Migrainous vertigo presenting as episodic positional vertigo

Migraine can cause vestibular symptoms including positional vertigo. Of 362 consecutive patients presenting with positional vertigo, 10 with migrainous vertigo mimicking benign paroxysmal positional vertigo (BPPV) were identified. The following factors help to distinguish migrainous positional vertigo from BPPV: short-duration symptomatic episodes and frequent recurrences, manifestation early in life, migrainous symptoms during episodes with positional vertigo, and atypical positional nystagmus.     

Infantile spinocerebellar ataxia type 6: relationship to episodic ataxia type 6

Spinocerebellar ataxia type 6 is one of the hereditary progressive cerebellar ataxias first described in 1997. Genetic studies have identified the defect as abnormal expansion of CAG trinucleotide repeat in 1 alpha subunit of the calcium channel gene located on chromosome 19p13. The symptomatic individuals have 20 or 23 repeats in contrast to normal individuals who manifest 19 or less CAG repeats. Most of the earlier reports indicate the age of onset of symptoms to be after the third decade. This report presents a patient with episodic symptoms soon after birth, which is unusual, and to our knowledge this is the youngest reported case. The clinical features of spinocerebellar ataxia type 6 are variable. The mode of inheritance and the common symptoms of this condition are also discussed.     

Familial paroxysmal ataxia responsive to acetazolamide

From their early twenties, a 56 year-old french woman and her 33 year-old son suffered from paroxysmal attacks of gait ataxia, incoordination of both hands, dysarthria and nystagmus. These attacks lasted from one to three hours and occurred at the rate of one to seven per week. On examination between attacks, there was only a bilateral horizontal and upward-beating gaze nystagmus. This was documented by E.O.G. Biological investigations were normal with the exception of a mild elevation of glucose blood level. Treatment with acetazolamide 250 mg daily, completely abolished the attacks in both patients. These cases meet the criteria of familial paroxysmal ataxia, a disorder only described in the United States up to the present. Although rare, this disease should be recognized because of its dramatic response to acetazolamide.     

Spinocerebellar ataxia type 20

Spinocerebellar ataxia type 20 (SCA20) was reported in 2004 in a single Australian Anglo-Celtic pedigree. The phenotype is distinctive, with palatal tremor, and hypermetric saccades, and early dentate (but not pallidal) calcification in the absence of abnormalities of calcium metabolism. Dysarthria, rather than gait ataxia, was the initial symptom in most, and was typically conjoined with dysphonia, clinically resembling adductor spasmodic dysphonia. The onset of these speech abnormalities was abrupt in some cases. MRI scanning showed mild to moderate pancerebellar atrophy with dentate calcification, with olivary pseudohypertrophy in some cases, in the absence of other brainstem or cerebral changes. Nerve conduction studies were normal. Progression appeared to be slow. SCA20 is probably rare, as despite the distinctive phenotype, only this one pedigree has been described. The locus mapped to the pericentromeric region of chromosome 11 with a LOD score of 4.47, and its candidate region overlaps that of SCA5. It seems probable that these two SCAs may be separate genetic entities, on the basis of their divergent clinical features, but formal proof awaits discovery of one or both responsible genes.     

Spinocerebellar ataxia type 15

Spinocerebellar ataxia type 15 (SCA15) was first reported in 2001 on the basis of a single large Anglo-Celtic family from Australia, the locus mapping to chromosomal region 3p24.2-3pter. The characteristic clinical feature was of very slow progression, with two affected individuals remaining ambulant without aids after over 50 years of symptoms. Head and/or upper limb action tremor, and gaze-evoked horizontal nystagmus were seen in several persons. MRI brain scans showed predominant vermal atrophy, sparing the brainstem. In 2004, a Japanese pedigree was reported, which displayed very similar clinical features to the original SCA15 family, and which mapped to an overlapping candidate region. These two families might plausibly reflect a locus homogeneity, but for the present this remains an open question.     

