- Email: [email protected]
Bilateral striatal lesions
128. CHILDHOOD ENCEPHALOPATHY: A PROSPECTIVE STUDY Hussain I.H.M. Ismail, Sofiah Ali, and Ayesha Tajuddin, Kuala Lumpur, Malaysia A prospective study to determine the etiology and outcome of acute encephalopathy in children was undertaken at our institute from March to October, 1992. A total of 116 patients were enrolled and were classified as follows: infection 80 (68.9%), toxic solidus metabolic 15 (13%), hypoxic 6 (5.2%), hemorrhagic 4 (3.4%), and others 11 (9.5%). Within the infection group, 42 patients (51%) were affected by bacterial meningoencephalitis and 23 (28.7%) by viral encephalitis. The overall sex ratio of boys to girls was 2:1. Fifty percent of patients were younger than 1 year, 13% 1-2 years, and only 13.8% older than 6 years. Thirty-nine patients (33.6%) died during acute illness-26 from the infection group. Eighteen months later, 39 patients remained well and 31 (26.7%) had persistent neurologic deficit. Seven patients were lost to follow-up. The best outcome occurred in the toxic/metabolic group with 60% well at discharge, compared to only 35% in the infection group.
129. CLINICAL HETEROGENEITY IN mtDNA 8993 T>c POINT MUTATION Suk-Chun Mak, Filippo M. Santorelli, Marta E. VazquezMemije, Sara Shanske, Pamela Kranz-Eble, Daniel L. Bluestone, Darryl C. De Vivo, and Salvatore DiMauro, New York, New York and San Francisco, California A mitochondrial DNA (mtDNA) point mutation at position nt 8993T>c has been reported in association with neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) [1] and, when present in high percentage (>95%), with maternally inherited Leigh syndrome (MILS) [2]. LS patients bearing this mutation are severely affected and usually die in early infancy. Recently, a novel 8993T>c point mutation has been described in 4 siblings with a juvenile form of LS [3]. We studied 4 unrelated patients with the 8993T>c point mutation who demonstrated diverse clinical manifestations. Patient 1 (5-year-old boy) exhibited developmental delay, hypotonia, and ataxia. He had recurrent exacerbations during intercurrent illnesses, and eventually developed respiratory insufficiency and apnea. Patient 2 (13year-old boy) presented with a typical NARP phenotype, with neuropathy, ataxia, progressive visual loss due to retinitis pigmentosa, and mild developmental delay. Family history was suggestive of maternal inheritance. Patient 3 (4-year-old boy) had developmental delay, mild hypotonia, and ataxia. Intercurrent febrile episodes exacerbated the clinical course. MRI revealed bilateral lucencies in the basal ganglia on T2-weighted images. Patient 4 (19-year-old woman) demonstrated progressive muscle weakness, generalized seizures, and received a diagnosis of spinocerebellar ataxia. MRI disclosed bilateral abnormalities in the anterior aspect of the putamen. Total genomic DNA was extracted either from blood or muscle, and a 641 bp fragment encompassing the region of the NARP mutation was amplified by PCR, then purified. Both RFLP and sequencing analysis demonstrated a T > C point mutation at position nt 8993 of the mtDNA. The mutation was present in high percentage (>90%) in all 4 patients and was heteroplasmic in 20 maternal relatives. These findings suggest high phenotypic variability for the nt 8993T>c mutation. In contrast with the T > G change at the
118 PEDIATRICNEUROLOGY Vol. 11 No. 2
same position, the T > C mutation appears to cause milder clinical manifestations. References: [1] Holt IJ, Harding AE, Petty RKH, Morgan-Hughes JA. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 1990;46:428-33. [2] Tatuch Y, Christodoulou J, Feigenbaum A, et al. Heteroplasmic mtDNA mutation (T- > G) at 8993 can cause Leigh's disease when the percentage of abnormal mtDNA is high. Am J Hum Genet 1992;50:852-8. [3] de Vries DD, van Engelen BGM, Gabre~ls FJM, et al. A second missense mutation in the mitochondrial ATPase6 gene in Leigh's syndrome. Ann Neurol 1993;34:410-2.
