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PubMedDate not supplied

Nerve conduction study, electromyography and somatosensory evoked potentials in non-Friedreich early onset cerebellar ataxia. A comparative study with Friedreich's ataxia and late onset cerebellar ataxia.

Electrophysiological findings in 14 patients with non-Friedreich early onset cerebellar ataxia are reported. Nerve conduction studies showed reduction of sensory action potential amplitudes in 7 cases associated in 3 with a decrease of sensory conduction velocities. Six subjects also exhibited a chronic neurogenic pattern to standard needle electromyography. Motor conduction velocities were normal in all cases; only two cases showed an increase in distal motor latencies. Short-latency somatosensory evoked potentials following median nerve stimulation revealed a prolonged central conduction time (N13-N20 interpeak latency) in 7 cases, compatible with supraspinal damage of the somatosensory pathways. These electrophysiological data are compared with those obtained in two reference groups of patients, respectively affected by Friedreich's ataxia and olivo-ponto-cerebellar atrophy.

Action Potentials↗
PubMed2025

Spinocerebellar Ataxia 27 A with Episodic Ataxia: Case Series of Fibroblast Growth Factor 14 (FGF14) Microdeletions.

Spinocerebellar ataxia 27&#xa0;A (SCA27A) is a form of progressive cerebellar ataxia due to pathogenic variants in the Fibroblast Growth Factor 14 (FGF14) gene. The objective of this paper is to characterise the clinical spectrum of SCA27A microdeletions (>&#x2009;50&#xa0;bp, <2Mbp), and report two novel cases.&#xa0;Literature searches of PubMed, OMIM and ClinVar were carried out. We identified SCA27A microdeletions in 32 cases across 11 families. The phenotypic presentation is: 75% (24/32) nystagmus, 46% (15/32) ataxia, 21% (7/32) episodic ataxia, 21% (7/32) tremor, 15% (5/32) dysarthria, 34% (11/32) learning disability, 28% (8/32) neuropsychiatric disease. The presentation is variable within and between families. Episodic symptoms, nystagmus, learning disability and neuropsychiatric symptoms occur at an earlier age. Patient 1 represents the first case with a 58 kb FGF14 deletion who presented with a paroxysmal movement disorder. Patient 2 carries a 545&#xa0;kb deletion and developed episodic ataxia and trigeminal neuralgia, a novel feature not previously described in this cohort. We report two cases of heterozygous FGF14 microdeletions: Patient 1 (58&#xa0;kb) and Patient 2 (545&#xa0;kb), expanding the phenotypic spectrum of FGF14 structural variants to 32 cases across 11 families. We review potential mechanism from pre-clinical studies relating FGF14 haploinsufficiency to cerebellar, cognitive, neuropsychiatric symptoms, as well as trigeminal neuralgia. We propose the hypothesis that the episodic symptoms in SCA27A align with the molecular pathology of a channelopathy and propose management strategies based on this insight.

Humans↗
PubMed2026

Downbeat nystagmus without ataxia as an early manifestation of spinocerebellar ataxia, autosomal recessive type 10 (SCAR10): a case report.

The differential diagnosis of dizziness is broad and can include both vestibular and autonomic pathology. Vestibular dizziness is typically described as a sensation of movement (e.g. the world is spinning) while dizziness related to autonomic dysfunction is typically described as symptoms of orthostatic intolerance (e.g. postural lightheadedness). It is important to differentiate the type of dizziness to guide proper diagnostic and therapeutic workup. We describe the case of a young patient evaluated in the autonomic clinic for dizziness, ultimately found to have a rare cerebellar neurodegenerative disorder.&#xa0;A 23-year-old female with a past medical history of migraine without aura presented in autonomic clinic with a four-month history of slow, progressive onset of vestibular dizziness. Neurological exam was notable for downbeat nystagmus, but no appendicular or truncal ataxia was appreciated. Subsequent vestibular evaluation was consistent with central vestibular dysfunction. Magnetic resonance imaging (MRI) of the brain with and without contrast was notable for severe cerebellar atrophy. The patient subsequently underwent genetic testing which demonstrated a pathogenic and likely pathogenic variant in the Anoctamin 10 (ANO10) gene, which is seen in Autosomal Recessive Spinocerebellar Ataxia, Autosomal Recessive Type 10 (SCAR10).&#xa0;To our knowledge, this case represents the first reported instance of SCAR10 presenting with the sole neurologic exam finding of downbeat nystagmus without cerebellar ataxia. Additionally, the finding of severe cerebellar atrophy seen on MRI, without gait or limb ataxia on exam is an interesting clinicoradiological dissociation. This case suggests that nystagmus may represent an early disease marker, even in the absence of clinical ataxia in patients with SCAR10.

