Encephalitis and HSV encephalitis

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

Encephalitis is a syndrome rather than a single organism. HSV-1 is the most important treatable sporadic cause in UK adults, while VZV may occur with or without rash. Enteroviruses, travel-related arboviruses, tuberculosis, HIV-associated infections and immune-mediated disease enter the differential according to host and exposure. Sepsis-associated delirium, metabolic disturbance, toxic ingestion, primary psychiatric illness, stroke, tumour and non-convulsive status can mimic inflammation, so parallel testing is safer than a sequential search for one favoured diagnosis.

The defining clinical problem is altered brain function. Confusion, reduced consciousness, new personality or memory change, dysphasia, focal weakness, movement disorder and seizure may occur. Fever or cerebrospinal-fluid pleocytosis can be absent early or in immunosuppression. Temporal-lobe symptoms are evocative of HSV but not compulsory. A first psychiatric presentation with fluctuation, seizures, catatonia, dyskinesia or autonomic instability needs neurological assessment rather than being assumed functional or primary psychiatric.

Treatment and diagnostics run concurrently. Intravenous aciclovir and, until bacterial infection is excluded, appropriate empirical antibiotics are started promptly. MRI, lumbar puncture and EEG then refine the syndrome. If HSV tests remain negative but suspicion persists, repeat sampling and senior virology review are safer than premature cessation. If infection evidence wanes, autoimmune testing and oncological screening may be indicated, with immunotherapy decided by specialists because steroids or other suppression can worsen an unrecognised infection.

Key points

Encephalitis is brain parenchymal inflammation causing altered mental status, behaviour or cognition, usually lasting at least 24 hours, with supporting fever, seizure, focal findings, cerebrospinal-fluid inflammation, MRI change or EEG abnormality.
HSV encephalitis commonly affects temporal and inferior frontal regions, producing fever, personality change, memory disturbance, aphasia, olfactory phenomena or focal seizures, but early disease can be non-specific.
Start intravenous aciclovir promptly when viral encephalitis is suspected; its benefit is greatest before extensive necrotic injury and treatment should not await diagnostic confirmation.
Obtain lumbar puncture as soon as safely possible for cells, protein, paired glucose, bacterial studies and HSV or VZV PCR, but stabilisation and treatment come first.
An early HSV PCR can be falsely negative, especially very soon after symptom onset; continue aciclovir and repeat cerebrospinal-fluid testing when clinical or MRI suspicion remains high.
MRI is more sensitive than CT for temporal inflammation, haemorrhage and alternative diagnoses; CT remains useful when urgent mass effect, haemorrhage or lumbar-puncture safety is being assessed.
EEG can reveal temporal periodic discharges, focal seizures or non-convulsive status and is essential when consciousness fails to improve despite no visible convulsions.
Autoimmune encephalitis, including anti-NMDA-receptor disease, may resemble viral infection; psychiatric symptoms, dyskinesia, autonomic instability and refractory seizures should prompt paired serum and cerebrospinal-fluid specialist testing.
Adjust aciclovir for kidney function, provide adequate hydration and monitor creatinine because crystal nephropathy can cause both kidney injury and drug neurotoxicity.
Survivors often have memory, language, epilepsy, fatigue, mood and behavioural sequelae; rehabilitation and family support should begin during admission rather than after crisis discharge.
In England, suspected acute encephalitis is a notifiable disease: report it through the online service within 3 days without waiting for PCR or serology, and telephone the local health-protection team urgently if another urgent disease or an immediate public-health risk is suspected; use equivalent devolved-nation routes elsewhere.

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

Herpes-family viruses

HSV is a major treatable sporadic cause and often targets temporal or inferior frontal regions; VZV may cause encephalitis with or without a visible rash.

Other infectious agents

Enteroviruses, arboviruses, bacteria, fungi and parasites become relevant according to season, geography, exposure and immune status.

Autoimmune encephalitis

Neuronal surface, synaptic or paraneoplastic immunity can mimic infection with psychiatric change, seizures, movement disorder and dysautonomia.

Immunosuppression-related disease

HIV, transplantation, malignancy and immune-modifying treatment widen the pathogen range and may blunt fever, cerebrospinal-fluid inflammation or imaging responses.

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

1
Neural entry and replication
A pathogen reaches brain tissue through neural or bloodstream routes and infects susceptible neurons or supporting cells.
2
Parenchymal inflammation
Viral cytotoxicity and host immune responses disrupt the blood–brain barrier, causing oedema, haemorrhage and focal or diffuse neuronal dysfunction.
3
Temporal and network injury
HSV often damages limbic and language networks, producing memory change, personality disturbance, aphasia and focal seizures.
4
Secondary excitotoxic damage
Ongoing seizures, raised pressure, hypoxia and systemic illness extend tissue injury beyond direct infection and influence long-term disability.

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

Temporal-lobe syndrome

Fever with new short-term memory loss, personality change, dysphasia, olfactory hallucination or focal seizure is highly concerning for HSV encephalitis.