130. PERVASIVE DEVELOPMENTAL DISORDERS AND THE CHILD NEUROLOGIST Roberto F. Tuchman, Miami, Florida Children with pervasive developmental disorders (i.e., autism and pervasive developmental disorders not otherwise specified) present to child neurologists with abnormal language development, behavioral problems, or general developmental delay. Pervasive developmental disorders are behaviorally defined but associated with a variety of neurobiologic abnormalities. The purpose of this study is to determine the types of neurobiologic problems commonly identified by a child neurologist assessing children with pervasive developmental disorders in clinical practice. From July, 1991 to April, 1994, 340 patients with pervasive developmental disorders seen by one child neurologist were entered into an ongoing database. High-functioningindividuals accounted for a total of 14% of these patients. Motor abnormalities occurred in 18% of the total population with hypotonia being the most common motor manifestation. Stereotypies were present in 67%. Regression of language was reported by 25% of all parents. Chromosomal abnormalities were found in 4% of children (1.5% with fragile X and 2.5% with other chromosomal abnormalities). Ten families (3%) had more than 1 child with a pervasive developmental disorder. Seizures occurred in 13% and abnormal EEGs were present in 31%. Of those individuals who underwent MRI, abnormalities were found in 15%. High levels of anxiety were reported by parents in 22% of the children and sleep problems occurred in 19%. This study supports the importance of neurologic assessment of all children with pervasive developmental disorders. The child neurologist in clinical practice needs to be cognizant of the spectrum of behavioral and neurobiologic manifestations of children with pervasive developmental disorders. Neurologic assessment of these individuals is crucial for appropriate management and to provide families with genetic and prognostic information. In addition, the data presented suggest areas in need of further clinical and basic science research.
131. BILATERAL STRIATAL LESIONS Joaquin A. Pefia, Eduardo Mora, and Enoe E. Medrano, Maracaibo, Venezuela Selective lesions of the basal ganglia have been described in children with acute, subacute, and chronic diseases. The diagnosis of acute or persistent neurologic dysfunction associated with bilateral striatal lesions in childhood (BSLC) can be accomplished by serial CT and MRI. Since 1985 we have identified 9
children with BSLC; ages ranged from 15 months to 10 years. The presenting symptoms included extrapyramidal signs (tremor 1, hypotonia 3, dystonia 8, rigidity 2), disturbed consciousness in 3, and seizures in 2. The final outlook of the whole group was poor with significant motor impairment in 7 patients, 1 death, and striking improvement in 2 patients. Our results support the findings of others [1,2] and confirm the need for early recognition of this clinical radiologic association for better approach and management. References: [1] Roig M, et al. Pediatr Neurol 1993;9:349-58. [2] Natsutoshi F, et al. Pediatr Neurol 1994;10: 157-60. 132. POSTOPERATIVE NEUROLOGIC MORBIDITY AND MORTALITY F O L L O W I N G OPEN HEART SURGERY DURING E A R L Y I N F A N C Y : P R O S P E C T I V E STUDY Geoffrey Miller, Kathleen D. Eggli, Charles F. Contant, Barry G. Baylen, and John L. Meyers, Houston, Texas and Hershey, Pennsylvania
In a systematic prospective study we analyzed mortality and neurologic morbidity following 100 open heart operations on unselected term infants younger than 6 months. Fifty-six percent were younger than 1 month and 37% younger than 1 week. Preand postoperative variables included neurologic findings, patient characteristics, cardiac and metabolic status, intraoperative variables, such as duration of and temperature at circulatory arrest or low flow bypass, and cranial ultrasound, among others. Overall mortality was 18%, of which 41% died less than 1 month after operation. Of those who died 59% had an interrupted aortic or hypoplastic left heart syndrome and the mortality from these lesions was 40%. Seizures unrelated to infection, metabolic abnormality, or any other variables, occurred in 14% of which 70% were focal. By the end of first and second postoperative week 36% and 21%, respectively, demonstrated reduced alertness which continued in 10% prior to discharge. Mild hypotonia was common and found in 30% prior to discharge. Severe hypotonia was present in 12% and persisted in 8%. A generalized increase in tone or pyramidal findings were present in 7% and asymmetry of tone and movement in 5%; these findings were unrelated to any variables. Hyperkinetic dyskinesia was noted in 11% and usually