- Email: [email protected]
Effects of long-term treatment with antiepileptic drugs on serum lipid levels in epileptic children
retarded children, ages 1-7. All of them had reliable histories in utero hypoxic-ischemic encephalopathy (HIE) or neonatal intracranial hemorrhage. Twenty-nine of them were low-grade, 31 were average, and 31 were advanced. Cranial CT showed that 46 cases had atrophy or circumscribed cerebromalacia. We compared these findings with a control group of 50 normal children, ages 1-7. The results demonstrated that in the mentally retarded group the activity of T-SOD, Mn-SOD, and CuZa-SOD (P < 0.01) and GSH were significantly reduced (P < .01). The research indicates that in the children with mentally retarded sequelae caused by brain injury in perinatal period, lipid peroxidation is still high, antioxidant capacity is reduced, and the capacity of elminating oxygen free radicals is reduced. Proposed: Free radicals participate in the course of pathogenesis of MR caused by brain injury in the perinatal period.
87. DOES NORMAN SYNDROME BEGIN BY PRIMARY DEGENERATION OF GRANULAR LAYER OF CEREBELLUM? Ignacio Pascual-Castroviejo, Manuel Gutierrez, A. Martinez Bermejo, C. Morales, and J.L. Hernandez Moneo, Madrid, Spain
Primary degeneration of the granular layer of the cerebellum (Norman syndrome) is an autosomal-recessive disorder that has as definite clinical features: hypotonia, strabismus, delayed motor development, nonprogressive ataxia, retarded language and dysarthria, and mental retardation. MRI reveals severe cerebellar atrophy in all cases, even during the first months of life. Histologic studies in autopsied cases confirm severe, generalized cerebellar atrophy with cell loss of the granular cell and diverse abnormalities of the Purkinje cells, such as cactus-like dendritic images. A 13-month-old girl, whose parents were first-degree cousins, presented with a clinical and neuroradiologic picture very suspicious of Norman syndrome. Because she was the first child of the couple and histology was the only definitive study to confirm the diagnosis, the parents agreed to cerebellar biopsy. Histologic study of the biopsied sample did not demonstrate significant changes in the internal and external granular layers. On the contrary, Purkinje cells and molecular layer revealed the presence of early changes. These mainly were isolated ectopies in the cellular layer and irregular loss of Purkinje cells which also presented as cactus-like dendritic abnormalities. This is the only study of Norman syndrome by biopsy. It was also performed in a very young patient. These findings may suggest that cerebellar degeneration begins in the cellular and Purkinje layers, although later changes become more severe in the granular layer.
88. GIANT CELL ASTROCYTOMA OF RETINA AND BRAIN IN TUBEROUS SCLEROSIS Ignacio Pascual-Castroviejo, F. Carceller, Mercedes Patron, Manuel Gutierrez, and Samuel I. Pascual-Pascual, Madrid, Spain This 24-year-old patient had surgery for giant cell astrocytoma of the left eye and right cerebral hemisphere. He had been diagnosed with tuberous sclerosis (TS) at 9 months of age because of infantile spasms, hypochromic skin spots, and left microphthalmos with crystalline opacity. Seizures were controlled with an-
108 PEDIATRIC NEUROLOGY Vol. 11 No. 2
tiepileptic drugs, but he developed severe mental retardation and autistic behavior. At age 19 years, he suddenly developed exophthalmos of the left eye associated with severe local pain; the eye was removed and histologic study revealed a giant cell astrocytoma of the retina. At 23 years of age, he complained of headache and MRI showed a great pariventricular mass in the frontal zone of the right cerebral hemisphere; it was removed and the histology demonstrated a giant cell astrocytoma. Even though the TS is frequently associated with isolated cerebral or eye giant cell astrocytoma, the presence of the tumor in both locations in the same patient is extremely rare. The benign nature of the tumor permits a long survival for these patients. Both the eye and the cerebral tumors presented as calcified masses on radiologic studies.
89. CEREBROSPINAL FLUID PURINE METABOLITES AND PYRIMIDINE BASES FOLLOWING SHORT FEBRILE CONVULSIONS M. Castro-Gago, E. Cid, S. Trabazo, F. Camifia, S. Rodriguez-Segade, I. Novo, J. Eiris Pufial, and A. RodriguezNufiez, Santiago de Compostcla, Spain The effects of febrile seizures on cerebral metabolism are not well understood. In a preliminary study of 18 children with febrile seizures, we did not observe statistically significant differences with respect to the control group in CSF concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid. cytosine, thymine, and uracil. In view of the small number of patients studied, we believe that a large-scale prospective study of CSF children is necessary to obtain more conclusive results. We determined CSF levels of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid, and pyrimidines bases (i.e., cytosine, thymine, uracil) by HPLC, in 52 children (28 boys and 24 girls, ages 4-48 months; median: 14.5 months) after simple febrile seizures, and in a control group of 63 children (40 boys and 23 girls, ages 1 month to 13 years; median: 36 months). There was no statistically significant difference between the two groups for any of these metabolites. This finding suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuronal adenosine ATP levels. Therefore, they do not appear to constitute a threat of neuronal damage. (Supported by the FIS 93/0740 and by XUGA 90201B91 of Spain.)
90. EFFECTS OF LONG-TERM TREATMENT WITH ANTIEPILEPTIC DRUGS ON SERUM LIPID LEVELS IN EPILEPTIC CHILDREN M. Castro-Gago, I. Novo, S. Lojo, M.C. del Rio, M. del Rio, and J. Eirfs, Santiago de Compostela, Spain
We determined serum levels of total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 epileptic children who had been receiving carbamazepine (58 children), phenobarbital (22 children), or valproic acid (39
children) for 7 months to 10.5 years (mean: 5.8 years). None of the variables considered was significantly correlated with time elapsed since the start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant except for LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TGs level differ significantly from the corresponding control group mean. In contrast to previous reports, our results suggest that the effects on the serum lipid profile of long-term treatment with hepatic-enzymeinducing antiepileptic drugs, such as carbamazepine and phenobarbital, are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in epileptic children receiving carbamazepine or phenobarbital. 91. CLINICAL STUDY ON MICROCIRCULATION OF PATIENTS W I T H OBSTINATE EPILEPSY Zhen-Huan Liu and Nal-Qiang Du, Yang-Quan, Shan Xi, China In order to determine the pathogenesis of obstinate epilepsy and the treatment with hyoscyamus, we studied the microcirculation of 50 cases with epilepsy clinically. Among 50 cases, 28 were males and 22 females. The ages of 37 cases were 5-14, and 13 were 15-50. The length of the disease of 44 cases was 5-10 years and 6 cases 10-20 years. The morbidity rate of 45 cases was more than 30 times every month and 5 was less than 10 times every month. Thirty-six cases had primary epilepsy and 14 had secondary epilepsy. Through a WX-753 polyhedron Microcirculating Microscope and a DWX-89 Micrangium Surveyor, we observed and compared their nailfold, microcirculation shape and fluid of the bulbar conjunctiva of both the epilepsy group and a control group which consisted of 30 healthy persons who had no differences in age or sex with the epilepsy group. The results revealed that the incidence rate of micrangium spasm arrangement disturbance, micrangium malformation, RBC aggregation, slow blood flow and sludging of blood, and blood stasis are significantly higher in the epilepsy group than the control group, P < .01. TCD examination indicated that arteriospasms in brain and blood volume were reduced in 37 of 50 cases (74%). All epilepsy patients were given large quantities of 654-2 as adjuvant treatment for 6 months. As a result, the effective rate reached 60%. After treatment, the incidence rate of bulbar conjunctiva arteriospasm according to the observation index of nailfold circulation, slow blood flow, RBC aggregation, etc. were evidently reduced, P < .01. This study confirms that the disturbance of brain microcirculation exists in obstinate epilepsy patients which may be one of the main factors of pathogenesis and the reason why it is difficult to treat. 92. SLEEP DISORDERS: TREATABLE CAUSES OF BEHAVIORAL AND ATTENTION-DEFICIT DISORDERS Frank Buda, Atlanta, Georgia
Previous investigations into pediatric sleep have demonstrated
that obstructive sleep apnea syndrome (OSAS) may produce attention deficit disorder (ADD) and/or behavioral disorders (BDs). In this study, other sleep disorders have been identified as etiologic in producing ADD and/or BDs in children. Ten children and young adolescents are presented. All patients met the following criteria: (1) had symptoms of ADD and/or BDs, (2) were evaluated by an overnight polysonmogram (PSG) and if indicated, a median sleep latency test and/or a 24-hour pH probe, (3) had a positive sleep history and/or physical examination, and (4) received a urine drug screen and personality profile if indicated. Six of 10 patients had excessive daytime somnolence (EDS). A definitive diagnosis was made by PSG in 9 of 10 patients (90%). The one patient with a normal study was later found to be noncompliant with medication. Fifty percent (5 patients) had OSAS and responded to removal of tonsils and adnoids. In 2 patients (20%), periodic leg movement syndrome was found and responded to clonazepam. In 1 patient (10%) gastroesophageal reflux was diagnosed and was treated with ranitidine. One patient (10%) had narcolepsy and responded to methylphenidate. Of six patients with EDS, 5 had OSAS (83%) and 1 (17%) narcolepsy. Various sleep disorders in children and young adolescents may produce ADD or BDs. Once recognized, they are readily treatable and remarkably positive changes can Occur.
