Human rhinovirus-associated febrile infection-related epilepsy syndrome with claustral involvement: a case report

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Severe neurological complications, including febrile infection-related epilepsy syndrome (FIRES), are exceptionally rare. Case Presentation: We report a case of HRV-associated FIRES with bilateral claustral involvement identified at the General Hospital of Ningxia Medical University in April 2025. The patient presented with acute refractory status epilepticus following prodromal fever. Neuroimaging revealed bilateral claustral hyperintensities and symmetrical thalamic lesions, while continuous electroencephalographic monitoring demonstrated burst-suppression patterns with frontotemporal discharges. Nucleic acid testing confirmed HRV infection. Conclusions This case underscores the importance of considering HRV-associated FIRES in patients with acute encephalopathy following respiratory infection. Early recognition through comprehensive neuroimaging and electroencephalographic monitoring, combined with aggressive immunomodulatory therapy and optimized antiseizure medications, is essential for improving neurological outcomes. We further delineate putative cytokine-mediated pathophysiological mechanisms through systematic literature review. Rhinovirus Magnetic resonance imaging Electroencephalography Tocilizumab Febrile infection-related epilepsy syndrome Introduction Human rhinovirus (HRV), belonging to the Picornaviridae family and Enterovirus genus, represents the predominant viral pathogen implicated in community-acquired upper respiratory tract infections across both pediatric and adult populations. The prototypical clinical manifestation of HRV infection is the common cold; however, a subset of patients may develop influenza-like symptoms including fever, malaise, and myalgia. Notably, in contradistinction to influenza virus, HRV infections typically follow a self-limited course, rarely progress to severe systemic illness, and are exceptionally infrequently implicated as direct causative agents of neurological complications.Globally, documentation of HRV-associated central nervous system infections remains exceedingly scarce. To date, no prior reports have specifically described the association between HRV infection and febrile infection-related epilepsy syndrome (FIRES) with claustral involvement. Herein, we report the first documented case of FIRES characterized by bilateral claustral lesions secondary to confirmed HRV infection, admitted to the General Hospital of Ningxia Medical University on April 6, 2025. We further provide a comprehensive review of the pertinent literature to elucidate the putative pathophysiological mechanisms, distinctive electroencephalographic features, relevant ancillary investigations, and therapeutic strategies. Case presentation A 25-year-old female was admitted to the Neuro-intensive Care Unit (NICU) of our institution in April 2025 with a chief complaint of "fever for 8 days, worsening with limb convulsions and altered consciousness for 5 days." Her past medical history was unremarkable, and no family history of similar neurological conditions was reported.Following the onset of fever, the patient developed convulsive seizures characterized by sudden loss of consciousness, leftward conjugate gaze deviation, facial cyanosis, tongue biting, and tonic posturing of the left extremities with perioral twitching. Individual ictal episodes lasted approximately one minute; however, the patient failed to regain awareness between seizures, manifesting as continuous postictal altered consciousness. She experienced more than 10 such episodes during this period, with persistent loss of consciousness maintained throughout the interictal intervals.The patient was subsequently admitted to a local tertiary-care hospital for further evaluation and management. Lumbar puncture revealed a leukocyte count of 17/mm³ with 100% lymphocytes. Despite receiving endotracheal intubation with mechanical ventilation, antipyretic therapy, empirical antimicrobial treatment, and antiseizure medications, her neurological status showed no improvement. Consequently, she was transferred to our institution for advanced care. Upon admission, physical examination revealed a deeply comatose patient with a Glasgow Coma Scale (GCS) score of 6T (E1, VT, M4). Both pupils were approximately 3 mm in diameter with sluggish direct and consensual light reflexes. No motor response was elicited upon painful stimulation. Muscle tone was diffusely decreased in all extremities, and deep tendon reflexes were absent bilaterally. Plantar responses were neutral, and pathological reflexes were negative bilaterally. Meningeal signs were not present.Comprehensive laboratory investigations, including complete blood count, thyroid function panel (7 items), purified protein derivative (PPD) test, TORCH panel (8 pathogens), cranial computed tomography (CT), chest CT, and inherited metabolic disease screening, yielded unremarkable results. Whole-exome sequencing was declined by the family. Lumbar puncture revealed an opening pressure of 230 mmH₂O. Cerebrospinal fluid (CSF) biochemical analysis (protein, glucose, chloride, total bilirubin, conjugated bilirubin, and unconjugated bilirubin) demonstrated no significant abnormalities. CSF cytology showed a leukocyte count of 12×10⁶/L (lymphocytes: 77×10⁶/L; neutrophils: 17×10⁶/L). CSF immunoglobulin G (IgG) was 22.10 mg/g. Microbiological cultures of blood, sputum, and CSF were all negative.Autoimmune encephalitis antibodies, paraneoplastic antibodies, demyelination-associated antibodies, and astrocytopathy-related antibodies were negative in both serum and CSF. CSF cytokine analysis revealed interleukin (IL)-1β: 14.38 pg/mL, IL-6: 121.93 pg/mL, and IL-12p70: 4.16 pg/mL. Serum IL-6 level was 97.1 pg/mL (Figure 1).Cranial magnetic resonance imaging (MRI) demonstrated bilateral claustral and thalamic hyperintensities on diffusion-weighted imaging (DWI) (Figure 2).Continuous electroencephalographic (EEG) monitoring revealed a background pattern predominantly composed of medium-to-high amplitude delta activity admixed with fast frequencies. Sharp waves, sharp-and-slow-wave complexes, and polyspike-and-slow-wave discharges were observed over bilateral frontopolar, frontal, and temporal regions. The overall pattern demonstrated a burst-suppression tendency with interburst intervals shortened to approximately 1–2 seconds, exhibiting quasi-periodic discharges. Concurrently, frequent electrographic seizures were detected, originating from the left or right frontopolar, frontal, and temporal regions, manifesting as either partial-onset seizures or partial seizures with secondary generalization, lasting 1–2 minutes—findings consistent with electroclinical status epilepticus (Figure 3).Following admission, the patient received supportive care including mechanical ventilation, enteral nutrition, fluid resuscitation to maintain water-electrolyte balance, and antimicrobial therapy. On hospital day 1, intravenous dexamethasone was administered for 2 consecutive days, and human immunoglobulin was given for 5 days. Antiseizure therapy was initiated with midazolam, sodium valproate, propofol, phenobarbital, and levetiracetam (Figure 4).On hospital day 2, sodium valproate was discontinued due to elevated blood ammonia