Herpes Simplex Encephalitis (Asymmetric Limbic Hyperintensity & Acyclovir Protocol)

• Seen in patients of any age (bimodal peak: children <20 years and older adults >50 years, equal sex distribution) presenting acutely with the classic clinical triad: (1) acute high fever and severe headache, (2) rapidly progressive altered mental status, confusion, personality changes, or bizarre psychotic behavior, and (3) focal neurological deficits, aphasia, or focal seizures (particularly temporal lobe seizures). Mortality exceeds 70% if untreated.
• Caused by fulminant necrotizing, hemorrhagic viral encephalitis caused almost exclusively by Herpes Simplex Virus Type 1 (HSV-1, >95% in adults; HSV-2 causes neonatal encephalitis and benign recurrent aseptic meningitis [Mollaret meningitis]):
• (1)
  Pathogenesis: Reactivation of latent HSV-1 within the trigeminal ganglion (gasserian ganglion), traveling retrogradely along the tentorial sensory branches of the trigeminal nerve to invade the adjacent anterior and medial temporal lobes and inferior frontal lobes.
• (2)
  Pathological Hallmarks: Severe, necrotizing, hemorrhagic liquefaction of gray and white matter, accompanied by intense lymphocytic perivascular cuffing and Cowdry A eosinophilic intranuclear inclusion bodies within neurons and glial cells.
• (3)
  Strict Anatomical Sparing: Characteristically involves the limbic system (temporal lobes, insular cortex, subfrontal gyri, and cingulate gyri) while strictly SPARING the basal ganglia and thalamus (the 'basal ganglia sparing' rule).

Imaging Findings

• Magnetic Resonance Imaging (Brain MRI - Diagnostic Gold Standard Framework):
• –
  Asymmetric Temporal & Limbic Involvement: Symmetrical or characteristically strikingly asymmetric, confluent, geographic high signal intensity on T2WI and FLAIR involving the medial and anterior temporal lobes, amygdala, hippocampus, insular cortex, and inferior frontal lobes.
• –
  The 'Basal Ganglia Sparing' Rule: Pathognomonic anatomical boundary. The edema and cortical swelling track across the insular cortex directly up to the external capsule, with sharp, strict sparing of the adjacent putamen and globus pallidus.
• –
  Diffusion-Weighted Imaging (DWI - Earliest Radiologic Sign):
• 1.
  Marked, intense restricted diffusion (high signal on DWI b=1000, low on ADC) involving the swollen cortical ribbon and medial temporal structures within the first 24–48 hours, preceding FLAIR signal changes.
• –
  Susceptibility-Weighted Imaging (SWI / GRE):
• 1.
  Petechial micro-hemorrhages and cortical necrosis manifested as dark, blooming punctate or gyral signal voids.
• –
  Post-Contrast T1WI: Patchy, delicate, irregular gyriform cortical enhancement or meningeal enhancement seen after the first 3–7 days.
• –
  DWI / ADC (Earliest MRI Finding): Cortical and subcortical diffusion restriction (high DWI, low ADC) in the medial temporal lobe, insula, and cingulate gyrus appears earlier and more extensively than T2/FLAIR hyperintensity.
• –
  **SWI / T2* GRE: Demonstrates gyriform petechial blooming microhemorrhages** within the necrotizing limbic cortex (a key feature distinguishing HSV-1 encephalitis from autoimmune limbic encephalitis or low-grade glioma).
• Computed Tomography (CT Head - Unreliable in Early Disease):
• –
  Completely normal in up to 30–50% of patients during the first 24–48 hours of symptoms; later displays subtle hypo-attenuation, loss of insular ribbon definition, and temporal lobe mass effect.

Differential Diagnosis

Important Points to Remember

• Diagnostic Pitfall: Awaiting MRI or lumbar puncture confirmation before starting intravenous Acyclovir! In emergency clinical practice, immediate empirical treatment is critical. Mortality from HSV encephalitis increases by >1% for every single hour of delayed treatment. If HSV encephalitis is suspected clinically, you MUST state immediately that empirical intravenous Acyclovir must be commenced instantly, BEFORE sending the patient for MRI or awaiting CSF PCR results! Discharging or delaying antiviral therapy while awaiting imaging will cause irreversible brain necrosis and death.
• Crucial Review Areas:
• 1.
  Medial temporal lobes and hippocampi on coronal FLAIR and DWI: asymmetric hyperintensity and restricted diffusion.
• 2.
  Insular cortex and subfrontal gyri: swelling with sharp sparing of the adjacent lentiform nucleus.
• 3.
  SWI or GRE sequences for petechial punctate blooming artifacts indicating necrotizing hemorrhagic transformation.
• 4.
  Basal cisterns and uncus for medial herniation (uncal herniation) due to massive temporal lobe edema.
• Radiologist Safe Practice & Management:
• 1.
  Immediate Critical Verbal Alert: Instant telephone notification to the Emergency / Acute Neurology Consultant; HSV encephalitis is an extreme neurological emergency.
• 2.
  Immediate Empirical Antiviral Therapy: Instant administration of intravenous Acyclovir (10 mg/kg TDS for 14–21 days) without waiting for imaging or lumbar puncture.
• 3.
  Emergency Brain MRI: Urgent multiplanar MRI including coronal FLAIR, DWI, and SWI sequences to confirm limbic involvement.
• 4.
  Diagnostic Lumbar Puncture: CSF analysis with high-sensitivity viral PCR for HSV-1/2 DNA; elevated protein, lymphocytic pleocytosis, and normal/low glucose.
• 5.
  Repeat Lumbar Puncture Surveillance: Repeat CSF HSV PCR at day 14–21 prior to discontinuing IV Acyclovir to ensure complete virological clearance and prevent relapse.