A 35-year-old adult with severe herpes simplex encephalitis complicated by rhabdomyolysis, acute kidney injury and refractory epilepsy after ECMO weaning: a case report

A 35-year-old adult with severe herpes simplex encephalitis complicated by rhabdomyolysis, acute kidney injury and refractory epilepsy after ECMO weaning: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A 35-year-old adult with severe herpes simplex encephalitis complicated by rhabdomyolysis, acute kidney injury and refractory epilepsy after ECMO weaning: a case report Yuchen Duan, Xuezhen Lin, Gui Jiang, Yamin Gao, Wenbo Qin, Lin Han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9606715/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background： Herpes simplex encephalitis (HSE) is the most common sporadic fulminant necr-otizing encephalitis with a high incidence of epilepsy. Rhabdomyolysis is a severe complicationusually associated with status epilepticus. However, HSE combined with rhabdomyolysis, acute kidney injury, coagulopathy requiring ECMO support, and persistent seizures after ECMO wea-ning is extremely rare, with unclear mechanisms and management. Case presentation： A 35-year-old male was admitted with fever, recurrent seizures, impaired consciousness, myalgia and oliguria. Laboratory tests showed peak CK 16940 U/L, myoglobin >3000 μg/L, acute kidney injury and coagulopathy. Cranial MRI demonstrated symmetric lesions in bilateral frontal, parietal, temporal, occipital lobes and thalami. Cerebrospinal fluid mNGS confirmed HSV‑1 infection.He developed respiratory‑circulatory failure and received 5 daysof ECMO support. Following comprehensive treatment, he was successfully weaned off ECMO, with obvious improvement in organ function. However, recurrent seizures persisted after wea-ning, accompanied by continuous epileptiform discharges on EEG. Conclusions： Severe HSE can induce life‑threatening rhabdomyolysis and acute kidney injury. ECMO is an effective life‑support therapy. Even after viral control and organ recovery, persistent epileptogenic injury in the central nervous system may lead to refractory epilepsy. Longterm seizure monitoring and individualized antiepileptic treatment are essential for HSE patients Herpes simplex encephalitis Rhabdomyolysis Epilepsy ECMO Acute kidney injury Central nervous system inflammation Figures Figure 1 Introduction Herpes simplex encephalitis (HSE) is an acute necrotizing encephalitis caused by herpes simpl-ex virus type 1 (HSV‑1) infection, characterized by acute onset, rapid progression and high m- ortality. More than 50% of patients develop seizures during the disease course [ 1 , 2 ] . HSE trigg-ers intense central and systemic inflammatory responses, which may lead to severe complicati- ons including rhabdomyolysis, AKI, coagulopathy, and even multiple organ dysfunction syndro- me (MODS) in critical cases [ 3 , 4 ] . Rhabdomyolysis is a life-threatening syndrome featured by disruption of skeletal muscle cell membranes, leading to massive release of myoglobin and CK into the circulation, which often induces AKI [ 5 ] . Although status epilepticus, trauma and infection are well-recognized causes, cases of severe rhabdomyolysis directly induced by HSE remain rare [ 6 , 7 ] . Here, we report a 35-year-old male with severe HSE who developed fulminant rhabdomyolysis,AKI and respiratory-circulatory failure requiring 5 days of ECMO support. After successful we-aning from ECMO, the patient suffered from persistent refractory epilepsy. We analyze the cli-nical characteristics, pathogenesis, diagnosis and treatment of this case to improve clinical reco-gnition and management of this rare and critical phenotype. Case presentation 1. Demographics and medical history A 35-year-old male was admitted to our hospital with a 5-day history of fever, and a 2 day history of recurrent seizures, impaired consciousness, myalgia and oliguria. His past medical hi-story was unremarkable, with no prior epilepsy, hypertension, diabetes, liver or kidney diseases,trauma, poisoning, blood transfusion or family history of genetic disorders. 2. Clinical manifestations Five days before admission, the patient developed fever with a maximum temperature of 38.9 °C, accompanied by headache and fatigue, without improvement after symptomatic treatment. Two days before admission, he suffered sudden loss of consciousness and generalized tonicclo-nic seizures, lasting 1–2 minutes and occurring repeatedly. Confusion and delirium gradually developed, accompanied by significant myalgia in the extremities, dark urine and oliguria. On admission, the patient was somnolent, tachypneic and hemodynamically unstable, requiring emergency tracheal intubation, mechanical ventilation and vasopressor support. 