) investigate the relationship between the speech outcome and the clinical factors of disease progression. The study included 38 individuals (21 female, 17 male) with a confirmed diagnosis of FRDA. A group of 20 non-neurologically impaired individuals served as controls. Perceptual analysis, investigating 30 different dimensions of speech, was conducted on a speech sample obtained from each participant. In addition, the Assessment of Intelligibility of Dysarthria Speech was administered. All FRDA participants presented with dysarthria with severities ranging from mild to moderate. Cluster analysis revealed 3 subgroups, the first presenting with mild dysarthric symptoms, the second with increased velopharyngeal involvement and the third characterized by increased laryngeal dysfunction. Dysarthria severity showed a significant correlation to disease duration but to no other clinical measure. The findings support the notion of subgroups in FRDA dysarthria, representing distinct impairments of the speech mechanism and perhaps reflective of differing evolutions beyond the cerebellum.

  11. Ataxia-telangiectasia. (Clinical and immunological aspects).

    Science.gov (United States)

    Boder, E; Sedgwick, R P

    1970-01-01

    This syndrome was defined by the authors in 1947. Earlier publications of similar disease descriptions were by Syllaba and Henner (1926), Louis-Bar (1941). The authors at present have a stock of 253 cases. The cardinal symptoms of this phakomatosis are: Cerebellar ataxia which begin in infancy and take a slowly progressive course. In the late stages free walking and standing are no longer possible. Progressive atactic speech disorders, cerebellar atrophy in the pneumoencephalogram. Slowly progressing symmetrical skin and mucosal telangiectasia in the face and especially on the conjunctivae at the age of 3 to 6 years. Relapsing sinopulmonary infections with a tendency toward the development of bronchiectases. Apraxia of eye movements. Atrophy of facial skin and premature graying of hair. Recessively hereditary disorder with a high familial manifestation. This syndrome combines the spinocerebellar degeneration, phakomatoses, and infantile dementia processes. Such other conditions as abnormity or absence of thymus, reduction in gamma globulins, amino-aciduria, autosomal-recessive inheritance suggest a genetically determined "error of metabolism".

  12. An investigation of diffusion imaging techniques in the evaluation of spinocerebellar ataxia and multisystem atrophy.

    Science.gov (United States)

    Rozenfeld, Michael N; Nemeth, Alexander J; Walker, Matthew T; Mohan, Prasoon; Wang, Xue; Parrish, Todd B; Opal, Puneet

    2015-01-01

    Multisystem system atrophy and spinocerebellar ataxia are rare neurodegenerative ataxias that can be difficult to diagnose, with important prognostic and treatment implications. The purpose of this study is to evaluate various methods of diffusion imaging and tractography in their effectiveness at differentiating these diseases from control subjects. Our secondary aim is determining whether diffusion abnormalities correspond with clinical disease severity. Diffusion imaging and tractography were performed on five patients and seven age-matched controls. Fractional anisotropy, generalized fractional anisotropy, and apparent diffusion coefficient values and corticospinal tract volumes were measured within various diffusion and probabilistic tractography models, including standard diffusion tensor and Q-ball tractography. Standard diffusion based fractional anisotropy and apparent diffusion coefficient values were significantly altered in patients versus controls in the middle cerebellar peduncles and central pons. Tractography based fractional anisotropy and generalized fractional anisotropy values were significantly lower in patients versus controls when corticospinal tracts were drawn in a craniocaudal direction (bilaterally using Q-ball imaging, only on the right using diffusion tensor imaging). The right corticospinal tract volume was significantly smaller in patients versus controls when created using Q-ball imaging in a caudocranial direction. There was no correlation between diffusion alteration and clinical symptomatology. In conclusion, various diffusion-based techniques can be effective in differentiating ataxic patients from control subjects, although the selection of diffusion algorithm and tract growth technique and direction is non-trivial.

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

    Science.gov (United States)

    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

    2014-10-03

    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.

  14. Ataxias cerebelares hereditárias: do martelo ao gen Hereditary cerebellar ataxias from neurological hammer to genetics

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda

    1997-09-01

    Full Text Available As heredoataxias constituem grupo complexo de doenças neurodegenerativas hereditárias, para o qual várias formas de classificação clínica e patológica foram propostas com sucesso variável. O desenvolvimento das técnicas de biologia molecular trouxe informações importantes que têm permitido caracterizar geneticamente as ataxias cerebelares hereditárias. O reconhecimento das doenças causadas por expansões de trinucleotídeos abre novo capítulo para a pesquisa sobre outros mecanismos de doenças, como na ataxia de Friedreich e nas várias formas de ataxia cerebelar autossômica dominante(SCAl a SCA7, das quais a doença de Machado-Joseph / SCA3 parece ser a mais comum no nosso meio. A deficiência familial de vitamina E (cromossomo 8q leva a quadro semelhante ao da ataxia de Friedreich (cromossomo 9p, mas responde à reposição oral de tocoferol. Formas familiais de ataxia periódica com (cromossomo 12p ou sem (cromossomo 19p mioquimia foram caracterizadas, a primeira resultado de mutações dos gens de canais de potássio. Os portadores do gen da ataxia-teleangiectasia (cromossomo 1 lq representam 1-3% da população e são suscetíveis aos efeitos oncogênicos da radiação iônica. Sem olvidar da importância da avaliação clínica neurológica, a avaliação genética laboratorial passa a ser valiosa ferramenta para o diagnóstico e aconselhamento genético, além do melhor entendimento da patogênese dessas doenças.The hereditary ataxias comprise a complex group of neurological disorders involving the cerebellum and its connections. Several classifications based on clinical and/or pathological data have been only partially successful. Recent progress in molecular genetics has identified the genic loci of hereditary ataxias and has allowed a more precise diagnosis of distinct genetic diseases. Trinucleotide repeat expansions has been recognized as a mechanism of disease in some autosomal dominant spinocerebellar ataxias (ADCA

  15. Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients.

    Science.gov (United States)

    Voghel, Guillaume; Thorin-Trescases, Nathalie; Farhat, Nada; Mamarbachi, Aida M; Villeneuve, Louis; Fortier, Annik; Perrault, Louis P; Carrier, Michel; Thorin, Eric

    2008-05-01

    Endothelial senescence may contribute to the pathogenesis of age-related vascular disorders. Furthermore, chronic exposure to risk factors for cardiovascular disease (CVD) accelerates the effects of chronological aging by generating stress-dependent damages, including oxidative stress, therefore promoting stress-induced premature senescence. Our objective was to determine whether a chronic treatment with an antioxidant (N-acetyl-cystein, NAC) could delay senescence of endothelial cells (EC) isolated and cultured from arterial segments of patients with severe coronary artery disease. If EC were considered as one population (n=26), chronic NAC treatment slightly shortened telomere attrition rate associated with senescence but did not significantly delay the onset of endothelial senescence. However, in a subgroup of NAC-treated EC (n=15) cellular senescence was significantly delayed, NAC decreased lipid peroxidation (HNE), activated the catalytic subunit of telomerase (hTERT) and inhibited telomere attrition. In contrast, in another subgroup of EC (n=11) characterized by initial short telomeres, no effect of NAC on HNE and high levels of DNA damages, the antioxidant was not beneficial on senescence, suggesting an irreversible stress-dependent damage. In conclusion, chronic exposure to NAC can delay senescence of diseased EC via hTERT activation and transient telomere stabilization, unless oxidative stress-associated cell damage has become irreversible.

  16. Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

    Science.gov (United States)

    Feurecker, M.; Mayer, W.; Gruber, M.; Muckenthaler, F.; Draenert, R.; Bogner, J.; Kaufmann, I.; Crucian, B.; Rykova, M.; Morukov, B.; Sams, C.; Chouker, A.