levels, and lacosamide was added. On day 3, frequent left-sided convulsive seizures persisted; given the absence of significant improvement in status epilepticus, the patient was diagnosed with super-refractory status epilepticus (SRSE), confirming the diagnosis of FIRES-C. Following intravenous diazepam bolus administration, electroencephalographic improvement was observed. Continuous intravenous diazepam infusion was subsequently initiated in combination with clonazepam. On day 3, pulse corticosteroid therapy with methylprednisolone sodium succinate was administered for 6 days, followed by transition to oral prednisone acetate 50 mg/day with a tapering regimen of 1 tablet every 2 weeks.On hospital day 5, status epilepticus remained refractory. Following comprehensive informed consent, tocilizumab (4 mg/kg per dose) was administered intravenously once. On day 6, repeat CSF cytokine analysis revealed IL-1β: 14.90 pg/mL, IL-6: 14.36 pg/mL, and IL-12p70: 4.04 pg/mL. By day 10, electroclinical seizures decreased to 1–2 episodes per day. By day 16, the patient remained seizure-free; EEG background demonstrated predominant theta activity admixed with abundant fast frequencies and sleep spindles, with occasional sporadic spike-and-slow-wave and sharp-and-slow-wave discharges over the right frontal and temporal regions, and preserved stage II–III sleep architecture (Figure 3). Propofol was gradually tapered and discontinued. On day 18, midazolam was tapered and discontinued. On day 22, diazepam was gradually tapered and discontinued, and the patient regained full consciousness.On day 23, the patient was successfully weaned from mechanical ventilation and transitioned to Venturi mask oxygen therapy. Repeat cranial MRI demonstrated significant resolution of bilateral claustral and thalamic DWI hyperintensities (Figure 2). On day 30, breakthrough seizures recurred, characterized by loss of consciousness, left-sided convulsions, and leftward conjugate gaze deviation, lasting 1–2 minutes with subsequent recovery of consciousness. Oxcarbazepine was added to the antiseizure regimen. The patient was discharged on hospital day 45 without further seizure recurrence.Discharge physical examination revealed: alert and oriented; pupils equal, round, and reactive to light (3 mm bilaterally); symmetric facial movements; tongue midline; muscle strength grade 5/5 in all extremities; normal muscle tone; absent deep tendon reflexes bilaterally; negative pathological reflexes; and negative meningeal signs. Modified Rankin Scale (mRS) score was 0. At 60-day post-discharge follow-up, the patient experienced one breakthrough seizure during clonazepam dose reduction, manifesting as left-sided convulsions with leftward gaze deviation lasting 1–2 minutes with full recovery. Repeat cranial MRI demonstrated complete resolution of bilateral claustral and thalamic hyperintensities on DWI (Figure 1). Neurocognitive assessment revealed Mini-Mental State Examination (MMSE) score of 23 and Montreal Cognitive Assessment (MoCA) score of 21; longitudinal follow-up is ongoing. Discussion Human rhinovirus (HRV) belongs to the Picornaviridae family and has been associated with a broad spectrum of clinical manifestations (1)，It demonstrates tropism for epithelial cells and induces a broad spectrum of respiratory tract infections. However, central nervous system involvement by human rhinovirus (HRV) remains exceedingly rare in the medical literature(2–5)，It demonstrates tropism for epithelial cells and induces a broad spectrum of respiratory tract infections. However, central nervous system involvement by human rhinovirus (HRV) remains exceedingly rare in the medical literature(6,7)。Recent evidence suggests that human rhinovirus (HRV) may lead to severe central nervous system (CNS) complications through dual mechanisms involving direct neuroinvasion and cytokine storm(1–3,8), In contrast to influenza virus and SARS-CoV-2, human rhinovirus (HRV) elicits an immune response characterized by an IL-6/IL-1β-dominant inflammatory profile(5). Based on the clinical manifestations, laboratory findings, and metagenomic next-generation sequencing (mNGS) data, we postulate that human rhinovirus (HRV) represents the sole causative pathogen responsible for the observed neurological complications. Diagnostic criteria for febrile infection-related epilepsy syndrome (FIRES) with claustral involvement include: (1) acute onset of neuropsychiatric manifestations—including encephalopathy, epileptic seizures, or altered consciousness—during the acute phase of systemic infection (predominantly acute respiratory viral infection), occurring within 1 day to several days post-infection; (2) cerebrospinal fluid (CSF) pleocytosis absent or mild, with significantly elevated IL-6 levels detectable in CSF and/or serum, and negative autoimmune encephalitis antibodies; (3) reasonable exclusion of alternative etiologies; and (4) magnetic resonance imaging (MRI) demonstrating abnormal signal intensities in the bilateral claustrum, potentially accompanied by bilateral hippocampal abnormalities. Notably, initial MRI at disease onset may appear unremarkable, with claustral lesions becoming evident on follow-up imaging (median interval from symptom onset to lesion documentation: 12.5 days)(9–12); In this report, the adult female patient developed refractory status epilepticus (RSE) five days after fever onset (latency period: 5 days), fulfilling the diagnostic criteria for febrile infection-related epilepsy syndrome with claustral involvement (FIRES-C). Comprehensive investigations excluded identifiable metabolic or genetic etiologies. Refractoriness to multiple antiepileptic drugs (AEDs), anesthetic agents, ketogenic diet, and first-line immunotherapy further substantiated the definitive diagnosis of FIRES-C.The secondary seizures observed in this syndrome are categorized as acute symptomatic seizures following infection, typically arising from the interplay of multiple pathogenic factors. Specifically, activation of the inflammatory cascade and the consequent release of pro-inflammatory cytokines constitute the central underlying mechanisms common to most central nervous system (CNS) infections. This pathophysiological concept has been extensively corroborated by clinical and basic studies in prevalent CNS infectious diseases, including meningitis and encephalitis(13,14).An alternative pathophysiological mechanism underlying seizure generation involves the claustrum serving as a critical anatomical hub that mediates the propagation and synchronization of epileptiform discharges across multiple cortical regions(15)。When rhinovirus-induced inflammatory mediators damage the claustrum, the resulting functional dysregulation of its role as a "neural network modulator" facilitates the rapid generalization of epileptiform discharges from localized foci to widespread cortical territories, culminating in a state of super-refractory epilepsy(11). Therefore, these neuroimaging findings presumably exhibit a close association with seizure genesis(16,17)。While this clinico-radiological association has garnered preliminary recognition, the precise pathophysiological mechanisms underlying the "fever-epilepsy-claustral lesion" cascade remain elusive, with existing studies yielding conflicting interpretations. Alternatively, some investigators have posited that seizure activity per se may precipitate transient, reversible MRI signal alterations, challenging the assumption of a direct causal link with the infectious process(18): Upon achieving effective seizure control and symptomatic remission, repeat cranial magnetic resonance imaging (MRI) may demonstrate complete resolution of the previously observed claustral lesions. Based on these clinico-radiological characteristics, it cannot be excluded that the imaging changes within the claustrum represent secondary manifestations triggered by status epilepticus, rather than constituting primary pathological lesions directly involved in the pathogenesis of epilepsy. This study demonstrated a well-defined temporal evolution of clinical manifestations in patients with febrile infection-related epilepsy syndrome (FIRES) with claustral involvement, consistent with prior reports(19): The mean age of affected patients was 25 years. The prodromal phase was characterized by fever and altered mental status, followed by the onset of epileptic seizures. The mean interval between fever onset and seizure occurrence was 6 days, demonstrating a well-defined temporal progression of the clinical course.Seizures in this syndrome represented the acute ictal phase of the disease. One of the most prominent features was the rapid dynamic evolution of both seizure semiology and electroencephalographic (EEG) manifestations. Initially, seizures typically manifested as bilateral motor seizures, specifically including focal seizures with clonic activity and multifocal myoclonic seizures with alternating involvement of bilateral limbs. These subsequently progressed rapidly to generalized non-convulsive status epilepticus (NCSE) or subtle/myoclonic status epilepticus. Management of these patients typically required transfer to the neuro-intensive care unit (NICU) and administration of intravenous anesthetic agents for seizure control(20). Radiologically, claustral lesions typically emerged approximately 8 days after disease onset, with the bilateral claustrum demonstrating either symmetrical or asymmetrical signal abnormalities. Notably, these claustral changes resolved following the amelioration of status epilepticus in the majority of reported cases; however, subsequent magnetic resonance imaging (MRI) revealed varying degrees of cortical and/or hippocampal atrophy.Although the clinical presentation and disease course bear resemblance to autoimmune encephalitis, all reported patients tested negative for known autoimmune encephalitis antibodies in both peripheral blood and cerebrospinal fluid (CSF).Regarding therapeutic strategies, current literature indicates that first-line immunomodulatory therapy should be initiated within the initial 72 hours following the onset of status epilepticus (SE) in FIRES-C, potentially encompassing corticosteroids (CS) and intravenous immunoglobulin (IVIG)(21). Notably, the majority of respondents also advocated initiating these therapeutic interventions within 48 hours of disease onset or immediately following the exclusion of common infectious etiologies. Early implementation of pulse corticosteroid therapy combined with intravenous immunoglobulin may significantly improve neurological outcomes(22). In the immunotherapeutic management of FIRES-C, tocilizumab (an IL-6 receptor antagonist) and anakinra (an IL-1 receptor antagonist) represent the primary options for second-line treatment, with a growing clinical trend favoring their earlier implementation(23). In clinical practice, prompt recognition and diagnosis of febrile infection-related epilepsy syndrome with claustral involvement (FIRES-C), coupled with immediate initiation of intensive immunomodulatory therapy, constitute critical management imperatives. We anticipate that cumulatively accumulated research evidence and clinical experience will establish the necessary foundation for formulating diagnostic and therapeutic consensus regarding this syndrome. Notably, for patients manifesting such refractory status epilepticus, the primary therapeutic objective should be the immediate cessation of ongoing seizure activity(13,24). However, the present case demonstrated refractoriness to multiple antiseizure medications (ASMs) and sedative-hypnotic agents. Notably, following tocilizumab administration, serum and cerebrospinal fluid (CSF) interleukin-6 (IL-6) levels exhibited a measurable reduction(25), Seizure frequency also improved markedly; however, no correlation was observed between the frequency of epileptic seizures and serum interleukin-6 (IL-6) levels in this patient(26). Furthermore, continuous electroencephalographic (EEG) monitoring enables the assessment of cerebral electrical activity under naturalistic conditions and sleep-wake cycles, providing valuable data for the selection of antiseizure medications (ASMs), dosage titration, and determination of discontinuation criteria. Early implementation of comprehensive EEG evaluation, coupled with medication adjustment under continuous monitoring, represents a critical therapeutic priority(27–29). Conclusions In patients presenting with neuropsychiatric manifestations, epileptic seizures, and altered consciousness following human rhinovirus (HRV) infection, clinicians should maintain a high index of suspicion for rhinovirus-associated febrile infection-related epilepsy syndrome (FIRES) with claustral involvement, as the early recognition of this clinico-radiological entity remains a significant diagnostic challenge. Cranial magnetic resonance imaging (MRI), serving as one of the most sensitive diagnostic modalities currently available, combined with cerebrospinal fluid (CSF) analysis and comprehensive neurological assessment, holds substantial diagnostic value in patients exhibiting altered consciousness following respiratory viral infections, providing critical evidence for early identification.From a pathophysiological perspective, the central mechanism underlying FIRES with claustral involvement lies not in direct neuroinvasion by the pathogen, but rather in cytokine-mediated neuroinflammation via innate immune inflammatory mediators. Emerging evidence suggests that early initiation of antiseizure medications (ASMs) combined with intensive immunomodulatory therapy, with continuous electroencephalographic (EEG) monitoring-guided optimization of pharmacological regimens, may potentially disrupt the vicious cycle between epileptic activity and neuroinflammation, thereby reducing the risk of progression to refractory epilepsy. This underscores the critical importance of early immunotherapeutic intervention. Therefore, in clinical practice, prompt evaluation of serum and CSF cytokine profiles, alongside cranial MRI, is imperative upon clinical suspicion. Once the diagnosis is established, immediate commencement of immunomodulatory therapy may substantially ameliorate long-term neurological outcomes. Declarations Ethics approval and consent to participate ： The studies involving humans were approved by Ningxia Medical University (approval number: KYLL-2025-2457). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. The animal studies were approved by Ningxia Medical University (approval number: KYLL-2025-2457). The studies were conducted in accordance with the local legislation and institutional requirements. Consent for publication ： Written informed consent for publication of this case report and any accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor of this journal. Availability of data and materials ： The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Competing interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding: The author(s) declare that financial support was received for the research and/or publication of this article. the Ningxia Provincial Natural Science Foundation of China(No.2025AAC020092). Authors' contributions ： Y.T. (Yang Tiejun) conceived the case report, collected and curated the patient data,and prepared the medical images/visualizations. L.W. (Wang Longnan) assisted with clinical investigation.C.J. (Ji Chunbo) participated in clinical investigationand prepared the figures. S.M. (Ma Siqing) prepared the visualizations and contributed to manuscript review. D.D. (Dong Danyang) curated the clinical data and provided resources. P.Y. (Yang Ping), as the corresponding author, designed the study and reporting, acquired funding, administered the project, and critically revised the manuscript. All authors reviewed the final manuscript, approved the submitted version, and agree to be accountable for all aspects of the work. Acknowledgments ： The authors gratefully acknowledge the patient for permitting us to disclose details relating to this case. The authors thank the family members for participation in this study. References Olive DM, Al-Mufti S, Al-Mulla W, Khan MA, Pasca A, Stanway G, et al. Detection and differentiation of picornaviruses in clinical samples following genomic amplification. J Gen Virol. 1990;71(Pt 9):2141–7. 10.1099/0022-1317-71-9-2141 . Holzel A, Smith PA, Tobin JO. A new type of meningo-encephalitis associated with a rhinovirus. Acta Paediatr Scand. 1965;54:168–74. 10.1111/j.1651-2227.1965.tb06358.x . Soma N, Aizawa Y, Matsunaga M, Saitoh A. 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Supplementary Files 1.jpg Temporal changes in serum and cerebrospinal fluid interleukin- 6(IL-6)levels in the patient. 2.jpg 2-A shows the diffusion- weighted imaging of the head on the first day of admission, indicating high signal intensity in the bilateral reticular nucleus and thalamus DWI. Figure 2-B shows the diffusion-weighted imaging of the head on the 23rd day of admission, which indicates a significant reduction in high signal intensity in the bilateral reticular nucleus and thalamus DWI compared to before. Figures 2-C and 2-D show the diffusion- weighted images of the head after discharge, which indicate no high signal in the bilateral caudate nucleus and thalamus. 3.jpg A shows the rhythm changes of the electroencephalogram on the first day of admission, with medium high amplitude delta waves as the main slow wave mixed with fast waves. Sharp waves, sharp slow waves, and multiple sharp slow waves can be seen in the bilateral frontal pole, frontal and temporal regions, with an overall trend of explosion inhibition. The inhibition period is shortened from before,about 1-2 seconds, showing a quasi periodic pattern;At the same time, frequent partial seizures or partial secondary generalized seizures originating from the left or right frontal pole, frontal, and temporal regions were detected, lasting for 1-2 minutes, indicating electrical clinical status epilepticus. Figure 3-B shows the electroencephalogram(EEG)on the 16th day of admission. The background of the EEG is mainly composed of a large number of fast wave rhythms and spindle wave rhythms combined with theta waves.A small amount of slow and sharp waves are scattered in the right frontal and temporal regions, and the sleep state II-III phase changes are good; 4.jpg treatment flowchart and clinical course of case 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9562813","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":639233726,"identity":"1d2bc556-5efd-424e-afa1-d1556a78e687","order_by":0,"name":"Tie-jun Yang","email":"","orcid":"","institution":"The First Clinical Medical College of Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tie-jun","middleName":"","lastName":"Yang","suffix":""},{"id":639233727,"identity":"5e862d05-8d5f-44f7-972d-6ac6682dcd77","order_by":1,"name":"Long-nan wang","email":"","orcid":"","institution":"The First Clinical Medical College of Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Long-nan","middleName":"","lastName":"wang","suffix":""},{"id":639233730,"identity":"127f9b82-0cb4-4a19-9398-59ae24d0efe4","order_by":2,"name":"Chun-bo JI","email":"","orcid":"","institution":"General Hospital of Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chun-bo","middleName":"","lastName":"JI","suffix":""},{"id":639233732,"identity":"b399ce6e-3c1d-43c9-8940-6b4899c7bd1e","order_by":3,"name":"Si-qing MA","email":"","orcid":"","institution":"General Hospital of Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Si-qing","middleName":"","lastName":"MA","suffix":""},{"id":639233733,"identity":"3e24b55c-7fb9-4cf6-9a76-f8c1a05e4b61","order_by":4,"name":"Dan-yang DONG","email":"","orcid":"","institution":"The First Clinical Medical College of Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Dan-yang","middleName":"","lastName":"DONG","suffix":""},{"id":639233734,"identity":"9c37f950-88e6-4af3-9cb0-49e7d5ea593c","order_by":5,"name":"Ping YANG","email":"data:image/png;base64,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","orcid":"","institution":"General Hospital of Ningxia Medical University","correspondingAuthor":true,"prefix":"","firstName":"Ping","middleName":"","lastName":"YANG","suffix":""}],"badges":[],"createdAt":"2026-04-29 08:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9562813/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9562813/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109296361,"identity":"14041986-c0e6-4f86-8e67-51f740cc3f9c","added_by":"auto","created_at":"2026-05-15 08:46:38","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":341295,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal changes in serum and cerebrospinal fluid interleukin- 6(IL-6)levels in the patient.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9562813/v1/8ec6300d9636af6b93489eff.jpg"},{"id":109257114,"identity":"5e46927f-3110-4358-beec-0b6ed2f9583e","added_by":"auto","created_at":"2026-05-14 10:20:19","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":306924,"visible":true,"origin":"","legend":"\u003cp\u003e2-A shows the diffusion- weighted imaging of the head on the first day of admission, indicating high signal intensity in the bilateral reticular nucleus and thalamus DWI. Figure 2-B shows the diffusion-weighted imaging of the head on the 23rd day of admission, which indicates a significant reduction in high signal intensity in the bilateral reticular nucleus and thalamus DWI compared to before. Figures 2-C and 2-D show the diffusion- weighted images of the head after discharge, which indicate no high signal in the bilateral caudate nucleus and thalamus.