Spinocerebellar ataxia type 4

The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a clinically and genetically heterogeneous group of neurodegenerative disorders. To date 24 different loci have been identified for these conditions. A locus at chromosome 16q22.1 co–segregates with the disease phenotype in families of Scandinavian, Japanese and German origin. The corresponding SCA4 locus was narrowed down to 7.94 Mb for the two European and to 1.25 Mb for Japanese pedigrees. Unfortunately, because of the phenotypic differences between patients from Japan and Europe it is not possible to decide if SCA families linked to chromosome 16q22.1 share a common disease genotype or not. To look for mutations in the German family we screened 34 candidate genes in a 3.69 cM region. With the exception of two cSNPs, no segregation of DNA variations with the disease phenotype was found.     

Spinocerebellar ataxia type 3 presenting with writer's cramp without ataxia

Aim of the study: Spinocerebellar ataxia type 3 is the most common cause of autosomal dominant inherited ataxia worldwide.

Material and methods: Clinically, it exhibits wide phenotypic variability. Presentation as isolated dystonia is exceptional.

Results: Here, the case of a woman with writers cramp without ataxia is presented as a paucisymptomatic manifestation of this disease.

Conclusions: This association has not been described to date and extends the clinical variability of the disease.     

Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds

OBJECTIVE—Spinocerebellar ataxia type 6 (SCA6) isan autosomal dominant cerebellar ataxia (ADCA) of which the mutationcausing the disease has recently been characterised as an expanded CAGtrinucleotide repeat in the gene coding for theα_1A-subunit of the voltage dependent calcium channel. Theaim was to further characterise the SCA6 phenotype
METHODS—The SCA6 mutation was investigated in 69 German families with ADCA and 61 patients with idiopathic sporadiccerebellar ataxia and the CAG repeat length of the expanded allele wascorrelated with the disease phenotype.
RESULTS—Expanded alleles were found in nine of 69 families as well as in four patients with sporadic disease. Diseaseonset ranged from 30 to 71 years of age and was significantlylater than in other forms of ADCA. Age at onset correlated inverselywith repeat length. The SCA6 phenotype comprises predominantlycerebellar signs in concordance with isolated cerebellar atrophy onMRI. Non-cerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Neither these clinical signs nor progression rate correlated with CAGrepeat length.
CONCLUSIONS—This study provides the first detailedcharacterisation of the SCA6 phenotype. Clinical features apart fromcerebellar signs were highly variable in patients with SCA6. Bycomparison with SCA1, SCA2, and SCA3 no clinical orelectrophysiological finding was specific for SCA6. Therefore, themolecular defect cannot be predicted from clinical investigations. InGermany, SCA6 accounts for about 13% of families with ADCA. However,up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadicdisease due to late manifestation in apparently healthy parents.Genetic testing is therefore recommended for the SCA6 mutation also inpatients with putative sporadic ataxia.

     

Spinocerebellar ataxia type 6: founder effect in Western Japan

An accumulation of SCA6 cases has been observed in the Chugoku area of Western Japan. In the Tottori prefecture, located in the northeastern part of the Chugoku district, we observed a cluster of SCA6 families within the eastern area, suggesting that there may be a founder in the Japanese SCA6 population. Genotyping with DNA microsatellite markers linked to the CACNL1A4 gene on chromosome 19p13 demonstrated shared allelic characteristics and revealed a common haplotype in the majority of Japanese families. The common haplotype of the shared (CAG)(22) repeat found in this study may indicate the meiotic stability of CAG repeats in SCA6 patients.     

Spinocerebellar ataxia type 6 in relation to CAG repeat length

The purpose of the present study was to assess the relationship between clinical characteristics of spinocerebellar ataxia type 6 (SCA6) and CAG repeat length. MATERIALS AND METHODS: We examined clinical symptoms of 54 patients with SCA6. CAG repeat length was compared among subgroups divided by clinical manifestations. RESULTS: The major symptom was progressive cerebellar ataxia. Truncal or limb ataxia, dysarthria, and nystagmus were observed in more than 80% of the patients. In analysis of CAG repeat length in patients with different types of nystagmus, CAG repeat length was the longest when both upbeat and downbeat nystagmus existed (P < 0.01). In addition, CAG repeat length was longer when the initial symptom was ataxic gait and was shorter when the initial symptom was dysarthria or ocular symptom (P < 0.05). CONCLUSION: Clinical features of SCA6 might be influenced by the length of abnormal CAG repeat.     

