Neuro-Syphilis Initially Presenting as Non-convulsive Status Epilepticus: A Case Report

Neuro-Syphilis Initially Presenting as Non-convulsive Status Epilepticus: 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 Neuro-Syphilis Initially Presenting as Non-convulsive Status Epilepticus: A Case Report Xinyi Fei, Xinxin Li, Meiyan Shao, Rui Zhang, Shan Yu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8680108/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 33 You are reading this latest preprint version Abstract Background: Neurosyphilis is a renowned "great imitator" in clinical practice. While it can cause seizures, its presentation as non-convulsive status epilepticus (NCSE) is exceptionally rare and diagnostically challenging. Case presentation: A 67-year-old female with a history of prior cerebral infarction presented acutely with recurrent episodes of impaired consciousness and conjugate eye deviation, without convulsive limb movements. Critically, her consciousness did not fully normalize between episodes. Neurological examination revealed stupor, mixed aphasia, bilateral miotic pupils with absent light reflexes, and bilateral Babinski signs. Neuroimaging (MRI) showed findings suggestive of prior infarcts and possible hydrocephalus. Long-term video-EEG monitoring revealed epileptiform discharges over the left temporo-occipital region, fulfilling diagnostic criteria for NCSE. Serological and cerebrospinal fluid (CSF) analysis confirmed active neurosyphilis (positive serum and CSF RPR). The patient was diagnosed with neurosyphilis presenting as NCSE, alongside syphilitic encephalitis and general paresis. Treatment with benzathine penicillin G and levetiracetam led to significant improvement in consciousness and cessation of seizure activity. Conclusion: This case underscores that neurosyphilis must be considered in the differential diagnosis of NCSE, especially in patients with stroke-like symptoms but with contraindications to thrombolysis. Early CSF analysis and syphilis serology are critical for accurate diagnosis and timely initiation of antibiotic therapy, which can prevent permanent neurological damage. It emphasizes the importance of considering infectious etiologies in cases of unexplained altered mental status and seizures. Neurosyphilis Non-Convulsive Status Epilepticus Syphilitic encephalitis General paresis Antibiotic therapy Diagnostic challenge Case Report Figures Figure 1 Figure 2 Figure 3 Introduction Neurosyphilis, caused by the invasion of Treponema pallidum into the central nervous system, remains a formidable diagnostic challenge in modern neurology. Its moniker, "the great imitator," is well-earned, as it can mimic a vast spectrum of neurological and psychiatric disorders, including dementia, stroke, myelopathy, and psychiatric illnesses 1 . The clinical presentation of neurosyphilis has evolved in the antibiotic era, with a higher prevalence of atypical and subtle manifestations, often leading to delayed or missed diagnosis. While the relationship between neurosyphilis and seizures is established, the occurrence of status epilepticus is uncommon. Particularly, non-convulsive status epilepticus (NCSE)—a state of prolonged seizure activity manifesting primarily as altered consciousness without prominent motor signs—as the heralding presentation of neurosyphilis is a rare phenomenon. This presentation is perilous because its symptomatology, such as impaired consciousness and focal neurological deficits, can be indistinguishable from that of an acute large-vessel ischemic stroke. This similarity poses a critical risk, as the administration of thrombolytic therapy, which is standard for ischemic stroke, is contraindicated in the presence of seizures and could lead to catastrophic hemorrhagic complications if the underlying etiology is in fact NCSE. The purpose of this case report is to describe the clinical course, diagnostic challenges, and successful management of an elderly patient who presented with NCSE secondary to previously undiagnosed neurosyphilis. We aim to highlight the critical importance of including neurosyphilis in the differential diagnosis of NCSE to avoid misdiagnosis as cerebrovascular disease and to facilitate prompt, appropriate treatment. Case 1. Presentation A 67-year-old female presented acutely to our emergency department with a 4-hour history of episodic impaired consciousness and conjugate eye deviation. According to her family, the episodes began abruptly, without obvious provocation, and were characterized by unresponsiveness to verbal cues, ocular deviation, and akinesia. Each episode lasted several minutes and was repeated four times. Critically, her consciousness did not fully normalize between episodes. Associated symptoms included three episodes of nausea and vomiting, with coffee-ground emesis. She was transported via emergency medical services for further evaluation and was admitted to our neurology department for "Altered Mental Status (Etiology Unknown)." Her baseline health was unremarkable, with no significant recent weight change, and no abnormalities in mental status, diet, sleep, or bowel/bladder habits. Past medical history included an acute cerebral infarction five months prior, resulting in residual right-sided hemiparesis, manifested as clumsiness in right upper limb fine motor tasks and a slightly dragging gait. 2. Physical Examination Vital signs on admission: pulse 89 bpm, respiration 16 breaths/min, blood pressure 98/66mmHg. Neurologically, she was stuporous with mixed aphasia and was uncooperative. Both eyes demonstrated conjugate left gaze preference. Pupils were bilaterally constricted (approximately 1.5 mm) with absent direct and indirect light reflexes. Facial symmetry was preserved. Limb muscle tone was generally reduced. Muscle strength was graded 4/5 on the right and 5/5 on the left. Bilateral pathologic reflexes (Babinski sign) were present. Further detailed neurological assessment was limited by her uncooperative nature. The Mini-Mental State Examination (MMSE) score was 7. 