HSV encephalitis and other viral encephalitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Encephalitis is inflammation of brain parenchyma causing altered mental status for more than a transient period, usually with fever, seizure, focal neurology, CSF inflammation, MRI change or EEG abnormality. HSV-1 is the critical immediately treatable cause; VZV, enterovirus, arboviruses and immune-suppressed pathogens follow exposure and host context.

HSV reaches the brain through neural pathways and preferentially injures temporal and inferior frontal structures, causing haemorrhagic necrosis, oedema and seizure. The clinical syndrome may precede PCR positivity or MRI evolution. Aciclovir is therefore empirical, while parallel testing seeks bacterial, autoimmune, toxic and structural causes and prevents premature closure.

Key points

Encephalitis means brain dysfunction with evidence of inflammation; meningism can coexist but altered cognition and focal features are decisive.
HSV-1 is the most important treatable sporadic cause in adults, often affecting temporal lobes and producing memory, language, behaviour or seizure symptoms.
Start aciclovir 10 mg/kg intravenously every 8 hours immediately, using protocol weight, hydration and renal adjustment.
Perform lumbar puncture when safe for cells, glucose, protein and HSV, VZV and selected pathogen PCR, without postponing aciclovir.
MRI is more sensitive than CT for temporal and limbic inflammation; EEG detects temporal periodic activity and non-convulsive seizures.
Repeat HSV PCR after 24 to 72 hours when an early negative result conflicts with a strong syndrome or characteristic MRI.
Treat proven HSV encephalitis for at least 14 days in immunocompetent adults and commonly 21 days in immune suppression, with repeat CSF before stopping when indicated.
Investigate autoimmune encephalitis, metabolic, toxic, epileptic and structural alternatives when virology is negative or recovery is atypical.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Herpesvirus neuroinvasion

HSV-1, HSV-2 and VZV enter or reactivate in sensory pathways and spread into brain, meninges or cerebral vessels.

Exposure-specific viruses

Enteroviruses, arboviruses and animal-associated viruses cause encephalitis according to travel, season, vector, vaccine and immune context.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Temporal haemorrhagic necrosis
HSV replication and immune injury destroy temporal and inferior frontal tissue, causing oedema, haemorrhage and focal seizure.
2
Network electrical disruption
Inflamed cortex produces convulsive or non-convulsive seizures that worsen cerebral metabolic demand and secondary neuronal injury.
3
Post-infectious autoimmunity
Neuronal antigens exposed during infection can trigger later antibody-mediated encephalitis, especially during recovery from confirmed HSV encephalitis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Temporal-lobe syndromeRed flag

Fever, memory failure, dysphasia, personality change, olfactory symptoms or focal seizure strongly supports HSV encephalitis.

VZV vasculitic diseaseRed flag

Recent zoster, cranial neuropathy, multifocal infarction or vascular headache raises VZV even without rash.

Non-convulsive statusRed flag

Persistent reduced awareness, subtle twitching or fluctuating cognition can be ongoing seizure and requires urgent EEG.

Red flags requiring action

New focal seizure, temporal-lobe symptom or personality change with fever is HSV encephalitis until urgently assessed.
Falling consciousness, recurrent seizure or airway compromise requires critical care and continuous neurological monitoring.
A negative HSV PCR very early in illness does not exclude disease and should prompt repeat CSF when probability remains high.
Rising creatinine, myoclonus or worsening confusion during aciclovir can be crystal nephropathy or neurotoxicity as well as infection.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
CSF PCR and inflammatory profileFirst step
Why
Detect HSV, VZV and selected viruses while characterising meningeal inflammation.
Interpretation and limitations
Lymphocytes and elevated protein support inflammation. Early HSV PCR can be negative; repeat at 24 to 72 hours if clinical and MRI probability remains high.
02
MRI brain
Why
Identify temporal, limbic, brainstem or multifocal patterns and alternative lesions.
Interpretation and limitations
Temporal T2 or diffusion change supports HSV but normal early imaging does not exclude it; distribution can suggest autoimmune or arboviral disease.
03
EEG
Why
Detect non-convulsive seizure and supportive temporal abnormalities.
Interpretation and limitations
Periodic lateralised discharges support HSV but are not specific. Continuous monitoring is needed when consciousness fluctuates or seizures recur.
04
Metabolic, toxic and autoimmune screen
Why
Find reversible mimics and antibody-mediated disease when the course is atypical.
Interpretation and limitations
Check glucose, electrolytes, liver, renal, toxins and medication; send paired serum and CSF neuronal antibodies after infection sampling, not instead of it.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bacterial meningitis or abscess

Fever, altered consciousness and seizure can result from purulent meningeal or focal infection and requires simultaneous antibacterial assessment.

