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Autosomal-dominant olivopontocerebellar atrophy with retinal degeneration
difficult by tic variability, brief suppressibility, exacerbation by stress, anxiety, or fatigue, and parental over- or underestimation. Using data obtained from a behavior management study, we compared results obtained on 5 scales frequently used to evaluate the severity of tic symptoms. Sixteen patients with TS (14 males, 2 females), ages ranged 8-18 years, with normal IQs, had serial assessment of tic severity using 5 different instruments: Hopkins Motor and Vocal Tic Severity Scale (HMVTSS), Yale Global Tic Severity Scale (YGTSS), Tourette Syndrome Severity Scale (TSSS), Parent Linear Analog Scale (PLAS), and Goetz Videotape Scale (GVS). Scales were rated independently by at least 2 investigators. Interrater reliability was excellent. Using a Pearson Correlation Coefficient the HMVTSS strongly correlated with both the YGTSS and TSSS (r > 0.8; P < .001). Results comparing either the PLAS or the GVS with other instruments gave correlations of < 0.6 and 0.5, respectively. This study further establishes the equivalent effectiveness of HMVTSS, YGTSS, and TSSS as instruments in the evaluation of overall severity of tic symptoms. Although brief videotaped assessments contain important objective data, their significance in indicating overall behavior remains questionable.
147. AUTOSOMAL-DOMINANT OLIVOPONTOCEREBELLAR ATROPHY WITH RETINAL DEGENERATION Sergio Rosemberg, Fernado Arita, and Suzana Kliemann, S~o Paulo, Brazil OPCA with retinal degeneration is an exceedingly rare disease with only a few families reported in the literature. Our propositus, a 10-year-old white girl had uneventful development until age 8 years, when she presented with progressive visual loss, followed about 8 months later by gait disturbance. Neurologic examination disclosed an intelligent girl with an ataxic gait, unstable station, intention tremor, dysdiadochokineses, brisk tendon reflexes, and flexor plantar responses. Visual acuity was markedly impaired. The mother, age 37 years, manifested a gait disturbance when she was 26 years, followed 5 years later by progressive visual loss. Neurologic examination disclosed global cerebellar ataxia--unable to walk without support--hyperreflexia, ankle clonus, and Babinski sign. She became completely blind. In both patients, ophthalmologic examination revealed retinal degeneration and CT disclosed marked atrophy of the pons and cerebellum. The father and 2 aunts, as well as a brother and a sister of the mother's, has died from the same disease, which started in the third and fourth decades of life. Lymphocytes DNA analysis by Southern blotting and PCR failed to demonstrate a linkage to chromosome 6 as it occurs in some OPCA without retinal involvement. Similar to other families with this condition, the chronologic events in our patients suggest an anticipation phenomenon.
148. DEMYELINATION IN NIEMANN-PICK DISEASE, TYPE C Marc C. Patterson, Colette C. Parker, and Joseph J. Parisi, Bethesda, Maryland
Niemann-Pick disease, type C, (NPC) is a cellular cholesterol lipidosis with protean clinical manifestations, including developmental delay, apparent learning disability preceding frank de-
mentia, vertical supranuclear gaze palsy, ataxia, dysarthria, dysphagia, dystonia, spasticity, seizures, and gelastic cataplexy. Confirmation of the diagnosis is difficult, requiring complex biochemical testing available at only a limited number of centers. Cerebral and cerebellar atrophy are nonspecific findings that have been recognized on imaging studies and at autopsy in patients with NPC. We recognized 6 patients with NPC whose MRI scans demonstrated increased signal intensity in the periventricular white matter on T2-weighted images in addition to atrophy. In 1 patient, there was markedly increased fat signal in the marrow of cranial bones, consistent with lipid storage. We performed detailed neuropathologic studies on 1 patient. Macroscopic findings included cerebral, and particularly marked cerebellar vermis atrophy, with evidence of gliosis in the posterior periventricular regions. Microscopic study confirmed widespread neuronal loss with ballooning of surviving neurons. There was marked demyelination in the posterior periventricular white matter with less marked changes elsewhere. The neuropathologic findings correlated with the changes observed on MRI. We believe that the appearance of increased signal from the posterior periventficular white matter on T2-weighted MRI, with or without increased fat signal in the marrow of cranial bones, is a useful marker for NPC, and that its detection should prompt definitive diagnostic testing.
149. CLINICAL EXPERIENCE WITH FELBAMATE Warren A. Marks, Susan Rearden, Howard Kelfer, Mark Laney, Sharon Wilson, and Ronda August, Fort Worth, and Dallas, Texas Between August, 1993 and the end of March, 1994, we initiated felbamate in 78 children, ages 1-21 years (mean: 9.2 yrs; median: 8 yrs) with a variety of seizure types and epilepsy syndromes. The patients had been on an average of 3.6 (range 0-8) antiepileptic drugs prior to the addition of felbamate. Using average initial doses of 17 mg/kg, and titrating to maximal effective or tolerated doses (max: 91 mg/kg; mean: 49 mg/kg) effectiveness of therapy was determined as follows: improvement of 0-25% occurred in 16.7%; 25-50% in 16.7%; 50-75% in 23.6%; and 75-100% in 43.0%. Of 77 patients available for ongoing follow-up, felbamate has subsequently been discontinued in 18 (23.4%) because of rash in 4 (5.2%), gastrointestinal upset 2 (2.6%), ineffectiveness 4 (5.2%), and behavior/sleep disturbance 8 (10.4%). Lesser effects on behavior, both positive and negative, have been observed as well. Felbamate appears to offer a broad spectrum of antiepileptic efficacy. When tolerated, it can be an effective antiepileptic drug in selected pediatric patients, including many who had been refractory to other medications.