93. ISOLATED ANGIITIS OF THE NERVOUS SYSTEM Y. Futatsugi, M.S. Wise, and S.L. Rutledge, Birmingham, Alabama We present a 10-year-old white male with isolated angiitis of the central nervous system. He had a 2-week history of severe headache with vomiting, then developed a dense left hemiplegia. Hemiplegia resolved spontaneously but severe bifrontal headache and vomiting continued. Evaluation yielded the following normal results: CBC, electrolytes, ESR, lipid profile, CSF, proteins C and S, anticardiolipid antibody, ANA, rheumatoid factor, C 3, and Ca. Cranial MRI revealed a focal abnormality in the right posterior temporal lobe compatible with a vascular abnormality and a small area of cerebellar edema. Cerebral arteriography revealed bilateral multifocal narrowing of blood vessels with a beaded appearance compatible with vasculitis. The patient was treated with high-dose steroids with complete resolution of symptoms. Repeat angiography was normal. There are few reports of isolated angiitis of the CNS in children. Clinical findings are nonspecific and appropriate diagnostic tests (e.g., leptomeningeal biopsy and arteriorgram) are not done. As evidenced by our patient, this condition does occur in children and can be successfully treated with high-dose steroids.
94. CAN CYTOTOXIC DRUGS A M E L I O R A T E SUBACUTE SCLEROSING PANENCEPHALITIS? Saad M. A1 Rajeh, Mohammad M. Uddin Kabiraj, lbrahim M. lbrahim A1-Fawaz, Mohammad Abdulkader Daif, and Ahmed I. Jarallah, Riyadh, Saudi Arabia We report a 12-year-old Saudi girl with subacute sclerosing panencephalitis (SSPE) and acute lymphoblastic leukemia (ALL). The initial video-EEG (VEEG) was consistent with SSPE. The measles IgG antibody serum titer was >1:1024 and CSF titer was >1:128. Following successful induction remission of leu-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 109
87. DOES NORMAN SYNDROME BEGIN BY PRIMARY DEGENERATION OF GRANULAR LAYER OF CEREBELLUM? Ignacio Pascual-Castroviejo, Manuel Gutierrez, A. Martinez Bermejo, C. Morales, and J.L. Hernandez Moneo, Madrid, Spain
Primary degeneration of the granular layer of the cerebellum (Norman syndrome) is an autosomal-recessive disorder that has as definite clinical features: hypotonia, strabismus, delayed motor development, nonprogressive ataxia, retarded language and dysarthria, and mental retardation. MRI reveals severe cerebellar atrophy in all cases, even during the first months of life. Histologic studies in autopsied cases confirm severe, generalized cerebellar atrophy with cell loss of the granular cell and diverse abnormalities of the Purkinje cells, such as cactus-like dendritic images. A 13-month-old girl, whose parents were first-degree cousins, presented with a clinical and neuroradiologic picture very suspicious of Norman syndrome. Because she was the first child of the couple and histology was the only definitive study to confirm the diagnosis, the parents agreed to cerebellar biopsy. Histologic study of the biopsied sample did not demonstrate significant changes in the internal and external granular layers. On the contrary, Purkinje cells and molecular layer revealed the presence of early changes. These mainly were isolated ectopies in the cellular layer and irregular loss of Purkinje cells which also presented as cactus-like dendritic abnormalities. This is the only study of Norman syndrome by biopsy. It was also performed in a very young patient. These findings may suggest that cerebellar degeneration begins in the cellular and Purkinje layers, although later changes become more severe in the granular layer.