appeared after the first postoperative week, but did not persist. Alertness, severe hypotonia, and dyskinesia were related to the duration of deep hypothermia (P < .05) and occurred with both low flow and circulatory arrest. Cranial ultrasound performed on 41 infants was abnormal in 24% and in 50% the changes were present preoperatively and included thalamic echodensities, periventricular cystic change, and ventriculomegaly. Changes found following operation were increased in ventricular size and focal hemorrhage or infarction. Thus, most infants who undergo open heart surgery have uneventful neurologic courses. Mortality and neurologic morbidity may be due to several factors which include type of congenital heart defect, preoperative congenital or acquired brain lesions, duration of deep hypothermia, and strokes. 133. FOLLOW-UP OF SUBACUTE SCLEROSING PANENCEPHALITIS TREATED WITH TRIHEXIPHENIDIL AND ISOPRINOSINE Magda Lahorgue Nunes, Jaderson Costa da Costa, and Luis Fernando Garcias da Silva, Porto Alegre, Brazil
From 1985 to the present, we diagnosed 6 patients with subacute sclerosing panencephalitis (SSPE) at S~o Lucas Hospital. Five patients were in stage 2, and 1 in stage 3. Isoprinosine (100 mg/kg/day) was given to 5. The antiepileptic drug (AED) of choice was valproic acid (VPA). Three patients had myoclonic seizures refractory to VPA and the usual AED, trihexiphenidyl (THP), was administered in these patients. In one patient, we had total control of seizures and the others had a reduction in the number of seizures. The use of THP (an anticholinergic drug) on the treatment of refractory seizures was suggested by Jabbary (Epilepsia 1989;30:5). The follow-up of these patients demonstrated: B.M. is demented and seizure free for 4 years and stopped medication 1 year ago; L.S.P. does not use isoprinosine and as far as we know just had a partial reduction in the number of seizures; and P.C.M. was seizure-free and had partial recovery of speech and gait for 3 months; treatment was interrupted by the parents, seizures returned, and developmental delay ensued. In the group that was treated with isoprinosine plus VPA followup was lost in 2 patients. L.C.L. is now 10-years-old, seizure free, and with normal neuropsychologic development. Prognosis can be related to early diagnosis associated with treatment. Reduction of seizures in patients who used THP suggests the participation of cholinergic mechanisms in the physiologic genesis of seizures in SSPE. 134. ATHETOSIS AND ASSOCIATED EPILEPSY Erzs6bet Balogh and Anna Varga-Kiss, Budapest, Hungary The frequency of additional or associated symptoms in cerebral palsy (CP) varies remarkably and is due to the different origins of CP. The convulsive predisposition, 64 of 234 athetoid patients, born between 1972 and 1992, applying for conductive education reaches the incidence of quadriplegic epilepsy in certain age groups. Almost one-third of athetoid patients suffer from epilepsy. One-fifth of the epileptic group and one-third of the nonepileptic group were born prematurely. Prematurity thus hardly can be indicated as the main cause of this motor dysfunction. The rate of jaundice in newborns with athetosis and epilepsy is significantly lower than that of the "pure" athetoid patient. The incidence of perinatal hypoxia and icterus together was found relatively rarely; the incidence of these two risk factors is alternative. The groups of athetosis patients with and without epilepsy are practically the same (i.e., hypoxia afflicts every second child). None of the other risk factors is experienced so commonly. Seizures during the first 5 days of life were registered with one-tenth of those without epilepsy and one-third of athetosis with epilepsy. Perinatal convulsions without hypoxic preliminaries was rarely registered in the nonepileptic group. Perinatal convulsion cannot be considered of predictive value in athetosis either with or without epilepsy. The number of premature patients is significantly lower in athetosis with epilepsy. The rate of prematurity without perinatal convulsions is double among athetosis patients without epilepsy. Most of the 64 epileptic children displayed the first seizure within the first year of life. When ventilation is relatively higher, icterus is less frequent in the cases of the future epileptic group. Prematurity does not have a major pathogenetic role in inducing either basic dysfunction or associated diseases. The rate of perinatal convulsions is high in athetosis, irrespective of the development of epilepsy. Only an insignificant minority of the epileptic have first seizures after the age of 3. Conductive education is applied to a positive selection from the aspect of intelligence of the motor disabled.
