Toshio Hiyoshi

Anticonvulsive effect of dapsone (4,4'-diaminodiphenyl sulfone) on amygdala-kindled seizures in rats and cats

Dapsone (4,4-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.

Localizing Value of Seizure Manifestations of Temporal Lobe Epilepsies and the Consequence of Analyzing Their Sequential Appearance

We investigated the localizing and lateralizing value of principal seizure manifestations in temporal lobe epilepsies (signal symptoms, oroalimentary automatisms, somatomotor manifestations, unilateral dystonic posturing, ictal speech, motionless stare) of 223 complex partial seizures in 50 patients. All the patients had invasive long‐term monitoring with the combined implantation of intracerebral electrodes in and subdural electrodes on the bilateral temporal lobes. Postoperative freedom from seizures was ascertained for longer than one year. We found that 35 patients had amygdalohippocampal seizures and 15 had lateral temporal seizures. The value of the manifestations was established in relation to the site and side of seizure origin and to the progression of seizure discharges within the unilateral temporal lobe or to the contralateral cerebral hemisphere. Several signs among the manifestations were found to be reliable in predicting the site or side of the temporal lobe seizure focus. We emphasized the importance of investigating sequential changes of seizure manifestations in relation to ictal EEG findings by means of simultaneous recording.

Anticonvulsant Effect of Topiramate [2, 3:4, 5‐bis‐O‐(1‐methylethylidene‐β‐D‐fructopyranose sulfate] on Amygdaloid Kindled Seizures in the Cat

The anticonvulsant properties of topiramate [2, 3:4, 5-bis-0-( l-methylethylidene8-D-fructopyranose sulfate], a newly developed anticonvulsant, have been studied in seizure models in mice, rats and rabbits. In amygdaloid (AM) kindled rats, a single dose of topiramate exerted moderate inhibition on the kindling score. In the present study, we conducted a series of experiments using chronic oral administration of topiramate in AM kindled cats.

Surgical treatment of epilepsy in the comprehensive care program : advantages and considerations

Abstract: To properly establish the surgical treatment of epilepsy in the comprehensive care program, we planned a surgical strategy mainly for a temporal lobe epilepsy and have performed 60 temporal lobectomies. The surgical candidates were selected from 142 patients who met the initial criteria, and passed the initial evaluation for surgical intervention. Forty‐five patients had long‐term intracranial EEG recording, and circumscribed organic lesions were disclosed in 27 patients by neuroimaging techniques. The outcome of 23 patients who were followed for 2 years postoperatively was complete freedom from complex partial seizures in 17 patients (74%) and an increase in full employment from 2 to 10 patients. Despite the possible surgical complications, including detrimental effects on the higher cerebral functions, it is essential that the surgical treatment of epilepsy should be established as a part of the comprehensive care program. Our experiences and analyses of the state of the art in surgical intervention also suggest that surgical indications for more intractable patients whose social adjustment is less hopeful should be established and the surgical care system for these patients should also be planned. Furthermore, some patients may be free from recurrent seizures postoperatively, but still have difficulties in social rehabilitation. The problems for such patients remain unsolved.

Conditions for Omitting Invasive Long‐Term Monitoring before Surgical Resection in Patients with Temporal Lobe Epilepsy

Abstract: The omission of invasive long‐term monitoring before surgical resection in patients with epilepsy should be permitted only for those in whom the epileptogenic focus is presumed to localize unilaterally in the mesial aspect of the temporal lobe. The localization may well be confirmed through noninvasive measures. Retrospective analyses of data obtained from noninvasive investigations (scalp‐recorded and sphenoidal EEG, neu‐rolmages, and electroclinical seizure manifestations) were carried out in 58:patients. The localization of their epileptogenic focus was subsequently confirmed by the implantation of both intracerebral and subdural electrodes; the focus had an amygdalohippocampal origin in 41:patients and a lateral temporal origin in 17:patients. From the comparison of noninvasive Andings between these two groups, we propose the following indispensable conditions for omitting an invasive evaluation: 1. Appearance of focal epileptic discharges unilaterally in the sphenoidal lead observed during the simple phase of partial seizures, or unilateral discharges with predominancy in the sphenoidal lead during the early phase of complex partial seizures. 2. Interictal spikes on scalp‐recorded EECs localizing unilaterally in the anterior region of the temporal lobe, and if bilaterally independent, presenting with unilateral predominancy in a ratio of greater than 41. 3. Presence of autonomic signs in the initial phase of signal symptoms. 4. Neuroimaging Andings in the mesial temporal region: elongated T2 on MRI and hippocampal atrophy, or a tumorous lesion. The lateralhation conforms to interictal and ictal paroxysmal EEC findings. There were 8:patients with seizures of amygdalohippocampal origin who satisfied all the indispensable condition, but not a single patient with seizures of lateral temporal origin. Thus, the conditions we propose are surely useful for determining whether patienta with lateral temporal seizures should be excluded from invasive long‐term monitoring before surgical resection.