3. Diagnostic Investigations Non-contrast Head CT: Revealed lacunar infarcts in the bilateral basal ganglia and corona radiata; changes in the posterior horns of the lateral ventricles suggestive of possible hydrocephalus; white matter demyelination; and cerebral atrophy. Diffusion-Weighted Imaging (DWI): Demonstrated slight hyperintensity in the left temporo-occipital gyrus with corresponding reduced signal on the ADC map(Fig. 1 A,B). Brain MRI: Showed iso- to slightly hypointense T1 and hyperintense T2 signals in the left temporo-occipital lobe, with slight hyperintensity on FLAIR. Additionally, multiple lacunar infarcts were noted in the left thalamus, bilateral basal ganglia, corona radiata, and centrum semiovale, alongside other ischemic foci, white matter demyelination, ventricular dilatation (suggesting hydrocephalus)(Fig. 2 A,B,C.). Magnetic Resonance Angiography (MRA): Indicated a relatively slender right vertebral artery compared to the left and focal mild stenosis in the P2 segment of the left middle cerebral artery. Chest CT: Showed nodular opacities in the left upper and lower lobes, potentially inflammatory; subpleural inflammation in the right upper, middle, and both lower lobes; linear scars in the right middle lobe and lingula; and bilateral pleural thickening. Vascular Ultrasound: Carotid and right subclavian artery atherosclerosis with plaque formation. Echocardiography revealed aortic sclerosis with mild aortic regurgitation and normal left ventricular systolic function. Lower extremity ultrasound confirmed bilateral arterial sclerosis. Long-term Video-EEG Monitoring: Background activity showed low-amplitude 7–8 Hz alpha rhythm over the occipital regions, suppressed by eye opening. Interictally, sharp waves, and slow-wave discharges were observed over the left fronto-temporal regions. No electrographic or clinical seizures were captured (Fig. 3 ). Blood Routine: Notable for leukocytosis (20.34×10/L) with neutrophilia (93.3%) and lymphopenia (2.1%). Procalcitonin was elevated at 18 ng/mL. Lactate was 8.20 mmol/L. Serological tests were positive for Treponema pallidum antibody (26.07 S/CO) and RPR (titer 1:32). Routine biochemistry was unremarkable. Urine: Significant for pyuria and bacteriuria. Gastric Fluid: Occult blood positive. Cerebrospinal Fluid (CSF): Opening pressure 160 mmH 2 O. CSF was clear and colorless with a positive Pandy's test, pleocytosis (35 cells/µL), decreased glucose (2.7 mmol/L), elevated protein (0.64 g/L), and normal chloride. CSF RPR was positive (titer 1:16). Autoimmune Encephalitis Antibody Panel: Negative. 4. Diagnosis and Clinical Course Based on the constellation of clinical and paraclinical findings, the patient was diagnosed with neurosyphilis, syphilitic encephalitis, non-convulsive status epilepticus (NCSE), general paresis, stress-related gastrointestinal bleeding, and multiple lacunar infarcts. Treatment included supportive care (gastrointestinal decompression, urinary catheterization), antiseizure medication (levetiracetam, 0.5 g twice daily), plaque stabilization (atorvastatin, 40 mg daily), and anti-syphilitic therapy (benzathine penicillin G, 2.4 million units IM weekly for 3 doses). Her consciousness and motor function improved significantly following treatment. A follow-up examination noted clear consciousness, fluent speech, but persistent cognitive deficits (MMSE = 7), bilateral miotic pupils with absent light reflexes, normal muscle tone, right-sided muscle strength of 4/5, and bilateral extensor plantar responses. 5. Outcome At discharge, the patient was afebrile, with motor function returned to pre-admission levels and no further seizures. Neurological examination findings were largely unchanged from the previous assessment, except for noted improvement in cognitive domains (calculation, memory, orientation). Discussion This article reports a rare case of neurosyphilis. This elderly female patient initially presented with non-convulsive status epilepticus (NCSE), accompanied by complex conditions including syphilitic encephalitis, general paresis/paralytic dementia, and stress-related gastrointestinal bleeding. Combined with the stroke-like onset, status epilepticus, and related clinical signs, it was highly susceptible to misdiagnosis as a large-area cerebral infarction, undoubtedly posing significant challenges for diagnosis and treatment. However, due to the presence of seizures and active gastrointestinal bleeding, which are relative and absolute contraindications to thrombolysis, respectively, thrombolytic and antithrombotic therapies were not administered. Subsequently, symptoms such as fever and cognitive dysfunction suggested the possibility of an infectious or inflammatory etiology. Further cerebrospinal fluid and serum testing ultimately confirmed the diagnosis of neurosyphilis. Neurosyphilis is a clinical syndrome caused by the invasion of the central nervous system by Treponema pallidum, characterized by variable and often non-specific symptoms, earning it the moniker "the great imitator" 1 . T. pallidum can invade the CNS within days of infection. Subsequent neurosyphilis can be asymptomatic or symptomatic. Neurosyphilis can manifest at any stage of the disease. Early infection often presents as aseptic meningitis or meningovascular syphilis. Late neurosyphilis most commonly presents as parenchymatous syphilis, specifically general paresis or tabes dorsalis 2 , 3 . Studies suggest that compared to syphilis patients without neurosyphilis or non-syphilis patients, neurosyphilis patients have significantly elevated levels of CD8 + IFN-γ + cells in peripheral blood, while levels of Th2, Th9, CD8 + IL-4+, CD8 + IL-9+, and CD8 + IL-17 + cells are lower. Symptomatic neurosyphilis patients exhibit high expression of CD8 + IFN-γ + cells and low expression of CD8 + IL-17 + cells, which might be a relevant mechanism for symptom manifestation 4 . The temporal relationship between neurosyphilis syndromes and primary, secondary, or tertiary syphilis is not precise. Some patients have multiple sites of CNS involvement, and classifications often overlap.3 Reports indicate that the incidence