    2010-01-01

    Goal:i) Characterization of the role of the main immune reactive cell types contributing to the cellular immune response in the in-vitro DTH and ii) Validation of the in-vitro DTH under different clinical and field conditions. Methods:As positive control whole blood was incubated in the in-vitro DTH, supernatants were gathered after 12, 24 and 48h. Readout parameters of this test are cytokines in the assay's supernatant. To determine the role of T-cells, monocytes and natural killer (NK), these cell populations were depleted using magnetic beads prior to in-vitro-DTH incubation. Validation of the test has occurred under clinical (HIV-patients, ICU) and field-conditions (parabolic/space-flights, confinement). Results:T-cell depletion abandoned almost any IL-2 production and reduced IFN-gamma production irrespective of the type of antigen, whereas CD56 depleted cultures tended to lower IL-2 secretion and IFN-gamma and to parallel a IL-10-increase after viral challenge. This IL-10-increase was seen also in CD14-depleted setups. DTH read-out was significantly different under acute stress (parabolic flight) or chronic stress (ISS), respectively. Preliminary data of HIV infected patients demonstrate that this test can display the contemporary immune status during an antiviral therapy. Conclusion:The in-vitro DTH mirrors adaptive and innate immune activation and may serve as tool also for longitudinal follow up of Th1/Th2 weighed immune response under adverse life conditions on earth and in space. It is planned to implement the assay in the on the ISS (MoCISS).

  17. 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

    was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.

  18. Ataxia crónica en pediatría

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    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.

  19. Genetics Home Reference: autosomal recessive spastic ataxia of Charlevoix-Saguenay

    Science.gov (United States)

    ... Genetics Home Health Conditions ARSACS autosomal recessive spastic ataxia of Charlevoix-Saguenay Enable Javascript to view the ... Open All Close All Description Autosomal recessive spastic ataxia of Charlevoix-Saguenay , more commonly known as ARSACS , ...

  20. New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease)

    NARCIS (Netherlands)

    Rueb, Udo; Brunt, Ewout R.; Deller, Thomas

    2008-01-01

    Purpose of review This review summarizes recent neuropathological findings in spinocerebellar ataxia type 3 and discusses their relevance for clinical neurology. Recent findings The extent of the spinocerebellar ataxia type 3 related central nervous neurodegenerative changes has been recently system

  1. 2 SISTERS WITH MENTAL-RETARDATION, CATARACT, ATAXIA, PROGRESSIVE HEARING-LOSS, AND POLYNEUROPATHY

    NARCIS (Netherlands)

    BEGEER, JH; SCHOLTE, FA; VANESSEN, AJ

    1991-01-01

    Two sisters are described with a disorder characterised by mental retardation, congenital cataract, progressive spinocerebellar ataxia, sensorineural deafness, and signs of peripheral neuropathy. Progressive hearing loss, ataxia, and polyneuropathy became evident in the third decade. The differentia

  2. Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity with no epileptic attacks in two family members.

    Science.gov (United States)

    Kaido, Misako; Furuta, Mitsuru; Nakamori, Masayuki; Yuasa, Yoshihito; Takahashi, Masanori P

    2016-04-28

    Here, we report two cases of episodic ataxia type 2 (EA2) in a 63-year-old woman and her 36-year-old daughter. The mother experienced recurrent attacks of cerebellar dysfunction lasting 4 to 5 hours since the age of 41 years. On several occasions, she was admitted to the emergency room, where she was diagnosed with epilepsy or stroke. Based on these diagnoses, she was treated with antiepileptic or anticoagulant drugs, but both treatments were eventually discontinued. The frequency of the attacks increased after the patient reached the age of 62. Interictal neurological examination demonstrated signs of slight cerebellar ataxia, i.e. saccadic eye movements, gaze-directed nystagmus, and mild truncal ataxia. Brain magnetic resonance imaging (MRI) showed cerebellar vermis atrophy. Electroencephalography (EEG) revealed various spike and wave patterns: solitary spikes, spike-and-slow wave complexes, and slow wave bursts. Photoparoxysmal response (PPR) type 3 was also observed. Treatment with acetazolamide abolished the patient's attacks almost completely. The daughter started experiencing 5- to 10-minute ataxic episodes at the age of 16 years. Based on her epileptiform EEG activities with PPR (type 2), antiepileptic drugs (valproate and zonisamide) were prescribed. Despite pharmacological treatment, the attacks recurred; however, their frequency gradually decreased with time, until they almost entirely disappeared when the patient was 33. Unfortunately, migraine-like headaches arose instead. Subtle truncal ataxia was observed during interictal periods. Sanger sequencing of the exons of the CACNA1A gene revealed a novel single base deletion (c.3575delA) in both patients. Despite the difference in age of onset and clinical course, both patients showed clearly epileptiform EEG activities without experiencing the concurrent epileptic episodes. Thus, EA2 is a disease that may be misdiagnosed as epilepsy or stroke in the field of emergency medicine.

  3. 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.

  4. Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3

    DEFF Research Database (Denmark)

    Hansen, Susanne K; Stummann, Tina C; Borland, Helena;

    2016-01-01

    The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method...... displaying synchronized spontaneous calcium oscillations within 28days of maturation, and expressed the mature neuronal markers NeuN and Synapsin 1 implying a relatively advanced state of maturity, although not comparable to that of the adult human brain. Interestingly, we were not able to recapitulate...

  5. Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy.

    Science.gov (United States)

    Kikuchi, Akio; Takeda, Atsushi; Sugeno, Naoto; Miura, Emiko; Kato, Kazuhiro; Hasegawa, Takafumi; Baba, Toru; Konno, Masatoshi; Oshima, Ryuji; Watanuki, Shoichi; Hiraoka, Kotaro; Tashiro, Manabu; Aoki, Masashi

    2016-01-01

    We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.

  6. Sensory ataxia as a prominent clinical presentation in three families with mutations in CYP7B1.

    Science.gov (United States)

    Di Fabio, Roberto; Marcotulli, Christian; Tessa, Alessandra; Leonardi, Luca; Storti, Eugenia; Pierelli, Francesco; Santorelli, Filippo M; Casali, Carlo

    2014-04-01

    Pathogenic mutations in CYP7B1 account for SPG5, an autosomal recessive hereditary spastic paraplegia characterized by a complex phenotype including visual problems and cerebellar dysfunction. Sensory ataxia is not usually regarded as a typical clinical feature of SPG5. The purpose of this study was to describe six patients showing features of sensory ataxia as the prominent and/or initial symptoms of SPG5. Six patients from three distinct pedigrees (three women, three men; age 49.5 ± 18.2 years), all presenting gait unsteadiness and frequent falls since childhood, underwent clinical and molecular investigations. All showed marked sensory ataxic gait with positive Romberg's sign, as well as severely impaired position and vibration sense. Comparatively minor signs of pyramidal involvement were also detected. In four of the patients, brain MRI showed white matter hyperintensities on T2-weighted images. An already reported homozygous c.889A>G (p.T297A) mutation in SPG5/CYP7B1 was found in five patients from two families, whereas the remaining case harbored the novel c.250_251delC/p.L84Ffs*6 and c.266A>C/p.Y89S variants. Marked and enduring sensory ataxia can be a pivotal sign in SPG5, and expands the phenotypic spectrum associated with mutations in CYP7B1.

  7. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  8. Presentation and progression of Friedreich ataxia and implications for physical therapist examination.

    Science.gov (United States)

    Maring, Joyce R; Croarkin, Earllaine

    2007-12-01

    Friedreich ataxia, although rare, is the most prevalent inherited ataxia. Recent insight into the disease pathogenesis is creating new hope for effective therapies. The purposes of this update are: (1) to review the etiology, presentation, and progression of Friedreich ataxia and (2) to describe a comprehensive physical therapist examination emphasizing valid and reliable performance measurements associated with disease progression. Early identification of individuals with Friedreich ataxia and precise characterization of impairments and functional limitations gain importance as new drug therapies are considered.