Autoimmune encephalitis

Psychosis, movement disorder, dysautonomia and characteristic antibodies support immune disease after infection remains covered and sampled.

Metabolic, toxic or epileptic encephalopathy

Hypoglycaemia, sodium disorder, hepatic or renal failure, medicines and non-convulsive status can all produce potentially reversible altered cognition.

Additional chapter-specific clues

Autoimmune mimicRed flag

Psychosis, dyskinesia, autonomic instability and seizures with negative infectious tests raises autoimmune encephalitis but does not justify early aciclovir omission.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ASSESSStart aciclovir on suspicionFirst stepEncephalitis is possible from altered mental status plus fever, seizure or focal findings.

1Stabilise airway, breathing, circulation and glucose, treat convulsive seizure and obtain senior neurology and critical-care review.
2Give intravenous aciclovir immediately with renal-adjusted dosing and continue ceftriaxone when bacterial meningitis remains plausible.
3Perform lumbar puncture when safe and send sufficient CSF for bacterial and viral PCR, culture and later autoimmune testing.
4AlternativeArrange urgent MRI and EEG; use CT only for immediate mass-effect or alternative emergencies, not as a gate before aciclovir.

02TREATConfirm cause without delayInitial stabilisation and empirical therapy are underway.

1Review timing of CSF sampling and repeat HSV PCR after an early negative when syndrome or MRI remains convincing.
2Expand viral tests using travel, vector, animal, immune and rash history and notify public health for relevant arboviruses.
3Investigate autoimmune encephalitis, tumour, toxins, metabolic disease and non-convulsive status in parallel when evidence diverges.
4AlternativeAvoid stopping aciclovir on one early negative result without a documented alternative explanation.

03REVIEWComplete treatment and rehabilitationHSV or another cause is established and acute physiology is improving.

1Treat HSV for the guideline duration, repeat CSF near the stop point when indicated and extend if PCR remains positive.
2Monitor creatinine, fluid balance and neurological toxicity daily and change dose promptly with renal deterioration.
3Assess memory, language, mood, epilepsy, mobility, swallowing and occupational needs and begin multidisciplinary rehabilitation early.
4Plan seizure therapy, driving advice, neuropsychology, community support and relapse review before discharge.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Provides time-critical inhibition of herpesvirus DNA replication and reduces mortality when started early.

Intravenous aciclovir

Give aciclovir 10 mg/kg intravenously every 8 hours using protocol weight, renal adjustment and adequate hydration for suspected HSV encephalitis.

Infuse appropriately, monitor creatinine and neurological state and consider crystal nephropathy or accumulation when renal function or cognition worsens.

Prevents ongoing excitotoxic brain injury and supports safe airway and diagnostic assessment.

Antiseizure treatment

Use the current emergency benzodiazepine and longer-acting antiseizure protocol for convulsive or electrographic seizures.

Dose for organ function and interactions and use EEG to avoid both untreated non-convulsive status and unnecessary prolonged sedation.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Death and severe disability

Cerebral oedema, herniation, status epilepticus and extensive necrosis remain potentially fatal or permanently disabling despite appropriate antiviral treatment.

Post-encephalitic epilepsy

Cortical scarring creates recurrent seizures requiring long-term neurological follow-up, antiseizure treatment assessment and formal driving restriction.

Cognitive and psychiatric sequelae

Memory, language, executive, personality and mood changes often dominate long-term functional outcome and ongoing rehabilitation needs.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record consciousness, language, memory, pupils, focal deficits and seizures at frequent intervals and use continuous EEG when indicated.
Check renal function and fluid balance at least daily during intravenous aciclovir and after every physiological change.
Review CSF timing, PCR, MRI and EEG together before stopping therapy or assigning an autoimmune diagnosis.
Arrange neuropsychology, epilepsy, rehabilitation, mood, driving and occupational follow-up because deficits may emerge after physical recovery.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Treatment precedes proof

The preventable harm of delayed aciclovir outweighs the short initial exposure in a credible encephalitis syndrome.

Early PCR can miss HSV

Low early viral burden means one negative sample near symptom onset cannot overrule temporal features and MRI.

Drug toxicity mimics disease

Renal aciclovir accumulation causes tremor, myoclonus and confusion, demanding simultaneous dose and infection reassessment.

Recovery is multidimensional

Memory, executive function, language, mood and fatigue may limit independence despite normal strength and improving scans.

11Common pitfallsFrequent interpretation and management errors.

01
Waiting for MRI or CSF PCR before the first intravenous aciclovir dose.
02
Stopping aciclovir after one early negative HSV PCR despite a convincing temporal syndrome.
03
Ignoring renal adjustment and mislabelling aciclovir neurotoxicity as worsening encephalitis.
04
Discharging without seizure, cognition, mood, driving and rehabilitation planning.