Cerebellar Ataxia as the Initial Manifestation of Anti-NMDAR Encephalitis Without Prodrome: A Case report

Cerebellar Ataxia as the Initial Manifestation of Anti-NMDAR Encephalitis Without Prodrome: 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 Cerebellar Ataxia as the Initial Manifestation of Anti-NMDAR Encephalitis Without Prodrome: A Case report Ayesha Panigrahi, Ayesha Mubeen Farooq, Sameer Kumar Majety, Mohammed Zain Alam, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8757814/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially reversible autoimmune encephalitis, most commonly affecting young women and children. It typically follows a prodromal illness and progresses to prominent neuropsychiatric symptoms, movement disorders, seizures, and autonomic instability. While cerebellar ataxia may occur during the disease course, it is rarely the initial or isolated presenting feature, particularly in adults, and may result in diagnostic delay. Case Presentation: We report a case of a woman in her 20s with no prior medical history who presented with progressive cerebellar ataxia, including unsteady gait and impaired fine motor coordination, without preceding systemic or prodromal symptoms. Three days after admission, she developed a generalised tonic-clonic seizure followed by rapid-onset behavioural changes, hallucinations, and cognitive decline. Neurological examination revealed cerebellar signs including dysmetria, horizontal nystagmus, and a positive Romberg test. Brain MRI was unremarkable. Electroencephalography showed diffuse delta slowing. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and tested positive for anti-NMDAR antibodies. There was no evidence of malignancy on pelvic ultrasound or CT imaging. The patient was treated with first-line immunotherapy, including intravenous immunoglobulin and corticosteroids. Her neuropsychiatric symptoms improved significantly over the following two weeks. At one-month follow-up, she had near-complete recovery in mobility and cognition. Conclusion: This case highlights an unusual adult presentation of anti-NMDAR encephalitis in which cerebellar ataxia appeared before other symptoms. Clinicians should consider autoimmune encephalitis in patients with isolated cerebellar signs followed by rapid neurological decline, even without prodromal features or imaging abnormalities. Early diagnosis and prompt immunotherapy are essential for favourable outcomes. Anti-NMDAR encephalitis Cerebellar ataxia Autoimmune encephalitis Atypical presentation Immunotherapy Figures Figure 1 Figure 2 Figure 3 Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a treatable form of autoimmune encephalitis, is typically seen in young females and children and commonly follows a characteristic clinical pattern. This pattern includes a prodrome resembling a viral illness, followed by the onset of neuropsychiatric manifestations, sleep disturbances, movement disorders, seizures, autonomic instability, and central hypoventilation [ 1 , 4 ]. Seizures represent a common manifestation of the disease and often serve as an early trigger for neurological evaluation [ 7 ]. Additionally, a close association with ovarian teratomas has been recognised in females, with approximately one-third of patients reported to have an underlying tumour [ 3 ]. Cerebellar dysfunction, manifesting as ataxia, has been reported in the paediatric population early in the disease course but remains an atypical presenting feature in adults [ 5 , 14 ]. When cerebellar involvement occurs, it is usually accompanied by other neurological or behavioural abnormalities, rather than presenting in isolation. This disorder must be distinguished from primary psychiatric and other neurological conditions through careful clinical assessment, as overlapping symptoms can lead to misdiagnosis or delayed initiation of appropriate therapy [ 6 ]. Here, we report a unique case of anti-NMDAR encephalitis in a woman in her 20s, who presented exclusively with solitary cerebellar dysfunction manifesting as an unsteady gait. Notably, there were no preceding prodromal symptoms, neuropsychiatric features, or identifiable ovarian teratoma, distinguishing this presentation from the more commonly recognised clinical spectrum of anti-NMDAR encephalitis. Case presentation A woman in her 20s with no significant past medical history was admitted following a generalised tonic-clonic seizure. Collateral history obtained from family members indicated that the episode began with a sudden loud cry, after which she was found lying on the floor with outstretched limbs, frothing at the mouth, and upward rolling of the eyes. The seizure lasted approximately one to two minutes and was followed by postictal drowsiness lasting around 30 minutes. On detailed history-taking, the patient reported progressive unsteadiness of gait for seven days prior to admission. This was characterised by frequent loss of balance and swaying to either side while walking. She also described gradual instability of both hands, affecting fine motor tasks, consistent with a cerebellar ataxic process. Speech and sensory modalities remained unaffected at this stage. Within three days of admission, the family observed behavioural changes. The patient became increasingly irritable, had sudden episodes of crying, and began experiencing auditory and visual hallucinations. She subsequently developed multiple seizure episodes, prompting escalation of anti epileptic therapy. Despite this, her sensorium progressively deteriorated over the following week. She became drowsy, was unable to recognise family members, and responded only to painful stimuli. Hearing, vision, olfaction, and other cranial nerve functions remained intact. Neurological examination (Table 2, and Fig. 3 ) revealed bilateral horizontal nystagmus, a positive Romberg test, rebound phenomenon, and dysmetria on finger-to-nose testing, collectively suggestive of cerebellar dysfunction. The Mini-Mental State Examination score (Table 1 ) was 27 out of 30 on the first day of admission. By day three, there was a marked decline in cognitive function, including impaired verbal fluency, reduced spontaneous speech, inability to follow pointing commands, impaired gesture imitation, and loss of reading and writing abilities. She was unable to recall her location, the date, or recent events. Remote memories remained preserved, including recollection of her place of birth and details about her family and schooling. One week after admission, the Mini-Mental State Examination score had declined to 12 out of 30, and by day 14 formal cognitive assessment was no longer possible as the patient progressed to a stuporous state. Table 1 Evolution of higher mental functions and Mini-Mental State Examination scores. Cognitive domain Day 1 Day 3 Day 7 Day 14 Level of consciousness Alert Alert Drowsy Stuporous MMSE score 27/30 - 12/30 Not testable Orientation Intact Impaired (time, place Severely impaired Not testable Attention Mildly reduced Markedly impaired Severely impaired Not testable Language output Normal Reduced, scanning dysarthria Minimal Not testable Comprehension Intact Impaired (pointing commands lost) Severely impaired Not testable Repetition Intact Lost Lost Not testable Reading Intact Reading aloud preserved, comprehension lost Lost Not testable Writing Intact Unable Unable Not testable Recent memory Intact Impaired Severely impaired Not testable Remote memory Preserved Preserved Preserved Not testable Praxis Intact Ideomotor apraxia present Worsened Not testable Executive function Intact Impaired (abstraction, judgement) Severely impaired Not testable Table 2: Neurological examination findings during the disease course. Neurological system Findings Cranial nerves Intact; vision, hearing, smell, facial movements, swallowing preserved Motor system Normal bulk, tone, and power in all four limbs Sensory system Fine touch, pain, temperature, vibration, and joint position sense intact Cerebellar signs Bilateral gaze-evoked horizontal nystagmus, positive finger–nose and heel–shin tests, rebound phenomenon present, positive Romberg sign Meningeal signs Absent Cortical sensory functions Impaired interpretation in later course Autonomic nervous system No autonomic dysfunction A comprehensive laboratory evaluation, including renal and liver function tests, was unremarkable except for mild anemia and elevated inflammatory markers. Cerebrospinal fluid analysis demonstrated lymphocytic pleocytosis, with negative results for viral pathogens including herpes simplex virus, Japanese encephalitis virus, and varicella zoster virus, as well as no bacterial growth. Cerebrospinal fluid autoimmune encephalitis testing was positive for anti-N-methyl-D-aspartate receptor antibodies. The timeline of clinical presentation, investigations, and treatment course was illustrated in Fig. 1 . Investigations The acute onset of behavioural disturbances and rapidly progressive deterioration in sensorium suggested a diagnosis more complex than isolated cerebellar ataxia, warranting a comprehensive laboratory and imaging evaluation to enable prompt diagnosis and targeted management. Routine laboratory investigations revealed mild anaemia (Hb = 11.2) and elevated inflammatory markers. Renal and liver function tests, as well as serum electrolytes, were within normal limits. Antinuclear antibody screening and infectious disease work-up, including blood and urine cultures, were unremarkable. Imaging studies, including contrast-enhanced magnetic resonance imaging of the brain (Fig. 2 ), computed tomography of the chest, and ultrasonography of the abdomen and pelvis, did not reveal any abnormalities. Electroencephalography demonstrated diffuse slowing with predominant delta activity, suggestive of an underlying encephalopathic process. Given the constellation of clinical features and normal structural neuroimaging, cerebrospinal fluid analysis was pursued. Cerebrospinal fluid examination demonstrated lymphocytic pleocytosis with normal glucose levels, with negative testing for viral pathogens including herpes simplex virus, Japanese encephalitis virus, and varicella zoster virus, and no evidence of bacterial growth. Autoimmune encephalitis testing of the cerebrospinal fluid was positive for anti-N-methyl-D-aspartate receptor antibodies. Differential diagnosis Given the overlapping features of autoimmune, infectious, metabolic, and paraneoplastic aetiologies, a broad and systematic diagnostic approach was adopted to determine the underlying cause of the encephalopathy. The concurrent presence of seizures and altered sensorium raised initial suspicion for viral encephalitis, particularly herpes simplex virus and varicella zoster virus. The preceding history of cerebellar ataxia also prompted consideration of bacterial infections such as Listeria monocytogenes, Mycoplasma pneumoniae, and Borrelia burgdorferi, which can involve the cerebellum and present with rhombencephalitis. However, the absence of a prodromal febrile illness, together with negative cerebrospinal fluid and serum studies including polymerase chain reaction testing, cultures, and serology, and normal magnetic resonance imaging findings, effectively excluded these infectious aetiologies [ 9 , 10 ]. Cerebellar ataxia has been described in several autoimmune encephalitides, including anti-glutamic acid decarboxylase 65 antibody–associated encephalitis and anti-contactin-associated protein-like 2 antibody–associated disease [ 11 ]. However, cerebellar involvement occurs in only approximately 5 percent of patients with anti-N-methyl-D-aspartate receptor encephalitis, highlighting that ataxia is an uncommon presenting feature in this subtype [ 8 ]. Anti-glutamic acid decarboxylase 65 antibody–associated cerebellar ataxia is frequently associated with type 1 diabetes mellitus or other autoimmune disorders and typically lacks prominent psychiatric manifestations, while anti-contactin-associated protein-like 2 antibody–associated disease predominantly affects older men and is characterised by peripheral nerve hyperexcitability and autonomic dysfunction [ 12 , 13 ]. In this patient, both serum and cerebrospinal fluid testing were negative for anti-glutamic acid decarboxylase 65 and anti-contactin-associated protein-like 2 antibodies, making these diagnoses unlikely. Other autoimmune causes, including lupus cerebritis, Hashimoto’s encephalopathy, and paraneoplastic autoimmune encephalitis, were considered but deemed unlikely due to negative antinuclear antibody titres, non-reactive thyroid antibody testing, and the absence of systemic features [ 2 ]. Metabolic encephalopathies, such as hepatic and uraemic encephalopathy, were excluded on the basis of normal liver and renal function tests. Toxic or drug-induced encephalopathy was also considered unlikely, given the absence of relevant exposure history and a negative toxicology screen. Given the patient’s age and emerging behavioural changes, a primary psychiatric disorder, including acute psychosis, was initially considered [ 15 ]. However, the atypical neurological presentation with early isolated cerebellar ataxia, followed by rapid cognitive decline and neuropsychiatric deterioration, argued against a primary psychiatric diagnosis. The combination of progressive speech dysfunction, abnormal electroencephalography demonstrating diffuse delta slowing, lymphocytic pleocytosis in the cerebrospinal fluid, and the detection of anti-N-methyl-D-aspartate receptor antibodies fulfilled established diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis, supporting this diagnosis as the unifying explanation for the patient’s clinical course [ 16 ]. Treatment Following multiple seizure episodes on day 3, levetiracetam was administered intravenously at a dose of 1.5 g/ day. On day 14, the patient was initiated on first-line immunotherapy , consisting of