PEDIATRIC NEUROLOGY Vol. 11 No. 2 119
129. CLINICAL HETEROGENEITY IN mtDNA 8993 T>c POINT MUTATION Suk-Chun Mak, Filippo M. Santorelli, Marta E. VazquezMemije, Sara Shanske, Pamela Kranz-Eble, Daniel L. Bluestone, Darryl C. De Vivo, and Salvatore DiMauro, New York, New York and San Francisco, California A mitochondrial DNA (mtDNA) point mutation at position nt 8993T>c has been reported in association with neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) [1] and, when present in high percentage (>95%), with maternally inherited Leigh syndrome (MILS) [2]. LS patients bearing this mutation are severely affected and usually die in early infancy. Recently, a novel 8993T>c point mutation has been described in 4 siblings with a juvenile form of LS [3]. We studied 4 unrelated patients with the 8993T>c point mutation who demonstrated diverse clinical manifestations. Patient 1 (5-year-old boy) exhibited developmental delay, hypotonia, and ataxia. He had recurrent exacerbations during intercurrent illnesses, and eventually developed respiratory insufficiency and apnea. Patient 2 (13year-old boy) presented with a typical NARP phenotype, with neuropathy, ataxia, progressive visual loss due to retinitis pigmentosa, and mild developmental delay. Family history was suggestive of maternal inheritance. Patient 3 (4-year-old boy) had developmental delay, mild hypotonia, and ataxia. Intercurrent febrile episodes exacerbated the clinical course. MRI revealed bilateral lucencies in the basal ganglia on T2-weighted images. Patient 4 (19-year-old woman) demonstrated progressive muscle weakness, generalized seizures, and received a diagnosis of spinocerebellar ataxia. MRI disclosed bilateral abnormalities in the anterior aspect of the putamen. Total genomic DNA was extracted either from blood or muscle, and a 641 bp fragment encompassing the region of the NARP mutation was amplified by PCR, then purified. Both RFLP and sequencing analysis demonstrated a T > C point mutation at position nt 8993 of the mtDNA. The mutation was present in high percentage (>90%) in all 4 patients and was heteroplasmic in 20 maternal relatives. These findings suggest high phenotypic variability for the nt 8993T>c mutation. In contrast with the T > G change at the
118 PEDIATRICNEUROLOGY Vol. 11 No. 2
same position, the T > C mutation appears to cause milder clinical manifestations. References: [1] Holt IJ, Harding AE, Petty RKH, Morgan-Hughes JA. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 1990;46:428-33. [2] Tatuch Y, Christodoulou J, Feigenbaum A, et al. Heteroplasmic mtDNA mutation (T- > G) at 8993 can cause Leigh's disease when the percentage of abnormal mtDNA is high. Am J Hum Genet 1992;50:852-8. [3] de Vries DD, van Engelen BGM, Gabre~ls FJM, et al. A second missense mutation in the mitochondrial ATPase6 gene in Leigh's syndrome. Ann Neurol 1993;34:410-2.