Spinocerebellar ataxia type 1 in Russia

Spinocerebellar ataxia type 1 (SCA1) is one form of autosomal dominant cerebellar ataxia (ADCA) caused by trinucleotide (CAG) repeat expansion within a mutant gene. We investigated 25 patients from 15 Russian ADCA families for SCA1 mutation and found an expanded CAG repeat in 5 families. Mutant chromosomes contained 41–51 CAG repeats (mean 46.1, SD 3.1), and normal chromosomes displayed 21–27 repeat units (mean 24.7, SD 1.3). Progressive cerebellar ataxia in our series of SCA1 patients was very commonly associated with dysarthria (in all cases) and pyramidal signs (in 10 of 11 cases). In three patients from one family we found optic atrophy, which has never been described before in genetically proven cases of SCA1. We observed no specific clinical features distinguishing SCA1 from non-SCA1 patients. In contrast to the high frequency of SCA1 in our series, we found no patients with Machado-Joseph disease, another form of ADCA caused by expanded CAG repeat.     

Spinocerebellar ataxia type 6 in eastern India: Some new observations

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.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.     

Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family

The clinical spectrum of spinocerebellar ataxia 3 (SCA 3) disease is wide and varied. We describe a Chinese patient with a mutation at the SCA 3 locus with clinical features of levodopa-responsive dystonia. The family history was suggestive of being autosomally dominant. Levodopa responsiveness though rare has been described in families with features of parkinsonism. Noteworthy is the relatively late onset of disease (>40 years) possibly explained by the low number of affected alleles at 59, the usual range being from 62 to 86, with the lowest recorded number at 56. This expands the wide and varied phenotypic manifestations of SCA 3, and highlights the observation that features suggestive of levodopa-responsive dystonia (DRD) such as focal dystonia, gait difficulty with diurnal fluctuation of symptoms, and a marked response to low doses of levodopa can be presenting features of SCA 3. SCA 3 should be considered a differential diagnosis in adult patients who present with DRD phenotype and with a positive family history.     

Spinocerebellar ataxia type 2 with glial cell cytoplasmic inclusions

Glial cell cytoplasmic inclusions were identified in a case of spinocerebellar ataxia type 2. These have not been reported before. The inclusions were found in low frequency in the dentate nucleus, cerebellar white matter, pontine transverse fibres, and the inferior olivary nucleus. They were of variable size and shape and expressed ubiquitin, thus resembling glial cytoplasmic inclusions in multiple system atrophy. However, their immunohistochemical profile was different as they did not show immunoreactivity for either tau protein or alpha-synuclein. There was no evidence of expanded polyglutamine tracts in these inclusions, which also failed to label with silver stains. As in many other neurodegenerative diseases, in spinocerebellar ataxia type 2 there may be pathogenic contributions of glial cells other than the common astrogliotic response to neuronal damage.     

Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese

OBJECTIVE: To describe the clinical and molecular genetic analysis of a large family of northern Chinese descent with a mutation at the SCA2 locus causing carbidopa-levodopa-responsive parkinsonism. BACKGROUND: Most causes of parkinsonism remain unknown. However, molecular genetic analysis of families with parkinsonism has recently identified five distinct loci and pathogenic mutations in four of those. Additionally, some of the spinocerebellar ataxia syndromes (SCA), particularly Machado-Joseph syndrome (SCA3), are known to cause parkinsonism. Spinocerebellar ataxia type 2 (SCA2) has not previously been described as causing a typical dopamine-responsive asymmetric PD phenotype. METHODS: A large family was evaluated clinically and molecularly for apparent autosomal dominant parkinsonism. RESULTS: The phenotype includes presentation consistent with typical dopamine-responsive parkinsonism. Other presentations in this family include a parkinsonism/ataxia phenotype, which is classic for SCA2 and parkinsonism, resembling progressive supranuclear palsy. CONCLUSIONS: Patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion.