11/619. A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy. Episodic ataxia type 1 (EA1) is a rare autosomal dominant disorder characterized by brief episodes of ataxia associated with continuous interattack myokymia. Point mutations in the human voltage-gated potassium channel (Kv1.1) gene on chromosome 12p13 have recently been shown to associate with EA1. A Scottish family with EA1 harbouring a novel mutation in this gene is reported. Of the five affected individuals over three generations, two had partial epilepsy in addition to EA1. The detailed clinical, electrophysiological and molecular genetic findings are presented. The heterozygous point mutation is located at nucleotide position 677 and results in a radical amino acid substitution at a highly conserved position in the second transmembrane domain of the potassium channel. Functional studies indicated that mutant subunits exhibited a dominant negative effect on potassium channel function and would be predicted to impair neuronal repolarization. potassium channels determine the excitability of neurons and blocking drugs are proconvulsant. A critical review of previously reported EA1 families shows an over-representation of epilepsy in family members with EA1 compared with unaffected members. These observations indicate that this mutation is pathogenic and suggest that the epilepsy in EA1 may be caused by the dysfunctional potassium channel. It is possible that such dysfunction may be relevant to other epilepsies in man. ( info) |
12/619. intracranial hypotension with parkinsonism, ataxia, and bulbar weakness. OBJECTIVE: To describe a case of spontaneous intracranial hypotension with a previously unreported constellation of presenting features. DESIGN: Case report. SETTING: Tertiary care center. MAIN OUTCOME AND RESULTS: We describe a patient with intracranial hypotension who presented with a parkinsonian syndrome and later development of ataxia and prominent bulbar symptomatology. headache was not a feature of her initial presentation and was only reported after repeated questioning during later evaluations. magnetic resonance imaging of the patient's head revealed findings characteristic of intracranial hypotension. An [18F]fluoro-m-tyrosine positron emission tomographic scan showed normal striatal activity, suggesting intact presynaptic nigrostriatal function. Opening pressure on lumbar puncture was reduced at 40 mm H2O. A source of cerebrospinal fluid leakage was not identified on nuclear cisternography and the patient underwent lumbar epidural blood patching, which resulted in complete resolution of her signs and symptoms as well as in a marked improvement in her imaging findings. CONCLUSIONS: The clinical spectrum of intracranial hypotension can be broadened to include parkinsonism, cerebellar ataxia, and prominent bulbar dysfunction. As with more common manifestations of the disorder, these features may resolve after appropriate treatment. ( info) |
13/619. Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia. Non-specific X-linked mental retardation is a heterogeneous group of disorders with an incidence of approximately 1 in 500 males. A recently identified gene in Xq12, encoding a Rho-GTPase-activating protein, was found to be mutated in individuals with mental retardation. We describe here two sisters with a 46,XY karyotype and a microdeletion of the oligophrenin-1 gene and 1.1 Mb of flanking dna. We have characterised the molecular interval defining this microdeletion syndrome with the fibre-FISH technique. A visual physical map of 1.2 Mb was constructed which spans the oligophrenin-1 gene and the androgen receptor gene. The analysis of the patients revealed a deletion which extended from the 5' end of the AR gene to a region approximately 80 kb proximal to the EPLG2 gene. The clinical manifestations of the two sisters include psychomotor retardation, seizures, ataxia, hypotonia and complete androgen insensitivity. Cranial MRI scans show enlargement of the cerebral ventricles and cerebellar hypoplasia. Our findings give further support for the involvement of the oligophrenin-1 gene in specific morphological abnormalities of the brain which is of importance in the investigation of male patients presenting with mental retardation. In combination with our results from physical mapping we suggest that a region around the oligophrenin-1 locus is relatively bereft of vital genes. ( info) |
| In rare cases, miller fisher syndrome (MFS) has been known to recur. However, clinical features of recurrent MFS have not been well analyzed, and the precipitating factors relating to recurrence remain unknown. From 1981 to 1996, we examined four patients with recurrent MFS among 28 Japanese MFS patients. In the four patients, the recurrent episodes occurred after long asymptomatic intervals, ranging from 2.5 to 12.5 years. The clinical and laboratory features of recurrent episodes were similar either to those of the initial episodes or to those of the 24 non-recurrent patients. Of the two patients tested for serum IgG anti-GQ1b antibody, both were positive. Serological HLA typing showed that all recurrent patients were both HLA-Cw3 and -DR2 positive. However, out of 13 non-recurrent patients examined, six had HLA-Cw3, and four had HLA-DR2. The frequency of HLA-DR2 among the recurrent patients was significantly higher than among healthy controls (corrected P = 0.038), and was also higher than among the non-recurrent patients but not significantly. These findings suggest that recurrent MFS is clinically the same as typical MFS and that HLA-DR2 is possibly associated with recurrence. ( info) |