Encephalopathy plus inflammation

Altered cognition or consciousness persisting beyond 24 hours gains support from fever, cerebrospinal-fluid white cells, MRI inflammation or an inflammatory EEG pattern.

Non-convulsive seizure

Fluctuating responsiveness, subtle facial twitching, eye deviation or unexplained failure to wake can represent ongoing electrical seizure activity despite no generalised movements.

Autoimmune phenotype

Prominent psychiatric change followed by seizures, abnormal movements, catatonia or autonomic instability suggests anti-NMDA-receptor or another immune-mediated encephalitis.

Raised-pressure complicationRed flag

Falling consciousness, unequal pupils, Cushing physiology or new extensor posturing indicates possible cerebral oedema or herniation and requires immediate critical-care and neuroimaging action.

Exposure-defined cause

Travel, mosquito or tick exposure, animal contact, immunosuppression, shingles, sexual risk and tuberculosis history direct additional pathogen testing and public-health discussion.

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
MRI brain with appropriate sequencesFirst step
Why
Detect inflammatory brain lesions, haemorrhage and important mimics.
Interpretation and limitations
Asymmetric medial temporal and inferior frontal signal supports HSV, while other distributions may suggest autoimmune, vascular, demyelinating or pathogen-specific disease; early MRI can be normal.
02
Lumbar puncture and paired blood glucose
Why
Characterise inflammation and obtain bacterial, viral and immune studies.
Interpretation and limitations
A lymphocytic pleocytosis and raised protein support viral disease; red cells may occur in haemorrhagic HSV injury but are neither required nor specific.
03
Cerebrospinal-fluid HSV and VZV PCR
Why
Confirm a treatable herpetic cause and guide duration.
Interpretation and limitations
Sensitivity is high after the earliest phase, but a negative early sample does not safely stop aciclovir when phenotype or MRI remains convincing; repeat testing is then required.
04
Electroencephalography
Why
Detect focal cerebral dysfunction, non-convulsive seizures and status epilepticus.
Interpretation and limitations
Temporal slowing or periodic discharges support but do not prove HSV; electrographic seizures require prompt antiseizure treatment and monitoring.
05
Blood cultures, metabolic and toxic screen
Why
Identify sepsis, organ dysfunction and reversible mimics of encephalopathy.
Interpretation and limitations
Check glucose, electrolytes, calcium, renal and liver function, blood count, inflammatory markers and toxic exposures according to context while treating the neurological emergency.
06
Paired autoimmune encephalitis studies
Why
Investigate immune-mediated disease when infection is unconfirmed or phenotype is suggestive.
Interpretation and limitations
Send both cerebrospinal fluid and serum through a neurology-led panel; isolated low-specificity serum results require clinical correlation and must not trigger unsupervised immunosuppression.
07
Body imaging or pelvic ultrasonography
Why
Search for an associated tumour when a specific autoimmune syndrome warrants it.
Interpretation and limitations
The antibody, age and sex determine screening, repetition and modality; ovarian teratoma is particularly relevant in anti-NMDA-receptor encephalitis.

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

Bacterial or viral meningitis

Headache, fever and neck stiffness with preserved cognition favour meningeal disease, while substantial behaviour, memory, focal or seizure disturbance indicates parenchymal involvement.

Primary psychiatric illness

A primary psychiatric presentation may resemble encephalitis, but fluctuating cognition, seizure, catatonia, dyskinesia or autonomic instability requires renewed neurological assessment.

Toxic or metabolic encephalopathy

Organ failure, medicines, hypoglycaemia and electrolyte disturbance usually cause diffuse dysfunction without focal temporal inflammation, but concurrent illness is common.

Tumour, abscess or stroke

A mass lesion or vascular-territory pattern on imaging redirects diagnosis; ring enhancement, diffusion and haemorrhage characteristics help distinguish focal structural causes.

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

01First six hoursProtect brain and start empirical treatmentFirst stepAcute altered cognition or consciousness is accompanied by fever, seizure or focal findings.

1Stabilise airway, breathing and circulation, check glucose, treat convulsive status promptly and obtain blood cultures and metabolic samples without delaying therapy.
2Give intravenous aciclovir at the encephalitis regimen and empirical antibacterial meningitis cover as indicated, recording symptom and administration times.
3PreferredInvolve neurology, infection and critical care early, using urgent CT only for emergency pathology or lumbar-puncture safety while arranging MRI as the preferred brain study.
4Report suspected acute encephalitis through the statutory health-protection route without awaiting diagnostic confirmation; urgent telephone contact is additionally required when another urgent notifiable disease or immediate public-health risk is suspected.

02Diagnostic coreCombine fluid, MRI and EEG evidenceThe patient is stable enough for targeted neurological investigation.

1Perform lumbar puncture when safe, retaining enough cerebrospinal fluid for bacterial culture, cells, chemistry, HSV and VZV PCR and later specialist tests.
2Obtain MRI promptly and EEG urgently for seizure, fluctuation or unexplained impaired consciousness, then interpret all three modalities against timing.
3If an early HSV PCR is negative but suspicion remains, continue aciclovir and plan repeat lumbar puncture with virology advice rather than declaring exclusion.