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9562813/v1/bc611729b89d483c700ea121.jpg"},{"id":109257115,"identity":"55d7cd10-5adf-49c1-851a-9d68dbd611b3","added_by":"auto","created_at":"2026-05-14 10:20:19","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":904705,"visible":true,"origin":"","legend":"\u003cp\u003eA shows the rhythm changes of the electroencephalogram on the first day of admission, with medium high amplitude delta waves as the main slow wave mixed with fast waves. Sharp waves, sharp slow waves, and multiple sharp slow waves can be seen in the bilateral frontal pole, frontal and temporal regions, with an overall trend of explosion inhibition. The inhibition period is shortened from before,about 1-2 seconds, showing a quasi periodic pattern;At the same time, frequent partial seizures or partial secondary generalized seizures originating from the left or right frontal pole, frontal, and temporal regions were detected, lasting for 1-2 minutes, indicating electrical clinical status epilepticus. Figure 3-B shows the electroencephalogram(EEG)on the 16th day of admission. The background of the EEG is mainly composed of a large number of fast wave rhythms and spindle wave rhythms combined with theta waves.A small amount of slow and sharp waves are scattered in the right frontal and temporal regions, and the sleep state II-III phase changes are good;\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9562813/v1/bb0044db508ce04606a89150.jpg"},{"id":109257117,"identity":"10911acc-4eb9-4d3b-a58f-1b38ba0339b4","added_by":"auto","created_at":"2026-05-14 10:20:19","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":531263,"visible":true,"origin":"","legend":"\u003cp\u003etreatment flowchart and clinical course of case\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9562813/v1/a1f4ba6b2b4bebf9ca0358bd.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Human rhinovirus-associated febrile infection-related epilepsy syndrome with claustral involvement: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHuman rhinovirus (HRV), belonging to the Picornaviridae family and Enterovirus genus, represents the predominant viral pathogen implicated in community-acquired upper respiratory tract infections across both pediatric and adult populations. The prototypical clinical manifestation of HRV infection is the common cold; however, a subset of patients may develop influenza-like symptoms including fever, malaise, and myalgia. Notably, in contradistinction to influenza virus, HRV infections typically follow a self-limited course, rarely progress to severe systemic illness, and are exceptionally infrequently implicated as direct causative agents of neurological complications.Globally, documentation of HRV-associated central nervous system infections remains exceedingly scarce. To date, no prior reports have specifically described the association between HRV infection and febrile infection-related epilepsy syndrome (FIRES) with claustral involvement. Herein, we report the first documented case of FIRES characterized by bilateral claustral lesions secondary to confirmed HRV infection, admitted to the General Hospital of Ningxia Medical University on April 6, 2025. We further provide a comprehensive review of the pertinent literature to elucidate the putative pathophysiological mechanisms, distinctive electroencephalographic features, relevant ancillary investigations, and therapeutic strategies.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 25-year-old female was admitted to the Neuro-intensive Care Unit (NICU) of our institution in April 2025 with a chief complaint of \u0026quot;fever for 8 days, worsening with limb convulsions and altered consciousness for 5 days.\u0026quot; Her past medical history was unremarkable, and no family history of similar neurological conditions was reported.Following the onset of fever, the patient developed convulsive seizures characterized by sudden loss of consciousness, leftward conjugate gaze deviation, facial cyanosis, tongue biting, and tonic posturing of the left extremities with perioral twitching. Individual ictal episodes lasted approximately one minute; however, the patient failed to regain awareness between seizures, manifesting as continuous postictal altered consciousness. She experienced more than 10 such episodes during this period, with persistent loss of consciousness maintained throughout the interictal intervals.The patient was subsequently admitted to a local tertiary-care hospital for further evaluation and management. Lumbar puncture revealed a leukocyte count of 17/mm\u0026sup3; with 100% lymphocytes. Despite receiving endotracheal intubation with mechanical ventilation, antipyretic therapy, empirical antimicrobial treatment, and antiseizure medications, her neurological status showed no improvement. Consequently, she was transferred to our institution for advanced care.\u003c/p\u003e\n\u003cp\u003eUpon admission, physical examination revealed a deeply comatose patient with a Glasgow Coma Scale (GCS) score of 6T (E1, VT, M4). Both pupils were approximately 3 mm in diameter with sluggish direct and consensual light reflexes. No motor response was elicited upon painful stimulation. Muscle tone was diffusely decreased in all extremities, and deep tendon reflexes were absent bilaterally. Plantar responses were neutral, and pathological reflexes were negative bilaterally. Meningeal signs were not present.Comprehensive laboratory investigations, including complete blood count, thyroid function panel (7 items), purified protein derivative (PPD) test, TORCH panel (8 pathogens), cranial computed tomography (CT), chest CT, and inherited metabolic disease screening, yielded unremarkable results. Whole-exome sequencing was declined by the family.\u003c/p\u003e\n\u003cp\u003eLumbar puncture revealed an opening pressure of 230 mmH₂O. Cerebrospinal fluid (CSF) biochemical analysis (protein, glucose, chloride, total bilirubin, conjugated bilirubin, and unconjugated bilirubin) demonstrated no significant abnormalities. CSF cytology showed a leukocyte count of 12\u0026times;10⁶/L (lymphocytes: 77\u0026times;10⁶/L; neutrophils: 17\u0026times;10⁶/L). CSF immunoglobulin G (IgG) was 22.10 mg/g. Microbiological cultures of blood, sputum, and CSF were all negative.Autoimmune encephalitis antibodies, paraneoplastic antibodies, demyelination-associated antibodies, and astrocytopathy-related antibodies were negative in both serum and CSF. CSF cytokine analysis revealed interleukin (IL)-1\u0026beta;: 14.38 pg/mL, IL-6: 121.93 pg/mL, and IL-12p70: 4.16 pg/mL. Serum IL-6 level was 97.1 pg/mL (Figure 1).Cranial magnetic resonance imaging (MRI) demonstrated bilateral claustral and thalamic hyperintensities on diffusion-weighted imaging (DWI) (Figure 2).Continuous electroencephalographic (EEG) monitoring revealed a background pattern predominantly composed of medium-to-high amplitude delta activity admixed with fast frequencies. Sharp waves, sharp-and-slow-wave complexes, and polyspike-and-slow-wave discharges were observed over bilateral frontopolar, frontal, and temporal regions. The overall pattern demonstrated a burst-suppression tendency with interburst intervals shortened to approximately 1\u0026ndash;2 seconds, exhibiting quasi-periodic discharges. Concurrently, frequent electrographic seizures were detected, originating from the left or right frontopolar, frontal, and temporal regions, manifesting as either partial-onset seizures or partial seizures with secondary generalization, lasting 1\u0026ndash;2 minutes\u0026mdash;findings consistent with electroclinical status epilepticus (Figure 3).Following admission, the patient received supportive care including mechanical ventilation, enteral nutrition, fluid resuscitation to maintain water-electrolyte balance, and antimicrobial therapy. On hospital