3. Physical examination Body temperature 38.6°C, heart rate 118 beats/min, respiratory rate 26 breaths/min, blood pres-sure maintained by norepinephrine.Neurological examination: somnolence, mild neck stiffness, b-ilateral pupils equal and round (3.0 mm) with reactive light reflex, increased muscle tone in e-xtremities, and positive bilateral Babinski signs.General examination: marked tenderness of limbmuscles, no skin rash or herpes, no edema, and no obvious abnormalities in cardiopulmonary or abdominal systems. 4. Auxiliary examinations 4.1 Laboratory tests Rhabdomyolysis markers: peak CK 16940 U/L, myoglobin > 3000 µg/L, significantly elevated LDH.Renal function: peak serum creatinine 435 µmol/L, elevated BUN, accompanied by oligur-ia.Coagulation profile: prolonged APTT, markedly elevated D‑dimer, indicating inflammation-rel-ated coagulation activation.Brain injury markers: significantly elevated blood ammonia and cere-brospinal fluid (CSF) lactate.CSF analysis: mildly elevated leukocytes and protein, normal gluc-ose and chloride; HSV‑1 was detected by mNGS, with no evidence of other viruses, bacteria, fungi or tuberculosis [ 8 ] . 4.2 Imaging and neurophysiological examinations Cranial MRI: approximately symmetrical abnormal signals in the cortex and subcortical white matter of bilateral frontal, parietal, temporal and occipital lobes as well as bilateral thalami, h-yperintense on T2WI/FLAIR(Fig. 1 b and c), consistent with typical HSE manifestations [ 9 ] . Transcranial Doppler (TCD): abnormally increased blood flow velocities in bilateral middle cer-ebral arteries, suggesting cerebral perfusion disturbance and vasospasm.(Fig. 1 d 、e、f and g). EEG: diffuse background slow waves with frequent spike and spike‑wave discharges(Fig. h and i), consistent with clinical seizures [ 10 ] . 5. Final diagnosis Herpes simplex encephalitis (HSV‑1) Severe rhabdomyolysis syndrome Acute kidney injury Symptomatic epilepsy, refractory epilepsy, generalized tonic-clonic seizures Coagulation disorder Multiple organ dysfunction syndrome Respiratory and circulatory failure (after ECMO support) Treatment course Due to critical condition and rapid progression to respiratory-circulatory failure, the patient rec-eived immediate combined treatment:Life support: tracheal intubation and mechanical ventilation,vasopressors, VA‑ECMO support for 5 days [ 11 ] .Antiviral therapy: intravenous acyclovir at ade-quate dosage, adjusted according to renal function [ 12 ] .Management of rhabdomyolysis and AKI:vigorous fluid resuscitation, urine alkalization, and hemodialysis [ 5 , 13 ] .Antiepileptic therapy:combi-ned antiepileptic drugs; sedatives were administered for aggravated seizures.Anti-inflammatory and neuroprotection: short-term corticosteroids to relieve cerebral edema, temperature control, sedation and intracranial pressure reduction.After treatment, the patient achieved hemodynamic and respiratory stability, successfully weaned off ECMO and mechanical ventilation. Follow up tests showed marked reduction in CK and myoglobin (Fig. 1 a ), recovery of renal function and coagulation profile. However, recurrent seizures, occasionally generalized tonic-clonic seizures, persisted after ECMO weaning. Seizure frequency decreased but was not fully controlled after adjustment of antie-pileptic regimen, and continuous epileptiform discharges remained on EEG. Results Laboratory markers: muscle enzymes, renal function and coagulation parameters improved signi-ficantly and gradually normalized.Organ function: respiration, circulation and renal function fully recovered; the patient was liberated from life support.Neurological status: consciousness impr-oved, but refractory recurrent seizures persisted with persistent abnormal EEG findings.Imaging findings: follow-up cranial MRI showed reduced cerebral edema and alleviated abnormal signals in bilateral cerebral lobes and thalami, but persistent structural lesions remained. Discussion 1. Possible mechanisms of HSE-induced rhabdomyolysis Early-onset severe rhabdomyolysis in this patient may be attributed to the following mechanis-ms: (1) Repetitive seizures caused sustained and intense muscle contraction, leading to direct muscle cell injury [ 6 , 7 ] ; (2) HSV‑1 directly invades muscle tissue or releases toxins that induce myocyte necrosis [ 4 , 14 ]; (3) Severe encephalitis triggers systemic inflammatory response syndrome and cytokine storm, exacerbating muscle and renal injury [ 3 , 15 ] ; (4) Hypotension, hypoperfusion and hypoxia further promote rhabdomyolysis. 2. Value of ECMO in severe HSE In this case, 5 days of ECMO support provided a critical time window for treatment of the p-rimary disease and was a key factor for successful rescue. This indicates that ECMO is a safeand effective life-support strategy for severe HSE patients with refractory respiratory-circulatoryfailure [ 11 ] . 