Humans↗
PubMed1979

Electromyography and nerve conduction studies in Friedreich's ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Twenty four ataxic patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction. The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct from Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.

Action Potentials↗
PubMed1978

Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins.

A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.

Adolescent↗
PubMed1992

Ataxia-telangiectasia: linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome.

Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several "A-T-like" genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-T families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A. In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-T and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to 11q23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.

Ataxia↗
PubMed1979

Electroencephalographic findings in Friedreich's ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Electroencephalographic studies have been done in two groups of hereditary ataxia: a group bearing the classical features of Friedreich's ataxia and a group clinically different described as autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The qualitative anomalies observed in the two groups were similar and were comparable with the data reported in the literature. However, the main difference between the two groups is the greater incidence of EEG abnormalities in the ARSACS group, which suggests more involvement of the cortical and subcortical structures. This is reinforced by the lower I.Q. performance in the latter patients. Some comments are made about focal EEG findings, behavior and I.Q. In general, EEG was not considered a valuable instrument for diagnosis since no qualitative electric pattern could be identified. With regard to prognosis, EEG cannot be used as a criterion, since there is no relation between the degree of anomalies and the severity of the disease and since EEG does not worsen with the progression of the disease.

Adolescent↗
PubMed1978

Familial myoclonic epilepsy with ataxia and neuropathy with additional features of Friedreich's ataxia and peroneal muscular atrophy.

A family is described in which a mother and three of her five children showed myoclonic epilepsy. The mother and one son were also ataxic; one other son had additional features of Friedreich's ataxia, and a daughter had peroneal muscular atrophy as well as myoclonic epilepsy and ataxia. Although some of these disorders have been associated in previously reported families, the occurrence of all three disorders in members of one family seems to be unique. It is concluded that this family shows the manifestations of one, probably dominant, gene. The differences in age of onset and manifestations may be explained by the action of one or more subsidiary genes.

Adult↗
PubMed1992

Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia.

An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.

Adolescent↗
PubMed1978

Ataxia and disorders of purine metabolism: defects in hypoxanthine guanine phosphoribosyl transferase and clinical ataxia.

A relationship between disordered metabolism of purines and the central nervous system has been established by the Lesch-Nyhan syndrome. In this disorder a virtually complete defect in the activity of HGPRT is associated with a syndrome of severe mental retardation, choreoathetoid cerebral palsy, and bizarre, self-mutilative behavior. In patients with partial defects in HGPRT, two have had symptoms that have been labeled spinocerebellar. Neither were appreciably ataxic, and the relationship between the symptoms and the enzyme defect remains to be established. Analysis of HGPRT in members of a large kindred with spinocerebellar degeneration revealed normal levels of the enzyme. These observations suggest that a relationship between the activity of HGPRT and clinical ataxia is remote.

Ataxia↗
PubMed1992

Abnormal processing of transfected plasmid DNA in cells from patients with ataxia telangiectasia.