130. PERVASIVE DEVELOPMENTAL DISORDERS AND THE CHILD NEUROLOGIST Roberto F. Tuchman, Miami, Florida Children with pervasive developmental disorders (i.e., autism and pervasive developmental disorders not otherwise specified) present to child neurologists with abnormal language development, behavioral problems, or general developmental delay. Pervasive developmental disorders are behaviorally defined but associated with a variety of neurobiologic abnormalities. The purpose of this study is to determine the types of neurobiologic problems commonly identified by a child neurologist assessing children with pervasive developmental disorders in clinical practice. From July, 1991 to April, 1994, 340 patients with pervasive developmental disorders seen by one child neurologist were entered into an ongoing database. High-functioningindividuals accounted for a total of 14% of these patients. Motor abnormalities occurred in 18% of the total population with hypotonia being the most common motor manifestation. Stereotypies were present in 67%. Regression of language was reported by 25% of all parents. Chromosomal abnormalities were found in 4% of children (1.5% with fragile X and 2.5% with other chromosomal abnormalities). Ten families (3%) had more than 1 child with a pervasive developmental disorder. Seizures occurred in 13% and abnormal EEGs were present in 31%. Of those individuals who underwent MRI, abnormalities were found in 15%. High levels of anxiety were reported by parents in 22% of the children and sleep problems occurred in 19%. This study supports the importance of neurologic assessment of all children with pervasive developmental disorders. The child neurologist in clinical practice needs to be cognizant of the spectrum of behavioral and neurobiologic manifestations of children with pervasive developmental disorders. Neurologic assessment of these individuals is crucial for appropriate management and to provide families with genetic and prognostic information. In addition, the data presented suggest areas in need of further clinical and basic science research.
131. BILATERAL STRIATAL LESIONS Joaquin A. Pefia, Eduardo Mora, and Enoe E. Medrano, Maracaibo, Venezuela Selective lesions of the basal ganglia have been described in children with acute, subacute, and chronic diseases. The diagnosis of acute or persistent neurologic dysfunction associated with bilateral striatal lesions in childhood (BSLC) can be accomplished by serial CT and MRI. Since 1985 we have identified 9
children with BSLC; ages ranged from 15 months to 10 years. The presenting symptoms included extrapyramidal signs (tremor 1, hypotonia 3, dystonia 8, rigidity 2), disturbed consciousness in 3, and seizures in 2. The final outlook of the whole group was poor with significant motor impairment in 7 patients, 1 death, and striking improvement in 2 patients. Our results support the findings of others [1,2] and confirm the need for early recognition of this clinical radiologic association for better approach and management. References: [1] Roig M, et al. Pediatr Neurol 1993;9:349-58. [2] Natsutoshi F, et al. Pediatr Neurol 1994;10: 157-60. 132. POSTOPERATIVE NEUROLOGIC MORBIDITY AND MORTALITY F O L L O W I N G OPEN HEART SURGERY DURING E A R L Y I N F A N C Y : P R O S P E C T I V E STUDY Geoffrey Miller, Kathleen D. Eggli, Charles F. Contant, Barry G. Baylen, and John L. Meyers, Houston, Texas and Hershey, Pennsylvania
In a systematic prospective study we analyzed mortality and neurologic morbidity following 100 open heart operations on unselected term infants younger than 6 months. Fifty-six percent were younger than 1 month and 37% younger than 1 week. Preand postoperative variables included neurologic findings, patient characteristics, cardiac and metabolic status, intraoperative variables, such as duration of and temperature at circulatory arrest or low flow bypass, and cranial ultrasound, among others. Overall mortality was 18%, of which 41% died less than 1 month after operation. Of those who died 59% had an interrupted aortic or hypoplastic left heart syndrome and the mortality from these lesions was 40%. Seizures unrelated to infection, metabolic abnormality, or any other variables, occurred in 14% of which 70% were focal. By the end of first and second postoperative week 36% and 21%, respectively, demonstrated reduced alertness which continued in 10% prior to discharge. Mild hypotonia was common and found in 30% prior to discharge. Severe hypotonia was present in 12% and persisted in 8%. A generalized increase in tone or pyramidal findings were present in 7% and asymmetry of tone and movement in 5%; these findings were unrelated to any variables. Hyperkinetic dyskinesia was noted in 11% and usually appeared after the