Akio Takeda

Protein binding of four antiepileptic drugs in maternal and umbilical cord serum

The total and protein free levels of 4 antiepileptic drugs (AEDs) in serum from 35 maternity patients who had been treated with AED monotherapy throughout pregnancy were studied. Results were compared with those in the umbilical cord serum at the time of delivery, and the placental transfer of AEDs was evaluated from the viewpoint of the protein binding capacity of the drug. The materials consisted of 35 samples of maternal and umbilical cord serum in total and included 13 patients on phenobarbital (PB), 7 on phenytoin (PHT), 7 on carbamazepine (CBZ) and 8 on valproic acid (VPA). The mean fetal/maternal total concentration ratios were 0.86, 0.91, 0.73 and 1.59 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being above 1. On the other hand, the mean fetal/maternal free fraction ratios were 1.13, 1.10, 1.42 and 0.50 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being less than 1. Correlation of the 2 ratios showed a reciprocal proportion with a correlation coefficient of -0.90 (P < 0.005). It was considered that the fetal/maternal total concentration ratio of 4 AEDs was regulated by the fetal/maternal free fraction ratio of the corresponding AEDs and that the difference in fetal/maternal free fraction ratio depended on the type of drug being administered.

Infarction of Superior Cerebellar Artery Presenting as Cerebellar Symptoms

BACKGROUND MRI of the brain has facilitated the diagnosis of cerebellar infarction in the territory of the superior cerebellar artery (SCA). We analyzed the data on patients with SCA infarction who presented with only cerebellar symptoms in an attempt to define its underlying pathophysiology. SUMMARY OF REPORT Ten patients with SCA infarction who presented with cerebellar symptoms were studied by brain MRI, angiography, and underlying pathology. Brain MRI demonstrated an infarct in the SCA territory in the anterior rostral cerebellum of all patients. None had abnormalities in the brain stem. In four patients, a hemorrhagic infarct was present in the same region. Cerebral angiography revealed no obvious SCA occlusion or atherosclerotic vascular disease in any patient. Eight of the 10 patients had heart disease, such as atrial fibrillation or old myocardial infarction. The presumed diagnosis was occlusion of the SCA in its periphery due to cardiogenic embolism. CONCLUSIONS When a patient presents with only cerebellar symptoms and has cerebellar infarction demonstrated by brain MRI, the SCA branch is probably occluded by cardiogenic embolism.

Teratogenicity of Antiepileptic Drugs and Drug Specific Malformations

Antiepileptic drug (AED) treatment during pregnancy leads to a high incidence of malformations in the infants of epileptic mothers (IEM).3 The increased incidence of malformations has been ascribed to AEDs rather than to other background factors such as the seizure type and occurrence of seizures during the 1st trimester of pregnan~y.~ However, the relative contribution of each AED to the occurrence of malformations in IEM is unknown. On the other hand, shortly after Robert and Guibert reported a specific association between the use of valproate (VPA) by epileptic women and the occurrence of spina bifida in their offspring6, carbamazepine (CBZ) was also implicated5 ’. Thus, the aim of the present study was to evaluate the teratogenic effect of each AED and to clarify the relationship between the type of malformations and individual AEDs.

Epilepsy and driving in Japan: Current status as investigated in a prospective survey

People with epilepsy in Japan are prohibited by law from driving a motor vehicle regardless of whether their epilepsy is active or dormant. Nevertheless, some people with epilepsy illegally obtain drivers licenses. A total of 3,522 people with epilepsy throughout Japan, of whom 52.6% were men and 47.4% were women, were prospectively surveyed by a questionnaire regarding their automobile driving practices. Overall, 48.6% illegally held a drivers license and 38.9% actually drove. The automobile accident rate was 7.4%. The rate was 9.6% for patients with uncontrolled seizures, and 5.3% for those with controlled seizures. The incidence of accidents directly caused by seizures at the wheel was 1.6%. Complex partial seizures without auras were the most hazardous, and the risk became increasingly higher with increasing frequency of seizures. It was pointed out that the current law in Japan should be amended to conform with the more realistic regulations of Western countries.

