今日の臨床サポート 今日の臨床サポート

著者: 久保田有一 東京女子医科大学附属足立医療センター脳神経外科

監修: 永山正雄 国際医療福祉大学医学部・成田病院 脳神経内科、集中治療部

著者校正済:2024/12/25
現在監修レビュー中
参考ガイドライン:
  1. 日本神経学会:てんかん診療ガイドライン2018 第8章 てんかん重積状態
  1. 米国臨床神経生理学会:Standardized Critical Care EEG Terminology: 2021 Version
患者向け説明資料

改訂のポイント:
  1. 定期レビューを行い、下記の点を加筆・修正した。
  1. てんかん重積の定義を、ILAE(国際抗てんかん連盟)の2015年定義に従って加筆・修正した。
  1. 「抗てんかん薬」を、日本てんかん学会のてんかん用語集第6版を参考に「抗てんかん発作薬」に統一した。
  1. 症例を2例追加した。

概要・推奨   

  1. てんかん重積状態は、痙攣性てんかん重積状態(convulsive status epilepticus、CSE)と非痙攣性てんかん重積状態(nonconvulsive status epilepticus、NCSE)に分けられる。
  1. NCSEはさまざまな原因で起こり、意識障害の程度は軽度から重度までさまざまである。原因不明の意識障害の場合には、診断のため脳波モニタリングを考慮する(推奨度2)
  1. NCSEはまれな病態ではなく、時に予後不良因子でもあるため、速やかに脳波検査を施行する(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご

病態・疫学・診察 

疾患情報(疫学・病態)  
  1. てんかん重積状態は、2015年国際抗てんかん連盟により「発作が自然停止しにくくなるt1時間、長期的な後遺症を残すt2時間に分けられ、けいれん性てんかん重積である強直間代発作重積状態では,t1時間が5分,t2時間が30分、NCSEでは,焦点意識減損発作重積状態(focal status with impairment of consciousness)ならt1時間が10分,t2時間が60分以上、欠神発作重積状態(absence status epilepticus)なら t1時間は10~15分」と定義されている[1]
  1. てんかん重積状態は、痙攣性てんかん重積状態(convulsive status epilepticus、CSE)と非痙攣性てんかん重積状態(nonconvulsive status epilepticus、NCSE)に分けられる。CSEには、全身痙攣重積状態(generalized convulsive status epilepticus、GCSE)と部分痙攣重積状態(epilepsia partialis continua)があるが、生命に危機が及び臨床的に重要なのはGCSEである。
  1. 抗てんかん発作薬2剤による適切な初期治療を行っても発作が終息しない場合、難治性てんかん重積状態(refractory status epilepticus、RSE)と呼ぶ。
  1. NCSEの症状は、意識障害が主体である。全身痙攣を起こすことなく、眼振、凝視、反復性の瞬目・咀嚼・嚥下運動、顔面、四肢のミオクローヌス、自動症を呈する。
  1. 非痙攣性てんかん発作(nonconvulsive seizure、NCS)が持続あるいは反復する重篤な状態であるNCSEの認識はいまだ不十分である。
 
  1. 非痙攣性てんかん重積状態(NCSE)はまれな病態ではなく、予後不良因子でもあるため、原因不明の意識障害例には速やかに脳波検査を施行することが推奨される(推奨度2、エビデンスレベルO)[2]
  1. 入院時に意識障害を伴ったてんかん重積状態患者連続94例を対象とした検討では、うち24例(25.5%)が非痙攣性てんかん重積状態(NCSE)であり、入院後にNCSEとなった例も含めると32例(34.0%)であった。
  1. SEの予後因子については、経過中にNCSEとなった例や脳血管障害を契機にSEとなった例は、年齢、性別、その他の基礎疾患と独立して有意に予後不良であった。NCSEはまれな病態ではなく、予後不良因子でもあるため、原因不明の意識障害例には速やかに脳波検査を施行するべきである。
病歴・診察のポイント  
  1. NCSEは、何らかの原因があるため、その原因を検索する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH.
A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.
Epilepsia. 2015 Oct;56(10):1515-23. doi: 10.1111/epi.13121. Epub 2015 Sep 4.
Abstract/Text The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: name of pattern, morphology, location, time-related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly.

Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
PMID 26336950
Yoshimura H, Takano S, Kawamoto M, Beppu M, Ohara N, Kobayashi J, Kuzuya A, Yamagami H, Kohara N.
[Clinical characteristics of status epilepticus in an emergency hospital: importance of nonconvulsive status epilepticus].
Rinsho Shinkeigaku. 2008 Apr;48(4):242-8. doi: 10.5692/clinicalneurol.48.242.
Abstract/Text Although nonconvulsive status epilepticus (NCSE) is a major neurological emergency, its frequency and clinical course are not well clarified. We investigated the clinical characteristics of status epilepticus focusing on the significance of NCSE. One thousand seven hundred twenty-three patients were admitted as neurological emergency cases in our hospital between October 2003 and September 2006. Of these cases, 94 (5.5%) were diagnosed as status epilepticus of which, 24 (25.5%) were diagnosed with NCSE on admission. Moreover, 8 patients who presented with convulsive status epilepticus on admission had episodes of NCSE during hospitalization. Thus, 32 patients (34.0%) suffered from NCSE during their clinical course. We analyzed the prognostic factors of status epilepticus using the Glasgow Outcome Scale. Poor outcome was significantly correlated with NCSE (p = 0.003) and acute cerebrovascular disease (p = 0.010), independent of age, sex, history of epilepsy, and other etiologies. Our study revealed that NCSE is not a rare condition and results in a poor outcome. Careful EEG evaluation of patients with consciousness disturbance might increase the diagnostic accuracy of NCSE, and aggressive treatment of patients with NCSE should be necessary to improve the prognosis of NCSE.

PMID 18453155
Shimogawa T, Morioka T, Sayama T, Haga S, Kanazawa Y, Murao K, Arakawa S, Sakata A, Iihara K.
The initial use of arterial spin labeling perfusion and diffusion-weighted magnetic resonance images in the diagnosis of nonconvulsive partial status epileptics.
Epilepsy Res. 2017 Jan;129:162-173. doi: 10.1016/j.eplepsyres.2016.12.008. Epub 2016 Dec 21.
Abstract/Text BACKGROUND: In the diagnosis of nonconvulsive status epilepticus (NCSE), capture of ongoing ictal electroencephalographic (EEG) findings is the gold standard; however, this is practically difficult without continuous EEG monitoring facilities. Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and perfusion MRI with arterial spin labeling (ASL), have been applied mainly in emergency situations. Recent reports have described that ictal MRI findings, including ictal hyperperfusion on ASL and cortical hyperintensity of cytotoxic edema on DWI, can be obtained from epileptically activated cortex. We demonstrate the characteristics and clinical value of ictal MRI findings.
METHODS: Fifteen patients diagnosed as having NCSE (eight had complex partial status epilepticus (SE) and seven subtle SE) who underwent an initial MRI and subsequent EEG confrmation, participated in this study. Follow-up MRI and repeated routine EEG were performed.
RESULTS: In 11 patients (73%), ictal MRI findings were obtained on both DWI and ASL, while in four (27%) patients, ictal hyperperfusion was found on ASL without any DWI findings being obtained. In all 10 patients with an epileptogenic lesion, there was a tight topographical relationship between the lesion and the localization of ictal MRI findings. In the other five patients, ictal MRI findings were useful to demonstrate the pathophysiological mechanism of NCSE of non-lesional elderly epilepsy, or 'de novo' NCSE of frontal origin as situation-related NCSE. Ictal MRI findings are generally transient; however, in three cases they still persisted, even though ictal EEG findings had completely improved.
CONCLUSION: The present study clearly demonstrates that the initial use of ASL and DWI could help to diagnose partial NCSE and also combined use of the MRI and EEG allows documentation of the pathophysiological mechanism in each patient.

Copyright © 2016 Elsevier B.V. All rights reserved.
PMID 28092848
Nagayama M, Matsushima K, Nagayama T, Shinohara Y.
Persistent but reversible coma in encephalitis.
Neurocrit Care. 2005;2(3):252-7. doi: 10.1385/NCC:2:3:252.
Abstract/Text INTRODUCTION: Nontraumatic coma in adults has a poor prognosis, and late recovery of consciousness is unlikely. Functional recovery is usually extremely poor. However, a few nontraumatic comatose patients have shown late recovery of both awareness and function.
METHODS: A retrospective survey was conducted by reviewing the medical records of all inpatients to our department during the 1990s. Patients with persistent but reversible nontraumatic coma were identified according to the following criteria: (a) deep coma with a Glasgow Coma Scale (GCS) score of 7 or less on admission; (b) nontraumatic cause; (c) persistence of unconsciousness for longer than 1 month; and (d) subsequent recovery of GCS (total) to normal. The clinical spectrum of patients meeting these criteria was evaluated.
RESULTS: Six patients (ages 16-75 years) met the criteria. Viral encephalitis was diagnosed in five (two with herpes simplex virus, two with cytomegalovirus, and one with Epstein-Barr virus or cytomegalovirus). Two young female patients with encephalitis manifested extremely protracted coma persisting for 3 and 18 months, respectively. Complications included nonconvulsive status epilepticus in two patients and relative overdose of clonazepam in one patient.
CONCLUSION: Recognition of the clinical spectrum of persistent but reversible nontraumatic coma is important.

