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Results for “Hereditary ataxia”

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At least 19 recordsLinked to original sources
PubMed1975

Protein patterns of cerebrospinal fluid in hereditary ataxias and hereditary spastic paraplegia.

The CSF findings in hereditary ataxias and allief disorders have hitherto mostly been reported as normal if one excludes Refsum's syndrome. The CSF-protein patterns found on isoelectric focusing and quantitative paper electrophoresis were studied in 12 patients with hereditary ataxias and hereditary spastic paraplegia. Using a recently-developed technique of isoelectric focusing of CSF-proteins in flat beds of polyacrylamide gel, the authors could show abnormal CSF-protein patterns in all but 1 of the present cases. The aberrant CSF-protein patterns found showed differences between the syndromes studied. Two unique patterns with conspicuous fractions in the acid range were observed in patients with Marie-Sanger-Brown's ataxia (mother and daughter) and Holmes' ataxia. A third CSF-protein pattern was found in a sibship with Friedreich's ataxia including a double fraction in the acid region (pI 5.9-6.1) in all 4 subjects and a highly alkaline fraction (HAF) with pI about 9.3, in 3 of them. Similar acid fractions (pI 5.9-6.1) were also detected in 3 of 4 patients with hereditary spastic paraplegia, a brother and sister showing a very similar CSF-protein pattern. Double fractions with pI 5.9-6.1 and/or HAF may also occur in other neurological diseases, mostly, however, associated with other distinctive features of their CSF-protein patterns. A possibility in the future of distinguishing hereditary CNS-diseases by examination of the CSF-protein pattern is suggested.

Abetalipoproteinemia↗
PubMed1978

Computerized tomography in hereditary ataxias.

Thirty-nine patients with hereditary ataxia (HA), hereditary spastic paraplegia or Charcot-Marie-Tooth disease were investigated with computerized cranial tomography (CT). Infratentorial as well as supratentorial atrophies were registrated and scored. These were compared with the patient's neurological symptoms, which were related to the lesion in the central nervous system, and scored. There was correlation between the distribution of brainstem/cerebellar symptoms and the distribution and degree of infratentorial atrophy. HA cases with cerebral cortical atrophy had significantly higher dementia scores than those without wide sulci. Intravenous injection with contrast medium was of no diagnostic aid, as no focal changes were found. It is concluded that CT is an aid in the diagnosis of hereditary ataxias and hereditary spastic paraplegia.

Adult↗
PubMed1978

HLA--determination in families with hereditary ataxia.

In three families with hereditary ataxia, where the inheritance pattern was autosomal and dominant, HLA antigens were determined in 25 members. In two of the families, HLA linkage of disease was suggested, whereas in the third family, the data did not directly support this concept, since two recombinational events between the postulated locus for disease and the HLA region had to be assumed. However, with this assumption, our data are compatible with those of one family described recently (Jackson et al. 1977) implying the presence on the sixth chromosome, outside the HLA region, of a locus that determines the development of spino cerebellar ataxia (SCA). Further tests with definition of enzyme markers will have to be performed before conclusions as to HLA linkage of a postulated SCA gene can be made.

Adolescent↗
PubMed1977

Adult-onset hereditary ataxia in Scotland.

A systematic search for cases of adult-onset hereditary ataxia was conducted on location in Scotland. The investigation resulted in the discovery of eight pedigrees with 42 patients of whom 16 were alive in 1975. Nine patients were examined by the authors and recent hospital records were available on the remaining seven. The clinical features were quite variable. In declining order of frequency, findings were gait and limb ataxia, dysarthria, hyperreflexia, extrapyramidal motor disturbances, impaired vibratory sense, spasticity, defects of extraocular movements and nystagmus, reflex depression, Babinski signs, impaired joint position sense, muscle weakness, optic atrophy, and mental abnormalities. Foot deformity occurred only once. Inheritance was compatible with autosomal dominant transmission, but complicated by consanguinity in two families. The minimum prevalence was calculated as 0.31/100,000. Autopsy in two members in one family revealed olivopontocerebellar degeneration.

Adult↗
PubMed1978

Computed tomography in hereditary ataxias.

Cranial CT in 39 patients (23 belonged to 8 families) with four different groups of hereditary ataxia (HA) showed mainly three combinations of atrophic findings: (1) cerebellar ataxia (CA, n = 17) had marked atrophy of the cerebellum and/or the brain stem combined with moderate cerebral atrophy; (2) an intermediate group consisting of hereditary spastic paraplegia (HSP, n = 10) and Friedreich's ataxia (FA, n = 7), both with moderate infra- and supratentorial atrophy; (3) atrophy was hardly demonstrated in the group of Charcot-Marie-Tooth disease (CMT, n = 5). HA cases with atrophy could be distinguished from multiple sclerosis (MS) by CT.