3. Causes of refractory epilepsy after ECMO weaning Persistent seizures after weaning may result from: (1) HSE directly damages bilateral cerebral cortices and thalami, forming permanent epileptoge-nic foci [ 1 , 2 , 10 ] ; (2) Sustained immune activation, gliosis and synaptic remodeling in the central nervous system persist after viral clearance; (3) Immune-mediated secondary brain injury contributes to refractory epilepsy. This suggests that HSE-related epilepsy may persist long-term beyond the acute phase, requiring long-term follow-up and treatment. 4. Clinical implications (1) CK and myoglobin should be measured as early as possible in patients with encephalitis, seizures, myalgia and dark urine [ 5 , 13 ] ; (2) HSE can induce early-onset rhabdomyolysis and AKI, requiring prompt intervention; (3) ECMO effectively rescues patients with severe HSE complicated by respiratory-circulatory failure [ 11 ] ; (4) Long-term EEG monitoring and standardized antiepileptic therapy are mandatory even after life support withdrawal and organ function recovery. Conclusions Severe HSE in young adults can rapidly induce fulminant rhabdomyolysis, AKI and coagulopa-thy.ECMO is an effective rescue strategy for severe HSE with respiratory-circulatory failure. Refractory epilepsy may occur after ECMO weaning and organ function recovery, indicating p-ersistent structural and functional injury in the central nervous system.Intensive long-term man- agement of epilepsy is essential to improve the long-term prognosis of patients with severe HSE. Declarations Funding This study was supported by the Self-funded Scientific Research Project of Health Committee of Guangxi Zhuang Autonomous Region (No. Z-A20250072), the Guangxi Zhuang Autonomous Region Clinical Medical Research Center for Severe Treatment Major Infectious Disease (No. Guike AD22035101), and the Guangxi Key Laboratory of Diagnosis and Treatment of Acute Respiratory Distress Syndrome (No. ZZH2020013). The funders had no role in study design, data collection, analysis, manuscript writing, or the decision to submit for publication. Competing interests The authors declare that they have no competing interests. Author contributions Yuchen Duan collected the clinical data, performed the literature review, prepared the figures and drafted the initial manuscript.Xuezhen Lin contributed to the literature review and data interpretation. Gui Jiang performed the neuroimaging and electroencephalographic analysis.Yamin Gao contributed to data analysis and clinical follow-up of the patient.Lin Han conceptualized and designed the study, supervised the whole research process, and served as co-corresponding author.Wenbo Qin critically revised the manuscript and served as co-corresponding author.Both co-corresponding authors take final responsibility for the integrity and accuracy of the work.All authors read and approved the final version of the manuscript.All authors read and approved the final manuscript. Acknowledgements Not applicable. Data availability The datasets analyzed during the current study are available from the two co-corresponding authors upon reasonable request. Ethics approval and consent to participate This retrospective case report was approved by the Ethics Committee of the People’s Hospital of Guangxi Zhuang Autonomous Region. The study was conducted in accordance with the Declaration of Helsinki and institutional guidelines. Written informed consent for participation was waived by the ethics committee due to the retrospective nature of the study. However, written informed consent for publication of potentially identifiable clinical images and data was obtained from the patient’s legal representative. Consent for publication Written informed consent for publication was obtained from the patient’s legal guardian. References Yu Q, Han C, Pei L, et al. A rare case of adult herpes simplex encephalitis complicated with rhabdomyolysis. BMC Infect Dis. 2021;21(1):110. Misra UK, Tan CT, Kalita J. Viral encephalitis and epilepsy. Epilepsia. 2008;49(Suppl 6):13–8. Bradshaw MJ, Venkatesan A. Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics. 2016;13(3):493–508. Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis. 1996;22(4):642–9. Bagley WH, Yang H, Shah KH. Rhabdomyolysis Intern Emerg Med. 2007;2(3):210–8. Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med. 2009;67(9):272–83. McMahon GM, Zeng X, Waikar SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821–8. Chinese Medical Association Neurology Branch. Guidelines for the diagnosis and treatment of herpes simplex encephalitis (2021 edition). Chin J Neurol. 2021;54(2):98–104. Wang T, Huang JS, Xu Y. Advances in diagnosis and treatment of herpes simplex encephalitis. Chin J Neurol. 2020;53(8):610–5. Chinese Association Against Epilepsy. Clinical guidelines for epilepsy. Natl Med J Chin. 2021;101(23):1836–50. Chinese Medical Association Critical Care Medicine Branch. Clinical practice guidelines for extracorporeal membrane oxygenation in adults (2023). Chin J Intern Med. 2023;62(6):610–26. Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: Clinical review. Semin Neurol. 