day 1, intravenous dexamethasone was administered for 2 consecutive days, and human immunoglobulin was given for 5 days. Antiseizure therapy was initiated with midazolam, sodium valproate, propofol, phenobarbital, and levetiracetam (Figure 4).On hospital day 2, sodium valproate was discontinued due to elevated blood ammonia levels, and lacosamide was added. On day 3, frequent left-sided convulsive seizures persisted; given the absence of significant improvement in status epilepticus, the patient was diagnosed with super-refractory status epilepticus (SRSE), confirming the diagnosis of FIRES-C. Following intravenous diazepam bolus administration, electroencephalographic improvement was observed. Continuous intravenous diazepam infusion was subsequently initiated in combination with clonazepam. On day 3, pulse corticosteroid therapy with methylprednisolone sodium succinate was administered for 6 days, followed by transition to oral prednisone acetate 50 mg/day with a tapering regimen of 1 tablet every 2 weeks.On hospital day 5, status epilepticus remained refractory. Following comprehensive informed consent, tocilizumab (4 mg/kg per dose) was administered intravenously once. On day 6, repeat CSF cytokine analysis revealed IL-1\u0026beta;: 14.90 pg/mL, IL-6: 14.36 pg/mL, and IL-12p70: 4.04 pg/mL. By day 10, electroclinical seizures decreased to 1\u0026ndash;2 episodes per day. By day 16, the patient remained seizure-free; EEG background demonstrated predominant theta activity admixed with abundant fast frequencies and sleep spindles, with occasional sporadic spike-and-slow-wave and sharp-and-slow-wave discharges over the right frontal and temporal regions, and preserved stage II\u0026ndash;III sleep architecture (Figure 3). Propofol was gradually tapered and discontinued. On day 18, midazolam was tapered and discontinued. On day 22, diazepam was gradually tapered and discontinued, and the patient regained full consciousness.On day 23, the patient was successfully weaned from mechanical ventilation and transitioned to Venturi mask oxygen therapy. Repeat cranial MRI demonstrated significant resolution of bilateral claustral and thalamic DWI hyperintensities (Figure 2). On day 30, breakthrough seizures recurred, characterized by loss of consciousness, left-sided convulsions, and leftward conjugate gaze deviation, lasting 1\u0026ndash;2 minutes with subsequent recovery of consciousness. Oxcarbazepine was added to the antiseizure regimen. The patient was discharged on hospital day 45 without further seizure recurrence.Discharge physical examination revealed: alert and oriented; pupils equal, round, and reactive to light (3 mm bilaterally); symmetric facial movements; tongue midline; muscle strength grade 5/5 in all extremities; normal muscle tone; absent deep tendon reflexes bilaterally; negative pathological reflexes; and negative meningeal signs. Modified Rankin Scale (mRS) score was 0. At 60-day post-discharge follow-up, the patient experienced one breakthrough seizure during clonazepam dose reduction, manifesting as left-sided convulsions with leftward gaze deviation lasting 1\u0026ndash;2 minutes with full recovery. Repeat cranial MRI demonstrated complete resolution of bilateral claustral and thalamic hyperintensities on DWI (Figure 1). Neurocognitive assessment revealed Mini-Mental State Examination (MMSE) score of 23 and Montreal Cognitive Assessment (MoCA) score of 21; longitudinal follow-up is ongoing.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHuman rhinovirus (HRV) belongs to the \u003cem\u003ePicornaviridae\u003c/em\u003e family and has been associated with a broad spectrum of clinical manifestations (1)，It demonstrates tropism for epithelial cells and induces a broad spectrum of respiratory tract infections. However, central nervous system involvement by human rhinovirus (HRV) remains exceedingly rare in the medical literature(2\u0026ndash;5)，It demonstrates tropism for epithelial cells and induces a broad spectrum of respiratory tract infections. However, central nervous system involvement by human rhinovirus (HRV) remains exceedingly rare in the medical literature(6,7)。Recent evidence suggests that human rhinovirus (HRV) may lead to severe central nervous system (CNS) complications through dual mechanisms involving direct neuroinvasion and cytokine storm(1\u0026ndash;3,8),\u0026nbsp;In contrast to influenza virus and SARS-CoV-2, human rhinovirus (HRV) elicits an immune response characterized by an IL-6/IL-1\u0026beta;-dominant inflammatory profile(5). Based on the clinical manifestations, laboratory findings, and metagenomic next-generation sequencing (mNGS) data, we postulate that human rhinovirus (HRV) represents the sole causative pathogen responsible for the observed neurological complications.\u003c/p\u003e\n\u003cp\u003eDiagnostic criteria for febrile infection-related epilepsy syndrome (FIRES) with claustral involvement include: (1) acute onset of neuropsychiatric manifestations\u0026mdash;including encephalopathy, epileptic seizures, or altered consciousness\u0026mdash;during the acute phase of systemic infection (predominantly acute respiratory viral infection), occurring within 1 day to several days post-infection; (2) cerebrospinal fluid (CSF) pleocytosis absent or mild, with significantly elevated IL-6 levels detectable in CSF and/or serum, and negative autoimmune encephalitis antibodies; (3) reasonable exclusion of alternative etiologies; and (4) magnetic resonance imaging (MRI) demonstrating abnormal signal intensities in the bilateral claustrum, potentially accompanied by bilateral hippocampal abnormalities. Notably, initial MRI at disease onset may appear unremarkable, with claustral lesions becoming evident on follow-up imaging (median interval from symptom onset to lesion documentation: 12.5 days)(9\u0026ndash;12); In this report, the adult female patient developed refractory status epilepticus (RSE) five days after fever onset (latency period: 5 days), fulfilling the diagnostic criteria for febrile infection-related epilepsy syndrome with claustral involvement (FIRES-C). Comprehensive investigations excluded identifiable metabolic or genetic etiologies. Refractoriness to multiple antiepileptic drugs (AEDs), anesthetic agents, ketogenic diet, and first-line immunotherapy further substantiated the definitive diagnosis of FIRES-C.The secondary seizures observed in this syndrome are categorized as acute symptomatic seizures following infection, typically arising from the interplay of multiple pathogenic factors. Specifically, activation of the inflammatory cascade and the consequent release of pro-inflammatory cytokines constitute the central underlying mechanisms common to most central nervous system (CNS) infections. This pathophysiological concept has been extensively corroborated by clinical and basic studies in prevalent CNS infectious diseases, including meningitis and encephalitis(13,14).An alternative pathophysiological mechanism underlying seizure generation involves the claustrum serving as a critical anatomical hub that mediates the propagation and synchronization of epileptiform discharges across multiple cortical regions(15)。When rhinovirus-induced inflammatory mediators damage the claustrum, the resulting functional dysregulation of its role as a \u0026quot;neural network modulator\u0026quot; facilitates the rapid generalization of epileptiform discharges from localized foci to widespread cortical territories, culminating in a state of super-refractory epilepsy(11).