1/390. Manifestation of Hashimoto's encephalopathy years before onset of thyroid disease. patients with Hashimoto's encephalopathy (HE), a steroid-responsive disorder, associated with Hashimoto's disease and high levels of thyroid-related autoantibodies usually present with a subacute onset of confusion, focal or generalized seizures. Frequent EEG abnormalities include generalized, rhythmic bifrontal or temporal slowing. Elevated protein levels or an intrathecal IgG synthesis may be present in cerebrospinal fluid (CSF). A 39-year-old woman underwent a relapsing course of myocloni and generalized seizures. Initially, thyroid function, thyroid-related autoantibody screening and cerebral MRI were unrevealing. CSF showed oligoclonal bands. Short-term treatment with high doses of prednisolone resolved the myocloni. During the 5th episode of myocloni, signs of hyperthyroidism and elevation of thyroid microsomal antibody titer developed. Hashimoto's thyroiditis and HE were diagnosed. After subtotal thyroidectomy the patient remained asymptomatic. ( info) |
2/390. Clinical, pathologic, and neurochemical studies of an unusual case of neuronal storage disease with lamellar cytoplasmic inclusions: a new genetic disorder? A child of first-cousin Puerto Rican parents had global developmental delay, failure to thrive, and hypotonia since early infancy. At 1 1/2 years of age, she developed clinical and electrophysiologic evidence of progressive motor and sensory neuropathy. At 2 1/2 years, she developed visual impairment and optic atrophy followed by gradual involvement of the 7th, 9th, 10th, and 12th cranial nerves. Uncontrollable myoclonic seizures began at 4 years and she died at 6 years of age. Motor nerve conduction velocities were initially normal and later became markedly slowed. Sensory distal latency responses were absent. Lysosomal enzyme activities in leukocytes and fibroblasts were normal. sural nerve and two muscle biopsies showed only nondiagnostic abnormalities. Electron microscopy of lymphocytes, skin, and fibroblasts showed cytoplasmic inclusions. Light microscopy of frontal cortex biopsy showed neuronal storage material staining positively with Luxol fast blue, and electron microscopy showed cytoplasmic membranous bodies in neurons, suggesting an accumulation of a ganglioside. At autopsy, all organs were small but otherwise normal and without abnormal storage cells in the liver, spleen, or bone marrow. Anterior spinal nerve roots showed loss of large myelinated axons. The brain was small and atrophic; cortical neurons showed widespread accumulation of storage material, most marked in the pyramidal cell layer of the hippocampus. Subcortical white matter was gliotic with loss of axons and myelin sheaths. In cortical gray matter there was a 35% elevation of total gangliosides, with a 16-fold increase in GM3, a three- to four-fold increase in GM2 gangliosides, and a 15-fold elevation of lactosyl ceramide. GM3 sialidase activity was normal in gray matter at 3.1 nmols/mg protein per hour and lactosyl ceraminidase I and II activities were 70% to 80% of normal. In white matter, total myelin was reduced by 50% but its composition was normal. Phospholipid distribution and sphingomyelin content were normal in gray matter, white matter, and in the liver. These biochemical findings were interpreted as nonspecific abnormalities. The nature of the neuronal storage substance remains to be determined. ( info) |
3/390. Long-term follow-up of an individual with vitamin B6-dependent seizures. We report on a 31-year-old female with vitamin B6-dependent seizures whose seizure onset was in the neonatal period. Her elder brother had the same disorder and died in infancy. Administration of vitamin B6 was initiated in the postnatal period. At the age of 12 years 1 month, 2 months after withdrawal of vitamin B6, visual seizures began to occur frequently. Myoclonic seizures and occasional generalized convulsive seizures were also observed. At the same time, photoparoxysmal response and spontaneous diffuse spike-wave bursts were seen on her EEG. Myoclonic seizures were provoked by intermittent photic stimulation during the EEG. It is distinctive that visual seizures were one of the main seizure types in this patient, that her clinical course was relatively benign, and that she has normal intellectual outcome. ( info) |
4/390. A novel mutation (8342G-->A) in the mitochondrial tRNA(Lys) gene associated with progressive external ophthalmoplegia and myoclonus. We describe a patient who suffered from impaired ocular motility from age 10 years and at 16 years developed ptosis, proximal weakness and progressive fatigability. At 35 years she developed massive myoclonic jerks, and head and distal tremor. A muscle biopsy showed a high percentage of cytochrome c oxidase negative fibers but no ragged-red fibers. A novel heteroplasmic mutation (8342G-->A) was found in the mitochondrial transfer rna(Lys) gene by single-strand conformation polymorphism screening, followed by sequence and restriction fragment length polymorphism analysis. Approximately 80% of muscle mitochondrial dna (mtDNA) harbored the mutation, while the mutation was absent in lymphocyte dna of the proband, as well as of her mother, daughter and a maternal aunt. However, the pathogenicity of the mutation was confirmed by restriction fragment length polymorphism analysis of single muscle fibers, which revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase negative over cytochrome c oxidase positive fibers. ( info) |