15/619. A case of paroxysmal tonic upgaze of childhood with ataxia. Paroxysmal tonic upgaze of childhood is a rare, distinctive, childhood syndrome that may be associated with ataxia and sometimes strabismus or amblyopia. Neurological examination as well as metabolic studies, electroencephalogram and neuroradiological investigations are normal in these patients. Although it has been considered as an age-related, dopa-sensitive dystonia, the exact pathogenetic mechanism is still unknown. Aggravation of attacks by fatigue, intercurrent infection or vaccination, and possible corticomesencephalic dysmaturation may underlie this abnormality. We report on a sporadic case of paroxysmal tonic upgaze with ataxia in which there was prompt aggravation of symptoms with sleep without response to levodopa treatment. This case suggests a different underlying pathogenetic mechanism from dopaminergic pathways for this syndrome. ( info) |
| The authors report on a 17-year-old boy who suffered from slowly progressive and long-standing symptoms of ataxia, neck pain, and headache. Computerized tomography (CT) and magnetic resonance (MR) imaging revealed a tumor arising from the floor of the fourth ventricle that resulted in a moderate hydrocephalus. A partial resection was performed. Histological and immunohistological findings led to the diagnosis of an atypical central neurocytoma of the fourth ventricle. The imaging features on CT scanning, MR imaging, and proton MR spectroscopy studies, the clinical picture, and the prognosis of this very unusual tumor are discussed. Three cases of neurocytomas in the posterior fossa have been described to date; however, in all three cases some atypical aspects were present. In the present case, with the exception of the very unusual location, both imaging findings and clinical history perfectly met the definition of this rare tumor. ( info) |
17/619. time constraints improve reaching movements in an ataxic patient. We report on a patient (AM) with a post-traumatic ataxia who has uncoordinated reaching movements to resting targets, but is able to catch moving objects. AM participated in three experiments to identify factors responsible for the favorable effect of object motion on her performance. In the first experiment, the task was to catch an object that moved away from AM. The speed of the object to be grasped (target object) varied. In experiment 2, the effect of time constraints on reaching performance was examined. AM had to reach for and grasp a stationary object and was allowed either 600 ms or 2000 ms to perform the task. In the third experiment, liquid crystal shutter glasses were used to manipulate the time that the subject was able to view the stationary target object and her reaching movements (vision-on time). While increased speed of the object, tighter time constraints, and short vision-on time hardly affected the performance of AM's unaffected left hand, they greatly improved her right-hand performance. These results are discussed in light of the hypothesis that the brain mechanisms controlling externally triggered movements differ from those controlling internally regulated movements. ( info) |
18/619. A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? To investigate whether the expansion of CAG repeats of the TATA-binding protein (TBP) gene is involved in the pathogenesis of neurodegenerative diseases, we have screened 118 patients with various forms of neurological disease and identified a sporadic-onset patient with unique neurologic symptoms consisting of ataxia and intellectual deterioration associated with de novo expansion of the CAG repeat of the TBP gene. The mutant TBP with an expanded polyglutamine stretch (63 glutamines) was demonstrated to be expressed in lymphoblastoid cell lines at a level comparable with that of wild-type TBP. The CAG repeat of the TBP gene consists of impure CAG repeat and the de novo expansion involves partial duplication of the CAG repeat. The present study provides new insights into sporadic-onset trinucleotide repeat diseases that involve de novo CAG repeat expansion. ( info) |
19/619. IgG anti-GQ1b positive acute ataxia without ophthalmoplegia. IgG anti-GQ1b antibody was present in a patient with acute ataxia and areflexia without ophthalmoplegia or elementary sensory loss. Sensory nerve conduction studies and somatosensory evoked potentials were normal, but postural body sway analysis showed dysfunction of the proprioceptive afferent system. The clinical presentation and laboratory results for this patient resemble those of miller fisher syndrome, except for the lack of ophthalmoplegia. This case may represent part of an IgG anti-GQ1b syndrome. ( info) |
20/619. Clinical range and MRI in Creutzfeldt-Jakob disease with heterozygosity at codon 129 and prion protein type 2. A 68 year old woman with sporadic Creutzfeldt-Jakob disease is described, who neither showed characteristic EEG abnormalities nor a positive test of the neuronal protein 14-3-3 or neuron specific enolase (NSE) in CSF, despite a clinical presentation with ataxia of cerebellar type, rapidly progressive dementia, myoclonus, and marked hyperintense signal abnormalities in the deep cortical layers and the basal ganglia on T2 and diffusion weighted MRI. Moreover she showed atypical clinical features with a syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) and a peripheral sensorimotor polyneuropathy. Whether these disturbances are independent of Creutzfeldt-Jakob disease or a feature of it is discussed. It has recently been shown that in Creutzfeldt-Jakob disease different clinical and pathological phenotypes correlate with the polymorphism at codon 129 of the prion protein gene (PRNP) and the type of the protease resistant fragment that accumulates in the brain. According to the new classification at least six sporadic variants of Creutzfeldt-Jakob disease exist. The molecular genetic analysis showed heterozygosity of PRNP at codon 129 for methionine and valine and the presence of PrP(CJD) type 2 in the brain of this patient. As a new feature of changes on MRI, striking cortical changes of hyperintense signals are described in diffusion weighted as well as T2 weighted MRI that directly correlate with the histomorphological spongy degeneration of the brain in this region. In cases of rapidly progressive dementia, Creutzfeldt-Jakob disease always needs to be considered even if unusual features are present and current diagnostic criteria are not in favour of this disease. ( info) |