vpa metabolites in serum and urine with high-dose vpa monotherapy: 4-en-vpa, valproylcarnitine, and...

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the DSM-III-R criteria may fall under other diagnoses, such as oppositional conduct, defiance and anxiety disorders, it is im- portant to have other tools to make a more precise diagnosis. Our study evaluates the prevalence of ADHD in 484 patients (mean age: 7.5 years; range: 6.0-11.5 years) using DSM-III-R and neu- ropsychologic criteria (neuroevolutional, psychometric, behav- ioral, and learning aspects). The variables evaluated included sex, age, race, weight, nutritional state, evolutional neurologic examination, WISC-R subtests (i.e., arithmetic and picture com- pletion), DSM-III-R items, and school performance. The diag- nosis of ADHD was made in 87 children (18%) using DSM-III-R and in 17 children (3.5%) by neuropsychologic criteria. These results suggest that neuropsychologic tests have greater diagnos- tic specificity than DSM-III-R criteria which should be used more as a screening tool. 112. DEFICIENCY OF PROTEIN C AS CAUSE OF CE- REBROVASCULAR OCCLUSION Surang Chiemchanya, Ampaiwan Chuansumrit, and Pongsakdi Visudhiphan, Bangkok, Thailand Hemostatic disorders, either hereditary or acquired, have been known to cause cerebral occlusive events. During October 1988 to July 1993, levels of the natural anticoagulants antithrombin III, protein C (PC), and protein S (PS) were measured in children younger than 15 years of age with cerebrovascular occlusion, who were admitted to the Department of Pediatrics, Ramathibodi Hospital. Those with explainable causes were excluded. Ten patients were enrolled in this study, 6 of whom had arterial occlusions; the rest had venous sinus occlusions. Their ages ranged from 1 year, 7 months to 14 years (9 boys, 1 girl). Patients with arterial occlusions presented with acute focal neu- rologic deficits. CT revealed areas of cerebral infarction in 4 of the 5 and cerebral angiography demonstrated occlusions in 3 of 4 patients studied. Patients with venous sinus occlusions pre- sented with increased intracranial pressure. Venous sinus occlu- sions were demonstrated by CT and/or angiography. The level of AT III, PC, and PS were normal in all arterial occlusions pa- tients. Decreased PC levels were observed in 2 of 4 patients with venous sinus occlusions (34% and 52% of normal). In children, cerebral thromboembolism has been known to be associated with cardiac disease, vasculitis, dehydration, and intracranial infec- tions, Excluding these common causes, a hemostatic disorder is usually caused by L-asparaginase toxicity. The pathogenesis of a hemostatic disorder could be found in 20-30% of patients. Screening for deficiencies of AT III, PC, and PS in this group of 10 patients found PC deficiency in 2 patients. Excluding com- mon associations of cerebral thromboembolism, PC deficiency should be looked for especially in patients with venous sinus occlusions. dren who suffered from stroke were admitted to the Department of Pediatrics, Ramathibodi Hospital. Forty-three were boys and the ages ranged from 5 months to 15 years. Thirty-one patients had hemorrhagic stroke (HS). The diagnosis was verified by CT, MRI, angiography, or CSF examination demonstrating intracra- nial hematoma or subarachnoid hemorrhage. The causes of HS included vascular malformations, bleeding disorders, hyperten- sion, mycotic aneurysm, and gnathostomiasis in 14, 6, 4, 3, and 1 patients, respectively. The cause was not known in 3 patients. Ischemic stroke (IS) occurred in 38 patients. CT or MRI dem- onstrated cerebral ischemia or infarction; cerebral angiography showed irregularity or occlusion of blood vessels. The causes included hyperviscosity or hypercoagulability in 7 and cardiac pathology as the sources of embolism in 8 patients; other patho- logic findings included arteriovenous malformation, Takayasu arteritis, SLE, and moya-moya disease. The causes were unde- termined in 12 patients. Headache, vomiting, and abnormal optic fundi had greater incidences in HS, while unilateral neurologic deficit occurred in IS. Complete recovery was observed in 45%, residual deficit in 39%, death in 7%, and lost to follow-up in 9% of HS patients; in IS patients, the percentages were 24, 52, 13, and 11, respectively. 114. VPA METABOLITES IN SERUM AND URINE WITH HIGH-DOSE VPA MONOTHERAPY: 4-EN-VPA, VALPROYLCARNITINE, AND BETA-OXIDATION ME- TABOLITES OF VPA Tateo Sugimoto, Hideki Muro, Man Woo, Naoki Nishida, and Kiyotaka Murakami, Yawata and Osaka, Japan In high-dose VPA monotherapy with L-camitine, serum and urine VPA metabolites and carnitine levels and urine valproyl- camitine were analyzed by GC/MS/SIM and HPLC. Levels of S-4-en-VPA were significantly higher than those in the standard VPA dose and the increase of 4-en-VPA did not correlate with levels of SGOT. The ratio of [S-13-oxidation metabolites/(to + tol) oxidation metabolites] was distinctly decreased compared with standard therapy. Urinary valproylcarnitine levels corre- lated well with the levels of total VPA, B-oxidation metabolites, (to + tol) metabolites, 4-en-VPA, total camitine, free camitine, and acylcamitine in urine, but not with the blood ammonia lev- els. No patient developed severe liver dysfunction during the 4-year VPA monotherapy. The high-dose VPA monotherapy was concluded to be comparatively safe. From a viewpoint of VPA metabolism in high-dose monotherapy, the mechanisms of VPA-hepatotoxicity could not be ascribed to the increase in S-4- en-VPA and/or toxic acyl-CoA, including valproyl-CoA in this study. 113. STROKE IN CHILDREN Pongsakdi Visudhiphan, Duangrurdee Wattanasirichaigoon, and Surang Chiemchanya, Bangkok, Thailand Stroke refers to a clinical syndrome characterized by sudden neurologic deficit caused by cerebrovascular diseases. During a 13-year period from January, 1979 to December, 1991, 69 chil- 115. DIAGNOSTIC SIGNIFICANCE OF GIANT SEP AND ABSENT SEP Akihiro Yasuhara, Atsushi Araki, Ayako Ochi, Yoshiaki Harada, and Yohnosuke Kobayashi, Osaka, Japan We observed giant somatosensory evoked potentials (SEPs) or absence of SEPs in children with specific neurologic disorders. Especially giant SEPs were related to myoclonic epilepsy. To 114 PEDIATRIC NEUROLOGY Vol. II No. 2