Subtypes of Temporal Lobe Epilepsies: A Clinical Point of View

Abstract: We studied 40 patients with temporal lobe epilepsies who had long‐term intracranial EEC recordings and temporal lobectomies. They were divided into 3 groups on the basis of the anatomical site of seizure origin. An electrode implantation technique combined intracerebral depth electrodes with subdural strip electrodes. The seizures were of amygdalo‐hippocampal origin in 18 patients, lateral temporal in 13 patients, and temporo‐basal in 9 patients. The clinical and EEG features were reviewed retrospectively with regard to 3 factors in each patient: localization of interictal spikes in the scalp‐recorded EEG, signal symptoms (auras), and presumed etiologies. Epilepsy with amygdalo‐hippocampal and lateral temporal seizures was found to be distinguishable by the electroclinical features. It seems practical to classify these 2 subtypes of temporal lobe epilepsies as in the 1989 Classification of Epilepsies and Epileptic Syndromes. Temporal lobe epilepsies thus defined can be regarded as epileptic syndromes rather than a cluster of seizure manifestations.

Complex partial seizures with unilateral discharges originating from temporal lobe.

難治側頭葉てんかんの外科治療の術前評価のために行った長時間頭蓋内脳波記録について, 24症例, 計123回の複雑部分発作の脳波・発作症状相関を検討した。側頭葉起源の複雑部分発作は, 1) 自己維持性の律動性発作発射が起源側の側頭葉にとどまる一側性複雑部分発作と, 2) 対側半球の側頭葉に伝播する両側化複雑部分発作に二分することができた。 意識減損時の発作発射は必ずしも両側側頭葉を巻き込むことを必要としない。しかし, 焦点側側頭葉の内側構造 (海馬, 扁桃核) と外側皮質はともに発作発射に巻き込まれていた。一側性と両側化複雑部分発作の臨床症状を比較すると, 前発作では外来刺激に対する反応性が部分的に保たれ, 意識減損からの回復は速やかである傾向がみられ, 反応性の喪夫によって特徴づけられる無動・凝視状態は認められなかった。複雑部分発作の意識減損にかかわる側頭葉と脳幹の機能関連について考察を加えた。

Symptomatology: Complex Partial Seizures with Unilateral Discharge Originating from Temporal Lobe

It is commonly assumed that complex partial seizures sometimes have not only unilateral but frequently bilateral hemispheric ictal involvement (Commission on Classification and Terminology, International League against Epilepsy, 1981; Gloor and Olivier, 1980l 2). However, the actual features especially of the former have not been well described. Therefore, it is of practical and theoretical significance to explore the possible differences in the ictal symptomatology between those having unilateral and bilateral involvement. In this study, we reviewed the records of patients with temporal lobe epilepsy whose complex partial seizures (CPS) were documented by a simultaneous video-audio-intracranial-electroencephalogram (EEG ) recording. All of the patients were potential candidates for resection surgery because of their intractable CPSs occurring more than once every week, and their speech laterality had been evaluated by means of the Wada test (Wada and Rasmussen, 1960”). An intracranial EEG was obtained through the intracranial and subdural electrodes implanted bilaterally in the mesial (amygdalo-hippocampal) and lateral (neocortical) temporal structures, and those implanted unilaterally in the orbito-frontal cortex (Mihara et al., 1987*). An impairment of consciousness during the seizures was assessed through the patient’s responsiveness and/or awareness to externally applied stimuli. Of 23 patients studied, 1 1 1 videotaped CPSs were selected based on their clear-cut electroclinical documentation. The side of seizure origin was right in 76 seizures of 14 patients and left in 35 seizures of 9 patients, and the site of seizure origin was the mesial temporal in 70 seizures of 14 patients and the lateral temporal structures in 41 seizures of 9 patients. In the majority of these seizures (88 of l l l ) , the ictal discharge spread bilaterally involving both the temporal lobes in a widespread manner. However, in 23 seizures, there was no evidence that the seizure discharge had spread to the contralateral side, nor was there any clear evidence that the contralateral EEG had been significantly altered in any other way. In the latter, it was confirmed in 5 out of 8 patients that the clinicoelectrographic features were reproduci-