Medicine – Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is an acute, potentially fatal viral infection of the brain caused most commonly by herpes simplex virus type 1 (HSV-1) in adults. It characteristically produces a necrotising encephalitis involving the temporal lobes, particularly the medial and inferior temporal regions.

It is one of the most important treatable causes of sporadic viral encephalitis. Because neurological damage can progress rapidly, intravenous aciclovir should be started immediately when HSV encephalitis is suspected, without waiting for definitive PCR confirmation.

1. Cause

In adults and older children, herpes simplex encephalitis is most commonly caused by:

HSV-1.

HSV-2 is less commonly responsible for encephalitis in adults but is particularly important in neonatal HSV infection and can also cause meningitis.

2. Temporal Lobe Predilection

HSV encephalitis has a characteristic tendency to involve the:

Temporal lobes.

The pathology particularly affects the:

Medial temporal lobes.

Inferior temporal lobes.

Insular cortex.

The frontal lobes may also become involved.

The original description of anterior temporal lobe pathology therefore captures an important feature, although involvement is often broader than the anterior temporal region alone.

3. Pathology

HSV produces a severe:

Necrotising haemorrhagic encephalitis.

There is inflammation, neuronal destruction, cerebral oedema, and often small areas of haemorrhage.

This explains why red blood cells may sometimes be found in the CSF.

4. Cerebral Oedema

Significant cerebral oedema can develop.

Severe cerebral swelling may increase intracranial pressure and contribute to:

Reduced consciousness.

Seizures.

Neurological deterioration.

Brain herniation in extreme cases.

Therefore, severe cases require close neurological and critical-care monitoring.

5. Clinical Presentation

HSV encephalitis typically presents as an acute febrile encephalopathy.

Important features include:

Fever.

Headache.

Confusion.

Altered behaviour or personality.

Reduced consciousness.

Seizures.

Focal neurological deficits.

The combination of fever + altered mental state + seizures or focal neurological signs should raise suspicion for encephalitis.

6. Behavioural and Psychiatric Changes

Because the temporal and limbic regions are commonly involved, patients may develop striking behavioural abnormalities.

These can include:

Personality change.

Agitation.

Confusion.

Memory disturbance.

Hallucinations or unusual behaviour.

Occasionally, the initial presentation can resemble a primary psychiatric disorder.

7. Memory Disturbance

Temporal-lobe and limbic-system involvement can produce significant:

Short-term memory impairment.

Patients who survive severe disease may be left with persistent memory problems because the medial temporal structures are important for memory formation.

8. Seizures

Seizures are common in HSV encephalitis.

They may be:

Focal seizures.

Focal to bilateral tonic-clonic seizures.

or

Generalised convulsive seizures.

Temporal-lobe involvement makes focal seizures particularly understandable.

9. Focal Neurological Features

Patients may develop focal abnormalities such as:

Dysphasia.

Hemiparesis.

Focal seizures.

Visual-field abnormalities.

The exact deficit depends on the distribution and severity of cerebral involvement.

10. CSF Examination

Lumbar puncture is an important investigation when it can be performed safely.

The characteristic CSF pattern is:

Lymphocytic pleocytosis.

Mild to moderately raised protein.

Usually normal glucose.

This is broadly the pattern expected in viral encephalitis.

11. CSF Lymphocytosis

The CSF white cell count is usually elevated with predominantly:

Lymphocytes.

Early in the illness, however, neutrophils can occasionally predominate before the typical lymphocytic pattern develops.

Therefore, an early neutrophilic CSF does not completely exclude viral encephalitis.

12. CSF Protein

CSF protein is generally:

Mildly to moderately elevated.

This reflects inflammation and disruption of the blood–brain barrier.

Very marked protein elevation should encourage consideration of additional or alternative diagnoses.

13. CSF Glucose

CSF glucose is usually:

Normal.

This helps distinguish typical viral encephalitis from conditions such as:

Bacterial meningitis.

Tuberculous meningitis.

Fungal meningitis.

where CSF glucose is commonly reduced.

14. Red Blood Cells in CSF

HSV causes haemorrhagic necrosis, particularly in the temporal lobes.

Therefore, CSF may sometimes contain:

Red blood cells.

However, this finding is neither sufficiently sensitive nor specific to diagnose HSV encephalitis.

A traumatic lumbar puncture can also introduce red cells into CSF.

15. HSV PCR

The most important specific CSF investigation is:

HSV polymerase chain reaction (PCR).

HSV PCR detects viral DNA in the CSF and is the key diagnostic test for HSV encephalitis.

16. Early Negative HSV PCR

An important clinical point is that PCR can occasionally be negative very early in the disease.

Therefore, if clinical suspicion remains high despite an early negative result:

Aciclovir should generally be continued and repeat CSF HSV PCR may be required.

A single early negative PCR should not automatically override a strongly suggestive clinical picture.

17. MRI Brain

MRI is the preferred brain imaging investigation for suspected HSV encephalitis.

Typical abnormalities involve:

Medial temporal lobes.

Inferior temporal lobes.

Insular cortex.

Sometimes the frontal lobes are also involved.

18. MRI Appearance

MRI may demonstrate:

T2/FLAIR hyperintensity.

Cerebral oedema.

Restricted diffusion.

Haemorrhagic changes in some patients.