  9. ELOVL5 Mutations Cause Spinocerebellar Ataxia 38

    Science.gov (United States)

    Di Gregorio, Eleonora; Borroni, Barbara; Giorgio, Elisa; Lacerenza, Daniela; Ferrero, Marta; Lo Buono, Nicola; Ragusa, Neftj; Mancini, Cecilia; Gaussen, Marion; Calcia, Alessandro; Mitro, Nico; Hoxha, Eriola; Mura, Isabella; Coviello, Domenico A.; Moon, Young-Ah; Tesson, Christelle; Vaula, Giovanna; Couarch, Philippe; Orsi, Laura; Duregon, Eleonora; Papotti, Mauro Giulio; Deleuze, Jean-François; Imbert, Jean; Costanzi, Chiara; Padovani, Alessandro; Giunti, Paola; Maillet-Vioud, Marcel; Durr, Alexandra; Brice, Alexis; Tempia, Filippo; Funaro, Ada; Boccone, Loredana; Caruso, Donatella; Stevanin, Giovanni; Brusco, Alfredo

    2014-01-01

    Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases. PMID:25065913

  10. The pathogenesis of cardiomyopathy in Friedreich ataxia.

    Directory of Open Access Journals (Sweden)

    Arnulf H Koeppen

    Full Text Available Friedreich ataxia (FA is an autosomal recessive disease with a complex neurological phenotype, but the most common cause of death is heart failure. This study presents a systematic analysis of 15 fixed and 13 frozen archival autopsy tissues of FA hearts and 10 normal controls (8 frozen by measurement of cardiomyocyte hypertrophy; tissue frataxin assay; X-ray fluorescence (XRF of iron (Fe and zinc (Zn in polyethylene glycol-embedded samples of left and right ventricular walls (LVW, RVW and ventricular septum (VS; metal quantification in bulk digests by inductively-coupled plasma optical emission spectrometry (ICP-OES; Fe histochemistry; and immunohistochemistry and immunofluorescence of cytosolic and mitochondrial ferritins and of the inflammatory markers CD68 and hepcidin. FA cardiomyocytes were significantly larger than normal and surrounded by fibrotic endomysium. Frataxin in LVW was reduced to less than 15 ng/g wet weight (normal 235.4 ± 75.1 ng/g. All sections displayed characteristic Fe-reactive inclusions in cardiomyocytes, and XRF confirmed significant regional Fe accumulation in LVW and VS. In contrast, ICP-OES analysis of bulk extracts revealed normal total Fe levels in LVW, RVW, and VS. Cardiac Zn remained normal by XRF and assay of bulk digests. Cytosolic and mitochondrial ferritins exhibited extensive co-localization in cardiomyocytes, representing translational and transcriptional responses to Fe, respectively. Fe accumulation progressed from a few small granules to coarse aggregates in phagocytized cardiomyocytes. All cases met the "Dallas criteria" of myocarditis. Inflammatory cells contained CD68 and cytosolic ferritin, and most also expressed the Fe-regulatory hormone hepcidin. Inflammation is an important factor in the pathogenesis of FA cardiomyopathy but may be more evident in advanced stages of the disease. Hepcidin-induced failure of Fe export from macrophages is a likely contributory cause of damage to the heart in FA

  11. Is Friedreich ataxia an epigenetic disorder?

    Directory of Open Access Journals (Sweden)

    Kumari Daman

    2012-01-01

    Full Text Available Abstract Friedreich ataxia (FRDA is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit is the triplet GAA•TTC and the tandem array is located in the first intron of the frataxin (FXN gene. Pathology arises because expanded alleles make lower than normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN gene product. The repeats form a variety of unusual DNA structures that have the potential to affect gene expression in a number of ways. For example, triplex formation in vitro and in bacteria leads to the formation of persistent RNA:DNA hybrids that block transcription. In addition, these repeats have been shown to affect splicing in model systems. More recently, it has been shown that the region flanking the repeats in the FXN gene is enriched for epigenetic marks characteristic of transcriptionally repressed regions of the genome. However, exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the subject of much debate. Identifying the mechanism or mechanisms responsible for the FXN mRNA deficit in FRDA is important for the development of treatments for this currently incurable disorder. This review discusses evidence for and against different models for the repeat-mediated mRNA deficit.

  12. ELOVL5 mutations cause spinocerebellar ataxia 38.

    Science.gov (United States)

    Di Gregorio, Eleonora; Borroni, Barbara; Giorgio, Elisa; Lacerenza, Daniela; Ferrero, Marta; Lo Buono, Nicola; Ragusa, Neftj; Mancini, Cecilia; Gaussen, Marion; Calcia, Alessandro; Mitro, Nico; Hoxha, Eriola; Mura, Isabella; Coviello, Domenico A; Moon, Young-Ah; Tesson, Christelle; Vaula, Giovanna; Couarch, Philippe; Orsi, Laura; Duregon, Eleonora; Papotti, Mauro Giulio; Deleuze, Jean-François; Imbert, Jean; Costanzi, Chiara; Padovani, Alessandro; Giunti, Paola; Maillet-Vioud, Marcel; Durr, Alexandra; Brice, Alexis; Tempia, Filippo; Funaro, Ada; Boccone, Loredana; Caruso, Donatella; Stevanin, Giovanni; Brusco, Alfredo

    2014-08-07

    Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases.

  13. The spinocerebellar ataxias: clinical aspects and molecular genetics.

    Science.gov (United States)

    Matilla-Dueñas, Antoni; Corral-Juan, Marc; Volpini, Victor; Sanchez, Ivelisse

    2012-01-01

    Spinocerebellar ataxias (SCAs) are a highly heterogeneous group of inherited neurological disorders, based on clinical characterization alone with variable degrees of cerebellar ataxia often accompanied by additional cerebellar and noncerebellar symptoms which in most cases defy differentiation. Molecular causative deficits in at least 31 genes underlie the clinical symptoms in the SCAs by triggering cerebellar and, very frequently, brain stem dysfunction. The identification of the causative molecular deficits enables the molecular diagnosis of the different SCA subtypes and facilitates genetic counselling. Recent scientific advances are shedding light into developing therapeutic strategies. The scope of this chapter is to provide updated details of the spinocerebellar ataxias with particular emphasis on those aspects aimed at facilitating the clinical and genetic diagnoses.

  14. Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian population

    Institute of Scientific and Technical Information of China (English)

    HAN Yan; YU Long; ZHENG Hui-min; GUAN Yang-tai

    2010-01-01

    Background Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years.However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people.The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population.Methods A search for publications on SCA7 was performed by using the "PubMed" database with the published language limited in English.Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed.Results The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously.The clinical manifestations were typically present at the 30's of its victims (median, 29 years; interquartile range (IQR),19.5-36.5 years), and the symptoms appeared 15 years ((15.17±4.22) years) earlier on average in the offspring than in the parents.Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described.Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and the offspring had 13 more repeats on average compared with their parents (12.62±19.03).A strong negative correlation was found between CAG repeat size and the onset age of patients (r=-0.739, P=0.000).In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom (P=0.476).Conclusions The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people.However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms

  15. Early onset cerebellar ataxia with retained tendon reflexes : foot deformity in a first grade family member

    NARCIS (Netherlands)

    Schelhaas, HJ; Van der Hulst, M; Ippel, E; Prevo, RL; Hageman, G

    1999-01-01

    Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich's ataxia (FA) mainly by the preservation o

  16. Large Genomic Deletions in CACNA1A Cause Episodic Ataxia Type 2

    Directory of Open Access Journals (Sweden)

    Jijun eWan

    2011-09-01

    Full Text Available Episodic ataxia (EA syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. Episodic ataxia type 2 (EA2, the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4-40kb in EA2. In 47 subjects with EA (26 with EA2-like features who tested negative for mutations in the known EA genes, we used Multiplex Ligation-dependent Probe Amplification (MLPA to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2.

