Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Autoimmune encephalitis
Neurology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Time-critical presentation
Rapid behavioural change with seizures, reduced consciousness, dyskinesia, autonomic instability, hypoventilation or fever is a neurological emergency. Stabilise first, treat plausible herpes encephalitis empirically, control seizures and involve neurology and critical care while autoimmune testing proceeds.
Overview
Recognise subacute immune-mediated encephalopathy among psychiatric, epileptic and infectious mimics, obtain paired diagnostic samples and coordinate early neurological, tumour and critical-care treatment.
Antibodies against neuronal cell-surface or synaptic proteins can alter receptor function and provoke potentially reversible network dysfunction. NMDAR, LGI1, CASPR2, GABA-B and AMPA receptor syndromes are important examples. Antibodies against intracellular antigens more often mark a cytotoxic T-cell and paraneoplastic process, which may respond less completely to immunotherapy and increases the urgency of cancer treatment. Seronegative autoimmune encephalitis remains possible when the clinicoradiological syndrome is strong and alternatives have been rigorously excluded.
Presentation is shaped by the neural circuit involved. Limbic inflammation causes short-term memory failure, temporal seizures, anxiety and behavioural change. Diffuse receptor dysfunction produces psychosis, catatonia, movement disorder, dysautonomia and reduced consciousness. Brainstem or peripheral hyperexcitability may accompany CASPR2 disease. Fever and headache can occur in both infection and autoimmunity, so apparent inflammatory clues do not remove the need for microbiological testing and empiric aciclovir.
Aetiology
01
Neuronal surface antibodies
Antibodies targeting NMDAR, LGI1, CASPR2 and other surface or synaptic proteins can disrupt receptor function and produce potentially reversible network dysfunction.
02
Paraneoplastic intracellular immunity
Antibodies to intracellular antigens often mark a tumour-driven cytotoxic T-cell response, making cancer identification central and neurological recovery less predictably responsive to immunotherapy.
03
Seronegative immune encephalitis
A convincing clinicoradiological inflammatory syndrome may lack an identified antibody after rigorous testing; infection, malignancy, toxic and primary psychiatric alternatives should then be excluded carefully.
Pathophysiology
1
Loss of immune tolerance
Tumour antigens, infection or unexplained immune dysregulation activates B-cell, antibody or cytotoxic T-cell responses against neuronal targets.
2
Limbic and network dysfunction
Immune effectors enter the central nervous system and alter synaptic receptors or injure neurons, particularly within memory, seizure, behavioural and autonomic networks.
3
Escalating cerebral instability
Continuing inflammation produces seizures, psychosis, catatonia, dyskinesia, impaired consciousness and dysautonomia; receptor dysfunction may be reversible even when early recovery appears slow.
Clinical features and red flags
NMDAR phenotypeRed flag
A younger patient develops anxiety, insomnia, psychosis or cognitive change, then seizures, catatonia, oro-lingual or limb dyskinesia, autonomic swings and central hypoventilation. An ovarian teratoma is an important association.
LGI1 patternRed flag
An older adult has dozens of brief unilateral face-and-arm dystonic episodes, new memory impairment and hyponatraemia. These seizures may precede full limbic encephalitis and warrant urgent specialist recognition.
Limbic syndromeRed flag
Subacute anterograde amnesia, confusion, mood or behavioural change and focal temporal seizures accompany mesial-temporal MRI signal or EEG abnormalities. HSV and tumour-associated causes remain key alternatives.
Critical deteriorationRed flag
Status epilepticus, reduced consciousness, temperature or blood-pressure instability, arrhythmia, hypersalivation and hypoventilation indicate severe network and autonomic involvement requiring intensive monitoring.
Red flags against autoimmunity
A toxic exposure, metabolic derangement, medication effect, primary infection, rapidly growing tumour, prion-like progression or isolated chronic psychiatric symptoms without neurological evolution should redirect or broaden investigation.
Relapse or aftermath
New objective seizures, behavioural change or cognitive decline after recovery may be relapse, while fatigue, executive difficulty, mood symptoms and sleep disruption can persist without fresh inflammation; specialist reassessment distinguishes them.
Investigations
01MRI brain with contrastFirst step
Why
Identify limbic or extra-limbic inflammation and exclude stroke, tumour, abscess, demyelination and other structural causes.