88. GIANT CELL ASTROCYTOMA OF RETINA AND BRAIN IN TUBEROUS SCLEROSIS Ignacio Pascual-Castroviejo, F. Carceller, Mercedes Patron, Manuel Gutierrez, and Samuel I. Pascual-Pascual, Madrid, Spain This 24-year-old patient had surgery for giant cell astrocytoma of the left eye and right cerebral hemisphere. He had been diagnosed with tuberous sclerosis (TS) at 9 months of age because of infantile spasms, hypochromic skin spots, and left microphthalmos with crystalline opacity. Seizures were controlled with an-
108 PEDIATRIC NEUROLOGY Vol. 11 No. 2
tiepileptic drugs, but he developed severe mental retardation and autistic behavior. At age 19 years, he suddenly developed exophthalmos of the left eye associated with severe local pain; the eye was removed and histologic study revealed a giant cell astrocytoma of the retina. At 23 years of age, he complained of headache and MRI showed a great pariventricular mass in the frontal zone of the right cerebral hemisphere; it was removed and the histology demonstrated a giant cell astrocytoma. Even though the TS is frequently associated with isolated cerebral or eye giant cell astrocytoma, the presence of the tumor in both locations in the same patient is extremely rare. The benign nature of the tumor permits a long survival for these patients. Both the eye and the cerebral tumors presented as calcified masses on radiologic studies.
89. CEREBROSPINAL FLUID PURINE METABOLITES AND PYRIMIDINE BASES FOLLOWING SHORT FEBRILE CONVULSIONS M. Castro-Gago, E. Cid, S. Trabazo, F. Camifia, S. Rodriguez-Segade, I. Novo, J. Eiris Pufial, and A. RodriguezNufiez, Santiago de Compostcla, Spain The effects of febrile seizures on cerebral metabolism are not well understood. In a preliminary study of 18 children with febrile seizures, we did not observe statistically significant differences with respect to the control group in CSF concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid. cytosine, thymine, and uracil. In view of the small number of patients studied, we believe that a large-scale prospective study of CSF children is necessary to obtain more conclusive results. We determined CSF levels of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid, and pyrimidines bases (i.e., cytosine, thymine, uracil) by HPLC, in 52 children (28 boys and 24 girls, ages 4-48 months; median: 14.5 months) after simple febrile seizures, and in a control group of 63 children (40 boys and 23 girls, ages 1 month to 13 years; median: 36 months). There was no statistically significant difference between the two groups for any of these metabolites. This finding suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuronal adenosine ATP levels. Therefore, they do not appear to constitute a threat of neuronal damage. (Supported by the FIS 93/0740 and by XUGA 90201B91 of Spain.)
90. EFFECTS OF LONG-TERM TREATMENT WITH ANTIEPILEPTIC DRUGS ON SERUM LIPID LEVELS IN EPILEPTIC CHILDREN M. Castro-Gago, I. Novo, S. Lojo, M.C. del Rio, M. del Rio, and J. Eirfs, Santiago de Compostela, Spain
We determined serum levels of total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 epileptic children who had been receiving carbamazepine (58 children), phenobarbital (22 children), or valproic acid (39
children) for 7 months to 10.5 years (mean: 5.8 years). None of the variables considered was significantly correlated with time elapsed since the start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant except for LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TGs level differ significantly from the corresponding control group mean. In contrast to previous reports, our results suggest that the effects on the serum lipid profile of long-term treatment with hepatic-enzymeinducing antiepileptic drugs, such as carbamazepine and phenobarbital, are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in epileptic children receiving carbamazepine or phenobarbital. 91. CLINICAL STUDY ON MICROCIRCULATION OF PATIENTS W I T H OBSTINATE EPILEPSY Zhen-Huan Liu and Nal-Qiang Du, Yang-Quan, Shan Xi, China In order to determine the pathogenesis of obstinate epilepsy and the treatment with hyoscyamus, we studied the microcirculation of 50 cases with epilepsy clinically. Among 50 cases, 28 were males and 22 females. The ages of 37 cases were 5-14, and 13 were 15-50. The length of the disease of 44 cases was 5-10 years and 6 cases 10-20 years. The morbidity rate of 45 cases was more than 30 times every month and 5 was less than 10 times every month. Thirty-six cases had primary epilepsy and 14 had secondary epilepsy. Through a WX-753 polyhedron Microcirculating Microscope and a DWX-89 