  17. Cerebellar ataxia as the presenting manifestation of Lyme disease.

    Science.gov (United States)

    Arav-Boger, Ravit; Crawford, Thomas; Steere, Allen C; Halsey, Neal A

    2002-04-01

    A 7-year-old boy from suburban Baltimore who presented with cerebellar ataxia and headaches was found by magnetic resonance imaging to have multiple cerebellar enhancing lesions. He had no history of tick exposure. He was initially treated with steroids for presumptive postinfectious encephalitis. Lyme disease was diagnosed 10 weeks later after arthritis developed. Testing of the cerebrospinal fluid obtained at the time cerebellar ataxia was diagnosed revealed intrathecal antibody production to Borrelia burgdorferi. Treatment with intravenous antibiotics led to rapid resolution of persistent cerebellar findings.

  18. Episodic ataxia : a case report and review of literature.

    Directory of Open Access Journals (Sweden)

    Singhvi J

    2000-01-01

    Full Text Available This report describes the clinical features of a 29 year female presenting with a 3 years history of episodes of cerebellar ataxia, dysarthria and nystagmus lasting 3-5 days, recurring almost every month. Sleep disturbance and buzzing in ears were noted 3-4 days before each episode. No other precipitant factor was present. Family history was negative. She was diagnosed as a case of episodic ataxia type-2 and was successfully treated with acetazolamide, a carbonic anhydrase inhibitor. She was asymptomatic at 2 year followup.

  19. Autosomal recessive ataxias: 20 types, and counting Ataxias autossômicas recessivas: 20 tipos e muito mais

    Directory of Open Access Journals (Sweden)

    Emília Katiane Embiruçu

    2009-12-01

    Full Text Available More than 140 years after the first description of Friedreich ataxia, autosomal recessive ataxias have become one of the more complex fields in Neurogenetics. Currently this group of diseases contains more than 20 clinical entities and an even larger number of associated genes. Some disorders are very rare, restricted to isolated populations, and others are found worldwide. An expressive number of recessive ataxias are treatable, and responsibility for an accurate diagnosis is high. The purpose of this review is to update the practitioner on clinical and pathophysiological aspects of these disorders and to present an algorithm to guide the diagnosis.Mais de 140 anos após a primeira descrição da ataxia de Friedreich, as ataxias autossômicas recessivas se transformaram em um dos mais complexos campos da Neurogenética. Atualmente, este grupo de doenças é composto por mais de 20 entidades clínicas e possui um número ainda maior de genes associados. Algumas doenças são muito raras, tendo sido observadas apenas em populações isoladas, enquanto que outras são encontradas no mundo todo. Um número expressivo de ataxias é tratável, e a responsabilidade em se fazer um diagnóstico correto é alta. A finalidade desta revisão é a de atualizar o neurologista a respeito dos principais aspectos clínicos e fisiopatológicos destas doenças e de apresentar um algoritmo para auxiliar a sua investigação e o seu diagnóstico.

  20. Effect of triamcinolone acetonide ammonia bromine joint hydrochloric acid on patients with secretory otitis media and on body's inflammatory factor and cellular immunologic parameters

    Institute of Scientific and Technical Information of China (English)

    Quan-Fu Hu; Shao-Ji Ouyang; Rong-Wei Yao; Xue-Jiang Xu; Jin-Hua He; Li-Li Zhang

    2016-01-01

    Objective:To explore the clinical effect of triamcinolone acetonide ammonia bromine joint hydrochloric acid on patients with secretory otitis media and the influences on the body's inflammatory factors and cellular immunologic parameters.Methods:A total of 40 cases of single ear secretory otitis media patients of the same period in our hospital were randomly selected as experimental group, using triamcinolone acetonide ammonia bromine joint hydrochloric acid treatment; And 40 cases of single ear secretory otitis media patients of the same period were randomly selected as control group, using dexamethasone treatment. To observe the clinical efficacy of two groups of patients and detect the inflammatory factors and cellular immune index level of the two groups of patients before and after treatment.Results:The total effective rate(90%) of treatment group is significantly higher than that (80%) of control group (P0.05). After treatment, the serum and ear effusion inflammatory cytokines levels of the two groups were significantly lower than that before treatment (P0.05); The CD4+/CD8+ levels of experimental group were significantly higher than the control group (P0.05). Conclusions: The triamcinolone acetonide ammonia bromine joint hydrochloric acid treatment is more conducive to improve the immune function of the secretory otitis media patients and treatment effect, which has important clinical significance on the treatment of secretory otitis media patients.

  1. A practical approach to late-onset cerebellar ataxia: putting the disorder with lack of order into order.

    NARCIS (Netherlands)

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

    2012-01-01

    The clinical management of cerebellar ataxia is challenging, mainly because ataxia is a symptom of many neurological diseases. Many types of ataxia disorders are genetic and some are extremely rare. Here, the authors suggest a diagnostic approach to ataxia developed around a case of sporadic, late-o

  2. Republished: A practical approach to late-onset cerebellar ataxia: putting the disorder with lack of order into order.

    NARCIS (Netherlands)

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

    2012-01-01

    The clinical management of cerebellar ataxia is challenging, mainly because ataxia is a symptom of many neurological diseases. Many types of ataxia disorders are genetic and some are extremely rare. Here, the authors suggest a diagnostic approach to ataxia developed around a case of sporadic, late-o

  3. Clinical Characteristics, Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias

    Institute of Scientific and Technical Information of China (English)

    Jian-Wen Chen; Li Zhao; Feng Zhang; Lan Li; Yu-Hang Gu; Jing-Yuan Zhou; Hui Zhang

    2015-01-01

    Background:Spinocerebellar ataxias (SCAs) are a group ofneurodegenerative disorders that primarily cause the degeneration in the cerebellum,spinal cord,and brainstem.We study the clinical characteristics,radiological features and gene mutation in Chinese families with SCAs.Methods:In this study,we investigated 10 SCAs Chinese families with SCA1,SCA3/Machado-Joseph disease (MJD),SCA7,SCAB.There were 27 people who were genetically diagnosed as SCA,of which 21 people showed clinical symptoms,and 6 people had no clinical phenotype that we called them presymptomatic patients.In addition,3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing.Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.Results:We found that SCA3/MJD was the most common subtype in Han population in China,and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats;the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score;and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.Conclusions:Collectively our study is a systematic research on SCAs in China,which may help for the clinical diagnosis and prenatal screening of this disease,and it may also aid toward better understanding of this disease.

  4. Neuronal nicotinic receptor agonists improve gait and balance in olivocerebellar ataxia.

    Science.gov (United States)

    Wecker, L; Engberg, M E; Philpot, R M; Lambert, C S; Kang, C W; Antilla, J C; Bickford, P C; Hudson, C E; Zesiewicz, T A; Rowell, Peter P

    2013-10-01

    Clinical studies have reported that the nicotinic receptor agonist varenicline improves balance and coordination in patients with several types of ataxia, but confirmation in an animal model has not been demonstrated. This study investigated whether varenicline and nicotine could attenuate the ataxia induced in rats following destruction of the olivocerebellar pathway by the neurotoxin 3-acetylpyridine (3-AP). The administration of 3-AP (70 mg/kg followed by 300 mg niacinamide/kg; i.p.) led to an 85% loss of inferior olivary neurons within one week without evidence of recovery, and was accompanied by a 72% decrease in rotorod activity, a 3-fold increase in the time to traverse a stationary beam, a 19% decrease in velocity and 31% decrease in distance moved in the open field, and alterations in gait parameters, with a 19% increase in hindpaw stride width. The daily administration of nicotine (0.33 mg free base/kg) for one week improved rotorod performance by 50% and normalized the increased hindpaw stride width, effects that were prevented by the daily preadministration of the nicotinic antagonist mecamylamine (0.8 mg free base/kg). Varenicline (1 and 3 mg free base/kg daily) also improved rotorod performance by approximately 50% following one week of administration, and although it did not alter the time to traverse the beam, it did improve the ability to maintain balance on the beam. Neither varenicline nor nicotine, at doses that improved balance, affected impaired locomotor activity in the open field. Results provide evidence that nicotinic agonists are of benefit for alleviating some of the behavioral deficits in olivocerebellar ataxia and warrant further studies to elucidate the specific mechanism(s) involved.

