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PubMed2006

Autosomal recessive cerebellar ataxias.

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2-4/100,000), ataxia-telangiectasia (1-2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, alpha-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia.

Abetalipoproteinemia↗
PubMed1993

[Molecular genetics and familial ataxia].

Linkage studies with DNA polymorphic markers allowed to map the loci of three inherited ataxia and to explore genetic heterogeneity in inherited ataxia in general. The locus of Friedreich ataxia, the most frequent of all recessive ataxias, has been mapped in 9q13-q21. In addition, Friedreich ataxia is an homogeneous genetic entity since all families from all populations tested (mainly European, North-American and from the Mediterranean basin) show linkage with this locus. But the severity of the disease varied in a few families. A form of recessive ataxia associated with a selective and severe serum vitamin E deficiency, which frequently presents clinically like typical Friedreich ataxia, is not linked to 9q13-q21 markers. The autosomal recessive spastic ataxia from Charlevoix-Saguenay (a region of Quebec) is also not linked to these markers. Both entities are therefore distinct genetically from Friedreich ataxia. Among dominant ataxias, the most important group is olivo-ponto-cerebellar ataxia which is heterogeneous and for which any classification is hindered by important intra-familial variability. This group corresponds to at least three distinct loci, two of which have been mapped, one in 6p23-p24, and the other, more recently, on chromosome 12. Prenatal and presymptomatic diagnosis based on linked markers can be made for the three mapped ataxias, but only in families with an affected individual for whom the diagnosis has been ascertained by through clinical investigation or by linkage analysis if the family is large enough (mainly for the dominant diseases). Linked markers are also the first tools for the search of the defective genes by positional cloning.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebellar Ataxia↗
PubMed2000

Genetic background of apparently idiopathic sporadic cerebellar ataxia.

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.

Age of Onset↗
PubMed2003

Primary degenerative cerebellar ataxias in ethnic Bengalees in West Bengal: some observations.

Seventy cases of primary degenerative cerebellar ataxias in ethnic Bengalees from southern West Bengal, India, were studied by the authors. Of these, 50 cases were of the familial type (hereditary ataxias) encountered in 23 families and the remaining 20 were of sporadic onset. 18 cases (from 11 families) were of "probable" autosomal recessive (AR) inheritance, 12 cases (8 families) had Friedreich's type ataxia (FA), 4 cases (2 families) had FA type ataxia with retained reflexes and in 2 cases (1 family) the exact phenotypic characterization could not be made. AR inheritance in these cases seemed most likely in view of the occurrence in a single generation with unaffected parents and history of consanguinity in many of the families studied. Genotypic confirmation of FA type ataxia and its variants could not be done in any case due to the non-availability of technology for studying the FA locus but some common dominant ataxia genotypes could be excluded. Thirty-two cases (from 12 families) with autosomal dominant ataxias (ADCA) were studied. Genotype analysis revealed 4 families with SCA2 genotype, 5 families with SCA3 and 3 families where genotypic characterization could not be made (phenotypically 2 were of ADCA I and 1 of ADCA II). No clear preponderance of one particular genotype of SCA over another could be demonstrated in our ethnic Bengalee patients. We also noted significant intra and inter-family variations in phenotypes within the same genotypic form as well as overlapping of clinical signs between different genotypes. Slow saccades and peripheral neuropathy were not seen consistently in our ethnic Bengalee subjects with SCA2 genotype. Similarly, extrapyramidal features, ophthalmoplegias and distal amyotrophy were seen in some but not all families with the SCA3 genotype. Phenotypic expression appeared to be an inconsistent marker of the SCA genotype in our patients. Of the 20 sporadic cases with cerebellar ataxia, genotype analysis revealed 2 cases with SCA1 and 1 with SCA2. Some of the sporadic ataxia cases had extracerebellar involvement and may warrant classification as Multiple System Atrophy. In all the 3 subjects with genotype characterization, phenotype correlation was lacking. The clinical pattern of hereditary ataxias in ethnic Bengalees seems to be somewhat different from that seen in Western India. The need for clinical and genetic studies of ataxias in different specific ethnic populations of India has been stressed.

Adolescent↗
PubMed1997

Ophthalmologic findings in patients with ataxia.