5/390. 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) |
6/390. Nonconvulsive status epilepticus in childhood localization-related epilepsy. PURPOSE: To report on three children with localization-related epilepsy who exhibited minor seizures (atypical absences, brief atonic, and myoclonic) and nonconvulsive status epilepticus (NCSE) consisting of these minor seizures, and to elucidate their significance. methods: We studied the electroclinical characteristics of these children. Ictal electroencephalograms (EEGs) of NCSE were evaluated by using simultaneous video-EEG-electromyogram (EMG) polygraphic recordings. RESULTS: All patients began to have partial seizures between the ages of 6 months and 2 years 7 months, with minor seizures appearing later, between the ages of 1 year 11 months and 6 years 6 months. These minor seizures evolved into NCSE. Complex partial seizures remained after suppression of the minor seizures. Interictal EEGs taken when the minor seizures appeared showed excessive diffuse epileptic discharges in addition to multifocal spike-waves. Before and after suppression of the minor seizures, focal epileptic discharges predominated on the EEGs. On ictal EEGs of brief atonic and myoclonic seizures, diffuse spike-wave and polyspike-wave bursts were detected. Ictal EEGs of the atypical absences revealed diffuse spike-wave bursts mixed with irregular high-voltage slow waves, often interspersed with brief atonic and myoclonic seizures. When atypical absences lasted for a long time, patients manifested NCSE. Polytherapy might be related to the occurrence of minor seizures and NCSE, because all patients were treated with polytherapy at their appearance, and simplification of antiepileptic drug (AED) therapy seemed to be effective. CONCLUSIONS: We concluded that this NCSE is a type of atypical absence status which is an age-dependent, transient, electroclinical condition. The mechanism of occurrence of these minor seizures might be related to secondary bilateral synchrony. ( info) |
7/390. Myoclonic encephalopathy and diabetes mellitus in a boy. We describe an 18-month-old boy with insulin-dependent diabetes mellitus who developed idiopathic myoclonic encephalopathy (dancing eye syndrome) at 26 months of age. The neurological symptomatology (multifocal myoclonus, opsoclonus, ataxia, behavioural disturbance) developed within 10 to 14 days after presentation. Biological, neuroradiological, and scintigraphic examination excluded CNS infectious diseases, intoxication, or tumours. At onset of diabetes mellitus, anti-glutamic-acid decarboxylase (GAD) antibodies were observed, and markedly increased in titre when myoclonic encephalopathy occurred. Corticosteroid treatment resulted in a decrease in anti-GAD autoantibody titres and the disappearance of neurological disturbances. As GAD is expressed both in pancreatic beta-cells and cerebellar purkinje cells, it is possible that a common autoimmune disorder in this patient may account for both the diabetes and myoclonic encephalopathy. ( info) |
8/390. Nonconvulsive status epilepticus in eyelid myoclonia with absences--evidence of provocation unrelated to photosensitivity. A 10-year old girl with eyelid myoclonia with absences (EMA) in whom nonconvulsive status epilepticus developed shortly after awakening is described. A video-polygraphic recording during the status showed the characteristic eye-closure provocation of eyelid myoclonia with upward deviation of the eyeballs and brief absences. Ictal EEG showed generalized polyspikes concomitant with eyelid myoclonia, while absences were accompanied by 3.5 Hz polyspike-wave complexes on EEG. This condition occurred even in total darkness as well as even after seizures precipitated by bright sunlight had been eliminated by medication. The present case suggests that the eye closure mechanism could be a more potent precipitating factor than photosensitivity in the pathophysiology of EMA. ( info) |
9/390. Emotion-induced myoclonic absence-like seizures in a patient with inv-dup(15) syndrome: a clinical, EEG, and molecular genetic study. We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient. ( info) |
10/390. Myoclonic status epilepticus following high-dosage lamotrigine therapy. An 8-year-old girl with Lennox-Gastaut syndrome showed a partial reduction in seizure frequency when lamotrigine (LTG), 15 mg/kg per day, was added to clobazam (CLB) and vigabatrin (VGB). An increase in LTG dosage to 20 mg/kg per day produced no further improvement and was followed by myoclonic status epilepticus. The condition developed insidiously and ultimately became stable. Video-EEG polygraphy and jerk-locked back-averaged EEG demonstrated continuous myoclonus of cortical origin. Discontinuation of LTG resulted in rapid disappearance of clinical and electrophysiological manifestations of myoclonic status epilepticus. No episodes of myoclonus occurred in the subsequent 2 years, during which CLB and VGB were kept unchanged. The striking response to drug discontinuation suggests that LTG may have played a role in the precipitation of status, possibly within the context of paradoxical intoxication. ( info) |