Can suspected mild encephalitis with a normal Magnetic Resonance Imaging (MRI) recover on its own?

Can Suspected Mild Encephalitis with Normal MRI Recover on Their Own?

No, suspected mild encephalitis should never be left untreated to "recover on its own," even with a normal MRI, because approximately 10% of HSV encephalitis cases can have normal initial imaging, and untreated HSV encephalitis carries significant mortality and severe neurological morbidity. 1, 2

Critical Understanding About Normal MRI in Encephalitis

A normal MRI does not exclude encephalitis and should never delay treatment. The evidence clearly demonstrates:

• MRI obtained within 48 hours is abnormal in approximately 90% of HSV encephalitis patients, meaning 10% will have normal initial imaging 1, 2
• Initial CT scans are even less sensitive, showing abnormalities in only 25-80% of HSV encephalitis cases 1
• In one recent study, 68.8% of PCR-proven HSV encephalitis patients had completely normal initial CT scans 3
• Remarkably, 22.2% of PCR-proven HSV encephalitis cases presented with normocellular CSF on admission, further complicating diagnosis 3

Why "Watchful Waiting" Is Dangerous

The clinical outcomes data make clear that untreated or delayed treatment leads to poor outcomes:

• Only 38.9% of HSV encephalitis patients achieved good clinical outcomes (Glasgow Outcome Score = 5) even with treatment 3
• HSV encephalitis remains "the most common form of sporadic lethal encephalitis worldwide" 3
• Some patients developed clinical deterioration despite acyclovir therapy, with one requiring decompressive craniotomy 3

The Correct Clinical Approach

Immediate empiric treatment with acyclovir is mandatory when encephalitis is suspected, regardless of imaging findings. 2, 4

Treatment Protocol:

• Start IV aciclovir 10 mg/kg every 8 hours immediately for adults and adolescents (20 mg/kg every 8 hours for children) 4
• Adjust dosing for renal impairment 4
• Continue for 14-21 days for confirmed HSV encephalitis 5
• Do not wait for imaging or laboratory confirmation to initiate therapy 4

Essential Diagnostic Workup (While Treatment Proceeds):

• Lumbar puncture for CSF analysis including HSV PCR (the gold standard for diagnosis) 2, 5
• EEG if subtle seizures suspected or to differentiate psychiatric from organic causes 1, 4
• Repeat MRI if initial imaging is normal but clinical suspicion remains high 1, 2
• Consider alternative diagnoses including autoimmune encephalitis (MOG antibody testing) if no response to acyclovir 6

Important Caveats and Pitfalls

Common diagnostic errors to avoid:

• Never rely on a single negative CSF PCR to rule out HSV encephalitis, as false negatives occur early in disease 4
• Never discontinue aciclovir based solely on normal imaging if clinical suspicion remains 4, 3
• Be aware that MRI deterioration can occur despite clinical recovery and may represent immune-mediated changes rather than true relapse 7
• Consider MOG antibody-associated disease in patients with suspected encephalitis, normal brain MRI, and no response to antibacterial therapy 6

Special Considerations for "Mild" Presentations

Even clinically "mild" encephalitis presentations require aggressive treatment because:

• Atypical presentations are more common than previously recognized 3
• Patients can deteriorate rapidly despite initial mild symptoms 3
• Some conditions mimicking mild viral encephalitis (like MERS) may have good prognosis with supportive care, but this diagnosis can only be made retrospectively after excluding treatable causes 8

The risk-benefit analysis overwhelmingly favors empiric treatment: acyclovir has an acceptable safety profile, while untreated HSV encephalitis has devastating consequences. 4, 3