of epilepsy as the initial symptom of neurosyphilis ranges from 14% to 60%, with status epilepticus being rare 5 , 6 . NCSE, as the initial presentation, is even rarer. Central nervous system infection is one etiology of epilepsy. When pathogens enter the brain parenchyma, they can directly infect neurons, leading to neuronal lysis and death, and releasing pro-inflammatory cytokines and cellular products (like ATP or DNA-derived N-formyl peptides) that act as danger signals, activating autoimmunity and generating an adaptive immune response, resulting in neuronal damage or dysfunction 7 . During the latent period between infection and seizure onset, a series of intracranial changes occur, including increased neuronal hyperexcitability driven by NMDA receptors and other glutamate-mediated mechanisms, neuronal loss and gliosis, molecular and structural reorganization, and epigenetic reprogramming. All these processes can ultimately lead to recurrent unprovoked seizures 8 . The structural brain damage caused by these CNS infections may form an epileptogenic focus, serving as the organic basis for recurrent epilepsy 9 . Non-convulsive status epilepticus (NCSE) is traditionally defined as continuous non-convulsive seizure activity lasting 30 minutes or recurrent seizures without regaining consciousness in the interictal periods. Recently, a proposal to shorten the duration to 5 minutes has been made, but it is not universally accepted 10 . In 2015, the ILAE classified NCSE as NCSE in coma and NCSE without coma. NCSE without coma is further subdivided into generalized (typical absence status epilepticus, atypical absence status epilepticus, myoclonic absence status epilepticus) and focal origin (absence status epilepticus of focal origin, focal status epilepticus without impaired awareness, focal status epilepticus with impaired awareness), and autonomic NCSE of unknown origin 11 . Diagnosis primarily relies on clinical manifestations and EEG. The Salzburg Consensus Criteria for NCSE propose EEG diagnostic criteria for patients without epileptic encephalopathy: 1. Epileptiform discharges > 2.5 Hz; OR 2. Epileptiform discharges ≤ 2.5 Hz or rhythmic delta/theta activity (> 0.5 Hz) AND one of the following: a. EEG and clinical improvement after IV antiseizure drugs (ASDs), b. Presence of subtle clinical ictal phenomena during the aforementioned EEG patterns, or c. Typical spatiotemporal evolution 12 . As sufficient clinical trials for NCSE treatment are still lacking, the optimal treatment regimen has not been established. Rapid termination of epileptic activity is the primary goal in treating NCSE patients in the neuro-ICU. Benzodiazepines are typically used as first-line treatment for NCSE 13 . The patient reported here presented to our emergency department with episodic consciousness disturbance and eye deviation for 4 hours. The episodes involved altered consciousness, and consciousness did not return to normal during the interictal periods, without convulsive limb activity. EEG showed abnormal waves in the left temporo-occipital region, with a frequency > 2.5 Hz, consistent with the high signal in the left temporo-occipital lobe on MRI. Therefore, NCSE was considered. After administration of antiseizure medication, no further seizures occurred. Treatment guidelines for neurosyphilis from the US, UK, Europe, and China emphasize penicillin as the first-line drug for immunocompetent patients. After administering Benzathine Penicillin to this patient, her symptoms improved significantly. Ceftriaxone is the only alternative recommended by the US CDC for penicillin-allergic patients. Azithromycin has been shown to be effective for early syphilis in several randomized trials; however, resistance to azithromycin and other macrolides (A→G mutation at position 2058 or 2059 in 23S ribosomal DNA) has been detected globally, and azithromycin should no longer be used for syphilis in most clinical settings 14 . A recent retrospective study on neurosyphilis investigated mRNA expression, levels of IL-27, IL-17, Th17, IL-17-producing CD4 + T cells, and CSF protein concentration and VDRL. Results showed a significant inverse relationship between CSF protein/VDRL concentration and CSF IL-27 levels, supporting the therapeutic potential of IL-27 in neurosyphilis and inflammatory processes 15 . For the prevention of neurosyphilis, a syphilis vaccine that prevents T. pallidum dissemination from the infection site could protect individuals from subsequent disease stages and progression to neurosyphilis. Studies show that immunization with a TprC/TprK/Tp0751 triple-antigen mixture can protect animals from progressive syphilitic lesions and significantly inhibit infection dissemination, although complete immunity has not yet been achieved 16 . The clinical manifestations of neurosyphilis lack specificity. Diagnosis is primarily based on specific clinical features, serum, and CSF tests. Patients often conceal infectious disease history and may lack skin lesions. Elderly patients often have cerebrovascular disease risk factors, and a head MRI may coincidentally show cerebral infarction lesions. Patients may also refuse a lumbar puncture for further investigation. Consequently, neurosyphilis is often misdiagnosed as cerebrovascular disease. In summary, the clinical presentation of neurosyphilis is complex and variable, often posing significant diagnostic challenges, leading to misdiagnosis, missed diagnosis, and delayed treatment. History-taking should pay attention to personal history. Serum and CSF syphilis tests should be promptly completed to achieve early diagnosis and treatment. Abbreviations NCSE Non-convulsive Status Epilepticus CNS Central Nervous System EEG Electroencephalogram CSF Cerebrospinal Fluid NMDA N Methyl D Aspartate. Declarations Ethics approval and consent to participate Not applicable. This is a single case report with no experimental intervention. Consent for Publication Written informed consent were signed and obtained from the patient prior to writing and submission for publication. Sociodemographic and clinical data