Hideki Kido

Diffuse cerebral hypoperfusion in epileptic patients observed from quantitative assessment with single photon emission computed tomography using N-isopropyl-(iodine-123)-p-iodoamphetamine

Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 15 epileptic adult patients receiving chronic high-dose antiepileptic drug therapy and 22 normal volunteers matched for sex and age, using single photon emission computed tomography with N-isopropyl-(iodine-123)-p-iodoamphetamine. The entire averaged rCBF value in the epileptic patients, i.e. 52.8 +/- 13.7 ml/10 g/min (range: 25-78 ml/100 g/min), was significantly lower as compared with that in the normal subjects, i.e. 69.1 +/- 14.2 ml/100 g/min (range: 46-102 ml/100 g/min). Six of the 15 patients showed absolute rCBF values less than the minimum of the normal range, i.e. 46 ml/100 g/min, in all or most of the measured brain tissues. There was a significant correlation between the diffuse cerebral hypoperfusion and simultaneous ingestion of phenytoin and phenobarbital. The possible effects of antiepileptic drugs on rCBF are discussed.

A pharmacokinetic study of clomipramine in regions of the brain

Abstract: The pharmacokinetic profiles of clomipramine (CMP) and the serial changes of its concentration in specific brain regions were investigated in rats after an acute treatment with intravenous CMP (10 mg/kg). The CMP concentrations in plasma declined triexponentially and fitted a three‐compartment open model. The brain to plasma concentration ratio showed a constant value, 22.2 ± 4.9, 30 minutes after the injection. Regional brain differences in the CMP distribution and accumulation were also found. Four hours after the injections, the hippocampus was found to have the highest drug concentration, and the concentrations in this region were in the following order; thalamus, striatum, amygdala, cortex > pons + medulla oblongata > hypothalamus, bulbus olfactorius + septum, mesencephalon > cerebellum. Particularly, unique kinetics were observed in the cortex, amygdala and hippocampus.

A new experimental model for drug studies: effects of phenobarbital and phenytoin on photosensitivity in the lateral geniculate-kindled cat.

Summary: Photosensitivity was acquired as a result of kindling in the lateral geniculate body (GL), and the GL‐kindled cat pretreated with DL‐allylglycine showed a stable level of photosensitivity. To test the usefulness as a model for the evaluation of anticonvulsant drugs, the effects of phenobarbital (PB) and phenytoin (PHT) on photosensitivity were studied in the GL‐kindled cat under DL‐allylglycine. PB (5 and 10 mg/kg intravenously, i.v.) completely suppressed photically induced seizures in most subjects at plasma concentrations of 7–16 μg/ml, and this anticonvulsant action persisted for at least 4 h after the injection. PHT (15 mg/kg, i.v.) at plasma concentrations of 9–15 μg/ml produced toxic signs, e.g., pupil dilatation, hypersalivation, and tachypnea. At this dose, PHT was inactive against photically induced myoclonus but prevented the elicitation of a generalized tonic‐clonic convulsion. From these results showing that the effects of anticonvulsant drugs on photically induced seizures can be assessed in relation to plasma concentration and acute neurologic toxicity, we suggest that the GL‐kindled cat is a potentially useful animal model of epilepsy for testing the efficacy of anticonvulsant drugs.

Correlations between quantitative EEG and regional cerebral blood flow (SPECT) in patients with partial epilepsy

During interictal periods in 9 patients with partial epilepsy we examined whether there were correlations between the relative power of background EEG (power spectral analysis) and the absolute values of regional cerebral blood flow (rCBF) measured by 99mTc hexamethylpropylene amine oxime (HMPAO) SPECT in each cerebral region. None of the patients had any organic cerebral lesions on X-ray CT examinations, neurological abnormalities or mental retardation. There was an inverse correlation between rCBF and the relative power of the theta band, and a direct correlation between rCBF and that of the alpha band of 10-12.8 Hz, in the right and/or left frontal, parietal and temporal regions. In the occipital regions, there was a direct correlation only between rCBF and the relative power of the beta band. These correlations were noted whether the analyzed regions were epileptic foci or not. These results suggest that background EEG and rCBF changes in epileptic patients are closely coupled.

Probable Cerebellar Abnormality on N-lsopropyl-(lodine-123)-p-lodoamphetamine Single Photon Emission Computed Tomography Scans in an Epileptic Patient Receiving Long-Term High-Dose Phenytoin Therapy

Quantitative assessment of regional cerebral blood flow (rCBF) was performed in a 22-year-old man with intractable temporal lobe epilepsy on long-term high-dose phenytoin (PHT) therapy, using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine-123)-p-iodoamphetamine. In all the SPECT scans repeated three times with changes in the PHT dose, absolute rCBF values were lower in most of the cerebral and cerebellar regions measured, as compared with 5 normal subjects matched for sex and age, and 22 normal subjects including the 5 men. Both the cerebellar to frontal rCBF ratio and cerebellar to cerebral rCBF ratio in the patient persistently showed low values, probably reflecting abnormal relative cerebellar hypoperfusion, whereas X-ray computed tomography and magnetic resonance brain imaging showed no abnormal findings. However, this probable cerebellar abnormality on SPECT was to some degree reversible with decreases in the PHT dose. These results suggest the utility of SPECT scans for early detection of cerebellar abnormalities known to be often present in epileptic patients, and imply a risk of long-term high-dose PHT therapy.