In order to assess spontaneous mutability and accuracy of DNA joining in ataxia telangiectasia, a disorder with spontaneous chromosome breakage, the replicating shuttle vector plasmid, pZ189, was transfected into SV40 virus-transformed fibroblasts from ataxia telangiectasia patients. The ataxia telangiectasia fibroblasts showed elevated frequency of micronuclei, a measure of chromosome breakage. The spontaneous mutation frequency was normal with circular plasmids passed through the ataxia telangiectasia line. These results were compared to those with transformed fibroblasts from a patient with xeroderma pigmentosum, and from a normal donor. Mutation analysis revealed spontaneous point mutations and deletions in the plasmids with all 3 cell lines, however, insertions or complex mutations were only detectable with the ataxia telangiectasia line. To assess DNA-joining ability, linear plasmids which require joining of the DNA ends by host cell enzymes for survival, were transfected into the cells. We found a 2.4-fold less efficient DNA joining in ataxia telangiectasia fibroblasts (p = 0.04) and a 2.0-fold higher mutation frequency (p less than 0.01) in the recircularized plasmids than with the normal line. Plasmid DNA joining and mutation frequency were normal with the xeroderma pigmentosum fibroblasts. These findings with the ataxia telangiectasia fibroblasts of abnormal types of spontaneous mutations in the transfected plasmid and inefficient, error-prone DNA joining may be related to the increased chromosome breakage in these cells. In contrast, an EB virus-transformed ataxia telangiectasia lymphoblast line with normal frequency of micronuclei showed normal types of spontaneous mutations in the transfected plasmid and normal frequency of DNA joining which was error-prone. These data indicate that mechanisms that produce chromosome breakage in ataxia telangiectasia cells can be reflected in processing of plasmid vectors.

Ataxia Telangiectasia↗
PubMed1976

Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia.

The 50 patients in this survey were classified by a panel of neurologists into 4 clinical sub-groups: Group Ia ("typical" Friedreich's ataxia, complete picture), Group Ib ("typical" Friedreich's ataxia, incomplete picture), Group IIa ("atypical" Frriedreich's ataxia, possible recessive Roussy-Levy syndrome), Group IIb (heterogeneous ataxias). The clinical symptoms and signs were analyzed for each of these groups. A constellation of signs constantly present in Friedreich's ataxia and obligatory for diagnosis was described. Other important symptoms, such as the Babinski sign, kyphoscoliosis and pes cavus were found to be progressive, but not essential for the diagnosis at any given time. Finally, a host of other symptoms can only be called accessory. The progression of scoliosis was found to be an important tool in the differential diagnosis of ataxias. Our study also indicates, in contrast to the opinion of some authors, that absent deep tendon reflexes in the lower limbs and early dysarthria are essential in "typical" Friedreich's ataxia.

Adolescent↗
PubMed1992

Cerebellar ataxia in the elderly.

In a retrospective study of 624 elderly patients referred with falls and gait disorders, 45 patients were found to have ataxia. Cerebrovascular diseases were the most common underlying cause of ataxia (15 patients, 37%). Nine patients had hereditary/degenerative cerebellar ataxia. History suggesting alcohol as an underlying cause was established in two patients with cerebellar ataxia. Three patients had normal pressure hydrocephalus and their condition improved remarkably after surgery. No definite cause was found in five patients. Cranial computed tomography (CT) showed cerebral atrophy in 16 patients and in three patients there was evidence of atrophy of the cerebellar vermis. Four patients had femoral neck fractures and three patients had other fractures. In a 5-year follow-up five patients died with bronchopneumonia (11% mortality) and patients with dementia showed rapid deterioration. All patients were referred to the day hospital for rehabilitation. The best treatment outcome was achieved in patients who had a single cerebrovascular accident with no cognitive impairment and in those whose ataxia was secondary to medication. Fourteen patients (44%) moved to residential care while 27 (66%) continued to live in their homes with community support. We concluded that there is no evidence of increased mortality in the elderly patients with cerebellar ataxia. CT scan is mainly helpful in diagnosing specific diseases such as tumours or hydrocephalus. A significant proportion of elderly patients with ataxia may have reversible or treatable conditions and can pursue an independent life.

Aged↗
PubMed2025

First Report of Co-Occurring FGF14 (SCA27B) and RFC1 (CANVAS) Repeat Expansions in Two of Three Siblings with Late-Onset Cerebellar Ataxia.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) and spinocerebellar ataxia type 27B (SCA27B) are two increasingly recognized types of late-onset ataxia caused by biallelic RFC1 AAGGG and heterozygous FGF14 GAA repeat expansions, respectively. We describe three siblings of Greek-Cypriot origin with late-onset cerebellar ataxia. Two brothers carried biallelic pathogenic RFC1 AAGGG expansions and heterozygous FGF14 GAA expansions (338-350 repeats), establishing a dual diagnosis of CANVAS and SCA27B. Both presented with progressive gait ataxia, vestibular dysfunction, and sensory neuronopathy; one also reported episodic symptoms typical of SCA27B. Their sister, heterozygous for RFC1 and carrying a pathogenic FGF14 expansion (325 repeats), showed a pure SCA27B phenotype with episodic fluctuations, but without neuropathy or vestibular involvement. Brain MRI in all three demonstrated mild-to-moderate vermian atrophy.&#xa0;To our knowledge, this is the first documented report of co-occurring CANVAS and SCA27B in the same individuals. The findings expand the phenotypic spectrum of late-onset ataxia and highlight the importance of continued genetic testing, even after an initial diagnosis has been made.