have been de-identified to protect patients’ privacy. Competing interests The author(s) report no conflicts of interest in this work. Funding No funding was received for this study. Author Contribution XF was responsible for collecting clinical data, drafting the manuscript, selecting appropriate journals, and submitting the manuscript. XL contributed to clinical decision-making and case analysis. MS also participated in diagnosis and treatment, as well as assisting with clinical data collection. RZ was involved in gathering reference materials, while SY participated in case management, analysis, and manuscript revision. Acknowledgement The successful completion of this case report was made possible through the collaborative efforts and steadfast support of a multidisciplinary team. We wish to extend our sincere gratitude to our colleagues from the Department of Neurology, Emergency Medicine, Laboratory Medicine, and Radiology for their exceptional professional support and expertise provided throughout the patient's diagnostic and therapeutic journey. Furthermore, we are deeply thankful to the patient's family for their active participation in providing a detailed medical history and for their cooperation during the treatment process, which was instrumental in clarifying complex clinical challenges.We hereby express our earnest appreciation to all peers and medical professionals who contributed to the management and scholarly discussion of this case. Availability of data and materials All data supporting the conclusions of this article are included within the manuscript. References Jancar N, Simoes M, Goncalves F, et al. Neurosyphilis: The Great Imitator. Cureus. 2022;14(12):e32747. 10.7759/cureus.32747 . Ropper AH, Neurosyphilis. N Engl J Med. 2019;381(14):1358–63. 10.1056/NEJMra1906228 . Zhou J, Zhang H, Tang K, et al. An Updated Review of Recent Advances in Neurosyphilis. Front Med (Lausanne). 2022;9:800383. 10.3389/fmed.2022.800383 . Liu LL, Liu WN, Jiang XY, et al. Changes of T lymphocyte subsets in patients with HIV-negative symptomatic neurosyphilis. Microb Pathog. 2019;130:213–18. 10.1016/j.micpath.2019.03.008 . Ances BM, Shellhaus R, Brown MJ, et al. Neurosyphilis and status epilepticus: case report and literature review. Epilepsy Res. 2004;59(1):67–70. 10.1016/j.eplepsyres.2004.03.007 . Kumari S, Hayton T, Jumaa P, et al. The great imitator': Neurosyphilis and new-onset refractory status epilepticus (NORSE) syndrome. Epilepsy Behav Case Rep. 2015;3:33–5. 10.1016/j.ebcr.2015.02.001 . Vezzani A, Fujinami RS, White HS, et al. Infections, inflammation and epilepsy. Acta Neuropathol. 2016;131(2):211–34. 10.1007/s00401-015-1481-5 . Ngarka L, Siewe Fodjo JN, Aly E, et al. The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa. Front Immunol. 2021;12:803475. 10.3389/fimmu.2021.803475 . Falco-Walter JJ, Scheffer IE, Fisher RS. The new definition and classification of seizures and epilepsy. Epilepsy Res. 2018;139:73–9. 10.1016/j.eplepsyres.2017.11.015 . Kinney MO, Craig JJ, Kaplan PW. Hidden in plain sight: Non-convulsive status epilepticus-Recognition and management. Acta Neurol Scand. 2017;136(4):280–92. 10.1111/ane.12732 . Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus–Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23. 10.1111/epi.13121 . Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013;54(Suppl 6):28–9. 10.1111/epi.12270 . Wang X, Yang F, Chen B, et al. Non-convulsive seizures and non-convulsive status epilepticus in neuro-intensive care unit. Acta Neurol Scand. 2022;146(6):752–60. 10.1111/ane.13718 . Ghanem KG, Ram S, Rice PA. The Modern Epidemic of Syphilis. N Engl J Med. 2020;382(9):845–54. 10.1056/NEJMra1901593 . Zhao W, Luo H. Investigation of the role of interleukin 27 in the immune regulation of Treg and Th17 cells in neurosyphilis patients. Folia Neuropathol. 2023;61(4):387–95. 10.5114/fn.2023.132099 . Lukehart SA, Molini B, Gomez A, et al. Immunization with a tri-antigen syphilis vaccine significantly attenuates chancre development, reduces bacterial load, and inhibits dissemination of Treponema pallidum. Vaccine. 2022;40(52):7676–92. 10.1016/j.vaccine.2022.11.002 . Additional Declarations No competing interests reported. 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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-8680108","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":591766709,"identity":"df45303d-00ee-4bd2-a754-4c670320aab2","order_by":0,"name":"Xinyi Fei","email":"","orcid":"","institution":"Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Xinyi","middleName":"","lastName":"Fei","suffix":""},{"id":591766711,"identity":"1722ea30-6c30-44b5-9360-196736e15943","order_by":1,"name":"Xinxin Li","email":"","orcid":"","institution":"Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Xinxin","middleName":"","lastName":"Li","suffix":""},{"id":591766713,"identity":"947edfaa-2934-483d-9417-0e647760915b","order_by":2,"name":"Meiyan Shao","email":"","orcid":"","institution":"Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Meiyan","middleName":"","lastName":"Shao","suffix":""},{"id":591766714,"identity":"01faede0-f948-4409-a993-a60591a2384b","order_by":3,"name":"Rui Zhang","email":"","orcid":"","institution":"Beijing Jingmei Group General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Zhang","suffix":""},{"id":591766718,"identity":"8721584c-1d88-4a81-a1f2-6cffc93d498a","order_by":4,"name":"Shan Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYHACNiCW4GFjZj5g8ADEP0CcFgsZfna2BIMEErRU2Ej28xgwEKXF4Eb6swc/d0jwGBzm+VCQ2MYgx3cjgfFzAV4tOeaGvWdAWng3GAC1GEveSGCWnoFfC5sEbxtCS+KGGwlszDwEHCb5F6yF5wFISz0RWhLMpEG2SDbzMIC0JBgQ0iJ55o2ZtCxQCz8zm4FBwjkJw5lnHjZL49PCdxzosLdtdfZs/IefGXwos5HnO5588DM+LQoHEGw2A2AyANKMDXg0MDDII0kzP8CrdBSMglEwCkYsAABgoEgpYNuvggAAAABJRU5ErkJggg==","orcid":"","institution":"Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Shan","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2026-01-23 14:23:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8680108/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8680108/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102962526,"identity":"4d90c4b6-f3b0-457c-a347-e27d3b9bc05c","added_by":"auto","created_at":"2026-02-19 04:09:39","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":105958,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8680108/v1/b0999969315609176bd7c80f.jpeg"},{"id":102790833,"identity":"e63e55de-b162-4226-8dda-dc166889e91e","added_by":"auto","created_at":"2026-02-16 17:13:30","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":232704,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8680108/v1/d03c71438d5a7c872db573ec.jpeg"},{"id":102790832,"identity":"2cd87b24-78b0-43b7-a0b6-85ff5004b491","added_by":"auto","created_at":"2026-02-16 17:13:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":198593,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8680108/v1/be8add4e3f1cb490208a82d0.png"},{"id":102964850,"identity":"13832500-3e97-4ecf-a21e-a3a76c16ba77","added_by":"auto","created_at":"2026-02-19 04:28:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":852884,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8680108/v1/d06d0366-3705-42fb-8b39-1d575bf4a981.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neuro-Syphilis Initially Presenting as Non-convulsive Status Epilepticus: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNeurosyphilis, caused by the invasion of Treponema pallidum into the central nervous system, remains a formidable diagnostic challenge in modern neurology. Its moniker, \"the great imitator,\" is well-earned, as it can mimic a vast spectrum of neurological and psychiatric disorders, including dementia, stroke, myelopathy, and psychiatric illnesses\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The clinical presentation of neurosyphilis has evolved in the antibiotic era, with a higher prevalence of atypical and subtle manifestations, often leading to delayed or missed diagnosis.\u003c/p\u003e \u003cp\u003eWhile the relationship between neurosyphilis and seizures is established, the occurrence of status epilepticus is uncommon. Particularly, non-convulsive status epilepticus (NCSE)\u0026mdash;a state of prolonged seizure activity manifesting primarily as altered consciousness without prominent motor signs\u0026mdash;as the heralding presentation of neurosyphilis is a rare phenomenon. This presentation is perilous because its symptomatology, such as impaired consciousness and focal neurological deficits, can be indistinguishable from that of an acute large-vessel ischemic stroke. This similarity poses a critical risk, as the administration of thrombolytic therapy, which is standard for ischemic stroke, is contraindicated in the presence of seizures and could lead to catastrophic hemorrhagic complications if the underlying etiology is in fact NCSE.\u003c/p\u003e \u003cp\u003eThe purpose of this case report is to describe the clinical course, diagnostic challenges, and successful management of an elderly patient who presented with NCSE secondary to previously undiagnosed neurosyphilis. We aim to highlight the critical importance of including neurosyphilis in the differential diagnosis of NCSE to avoid misdiagnosis as cerebrovascular disease and to facilitate prompt, appropriate treatment.\u003c/p\u003e"},{"header":"Case","content":"\u003cp\u003e1. \u003cb\u003ePresentation\u003c/b\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003eA 67-year-old female presented acutely to our emergency department with a 4-hour history of episodic impaired consciousness and conjugate eye deviation. According to her family, the episodes began abruptly, without obvious provocation, and were characterized by unresponsiveness to verbal cues, ocular deviation, and akinesia. Each episode lasted several minutes and was repeated four times. Critically, her consciousness did not fully normalize between episodes. Associated symptoms included three episodes of nausea and vomiting, with coffee-ground emesis. She was transported via emergency medical services for further evaluation and was admitted to our neurology department for \"Altered Mental Status (Etiology Unknown).\" Her baseline health was unremarkable, with no significant recent weight change, and no abnormalities in mental status, diet, sleep, or bowel/bladder habits. Past medical history included an acute cerebral infarction five months prior, resulting in residual right-sided hemiparesis, manifested as clumsiness in right upper limb fine motor tasks and a slightly dragging gait.\u003c/p\u003e\n\u003ch3\u003e2. Physical Examination\u003c/h3\u003e\n\u003cp\u003eVital signs on admission: pulse 89 bpm, respiration 16 breaths/min, blood pressure 98/66mmHg. Neurologically, she was stuporous with mixed aphasia and was uncooperative. Both eyes demonstrated conjugate left gaze preference. Pupils were bilaterally constricted (approximately 1.5 mm) with absent direct and indirect light reflexes. Facial symmetry was preserved. Limb muscle tone was generally reduced. Muscle strength was graded 4/5 on the right and 5/5 on the left. Bilateral pathologic reflexes (Babinski sign) were present. Further detailed neurological assessment was limited by her uncooperative nature. The Mini-Mental State Examination (MMSE) score was 7.\u003c/p\u003e\n\u003ch3\u003e3. Diagnostic Investigations\u003c/h3\u003e\n\u003cp\u003eNon-contrast Head CT: Revealed lacunar infarcts in the bilateral basal ganglia and corona radiata; changes in the posterior horns of the lateral ventricles suggestive of possible hydrocephalus; white matter demyelination; and cerebral atrophy.\u003c/p\u003e \u003cp\u003eDiffusion-Weighted Imaging (DWI): Demonstrated slight hyperintensity in the left temporo-occipital gyrus with corresponding reduced signal on the ADC map(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA,B).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBrain MRI: Showed iso- to slightly hypointense T1 and hyperintense T2 signals in the left temporo-occipital lobe, with slight hyperintensity on FLAIR. Additionally, multiple lacunar infarcts were noted in the left thalamus, bilateral basal ganglia, corona radiata, and centrum semiovale, alongside other ischemic foci, white matter demyelination, ventricular dilatation (suggesting hydrocephalus)(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA,B,C.).