Micrangium Surveyor, we observed and compared their nailfold, microcirculation shape and fluid of the bulbar conjunctiva of both the epilepsy group and a control group which consisted of 30 healthy persons who had no differences in age or sex with the epilepsy group. The results revealed that the incidence rate of micrangium spasm arrangement disturbance, micrangium malformation, RBC aggregation, slow blood flow and sludging of blood, and blood stasis are significantly higher in the epilepsy group than the control group, P < .01. TCD examination indicated that arteriospasms in brain and blood volume were reduced in 37 of 50 cases (74%). All epilepsy patients were given large quantities of 654-2 as adjuvant treatment for 6 months. As a result, the effective rate reached 60%. After treatment, the incidence rate of bulbar conjunctiva arteriospasm according to the observation index of nailfold circulation, slow blood flow, RBC aggregation, etc. were evidently reduced, P < .01. This study confirms that the disturbance of brain microcirculation exists in obstinate epilepsy patients which may be one of the main factors of pathogenesis and the reason why it is difficult to treat. 92. SLEEP DISORDERS: TREATABLE CAUSES OF BEHAVIORAL AND ATTENTION-DEFICIT DISORDERS Frank Buda, Atlanta, Georgia
Previous investigations into pediatric sleep have demonstrated
that obstructive sleep apnea syndrome (OSAS) may produce attention deficit disorder (ADD) and/or behavioral disorders (BDs). In this study, other sleep disorders have been identified as etiologic in producing ADD and/or BDs in children. Ten children and young adolescents are presented. All patients met the following criteria: (1) had symptoms of ADD and/or BDs, (2) were evaluated by an overnight polysonmogram (PSG) and if indicated, a median sleep latency test and/or a 24-hour pH probe, (3) had a positive sleep history and/or physical examination, and (4) received a urine drug screen and personality profile if indicated. Six of 10 patients had excessive daytime somnolence (EDS). A definitive diagnosis was made by PSG in 9 of 10 patients (90%). The one patient with a normal study was later found to be noncompliant with medication. Fifty percent (5 patients) had OSAS and responded to removal of tonsils and adnoids. In 2 patients (20%), periodic leg movement syndrome was found and responded to clonazepam. In 1 patient (10%) gastroesophageal reflux was diagnosed and was treated with ranitidine. One patient (10%) had narcolepsy and responded to methylphenidate. Of six patients with EDS, 5 had OSAS (83%) and 1 (17%) narcolepsy. Various sleep disorders in children and young adolescents may produce ADD or BDs. Once recognized, they are readily treatable and remarkably positive changes can Occur.
93. ISOLATED ANGIITIS OF THE NERVOUS SYSTEM Y. Futatsugi, M.S. Wise, and S.L. Rutledge, Birmingham, Alabama We present a 10-year-old white male with isolated angiitis of the central nervous system. He had a 2-week history of severe headache with vomiting, then developed a dense left hemiplegia. Hemiplegia resolved spontaneously but severe bifrontal headache and vomiting continued. Evaluation yielded the following normal results: CBC, electrolytes, ESR, lipid profile, CSF, proteins C and S, anticardiolipid antibody, ANA, rheumatoid factor, C 3, and Ca. Cranial MRI revealed a focal abnormality in the right posterior temporal lobe compatible with a vascular abnormality and a small area of cerebellar edema. Cerebral arteriography revealed bilateral multifocal narrowing of blood vessels with a beaded appearance compatible with vasculitis. The patient was treated with high-dose steroids with complete resolution of symptoms. Repeat angiography was normal. There are few reports of isolated angiitis of the CNS in children. Clinical findings are nonspecific and appropriate diagnostic tests (e.g., leptomeningeal biopsy and arteriorgram) are not done. As evidenced by our patient, this condition does occur in children and can be successfully treated with high-dose steroids.
94. CAN CYTOTOXIC DRUGS A M E L I O R A T E SUBACUTE SCLEROSING PANENCEPHALITIS? Saad M. A1 Rajeh, Mohammad M. Uddin Kabiraj, lbrahim M. lbrahim A1-Fawaz, Mohammad Abdulkader Daif, and Ahmed I. Jarallah, Riyadh, Saudi Arabia We report a 12-year-old Saudi girl with subacute sclerosing panencephalitis (SSPE) and acute lymphoblastic leukemia (ALL). The initial video-EEG (VEEG) was consistent with SSPE. The measles IgG antibody serum titer was >1:1024 and CSF titer was >1:128. Following successful induction remission of leu-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 109