Humans↗
PubMed2026

Longitudinal progression, metrics, age-dependence, and modifiers of ataxia severity in SCA27B: a multicentre study of 219 patients.

BACKGROUND: Spinocerebellar Ataxia 27B (SCA27B) is a novel, frequent and likely treatable late-onset autosomal-dominant ataxia caused by GAA repeat-expansions in FGF14. For understanding disease evolution and imminent trial planning, metrics of the most widely used clinical outcome assessment (Scale for the Assessment and Rating of Ataxia/SARA), longitudinal progression and modifiers thereof are warranted. METHODS: Multicentre intercontinental observational study (2015-2024) of 661 assessments from 219 patients with SCA27B (age: 68 &#xb1; 10 years; SARA: 9 &#xb1; 6 points) with item-level distribution-based analyses to characterise SARA metrics relative to ageing-related impairment in 390 healthy controls; and linear mixed-effects modelling to determine longitudinal progression and demographic or genetic modifiers. FINDINGS: Ataxia severity in SCA27B as assessed by SARA was primarily attributable to gait, stance, and lower-limb impairment; other ataxia domains scored &#x2264;1 SARA point in 79-94% of patients. Discrimination of SCA27B motor performance from controls decreased with age due to ageing-related motor variability captured by SARA, thus limiting potential metric response windows for symptomatic treatments. Disease progression was faster in the presence of interfering ageing-related comorbidities in 14 (6%) patients. Overall longitudinal progression of SCA27B was 0.54 SARA points/year [95% CI: 0.37-0.71]. Expansions of (GAA)> 180 repeats were frequent also on the shorter allele (n = 18 (8%), range: 196-348 repeats), and associated with faster progression (+1.6 SARA points/year, [95% CI: 0.9-2.2]), including also otherwise less affected ataxia domains speech and sitting. INTERPRETATION: Disease progression in SCA27B is characterised by mild progression, ageing-related motor variabilities and comorbidities, and associated with repeat size on both alleles. FUNDING: Else-Kr&#xf6;ner-Fresenius-Stiftung, EU, DFG, BMBF, CIHR, NAF, Ataxia-UK, CSC.

Humans↗
PubMed1978

Evidence for a primary defect of lipoamide dehydrogenase in Friedreich's ataxia.

There is now a great deal of evidence to link genetic defects of pyruvate metabolism to brain disease. Experimental evidence is reviewed in Chapter 12, and clinical evidence has been reviewed above. Severe lesions of components of the pyruvate dehydrogenase complex are associated with severe generalized brain disease, and milder defects with inherited ataxias. Nearly half of one series of our ataxic patients had deficient activity of pyruvate dehydrogenase, and 40% of another series have deficient activity of the lipoamide dehydrogenase component. This last group corresponds to 60% of the patients with Friedreich's ataxia and its clinical variants at UCLA. There is an association between defective activity of lipoamide dehydrogenase and disease, and the data suggest there is a structural mutation of the gene for the enzyme. Preliminary studies suggest that obligate heterozygotes as a group have enzyme activities between those for controls and those for patients. Moreover, the obligate heterozygotes from families in which there are kinetic defects of lipoamide dehydrogenase also appear to have kinetic abnormalities of the enzyme. The ataxic patients with reduced lipoamide dehydrogenase activity currently fall into two clinical groups. One is ragged-red ataxia, and the other is a disorder that is a subgroup of the classic Friedreich's ataxia syndrome. Studies need to be undertaken on a larger group of patients, with more diverse inherited ataxias, to test the present clinical associations of the enzyme defect. A dietary treatment derived from a knowledge of the presumed defect has modified the ataxia that is associated with defects of pyruvate decarboxylase, but the diet has not yet been tested with defects of lipoamide dehydrogenase.

Ataxia↗