First-episode mania with catatonic features as the heralding presentation of anti-NMDA receptor encephalitis: a case report

Introduction

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially life-threatening but treatable autoimmune encephalopathy caused by IgG antibodies targeting the GluN1 subunit of the NMDA receptor.It predominantly affects young women and presents with a psychiatric prodrome-mood disturbance, psychosis, behavioral dysregulation-followed by catatonia, seizures, movement disorders and autonomic instability.Fluctuating agitation, catatonia and delirious features mimic primary psychiatric syndromes,delaying recognition.[1,2] Many are **misdiagnosed as primary psychiatric disorders-**first-episode psychosis, bipolar disorder, schizophrenia-leading to antipsychotic escalation without benefit and critical delays in immunotherapy.[3,4] We present a non-paraneoplastic anti-NMDAR encephalitis case in which excitatory catatonia and delirious mania constituted the heralding neuropsychiatric syndrome.

Case A 19-year-old woman with no prior psychiatric or neurological history presented with subacute-onset elevated mood,pressured speech,paranoid delusions,progressive irritability and aggression.Family reported a three-week antecedent history of hyperorality,inattention and perseveration.Sequential antipsychotic trials-olanzapine (up to 20 mg/day),quetiapine XR(300 mg/day),zuclopenthixol decanoate,paliperidone(6 mg/day) and adjunctive lithium(900 mg/day)-yielded no improvement.Admission neuropsychiatric assessment(BFCRS,CAM) is summarized in Table.The clinical picture was consistent with delirious mania (excitatory catatonia).DSM-5 criteria met mania,catatonia and delirium(concurrent).Clinical and radiological findings were not consistent with multiple sclerosis.A comprehensive workup was undertaken (Table).Cell-surface autoantibody screening (serum and CSF),paraneoplastic antibody panels and infectious etiologies were excluded.Vasculitis and systemic autoimmune disease markers were negative.CSF anti-NMDAR antibodies were positive (titer 1:320), with all other investigations negative.First-line immunotherapy:methylprednisolone 1 g/dayx10 days,followed by five plasma exchange sessions-no clinical improvement. IVIG was subsequently administered, with marked improvement within seven days (BFCRS:11→0;CAM:positive→negative).Rituximab was initiated for long-term immunomodulation, maintaining sustained remission at one year of follow-up.

Discussion

This case illustrates the diagnostic vulnerability inherent to anti-NMDAR encephalitis: an onset phenotype indistinguishable from a primary affective-psychotic syndrome, leading to ineffective antipsychotic escalation.Three clinical features warranted immediate departure from a primary psychiatric formulation:(1) antipsychotic non-response across multiple agents;(2) co-occurrence of **mania, catatonia, and delirium-**a phenotypic triad atypical for primary psychiatric disorders and (3) neurological signs on systematic examination.The structured exclusion of competing diagnoses was essential to diagnostic confidence.A comprehensive cell-surface autoantibody panel and paraneoplastic antibodies were all negative.Extensive infectious screening was negative.Vasculitis, systemic autoimmune and primary demyelinating disease (MS) were excluded.The absence of CSF pleocytosis did not exclude the diagnosis:anti-NMDAR antibody positivity at titer 1:320 in CSFwas the definitive serological marker.EEG delta-range anterior slow-wave activity and bilateral occipital PET hypometabolism provided corroborating functional evidence.Negative tumor workup confirmed the non-paraneoplastic phenotype.The dissociated immunotherapy response-steroid/PLEX failure with subsequent IVIG-mediated resolution-supports early escalation protocols in antibody-confirmed cases.[5]

Conclusion

Young women with first-episode mania,catatonia or psychosis unresponsive to antipsychotics must be systematically evaluated for autoimmune encephalitis.Structured exclusion of infectious,paraneoplastic,vasculitic and demyelinating etiologies is integral to diagnostic confidence.IVIG should be considered when first-line immunotherapy fails.Anti-NMDAR encephalitis is treatable;early diagnosis and immunotherapy enable full neuropsychiatric recovery.[5]

BFCRS Score and CAM	11.Excitement,Staring,Posturing/Catalepsy,Echopraxia/Echolalia,Verbigeration,Withdrawal,Impulsivity,Automatic Obedience,Perseveration / Positive-Delirium confirmed
Neurological Signs	Diplopia on bilateral lateral gaze,Gaze-evoked horizontal nystagmus,Brisk deep tendon reflexes (lower extremities)
Cranial MRI/18-FDG Cranial PET	T2/FLAIR hyperintensities-demyelinating/inflammatory pattern; no contrast enhancement;pattern inconsistent with primary demyelinating disease / Bilateral occipital hypometabolism
Thoracoabdominal-Pelvic CT/18-FDG Tumor PET	No pathological findings
EEG	Bilateral symmetric synchronous delta slow-wave paroxysms-anterior hemispheric regions
CSF	WBC:0/mm³,Protein:398.8 mg/dL,Albumin:2284 mg/L,IgG:278 mg/L,Oligoclonal bands:Type 2 (CSF-restricted),Anti-NMDAR antibodies:Positive-titer 1:320

References

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