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Page 1: VPA metabolites in serum and urine with high-dose VPA monotherapy: 4-en-VPA, valproylcarnitine, and beta-oxidation metabolites of VPA

the DSM-III-R criteria may fall under other diagnoses, such as oppositional conduct, defiance and anxiety disorders, it is im- portant to have other tools to make a more precise diagnosis. Our study evaluates the prevalence of ADHD in 484 patients (mean age: 7.5 years; range: 6.0-11.5 years) using DSM-III-R and neu- ropsychologic criteria (neuroevolutional, psychometric, behav- ioral, and learning aspects). The variables evaluated included sex, age, race, weight, nutritional state, evolutional neurologic examination, WISC-R subtests (i.e., arithmetic and picture com- pletion), DSM-III-R items, and school performance. The diag- nosis of ADHD was made in 87 children (18%) using DSM-III-R and in 17 children (3.5%) by neuropsychologic criteria. These results suggest that neuropsychologic tests have greater diagnos- tic specificity than DSM-III-R criteria which should be used more as a screening tool.

112. DEFICIENCY OF PROTEIN C AS CAUSE OF CE- REBROVASCULAR OCCLUSION Surang Chiemchanya, Ampaiwan Chuansumrit, and Pongsakdi Visudhiphan, Bangkok, Thailand

Hemostatic disorders, either hereditary or acquired, have been known to cause cerebral occlusive events. During October 1988 to July 1993, levels of the natural anticoagulants antithrombin III, protein C (PC), and protein S (PS) were measured in children younger than 15 years of age with cerebrovascular occlusion, who were admitted to the Department of Pediatrics, Ramathibodi Hospital. Those with explainable causes were excluded. Ten patients were enrolled in this study, 6 of whom had arterial occlusions; the rest had venous sinus occlusions. Their ages ranged from 1 year, 7 months to 14 years (9 boys, 1 girl). Patients with arterial occlusions presented with acute focal neu- rologic deficits. CT revealed areas of cerebral infarction in 4 of the 5 and cerebral angiography demonstrated occlusions in 3 of 4 patients studied. Patients with venous sinus occlusions pre- sented with increased intracranial pressure. Venous sinus occlu- sions were demonstrated by CT and/or angiography. The level of AT III, PC, and PS were normal in all arterial occlusions pa- tients. Decreased PC levels were observed in 2 of 4 patients with venous sinus occlusions (34% and 52% of normal). In children, cerebral thromboembolism has been known to be associated with cardiac disease, vasculitis, dehydration, and intracranial infec- tions, Excluding these common causes, a hemostatic disorder is usually caused by L-asparaginase toxicity. The pathogenesis of a hemostatic disorder could be found in 20-30% of patients. Screening for deficiencies of AT III, PC, and PS in this group of 10 patients found PC deficiency in 2 patients. Excluding com- mon associations of cerebral thromboembolism, PC deficiency should be looked for especially in patients with venous sinus occlusions.