first postoperative week, but did not persist. Alertness, severe hypotonia, and dyskinesia were related to the duration of deep hypothermia (P < .05) and occurred with both low flow and circulatory arrest. Cranial ultrasound performed on 41 infants was abnormal in 24% and in 50% the changes were present preoperatively and included thalamic echodensities, periventricular cystic change, and ventriculomegaly. Changes found following operation were increased in ventricular size and focal hemorrhage or infarction. Thus, most infants who undergo open heart surgery have uneventful neurologic courses. Mortality and neurologic morbidity may be due to several factors which include type of congenital heart defect, preoperative congenital or acquired brain lesions, duration of deep hypothermia, and strokes. 133. FOLLOW-UP OF SUBACUTE SCLEROSING PANENCEPHALITIS TREATED WITH TRIHEXIPHENIDIL AND ISOPRINOSINE Magda Lahorgue Nunes, Jaderson Costa da Costa, and Luis Fernando Garcias da Silva, Porto Alegre, Brazil
From 1985 to the present, we diagnosed 6 patients with subacute sclerosing panencephalitis (SSPE) at S~o Lucas Hospital. Five patients were in stage 2, and 1 in stage 3. Isoprinosine (100 mg/kg/day) was given to 5. The antiepileptic drug (AED) of choice was valproic acid (VPA). Three patients had myoclonic seizures refractory to VPA and the usual AED, trihexiphenidyl (THP), was administered in these patients. In one patient, we had total control of seizures and the others had a reduction in the number of seizures. The use of THP (an anticholinergic drug) on the treatment of refractory seizures was suggested by Jabbary (Epilepsia 1989;30:5). The follow-up of these patients demonstrated: B.M. is demented and seizure free for 4 years and stopped medication 1 year ago; L.S.P. does not use isoprinosine and as far as we know just had a partial reduction in the number of seizures; and P.C.M. was seizure-free and had partial recovery of speech and gait for 3 months; treatment was interrupted by the parents, seizures returned, and developmental delay ensued. In the group that was treated with isoprinosine plus VPA followup was lost in 2 patients. L.C.L. is now 10-years-old, seizure free, and with normal neuropsychologic development. Prognosis can be related to early diagnosis associated with treatment. Reduction of seizures in patients who used THP suggests the participation of cholinergic mechanisms in the physiologic genesis of seizures in SSPE. 134. ATHETOSIS AND ASSOCIATED EPILEPSY Erzs6bet Balogh and Anna Varga-Kiss, Budapest, Hungary The frequency of additional or associated symptoms in cerebral palsy (CP) varies remarkably and is due to the different origins of CP. The convulsive predisposition, 64 of 234 athetoid patients, born between 1972 and 1992, applying for conductive education reaches the incidence of quadriplegic epilepsy in certain age groups. Almost one-third of athetoid patients suffer from epilepsy. One-fifth of the epileptic group and one-third of the nonepileptic group were born prematurely. Prematurity thus hardly can be indicated as the main cause of this motor dysfunction. The rate of jaundice in newborns with athetosis and epilepsy is significantly lower than that of the "pure" athetoid patient. The incidence of perinatal hypoxia and icterus together was found relatively rarely; the incidence of these two risk factors is alternative. The groups of athetosis patients with and without epilepsy are practically the same (i.e., hypoxia afflicts every second child). None of the other risk factors is experienced so commonly. Seizures during the first 5 days of life were registered with one-tenth of those without epilepsy and one-third of athetosis with epilepsy. Perinatal convulsions without hypoxic preliminaries was rarely registered in the nonepileptic group. Perinatal convulsion cannot be considered of predictive value in athetosis either with or without epilepsy. The number of premature patients is significantly lower in athetosis with epilepsy. The rate of prematurity without perinatal convulsions is double among athetosis patients without epilepsy. Most of the 64 epileptic children displayed the first seizure within the first year of life. When ventilation is relatively higher, icterus is less frequent in the cases of the future epileptic group. Prematurity does not have a major pathogenetic role in inducing either basic dysfunction or associated diseases. The rate of perinatal convulsions is high in athetosis, irrespective of the development of epilepsy. Only an insignificant minority of the epileptic have first seizures after the age of 3. Conductive education is applied to a positive selection from the aspect of intelligence of the motor disabled.
PEDIATRIC NEUROLOGY Vol. 11 No. 2 119