  5. Genetic linkage studies in autosomal dominant ataxia families with an MJD phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, I.; Lopes-Cendes, I.; Paciel, P. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration which was originally described in patients originating from the Portuguese islands of the Azores. The first non-Portuguese kindred was described in 1979 and was an American black family originating from North Carolina. Since then the number of pedigrees of non-Azorean, non-Portuguese origin has increased with families being reported from other European countries, as well as Brazil, Japan, India, The United States and Australia. The autosomal dominant ataxias are a clinically and genetically heterogeneous group of disorders. To date, genetic analysis of families with autosomal dominant ataxias has permitted the identification of four loci, the SCA1 (spinocerebellar ataxia type 1) locus on chromosome 6p, the SCA2 locus on chromosome 12q, a third locus on chromosome 14q, the MJD/SCA3 and, more recently, the DRPLA (Dentatorubral-pallidoluysian atrophy) locus on chromosome 12p. We ascertained a total of 181 individuals with 60 affected from eight Indian, two Brazilian and one Sicilian-American family; all of them have received the clinical diagnosis of MJD. Recently, we have begun molecular genetic studies in these families in order to test these four candidate regions. The SCA1 mutation and the DRPLA mutation has been found to be an expansion of a CAG repeat. Direct analysis of the SCA1 and DRPLA expansion has been performed in all families and no expansion was found in the affected individuals. We are now running flanking markers for the SCA2 and MJD/SCA3 loci. These results will also be presented.

  6. Acute cerebellar ataxia in a young woman: Wernicke’s encephalopathy?

    Directory of Open Access Journals (Sweden)

    S. G. Dolgova

    2015-01-01

    Full Text Available Wernicke’s encephalopathy (WE is a rare but severe neurological syndrome caused by thiamine deficiency. According to the data of autopsy studies, the prevalence of WE in the general population varies from 0.4 to 2.8 per 100,000 population; the disease occurs many times more frequently in alcohol abusers than in people who lead a healthy lifestyle. These studies also showed that most cases of WE were diagnosed postmortem; less than 20% of patients with the disease were diagnosed in life. A healthy adult requires 1–2 mg of thiamine daily, depending on the carbohydrate intake. Body’s reserves of thiamine are only 30–50 mg so any malnutrition condition lasting more than 3–4 weeks can cause complete depletion of the vitamin’s stores. Classically, WE is characterized by the sudden onset of a typical triad of symptoms: an altered mental state, ophthalmoplegia, and ataxia. However, this clinical picture can be seen in only one-third of patients. The onset of the disease may sometimes look completely different: heart failure with hypotension and tachycardia; gastrointestinal symptoms (abdominal pain and nausea; hypothermia due to the involvement of the posterior hypothalamus; deafness affecting the thalamus; epileptic seizures in case of enhanced activity of the glutamatergic system.The paper describes a clinical case of acute cerebellar ataxia that is apparently caused by Wernicke’s encephalopathy in a young woman.

  7. Clinical and genetic study of a Chinese family with spinocerebellar ataxia type 7

    Directory of Open Access Journals (Sweden)

    Han Yan

    2010-01-01

    Full Text Available Spinocerebellar ataxia 7 (SCA7 is a rare disease, and only few SCA7 families have been reported, especially from East Asia. Clinical features of a genetically confirmed SCA7 Chinese family were evaluated. The onset of the disease varied from 4 years to 48 years, and the initial presenting feature was cerebellar ataxia or visual impairment, or both. There were abnormal findings on fundus photography, electroretinogram, flash visual evoked potential and oscillatory potentials. Abnormal mitochondria were also found in skeletal muscle or liver biopsies. The number of cytosine adenine guanine (CAG repeats ranged from 50 to 97, and the length of CAG repeat was inversely correlated with the age of onset (r=-0.867, P=0.025. Conclusion: The clinical manifestations and SCA7 gene of SCA7 patients were homogeneous in this study. Larger CAG repeats had not only resulted in earlier onset, but also related to the rapid progression and severity of the disease. Abnormal mitochondria may be a common finding in biopsy studies of various organs in SCA7 patients.

  8. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

    Science.gov (United States)

    ... but almost always with less severity. Most affected women have some degree of tremor and/or ataxia. While the psychiatric and mood disorders are also less frequent in females, they are at higher risk for anxiety and depression in general. Additional symptoms affecting some ...

  9. Speech Characteristics Associated with Three Genotypes of Ataxia

    Science.gov (United States)

    Sidtis, John J.; Ahn, Ji Sook; Gomez, Christopher; Sidtis, Diana

    2011-01-01

    Purpose: Advances in neurobiology are providing new opportunities to investigate the neurological systems underlying motor speech control. This study explores the perceptual characteristics of the speech of three genotypes of spino-cerebellar ataxia (SCA) as manifest in four different speech tasks. Methods: Speech samples from 26 speakers with SCA…

  10. Speech Perception Ability in Individuals with Friedreich Ataxia

    Science.gov (United States)

    Rance, Gary; Fava, Rosanne; Baldock, Heath; Chong, April; Barker, Elizabeth; Corben, Louise; Delatycki

    2008-01-01

    The aim of this study was to investigate auditory pathway function and speech perception ability in individuals with Friedreich ataxia (FRDA). Ten subjects confirmed by genetic testing as being homozygous for a GAA expansion in intron 1 of the FXN gene were included. While each of the subjects demonstrated normal, or near normal sound detection, 3…

  11. Protein-protein interaction networks in the spinocerebellar ataxias

    OpenAIRE

    David C Rubinsztein

    2006-01-01

    A large yeast two-hybrid study investigating whether the proteins mutated in different forms of spinocerebellar ataxia have interacting protein partners in common suggests that some forms do share common pathways, and will provide a valuable resource for future work on these diseases.

  12. 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.

  13. Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy.

    Science.gov (United States)

    Pena, S D J; Coimbra, R L M

    2015-02-01

    We have recently performed exome analysis in a 7 year boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy. Parents were not consanguineous and there was no family history of the disease. Exome analysis did not show any pathogenic variants in genes known to be associated with seizures and/or ataxia in children, including all known human channelopathies. However, we have identified a mutation in KCNA2 that we believe to be responsible for the disease in our patient. This gene, which encodes a member of the potassium channel, voltage-gated, shaker-related subfamily, has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions. The mutation is c.890C>A, leading to the amino acid substitution p.Arg297Gln, which involves the second of the critical arginines in the S4 voltage sensor. This mutation is characterized as pathogenic by five different prediction programs. RFLP analysis and Sanger sequencing confirmed the presence of the mutation in the patient, but not in his parents, characterizing it as de novo. We believe that this discovery characterizes a new channelopathy.

  14. Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations.

    Science.gov (United States)

    Nascimento, Fábio A; Andrade, Danielle M

    2016-09-01

    Progressive myoclonus epilepsy (PME) is a distinct group of seizure disorders characterized by gradual neurological decline with ataxia, myoclonus and recurring seizures. There are several forms of PME, among which the most recently described is MEAK - myoclonus epilepsy and ataxia due to potassium channel mutation. This particular subtype is caused by a recurrent de novo heterozygous mutation (c.959G>A, p.Arg320His) in the KCNC1 gene, which maps to chromosome 11 and encodes for the Kv3.1 protein (a subunit of the Kv3 subfamily of voltage-gated potassium channels). Loss of Kv3 function disrupts the firing properties of fast-spiking neurons, affects neurotransmitter release and induces cell death. Specifically regarding Kv3.1 malfunctioning, the most affected neurons include inhibitory GABAergic interneurons and cerebellar neurons. Impairment of the former cells is believed to contribute to myoclonus and seizures, whereas dysfunction of the latter to ataxia and tremor. Phenotypically, MEAK patients generally have a normal early development. At the age of 6 to 14 years, they present with myoclonus, which tends to progressively worsen with time. Tonic-clonic seizures may or may not be present, and some patients develop mild cognitive impairment following seizure onset. Typical electroencephalographic features comprise generalized epileptiform discharges and, in some cases, photosensitivity. Brain imaging is either normal or shows cerebellar atrophy. The identification of MEAK has both expanded the phenotypic and genotypic spectra of PME and established an emerging role for de novo mutations in PME.