PMID 16159071
Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ.
Detection of electrographic seizures with continuous EEG monitoring in critically ill patients.
Neurology. 2004 May 25;62(10):1743-8. doi: 10.1212/01.wnl.0000125184.88797.62.
Abstract/Text OBJECTIVE: To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure.
METHODS: Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after >24 hours of monitoring.
RESULTS: Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018).
CONCLUSIONS: CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required >24 hours of monitoring to detect the first electrographic seizure.

PMID 15159471
Hirsch LJ, Fong MWK, Leitinger M, LaRoche SM, Beniczky S, Abend NS, Lee JW, Wusthoff CJ, Hahn CD, Westover MB, Gerard EE, Herman ST, Haider HA, Osman G, Rodriguez-Ruiz A, Maciel CB, Gilmore EJ, Fernandez A, Rosenthal ES, Claassen J, Husain AM, Yoo JY, So EL, Kaplan PW, Nuwer MR, van Putten M, Sutter R, Drislane FW, Trinka E, Gaspard N.
American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2021 Version.
J Clin Neurophysiol. 2021 Jan 1;38(1):1-29. doi: 10.1097/WNP.0000000000000806.
Abstract/Text
PMID 33475321
Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR Jr, DeLorenzo RJ.
Prevalence of nonconvulsive status epilepticus in comatose patients.
Neurology. 2000 Jan 25;54(2):340-5. doi: 10.1212/wnl.54.2.340.
Abstract/Text BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a form of status epilepticus (SE) that is an often unrecognized cause of coma.
OBJECTIVE: To evaluate the presence of NCSE in comatose patients with no clinical signs of seizure activity.
METHODS: A total of 236 patients with coma and no overt clinical seizure activity were monitored with EEG as part of their coma evaluation. This study was conducted during our prospective evaluation of SE, where it has been validated that we identify over 95% of all SE cases at the Medical College of Virginia Hospitals. Only cases that were found to have no clinical signs of SE were included in this study.
RESULTS: EEG demonstrated that 8% of these patients met the criteria for the diagnosis of NCSE. The study included an age range from 1 month to 87 years.
CONCLUSION: This large-scale EEG evaluation of comatose patients without clinical signs of seizure activity found that NCSE is an underrecognized cause of coma, occurring in 8% of all comatose patients without signs of seizure activity. EEG should be included in the routine evaluation of comatose patients even if clinical seizure activity is not apparent.

PMID 10668693
Young GB, Jordan KG, Doig GS.
An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality.
Neurology. 1996 Jul;47(1):83-9. doi: 10.1212/wnl.47.1.83.
Abstract/Text Of 49 patients with nonconvulsive seizures studied with continuous EEG monitoring, the overall mortality was 33% (16/49). Of the 23 patients with nonconvulsive status epilepticus (NCSE), 13 died (mortality 57%). Individual variables significantly associated with mortality were age, presence of NCSE, seizure duration, hospital and NICU length of stay, and delay to diagnosis and etiology (acute illness versus remote symptomatic). With multivariate logistic regression, only seizure duration (p = 0.0057, OR = 1.131/hour) and delay to diagnosis (p = 0.0351, OR = 1.039/hour) were associated with increased mortality. Acute symptomatic cases could not be adequately classified as either absence, simple, or complex partial status epilepticus when the impairment of consciousness arose form the initial illness. Current classifications of status epilepticus are inadequate for such cases.

PMID 8710130
「てんかん診療ガイドライン」作成委員会:てんかん診療ガイドライン2018..
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
久保田有一 : 講演料(アルフレッサファーマ(株))[2024年]
監修:永山正雄 : 特に申告事項無し[2024年]

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