2018;38(3):341–8. Suzuki S, Tamura Y, Ichikawa T, et al. Rhabdomyolysis-associated acute kidney injury: Pathophysiology and management. Intern Med. 2020;59(12):1433–40. Shanmugam S, Seetharaman M. Viral rhabdomyolysis. South Med J. 2008;101(12):1271–2. Liu DW, Qiu HB, Yu KJ, et al. Diagnostic criteria and severity scoring system for multiple organ dysfunction syndrome. Chin J Intern Med. 2021;60(4):301–7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9606715","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":637854601,"identity":"db3b8722-ca8a-404b-8c9c-cbb1a7fab30f","order_by":0,"name":"Yuchen Duan","email":"","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Duan","suffix":""},{"id":637854602,"identity":"ccd390a1-18e7-49df-b607-60e6ae769c72","order_by":1,"name":"Xuezhen Lin","email":"","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Xuezhen","middleName":"","lastName":"Lin","suffix":""},{"id":637854603,"identity":"de5b1fd5-c778-427a-bbef-fedf1413f3b4","order_by":2,"name":"Gui Jiang","email":"","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Gui","middleName":"","lastName":"Jiang","suffix":""},{"id":637854604,"identity":"419b2696-a371-49ad-bfe5-eb813e89a89e","order_by":3,"name":"Yamin Gao","email":"","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Yamin","middleName":"","lastName":"Gao","suffix":""},{"id":637854605,"identity":"57cb8c85-06a0-480d-81c7-812bd76981ba","order_by":4,"name":"Wenbo Qin","email":"","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Wenbo","middleName":"","lastName":"Qin","suffix":""},{"id":637854606,"identity":"2049c4a0-1613-4f3f-a8a1-be291e3fdacd","order_by":5,"name":"Lin Han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYDACCSBO/CNR38/A2ECClo8NNowzG0jRAlSexrjhALHuMrjd/Owx747DzMbnD7c9+MFgJ6dLyDLJOcfMjXnPHGYzu5HYbtjDkGxsRsg6fokEM2ketsM8ZjcY2yR4GA4kbiOkhU0i/RtIi4Rx/8E2yT/EaOGXyDGTnNmWZmDAkNgmTZQtkjNyyiQ+nLFJkLgB1CJjQIRfDG6kb5NIqJBI4O8//kzyTYWdHEEt6CaQpnwUjIJRMApGAQ4AAKL4QKtVbSlqAAAAAElFTkSuQmCC","orcid":"","institution":"The People's Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":true,"prefix":"","firstName":"Lin","middleName":"","lastName":"Han","suffix":""}],"badges":[],"createdAt":"2026-05-04 09:40:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9606715/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9606715/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109264657,"identity":"54cf4ce7-81cb-4d1e-a760-4e6c99d73e91","added_by":"auto","created_at":"2026-05-14 12:10:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":253511,"visible":true,"origin":"","legend":"\u003cp\u003ethe changes of \u0026nbsp;MB and CK 、MRI images 、TCD images and EEG images before and after treatment. a \u0026nbsp;The trend of Mb and CK of the patient before and after treatment of CVVH. Mb, myoglobin. CK, creatine phosphokinase. b and c Bilateral approximately symmetrical abnormal signals in the cortex and subcortical white matter of bilateral frontal, parietal, temporal and occipital lobes as well as bilateral thalami, with hyperintensity on T2WI/FLAIR,before and after treatment,consistent with severe viral encephalitis.d and e Pre-treatment TCD (right and left MCA) showing significantly elevated peak systolic flow velocities (144 cm/s in right MCA, 158 cm/s in left MCA), with increased pulsatility index (PI, 1.07 in right MCA, 1.75 in left MCA) and resistive index (RI, 0.63 in right MCA, 0.81 in left MCA). These findings indicated cerebral hyperperfusion and vasospasm, consistent with severe inflammatory response in the setting of herpes simplex encephalitis.f and g Post-treatment TCD (right and left MCA) demonstrating a marked reduction in flow velocities (peak 81 cm/s in right MCA, 91 cm/s in left MCA) and normalized PI/RI values (PI 1.33/0.72, RI 0.70/0.49), reflecting improved cerebral hemodynamics after anti-inflammatory and supportive therapy.h Pre-treatment EEG (during ECMO support): The background rhythm was dominated by diffuse, high-amplitude delta/theta slowing with complete loss of normal alpha activity, indicating severe global cerebral dysfunction. Frequent, synchronized spike-and-wave discharges were observed diffusely across all channels, consistent with a high epileptogenic state and correlating with the patient’s clinical seizures.i Post-treatment EEG (after ECMO weaning): Background activity significantly improved, with a reduction in high-amplitude delta slowing and a shift towards dominant theta activity. Epileptiform discharges were markedly decreased in frequency and amplitude, although residual slowing and occasional spikes persisted, corresponding to residual structural brain injury on MRI and the patient’s persistent but less frequent seizures.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9606715/v1/4f9e5a92575eb5bacad1242c.jpg"},{"id":109264736,"identity":"e708a2bd-4a4c-4bce-9686-9c05541240c9","added_by":"auto","created_at":"2026-05-14 12:11:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":392248,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9606715/v1/3f00c232-2b4e-40a1-8ac4-62e658fb7290.