  15. Molecular and clinical correlations in spinocerebellar ataxia type I: Evidence for familial effects on the age at onset

    Energy Technology Data Exchange (ETDEWEB)

    Ranum, L.P.W.; Chung, M.; Schut, L.J.; Duvick, L.A. (Univ. of Minnesota, Minneapolis, MN (United States)); Banfi, S.; McCall, A. (Baylor College of Medicine, Houston, TX (United States)); Bryer, A.; Ramesar, R.; Subramony, S.H.; Goldfarb, L. (and others)

    1994-08-01

    The spinocerebellar ataxias are a group of debilitating neurodegenerative diseases for which a clinical classification system has proved unreliable. The authors have recently isolated the gene for spinocerebellar ataxia type 1 (SCA1) and have shown that the disease is caused by an expanded, unstable, CAG trinucleotide repeat within an expressed gene. Normal alleles have a size range of 19-36 repeats, while SCA1 alleles have 42-81 repeats. In this study, they examined the frequency and variability of the SCA1 repeat expansion in 87 kindreds with diverse ethnic backgrounds and dominantly inherited ataxia. All nine families for which linkage to the SCA1 region of 6p had previously been established showed repeat expansion, while 3 of the remaining 78 showed a similar abnormality. For 113 patients from the families with repeat expansion, inverse correlations between CAG repeat size and both age at onset and disease duration were observed. Repeat size accounted for 66% of the variation in age at onset in these patients. After correction for repeat size, interfamilial differences in age at onset remained significant, suggesting that additional genetic factors affect the expression of the SCA1 gene product. 48 refs., 4 figs.

  16. Cell death, chromosome damage and mitotic delay in normal human, ataxia telangiectasia and retinoblastoma fibroblasts after x-irradiation.

    Science.gov (United States)

    Zampetti-Bosseler, F; Scott, D

    1981-05-01

    We recently showed (Scott and Zampetti-Bosseler 1980) that X-ray sensitive mouse lymphoma cells sustain more chromosome damage, mitotic delay and spindle defects than X-ray resistant cells. We proposed that (a) chromosome aberrations contribute much more to lethality than spindle defects, and (b) that DNA lesions are less effectively repaired in the sensitive cells and give rise to more G2 mitotic delay and chromosome aberrations. Our present results on human fibroblasts with reported differential sensitivity to ionizing radiation (i.e. normal donors and patients with ataxia telangiectasia and retinoblastoma) support the first hypothesis since we observed a positive correlation between chromosome aberration frequencies and cell killing and no induced spindle defects. Our second hypothesis is however not substantiated since X-ray sensitive fibroblasts from the ataxia patient suffered less mitotic delay than cells from normal donors. A common lesion for mitotic delay and chromosome aberrations can still be assumed by adopting the hypothesis of Painter and Young (1981) that the defect in ataxia cells is not in repair but in a failure of DNA damage to initiate mitotic delay. In contrast to other reports, we found the retinoblastoma cells to be of normal radiation sensitivity (cell killing and aberration).

  17. Ocular-motor profile and effects of memantine in a familial form of adult cerebellar ataxia with slow saccades and square wave saccadic intrusions.

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    Francesca Rosini

    Full Text Available Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI and macrosaccadic oscillations (MSO. A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI. We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°-18° and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly, but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich's, in which saccadic intrusions are prominent.

  18. A voxel-based morphometry study of grey matter loss in fragile X-associated tremor/ataxia syndrome.

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    Hashimoto, Ryu-ichiro; Javan, Alireza K; Tassone, Flora; Hagerman, Randi J; Rivera, Susan M

    2011-03-01

    Fragile X-associated tremor/ataxia syndrome is a neurodegenerative disorder that primarily affects older male premutation carriers of the fragile X mental retardation gene. Although its core symptoms are mainly characterized by motor problems such as intention tremor and gait ataxia, cognitive decline and psychiatric problems are also commonly observed. Past radiological and histological approaches have focused on prominent neurodegenerative changes in specific brain structures including the cerebellum and limbic areas. However, quantitative investigations of the regional structural abnormalities have not been performed over the whole brain. In this study, we adopted the voxel-based morphometry method together with regions of interest analysis for the cerebellum to examine the pattern of regional grey matter change in the male premutation carriers with and without fragile X-associated tremor/ataxia syndrome. In a comparison with healthy controls, we found striking grey matter loss of the patients with fragile X-associated tremor/ataxia syndrome in multiple regions over the cortical and subcortical structures. In the cerebellum, the anterior lobe and the superior posterior lobe were profoundly reduced in both vermis and hemispheres. In the cerebral cortex, clusters of highly significant grey matter reduction were found in the extended areas in the medial surface of the brain, including the dorsomedial prefrontal cortex, anterior cingulate cortex and precuneus. The other prominent grey matter loss was found in the lateral prefrontal cortex, orbitofrontal cortex, amygdala and insula. Although the voxel-wise comparison between the asymptomatic premutation group and healthy controls did not reach significant difference, a regions of interest analysis revealed significant grey matter reduction in anterior subregions of the cerebellar vermis and hemisphere in the asymptomatic premutation group. Correlation analyses using behavioural scales of the premutation groups showed

  19. Stem cells from wildtype and Friedreich's ataxia mice present similar neuroprotective properties in dorsal root ganglia cells.

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    Jonathan Jones

    Full Text Available Many neurodegenerative disorders share a common susceptibility to oxidative stress, including Alzheimer's, Parkinson Disease, Huntington Disease and Friedreich's ataxia. In a previous work, we proved that stem cell-conditioned medium increased the survival of cells isolated from Friedreich's ataxia patients, when submitted to oxidative stress. The aim of the present work is to confirm this same effect in dorsal root ganglia cells isolated from YG8 mice, a mouse model of Friedreich's ataxia. In this disorder, the neurons of the dorsal root ganglia are the first to degenerate. Also, in this work we cultured mesenchymal stem cells isolated from YG8 mice, in order to compare them with their wildtype counterpart. To this end, dorsal root ganglia primary cultures isolated from YG8 mice were exposed to oxidative stress and cultured with conditioned medium from either wildtype or YG8 stem cells. As a result, the conditioned medium increased the survival of the dorsal root ganglia cells. This coincided with an increase in oxidative stress-related markers and frataxin expression levels. BDNF, NT3 and NT4 trophic factors were detected in the conditioned medium of both wild-type and YG8 stem cells, all which bind to the various neuronal cell types present in the dorsal root ganglia. No differences were observed in the stem cells isolated from wildtype and YG8 mice. The results presented confirm the possibility that autologous stem cell transplantation may be a viable therapeutic approach in protecting dorsal root ganglia neurons of Friedreich's ataxia patients.

