What diagnosis should be considered in an 18-50 year old patient with a history of recurrent episodes of sudden onset neuropsychiatric decompensation, obsessive-compulsive disorder (OCD), and severe headache, lasting 6 weeks and self-resolving, with a second episode occurring one year later?

Recurrent Autoimmune Encephalitis with Relapsing Course

The primary diagnosis to consider is autoimmune encephalitis (AE), particularly anti-NMDA receptor encephalitis, given the acute-onset neuropsychiatric symptoms, OCD features, severe headache, self-limited 6-week course, and recurrence one year later—a pattern consistent with relapsing autoimmune encephalitis. 1

Key Diagnostic Considerations

Autoimmune Encephalitis as the Leading Diagnosis

The clinical presentation strongly suggests autoimmune encephalitis based on several hallmark features:

• Acute/subacute onset with duration less than 3 months is characteristic of AE, with the immune reaction typically presenting over days to weeks rather than hyperacute (vascular) or chronic (neurodegenerative) timeframes 1

• Recurrent course with self-resolution is atypical for primary psychiatric disorders but can occur in AE, though relapses are relatively rare and often result from insufficient treatment or rapid immunotherapy interruption 1

• Polysyndromic presentation combining neuropsychiatric decompensation, OCD symptoms, and severe headache reflects the diffuse brain inflammation typical of AE, which may involve multifocal areas and occasionally meninges 1

• Anti-NMDA receptor encephalitis specifically presents with psychiatric symptoms including psychosis, mania, aggression, and obsessive-compulsive features, often accompanied by neurological symptoms 2, 3, 4

Why This Pattern Fits Autoimmune Encephalitis

The recurrence after one year is particularly telling:

• While AE typically follows a monophasic course, relapses can occur and should raise suspicion for autoimmune etiology rather than primary psychiatric illness 1

• The self-resolving nature over 6 weeks suggests immune-mediated inflammation that spontaneously remits, though incomplete resolution increases relapse risk 1

• Young adults (18-50 years) are the typical demographic for anti-NMDA receptor encephalitis, with a 4:1 female predominance 2

Critical Workup Required

Immediate Investigations When AE is Suspected

• Cerebrospinal fluid analysis with autoantibody panel including anti-NMDA receptor antibodies, anti-LGI1, anti-CASPR2, anti-GAD65, and other neural antibodies is essential for diagnosis confirmation 1, 2

• Brain MRI may show findings suggestive of autoimmune limbic encephalitis, though imaging can be normal in some cases 1, 2

• EEG is useful as electroencephalographic abnormalities are common in AE 1, 2

• Tumor screening is mandatory, as AE origin is often paraneoplastic, particularly ovarian teratoma in young women with anti-NMDA receptor encephalitis 2, 4

Assessment for Preceding Triggers

• Recent viral infection or prodrome should be documented, as AE may be triggered by HSV encephalitis or other infections 1

• Personal or family history of autoimmune disorders increases risk of idiopathic AE 1

• Cancer risk factors (smoking, weight loss) or known malignancy raise suspicion for paraneoplastic AE 1

Alternative Diagnoses to Consider

PANS/PANDAS (Pediatric Acute-onset Neuropsychiatric Syndrome)

While the evidence discusses PANDAS primarily in pediatric populations:

• Sudden onset of obsessive-compulsive symptoms following infections characterizes PANS/PANDAS 1

• The concept has broadened from streptococcal-only (PANDAS) to multiple infectious triggers (PANS), with sudden neuropsychiatric onset as the hallmark 1

• However, this diagnosis is less likely in the 18-50 age range and typically doesn't present with severe headache as a prominent feature 1

Primary OCD with Episodic Exacerbations

This is a less likely explanation because:

• Primary OCD rarely presents with such dramatic acute onset and complete self-resolution over 6 weeks 1, 5

• OCD typically requires symptoms consuming >1 hour daily with chronic course, not episodic 6-week periods separated by complete remission 1, 5, 6

• The severe headache component is not characteristic of primary OCD 1, 5

Neurological Lesions Causing Secondary OCD

• Basal ganglia lesions, frontal lobe lesions, or encephalitis lethargica can cause OCD symptoms 1

• However, these typically present with persistent rather than relapsing-remitting symptoms 1

Common Pitfalls to Avoid

Misdiagnosing as Primary Psychiatric Illness

• Anti-NMDA receptor encephalitis is frequently misdiagnosed as primary psychiatric disorder, particularly when psychiatric symptoms predominate early 2, 4

• Clinicians should maintain high suspicion for AE in patients with acute psychiatric symptoms who develop neurological signs or have treatment-refractory symptoms 3, 4

• The presence of autonomic instability, seizures, or movement abnormalities alongside psychiatric symptoms strongly suggests AE over primary psychiatric disease 3, 4

Delaying Autoantibody Testing

• CSF autoantibody testing should not be delayed while awaiting other workup, as early immunotherapy improves outcomes 1, 2

• Patients with long-term neuropsychiatric symptoms not responding to standard therapy should be screened for anti-NMDA receptor antibodies 3

Treatment Implications

If autoimmune encephalitis is confirmed:

• First-line immunotherapy includes IV methylprednisolone and plasmapheresis or IVIG 2

• Second-line therapy with rituximab or cyclophosphamide may be needed for refractory cases 2

• Tumor resection when indicated is critical for paraneoplastic cases 2, 4

• Maintenance immunosuppression may be necessary to prevent relapses, particularly given the recurrent course in this patient 1, 2