PURPOSE: To determine the frequency and spectrum of ophthalmologic findings in a large, heterogeneous group of patients with ataxia. METHODS: Medical records of 184 patients from a university-based ataxia clinic were retrospectively reviewed. Patients were classified as having Friedreich's ataxia, spinocerebellar degeneration, cerebellar degeneration, familial or sporadic olivo-pontocerebellar atrophy, multisystem atrophy, spastic ataxia, myoclonic ataxia, or other diagnoses such as mitochondrial myopathy. All had complete ophthalmologic examinations, and 107 underwent electro-oculography. RESULTS: Among 184 patients with ataxia, diplopia was present in 52 (28%), best-corrected visual acuity was decreased in 29 (16%), and oscillopsia was present in 10 (5%). Diplopia was usually caused by an intermittent, small-angle heterotropia. The reduction in best-corrected visual acuity varied from mild to profound and was caused by optic atrophy, retinal degeneration, or both. Optic atrophy was present most frequently in spastic ataxia (five of 22 patients) and myoclonic ataxia (two of eight patients), followed by Friedreich's ataxia (three of 26 patients). Retinal degeneration and ophthalmoplegia were most characteristically associated with familial olivopontocerebellar atrophy and mitochondrial myopathy. Laboratory testing of ocular motility showed frequent abnormalities in all groups. Fixation instability was most characteristic of Friedreich's ataxia, whereas saccadic slowing was noticeably absent from patients with purely cerebellar degenerations. CONCLUSIONS: The ataxias may be associated with visual dysfunction caused by retinal degeneration, optic atrophy, oculomotor disturbance, or a combination of these.

Adolescent↗
PubMed1998

Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia.

BACKGROUND: Ataxia is the commonest neurological manifestation of coeliac disease. Some individuals with genetic susceptibility to the disease have serological evidence of gluten sensitivity without overt gastrointestinal symptoms or evidence of small-bowel inflammation. The sole manifestation of disease in such patients may be ataxia. We describe the clinical, radiological, and neurophysiological features of this disorder. METHODS: Patients with ataxia attending the neurology outpatient clinics at the Royal Hallamshire Hospital, Sheffield, UK, were screened for gluten sensitivity as shown by the titre of antibody to gliadin. Those with other causes of ataxia were excluded. We carried out clinical, neurophysiological, neuroradiological, and, in two cases, neuropathological examinations. FINDINGS: 28 patients with gluten ataxia were identified. All had gait ataxia and most had limb ataxia. Those with more severe gait ataxia had longer disease duration. No patient had tremor or other extrapyramidal features. 19 patients showed some form of peripheral neuropathy on neurophysiological examination. 16 patients had no gastrointestinal symptoms. Distal duodenal biopsy showed lymphocytic infiltration in two patients, and changes compatible with coeliac disease in 11. Six patients had evidence of cerebellar atrophy on magnetic-resonance imaging. Necropsy was done on two patients who died; there was lymphocytic infiltration of the cerebellum, damage to the posterior columns of the spinal cord, and sparse infiltration of the peripheral nerves. INTERPRETATION: Gluten sensitivity is an important cause of apparently idiopathic ataxia and may be progressive. The ataxia is a result of immunological damage to the cerebellum, to the posterior columns of the spinal cord, and to peripheral nerves. We propose the term gluten ataxia to describe this disorder.

Adult↗
PubMed2003

Dietary treatment of gluten ataxia.

BACKGROUND: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. OBJECTIVE: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. METHODS: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. RESULTS: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. CONCLUSIONS: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

Adult↗
PubMed1995

Ataxia-oculomotor apraxia syndrome.

Ataxia-oculomotor apraxia is a distinct entity first comprehensively described in 1988. The features include early childhood onset of ataxia and oculomotor apraxia, mimicking ataxia telangiectasia but without the extraneurologic findings of ataxia telangiectasia. We add to the clinical description of the ataxia-oculomotor apraxia syndrome by reporting eight patients, ages 2 to 15 years, from four families, suggesting autosomal recessive inheritance, with the longest follow-up over 6 years. After initial gait deterioration, all had a nonprogressive course. We have postulated that ataxia-oculomotor apraxia should be established as a separate disease from ataxia telangiectasia or its variants not only by clinical history, examination findings, and course, but primarily by the biologic markers of normal chromosome breakage and radiation sensitivity studies. We found no increased chromosome breakage in the four patients studied and intermediate sensitivity to chronic ionizing radiation of cultured skin fibroblasts on the three patients studied. Family studies revealed an intermediate radiosensitivity from two patients, their asymptomatic parents, and a sister. The lack of chromosome breakage strongly separates ataxia-oculomotor apraxia from ataxia telangiectasia. The radiation sensitivity studies are compatible with two possibilities: (1) symptomatic ataxia telangiectasia heterozygotes, but this would be highly unusual because the degree of clinical involvement in the ataxia-oculomotor apraxia patients is not mild, as would be expected if they were heterozygotes and (2) a separable disease entity, which is the interpretation we favor.