  20. Friedreich's ataxia 1980. An overview of the physiopathology.

    Science.gov (United States)

    Barbeau, A

    1980-11-01

    Phase three of the Quebec Cooperative Study of Friedreich's Ataxia was devoted to an understanding of the physiopathology of individual symptoms on the basis of previously discovered biochemical leads. The present paper attempts to pull these results together by presenting, as a hypothesis, a unifying scheme of possible interactions and relationships. The central core of this hypothesis is the demonstration in Friedreich's ataxia of a state of mitochondrial energy deprivation. This is indirectly responsible for such associated and important symptoms as muscle weakness, dying-back neuropathy, scoliosis and hypertrophic cardiomyopathy. Secondarily, and possibly as an independent but linked-event, the entry of glucose into cells and pyruvate oxidation, are slowed down, favoring the development of diabetes. As a consequence, tissue concentrations of glutamic acid and aspartic acid are decreased, particularly in more vulnerable areas such as the cerebellum, brain stem and dorsal root ganglia. This tissue deficiency in putative excitatory neurotransmitters is directly responsible for the symptom of ataxia. This conclusion is reinforced by the correction of the ataxia in experimental animals, by the intraventricular injection of the same amino acids, and not by the injection of other stimulants of motricity. The observed mitochondrial energy deprivation could be the metabolic consequence of major changes in the linoleic acid (18.2) composition of inner mitochondrial membrane phospholipids, such as cardiolipin. Such decreases in membrane 18:2 could be the result of interference with the normal incorporation of this fatty acid to lipoproteins and/or cell membranes. It is at this level that the search for the specific enzyme defect in Friedreich's ataxia is continuing.

  1. Electronystagmography findings in spinocerebellar ataxia type 3 (SCA3 and type 2 (SCA2

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    Bianca Simone Zeigelboim

    2011-10-01

    Full Text Available OBJECTIVE: To describe the alterations observed in electronystagmography (ENG of patients with spinocerebellar ataxia (SCA types 2 and 3. METHOD: Sixteen patients were studied and the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluations. RESULTS: The clinical findings in the entire group of patients were: gait disturbances (93.75%, dysarthria (43.75%, headache (43.75%, dizziness (37.50% and dysphagia (37.50%. In the vestibular exam, the rotatory (62.50% and caloric (75% tests were among those which presented the largest indexes of abnormalities; the presence of alterations in the exams was 87.50%, with a predominance of central vestibular disorders in 68.75% of the exams. CONCLUSION: Vestibular exams could be an auxiliary tool to investigate SCAs, besides a precise clinical approach and, particularly, molecular genetic tests.

  2. Lower limb antagonist muscle co-activation and its relationship with gait parameters in cerebellar ataxia.

    Science.gov (United States)

    Mari, Silvia; Serrao, Mariano; Casali, Carlo; Conte, Carmela; Martino, Giovanni; Ranavolo, Alberto; Coppola, Gianluca; Draicchio, Francesco; Padua, Luca; Sandrini, Giorgio; Pierelli, Francesco

    2014-04-01

    Increased antagonist muscle co-activation, seen in motor-impaired individuals, is an attempt by the neuromuscular system to provide mechanical stability by stiffening joints. The aim of this study was to investigate the co-activation pattern of the antagonist muscles of the ankle and knee joints during walking in patients with cerebellar ataxia, a neurological disease that strongly affects stability. Kinematic and electromyographic parameters of gait were recorded in 17 patients and 17 controls. Ankle and knee antagonist muscle co-activation indexes were measured throughout the gait cycle and during the sub-phases of gait. The indexes of ataxic patients were compared with those of controls and correlated with clinical and gait variables. Patients showed increased co-activity indexes of both ankle and knee muscles during the gait cycle as well as during the gait sub-phases. Both knee and ankle muscle co-activation indexes were positively correlated with disease severity, while ankle muscle co-activation was also positively correlated with stance and swing duration variability. Significant negative correlations were observed between the number of self-reported falls per year and knee muscle co-activation. The increased co-activation observed in these cerebellar ataxia patients may represent a compensatory strategy serving to reduce gait instability. Indeed, this mechanism allows patients to reduce the occurrence of falls. The need for this strategy, which results in excessive muscle co-contraction, increased metabolic costs and cartilage degeneration processes, could conceivably be overcome through the use of supportive braces specially designed to provide greater joint stability.

  3. 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.

  4. Clinical manifestation, imaging, and genotype analysis of two pedigrees with spinocerebellar ataxia.

    Science.gov (United States)

    Peipei, Liu; Yang, Liu; Weihong, Gu; Xiaonan, Song

    2011-12-01

    The objective of this study was to analyze the clinical manifestation, imaging characteristics, genotype, and the relationship between the three aforementioned parameters in two pedigrees suffering from spinocerebellar ataxia. To evaluate the clinical manifestation of the two pedigrees and to compare the characteristics, we performed the MRI analysis of some patients from both pedigrees, while 2 ml of the peripheral blood sample was collected for gene analysis. The gene analysis data showed that pedigree 1 was certified spinocerebellar ataxia type-2 (SCA2); the CAG repeats in the proband, proband's mother, and proband's brother were 44, 36, and 38, respectively. The MRI revealed brainstem cerebellar atrophy and "cross sign" and "ordinate sign" of pons. Pedigree 2 was certified SCA1; the CAG repeats of the proband, proband's aunt, and proband's asymptomatic cousin were 60, 51, and 52, respectively. The MRI revealed cerebellar atrophy in these individuals. We, therefore, concluded that it was difficult to diagnose the SCA subset solely through the clinical manifestation. The imaging characteristics analysis and final diagnosis depended basically on gene analysis data.

  5. 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.

  6. Nerve Growth Factor for the Treatment of Spinocerebellar Ataxia Type 3: An Open-label Study

    Institute of Scientific and Technical Information of China (English)

    Song Tan; Rui-Hao Wang; Hui-Xia Niu; Chang-He Shi; Cheng-Yuan Mao; Rui Zhang; Bo Song

    2015-01-01

    Background:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide,and runs a slowly progressive and unremitting disease course.There is currently no curable treatment available.Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases,and possibly also in SCA3.The objective of this study was to test the efficacy of NGF in SCA3 patients.Methods:We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients.NGF was administered by intramuscular injection (18 μg once daily) for 28 days consecutively.All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA).Results:Twenty-one SCA3 patients (10 men and 11 women,mean age 39.14 ± 7.81 years,mean disease duration 4.14 ± 1.90 years,mean CAG repeats number 77.57 ± 2.27) were enrolled.After 28 days of NGF treatment,the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001).Subsections SARA scores also showed significant improvements in stance (P =0.003),speech (P =0.023),finger chase (P =0.015),fast alternating hand movements (P =0.009),and heel-shin slide (P =0.001).Conclusions:Our preliminary data suggest that NGF may be effective in treating patients with SCA3.

  7. Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

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    Adriana Moro

    2013-07-01

    Full Text Available Objective To investigate the relevance of the clinical finding of bulging eyes (BE in a large Brazilian cohort of spinocerebellar ataxias (SCA, to assess its importance in clinical differential diagnosis among SCA. Methods Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. Results BE was detected in 123 patients with SCA (33.3%, namely 109 of the 167 SCA3 patients (65.3% and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients. Conclusion BE was detected in the majority of patients with SCA3 (65.3% and could be used with a clinical tool for the differential diagnosis of SCA.

  8. Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus

    Energy Technology Data Exchange (ETDEWEB)

    Nikali, K.; Suomalainen, A.; Koskinen, T.; Peltonen, L. [Univ. of Helsinki (Finland); Terwilliger, J. [Univ. of Oxford (United Kingdom); Weissenbach, J. [Genethon, Evry (France)

    1995-05-01

    Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials. 30 refs., 3 figs., 2 tabs.

  9. Ataxia rating scales--psychometric profiles, natural history and their application in clinical trials.

    Science.gov (United States)

    Saute, Jonas Alex Morales; Donis, Karina Carvalho; Serrano-Munuera, Carmen; Genis, David; Ramirez, Luís Torres; Mazzetti, Pilar; Pérez, Luis Velázquez; Latorre, Pilar; Sequeiros, Jorge; Matilla-Dueñas, Antoni; Jardim, Laura Bannach

    2012-06-01

    We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.