Driving and Epilepsy: A Prospective Questionnaire Survey in Japan

A total of 3,522 patients with epilepsy, male 52.5% and female 47.396, with a mean age of 32.7 from 35 medical institutions throughout Japan was contacted by a questionnaire. Diagnostic categories in this series were temporal lobe epilepsy (TLE) in 33.70/0, primary generalized epilepsy (PGE) in 33.476, nontemporal lobe partial epilepsy (NTLE) in 24.5%, secondary generalized epilepsy (SGE) in 3.5% and others in 4.9%; types of seizure were complex partial seizure (CPS) with or without signal symptom in 39.376, grand ma1 seizure (GTC) in 3076, simple partial seizure (SPS) in 11.8%, partial onset generalized tonic-clonic seizure (pGTC) in 8.4%, mixed seizure (Mix) in 5.9% and others in 4.6%; frequencies of seizure were none (seizure-free more than 3 years) in 42.6%, once or more per year in 32.1%, per month in 17.2% and per week in 7.9% (Fig. 1).

Movement-Induced Focal Motor Seizures and Choreoathetosis As- sociated with Nonketotic Hyperglycemia: A Case Report

Case Report: We report the case of a diabetic woman who developed right‐sided reflex seizures and bilateral choreoathetosis during an episode of nonketotic hyperglycemia. The patient was a 67‐year‐old woman with a 14‐year history of HCV‐related liver cirrhosis who experienced polydipsia and polyuria in January 1998. She began to have episodes of abnormal hyperkinetic movements of the right upper extremity and tonic‐clonic seizures in the right arm triggered by voluntary movements of right or bilateral arms in the beginning of March 1998.The seizures increased in frequency and consequently left her disabled. She was admitted to our hospital with complaints of these abnormal motor phenomena on March 9, 1998. Neurological examinations revealed that she was alert, well‐oriented, and that cranial nerve functions were normal. Slight motor weakness of the right upper limb and deep tendon hyporeflexes were observed in all extremities. Sensations and cerebellar functions were intact. Choreic or athetotic involuntary movements were seen in the bilateral upper limbs and neck. These involuntary movements were increased by voluntary movement or posturing of the upper limbs. The focal tonic‐clonic seizures were easily triggered by voluntary movements such as knotting a cord. This seizure suddenly began by tonic movements in the right upper limb and gradually progressed to the right hemi‐face and neck without loss of consciousness.The average duration of seizures was about one minute. The laboratory data demonstrated mild leukocytopenia, thrombocytopenia, hepatic dysfunction, and hyperglycemia without ketosis. Fasting blood glucose was 41 I mg/dl, and HbAlc was 14.5%. Blood ammonia was within normal levels. Cranial CT revealed no abnormalities. Brain MRI on T I‐weighted images demonstrated bilateral high signal intensity in the putamen. An interictal EEG revealed a symmetrical slow background activity of 7–8 Hz. An ictal EEG recording showed a 2.5 4 Hz irregular sharp and slow wave discharge in the bilateral frontal‐central regions. Treatment with carbamazepine was ineffective for the seizures. However, the seizures completely disappeared after the administration of insulin on March 17. Under good control of the hyperglycemia, the abnormal involuntary movements decreased gradually and then completely disappeared; the patient became neurologically asymptomatic by March 30. The follow‐tip EEG demonstrated 9‐Hz alpha background activity without any epileptic discharges.

Alterations in the General Condition of Infants Born of Mothers Who Conceived while on a Long-Term Oral Antiepileptic Drug Treatment and Concentrations of Antiepileptic Drugs in Maternal and Cord Blood

It seems very interesting to investigate the influence of antiepileptic drugs (AED) on infants delivered of mothers who have conceived while receiving AED treatment. As an approach to this problem, the AED concentrations in both the maternal and fetal blood were determined, the infants born of them were evaluated for the general condition and health status during the first 6 days of life, and the results, upon being classified according to the type and blood levels of AED used, were compared with those in control babies born of nonepileptic mothers.