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMagnetic Resonance Angiography (MRA): Indicated a relatively slender right vertebral artery compared to the left and focal mild stenosis in the P2 segment of the left middle cerebral artery.\u003c/p\u003e \u003cp\u003eChest CT: Showed nodular opacities in the left upper and lower lobes, potentially inflammatory; subpleural inflammation in the right upper, middle, and both lower lobes; linear scars in the right middle lobe and lingula; and bilateral pleural thickening.\u003c/p\u003e \u003cp\u003eVascular Ultrasound: Carotid and right subclavian artery atherosclerosis with plaque formation. Echocardiography revealed aortic sclerosis with mild aortic regurgitation and normal left ventricular systolic function. Lower extremity ultrasound confirmed bilateral arterial sclerosis.\u003c/p\u003e \u003cp\u003eLong-term Video-EEG Monitoring: Background activity showed low-amplitude 7\u0026ndash;8 Hz alpha rhythm over the occipital regions, suppressed by eye opening. Interictally, sharp waves, and slow-wave discharges were observed over the left fronto-temporal regions. No electrographic or clinical seizures were captured (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBlood Routine: Notable for leukocytosis (20.34\u0026times;10/L) with neutrophilia (93.3%) and lymphopenia (2.1%). Procalcitonin was elevated at 18 ng/mL. Lactate was 8.20 mmol/L. Serological tests were positive for Treponema pallidum antibody (26.07 S/CO) and RPR (titer 1:32). Routine biochemistry was unremarkable. Urine: Significant for pyuria and bacteriuria. Gastric Fluid: Occult blood positive.\u003c/p\u003e \u003cp\u003eCerebrospinal Fluid (CSF): Opening pressure 160 mmH\u003csub\u003e2\u003c/sub\u003eO. CSF was clear and colorless with a positive Pandy's test, pleocytosis (35 cells/\u0026micro;L), decreased glucose (2.7 mmol/L), elevated protein (0.64 g/L), and normal chloride. CSF RPR was positive (titer 1:16).\u003c/p\u003e \u003cp\u003eAutoimmune Encephalitis Antibody Panel: Negative.\u003c/p\u003e\n\u003ch3\u003e4. Diagnosis and Clinical Course\u003c/h3\u003e\n\u003cp\u003eBased on the constellation of clinical and paraclinical findings, the patient was diagnosed with neurosyphilis, syphilitic encephalitis, non-convulsive status epilepticus (NCSE), general paresis, stress-related gastrointestinal bleeding, and multiple lacunar infarcts.\u003c/p\u003e \u003cp\u003eTreatment included supportive care (gastrointestinal decompression, urinary catheterization), antiseizure medication (levetiracetam, 0.5 g twice daily), plaque stabilization (atorvastatin, 40 mg daily), and anti-syphilitic therapy (benzathine penicillin G, 2.4\u0026nbsp;million units IM weekly for 3 doses).\u003c/p\u003e \u003cp\u003eHer consciousness and motor function improved significantly following treatment. A follow-up examination noted clear consciousness, fluent speech, but persistent cognitive deficits (MMSE\u0026thinsp;=\u0026thinsp;7), bilateral miotic pupils with absent light reflexes, normal muscle tone, right-sided muscle strength of 4/5, and bilateral extensor plantar responses.\u003c/p\u003e\n\u003ch3\u003e5. Outcome\u003c/h3\u003e \u003cp\u003eAt discharge, the patient was afebrile, with motor function returned to pre-admission levels and no further seizures. Neurological examination findings were largely unchanged from the previous assessment, except for noted improvement in cognitive domains (calculation, memory, orientation).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis article reports a rare case of neurosyphilis. This elderly female patient initially presented with non-convulsive status epilepticus (NCSE), accompanied by complex conditions including syphilitic encephalitis, general paresis/paralytic dementia, and stress-related gastrointestinal bleeding. Combined with the stroke-like onset, status epilepticus, and related clinical signs, it was highly susceptible to misdiagnosis as a large-area cerebral infarction, undoubtedly posing significant challenges for diagnosis and treatment. However, due to the presence of seizures and active gastrointestinal bleeding, which are relative and absolute contraindications to thrombolysis, respectively, thrombolytic and antithrombotic therapies were not administered. Subsequently, symptoms such as fever and cognitive dysfunction suggested the possibility of an infectious or inflammatory etiology. Further cerebrospinal fluid and serum testing ultimately confirmed the diagnosis of neurosyphilis.\u003c/p\u003e \u003cp\u003eNeurosyphilis is a clinical syndrome caused by the invasion of the central nervous system by Treponema pallidum, characterized by variable and often non-specific symptoms, earning it the moniker \"the great imitator\"\u003csup\u003e1\u003c/sup\u003e. T. pallidum can invade the CNS within days of infection. Subsequent neurosyphilis can be asymptomatic or symptomatic. Neurosyphilis can manifest at any stage of the disease. Early infection often presents as aseptic meningitis or meningovascular syphilis. Late neurosyphilis most commonly presents as parenchymatous syphilis, specifically general paresis or tabes dorsalis\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Studies suggest that compared to syphilis patients without neurosyphilis or non-syphilis patients, neurosyphilis patients have significantly elevated levels of CD8\u0026thinsp;+\u0026thinsp;IFN-γ\u0026thinsp;+\u0026thinsp;cells in peripheral blood, while levels of Th2, Th9, CD8\u0026thinsp;+\u0026thinsp;IL-4+, CD8\u0026thinsp;+\u0026thinsp;IL-9+, and CD8\u0026thinsp;+\u0026thinsp;IL-17\u0026thinsp;+\u0026thinsp;cells are lower. Symptomatic neurosyphilis patients exhibit high expression of CD8\u0026thinsp;+\u0026thinsp;IFN-γ\u0026thinsp;+\u0026thinsp;cells and low expression of CD8\u0026thinsp;+\u0026thinsp;IL-17\u0026thinsp;+\u0026thinsp;cells, which might be a relevant mechanism for symptom manifestation\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. The temporal relationship between neurosyphilis syndromes and primary, secondary, or tertiary syphilis is not precise. Some patients have multiple sites of CNS involvement, and classifications often overlap.3 Reports indicate that the incidence of epilepsy as the initial symptom of neurosyphilis ranges from 14% to 60%, with status epilepticus being rare\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. NCSE, as the initial presentation, is even rarer.