What is the recommended treatment for a patient suspected of having neuroimmune encephalitis?

Treatment of Suspected Neuroimmune Encephalitis

Immediately initiate empiric intravenous aciclovir (10 mg/kg three times daily) while simultaneously pursuing urgent diagnostic workup and autoimmune evaluation, as viral and autoimmune etiologies frequently overlap and early treatment is critical for reducing mortality and morbidity. 1

Immediate Management and Diagnostic Workup

Critical First Steps

• Perform lumbar puncture as soon as possible after hospital admission unless contraindications exist (signs of raised intracranial pressure, coagulopathy, or significant brain shift on imaging). 1
• If LP is contraindicated, obtain urgent CT scan first, then reassess LP feasibility on a case-by-case basis unless imaging reveals significant brain shift, tight basal cisterns, or alternative diagnosis. 1
• Obtain neuroimaging (MRI preferred over CT) and EEG within 24 hours, under general anesthesia if needed. 1
• CSF PCR results should be available within 24-48 hours to guide definitive therapy. 1

Autoimmune Evaluation

• Send autoimmune encephalitis antibody panel including NMDA receptor, voltage-gated potassium channel complex, IGLON5, and other neuronal antibodies from both serum and CSF. 1
• Check inflammatory markers: ESR, CRP, ANA, ENA, dsDNA, ANCA, complement levels, thyroid antibodies. 1
• Screen for malignancy with CT chest/abdomen/pelvis, as paraneoplastic associations occur in autoimmune encephalitis. 2

First-Line Immunotherapy for Autoimmune Encephalitis

Initiate high-dose intravenous methylprednisolone (1g daily for 3-5 days) combined with IVIG (0.4 g/kg/day for 5 days) immediately after excluding infection, as autoimmune encephalitis responds to aggressive early immunotherapy and delays worsen outcomes. 2, 3

Alternative First-Line Options

• Therapeutic plasma exchange (5-10 sessions every other day) can be used as alternative or additional therapy, particularly with severe presentation or contraindications to steroids/IVIG. 2, 4
• Evidence suggests TPE may be superior to steroids alone in anti-NMDA receptor encephalitis, with 70% showing improvement after TPE versus 30% after steroids alone. 4

Second-Line Therapy for Inadequate Response

Add rituximab (375 mg/m² weekly for 4 weeks) as the preferred second-line agent if no improvement occurs within 10-14 days of first-line therapy, as rituximab targets antibody-mediated autoimmunity and reduces relapse rates. 2, 3

When to Escalate

• Lack of clinical improvement after 10-14 days of first-line immunotherapy. 3
• Progressive neurological deterioration despite treatment. 5
• Steroid-resistant cases with prominent motor dysfunction may benefit from additional IVIg cycles. 6

Critical Care Management

Intensive Care Indications

• Patients with falling level of consciousness require urgent ICU assessment for airway protection, ventilatory support, management of raised intracranial pressure, optimization of cerebral perfusion pressure, and correction of electrolyte imbalances. 1
• Monitor for seizures, malignant raised intracranial pressure, aspiration risk, and systemic complications. 1

Specialist Consultation

• Obtain immediate neurological specialist opinion with clinical review within 24 hours of referral. 1
• Multidisciplinary team should include neurologists, infectious disease physicians, virologists, neurophysiologists, neuroradiologists, and intensive care staff. 1

Maintenance and Long-Term Management

Bridging Therapy

• Continue immunosuppression with gradual oral prednisone taper or monthly IVIG to prevent relapse after initial treatment response. 2
• Rituximab maintenance reduces relapse rates in antibody-mediated encephalitis. 3

Rehabilitation and Follow-Up

• All patients require comprehensive rehabilitation assessment before discharge, including neuropsychology, neuropsychiatry, speech/language therapy, physiotherapy, and occupational therapy. 1
• Arrange outpatient follow-up with specific plans for ongoing therapy, as 96% of encephalitis patients report ongoing complications. 1
• Monitor for delayed neuropsychiatric sequelae including anxiety, depression, obsessive behaviors, cognitive impairment, and fatigue. 1, 3

Common Pitfalls to Avoid

• Do not delay empiric aciclovir while awaiting autoimmune workup, as HSV encephalitis has high mortality without treatment and clinical features overlap significantly. 1
• Do not discharge patients without definitive or suspected diagnosis and rehabilitation assessment, as neurological sequelae may not be immediately apparent. 1
• Do not use corticosteroids routinely for flavivirus encephalitis (dengue, West Nile), as controlled trials show no benefit. 7
• Steroid unresponsiveness should prompt diagnostic review rather than continued escalation of steroids alone. 5
• Transfer to specialized neuroscience center within 24 hours if diagnosis unclear or patient fails to improve with initial therapy. 1