Adolescent↗
PubMed1978

[Epidemiology and clinical polymorphism of hereditary ataxia].

The paper is concerned with a clinico-genetical analysis of 66 patients with hereditary ataxia from 44 families. The authors describe typical and atypical variants of separate clinical forms, underline the intra-and interfamilial polymorphism of the clinical picture. The study contains a detailed description of intellectual and extraneuronal changes, a characteristics of the EEG, EMG and REG changes.

Adolescent↗
PubMed1979

Cellular hypersensitivity to brain antigen in children of a family with hereditary ataxia.

Sensitisation to brain antigen was demonstrated in eight of 24 clinically normal first generation children in a family with hereditary ataxia. This ratio is consistent with that expected in a dominantly inherited condition. It suggests that immunological reactivity may precede the clinical expression of disease, with important implications for presymptomatic diagnosis and for pathogenesis of degenerative disease.

Adolescent↗
PubMed2026

AAV-mediated CBLN1 replacement rescues hereditary ataxia caused by bi-allelic CBLN1 variants.

Cbln1 is a secreted synaptic organizer required for parallel fiber-Purkinje cell (PF-PC) synapse integrity, climbing fiber (CF) refinement, and cerebellar motor learning but has not previously been implicated in human disease. We identified bi-allelic CBLN1 missense variants (A63P and Y112C) in two unrelated families with early-onset cerebellar ataxia accompanied by oculomotor abnormalities, cerebellar atrophy, and variable cognitive delay. In heterologous cells, both variants showed reduced steady-state protein abundance, impaired maturation through the early secretory pathway, and little or no detectable secretion, resulting in markedly reduced extracellular CBLN1 availability. Consistently, cerebellar granule cells expressing CBLN1-Y112C failed to induce excitatory synapses onto glutamate receptor δ2 (GluD2)-expressing cells in vitro. A knockin mouse harboring Y112C lacked synaptic Cbln1 and recapitulated key features of Cbln1 deficiency, including disrupted PF-PC synapse organization, persistent CF multi-innervation, impaired PF-PC transmission, and long-term depression, and deficits in motor coordination and oculomotor learning. Notably, systemic delivery of an astrocyte-targeted adeno-associated virus expressing wild-type CBLN1 in adult mutant mice restored synaptic CBLN1 localization, cerebellar synaptic function, plasticity, and behavior. These findings establish CBLN1 deficiency as a cause of hereditary ataxia and identify extracellular CBLN1 replacement as a therapeutic strategy for a reversible cerebellar synaptopathy.

CBLN1↗
PubMed2025

Purkinje cell development and degeneration in the spastic Han-Wistar rat model of ataxia.

Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we aimed to determine the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, which coincided with a gradual loss of Purkinje cells in the cerebellum. Additionally, guided by pedigree analysis from a previous study indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. We used Sanger sequencing to exclude non-causal candidates. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia and broader neurodegenerative disorders.

Hereditary ataxia↗
PubMed1977

Slow eye movements, with absent saccades, in a patient with hereditary ataxia.

Saccadic and smooth eye movements are controlled by separate mechanisms within the nervous system. We describe a patient with familial ataxia, considered to be a form of olivopontocerebellar degeneration, who is incapable of generating reflex or voluntary saccades. She can, however, move her eyes smoothly to the normal limits of lateral gaze, even when her head is prevented from moving. Latency before onset of movement is prolonged, and the velocity of movement is abnormally slow. We postulate that the degenerative process may have affected selectively those cells of the ventral paramedian pontine tegmentum responsible for the generation of saccades; and the the prolonged latency from presentation of a visual stimulus to the onset of movement is related to an inability to generate burst discharges needed to overcome the viscoelastic properties of the orbital tissues.

Adult↗
PubMed1979

Computed tomography of posterior fossa in hereditary ataxias.

Nine cases of Friedreich's ataxia and seven cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) were submitted to neuroradiological procedures to determine the extent of atrophic processes in the central nervous system. All cases had a computerized cerebral tomography and five were studied with pneumoencephalography. The results show a correlation between the two tests and the comparison between Friedreich's ataxia and ARSACS. In Friedreich's ataxia, the radiological signs are variable and discrete in most of the cases. In ARSACS there are constant signs of cerebellar atrophy almost limited to the superior parts of the vermis and anterior lobes.

Adolescent↗