In a 77-year-old woman who developed high fever, a tonic‑clonic seizure, and generalized malaise a few days after an upper‑respiratory infection, with cerebrospinal fluid showing isolated elevated protein and MRI demonstrating temporal‑lobe hyperintensities, what is the most likely diagnosis?

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Diagnosis: Viral Encephalitis (HSV-1 Most Likely)

The diagnosis is viral encephalitis, specifically herpes simplex virus type 1 (HSV-1) encephalitis, based on the classic triad of fever, new-onset tonic-clonic seizure, and bilateral temporal lobe hyperintensities on MRI following a prodromal upper respiratory infection. 1, 2

Clinical Reasoning

Why HSV-1 Encephalitis is the Answer

  • HSV-1 accounts for 25-40% of all sporadic encephalitis cases worldwide and is the most common identified cause of nonendemic sporadic encephalitis 1, 3, 4

  • Bilateral temporal lobe involvement on MRI is nearly pathognomonic for HSV encephalitis, occurring in >90% of laboratory-confirmed cases 1, 2, 3

  • The classic triad of fever, seizures, and temporal lobe abnormalities strongly suggests HSV-1 encephalitis 2

  • A preceding upper respiratory infection is frequently reported in patients who later develop HSV-1 encephalitis 2

  • CSF showing isolated elevated protein with normal glucose is consistent with viral encephalitis, where CSF typically reveals mild-to-moderate protein elevation with mononuclear pleocytosis 1

Why NOT Multiple Sclerosis (Option B)

  • MS does not present with acute high fever and tonic-clonic seizures—these features are not typical of MS 2

  • MS typically shows periventricular white matter lesions, not acute bilateral temporal lobe hyperintensities 1

  • MS has a relapsing-remitting course rather than acute encephalitic presentation with systemic illness 1

Why NOT Primary Temporal Lobe Epilepsy (Option C)

  • Primary temporal lobe epilepsy does not produce fever or acute systemic illness 2

  • Epilepsy shows chronic structural lesions (hippocampal sclerosis, gliosis) rather than acute hyperintensities on MRI 2

  • The acute presentation following URI with high fever indicates an infectious/inflammatory process, not a primary seizure disorder 1, 2

Immediate Management Algorithm

Step 1: Initiate Empiric Antiviral Therapy Immediately

  • Start intravenous acyclovir 10 mg/kg every 8 hours for adults immediately without awaiting PCR confirmation 1, 2

  • Treatment should not be delayed by serological confirmation—early acyclovir dramatically decreases morbidity and mortality by 50% 3, 4

  • Adjust dose for renal impairment; continue for minimum 14-21 days 2, 5

Step 2: Obtain Diagnostic Confirmation

  • Perform lumbar puncture for CSF analysis including HSV PCR (sensitivity 96-98%, specificity 95-99% in adults) 1, 6

  • CSF PCR is the diagnostic gold standard and should be obtained between day 2-10 of illness for optimal sensitivity 6

  • Send CSF for cell count, protein, glucose, and bacterial culture 1

Step 3: Additional Diagnostic Testing

  • Throat and rectal swabs for enterovirus PCR should be obtained 1

  • EEG may show periodic lateralizing epileptiform discharges in temporal regions in 80% of HSV encephalitis cases 1

  • Serum acute and convalescent samples for viral serology 1

Critical Pitfalls to Avoid

  • Never delay acyclovir while awaiting imaging or laboratory confirmation—this increases mortality and morbidity 2, 4

  • Do not rely on a single negative CSF PCR to rule out HSE, as false negatives can occur within the first 72 hours of illness 6, 3

  • Hemoglobin or other PCR inhibitors in CSF can cause false-negative results 6

  • If initial CSF PCR is negative but clinical suspicion remains high, repeat CSF PCR 3-7 days later 6

  • Continue acyclovir despite negative PCR when temporal lobe abnormalities on MRI or characteristic clinical presentation strongly suggests HSV encephalitis 2, 6

Prognosis and Follow-up

  • CSF HSV PCR should become negative after 14 days of acyclovir treatment; persistent positive PCR should prompt consideration of additional or revised antiviral therapy 3

  • Follow-up MRI is recommended to evaluate evolving necrosis or demyelination and assess treatment response 2

  • Intracranial hemorrhage is a rare complication (2.7%) but requires close neurological monitoring 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Approach to MRI Brain Suggestive of Early Features of Encephalitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Update on herpes simplex encephalitis.

Reviews in neurological diseases, 2004

Research

Neurological Disorders Associated with Human Alphaherpesviruses.

Advances in experimental medicine and biology, 2018

Guideline

Sensitivity of CSF HSV PCR Testing

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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