\u003c/p\u003e \u003cp\u003eCentral nervous system infection is one etiology of epilepsy. When pathogens enter the brain parenchyma, they can directly infect neurons, leading to neuronal lysis and death, and releasing pro-inflammatory cytokines and cellular products (like ATP or DNA-derived N-formyl peptides) that act as danger signals, activating autoimmunity and generating an adaptive immune response, resulting in neuronal damage or dysfunction\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. During the latent period between infection and seizure onset, a series of intracranial changes occur, including increased neuronal hyperexcitability driven by NMDA receptors and other glutamate-mediated mechanisms, neuronal loss and gliosis, molecular and structural reorganization, and epigenetic reprogramming. All these processes can ultimately lead to recurrent unprovoked seizures\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The structural brain damage caused by these CNS infections may form an epileptogenic focus, serving as the organic basis for recurrent epilepsy\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNon-convulsive status epilepticus (NCSE) is traditionally defined as continuous non-convulsive seizure activity lasting 30 minutes or recurrent seizures without regaining consciousness in the interictal periods. Recently, a proposal to shorten the duration to 5 minutes has been made, but it is not universally accepted\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. In 2015, the ILAE classified NCSE as NCSE in coma and NCSE without coma. NCSE without coma is further subdivided into generalized (typical absence status epilepticus, atypical absence status epilepticus, myoclonic absence status epilepticus) and focal origin (absence status epilepticus of focal origin, focal status epilepticus without impaired awareness, focal status epilepticus with impaired awareness), and autonomic NCSE of unknown origin\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Diagnosis primarily relies on clinical manifestations and EEG. The Salzburg Consensus Criteria for NCSE propose EEG diagnostic criteria for patients without epileptic encephalopathy: 1. Epileptiform discharges\u0026thinsp;\u0026gt;\u0026thinsp;2.5 Hz; OR 2. Epileptiform discharges\u0026thinsp;\u0026le;\u0026thinsp;2.5 Hz or rhythmic delta/theta activity (\u0026gt;\u0026thinsp;0.5 Hz) AND one of the following: a. EEG and clinical improvement after IV antiseizure drugs (ASDs), b. Presence of subtle clinical ictal phenomena during the aforementioned EEG patterns, or c. Typical spatiotemporal evolution\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. As sufficient clinical trials for NCSE treatment are still lacking, the optimal treatment regimen has not been established. Rapid termination of epileptic activity is the primary goal in treating NCSE patients in the neuro-ICU. Benzodiazepines are typically used as first-line treatment for NCSE\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The patient reported here presented to our emergency department with episodic consciousness disturbance and eye deviation for 4 hours. The episodes involved altered consciousness, and consciousness did not return to normal during the interictal periods, without convulsive limb activity. EEG showed abnormal waves in the left temporo-occipital region, with a frequency\u0026thinsp;\u0026gt;\u0026thinsp;2.5 Hz, consistent with the high signal in the left temporo-occipital lobe on MRI. Therefore, NCSE was considered. After administration of antiseizure medication, no further seizures occurred.\u003c/p\u003e \u003cp\u003eTreatment guidelines for neurosyphilis from the US, UK, Europe, and China emphasize penicillin as the first-line drug for immunocompetent patients. After administering Benzathine Penicillin to this patient, her symptoms improved significantly. Ceftriaxone is the only alternative recommended by the US CDC for penicillin-allergic patients. Azithromycin has been shown to be effective for early syphilis in several randomized trials; however, resistance to azithromycin and other macrolides (A\u0026rarr;G mutation at position 2058 or 2059 in 23S ribosomal DNA) has been detected globally, and azithromycin should no longer be used for syphilis in most clinical settings\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. A recent retrospective study on neurosyphilis investigated mRNA expression, levels of IL-27, IL-17, Th17, IL-17-producing CD4\u0026thinsp;+\u0026thinsp;T cells, and CSF protein concentration and VDRL. Results showed a significant inverse relationship between CSF protein/VDRL concentration and CSF IL-27 levels, supporting the therapeutic potential of IL-27 in neurosyphilis and inflammatory processes\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. For the prevention of neurosyphilis, a syphilis vaccine that prevents T. pallidum dissemination from the infection site could protect individuals from subsequent disease stages and progression to neurosyphilis. Studies show that immunization with a TprC/TprK/Tp0751 triple-antigen mixture can protect animals from progressive syphilitic lesions and significantly inhibit infection dissemination, although complete immunity has not yet been achieved\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe clinical manifestations of neurosyphilis lack specificity. Diagnosis is primarily based on specific clinical features, serum, and CSF tests. Patients often conceal infectious disease history and may lack skin lesions. Elderly patients often have cerebrovascular disease