intravenous immunoglobulin at a dose of 0.4 g per kilogram per day for five days and intravenous methylprednisolone at a dose of 1 g per day for five days, followed by a course of oral corticosteroids. Levetiracetam was continued at a standard maintenance dose of 500 mg twice daily. Outcome and follow-up Outcome and follow-up After gradual improvement in neuropsychiatric symptoms over two weeks of treatment, the patient was discharged on an oral corticosteroid regimen. At one month following discharge, she was able to ambulate independently, although mild residual gait instability persisted. Upper limb coordination and hand stability had improved, allowing better performance of fine motor tasks. The patient’s cognitive function had largely recovered, and speech was fluent. Neurological examination revealed no evidence of nystagmus. Repeat laboratory investigations, including cerebrospinal fluid analysis, were performed during follow-up. Based on ongoing clinical improvement, the patient was continued on oral corticosteroid therapy with a gradual taper. Discussion This case report describes an unusual presentation of anti-N-methyl-D-aspartate receptor encephalitis , with isolated cerebellar ataxia as the initial manifestation. The absence of prodromal symptoms, systemic features, or an underlying neoplasm posed a significant diagnostic challenge, particularly in the early stages when characteristic neuropsychiatric features are typically expected. Anti-N-methyl-D-aspartate receptor encephalitis is a rare form of autoimmune encephalitis reported across all age groups but classically affects females in the third and fourth decades of life. Although the estimated incidence is approximately one case per 1.5 million individuals annually, it has been reported to occur more frequently than any infectious form of encephalitis in adults over 30 years of age [ 17 ]. A strong association with ovarian teratomas has been described, with approximately 50 percent of affected women reported to have an underlying tumour. Classically, the disease progresses through five clinical phases, beginning with a prodromal phase resembling a viral illness, followed by psychiatric symptoms and seizures, an unresponsive or catatonic phase, a hyperkinetic phase characterised by movement disorders and autonomic instability, and finally a recovery phase. The recovery phase typically begins after several months of immunotherapy and supportive treatment. The pathogenic mechanism involves immunoglobulin G antibodies, predominantly IgG1 and IgG3 subclasses, directed against the NR1 subunit of the N-methyl-D-aspartate receptor, leading to receptor internalisation. This process results in reduced neuronal calcium signalling and diminished receptor-mediated synaptic currents [ 15 ]. While cerebellar ataxia has been reported as a presenting feature of anti-N-methyl-D-aspartate receptor encephalitis in the paediatric population, and more commonly later in the disease course, it occurs very rarely in adults [ 6 ]. An observational cohort study involving 577 patients demonstrated that cerebellar ataxia was an atypical manifestation, occurring in approximately 5 percent of adolescents and 2 percent of adults [ 8 ]. A similar presentation was described in a woman in her 30s with isolated brainstem and cerebellar symptoms that did not progress to neuropsychiatric manifestations [ 5 ]. Another case reported anti-N-methyl-D-aspartate receptor encephalitis presenting with cerebellar symptoms in a woman in her 30s with a history of recurrent ovarian teratomas [ 14 ]. An additional report described gait ataxia associated with hyperintense cerebellar lesions on magnetic resonance imaging [ 18 ]. These reports highlight the heterogeneity of clinical presentations associated with anti-N-methyl-D-aspartate receptor encephalitis. In contrast to previously reported cases, our patient presented with isolated cerebellar dysfunction without radiological evidence of cerebellar involvement, had no history of ovarian teratoma, and progressed rapidly to develop neuropsychiatric symptoms, reaching a stuporous state within one week. This case emphasises the need to consider anti-N-methyl-D-aspartate receptor encephalitis even in the absence of prodromal symptoms or classical neuropsychiatric features when unexplained cerebellar ataxia is followed by rapid neurological deterioration. Conclusion This case underscores that anti-N-methyl-D-aspartate receptor encephalitis can initially manifest with isolated cerebellar ataxia in adults, preceding the onset of typical neuropsychiatric features. The absence of a prodromal illness or associated ovarian teratoma should not preclude consideration of the diagnosis. Additionally, normal neuroimaging does not exclude autoimmune encephalitis, highlighting the importance of cerebrospinal fluid analysis and antibody testing in patients with compatible clinical features. Early recognition and timely initiation of immunotherapy can lead to substantial neurological improvement, even in atypical presentations. Limitations This report has several limitations. As a single case, the findings may not be generalisable to all presentations of anti-N-methyl-D-aspartate receptor encephalitis. Advanced investigations such as serial antibody titres and long-term neuropsychological assessments were not available, which may have provided additional insight into disease evolution and recovery. Furthermore, although follow-up demonstrated significant clinical improvement, longer-term outcomes could not be assessed at the time of reporting. Despite these limitations, the case provides valuable clinical insight into an atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis and highlights important diagnostic consideration Patient Perspective: [As elicited in the patient’s own language and translated to English] I was completely healthy before this illness. A week before admission, I noticed imbalance while walking and hand tremors but thought it was just fatigue. After a seizure, I was brought to the hospital. I don’t remember much, but my family said my behavior changed and worsened. I was later diagnosed with a rare condition and started treatment. I gradually improved, recognised my family again, and the seizures stopped. I was discharged after two weeks and have been recovering well. I’m grateful to the doctors for their timely care. Abbreviations CT- Computed Tomography FLAIR- Fluid-Attenuated Inversion Recovery Hb – Haemoglobin IgG - Immunoglobulin G IgG1 – Immunoglobulin G subclass 1 IgG3 – Immunoglobulin G subclass 3 MMSE- Mini-Mental State Examination MRI- Magnetic Resonance Imaging NMDAR- Anti-N-methyl-D-aspartate receptor NR1 - N-methyl-D-aspartate receptor subunit 1 Declarations a) Ethics Statement : This case report was conducted in accordance with the principles outlined in the Declaration of Helsinki. Institutional Ethics Committee (IEC) approval was not required for this single case report as per institutional regulations. b) Consent for publication : Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. c) Acknowledgments : None d) Funding : No funding received. e) Conflict of Interest Statement :The authors declare no conflict of interest. f) Availability of data and materials : The data regarding the patient can be submitted by the corresponding author upon reasonable request. Author Contribution Conception or design of the work: Panigrahi A and Majety SKFirst Draft of the article: Panigrahi A, Farooq AM, and Alam MZCritical revision of the article: Majety SK and Muppana GSupervision of article: Majety SK, Muppana G, and Panigrahi AProject Administration: Panigrahi A, Farooq AM, and Alam MZ.Final approval of the version to be published: All Authors Responsibility of the material: All authors References Kumari K, Sahni N, Kumari V, Saini V. Anti-N-Methyl-D-Aspartate-Receptor Encephalitis in Young Females. Turk J Anaesthesiol Reanim. 2017;45(6):377–9. 10.5152/TJAR.2017.74508 . 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PMID: 32590126. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 02 May, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviews received at journal 19 Mar, 2026 Reviewers agreed at journal 19 Mar, 2026 Reviews received at journal 15 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers invited by journal 04 Feb, 2026 Editor invited by journal 03 Feb, 2026 Editor assigned by journal 03 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 01 Feb, 2026 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. 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16:53:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8757814/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8757814/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102296994,"identity":"8ecd07e9-25ff-4abe-82d5-814f4cc0e28e","added_by":"auto","created_at":"2026-02-10 10:24:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":143753,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTimeline of clinical presentation, investigations, and treatment course.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8757814/v1/a4e7efce4ba67e08c8aafb3f.png"},{"id":102209786,"identity":"ca99cfb7-01a7-41a8-8f2d-1bd895c0f5a4","added_by":"auto","created_at":"2026-02-09 12:14:14","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4216774,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAxial brain MRI images showing normal cortical and subcortical signal intensities.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A–D) demonstrate preserved brain parenchyma with no evidence of diffusion restriction, mass effect, or pathological FLAIR hyperintensities.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8757814/v1/9fb025d1ccf926f6fddcd2d2.jpg"},{"id":102209785,"identity":"23d8db58-6933-46c7-a98f-8a20f802b12d","added_by":"auto","created_at":"2026-02-09 12:14:14","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2161337,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNeuropsychological assessment drawings indicating visuospatial and executive dysfunction.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Distorted intersecting pentagons and 3D cube;\u003c/p\u003e\n\u003cp\u003e(B) Clock drawing with misplaced numbers and incorrect time setting;\u003c/p\u003e\n\u003cp\u003e(C) Trail Making Test showing disorganized sequencing and impaired set-shifting;\u003c/p\u003e\n\u003cp\u003e(D) Irregular alternating line pattern in the Luria hand sequence task.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8757814/v1/7e380d6ef82c4dbe005a931a.jpg"},{"id":102301744,"identity":"9a1b1061-0432-46a4-86af-8770f21b7151","added_by":"auto","created_at":"2026-02-10 11:23:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7198648,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8757814/v1/2869f3ee-3fb7-4f94-b9fb-9834869a8547.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebellar Ataxia as the Initial Manifestation of Anti-NMDAR Encephalitis Without Prodrome: A Case report","fulltext":[{"header":"Background","content":"\u003cp\u003eAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a treatable form of autoimmune encephalitis, is typically seen in young females and children and commonly follows a characteristic clinical pattern. This pattern includes a prodrome resembling a viral illness, followed by the onset of neuropsychiatric manifestations, sleep disturbances, movement disorders, seizures, autonomic instability, and central hypoventilation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Seizures represent a common manifestation of the disease and often serve as an early trigger for neurological evaluation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Additionally, a close association with ovarian teratomas has been recognised in females, with approximately one-third of patients reported to have an underlying tumour [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCerebellar dysfunction, manifesting as ataxia, has been reported in the paediatric population early in the disease course but remains an atypical presenting feature in adults [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. When cerebellar involvement occurs, it is usually accompanied by other neurological or behavioural abnormalities, rather than presenting in isolation. This disorder must be distinguished from primary psychiatric and other neurological conditions through careful clinical assessment, as overlapping symptoms can lead to misdiagnosis or delayed initiation of appropriate therapy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we report a unique case of anti-NMDAR encephalitis in a woman in her 20s, who presented exclusively with solitary cerebellar dysfunction manifesting as an unsteady gait. Notably, there were no preceding prodromal symptoms, neuropsychiatric features, or identifiable ovarian teratoma, distinguishing this presentation from the more commonly recognised clinical spectrum of anti-NMDAR encephalitis.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA woman in her 20s with no significant past medical history was admitted following a generalised tonic-clonic seizure. Collateral history obtained from family members indicated that the episode began with a sudden loud cry, after which she was found lying on the floor with outstretched limbs, frothing at the mouth, and upward rolling of the eyes. The seizure lasted approximately one to two minutes and was followed by postictal drowsiness lasting around 30 minutes.\u003c/p\u003e\n\u003cp\u003eOn detailed history-taking, the patient reported progressive unsteadiness of gait for seven days prior to admission. This was characterised by frequent loss of balance and swaying to either side while walking. She also described gradual instability of both hands, affecting fine motor tasks, consistent with a cerebellar ataxic process. Speech and sensory modalities remained unaffected at this stage.