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A 35-year-old adult with severe herpes simplex encephalitis complicated by rhabdomyolysis, acute kidney injury and refractory epilepsy after ECMO weaning: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHerpes simplex encephalitis (HSE) is an acute necrotizing encephalitis caused by herpes simpl-ex virus type 1 (HSV‑1) infection, characterized by acute onset, rapid progression and high m-\u003c/p\u003e \u003cp\u003eortality. More than 50% of patients develop seizures during the disease course \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. HSE trigg-ers intense central and systemic inflammatory responses, which may lead to severe complicati-\u003c/p\u003e \u003cp\u003eons including rhabdomyolysis, AKI, coagulopathy, and even multiple organ dysfunction syndro-\u003c/p\u003e \u003cp\u003eme (MODS) in critical cases \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRhabdomyolysis is a life-threatening syndrome featured by disruption of skeletal muscle cell\u003c/p\u003e \u003cp\u003emembranes, leading to massive release of myoglobin and CK into the circulation, which often induces AKI \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Although status epilepticus, trauma and infection are well-recognized causes,\u003c/p\u003e \u003cp\u003ecases of severe rhabdomyolysis directly induced by HSE remain rare \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHere, we report a 35-year-old male with severe HSE who developed fulminant rhabdomyolysis,AKI and respiratory-circulatory failure requiring 5 days of ECMO support. After successful we-aning from ECMO, the patient suffered from persistent refractory epilepsy. We analyze the cli-nical characteristics, pathogenesis, diagnosis and treatment of this case to improve clinical reco-gnition and management of this rare and critical phenotype.\u003c/p\u003e \n\n "},{"header":"Case presentation","content":"\u003cp\u003e \u003cb\u003e1. Demographics and medical history\u003c/b\u003e \u003c/p\u003e\u003cp\u003eA 35-year-old male was admitted to our hospital with a 5-day history of fever, and a 2 day\u003c/p\u003e\u003cp\u003ehistory of recurrent seizures, impaired consciousness, myalgia and oliguria. His past medical hi-story was unremarkable, with no prior epilepsy, hypertension, diabetes, liver or kidney diseases,trauma, poisoning, blood transfusion or family history of genetic disorders.\u003c/p\u003e\u003cp\u003e \u003cb\u003e2. Clinical manifestations\u003c/b\u003e \u003c/p\u003e\u003cp\u003eFive days before admission, the patient developed fever with a maximum temperature of 38.9\u003c/p\u003e\u003cp\u003e°C, accompanied by headache and fatigue, without improvement after symptomatic treatment.\u003c/p\u003e\u003cp\u003eTwo days before admission, he suffered sudden loss of consciousness and generalized tonicclo-nic seizures, lasting 1–2 minutes and occurring repeatedly. Confusion and delirium gradually\u003c/p\u003e\u003cp\u003edeveloped, accompanied by significant myalgia in the extremities, dark urine and oliguria.\u003c/p\u003e\u003cp\u003eOn admission, the patient was somnolent, tachypneic and hemodynamically unstable, requiring emergency tracheal intubation, mechanical ventilation and vasopressor support.\u003c/p\u003e\u003cp\u003e \u003cb\u003e3. Physical examination\u003c/b\u003e \u003c/p\u003e\u003cp\u003eBody temperature 38.6°C, heart rate 118 beats/min, respiratory rate 26 breaths/min, blood pres-sure maintained by norepinephrine.Neurological examination: somnolence, mild neck stiffness, b-ilateral pupils equal and round (3.0 mm) with reactive light reflex, increased muscle tone in e-xtremities, and positive bilateral Babinski signs.General examination: marked tenderness of limbmuscles, no skin rash or herpes, no edema, and no obvious abnormalities in cardiopulmonary\u003c/p\u003e\u003cp\u003eor abdominal systems.\u003c/p\u003e\u003cp\u003e \u003cb\u003e4. Auxiliary examinations\u003c/b\u003e \u003c/p\u003e\u003cp\u003e \u003cb\u003e4.1 Laboratory tests\u003c/b\u003e \u003c/p\u003e\u003cp\u003eRhabdomyolysis markers: peak CK 16940 U/L, myoglobin \u0026gt; 3000 µg/L, significantly elevated LDH.Renal function: peak serum creatinine 435 µmol/L, elevated BUN, accompanied by oligur-ia.Coagulation profile: prolonged APTT, markedly elevated D‑dimer, indicating inflammation-rel-ated coagulation activation.Brain injury markers: significantly elevated blood ammonia and cere-brospinal fluid (CSF) lactate.CSF analysis: mildly elevated leukocytes and protein, normal gluc-ose and chloride; HSV‑1 was detected by mNGS, with no evidence of other viruses, bacteria, fungi or tuberculosis \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e \u003cb\u003e4.2 Imaging and neurophysiological examinations\u003c/b\u003e \u003c/p\u003e\u003cp\u003eCranial MRI: approximately symmetrical abnormal signals in the cortex and subcortical white matter of bilateral frontal, parietal, temporal and occipital lobes as well as bilateral thalami, h-yperintense on T2WI/FLAIR(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb and c), consistent with typical HSE manifestations \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTranscranial Doppler (TCD): abnormally increased blood flow velocities in bilateral middle cer-ebral arteries, suggesting cerebral perfusion disturbance and vasospasm.