risk factors, and a head MRI may coincidentally show cerebral infarction lesions. Patients may also refuse a lumbar puncture for further investigation. Consequently, neurosyphilis is often misdiagnosed as cerebrovascular disease. In summary, the clinical presentation of neurosyphilis is complex and variable, often posing significant diagnostic challenges, leading to misdiagnosis, missed diagnosis, and delayed treatment. History-taking should pay attention to personal history. Serum and CSF syphilis tests should be promptly completed to achieve early diagnosis and treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCSE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-convulsive Status Epilepticus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral Nervous System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectroencephalogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebrospinal Fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNMDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eN Methyl D Aspartate.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eNot applicable. This is a single case report with no experimental intervention.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for Publication\u003c/strong\u003e \u003cp\u003e Written informed consent were signed and obtained from the patient prior to writing and submission for publication. Sociodemographic and clinical data have been de-identified to protect patients\u0026rsquo; privacy.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe author(s) report no conflicts of interest in this work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was received for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXF was responsible for collecting clinical data, drafting the manuscript, selecting appropriate journals, and submitting the manuscript. XL contributed to clinical decision-making and case analysis. MS also participated in diagnosis and treatment, as well as assisting with clinical data collection. RZ was involved in gathering reference materials, while SY participated in case management, analysis, and manuscript revision.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe successful completion of this case report was made possible through the collaborative efforts and steadfast support of a multidisciplinary team. We wish to extend our sincere gratitude to our colleagues from the Department of Neurology, Emergency Medicine, Laboratory Medicine, and Radiology for their exceptional professional support and expertise provided throughout the patient's diagnostic and therapeutic journey. Furthermore, we are deeply thankful to the patient's family for their active participation in providing a detailed medical history and for their cooperation during the treatment process, which was instrumental in clarifying complex clinical challenges.We hereby express our earnest appreciation to all peers and medical professionals who contributed to the management and scholarly discussion of this case.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eAll data supporting the conclusions of this article are included within the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJancar N, Simoes M, Goncalves F, et al. Neurosyphilis: The Great Imitator. 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Vaccine. 2022;40(52):7676\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.vaccine.2022.11.002\u003c/span\u003e\u003cspan address=\"10.1016/j.vaccine.2022.11.002\" 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":false,"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":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neurosyphilis, Non-Convulsive Status Epilepticus, Syphilitic encephalitis, General paresis, Antibiotic therapy, Diagnostic challenge, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-8680108/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8680108/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eNeurosyphilis is a renowned \"great imitator\" in clinical practice. While it can cause seizures, its presentation as non-convulsive status epilepticus (NCSE) is exceptionally rare and diagnostically challenging.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 67-year-old female with a history of prior cerebral infarction presented acutely with recurrent episodes of impaired consciousness and conjugate eye deviation, without convulsive limb movements. Critically, her consciousness did not fully normalize between episodes. Neurological examination revealed stupor, mixed aphasia, bilateral miotic pupils with absent light reflexes, and bilateral Babinski signs. Neuroimaging (MRI) showed findings suggestive of prior infarcts and possible hydrocephalus. Long-term video-EEG monitoring revealed epileptiform discharges over the left temporo-occipital region, fulfilling diagnostic criteria for NCSE. Serological and cerebrospinal fluid (CSF) analysis confirmed active neurosyphilis (positive serum and CSF RPR). The patient was diagnosed with neurosyphilis presenting as NCSE, alongside syphilitic encephalitis and general paresis. Treatment with benzathine penicillin G and levetiracetam led to significant improvement in consciousness and cessation of seizure activity.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eThis case underscores that neurosyphilis must be considered in the differential diagnosis of NCSE, especially in patients with stroke-like symptoms but with contraindications to thrombolysis. Early CSF analysis and syphilis serology are critical for accurate diagnosis and timely initiation of antibiotic therapy, which can prevent permanent neurological damage. It emphasizes the importance of considering infectious etiologies in cases of unexplained altered mental status and seizures.\u003c/p\u003e","manuscriptTitle":"Neuro-Syphilis Initially Presenting as Non-convulsive Status Epilepticus: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 17:13:25","doi":"10.21203/rs.3.rs-8680108/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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