dren who suffered from stroke were admitted to the Department of Pediatrics, Ramathibodi Hospital. Forty-three were boys and the ages ranged from 5 months to 15 years. Thirty-one patients had hemorrhagic stroke (HS). The diagnosis was verified by CT, MRI, angiography, or CSF examination demonstrating intracra- nial hematoma or subarachnoid hemorrhage. The causes of HS included vascular malformations, bleeding disorders, hyperten- sion, mycotic aneurysm, and gnathostomiasis in 14, 6, 4, 3, and 1 patients, respectively. The cause was not known in 3 patients. Ischemic stroke (IS) occurred in 38 patients. CT or MRI dem- onstrated cerebral ischemia or infarction; cerebral angiography showed irregularity or occlusion of blood vessels. The causes included hyperviscosity or hypercoagulability in 7 and cardiac pathology as the sources of embolism in 8 patients; other patho- logic findings included arteriovenous malformation, Takayasu arteritis, SLE, and moya-moya disease. The causes were unde- termined in 12 patients. Headache, vomiting, and abnormal optic fundi had greater incidences in HS, while unilateral neurologic deficit occurred in IS. Complete recovery was observed in 45%, residual deficit in 39%, death in 7%, and lost to follow-up in 9% of HS patients; in IS patients, the percentages were 24, 52, 13, and 11, respectively.

114. VPA METABOLITES IN SERUM AND URINE WITH HIGH-DOSE VPA MONOTHERAPY: 4-EN-VPA, VALPROYLCARNITINE, AND BETA-OXIDATION ME- TABOLITES OF VPA Tateo Sugimoto, Hideki Muro, Man Woo, Naoki Nishida, and Kiyotaka Murakami, Yawata and Osaka, Japan

In high-dose VPA monotherapy with L-camitine, serum and urine VPA metabolites and carnitine levels and urine valproyl- camitine were analyzed by GC/MS/SIM and HPLC. Levels of S-4-en-VPA were significantly higher than those in the standard VPA dose and the increase of 4-en-VPA did not correlate with levels of SGOT. The ratio of [S-13-oxidation metabolites/(to + tol) oxidation metabolites] was distinctly decreased compared with standard therapy. Urinary valproylcarnitine levels corre- lated well with the levels of total VPA, B-oxidation metabolites, (to + tol) metabolites, 4-en-VPA, total camitine, free camitine, and acylcamitine in urine, but not with the blood ammonia lev- els. No patient developed severe liver dysfunction during the 4-year VPA monotherapy. The high-dose VPA monotherapy was concluded to be comparatively safe. From a viewpoint of VPA metabolism in high-dose monotherapy, the mechanisms of VPA-hepatotoxicity could not be ascribed to the increase in S-4- en-VPA and/or toxic acyl-CoA, including valproyl-CoA in this study.

113. STROKE IN CHILDREN Pongsakdi Visudhiphan, Duangrurdee Wattanasirichaigoon, and Surang Chiemchanya, Bangkok, Thailand

Stroke refers to a clinical syndrome characterized by sudden neurologic deficit caused by cerebrovascular diseases. During a 13-year period from January, 1979 to December, 1991, 69 chil-

115. DIAGNOSTIC SIGNIFICANCE OF GIANT SEP AND ABSENT SEP Akihiro Yasuhara, Atsushi Araki, Ayako Ochi, Yoshiaki Harada, and Yohnosuke Kobayashi, Osaka, Japan

We observed giant somatosensory evoked potentials (SEPs) or absence of SEPs in children with specific neurologic disorders. Especially giant SEPs were related to myoclonic epilepsy. To

114 PEDIATRIC NEUROLOGY Vol. II No. 2