中枢刺激剤Na—β，β—pentamethylene—γ—hydroxybutyrateによる異常脳波賦活の検討（第1報）—新脳波賦活剤としての応用について

THE CLINICAL STUDIES ON THE EEG-ACTIVATING EFFECTS OF NA-β,β-PENTAMETHYLENE-r-HYDROXYBUTYRATE, A NEW CENTRAL STIMULANT.:Usefulness as an new EEG-activating agent

I．はじめに

　てんかんの診断にあたつて脳波検査の有する重要性については今さらいうまでもないが，てんかん患者の短時間の安静覚醒時の脳波がつねに発作性の律動異常paro—xysmal dysrhythmiaを示すとはかぎらない。てんかんの安静時の異常脳波の出現率は40％から70％といわれ，1回だけの安静時脳波で異常がみいだされぬからといつて，てんかんの診断を否定することはできない。脳にある種の刺激を与え，潜在する異常波を誘発し，あるいはすでに現われている異常波を増強する方法は，脳波の賦活activationと呼ばれ，過呼吸，閃光刺激，各種の痙攣剤の静注，自然睡眠あるいは誘発睡眠などが現在ひろく用いられている。

　このうちで，もつとも多く用いられているのはpenta—methylenetetrazol （Metrazol, Cardiazol, Pentazol以下Pと略す）およびbemegride （Megimide, Antibarbi以下Mと略す）であるが，この両剤は，異常波賦活閾値と，臨床発作誘発閾値の差が僅少で，脳波検査中に突然不測の臨床発作を惹起する場合が少なからずあり，また注射にさいして，各種の自律神経症状を中心とした不快な自覚症状を呈することが多く，年少者や神経質な患者では，副作用のため検査を中止せざるを得なかつたり，検査のさいの動きに伴う筋電図などのartefactsの混入が多く，判読のさいに支障をきたすなどの欠点があり，より安全で副作用の少ない賦活剤の出現がのぞまれていた。

Na-β, β-pentamethylene-r-hydroxybutyrate (PHB), used as analeptica and antidepressive psychostimulant therapeutically, is a derivative of γ-hydroxybutyric acid, one of the lower fatty acids reported as a new hyponotica which prolongs the stage of paradoxical sleep, and has a hexacyclic pentamethylene structure bonded with β-positioned carbon in this butyrate. It has been known recently by us that the oral admini-stration of a relatively small dose of PHB occasion-ally produced convulsions in two narcoleptics who had high threshold by pentylentetrazol EEG activa-tion. We surmised, therefore, that this activating effect for CNS could be utilized as EEG activating method for the diagnosis of epileptic disorders.

Intravenous slow injection at the rate of 2. 5mg / min. of 0.1% PHB solution (maximal dosis 20mg) was examind on 58 epileptic cases, 26 borderline cases (migraine, Meniere, posttraumatics, etc. ) and 41 control cases (psychosis and neurosis).

Results:

1) In 80.4% of 46 epileptics who did not show any paroxysmal pattern in interseizure record before EEG activation, 30.4% of borderline cases, and 12.2% of control cases, paroxysmal patterns were elicited within 20mg. of admistration. Most cases of epileptics were activated within 10mg (about< 0.2 mg/kg).

2) The activated patterns were diffuse spike-wave complex (75.5%), high voltage slow burst (16.3%) and focal spike or spike-wave complex. (8.2%)

3) The clinical seizures were provocated in 3 of 46 cases who had no paroxysm signs before activation, and in 5 of 12 cases who had any paroxysm signs before activation. Those were all their own habitual seizures, 3 grand mals, 1 focal convulsion, 3 psy-chomotor seizures and 1 petit mal. No uncomfortable side actions were observed.

From the results mentioned above, the activation with PHB seems a more effective and specific procedure for the differential diagnosis of epileptic disorders in comparison with hitherto used penty-lenetetrazol or bemegride activations.