(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed 、e、f and g).\u003c/p\u003e\u003cp\u003eEEG: diffuse background slow waves with frequent spike and spike‑wave discharges(Fig. h and i), consistent with clinical seizures \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e \u003cb\u003e5. Final diagnosis\u003c/b\u003e \u003c/p\u003e\u003cp\u003eHerpes simplex encephalitis (HSV‑1)\u003c/p\u003e\u003cp\u003eSevere rhabdomyolysis syndrome\u003c/p\u003e\u003cp\u003eAcute kidney injury\u003c/p\u003e\u003cp\u003eSymptomatic epilepsy, refractory epilepsy, generalized tonic-clonic seizures\u003c/p\u003e\u003cp\u003eCoagulation disorder\u003c/p\u003e\u003cp\u003eMultiple organ dysfunction syndrome\u003c/p\u003e\u003cp\u003eRespiratory and circulatory failure (after ECMO support)\u003c/p\u003e\u003ch3\u003eTreatment course\u003c/h3\u003e\u003cp\u003eDue to critical condition and rapid progression to respiratory-circulatory failure, the patient rec-eived immediate combined treatment:Life support: tracheal intubation and mechanical ventilation,vasopressors, VA‑ECMO support for 5 days \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.Antiviral therapy: intravenous acyclovir at ade-quate dosage, adjusted according to renal function \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.Management of rhabdomyolysis and AKI:vigorous fluid resuscitation, urine alkalization, and hemodialysis \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.Antiepileptic therapy:combi-ned antiepileptic drugs; sedatives were administered for aggravated seizures.Anti-inflammatory\u003c/p\u003e\u003cp\u003eand neuroprotection: short-term corticosteroids to relieve cerebral edema, temperature control,\u003c/p\u003e\u003cp\u003esedation and intracranial pressure reduction.After treatment, the patient achieved hemodynamic\u003c/p\u003e\u003cp\u003eand respiratory stability, successfully weaned off ECMO and mechanical ventilation. Follow up\u003c/p\u003e\u003cp\u003etests showed marked reduction in CK and myoglobin (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea ), recovery of renal function\u003c/p\u003e\u003cp\u003eand coagulation profile.\u003c/p\u003e\u003cp\u003eHowever, recurrent seizures, occasionally generalized tonic-clonic seizures, persisted after ECMO weaning. Seizure frequency decreased but was not fully controlled after adjustment of antie-pileptic regimen, and continuous epileptiform discharges remained on EEG.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eLaboratory markers: muscle enzymes, renal function and coagulation parameters improved signi-ficantly and gradually normalized.Organ function: respiration, circulation and renal function fully recovered; the patient was liberated from life support.Neurological status: consciousness impr-oved, but refractory recurrent seizures persisted with persistent abnormal EEG findings.Imaging findings: follow-up cranial MRI showed reduced cerebral edema and alleviated abnormal signals in bilateral cerebral lobes and thalami, but persistent structural lesions remained.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e1. Possible mechanisms of HSE-induced rhabdomyolysis\u003c/p\u003e \u003cp\u003eEarly-onset severe rhabdomyolysis in this patient may be attributed to the following mechanis-ms:\u003c/p\u003e \u003cp\u003e(1) Repetitive seizures caused sustained and intense muscle contraction, leading to direct muscle cell injury \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e(2) HSV‑1 directly invades muscle tissue or releases toxins that induce myocyte necrosis \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e];\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(3) Severe encephalitis triggers systemic inflammatory response syndrome and cytokine storm,\u003c/p\u003e \u003cp\u003eexacerbating muscle and renal injury \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e(4) Hypotension, hypoperfusion and hypoxia further promote rhabdomyolysis.