Adolescent↗
PubMed1997

[Clinical identification of hereditary ataxias. A study of 38 cases in Colombia].

INTRODUCTION: Hereditary ataxias are a complex group of degeneratives diseases of the CNS. Material and methods. We studied 38 patients who were diagnosed inherited ataxia according to recent classification and radiologic criteria. We proposed flow sheet in order to reduce the cost of the studies. RESULTS: The most frequent findings we encountered were the congenital ataxias and the late onset ataxia forms, olivopontocerebellar ataxias (OPCA) and the late cortical cerebellar ataxias (CCA), following were the Friedreich ataxias, the intermittent ataxias, and cerebellar ataxias with myoclonus. We found finally two multisystemic atrophies. We didn't find dominant inheritance in the late onset ataxias, some of these were recessive forms and the others could be the novo mutations or idiopathic cerebellar ataxias of adult onset. CONCLUSION: It would be appropriate to enlarge the studies in the metabolic and treatable forms and try to define the forms that have a known genetic mutation.

Adolescent↗
PubMed2001

Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.

BACKGROUND: The small-conductance calcium-activated potassium channel gene (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this repeat is not pathologically expanded in patients with schizophrenia, some studies have suggested an allelic association with schizophrenia. CAG expansions in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type 2. OBJECTIVES: To evaluate expansions in the hSKCa3 polyglutamine domain as causative for ataxia, and to study the association between the length of the polyglutamine repeat and the presence of ataxia. METHODS: We analyzed this repeat in 122 patients with autosomal dominant cerebellar ataxia, or sporadic ataxia, and compared allele distribution with 750 alleles seen in 2 healthy control groups and 172 alleles in patients with Parkinson disease. RESULTS: The distribution of alleles in ataxia patients and controls was significantly different by Wilcoxon rank test (P <.001). Twenty-two or more polyglutamine tracts were more common in ataxia patients compared with controls by chi2 analysis (P<.001). CONCLUSION: Longer stretches of polyglutamines in a human potassium channel are not causative for ataxia, but they are associated with the presence of ataxia. There is no association with the presence of Parkinson disease.

Age of Onset↗
PubMed1998

Molecular genetics of the hereditary ataxias.

One of us (MP) learned about the mapping of Huntington disease gene to chromosome 4 from the late Dr. Anita Harding. She got the news over the phone from her London office during a visit to Italy for a meeting on hereditary ataxias. In Britain, they receive Nature at least a week earlier than us. Dr. Harding was very excited, and she immediately said that that was the way to go if we wanted to understand the causes of hereditary ataxias, classify these diseases in a rational way, and eventually find a treatment. At that time, the challenge seemed, and indeed was, formidable. No clue was then available about the genetic basis of what Dr. Harding aptly called "hereditary ataxias of unknown cause," their classification was confused and controversial, and all attempts to find specific biochemical abnormalities had failed. Fourteen years later, the success of the molecular genetic studies is astounding. The defective genes have been identified for Friedreich ataxia, the major recessive "hereditary ataxia of unknown cause," and for five dominantly inherited "hereditary ataxias of unknown cause." Three more dominant ataxia genes have been mapped. The molecular pathogenesis of the dominant ataxias begins to be unraveled and animal models have been and are being developed. Information is also quickly accumulating about the defective protein in Friedreich ataxia. Direct molecular diagnosis is now possible. Classification has been revolutionized. Diagnostic criteria are being redefined in the light of the molecular discoveries. The goal of this review, dedicated to the memory of the late Dr. Harding, is to offer a concise summary of current knowledge about the molecular genetics of some of the hereditary ataxias that used to be classified as of "unknown cause."

Ataxia↗
PubMed1994

Molecular genetics of hereditary ataxias.