  10. Computational Insights into The Neuroprotective Action of Riluzole on 3-Acetylpyridine-Induced Ataxia in Rats

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    Mahyar Janahmadi

    2013-01-01

    Full Text Available Objective: Intra-peritoneal administration of riluzole has been shown to preserve the membrane properties and firing characteristics of Purkinje neurons in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP. However, the exact mechanism(s by which riluzole restores the normal electrophysiological properties of Purkinje neurons is not completely understood. Changes in the conductance of several ion channels, including the BK channels, have been proposed as a neuro protective target of riluzole. In this study, the possible cellular effects of riluzole on Purkinje cells from 3-AP-induced ataxic rats that could be responsible for its neuro protective action have been investigated by computer simulations.Materials and Methods: This is a computational stimulation study. The simulation environment enabled a change in the properties of the specific ion channels as the possible mechanism of action of riluzole. This allowed us to study the resulted changes in the firing activity of Purkinje cells without concerns about its other effects and interfering parameters in the experiments. Simulations were performed in the NEURON environment (Version 7.1 in a time step of 25 μs; analyses were conducted using MATLAB r2010a (The Mathworks. Data were given as mean ± SEM. Statistical analyses were performed by the student’s t test, and differences were considered significant if p<0.05.Results: The computational findings demonstrated that modulation of an individual ion channel current, as suggested by previous experimental studies, should not be considered as the only possible target for the neuro protective effects of riluzole to restore the normal firing activity of Purkinje cells from ataxic rats.Conclusion: Changes in the conductance of several potassium channels, including voltage-gated potassium (Kv1, Kv4 and big Ca2+-activated K+ (BK channels may be responsible for the neuro protective effect of riluzole against 3-AP induced alterations in

  11. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  12. GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.

    Science.gov (United States)

    Yuki, Nobuhiro; Fukami, Yuki; Yanaka, Chiaki; Koike, Saiko; Hirata, Koichi

    2014-08-01

    Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

  13. Multimodal evoked potentials in spinocerebellar ataxia types 1, 2, and 3

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    Vijay Chandran

    2014-01-01

    Full Text Available Aims: Spinocerebellar ataxias (SCA are a clinically heterogeneous group of disorders that are characterized by ataxia and an autosomal dominant pattern of inheritance. The aim of our study was to describe the findings of evoked potentials (EPs among genetically proven SCA types 1, 2, and 3 and to additionally evaluate if EPs can be used to differentiate between them. Materials and Methods: Forty-three cases of genetically proven SCA (SCA1 = 19, SCA2 = 13, and SCA3 = 11 were evaluated with median somatosensory-EP (mSSEP, visual-EP (VEP, and brainstem auditory-evoked response (BAER by standard procedures and compared with normative laboratory data. An EP was considered abnormal if latency was prolonged (>mean + 3 standard deviation (SD of laboratory control data or the waveform was absent or poorly defined. The waves studied were as follows: mSSEP - N20, VEP - P100 and BAER - interpeak latency 1-3 and 3-5. Results: EPs were abnormal in at least one modality in 90.9% of patients. The most common abnormality was of BAER (86.1% followed by VEP (34.9% and mSSEP (30.2%. The degree of abnormality in VEP, mSSEP, and BAER among patients with SCA1 was 42.1, 41.2, and 73.3%, respectively; among patients with SCA2 was 38.5, 27.3, and 100%, respectively; and among patients with SCA3 was 18.2, 37.5, and 88.9%, respectively. The differences between the subgroups of SCAs were not statistically significant. Conclusions: BAER was the most frequent abnormality in SCA types 1, 2, and 3; abnormalities of mSSEP were comparable in the three SCAs; whereas, abnormality of VEP was less often noted in SCA3.

  14. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

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    Sinha K K

    1999-01-01

    Full Text Available Twenty-four cases of sporadic olivo-ponto-cerebellar atrophy (OPCA of adult onset were studied over a period of two years. Results suggest that this disorder has its usual onset in the 5th and 6th decade of life with a male: female ratio of 2:1. It manifests clinically with gait ataxia in all, dysarthria, other cerebellar signs and autonomic involvement in vast majority. There were features of basal ganglia involvement in some. No known identifiable environmental cause was found and genetically they are quite distinct from the known autosomal dominant spinocerebellar ataxias though sporadic occurrence in recessive inheritance or a de novo mutation could not be ruled out completely, but it is unlikely.

  15. Inherited Ataxias%遗传性共济失调

    Institute of Scientific and Technical Information of China (English)

    蒋雨平; 邬剑军

    2011-01-01

    Inherited ataxia consists of spinal cord, cerebellum and brainstem degeneration. It also involves the peripheral nerves, optic nerve, brain and other regions. Although the causes of inherited ataxia were unknown, genetic, biochemical, metabolic abnormalities or other endogenous factors caused specific cell degeneration. Thisarticledescribedtheclinicalclassificationofhereditaryataxiaandsomeinterestingproblems.%遗传性共济失调是一组以脊髓、小脑、脑干为主的变性病,有时也累及周围神经、视神经、大脑等区域,病因不明.可能与遗传、生化代谢异常或尚未明确的内源性因素造成细胞变性有关.本文对遗传性共济失调的临床症状、分型和研究进展予以介绍.

  16. 遗传性共济失调%Hereditary ataxia

    Institute of Scientific and Technical Information of China (English)

    耿德勤; 刘春风

    2006-01-01

    @@ 共济失调是患者不能按一定的形式维持精细步态、完成精确动作的一种病理状态,任何累及小脑传入或传出途径的病变都可能导致共济失调,其中多数由遗传因素所致,故统称为遗传性共济失调(hereditary ataxia,HA).HA包括一组比较接近的变性疾病.病变部位主要在脊髓、小脑和脑干,故也称为脊髓-小脑-脑干疾病,或称为脊髓小脑共济失调( spinocerebellar ataxia, SCA) .

  17. A case of Spinocerebellar Ataxia from ethnic tribe of Assam

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    Kayal Ashok

    2011-01-01

    Full Text Available Here we present the case of a 17-year-old girl belonging to an ethnic tribe (Bodo tribe of Assam, presenting with bilateral cerebellar signs and with history suggestive of an autosomal dominant pattern of inheritance, who was found to have spinocerebellar ataxia 7 on genetic testing. This case throws light on the probability of more such cases in the multi-ethnic society of the North-Eastern Indian states, which are not studied or reported till date.

  18. Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy

    Science.gov (United States)

    Helmchen, Christoph; Kirchhoff, Jan-Birger; Göttlich, Martin; Sprenger, Andreas

    2017-01-01

    Background The cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia. Objectives The aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects. Methods Oculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM). Results Twenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg’s ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg’s ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients. Conclusions Postural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia. PMID:28056109

  19. In vivo venous assessment of red blood cell aggregate sizes in diabetic patients with a quantitative cellular ultrasound imaging method: proof of concept.

    Directory of Open Access Journals (Sweden)

    Julien Tripette

    Full Text Available Diabetic patients present higher level of red blood cell (RBC aggregation contributing to the development of vascular complications. While it has been suggested that this hematology/rheology parameter could bring additional prognostic information for the management of those patients, RBC aggregation screening is not included as a clinical practice. Most medical centers are not equipped to measure properly this parameter, although sedimentation tests can bring some indication. Here, we aimed at evaluating the feasibility of using ultrasound to assess in-vivo hyper-aggregation in type 2 diabetic patients.Seventeen diabetic patients and 15 control subjects underwent ultrasound measurements of RBC aggregation in both cephalic and great saphenous veins. Non-invasive in-vivo ultrasound measurements were performed using a newly developed cellular imaging technique, the structure factor size and attenuation estimator (SFSAE. Comparisons with an ex-vivo gold standard rheometry technique were done, along with measurements of pro-aggregating plasma molecule concentrations.In-vivo RBC aggregation was significantly higher in diabetic patients compared with controls for cephalic vein measurements, while a trend (p = 0.055 was noticed in the great saphenous vein. SFSAE measurements were correlated with gold standard in-vitro measures, fibrinogen and C-reactive protein plasma concentrations.RBC aggregation can be measured in-vivo in diabetic patients using ultrasound. Prospective studies are needed to determine whether the SFSAE method could help clinicians in the early management of vascular complications in this patient population.

  20. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

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    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.