Usefulness of the Newly Proposed International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders (1989): A Trial on Adult Patients in a Neuropsychiatric Clinic

Abstract: The utility of the “International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders,” proposed by ILAE in 1989, was investigated in a neuropsychiatric clinic with a patient population numbering 300. Two hundred and three patients (67.7%) had localization‐related epilepsies (LRE), including one idiopathic case. Sixty‐six patients (22%) had generalized epilepsies, 50 idiopathic, 2 Lennox‐Gastaut syndrome, and 14 symptomatic. Thirty‐one patients (10.3%) with generalized tonic‐clonic seizures occurring only during sleep had the epilepsies undetermined whether they are focal or generalized. In the symptomatic LRE cases, 34 cases could not be classified, and 7 of the cases with frontal lobe epilepsies were difficult to subtype. Eleven of the symptomatic LRE cases had some independent seizures, multiple foci in surface EEGs and were intractable. These cases may be defined as “multifocal epilepsies.”

Effects of Clomipramine on the Concentrations of Catecholamines, Indoleamines and Their Metabolites in 11 Rat Brain Regions

Abstract: The effects of clomipramine (CMP) treatment on the brain concentrations of catecholamines, indoleamines and their metabolites were evaluated in 11 rat brain regions. An acute CMP treatment (15 mg/kg) reduced only the 5‐hydroxyindole‐3‐acetic acid (5HIAA) concentrations in all regions. A long‐term CMP treatment (14 days, 10 mg/kg/day) decreased the concentrations of dopamine (DA), 5‐hydroxy‐tryptamine and 5HIAA in the mesencephalon, and increased the DA concentrations in the hippocampus. In comparison with the values for the long‐term treated rats, an acute injection of CMP (15 mg/kg) after a long‐term treatment increased the norepinephrine concentrations in the hypothalamus and amygdala, and the concentrations of DA, 3,4‐dihydroxyphenylacetic acid and homovanillic acid in the basal ganglia. On the other hand, it failed to decrease the 5HIAA concentrations in the basal ganglia, frontal cortex, hypothalamus, cerebellum, pons + medulla oblongata, and mesencephalon.

Utility of Quantitative Assessment of Regional Cerebral Blood Flow with 123I‐IMP SPECT: Diffuse Cerebral Hypoperfusion in Medicated Epileptic Patients

In the present study, we assessed the absolute values of regional cerebral blood flow (rCBF) in epileptic patients receiving chronic high dose antiepileptic drug therapy in comparison with those in normal volunteers matched for sex and age to examine the presence of rCBF abnormalities in such highly medicated patients. The present study focuses on the utility of the quantitative assessment of rCBF for clinical epilepsy.

Multi-institutional Study on Possibility of Prediction of Long-term Prognosis in Temporal Lobe Epilepsy.

側頭葉てんかんの長期予後予測の可能性を検討するため, 一定期間に受診し, その後, 10～20年間の治療, 経過観察をなしえた76例を対象として多施設共同研究を行った。治療開始後2年目の時点の臨床所見と長期予後との関係をみたところ, 治療開始後2年目に月1回以上の頻度で発作があり, しかも神経精神医学的合併症状がみられた11例では, 調査時点で全例が発作を有していたが, とくに, そのうちの7例は月1回以上の発作を示していた。これに対して, 治療開始後2年目の1年間に発作がみられず, その時点で神経精神医学的異常所見を示していなかった18例では, 16例 (89%) が発作抑制状態にあった。以上の結果から, 治療開始後2年目の臨床所見から長期予後の良否を予測することが, 少なくとも一部の例については, かなりの程度可能であるものと考えた。長期予後予測の治療的意義について若干の考察を加えた。

A Case of Epilepsy Characterized by Spike‐Wave Stupor Followed for Long Period

Abstract: A 34‐year‐old housewife with nonconvulsive status epilepticus was followed up for 20 years since the initial fit. She maintained some contact with reality during the stupor and recalled the episode to some extent, while the EEG showed continuous spike‐wave complexes. During the clinical course, the main type of seizures was spike‐wave stupor, of which the maximum frequency was several times a week in the hospital and the duration was many minutes to several hours, and also secondarily generalized convulsive seizures occurred approximately once a month. The lasting control of spike‐wave stupor was not achieved in spite of the various medications for the long follow‐up period. The ictal EEGs of spike‐wave stupor always showed the frontal origin. The meaning of the term “nonconvulsive status epilepticus” in this case was briefly discussed.