The hereditary ataxias are a very heterogeneous group of disorders characterized by cerebellar dysfunction that can be either isolated or accompanied by other neurological manifestations. The classification of the hereditary ataxias based on clinical or histopathological findings has been difficult because of the significant overlap of phenotypes among the various genotypes. The patterns of inheritance observed in ataxias include autosomal dominant, autosomal recessive and X-linked. Friedreich's ataxia, the most frequent form among the recessive ataxias, has been mapped to the long arm of chromosome 9 based on close linkage to the markers D9S5 and D9S15. This close linkage allows the use of these two DNA markers for prenatal diagnosis in families with one affected offspring. In the past year, significant research progress has been accomplished by applying molecular genetic studies to the dominantly inherited spinocerebellar ataxias. Spinocerebellar ataxia type 1 (SCA1), which maps to the short arm of chromosome 6, has been found to be caused by expansion of an unstable trinucleotide (CAG) repeat. This mutational mechanism explains the presence of the clinical phenomenon of anticipation in some families with SCA1. The finding of an unstable repeat in SCA1 will facilitate the diagnosis of SCA1 in familial and isolated cases and will allow preclinical and prenatal diagnosis in families with this disease. In addition to the cloning of the SCA1 gene, two dominantly inherited ataxias have been genetically mapped: SCA2, to the long arm of chromosome 12, and Machado-Joseph disease (MJD), to the long arm of chromosome 14. Given that anticipation has been observed in patients with SCA2 and MJD, it is likely that trinucleotide repeat expansion could be a common mechanism involved in all the spinocerebellar ataxias. Last, significant research progress has been accomplished in the field of hereditary ataxias associated with DNA repair defects which should facilitate our understanding of mechanisms involved in cerebellar degeneration.

Ataxia↗
PubMed2000

Extrapyramidal motor signs in degenerative ataxias.

BACKGROUND: Extrapyramidal motor signs (EPS) are well-known symptoms of degenerative ataxia. However, little is known about frequency and appearance of EPS in subtypes of ataxia. METHODS: We characterized 311 patients with ataxia clinically and genetically. Course of the disease and EPS were investigated according to a standardized protocol. Diagnostic and prognostic impact of EPS in subtypes of ataxia was analyzed by Kaplan-Meier plots. RESULTS: Extrapyramidal motor signs occurred in all forms of ataxia, but frequency and type of EPS varied between genetically and clinically defined subtypes. Postural tremor in hereditary ataxias was typical for spinocerebellar ataxia type 2 (SCA2). Dystonia was generally rare in ataxias, but, if present, suggested SCA3. We observed a parkinsonian variant of SCA3 in which parkinsonism was present in the beginning of the disease and responded well to levodopa therapy, leading to diagnostic confusion. Parkinsonism in SCA3 was independent of CAG repeat length but ran in families, suggesting modifying genes. In idiopathic sporadic cerebellar ataxia (ISCA), EPS are more frequent in late-onset than in early-onset forms. In 50% of ISCA patients with parkinsonism, the diagnosis of multiple system atrophy remained questionable because of normal autonomic function. CONCLUSIONS: Extrapyramidal motor signs can help to predict the genetic subtype of ataxia. Extrapyramidal motor signs were more frequent in genetic subtypes in which basal ganglia affection has been demonstrated by postmortem studies. However, no type of EPS was specific for an underlying mutation. In ISCA, EPS are an adverse prognostic factor. Parkinsonism is especially associated with a more rapid course of the disease. Arch Neurol. 2000;57:1495-1500

Aged↗
PubMed1987

Morphologic and functional characteristics of the heart in Friedreich's ataxia.

The purpose of this study was to characterize the heart in patients with Friedreich's ataxia by two-dimensional echocardiography, systolic time intervals, and heart biopsy. Ten patients with Friedreich's ataxia (seven females and three males, age 15 +/- 7 years) were compared with 10 age-matched normal subjects (five males and five females, age 16 +/- 7 years). The mean systolic blood pressure in the patients with Friedreich's ataxia was lower (114 +/- 9 mm Hg) than that in the control subjects (122 +/- 8 mm Hg; p less than 0.05); diastolic blood pressures were the same. The heart rate in the patients with Friedreich's ataxia (102 +/- 17 beats/minute) was greater than that in the control subjects (76 +/- 12 beats/minute; p less than 0.001). The interventricular septal wall thickness was much greater in Friedreich's ataxia (13 +/- 2 versus 8 +/- 1 mm, p less than 0.001) as was the posterior wall thickness (13 +/- 3 versus 8 +/- 1 mm, p less than 0.001). The left ventricular end-diastolic diameter was smaller in Friedreich's ataxia (35 +/- 6 mm versus 47 +/- 6 mm; p less than 0.01), and the fractional change of the left ventricular minor axis with systole was greater in Friedreich's ataxia (40 +/- 9 percent versus 33 +/- 5 percent; p less than 0.05). An 11th patient with Friedreich's ataxia (age 33) had clinical heart failure, but his course was complicated by alcohol abuse. Heart biopsy in three patients with Friedreich's ataxia demonstrated myocyte hypertrophy (21.5 +/- 2.0 microns diameter; normal, 14 to 17 microns) and increased fibrosis (16 +/- 9 percent; normal, less than 5 percent). Thus, heart disease in Friedreich's ataxia is characterized by myocyte hypertrophy, interstitial fibrosis, increased left ventricular wall thickness, decreased left ventricular cavity size, sinus tachycardia, and normal systolic function. Further biochemical analysis of tissues may lead to the link of the neurologic and cardiac diseases and eventually to more effective therapy of this condition.

