| Degenerative cerebellar ataxia with autoantibodies against glutamic acid decarboxylase (GAD) is a rare disorder and may represent a subset of ataxias previously classified as idiopathic. The authors report a patient with progressive cerebellar ataxia, insulin-dependent diabetes mellitus, and GAD antibodies who responded to i.v. immunoglobulins. ( info) |
2/539. Juvenile nephronophthisis associated with retinal pigmentary dystrophy, cerebellar ataxia, and skeletal abnormalities. A boy aged 9 3/4 years with interstitial nephritis, retinal pigmentary dystrophy, cerebellar ataxia, and skeletal abnormalities is described. The association may be due to a new genetic disorder, since 2 similar cases have been reported. ( info) |
3/539. Familial hemiplegic migraine with cerebellar ataxia and paroxysmal psychosis. Familial hemiplegic migraine is a rare autosomal dominant disorder associated with stereotypic neurologic aura phenomena including hemiparesis. So far two chromosomal loci have been identified. Families linked to the chromosome 19 locus display missense mutations within the CACNL1A4 gene. Here we report on a family with familial hemiplegic migraine and cerebellar ataxia with recurrent episodes of acute paranoid psychosis with anxiety and visual hallucinations associated with migraine attacks. Based on the clinical and haplotype evidence indicating linkage to chromosome 19 in this family, we hypothesize that a dysfunction of the mutated calcium channel may be involved not only in the development of hemiplegic migraine but also in the acute psychotic episodes observed in these patients. ( info) |
| A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic dna and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection. ( info) |
5/539. Juvenile neuroaxonal dystrophy: clinical, electrophysiological, and neuropathological features. We describe 2 brothers with progressive myoclonus epilepsy that began in the second decade and was associated with cerebellar ataxia and intellectual deterioration. Electroencephalographic and cerebral evoked potential studies showed findings associated with myoclonus epilepsy. Neuropathological examination of 1 of the brothers, who died at age 23 years, revealed widespread changes of neuroaxonal dystrophy without pigment deposition in the basal ganglia. We propose the term juvenile neuroaxonal dystrophy (JNAD) to distinguish this condition on clinical grounds from infantile neuroaxonal dystrophy on the one hand, and on clinical and pathological grounds from Hallervorden-Spatz disease on the other hand. JNAD, while exceedinly rare, must be considered in the differential diagnosis of the progressive myoclonus epilepsies. ( info) |
| bordetella pertussis (BP), the agent of whooping cough, has not been recognized so far as a cause of permanent cerebellar ataxia in human. We describe three patients who developed a disabling and permanent cerebellar syndrome soon after whooping cough. In two patients, diagnosis of BP infection was confirmed by culture of nasopharyngeal secretions. The infection occurred between the age of 13 and 15 years, with neurological symptoms beginning after a delay varying from 3 weeks to 3 months. In our three patients, the cerebellar syndrome was characterized by dysmetria of ocular saccades, scanning speech and ataxic gait. brain MRI demonstrated a pancerebellar atrophy. The pathogenesis of this cerebellar degeneration is not established. Experimental studies have demonstrated that the cerebellum is particularly vulnerable to lymphocytosis-promoting factor (LPF), one of the exotoxins from BP. The mechanism of this toxicity might be a marked increase in the cellular levels of 3',5'cyclic guanosine monophosphate (cGMP). Since whooping cough is a bacterial exotoxin-mediated disease, this is the first report of a cerebellar syndrome triggered by a bacterial exotoxin. ( info) |
7/539. movement-related cerebellar activation in the absence of sensory input. movement-related cerebellar activation may be due to sensory or motor processing. Ordinarily, sensory and motor processing are obligatorily linked, but in patients who have severe pansensory neuropathies with normal muscle strength, motor activity occurs in isolation. In the present study, positron emission tomography and functional magnetic resonance imaging in such patients showed no cerebellar activation with passive movement, whereas there was prominent movement-related cerebellar activation despite absence of proprioceptive or visual input. The results indicate that motor processing occurs within the cerebellum and do not support the recently advanced view that the cerebellum is primarily a sensory organ. ( info) |