\u0026nbsp;Therefore, these neuroimaging findings presumably exhibit a close association with seizure genesis(16,17)。While this clinico-radiological association has garnered preliminary recognition, the precise pathophysiological mechanisms underlying the \u0026quot;fever-epilepsy-claustral lesion\u0026quot; cascade remain elusive, with existing studies yielding conflicting interpretations. Alternatively, some investigators have posited that seizure activity per se may precipitate transient, reversible MRI signal alterations, challenging the assumption of a direct causal link with the infectious process(18):\u0026nbsp;Upon achieving effective seizure control and symptomatic remission, repeat cranial magnetic resonance imaging (MRI) may demonstrate complete resolution of the previously observed claustral lesions. Based on these clinico-radiological characteristics, it cannot be excluded that the imaging changes within the claustrum represent secondary manifestations triggered by status epilepticus, rather than constituting primary pathological lesions directly involved in the pathogenesis of epilepsy.\u003c/p\u003e\n\u003cp\u003eThis study demonstrated a well-defined temporal evolution of clinical manifestations in patients with febrile infection-related epilepsy syndrome (FIRES) with claustral involvement, consistent with prior reports(19): The mean age of affected patients was 25 years. The prodromal phase was characterized by fever and altered mental status, followed by the onset of epileptic seizures. The mean interval between fever onset and seizure occurrence was 6 days, demonstrating a well-defined temporal progression of the clinical course.Seizures in this syndrome represented the acute ictal phase of the disease. One of the most prominent features was the rapid dynamic evolution of both seizure semiology and electroencephalographic (EEG) manifestations. Initially, seizures typically manifested as bilateral motor seizures, specifically including focal seizures with clonic activity and multifocal myoclonic seizures with alternating involvement of bilateral limbs. These subsequently progressed rapidly to generalized non-convulsive status epilepticus (NCSE) or subtle/myoclonic status epilepticus. Management of these patients typically required transfer to the neuro-intensive care unit (NICU) and administration of intravenous anesthetic agents for seizure control(20). Radiologically, claustral lesions typically emerged approximately 8 days after disease onset, with the bilateral claustrum demonstrating either symmetrical or asymmetrical signal abnormalities. Notably, these claustral changes resolved following the amelioration of status epilepticus in the majority of reported cases; however, subsequent magnetic resonance imaging (MRI) revealed varying degrees of cortical and/or hippocampal atrophy.Although the clinical presentation and disease course bear resemblance to autoimmune encephalitis, all reported patients tested negative for known autoimmune encephalitis antibodies in both peripheral blood and cerebrospinal fluid (CSF).Regarding therapeutic strategies, current literature indicates that first-line immunomodulatory therapy should be initiated within the initial 72 hours following the onset of status epilepticus (SE) in FIRES-C, potentially encompassing corticosteroids (CS) and intravenous immunoglobulin (IVIG)(21). Notably, the majority of respondents also advocated initiating these therapeutic interventions within 48 hours of disease onset or immediately following the exclusion of common infectious etiologies. Early implementation of pulse corticosteroid therapy combined with intravenous immunoglobulin may significantly improve neurological outcomes(22). In the immunotherapeutic management of FIRES-C, tocilizumab (an IL-6 receptor antagonist) and anakinra (an IL-1 receptor antagonist) represent the primary options for second-line treatment, with a growing clinical trend favoring their earlier implementation(23). In clinical practice, prompt recognition and diagnosis of febrile infection-related epilepsy syndrome with claustral involvement (FIRES-C), coupled with immediate initiation of intensive immunomodulatory therapy, constitute critical management imperatives. We anticipate that cumulatively accumulated research evidence and clinical experience will establish the necessary foundation for formulating diagnostic and therapeutic consensus regarding this syndrome. Notably, for patients manifesting such refractory status epilepticus, the primary therapeutic objective should be the immediate cessation of ongoing seizure activity(13,24). However, the present case demonstrated refractoriness to multiple antiseizure medications (ASMs) and sedative-hypnotic agents. Notably, following tocilizumab administration, serum and cerebrospinal fluid (CSF) interleukin-6 (IL-6) levels exhibited a measurable reduction(25), Seizure frequency also improved markedly; however, no correlation was observed between the frequency of epileptic seizures and serum interleukin-6 (IL-6) levels in this patient(26). Furthermore, continuous electroencephalographic (EEG) monitoring enables the assessment of cerebral electrical activity under naturalistic conditions and sleep-wake cycles, providing valuable data for the selection of antiseizure medications (ASMs), dosage titration, and determination of discontinuation criteria. Early implementation of comprehensive EEG evaluation, coupled with medication adjustment under continuous monitoring, represents a critical therapeutic priority(27\u0026ndash;29).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn patients presenting with neuropsychiatric manifestations, epileptic seizures, and altered consciousness following human rhinovirus (HRV) infection, clinicians should maintain a high index of suspicion for rhinovirus-associated febrile infection-related epilepsy syndrome (FIRES) with claustral involvement, as the early recognition of this clinico-radiological entity remains a significant diagnostic challenge. Cranial magnetic resonance imaging (MRI), serving as one of the most sensitive diagnostic modalities currently available, combined with cerebrospinal fluid (CSF) analysis and comprehensive neurological assessment, holds substantial diagnostic value in patients exhibiting altered consciousness following respiratory viral infections, providing critical evidence for early identification.From a pathophysiological perspective, the central mechanism underlying FIRES with claustral involvement lies not in direct neuroinvasion by the pathogen, but rather in cytokine-mediated neuroinflammation via innate immune inflammatory mediators. Emerging evidence suggests that early initiation of antiseizure medications (ASMs) combined with intensive immunomodulatory therapy, with continuous electroencephalographic (EEG) monitoring-guided optimization of pharmacological regimens, may potentially disrupt the vicious cycle between epileptic activity and neuroinflammation, thereby reducing the risk of progression to refractory epilepsy. This underscores the critical importance of early immunotherapeutic intervention. Therefore, in clinical practice, prompt evaluation of serum and CSF cytokine profiles, alongside cranial MRI, is imperative upon clinical suspicion. Once the diagnosis is established, immediate commencement of immunomodulatory therapy may substantially ameliorate long-term neurological outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by Ningxia Medical University (approval number: KYLL-2025-2457). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants\u0026rsquo;\u0026nbsp;legal guardians/next of kin. The animal studies were approved by Ningxia Medical University (approval number: KYLL-2025-2457). The studies were conducted in accordance with the local legislation and institutional requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of this case report and any accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or\u0026nbsp;financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConflict of interest The authors declare that the research was conducted in the absence of any commercial or\u0026nbsp;financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that financial support was received for the research and/or publication of this article. the Ningxia Provincial Natural Science Foundation of China(No.2025AAC020092).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.T. (Yang Tiejun) conceived the case report, collected and curated the patient data,and prepared the medical images/visualizations. L.W. (Wang Longnan) assisted with clinical investigation.C.J. (Ji Chunbo) participated in clinical investigationand prepared the figures. S.M. (Ma Siqing) prepared the visualizations and contributed to manuscript review. D.D. (Dong Danyang) curated the clinical data and provided resources. P.Y. (Yang Ping), as the corresponding author, designed the study and reporting, acquired funding, administered the project, and critically revised the manuscript. All authors reviewed the final manuscript, approved the submitted version, and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the patient for permitting us to disclose details relating to this case. The authors thank the family members for participation in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOlive DM, Al-Mufti S, Al-Mulla W, Khan MA, Pasca A, Stanway G, et al. Detection and differentiation of picornaviruses in clinical samples following genomic amplification. J Gen Virol. 1990;71(Pt 9):2141\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/0022-1317-71-9-2141\u003c/span\u003e\u003cspan address=\"10.1099/0022-1317-71-9-2141\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolzel A, Smith PA, Tobin JO. A new type of meningo-encephalitis associated with a rhinovirus. 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Evaluating the utility of inpatient video-EEG monitoring. Epilepsia. 2004;45(8):928\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.0013-9580.2004.51003.x\u003c/span\u003e\u003cspan address=\"10.1111/j.0013-9580.2004.51003.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":false,"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":"Rhinovirus, Magnetic resonance imaging, Electroencephalography, Tocilizumab, Febrile infection-related epilepsy syndrome","lastPublishedDoi":"10.21203/rs.3.rs-9562813/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9562813/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHuman rhinovirus (HRV) is the predominant viral pathogen causing community-acquired upper respiratory tract infections, typically manifesting as mild coryzal symptoms. Severe neurological complications, including febrile infection-related epilepsy syndrome (FIRES), are exceptionally rare.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe report a case of HRV-associated FIRES with bilateral claustral involvement identified at the General Hospital of Ningxia Medical University in April 2025. The patient presented with acute refractory status epilepticus following prodromal fever. Neuroimaging revealed bilateral claustral hyperintensities and symmetrical thalamic lesions, while continuous electroencephalographic monitoring demonstrated burst-suppression patterns with frontotemporal discharges. Nucleic acid testing confirmed HRV infection.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case underscores the importance of considering HRV-associated FIRES in patients with acute encephalopathy following respiratory infection. Early recognition through comprehensive neuroimaging and electroencephalographic monitoring, combined with aggressive immunomodulatory therapy and optimized antiseizure medications, is essential for improving neurological outcomes. We further delineate putative cytokine-mediated pathophysiological mechanisms through systematic literature review.\u003c/p\u003e","manuscriptTitle":"Human rhinovirus-associated febrile infection-related epilepsy syndrome with claustral involvement: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 10:20:08","doi":"10.21203/rs.3.rs-9562813/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":"a711cb3f-4be7-41da-9073-d428797957f0","owner":[],"postedDate":"May 14th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-19T00:27:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-18T10:04:32+00:00","index":36,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T10:54:45+00:00","index":35,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T18:28:06+00:00","index":34,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T18:26:00+00:00","index":33,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-09T08:15:08+00:00","index":32,"fulltext":""},{"type":"reviewerAgreed","content":"316094791544905170307786203530715888126","date":"2026-05-08T11:02:39+00:00","index":30,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T05:35:23+00:00","index":29,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T05:33:52+00:00","index":28,"fulltext":""},{"type":"reviewerAgreed","content":"334516854485937887780212842396900560348","date":"2026-05-08T05:09:31+00:00","index":27,"fulltext":""},{"type":"reviewerAgreed","content":"84123532700129350883285630916147209968","date":"2026-05-08T03:06:41+00:00","index":26,"fulltext":""},{"type":"reviewerAgreed","content":"81613439585802481993699090531995619582","date":"2026-05-06T17:51:17+00:00","index":25,"fulltext":""},{"type":"reviewerAgreed","content":"295662916450875900090369488782992939760","date":"2026-05-06T16:57:41+00:00","index":24,"fulltext":""},{"type":"reviewerAgreed","content":"317676021346763610919570880918252591594","date":"2026-05-06T06:07:44+00:00","index":22,"fulltext":""},{"type":"reviewerAgreed","content":"302616047910137819321275374727576017934","date":"2026-05-06T04:40:59+00:00","index":21,"fulltext":""},{"type":"reviewerAgreed","content":"69104244340354213820138913146412888293","date":"2026-05-06T01:27:37+00:00","index":19,"fulltext":""},{"type":"reviewerAgreed","content":"221737142839646105009897181749691288239","date":"2026-05-06T01:25:21+00:00","index":18,"fulltext":""},{"type":"reviewersInvited","content":"12","date":"2026-05-06T01:23:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-03T23:14:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-03T23:13:26+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-19T00:39:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-14 10:20:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9562813","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9562813","identity":"rs-9562813","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}