Herpes Simplex Encephalitis (HSE)

A 42 year old male presents to the emergency department with 2 days of fever, severe headache, progressive confusion, and abnormal behavior. Family members report increasing irritability and episodes of disorganized speech. Shortly after arrival, he develops a focal seizure followed by decreased consciousness. Neurologic examination reveals mild expressive aphasia. MRI brain demonstrates hyperintense lesions involving the medial temporal lobe. Lumbar puncture shows lymphocytic pleocytosis, mildly elevated protein, normal glucose, and red blood cells in the CSF. Diagnosis?

Diagnosis is Herpes Simplex Encephalitis (HSE).

1. Definition

Herpes simplex encephalitis is an acute necrotizing viral encephalitis caused by herpes simplex virus (HSV) and is the most common cause of sporadic fatal viral encephalitis in adults.

1. HSV-1 is the most common cause in adults and older children
2. HSV-2 more commonly causes encephalitis in neonates

HSE characteristically involves the medial temporal lobes and inferior frontal lobes, producing focal neurologic and neuropsychiatric manifestations.

2. Etiology

1. Caused by herpes simplex virus infection
2. Common viral types:
• HSV-1 → adults and older children
• HSV-2 → neonates
3. Mechanism:
• Viral invasion of brain parenchyma
• Predilection for temporal and limbic structures

3. Pathophysiology

1. HSV reaches the CNS and infects brain tissue
2. Viral replication produces:
• Inflammation
• Edema
• Hemorrhagic necrosis
3. Predominant involvement:
• Medial temporal lobes
• Inferior frontal lobes
• Limbic system
4. Consequences:
• Memory dysfunction
• Behavioral abnormalities
• Seizures
• Altered consciousness

4. Clinical Features

4.1 Core Features

1. Fever
2. Headache
3. Altered mental status
4. Behavioral or personality changes
5. Memory impairment or amnesia
6. Seizures
7. Focal neurologic deficits (especially aphasia)

4.2 Associated Features

1. Psychiatric symptoms:
• Agitation
• Hallucinations
2. Temporal lobe manifestations:
• Memory disturbance
• Emotional changes
3. Rare manifestation:
• Klüver–Bucy syndrome (usually bilateral temporal involvement)

5. Diagnosis

5.1 Cerebrospinal Fluid (CSF) Analysis

Typical findings:

1. Lymphocytic pleocytosis
2. Mild to moderate protein elevation
3. Normal glucose
4. RBCs may be present due to hemorrhagic temporal lobe necrosis, but absence of RBCs does not exclude HSE

Lumbar puncture should generally follow neuroimaging if elevated intracranial pressure or mass effect is suspected

5.2 CSF HSV PCR

1. Diagnostic test of choice (gold standard)
2. Detects HSV DNA with high sensitivity and specificity

5.3 Neuroimaging

MRI Brain (preferred and most sensitive imaging modality)

1. T1:
• Hypointense signal
• May appear normal early
2. T2/FLAIR:
• Hyperintense signal
3. Typical findings:
• Medial temporal lobe involvement
• Inferior frontal lobe involvement
• Edema
• Hemorrhagic changes

CT Brain

1. May be normal early in disease
2. Later findings:
• Hypodensity
• Edema
• Mass effect
• Temporal lobe hemorrhagic lesions

5.4 EEG (supportive)

Typical findings:

1. Lateralized periodic discharges (LPDs) (formerly PLEDs)
2. Focal temporal abnormalities

Additional role:

• EEG may help identify nonconvulsive seizures or nonconvulsive status epilepticus, especially in confused or comatose patients

6. Management

6.1 Specific Treatment

1. Intravenous acyclovir
2. Start immediately when HSE is suspected
3. Do not wait for PCR confirmation

Typical duration:

• 14–21 days
• Severe disease or immunocompromised patients commonly receive 21 days

If initial CSF HSV PCR is negative but clinical suspicion remains high:

• Continue acyclovir
• Repeat CSF HSV PCR in 3–7 days

6.2 Supportive Management

1. Seizure control
2. Airway support if required
3. Hemodynamic stabilization
4. Management of raised intracranial pressure
5. Fluid and electrolyte management

7. Key Clinical Insight

Fever + altered mental status + seizures + temporal lobe involvement on MRI strongly suggests Herpes Simplex Encephalitis

8. Exam Level Pearls

1. Most common cause of sporadic fatal viral encephalitis in adults
2. HSV-1 causes most adult cases
3. Temporal lobe involvement is classic
4. CSF may contain RBCs due to hemorrhagic necrosis, but absence does not exclude disease
5. CSF HSV PCR is the diagnostic test of choice
6. Start IV acyclovir immediately and do not delay treatment for confirmatory testing
7. Repeat HSV PCR if initial testing is negative but suspicion remains high