Temporal-lobe abnormalities can be unilateral initially but frequently become bilateral or asymmetric.

19. CT Brain

CT is less sensitive than MRI early in HSV encephalitis.

It may initially be normal.

Later it may demonstrate:

Temporal-lobe oedema.

Low-density changes.

Mass effect.

Haemorrhage.

CT may nevertheless be useful urgently when MRI is unavailable or when evaluating for another intracranial process.

20. EEG

EEG commonly demonstrates abnormalities over the:

Temporal regions.

Possible findings include:

Focal slowing.

Epileptiform discharges.

Historically, periodic lateralised epileptiform discharges have been associated with HSV encephalitis, although they are not specific to the disease.

21. EEG and Non-Convulsive Seizures

EEG is particularly valuable when a patient remains confused or unconscious and non-convulsive status epilepticus is suspected.

Therefore, EEG can provide both:

Supportive evidence of temporal-lobe dysfunction

and

Detection of ongoing electrical seizure activity.

22. Treatment Is an Emergency

Suspected HSV encephalitis is a neurological emergency.

The key treatment is:

Intravenous aciclovir.

Treatment should be started as soon as the diagnosis is suspected.

23. Do Not Wait for PCR

A crucial management principle is:

Do not wait for the HSV PCR result before starting intravenous aciclovir.

Waiting for laboratory confirmation can allow further irreversible brain injury.

Therefore:

Suspected HSV encephalitis → take appropriate investigations + start IV aciclovir immediately.

24. Aciclovir Mechanism

Aciclovir is converted within infected cells to an active nucleotide analogue.

It inhibits viral:

DNA polymerase.

This suppresses HSV DNA replication and limits further viral proliferation.

25. Renal Considerations with Aciclovir

Intravenous aciclovir can cause renal toxicity, particularly through crystal-associated kidney injury.

Therefore, management includes attention to:

Adequate hydration.

Renal function monitoring.

Dose adjustment in renal impairment.

26. Treatment of Seizures

Seizures should be treated appropriately.

The original note lists:

Phenytoin.

Phenytoin can be used in seizure management, but it is no longer appropriate to regard it as the universal antiseizure drug specifically required for HSV encephalitis.

Modern treatment may use drugs such as:

Levetiracetam.

Fosphenytoin/phenytoin.

or other antiseizure medications depending on the clinical situation.

27. Acute Convulsive Seizures

If a prolonged convulsive seizure occurs, initial emergency treatment generally involves a:

Benzodiazepine.

If seizures continue, a longer-acting antiseizure medication is given according to the status epilepticus protocol.

Therefore:

Aciclovir treats the infection.

Antiseizure medication treats associated seizures.

28. Supportive Management

Severe HSV encephalitis may require:

Airway protection.

Mechanical ventilation.

Management of raised intracranial pressure.

Fluid and electrolyte management.

Treatment of seizures.

Nutritional support.

Critical-care monitoring.

29. Prognosis

Untreated HSV encephalitis carries a very high risk of severe neurological damage and death.

Early aciclovir treatment substantially improves outcome.

However, survivors may still develop persistent neurological problems such as:

Memory impairment.

Cognitive impairment.

Personality or behavioural changes.

Epilepsy.

Focal neurological deficits.

30. Herpes Simplex Encephalitis – Note Form

Main virus in adults: HSV-1.

Characteristic site: temporal lobes, especially medial/inferior temporal regions, with possible insular and frontal involvement.

Pathology: necrotising haemorrhagic encephalitis + cerebral oedema.

Clinical presentation: fever + headache + confusion/behavioural change + seizures ± focal neurological deficits.

CSF cells: lymphocytic pleocytosis.

CSF protein: mildly/moderately increased.

CSF glucose: usually normal.

CSF red cells: may occur because of haemorrhagic necrosis.

Specific investigation: CSF HSV PCR.

MRI: temporal-lobe/insular abnormalities.

EEG: focal temporal abnormalities ± epileptiform discharges.

Treatment: immediate intravenous aciclovir.

Seizures: treat with appropriate antiseizure therapy; phenytoin/fosphenytoin is one possible option rather than a mandatory specific treatment.

31. HSV Encephalitis versus Typical Viral Meningitis

HSV encephalitis:

Altered mental state prominent.

Behaviour/personality change.

Seizures common.

Focal neurological deficits may occur.

Temporal-lobe MRI abnormalities.

HSV PCR positive.

Viral meningitis:

Headache and meningism more prominent.

Consciousness usually relatively preserved.

Focal cerebral abnormalities are less characteristic.

Therefore, brain dysfunction is the key feature distinguishing encephalitis from uncomplicated meningitis.

Key Clinical Pattern

Think of herpes simplex encephalitis as:

FEVER + CONFUSION/BEHAVIOURAL CHANGE + SEIZURES + TEMPORAL-LOBE ABNORMALITY.

The classic investigation pattern is:

CSF lymphocytes ↑ + protein mildly ↑ + glucose usually normal + HSV PCR positive.

Imaging:

MRI → medial/inferior temporal-lobe ± insular lesions.

And the most important management rule is:

SUSPECT HSV ENCEPHALITIS → START IV ACICLOVIR IMMEDIATELY.

Do not wait for PCR confirmation before treating.