\u003c/p\u003e \u003cp\u003e2. Value of ECMO in severe HSE\u003c/p\u003e \u003cp\u003eIn this case, 5 days of ECMO support provided a critical time window for treatment of the p-rimary disease and was a key factor for successful rescue. This indicates that ECMO is a safeand effective life-support strategy for severe HSE patients with refractory respiratory-circulatoryfailure \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e3. Causes of refractory epilepsy after ECMO weaning\u003c/p\u003e \u003cp\u003ePersistent seizures after weaning may result from:\u003c/p\u003e \u003cp\u003e(1) HSE directly damages bilateral cerebral cortices and thalami, forming permanent epileptoge-nic foci \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e(2) Sustained immune activation, gliosis and synaptic remodeling in the central nervous system persist after viral clearance;\u003c/p\u003e \u003cp\u003e(3) Immune-mediated secondary brain injury contributes to refractory epilepsy.\u003c/p\u003e \u003cp\u003eThis suggests that HSE-related epilepsy may persist long-term beyond the acute phase, requiring long-term follow-up and treatment.\u003c/p\u003e \u003cp\u003e4. Clinical implications\u003c/p\u003e \u003cp\u003e(1) CK and myoglobin should be measured as early as possible in patients with encephalitis,\u003c/p\u003e \u003cp\u003eseizures, myalgia and dark urine \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e(2) HSE can induce early-onset rhabdomyolysis and AKI, requiring prompt intervention;\u003c/p\u003e \u003cp\u003e(3) ECMO effectively rescues patients with severe HSE complicated by respiratory-circulatory\u003c/p\u003e \u003cp\u003efailure \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e(4) Long-term EEG monitoring and standardized antiepileptic therapy are mandatory even after life support withdrawal and organ function recovery.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSevere HSE in young adults can rapidly induce fulminant rhabdomyolysis, AKI and coagulopa-thy.ECMO is an effective rescue strategy for severe HSE with respiratory-circulatory failure.\u003c/p\u003e \u003cp\u003eRefractory epilepsy may occur after ECMO weaning and organ function recovery, indicating p-ersistent structural and functional injury in the central nervous system.Intensive long-term man-\u003c/p\u003e \u003cp\u003eagement of epilepsy is essential to improve the long-term prognosis of patients with severe\u003c/p\u003e \u003cp\u003eHSE.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Self-funded Scientific Research Project of Health Committee of Guangxi Zhuang Autonomous Region (No. Z-A20250072), the Guangxi Zhuang Autonomous Region Clinical Medical Research Center for Severe Treatment Major Infectious Disease (No. Guike AD22035101), and the Guangxi Key Laboratory of Diagnosis and Treatment of Acute Respiratory Distress Syndrome (No. ZZH2020013). The funders had no role in study design, data collection, analysis, manuscript writing, or the decision to submit for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuchen Duan collected the clinical data, performed the literature review, prepared the figures and drafted the initial manuscript.Xuezhen Lin contributed to the literature review and data interpretation.\u003c/p\u003e\n\u003cp\u003eGui Jiang performed the neuroimaging and electroencephalographic analysis.Yamin Gao contributed to data analysis and clinical follow-up of the patient.Lin Han conceptualized and designed the study, supervised the whole research process, and served as co-corresponding author.Wenbo Qin critically revised the manuscript and served as co-corresponding author.Both co-corresponding authors take final responsibility for the integrity and accuracy of the work.All authors read and approved the final version of the manuscript.All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available from the two co-corresponding authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective case report was approved by the Ethics Committee of the People\u0026rsquo;s Hospital of Guangxi Zhuang Autonomous Region. The study was conducted in accordance with the Declaration of Helsinki and institutional guidelines. Written informed consent for participation was waived by the ethics committee due to the retrospective nature of the study. However, written informed consent for publication of potentially identifiable clinical images and data was obtained from the patient\u0026rsquo;s legal representative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the patient\u0026rsquo;s legal guardian.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYu Q, Han C, Pei L, et al. A rare case of adult herpes simplex encephalitis complicated with rhabdomyolysis. BMC Infect Dis. 2021;21(1):110.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra UK, Tan CT, Kalita J. Viral encephalitis and epilepsy. Epilepsia. 2008;49(Suppl 6):13\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBradshaw MJ, Venkatesan A. Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics. 2016;13(3):493\u0026ndash;508.