Interpretation and limitations
Mesial-temporal T2 or FLAIR signal supports limbic encephalitis but may be unilateral or absent. A normal MRI, especially in NMDAR disease, does not override a convincing evolving syndrome.
02CSF analysis and paired neuronal antibodies
Why
Investigate infection, demonstrate inflammation and improve the specificity of immune testing.
Interpretation and limitations
Send cell count, protein, glucose, cultures or PCR including HSV/VZV as indicated, oligoclonal bands, cytology when relevant and a phenotype-led antibody panel. Interpret serum and CSF together through the specialist laboratory.
03EEG with prolonged monitoring when required
Why
Detect focal or non-convulsive seizures, status epilepticus and diffuse cerebral dysfunction during fluctuating behaviour or consciousness.
Interpretation and limitations
Temporal discharges, slowing or an extreme-delta-brush pattern may support the syndrome, but no finding is sufficiently specific to replace clinical and antibody assessment. Repeated events need video-EEG correlation.
04Metabolic, toxic and infectious work-up
Why
Identify common reversible encephalopathies and safely determine how long empiric antimicrobial treatment is required.
Differential diagnosis
01
HSV or other infectious encephalitis
Fever, temporal seizures and cerebrospinal-fluid inflammation overlap substantially. Viral PCR, microbiology and MRI guide distinction while empirical aciclovir continues until infection is sufficiently excluded.
02
Primary psychiatric illness or catatonia
Isolated psychiatric symptoms may be primary, but new seizures, dyskinesia, fluctuating consciousness, memory loss or autonomic instability strongly support an organic neurological assessment.
03
Non-convulsive status epilepticus
Persistent altered behaviour or responsiveness may reflect ongoing electrical seizure activity; urgent EEG can distinguish a treatable ictal state from encephalitic dysfunction.
04
Toxic, metabolic or neoplastic disease
Medicine exposure, electrolyte or organ failure, lymphoma and infiltrative disease can mimic subacute encephalopathy and require history-led laboratory, imaging and sometimes tissue investigation.
Management
01Unstable presentationStabilise without diagnostic delayFirst stepEncephalopathy is accompanied by seizure, autonomic instability, hypoventilation or falling consciousness.+
1Use ABCDE, check bedside glucose, protect the airway, treat status epilepticus through the emergency protocol and obtain critical-care input for hypoventilation, dysrhythmia or severe autonomic fluctuation.
2After blood cultures and prompt lumbar puncture when safe, start intravenous aciclovir at the locally adjusted encephalitis dose while HSV remains plausible; add antibacterial therapy if meningitis cannot be excluded.
3Arrange urgent MRI and EEG, send paired serum and CSF antibodies, and involve neurology before sedating behavioural symptoms in ways that could conceal seizures or worsen autonomic instability.
4Use careful low-stimulus nursing, venous-thromboembolism prevention, nutrition, bladder, bowel, pressure and family-support plans during prolonged
Complications
01
Refractory seizures and brain injury
Frequent clinical or electrographic seizures can progress to status epilepticus, causing metabolic stress, aspiration and prolonged critical-care dependence.
02
Dysautonomia and hypoventilation
Severe receptor-mediated disease can destabilise heart rate, blood pressure, temperature and breathing, requiring continuous monitoring, airway protection or mechanical ventilation.
03
Persistent cognitive and psychiatric disability
Memory, executive function, mood, behaviour, communication and fatigue may recover slowly and unevenly, necessitating neuropsychology, rehabilitation and sustained family support.
04
Tumour or relapse risk
An associated neoplasm may progress unless identified and treated, while some antibody syndromes relapse and require surveillance or longer-term immune management.
Monitoring and follow-up
Use continuous or repeated EEG when consciousness fluctuates, abnormal movements are ambiguous or non-convulsive status remains possible despite apparent sedation.
Chart respiratory rate, blood gases when indicated, temperature, blood pressure, rhythm, urine output and autonomic episodes; NMDAR disease may require prolonged critical-care support.
Record seizure frequency, sedative exposure, movement phenotype, communication, swallowing and structured cognitive or functional milestones to detect slow improvement.
Follow blood count, renal and liver function, immunoglobulins, glucose and infection markers according to aciclovir, antiseizure and immunotherapy protocols.