150. CLINICAL COURSES OF 12 STURGE-WEBER SYNDROME PATIENTS AND EVALUATION OF NEUROLOGIC THERAPY Shin-ichi Niijima, Yasuhiro Arai, Masahiro Saitoh, Keiko Kuremoto, Keiichi Takahashi, Keijiro Yabuta, Kiyoshi Satoh, and Chikaya Ohtsuka, Tokyo, Japan
From the aspect of neuropathology, the essential manifestation of Sturge-Weber syndrome (SWS) is leptomeningeal angioma-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 123
147. AUTOSOMAL-DOMINANT OLIVOPONTOCEREBELLAR ATROPHY WITH RETINAL DEGENERATION Sergio Rosemberg, Fernado Arita, and Suzana Kliemann, S~o Paulo, Brazil OPCA with retinal degeneration is an exceedingly rare disease with only a few families reported in the literature. Our propositus, a 10-year-old white girl had uneventful development until age 8 years, when she presented with progressive visual loss, followed about 8 months later by gait disturbance. Neurologic examination disclosed an intelligent girl with an ataxic gait, unstable station, intention tremor, dysdiadochokineses, brisk tendon reflexes, and flexor plantar responses. Visual acuity was markedly impaired. The mother, age 37 years, manifested a gait disturbance when she was 26 years, followed 5 years later by progressive visual loss. Neurologic examination disclosed global cerebellar ataxia--unable to walk without support--hyperreflexia, ankle clonus, and Babinski sign. She became completely blind. In both patients, ophthalmologic examination revealed retinal degeneration and CT disclosed marked atrophy of the pons and cerebellum. The father and 2 aunts, as well as a brother and a sister of the mother's, has died from the same disease, which started in the third and fourth decades of life. Lymphocytes DNA analysis by Southern blotting and PCR failed to demonstrate a linkage to chromosome 6 as it occurs in some OPCA without retinal involvement. Similar to other families with this condition, the chronologic events in our patients suggest an anticipation phenomenon.
148. DEMYELINATION IN NIEMANN-PICK DISEASE, TYPE C Marc C. Patterson, Colette C. Parker, and Joseph J. Parisi, Bethesda, Maryland
Niemann-Pick disease, type C, (NPC) is a cellular cholesterol lipidosis with protean clinical manifestations, including developmental delay, apparent learning disability preceding frank de-
mentia, vertical supranuclear gaze palsy, ataxia, dysarthria, dysphagia, dystonia, spasticity, seizures, and gelastic cataplexy. Confirmation of the diagnosis is difficult, requiring complex biochemical testing available at only a limited number of centers. Cerebral and cerebellar atrophy are nonspecific findings that have been recognized on imaging studies and at autopsy in patients with NPC. We recognized 6 patients with NPC whose MRI scans demonstrated increased signal intensity in the periventricular white matter on T2-weighted images in addition to atrophy. In 1 patient, there was markedly increased fat signal in the marrow of cranial bones, consistent with lipid storage. We performed detailed neuropathologic studies on 1 patient. Macroscopic findings included cerebral, and particularly marked cerebellar vermis atrophy, with evidence of gliosis in the posterior periventricular regions. Microscopic study confirmed widespread neuronal loss with ballooning of surviving neurons. There was marked demyelination in the posterior periventricular white matter with less marked changes elsewhere. The neuropathologic findings correlated with the changes observed on MRI. We believe that the appearance of increased signal from the posterior periventficular white matter on T2-weighted MRI, with or without increased fat signal in the marrow of cranial bones, is a useful marker for NPC, and that its detection should prompt definitive diagnostic testing.
149. CLINICAL EXPERIENCE WITH FELBAMATE Warren A. Marks, Susan Rearden, Howard Kelfer, Mark Laney, Sharon Wilson, and Ronda August, Fort Worth, and Dallas, Texas Between August, 1993 and the end of March, 1994, we initiated felbamate in 78 children, ages 1-21 years (mean: 9.2 yrs; median: 8 yrs) with a variety of seizure types and epilepsy syndromes. The patients had been on an average of 3.6 (range 0-8) antiepileptic drugs prior to the addition of felbamate. Using average initial doses of 17 mg/kg, and titrating to maximal effective or tolerated doses (max: 91 mg/kg; mean: 49 mg/kg) effectiveness of therapy was determined as follows: improvement of 0-25% occurred in 16.7%; 25-50% in 16.7%; 50-75% in 23.6%; and 75-100% in 43.0%. Of 77 patients available for ongoing follow-up, felbamate has subsequently been discontinued in 18 (23.4%) because of rash in 4 (5.2%), gastrointestinal upset 2 (2.6%), ineffectiveness 4 (5.2%), and behavior/sleep disturbance 8 (10.4%). Lesser effects on behavior, both positive and negative, have been observed as well. Felbamate appears to offer a broad spectrum of antiepileptic efficacy. When tolerated, it can be an effective antiepileptic drug in selected pediatric patients, including many who had been refractory to other medications.
150. CLINICAL COURSES OF 12 STURGE-WEBER SYNDROME PATIENTS AND EVALUATION OF NEUROLOGIC THERAPY Shin-ichi Niijima, Yasuhiro Arai, Masahiro Saitoh, Keiko Kuremoto, Keiichi Takahashi, Keijiro Yabuta, Kiyoshi Satoh, and Chikaya Ohtsuka, Tokyo, Japan
From the aspect of neuropathology, the essential manifestation of Sturge-Weber syndrome (SWS) is leptomeningeal angioma-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 123