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis. 1996;22(4):642\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagley WH, Yang H, Shah KH. Rhabdomyolysis Intern Emerg Med. 2007;2(3):210\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan FY. Rhabdomyolysis: a review of the literature. Neth J Med. 2009;67(9):272\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcMahon GM, Zeng X, Waikar SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Medical Association Neurology Branch. Guidelines for the diagnosis and treatment of herpes simplex encephalitis (2021 edition). Chin J Neurol. 2021;54(2):98\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang T, Huang JS, Xu Y. Advances in diagnosis and treatment of herpes simplex encephalitis. Chin J Neurol. 2020;53(8):610\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Association Against Epilepsy. Clinical guidelines for epilepsy. Natl Med J Chin. 2021;101(23):1836\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Medical Association Critical Care Medicine Branch. Clinical practice guidelines for extracorporeal membrane oxygenation in adults (2023). Chin J Intern Med. 2023;62(6):610\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhitley RJ, Kimberlin DW. Herpes simplex encephalitis: Clinical review. Semin Neurol. 2018;38(3):341\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki S, Tamura Y, Ichikawa T, et al. Rhabdomyolysis-associated acute kidney injury: Pathophysiology and management. Intern Med. 2020;59(12):1433\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShanmugam S, Seetharaman M. Viral rhabdomyolysis. South Med J. 2008;101(12):1271\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu DW, Qiu HB, Yu KJ, et al. Diagnostic criteria and severity scoring system for multiple organ dysfunction syndrome. Chin J Intern Med. 2021;60(4):301\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Herpes simplex encephalitis, Rhabdomyolysis, Epilepsy, ECMO, Acute kidney injury, Central nervous system inflammation","lastPublishedDoi":"10.21203/rs.3.rs-9606715/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9606715/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground：\u003c/strong\u003eHerpes simplex encephalitis (HSE) is the most common sporadic fulminant necr-otizing encephalitis with a high incidence of epilepsy. Rhabdomyolysis is a severe complicationusually associated with status epilepticus. However, HSE combined with rhabdomyolysis, acute kidney injury, coagulopathy requiring ECMO support, and persistent seizures after ECMO wea-ning is extremely rare, with unclear mechanisms and management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation：\u003c/strong\u003eA 35-year-old male was admitted with fever, recurrent seizures, impaired consciousness, myalgia and oliguria. Laboratory tests showed peak CK 16940 U/L, myoglobin \u0026gt;3000 μg/L, acute kidney injury and coagulopathy. Cranial MRI demonstrated symmetric lesions in bilateral frontal, parietal, temporal, occipital lobes and thalami. Cerebrospinal fluid mNGS confirmed HSV‑1 infection.He developed respiratory‑circulatory failure and received 5 daysof ECMO support. Following comprehensive treatment, he was successfully weaned off ECMO, with obvious improvement in organ function. However, recurrent seizures persisted after wea-ning, accompanied by continuous epileptiform discharges on EEG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions：\u003c/strong\u003eSevere HSE can induce life‑threatening rhabdomyolysis and acute kidney injury. ECMO is an effective life‑support therapy. Even after viral control and organ recovery, persistent epileptogenic injury in the central nervous system may lead to refractory epilepsy. Longterm seizure monitoring and individualized antiepileptic treatment are essential for HSE patients\u003c/p\u003e","manuscriptTitle":"A 35-year-old adult with severe herpes simplex encephalitis complicated by rhabdomyolysis, acute kidney injury and refractory epilepsy after ECMO weaning: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 12:08:53","doi":"10.21203/rs.3.rs-9606715/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"64e03c89-7635-4b62-9f8a-6ddd8c6c642a","owner":[],"postedDate":"May 14th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-19T06:49:36+00:00","index":40,"fulltext":""},{"type":"reviewerAgreed","content":"253708896285024422307546634380209502862","date":"2026-05-19T04:32:37+00:00","index":39,"fulltext":""},{"type":"reviewerAgreed","content":"84123532700129350883285630916147209968","date":"2026-05-08T03:07:12+00:00","index":17,"fulltext":""},{"type":"reviewersInvited","content":"28","date":"2026-05-06T01:29:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-05T01:35:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-05T01:34:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Epileptologica","date":"2026-05-04T09:35:40+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T12:08:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-14 12:08:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9606715","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9606715","identity":"rs-9606715","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}