\u003c/p\u003e\n\u003cp\u003eWithin three days of admission, the family observed behavioural changes. The patient became increasingly irritable, had sudden episodes of crying, and began experiencing auditory and visual hallucinations. She subsequently developed multiple seizure episodes, prompting escalation of anti epileptic therapy. Despite this, her sensorium progressively deteriorated over the following week. She became drowsy, was unable to recognise family members, and responded only to painful stimuli. Hearing, vision, olfaction, and other cranial nerve functions remained intact.\u003c/p\u003e\n\u003cp\u003eNeurological examination (Table\u0026nbsp;2, and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) revealed bilateral horizontal nystagmus, a positive Romberg test, rebound phenomenon, and dysmetria on finger-to-nose testing, collectively suggestive of cerebellar dysfunction. The Mini-Mental State Examination score (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) was 27 out of 30 on the first day of admission. By day three, there was a marked decline in cognitive function, including impaired verbal fluency, reduced spontaneous speech, inability to follow pointing commands, impaired gesture imitation, and loss of reading and writing abilities. She was unable to recall her location, the date, or recent events. Remote memories remained preserved, including recollection of her place of birth and details about her family and schooling. One week after admission, the Mini-Mental State Examination score had declined to 12 out of 30, and by day 14 formal cognitive assessment was no longer possible as the patient progressed to a stuporous state.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eEvolution of higher mental functions and Mini-Mental State Examination scores.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCognitive domain\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDay 1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDay 3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDay 7\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDay 14\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLevel of consciousness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlert\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlert\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDrowsy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStuporous\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMMSE score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27/30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12/30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOrientation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImpaired (time, place\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverely impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAttention\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMildly reduced\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMarkedly impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverely impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLanguage output\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReduced, scanning dysarthria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMinimal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComprehension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImpaired (pointing commands lost)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverely impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRepetition\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLost\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLost\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReading\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReading aloud preserved, comprehension lost\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLost\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWriting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnable\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnable\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecent memory\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImpaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverely impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRemote memory\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreserved\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreserved\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreserved\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePraxis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIdeomotor apraxia present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWorsened\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eExecutive function\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntact\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImpaired (abstraction, judgement)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverely impaired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot testable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Neurological examination findings during the disease course.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable width=\"624\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e\u003cstrong\u003eNeurological system\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003e\u003cstrong\u003eFindings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eCranial nerves\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eIntact; vision, hearing, smell, facial movements, swallowing preserved\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eMotor system\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eNormal bulk, tone, and power in all four limbs\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eSensory system\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eFine touch, pain, temperature, vibration, and joint position sense intact\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eCerebellar signs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eBilateral gaze-evoked horizontal nystagmus, positive finger\u0026ndash;nose and heel\u0026ndash;shin tests, rebound phenomenon present, positive Romberg sign\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eMeningeal signs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eAbsent\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eCortical sensory functions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eImpaired interpretation in later course\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eAutonomic nervous system\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"422\"\u003e\n\u003cp\u003eNo autonomic dysfunction\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eA comprehensive laboratory evaluation, including renal and liver function tests, was unremarkable except for mild anemia and elevated inflammatory markers. Cerebrospinal fluid analysis demonstrated lymphocytic pleocytosis, with negative results for viral pathogens including herpes simplex virus, Japanese encephalitis virus, and varicella zoster virus, as well as no bacterial growth. Cerebrospinal fluid autoimmune encephalitis testing was positive for anti-N-methyl-D-aspartate receptor antibodies.