Maintain the antibody-specific tumour search and repeat surveillance schedule agreed by neurology and oncology, rather than treating one negative scan as permanent exclusion.
After discharge, assess relapse features separately from depression, trauma, fatigue, sleep disorder and residual executive impairment, with rapid re-access for objective deterioration.
Special situations
Normal MRI is compatible
NMDAR encephalitis may have severe clinical dysfunction despite an unremarkable scan, making serial examination, EEG and paired antibody testing crucial.
CSF prevents false labels
Some serum neuronal antibodies are nonspecific at low titres; a compatible syndrome and CSF result markedly improve diagnostic confidence.
FBDS is a treatment clue
Faciobrachial dystonic seizures can be extremely brief and frequent, and immune treatment may prevent evolution into disabling LGI1 limbic encephalitis.
Tumour links are patterned
The relevant search is guided by antibody, age and sex; indiscriminate investigations may still miss the anatomical site most associated with that syndrome.
Behaviour is neurology
Agitation, psychosis or catatonia can be the leading expression of receptor dysfunction and should be co-managed with psychiatry without surrendering medical ownership.
Recovery needs patience
A patient may show little early change yet later make substantial gains over months; objective trends and complication prevention are more reliable than a single bedside impression.
Common pitfalls
01
Attributing new psychosis to a primary psychiatric disorder despite seizures, dyskinesia, catatonia or autonomic instability.
02
Stopping aciclovir after one very early negative HSV PCR when the infectious phenotype remains convincing.
03
Diagnosing autoimmune encephalitis from an isolated low-positive serum antibody with no compatible syndrome or CSF support.
04
Waiting for the complete antibody panel while status epilepticus, hypoventilation or cognitive decline continues untreated.
05
Failing to search for and treat a phenotype-linked tumour as part of immune control.
06
Assuming abnormal movements are all seizures, or conversely that unusual motor activity cannot conceal electrographic status.
Practice
Two practice questions
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Question 1 of 2
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NeurologyOriginal SBA
Psychosis with neurological escalation
A 22-year-old develops insomnia and paranoid ideas, followed over ten days by seizures, oro-facial dyskinesia, fluctuating consciousness and labile blood pressure. MRI is normal. Which diagnosis should remain a leading concern?
Sources and review status4 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.
Management crosses traditional boundaries. Neurology leads syndrome classification and immune treatment; infectious diseases supports antimicrobial decisions; intensive care manages refractory seizures, dysautonomia and ventilation; psychiatry helps behavioural care without diagnostic overshadowing; oncology or gynaecology addresses a tumour; and rehabilitation treats cognitive, communication, swallowing and motor consequences. Early gains may be subtle, and treatment should not be abandoned because consciousness or behaviour fails to normalise immediately.
Key points
Autoimmune encephalitis typically evolves over days to fewer than three months with impaired memory, altered mental state or psychiatric change plus seizures, focal findings, CSF inflammation, EEG abnormalities or compatible MRI features.
A first psychotic presentation with catatonia, seizures, dyskinesia, fluctuating consciousness or autonomic disturbance needs an organic assessment; age alone must not divert the patient exclusively into a psychiatric pathway.
Anti-NMDA-receptor encephalitis often progresses from psychiatric and cognitive symptoms to seizures, oro-facial dyskinesia, autonomic instability and hypoventilation, especially in younger people.
LGI1 encephalitis is suggested by very brief frequent faciobrachial dystonic seizures, memory loss, temporal-lobe seizures and hyponatraemia, often before routine MRI or CSF becomes striking.
Send both CSF and serum neuronal-antibody panels through an accredited laboratory because sensitivity and specificity differ by antibody; a serum-only low-positive result can mislead.
Do not wait for an antibody result to give intravenous aciclovir when herpes simplex encephalitis remains possible, or to treat a compelling severe autoimmune syndrome after appropriate samples and specialist review.
Interpretation and limitations
Check glucose, electrolytes including sodium, calcium, liver and renal function, inflammatory markers, cultures, HIV and toxicology according to context; repeat HSV PCR if early sampling and suspicion remain high.
05Phenotype-directed tumour screening
Why
Find an associated malignancy whose removal or treatment is part of neurological disease control.
Interpretation and limitations
Choose pelvic imaging, CT chest-abdomen-pelvis, testicular ultrasound, mammography or whole-body metabolic imaging based on sex, age, antibody and risk; surveillance intervals need specialist agreement.