Adolescent↗
PubMed2002

The aetiology of sporadic adult-onset ataxia.

The nosology and aetiology of sporadic adult-onset ataxia are poorly understood. The aim of the present study was to answer the following questions: (i) How many sporadic ataxia patients have a genetic cause? (ii) How many sporadic ataxia patients suffer from multiple system atrophy (MSA)? (iii) Is there a specific association between sporadic ataxia and serum anti-glutamic acid decarboxylase (GAD) or antigliadin antibodies? and (iv) What are the clinical features of patients with unexplained sporadic ataxia? The study was performed in 112 patients who met the following inclusion criteria: (i) progressive ataxia; (ii) onset after 20 years; (iii) informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years); and (iv) no established symptomatic cause. Thirty-two patients (29%) met the clinical criteria of possible (7%) or probable (22%) MSA. The Friedreich's ataxia mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2 mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in seven (6%). The disease remained unexplained in 65 patients (58%). We did not detect anti-GAD antibodies in any of our patients. Antigliadin antibodies were present in 14 patients, 10 patients with unexplained ataxia (15%) and 4 patients with an established diagnosis (9%). Patients with unexplained sporadic ataxia had a median disease onset of 56.0 years. Decreased vibration sense (62%), decreased or absent ankle reflexes (40%), increased ankle reflexes (39%), dysphagia (38%) and extensor plantar responses and/or spasticity (34%) were the most frequent extracerebellar symptoms. Compared with MSA, disease progression was significantly slower.

Adult↗
PubMed1990

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias.

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.

Adult↗
PubMed2003

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

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

Autoantibodies↗
PubMed2003

[Clinico-urodynamic correlation in the hereditary ataxias].

OBJECTIVES: To evaluate lower urinary tract functional symptoms in a series of patients with ataxia and to determine by urodynamic studies the kind of bladder-urethra neurological dysfunction in each case. We posed the question if the clinical picture could be enough to establish the diagnosis and therapeutic management of these patients with hereditary ataxia, or on the contrary it would be necessary to perform urodynamic studies in all cases. METHODS: Due to the low incidence of hereditary ataxias and patients' mobility it was necessary to recruit patients from various hospitals. The urodynamic study protocol employed in this study included 1) Evaluation of urinary symptoms; 2) Neurological physical examination; 3) Flowmetry with post void residual; 4) Cystomanometry; and 5) Perineal electromyography. We analyzed the relationship between urinary symptoms and urodynamic diagnosis, considering variables such as age, gender, type of ataxia, and time of evolution of the disease. RESULTS: The series includes 34 patients with ataxia and urinary symptoms, 14 cases of Friedreich's ataxia (FA) (41.2%) and other 20 cases of other various forms of ataxia we name non-Friedreich's (NF) (58.8%). Mean age was 37.2 years in FA and 50 years in NF (p < 0.05). Mean time of disease evolution was 20.5 yr. for FA, and 14.9 yr. for NF ataxia (p < 0.1). A mixed urinary syndrome was predominant in 53% of the patients, and 41.1% presented pure irritative symptoms in relation to voiding urgency (85.2%). The most frequent urodynamic diagnosis was detrusor hyperreflexia (61.7%) (37.5% with dyssynergia), followed by areflexia (or hyporeflexia) (23.5%), and normal studies (14.7%). Detrusor hyperreflexia presented with irritative urinary symptoms in 85.7% of the patients, and areflexia or hyporeflexia presented with obstructive symptoms in 75% of the cases. CONCLUSION: Although there is a good clinical-urodynamic correlation in cases of ataxia, we consider it is necessary to perform a complete urodynamic study in males with hereditary ataxia in order to rule out bladder outlet obstruction due to BPH. On the other hand, due to the fact that progression of the lesions can modify the clinical picture of the patient (including urinary tract symptoms), we consider essential to re-evaluate ataxic patients periodically to adapt their treatment to the urodynamic diagnosis.

Adolescent↗