8/539. Detection of a rare Wilson disease mutation associated with arylsulfatase A pseudodeficiency. We have studied a patient with Wilson disease (WD), belonging to a family segregating late-onset, dominant cerebellar ataxia. Analysis of the WD gene showed that the patient is a compound heterozygote, carrying the 14His1069Gln mutation from the father and the 8Gly710Ser mutation from the mother. The 8Gly710Ser is a mutation described previously only in a Swedish patient. Our patient is also homozygous for arylsulfatase A pseudodeficiency. This genetic defect, which has been reported in association with other neuropsychiatric syndromes, has not been described in WD. ( info) |
9/539. genetic heterogeneity in Italian families with familial hemiplegic migraine. OBJECTIVE: To verify linkage to chromosome 19p13, to detect mutations in the CACNA1A gene, and to correlate genetic results to their clinical phenotypes in Italian families with familial hemiplegic migraine (FHM). BACKGROUND: FHM is an autosomal dominant disease, classified as a subtype of migraine with aura. Only a proportion of FHM patients have been associated with chromosome 19p13. Among these, four missense mutations within the CACNA1A gene in five unrelated families have been described. methods: A linkage study was performed in 19 patients affected by FHM from five families by studying microsatellite markers associated with the 19p13 region. All familial and seven additional sporadic patients with FHM were analyzed to search for mutations within the CACNA1A gene by applying the double gradient-denaturant gradient electrophoresis technique. RESULTS: lod score values did not establish significantly linkage to chromosome 19. However, seven new genetic variants were detected: six were new polymorphisms. The seventh was a missense mutation present in family 1, and it was associated with a hemiplegic migraine phenotype without unconsciousness and cerebellar ataxia. Because this missense mutation is absent in the general population and cosegregates with the disease, it may be a pathologic mutation. CONCLUSIONS: genetic heterogeneity of FHM has been shown in familial and sporadic FHM patients of Italian origin. The new missense mutation-G4644T-is associated with milder clinical features compared with typical FHM. ( info) |
10/539. A new CACNA1A gene mutation in acetazolamide-responsive familial hemiplegic migraine and ataxia. OBJECTIVE: To search for mutations in the calcium channel gene CACNA1A and to study the genotype-phenotype correlation in a family with a severe familial hemiplegic migraine (FHM) phenotype and a slowly progressive cerebellar ataxia. BACKGROUND: CACNA1A gene mutations on chromosome 19 are involved in approximately 50% of FHM families. The association of FHM and cerebellar ataxia has been reported in a small number of FHM families, all linked to chromosome 19. methods: The proband, in addition to typical hemiplegic migraine attacks, experienced severe episodes during which hemiplegia was associated with acutely altered consciousness and fever lasting several days. She, as well as her affected sister, developed a permanent, late-onset cerebellar ataxia and cerebellar atrophy evident on MRI. Linkage analysis was performed and the whole CACNA1A gene, 47 exon-intron boundaries, was analyzed by double gradient-denaturing gradient gel electrophoresis (DG-DGGE). RESULTS: Genetic studies suggested linkage to chromosome 19p13, and DG-DGGE analysis detected a heteroduplex fragment in exon 13 of the CACNA1A gene. By direct sequencing, a G-to-A substitution resulting in an arginine to glutamine change at codon 583 in the second putative voltage sensor domain of the channel alpha1A-subunit, was identified, possibly representing the disease-causing mutation. The proband and her affected sister were treated with acetazolamide, reporting freedom from new FHM attacks but no benefit in the progression of ataxia. CONCLUSIONS: The combination of episodic dysfunction and permanent deficit could depend on the variety of functions of calcium channels and their distribution in the nervous system. ( info) |