06Pretreatment and complication baseline
Why
Prepare safely for immunosuppression and quantify organ support, rehabilitation and safeguarding needs.
Interpretation and limitations
Use blood count, immunoglobulins, hepatitis, HIV and TB screening, pregnancy testing, ECG, swallow and respiratory assessment, pressure-risk review and a documented cognitive or functional baseline as clinically appropriate.
reduced consciousness
.
02Immune treatmentAct on a compelling syndromeInfection has been reasonably covered or excluded and clinical, CSF, EEG or MRI evidence strongly supports autoimmune encephalitis.+
1Secure pretreatment samples and infection screening without waiting passively for antibody completion when neurological decline is continuing.
2Under specialist direction, use high-dose intravenous corticosteroid with IV immunoglobulin or plasma exchange according to severity, access, thrombotic risk, autonomic stability and likely antibody biology.
3EscalationAssess objective change in seizure burden, arousal, movement disorder, autonomic support and cognition over an appropriate interval, then escalate to rituximab or cyclophosphamide for inadequate response.
4Identify and treat an associated tumour promptly because immune treatment without tumour control may produce an incomplete or short-lived response.
03Recovery phaseRehabilitate the whole syndromeSeizures and autonomic instability are controlled but cognitive, behavioural or physical disability remains.+
1Review antiseizure and psychoactive medicines frequently, reducing unnecessary burden cautiously while avoiding abrupt withdrawal or recurrence of status.
2Provide neuropsychology, occupational, physiotherapy and speech-and-language input for memory, executive function, communication, swallowing, mobility, fatigue and graded return to education or work.
3Agree relapse warning signs, tumour-surveillance and immunotherapy monitoring with a named specialist, and support carers who may be managing striking personality or dependency changes.
Key medicines and prescribing safety5 treatments · regimens, roles and cautions+
Treats possible herpes simplex or varicella-zoster encephalitis while microbiological evidence is pending.
Intravenous aciclovir
Use the local encephalitis regimen, commonly 10 mg/kg intravenously every eight hours with renal adjustment.
Dose by the locally specified weight and renal function, ensure appropriate hydration, monitor creatinine and neurological toxicity, and do not stop solely because the first early HSV PCR is negative.
Provides rapid first-line immunosuppression when autoimmune encephalitis is sufficiently likely.
Intravenous methylprednisolone
A common specialist immune regimen is 1 g once daily for three to five days.
Balance active infection risk and monitor glucose, blood pressure, potassium, sleep, mood and gastrointestinal complications; severe agitation may transiently worsen.
Modulates pathogenic immune activity and may accompany or follow corticosteroid in first-line treatment.
Intravenous immunoglobulin
A frequently used total course is 2 g/kg divided over two to five days by protocol.
Check product guidance and immunoglobulin A history; monitor thrombosis, renal injury, haemolysis, headache and fluid load, especially in immobile or critically ill patients.
Removes circulating antibody in severe disease or when steroid and IV immunoglobulin response is inadequate.
Therapeutic plasma exchange
Specialist teams often plan five to seven exchanges with timing adapted to clinical response.
Consider vascular access, hypotension, citrate reactions, coagulopathy, infection and removal of concomitant medicines or recently administered immunoglobulin.
MRI may be normal, particularly in NMDAR disease; EEG can reveal non-convulsive seizures or characteristic slowing but is rarely antibody-specific.
Search for a phenotype-linked tumour, such as ovarian teratoma with NMDAR antibodies or small-cell lung cancer with certain intracellular antibodies, and repeat screening when specialist guidance indicates.
First-line immunotherapy usually combines high-dose corticosteroid with intravenous immunoglobulin or plasma exchange; rituximab or cyclophosphamide is considered when response is inadequate.
Recovery is often slow and uneven, requiring neurorehabilitation, neuropsychology, speech and language therapy, epilepsy review and support for families long after inflammation is controlled.
Common second-line B-cell therapy for severe, refractory or relapsing cell-surface-antibody encephalitis.
Rituximab
Use a specialist induction and redosing schedule after infection screening and multidisciplinary review.
Screen hepatitis B and tuberculosis as indicated, review vaccination, blood counts and immunoglobulins, and monitor infusion reactions and prolonged infection susceptibility.