What part of the brain does Herpes Simplex Virus (HSV) attack?

Herpes Simplex Virus Primarily Attacks the Temporal and Frontal Lobes

Herpes simplex virus (HSV) encephalitis characteristically targets the medial temporal lobes, inferior frontal lobes, and cingulate gyrus, with bilateral temporal lobe involvement being nearly pathognomonic for HSV-1 infection. 1

Primary Brain Regions Affected

Temporal Lobe Structures (Most Common)

• The medial temporal lobes are the hallmark target, specifically involving the hippocampus and amygdala 1
• The entorhinal cortex is frequently affected 1
• MRI reveals bilateral temporal lobe edema with high signal intensity on T2-weighted and FLAIR sequences in approximately 90% of cases when performed within 48 hours 2
• Autopsy studies demonstrate hippocampal disease with HSV protein present in astrocytes and neurons, confirming local viral reactivation 1

Frontal Lobe Involvement

• The inferior frontal lobes show characteristic edema and hyperintensity on neuroimaging 1
• The cingulate gyrus demonstrates gyral edema on T1-weighted images and high signal intensity on T2/FLAIR sequences 2, 3

Regions Typically Spared

• The basal ganglia and thalami are nearly always spared in classic HSV encephalitis 4
• When thalamic involvement occurs, it represents an atypical and very rare presentation 4

Clinical Manifestations Related to Anatomic Involvement

Temporal Lobe Syndrome

• Memory impairment and short-term memory loss result from hippocampal damage 1
• Temporal lobe seizures are relatively frequent due to involvement of temporal structures 1
• Language and behavioral abnormalities reflect temporal and frontal lobe dysfunction 1

Less Common Presentations

• Brainstem encephalitis occurs in approximately 29% of cases as an isolated finding, though 71% show multifocal involvement including the brainstem 5
• HSV-1 accounts for 79% of brainstem cases, with HSV-2 responsible for 21% 5
• Brainstem involvement carries a mortality rate of 41%, though intravenous acyclovir reduces this significantly (22% vs 75% without treatment) 5

Imaging Characteristics by Location

MRI Findings

• Diffusion-weighted imaging (DWI) shows the highest sensitivity for early changes in affected temporal and frontal regions 2, 3
• T2-weighted and FLAIR sequences demonstrate hyperintense lesions that are circumscribed and non-enhancing in the medial temporal lobes 1
• Bilateral temporal lobe involvement on MRI is nearly pathognomonic for HSV-1 encephalitis 1, 2

Important Clinical Pitfalls

Atypical Anatomic Presentations

• While temporal lobe involvement is classic, focal neurological deficits are rare despite the localized nature of infection 1
• Hemorrhagic conversion can complicate HSV encephalitis in 2.7% of cases, requiring close neurological monitoring 6
• Normal initial MRI does not exclude HSV encephalitis, as imaging may be negative early in disease despite active infection 1

Diagnostic Considerations

• The characteristic temporal lobe predilection helps distinguish HSV from other viral encephalitides: HHV-6 affects frontal and parietal white matter or can cause limbic encephalitis 1, while VZV causes ischemic or hemorrhagic infarcts with arterial abnormalities 2
• CT scanning has only 25% sensitivity for initial diagnosis and may be normal in 69% of early HSV encephalitis cases, making it unreliable for excluding the diagnosis 2, 3