Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
HSV encephalitis and other viral encephalitis
Infectious diseases, microbiology and sexual health · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Suspected viral encephalitis
Fever with confusion, new behaviour, memory loss, focal seizure, dysphasia or focal deficit may be HSV encephalitis and delay in aciclovir causes avoidable death and disability.
Action: Use ABCDE, control seizures, obtain blood and CSF when safe and start renal-adjusted intravenous aciclovir immediately. Arrange urgent MRI and EEG and continue bacterial meningitis cover when that differential remains; do not wait for imaging or PCR.
Overview
Recognise encephalitis from altered cognition, focal seizure and behavioural change, start intravenous aciclovir before confirmation, use MRI, EEG and repeat cerebrospinal-fluid PCR correctly, and prevent renal and neurological treatment harm.
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.
Practice
Two practice questions
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Infectious diseases, microbiology and sexual healthOriginal SBA
Positive CSF after treatment
An immunocompetent adult has completed fourteen days of intravenous aciclovir for proven HSV encephalitis, but repeat CSF remains HSV-PCR positive. What is the safest next step?
Sources and review status3 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
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.
Aetiology
01
Herpesvirus neuroinvasion
HSV-1, HSV-2 and VZV enter or reactivate in sensory pathways and spread into brain, meninges or cerebral vessels.
02
Exposure-specific viruses
Enteroviruses, arboviruses and animal-associated viruses cause encephalitis according to travel, season, vector, vaccine and immune context.
Pathophysiology
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.
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.
Investigations
01CSF 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.
02MRI 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.
03EEG
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.
04Metabolic, 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.
Differential diagnosis
01
Bacterial meningitis or abscess
Fever, altered consciousness and seizure can result from purulent meningeal or focal infection and requires simultaneous antibacterial assessment.
02
Autoimmune encephalitis
Psychosis, movement disorder, dysautonomia and characteristic antibodies support immune disease after infection remains covered and sampled.
03
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.
Management
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.+
Complications
01
Death and severe disability
Cerebral oedema, herniation, status epilepticus and extensive necrosis remain potentially fatal or permanently disabling despite appropriate antiviral treatment.
Memory, language, executive, personality and mood changes often dominate long-term functional outcome and ongoing rehabilitation needs.
Monitoring and follow-up
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.
Special situations
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.
Common pitfalls
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.
1
Review 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.