What is the most appropriate management for a patient with abnormal movement, previous viral infection, and drowsiness, but normal CSF analysis?

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Management of Post-Viral Encephalitis with Normal CSF

This patient with abnormal movements, drowsiness, and recent viral infection with normal CSF findings most likely has autoimmune encephalitis (specifically NMDA receptor or VGKC-complex antibody-associated encephalitis), and should be treated immediately with high-dose corticosteroids (0.5 mg/kg/day oral prednisolone) combined with either intravenous immunoglobulin (0.4 g/kg/day) or plasma exchange. 1

Clinical Recognition and Diagnosis

This presentation is classic for autoimmune encephalitis following viral infection:

  • Abnormal movements (choreoathetosis, orofacial dyskinesia) with altered consciousness after a viral prodrome strongly suggests NMDA receptor antibody-associated encephalitis, which characteristically presents in two phases: initial confusion/seizures followed by movement disorders and autonomic dysfunction 1

  • Normal CSF does NOT exclude encephalitis—approximately 90% of NMDA receptor encephalitis cases have normal MRI initially, and CSF can be normal or show only mild lymphocytosis 1

  • The lymphocytic predominance you describe is consistent with viral or autoimmune encephalitis, though CSF may be completely normal in up to 10% of proven viral encephalitis cases, especially early in illness 1

Immediate Management Algorithm

Step 1: Neuroimaging and Further Investigations

  • Obtain MRI brain with gadolinium immediately (preferred over CT) to look for hippocampal or white matter signal changes, though normal imaging does not exclude diagnosis 1

  • Send serum and CSF for autoimmune antibody panels including NMDA receptor antibodies, VGKC-complex antibodies, and other neuronal antibodies 1

  • Screen for underlying malignancy, particularly ovarian teratoma in females (20-50% of female patients with NMDA receptor encephalitis have teratomas) 1

Step 2: Initiate Immunotherapy Without Delay

Do not wait for antibody results to start treatment—the clinical presentation warrants immediate immunosuppression:

  • Start oral corticosteroids at 0.5 mg/kg/day prednisolone 1

  • Add either IVIg (0.4 g/kg/day for 5 days) OR plasma exchange as combination therapy is superior to monotherapy 1

  • If no response within 2 weeks, escalate to second-line agents: rituximab or cyclophosphamide 1

Step 3: Supportive Care and Monitoring

  • Admit to monitored setting given drowsiness and risk of autonomic instability, hypoventilation, and seizures 1

  • Seizure prophylaxis may be needed as seizures occur in the first phase of NMDA receptor encephalitis 1

  • Arrange multidisciplinary rehabilitation including neuropsychology, neuropsychiatry, speech therapy, physiotherapy, and occupational therapy 1

Critical Pitfalls to Avoid

Do not discharge this patient without a definitive or suspected diagnosis and follow-up plan—96% of encephalitis patients report ongoing complications, yet 33% are discharged without outpatient follow-up 1

Do not assume viral encephalitis and stop at supportive care—the movement disorder component strongly suggests autoimmune etiology requiring immunosuppression 1

Do not delay treatment waiting for antibody confirmation—antibodies may take weeks to return, and early immunotherapy improves outcomes 1

Normal CSF should not reassure you—encephalitis can present with normal CSF, especially in immunocompromised patients or early in disease 1

Expected Clinical Course

  • With appropriate immunotherapy, confusion and seizures typically improve rapidly, but memory recovery may take months to years 1

  • Median hospital stay is 160 days for NMDA receptor encephalitis, with many requiring ICU admission 1

  • Approximately 30% of patients relapse despite treatment, necessitating long-term immunosuppression with agents like azathioprine 1

  • Antibody levels normalize within 3-6 months with treatment, and steroids can be tapered over 12 months once antibodies are undetectable 1

Long-term Follow-up

  • Schedule outpatient neurology follow-up before discharge with clear rehabilitation plans 1

  • Annual tumor screening for several years, particularly if treatment response is poor or relapses occur 1

  • Monitor for neuropsychiatric sequelae including anxiety, depression, and obsessive behaviors, which often emerge after discharge 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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