03Alternative causeBroaden when HSV does not explain the syndromeAlternativeStandard infection studies are negative, response is atypical or autoimmune features emerge.

1Revisit travel, immune status, medicines, toxins and systemic clues, extending testing for VZV, HIV, tuberculosis, fungi or arboviruses through specialists.
2Send paired cerebrospinal-fluid and serum autoimmune studies and tumour screening when phenotype supports it, while retaining infection cover until reasonably safe.
3Start corticosteroid, immunoglobulin, plasma exchange or other immunotherapy only through a neurology-led plan that addresses the residual infection risk.

04Recovery phasePlan for acquired brain-injury sequelaeAcute infection is controlled and consciousness begins to improve.

1Assess memory, language, executive function, behaviour, swallowing, mobility and seizures with early neuropsychology and multidisciplinary rehabilitation input.
2Create a clear antiseizure plan, driving advice and emergency instructions, avoiding indefinite therapy without review when seizures were purely acute symptomatic.
3Support relatives with prognosis and behavioural education, arrange neurological follow-up and phase return to work or study according to cognitive recovery.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Empirical and confirmed treatment for HSV encephalitis and important VZV central nervous system infection.

Aciclovir intravenous

Use the current BNF encephalitis regimen, commonly 10 mg/kg intravenously every 8 hours in adults, with renal and body-size adjustment agreed locally.

Start without diagnostic delay, ensure hydration and monitor renal function; accumulation can cause confusion, tremor or myoclonus that resembles worsening encephalitis.

A commonly selected antiseizure medicine when focal or generalised seizures complicate encephalitis.

Levetiracetam

Loading and maintenance doses for acute seizures follow the local status-epilepticus protocol, renal function and specialist direction rather than a universal encephalitis schedule.

Review renal dose, sedation, irritability and behavioural change; acute use does not automatically justify lifelong treatment after recovery.

Protects against bacterial meningitis during the clinically indistinguishable early phase.

Ceftriaxone-based empirical cover

Give the current adult meningitis dose intravenously, adding Listeria coverage when indicated, until bacterial infection has been reasonably excluded.

Check allergy and local microbiology guidance, collect cultures where possible without delay and narrow or stop only after senior review of fluid and culture evidence.

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

Status epilepticus and epilepsy

Inflamed and scarred cortex can generate prolonged acute seizures and later recurrent epilepsy, sometimes without visible convulsions.

Cerebral oedema and herniation

Severe inflammation raises intracranial pressure, reduces perfusion and can cause brain shift, respiratory failure or death.

Memory, language and behavioural disability

Limbic and frontal injury may leave amnesia, aphasia, mood change, disinhibition and loss of employment or independence.

Swallowing and mobility complications

Reduced consciousness and focal deficits increase aspiration, pressure injury, thrombosis and deconditioning during a prolonged admission.

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

Record frequent Glasgow Coma Scale, pupils, focal deficits and behaviour, escalating deterioration for airway protection and intracranial-pressure assessment.
Use continuous or repeated EEG when non-convulsive seizures are possible, and document electrographic as well as visible seizure control.
Check creatinine, electrolytes, fluid balance and aciclovir dose at least daily, responding quickly to oliguria or rising renal markers.
Track temperature, cultures, cerebrospinal-fluid PCR and antimicrobial days with infection specialists, documenting the evidence behind stopping each agent.
Monitor swallowing, nutrition, mobility, pressure risk and venous thrombosis during reduced consciousness and prolonged rehabilitation.
After discharge review seizures, cognition, mood, behaviour, sleep, driving, work and family burden rather than limiting follow-up to repeat imaging.

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

Treatment precedes proof

HSV causes preventable necrotic injury, so the threshold to start aciclovir is deliberately lower than the threshold to conclude the diagnosis.

Early PCR can miss

Sampling very early may yield a false negative; temporal MRI change or a compelling phenotype justifies continued therapy and repeat cerebrospinal fluid.

Drug toxicity can mimic relapse

Renally accumulated aciclovir causes neuropsychiatric and movement symptoms, making daily kidney and dose review diagnostically important.

Psychiatric does not mean primary

Rapid behavioural change with cognitive fluctuation, seizure or dyskinesia can be autoimmune or viral brain disease even when psychiatric symptoms dominate.

Recovery is multidimensional

A normal motor examination can conceal disabling amnesia, impaired planning, emotional lability and loss of social judgement after temporal or frontal injury.

11Common pitfallsFrequent interpretation and management errors.

01
Waiting for HSV PCR before starting intravenous aciclovir.
02
Stopping treatment after one very early negative PCR despite high suspicion.
03
Using CT as a substitute for more sensitive MRI.
04
Missing non-convulsive status in a patient who fails to wake.
05
Failing to adjust aciclovir as renal function deteriorates.
06
Assuming bizarre behaviour is a primary psychiatric disorder without neurology review.
07
Discharging without cognitive, epilepsy and family-support planning.