\u003c/p\u003e\n\u003cp\u003eThe timeline of clinical presentation, investigations, and treatment course was illustrated in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eInvestigations\u003c/h2\u003e\n\u003cp\u003eThe acute onset of behavioural disturbances and rapidly progressive deterioration in sensorium suggested a diagnosis more complex than isolated cerebellar ataxia, warranting a comprehensive laboratory and imaging evaluation to enable prompt diagnosis and targeted management.\u003c/p\u003e\n\u003cp\u003eRoutine laboratory investigations revealed mild anaemia (Hb\u0026thinsp;=\u0026thinsp;11.2) and elevated inflammatory markers. Renal and liver function tests, as well as serum electrolytes, were within normal limits. Antinuclear antibody screening and infectious disease work-up, including blood and urine cultures, were unremarkable.\u003c/p\u003e\n\u003cp\u003eImaging studies, including contrast-enhanced magnetic resonance imaging of the brain (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), computed tomography of the chest, and ultrasonography of the abdomen and pelvis, did not reveal any abnormalities. Electroencephalography demonstrated diffuse slowing with predominant delta activity, suggestive of an underlying encephalopathic process.\u003c/p\u003e\n\u003cp\u003eGiven the constellation of clinical features and normal structural neuroimaging, cerebrospinal fluid analysis was pursued. Cerebrospinal fluid examination demonstrated lymphocytic pleocytosis with normal glucose levels, with negative testing for viral pathogens including herpes simplex virus, Japanese encephalitis virus, and varicella zoster virus, and no evidence of bacterial growth. Autoimmune encephalitis testing of the cerebrospinal fluid was positive for anti-N-methyl-D-aspartate receptor antibodies.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eDifferential diagnosis\u003c/h3\u003e\n\u003cp\u003eGiven the overlapping features of autoimmune, infectious, metabolic, and paraneoplastic aetiologies, a broad and systematic diagnostic approach was adopted to determine the underlying cause of the encephalopathy.\u003c/p\u003e\n\u003cp\u003eThe concurrent presence of seizures and altered sensorium raised initial suspicion for viral encephalitis, particularly herpes simplex virus and varicella zoster virus. The preceding history of cerebellar ataxia also prompted consideration of bacterial infections such as Listeria monocytogenes, Mycoplasma pneumoniae, and Borrelia burgdorferi, which can involve the cerebellum and present with rhombencephalitis. However, the absence of a prodromal febrile illness, together with negative cerebrospinal fluid and serum studies including polymerase chain reaction testing, cultures, and serology, and normal magnetic resonance imaging findings, effectively excluded these infectious aetiologies [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eCerebellar ataxia has been described in several autoimmune encephalitides, including anti-glutamic acid decarboxylase 65 antibody\u0026ndash;associated encephalitis and anti-contactin-associated protein-like 2 antibody\u0026ndash;associated disease [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, cerebellar involvement occurs in only approximately 5 percent of patients with anti-N-methyl-D-aspartate receptor encephalitis, highlighting that ataxia is an uncommon presenting feature in this subtype [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Anti-glutamic acid decarboxylase 65 antibody\u0026ndash;associated cerebellar ataxia is frequently associated with type 1 diabetes mellitus or other autoimmune disorders and typically lacks prominent psychiatric manifestations, while anti-contactin-associated protein-like 2 antibody\u0026ndash;associated disease predominantly affects older men and is characterised by peripheral nerve hyperexcitability and autonomic dysfunction [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this patient, both serum and cerebrospinal fluid testing were negative for anti-glutamic acid decarboxylase 65 and anti-contactin-associated protein-like 2 antibodies, making these diagnoses unlikely.\u003c/p\u003e\n\u003cp\u003eOther autoimmune causes, including lupus cerebritis, Hashimoto\u0026rsquo;s encephalopathy, and paraneoplastic autoimmune encephalitis, were considered but deemed unlikely due to negative antinuclear antibody titres, non-reactive thyroid antibody testing, and the absence of systemic features [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. Metabolic encephalopathies, such as hepatic and uraemic encephalopathy, were excluded on the basis of normal liver and renal function tests. Toxic or drug-induced encephalopathy was also considered unlikely, given the absence of relevant exposure history and a negative toxicology screen.\u003c/p\u003e\n\u003cp\u003eGiven the patient\u0026rsquo;s age and emerging behavioural changes, a primary psychiatric disorder, including acute psychosis, was initially considered [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, the atypical neurological presentation with early isolated cerebellar ataxia, followed by rapid cognitive decline and neuropsychiatric deterioration, argued against a primary psychiatric diagnosis. The combination of progressive speech dysfunction, abnormal electroencephalography demonstrating diffuse delta slowing, lymphocytic pleocytosis in the cerebrospinal fluid, and the detection of anti-N-methyl-D-aspartate receptor antibodies fulfilled established diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis, supporting this diagnosis as the unifying explanation for the patient\u0026rsquo;s clinical course [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTreatment\u003c/h3\u003e\n\u003cp\u003eFollowing multiple seizure episodes on day 3, levetiracetam was administered intravenously at a dose of 1.5 g/ day. On day 14, the patient was initiated on \u003cstrong\u003efirst-line immunotherapy\u003c/strong\u003e, consisting of \u003cstrong\u003eintravenous immunoglobulin\u003c/strong\u003e at a dose of 0.4 g per kilogram per day for five days and intravenous methylprednisolone at a dose of 1 g per day for five days, followed by a course of oral corticosteroids. Levetiracetam was continued at a standard maintenance dose of 500 mg twice daily.\u003c/p\u003e\n\u003ch3\u003eOutcome and follow-up\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eOutcome and follow-up\u003c/div\u003e\n\u003cp\u003eAfter gradual improvement in neuropsychiatric symptoms over two weeks of treatment, the patient was discharged on an oral corticosteroid regimen. At one month following discharge, she was able to ambulate independently, although mild residual gait instability persisted. Upper limb coordination and hand stability had improved, allowing better performance of fine motor tasks.