Ripley David, Krese Kelly, Rosenow Joshua M, Patil Vijaya, Schuele Stephan, Pacheco Marilyn S, Roth Eliot, Kletzel Sandra, Livengood Sherri, Aaronson Alexandra, Herrold Amy, Blabas Brett, Bhaumik Runa, Guernon Ann, Burress Kestner Catherine, Walsh Elyse, Bhaumik Dulal, Bender Pape Theresa L
Author Affiliations: HealthBridge Complex Care (Dr Ripley), Arlington Heights, Illinois; Shirley Ryan AbilityLab Brain Innovation Center (Drs Ripley, Krese, Roth, and Kestner), Chicago, Illinois; The Department of Veterans Affairs (VA), Research Service (Drs Krese, Kletzel, Livengood, Aaronson, Herrold, Blabas, Guernon, Kestner, Walsh, and Pape), Department of Neurology (Dr Patil), The Department of Veterans Affairs Mental Health Service Line (Drs Pacheco and Aaronson), Cooperative Studies Program Coordinating Center (Dr D. Bhaumik), Edward Hines Jr. VA Hospital, Hines, Illinois; Department of Neurological Surgery & Neurology (Drs Rosenow and Schuele), Department of Physical Medicine and Rehabilitation (Drs Schuele, Roth, Livengood, Rosenow and Pape), Department of Psychiatry and Behavioral Sciences (Dr Herrold), Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Neurology, Stritch School of Medicine (Dr Patil), Loyola University, Chicago, Illinois; Department of Psychiatry (Dr Aaronson), Department of Psychiatry, Biostatistical Research Center, Division of Epidemiology and Biostatistics (Drs R. Bhaumik and D. Bhaumik), University of Illinois at Chicago, Chicago, Illinois; and Department of Speech-Language Pathology (Dr Guernon), Lewis University, Romeoville, Illinois.
J Head Trauma Rehabil. 2025;40(3):203-215. doi: 10.1097/HTR.0000000000000991. Epub 2024 Sep 5.
Repetitive Transcranial Magnetic Stimulation (rTMS) is emerging as a promising treatment for persons with disorder of consciousness (DoC) following traumatic brain injury (TBI). Clinically, however, there are concerns about rTMS exacerbating baseline seizure risk. To advance understanding of risks, this article reports evidence of DoC-TBI rTMS-related seizure risk.
Acute and sub-acute hospitals.
Persons in states of DoC 6.5 months to 15 years after TBI (n = 20) who received active rTMS (n = 17) or placebo rTMS (n = 3). After completing placebo procedures, placebo participants completed active rTMS procedures. These 3 participants are included in the active group.
Meta-analysis of data from 3 clinical trials; 2 within-subject, 1 double blind randomized placebo-controlled. Each trial used the same rTMS protocol, provided at least 30 rTMS sessions, and delivered rTMS to the dorsolateral prefrontal cortex.
During each study's rTMS treatment phase, seizure occurrences were compared between active and placebo groups using logistic regression. After stratifying active group by presence/absence of seizure occurrences, sub-groups were compared using contingency chi-square tests of independence and relative risk (RR) ratios.
Two unique participants experienced seizures (1 active, 1 placebo). Post seizure, both participants returned to baseline neurobehavioral function. Both participants received antiepileptics during remaining rTMS sessions, which were completed without further seizures. rTMS-related seizure incidence rate is 59 per 1000 persons. Logistic regression revealed no difference in seizure occurrence by treatment condition (active vs placebo) or when examined with seizure risk factors ( P > .1). Presence of ventriculoperitoneal shunt elevated seizure risk (RR = 2.0).
Collectively, findings indicate a low-likelihood that the specified rTMS protocol exacerbates baseline seizure rates in persons with DoC after TBI. In presence of VP shunts, however, rTMS likely elevates baseline seizure risk and mitigation of this increased risk with pharmacological seizure prophylaxis should be considered.
重复经颅磁刺激（rTMS）正逐渐成为创伤性脑损伤（TBI）后意识障碍（DoC）患者的一种有前景的治疗方法。然而在临床上，人们担心rTMS会增加基线癫痫发作风险。为了进一步了解相关风险，本文报告了与DoC-TBI的rTMS相关癫痫发作风险的证据。
急性和亚急性医院。
TBI后6.5个月至15年处于DoC状态的患者（n = 20），其中接受主动rTMS治疗的患者（n = 17），接受安慰剂rTMS治疗的患者（n = 3）。在完成安慰剂程序后，安慰剂组参与者完成主动rTMS程序。这3名参与者被纳入主动治疗组。
对来自3项临床试验的数据进行荟萃分析；2项为受试者内试验，1项为双盲随机安慰剂对照试验。每项试验都使用相同的rTMS方案，提供至少30次rTMS治疗，并将rTMS应用于背外侧前额叶皮质。
在每项研究的rTMS治疗阶段，使用逻辑回归比较主动治疗组和安慰剂组的癫痫发作情况。在根据癫痫发作情况对主动治疗组进行分层后，使用列联卡方独立性检验和相对风险（RR）比率对亚组进行比较。
两名患者出现癫痫发作（1名主动治疗组，1名安慰剂组）。癫痫发作后，两名患者均恢复到基线神经行为功能。两名患者在剩余的rTMS治疗期间均接受了抗癫痫药物治疗，后续治疗未再出现癫痫发作。rTMS相关癫痫发作发生率为每1000人中有59例。逻辑回归显示，治疗条件（主动治疗组与安慰剂组）或考虑癫痫发作风险因素时，癫痫发作情况无差异（P > 0.1）。存在脑室腹腔分流会增加癫痫发作风险（RR = 2.0）。
总体而言，研究结果表明，特定的rTMS方案增加TBI后DoC患者基线癫痫发作率的可能性较低。然而，在存在脑室腹腔分流的情况下，rTMS可能会增加基线癫痫发作风险，应考虑使用药物预防癫痫发作来降低这种增加的风险。