\u003c/p\u003e\n\u003cp\u003eThe patient\u0026rsquo;s cognitive function had largely recovered, and speech was fluent. Neurological examination revealed no evidence of nystagmus. Repeat laboratory investigations, including cerebrospinal fluid analysis, were performed during follow-up. Based on ongoing clinical improvement, the patient was continued on oral corticosteroid therapy with a gradual taper.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case report describes an unusual presentation of \u003cb\u003eanti-N-methyl-D-aspartate receptor encephalitis\u003c/b\u003e, with isolated cerebellar ataxia as the initial manifestation. The absence of prodromal symptoms, systemic features, or an underlying neoplasm posed a significant diagnostic challenge, particularly in the early stages when characteristic neuropsychiatric features are typically expected.\u003c/p\u003e \u003cp\u003eAnti-N-methyl-D-aspartate receptor encephalitis is a rare form of autoimmune encephalitis reported across all age groups but classically affects females in the third and fourth decades of life. Although the estimated incidence is approximately one case per 1.5\u0026nbsp;million individuals annually, it has been reported to occur more frequently than any infectious form of encephalitis in adults over 30 years of age [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A strong association with ovarian teratomas has been described, with approximately 50 percent of affected women reported to have an underlying tumour.\u003c/p\u003e \u003cp\u003eClassically, the disease progresses through five clinical phases, beginning with a prodromal phase resembling a viral illness, followed by psychiatric symptoms and seizures, an unresponsive or catatonic phase, a hyperkinetic phase characterised by movement disorders and autonomic instability, and finally a recovery phase. The recovery phase typically begins after several months of immunotherapy and supportive treatment. The pathogenic mechanism involves immunoglobulin G antibodies, predominantly IgG1 and IgG3 subclasses, directed against the NR1 subunit of the N-methyl-D-aspartate receptor, leading to receptor internalisation. This process results in reduced neuronal calcium signalling and diminished receptor-mediated synaptic currents [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile cerebellar ataxia has been reported as a presenting feature of anti-N-methyl-D-aspartate receptor encephalitis in the paediatric population, and more commonly later in the disease course, it occurs very rarely in adults [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. An observational cohort study involving 577 patients demonstrated that cerebellar ataxia was an atypical manifestation, occurring in approximately 5 percent of adolescents and 2 percent of adults [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A similar presentation was described in a woman in her 30s with isolated brainstem and cerebellar symptoms that did not progress to neuropsychiatric manifestations [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Another case reported anti-N-methyl-D-aspartate receptor encephalitis presenting with cerebellar symptoms in a woman in her 30s with a history of recurrent ovarian teratomas [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. An additional report described gait ataxia associated with hyperintense cerebellar lesions on magnetic resonance imaging [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese reports highlight the heterogeneity of clinical presentations associated with anti-N-methyl-D-aspartate receptor encephalitis. In contrast to previously reported cases, our patient presented with isolated cerebellar dysfunction without radiological evidence of cerebellar involvement, had no history of ovarian teratoma, and progressed rapidly to develop neuropsychiatric symptoms, reaching a stuporous state within one week. This case emphasises the need to consider anti-N-methyl-D-aspartate receptor encephalitis even in the absence of prodromal symptoms or classical neuropsychiatric features when unexplained cerebellar ataxia is followed by rapid neurological deterioration.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case underscores that anti-N-methyl-D-aspartate receptor encephalitis can initially manifest with isolated cerebellar ataxia in adults, preceding the onset of typical neuropsychiatric features. The absence of a prodromal illness or associated ovarian teratoma should not preclude consideration of the diagnosis. Additionally, normal neuroimaging does not exclude autoimmune encephalitis, highlighting the importance of cerebrospinal fluid analysis and antibody testing in patients with compatible clinical features. Early recognition and timely initiation of immunotherapy can lead to substantial neurological improvement, even in atypical presentations.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis report has several limitations. As a single case, the findings may not be generalisable to all presentations of anti-N-methyl-D-aspartate receptor encephalitis. Advanced investigations such as serial antibody titres and long-term neuropsychological assessments were not available, which may have provided additional insight into disease evolution and recovery. Furthermore, although follow-up demonstrated significant clinical improvement, longer-term outcomes could not be assessed at the time of reporting. Despite these limitations, the case provides valuable clinical insight into an atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis and highlights important diagnostic consideration\u003c/p\u003e\n\u003ch3\u003ePatient Perspective:\u003c/h3\u003e\n\u003cp\u003e[As elicited in the patient\u0026rsquo;s own language and translated to English]\u003c/p\u003e \u003cp\u003eI was completely healthy before this illness. A week before admission, I noticed imbalance while walking and hand tremors but thought it was just fatigue. After a seizure, I was brought to the hospital. I don\u0026rsquo;t remember much, but my family said my behavior changed and worsened. I was later diagnosed with a rare condition and started treatment. I gradually improved, recognised my family again, and the seizures stopped. I was discharged after two weeks and have been recovering well. I\u0026rsquo;m grateful to the doctors for their timely care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eCT-\u0026nbsp;\u003c/strong\u003eComputed Tomography\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFLAIR-\u0026nbsp;\u003c/strong\u003eFluid-Attenuated Inversion Recovery\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHb\u003c/strong\u003e – Haemoglobin\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIgG\u003c/strong\u003e- Immunoglobulin G\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIgG1\u003c/strong\u003e – Immunoglobulin G subclass 1\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIgG3\u003c/strong\u003e – Immunoglobulin G subclass 3\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMMSE-\u003c/strong\u003e Mini-Mental State Examination\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMRI-\u003c/strong\u003e Magnetic Resonance Imaging\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNMDAR-\u003c/strong\u003e Anti-N-methyl-D-aspartate receptor\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eNR1\u003c/strong\u003e- N-methyl-D-aspartate receptor subunit 1\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003ea) \u003cb\u003eEthics Statement\u003c/b\u003e: This case report was conducted in accordance with the principles outlined in the Declaration of Helsinki. Institutional Ethics Committee (IEC) approval was not required for this single case report as per institutional regulations.\u003c/p\u003e \u003cp\u003e\u003cb\u003eb) Consent for publication\u003c/b\u003e: Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.\u003c/p\u003e \u003cp\u003e \u003cb\u003ec) Acknowledgments\u003c/b\u003e: None\u003c/p\u003e \u003cp\u003e \u003cb\u003ed) Funding\u003c/b\u003e: No funding received.\u003c/p\u003e \u003cp\u003e \u003cb\u003ee) Conflict of Interest Statement\u003c/b\u003e:The authors declare no conflict of interest.\u003c/p\u003e \u003cp\u003e \u003cb\u003ef) Availability of data and materials\u003c/b\u003e: The data regarding the patient can be submitted by the corresponding author upon reasonable request.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConception or design of the work: Panigrahi A and Majety SKFirst Draft of the article: Panigrahi A, Farooq AM, and Alam MZCritical revision of the article: Majety SK and Muppana GSupervision of article: Majety SK, Muppana G, and Panigrahi AProject Administration: Panigrahi A, Farooq AM, and Alam MZ.Final approval of the version to be published: All Authors Responsibility of the material: All authors\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKumari K, Sahni N, Kumari V, Saini V. 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PMID: 40880226; PMCID: PMC12611002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang B, Wang C, Ren H, Guan H, Guo S. Cerebellar ataxia as the initial symptom with lesions involving the cerebellum in patient with anti-NMDAR encephalitis: A rare case report and literature review. J Neuroimmunol. 2020;346:577293. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2020.577293\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2020.577293\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 32590126.\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":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anti-NMDAR encephalitis, Cerebellar ataxia, Autoimmune encephalitis, Atypical presentation, Immunotherapy","lastPublishedDoi":"10.21203/rs.3.rs-8757814/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8757814/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially reversible autoimmune encephalitis, most commonly affecting young women and children. It typically follows a prodromal illness and progresses to prominent neuropsychiatric symptoms, movement disorders, seizures, and autonomic instability. While cerebellar ataxia may occur during the disease course, it is rarely the initial or isolated presenting feature, particularly in adults, and may result in diagnostic delay.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe report a case of a woman in her 20s with no prior medical history who presented with progressive cerebellar ataxia, including unsteady gait and impaired fine motor coordination, without preceding systemic or prodromal symptoms. Three days after admission, she developed a generalised tonic-clonic seizure followed by rapid-onset behavioural changes, hallucinations, and cognitive decline. Neurological examination revealed cerebellar signs including dysmetria, horizontal nystagmus, and a positive Romberg test. Brain MRI was unremarkable. Electroencephalography showed diffuse delta slowing. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and tested positive for anti-NMDAR antibodies. There was no evidence of malignancy on pelvic ultrasound or CT imaging. The patient was treated with first-line immunotherapy, including intravenous immunoglobulin and corticosteroids. Her neuropsychiatric symptoms improved significantly over the following two weeks. At one-month follow-up, she had near-complete recovery in mobility and cognition.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eThis case highlights an unusual adult presentation of anti-NMDAR encephalitis in which cerebellar ataxia appeared before other symptoms. Clinicians should consider autoimmune encephalitis in patients with isolated cerebellar signs followed by rapid neurological decline, even without prodromal features or imaging abnormalities. Early diagnosis and prompt immunotherapy are essential for favourable outcomes.\u003c/p\u003e","manuscriptTitle":"Cerebellar Ataxia as the Initial Manifestation of Anti-NMDAR Encephalitis Without Prodrome: A Case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 12:14:03","doi":"10.21203/rs.3.rs-8757814/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-02T16:48:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"107063726622196990508811943849160976876","date":"2026-04-23T22:58:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214678958546183326493466394788818372412","date":"2026-04-09T16:49:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-19T15:10:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"57376037133574164795596809960310026275","date":"2026-03-19T15:02:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T14:46:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290034820129409180218932770880616571333","date":"2026-02-08T17:17:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317676021346763610919570880918252591594","date":"2026-02-08T09:03:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-04T05:05:45+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-03T14:41:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-03T05:04:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T05:02:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-02-01T16:43:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9cbccf0d-4f3d-4570-a099-9319d43130f7","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-02T16:48:27+00:00","index":44,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T12:14:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 12:14:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8757814","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8757814","identity":"rs-8757814","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}