Autoimmune Encephalitis¶
VERSION: 1.0 CREATED: January 24, 2026 REVISED: January 24, 2026 STATUS: Draft - Pending Review
DIAGNOSIS: Autoimmune Encephalitis
ICD-10: G04.81 (Other encephalitis and encephalomyelitis, autoimmune), G04.90 (Encephalitis and encephalomyelitis, unspecified), G13.1 (Other systemic atrophy primarily affecting CNS in neoplastic disease)
SCOPE: Evaluation and management of autoimmune encephalitis in adults, including antibody-mediated (anti-NMDAR, LGI1, CASPR2, GABA-B, AMPA, etc.) and paraneoplastic encephalitis. Covers diagnostic workup, tumor screening, first-line and second-line immunotherapy, and long-term management. Excludes infectious encephalitis, Hashimoto's encephalopathy (SREAT), and pediatric-specific presentations.
CLINICAL SYNONYMS: Limbic encephalitis, anti-NMDA receptor encephalitis, paraneoplastic encephalitis, antibody-mediated encephalitis, voltage-gated potassium channel complex encephalitis (VGKC)
KEY CLINICAL FEATURES: - Subacute onset: Days to weeks (usually <3 months) - Psychiatric symptoms: Psychosis, paranoia, personality change, agitation, catatonia - Cognitive dysfunction: Memory impairment (especially short-term), confusion - Seizures: New-onset seizures (often refractory) - Movement disorders: Orofacial dyskinesia, choreoathetosis, dystonia, catatonia - Autonomic instability: Hyperthermia, blood pressure fluctuations, tachycardia, hypoventilation - Decreased level of consciousness: May progress to coma
MAJOR ANTIBODY SYNDROMES:
| Antibody | Clinical Features | Tumor Association | Demographics |
|---|---|---|---|
| Anti-NMDAR | Psychiatric, seizures, movement disorder, autonomic instability, coma | Ovarian teratoma (50% in women) | Young women > men |
| Anti-LGI1 | Faciobrachial dystonic seizures, hyponatremia, memory loss | Thymoma (<10%) | Older adults (>50) |
| Anti-CASPR2 | Neuromyotonia, limbic encephalitis, Morvan syndrome | Thymoma (20%) | Older men |
| Anti-GABA-B | Limbic encephalitis, prominent seizures | SCLC (50%) | Older adults |
| Anti-AMPA | Limbic encephalitis, psychiatric symptoms | SCLC, thymoma, breast (65%) | Older adults |
| Anti-GAD65 | Stiff person, cerebellar, limbic encephalitis | Rare | F > M |
| Anti-Hu (ANNA-1) | Limbic encephalitis, sensory neuropathy, cerebellar | SCLC (majority) | Older adults |
| Anti-Ma2/Ta | Limbic/brainstem encephalitis, sleep disorder | Testicular, SCLC, breast | Young men (testicular) |
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
⚡ TREATABLE CAUSE OF ENCEPHALITIS
Autoimmune encephalitis is treatable but time-sensitive. Earlier immunotherapy leads to better outcomes. Do not wait for antibody results to start treatment if clinical suspicion is high.
⚠️ TUMOR SEARCH CRITICAL
Many autoimmune encephalitides are paraneoplastic. Tumor identification and treatment are essential for neurological recovery.
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential | Infection screen, baseline | Normal | STAT | STAT | — | STAT |
| CMP (BMP + LFTs) | Electrolytes (hyponatremia in LGI1), renal/hepatic function | Na+ <135 suggests LGI1; otherwise normal | STAT | STAT | — | STAT |
| TSH | Hashimoto's encephalopathy differential | Normal | URGENT | ROUTINE | — | URGENT |
| Blood glucose | Metabolic encephalopathy screen | Normal | STAT | STAT | — | STAT |
| ESR, CRP | Inflammatory markers | Usually normal or mildly elevated | URGENT | ROUTINE | — | URGENT |
| PT/INR, PTT | Pre-LP | INR <1.5 | STAT | STAT | — | STAT |
| HIV antibody/antigen | Immunocompromise screen | Negative | — | ROUTINE | — | ROUTINE |
| RPR/VDRL | Neurosyphilis differential | Negative | — | ROUTINE | — | ROUTINE |
| Urinalysis, urine drug screen | Alternative diagnoses | Negative | STAT | ROUTINE | — | STAT |
| Ammonia | Metabolic encephalopathy | Normal | URGENT | ROUTINE | — | URGENT |
| B12, folate | Metabolic causes of encephalopathy | Normal | — | ROUTINE | — | ROUTINE |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Autoimmune encephalitis panel (serum) | Antibody identification | Identify specific antibody (NMDAR, LGI1, CASPR2, GABA-B, AMPA, GAD65, others) | — | STAT | — | STAT |
| Paraneoplastic panel (serum) | Tumor-associated antibodies | Identify Hu, Yo, Ri, Ma2/Ta, CV2, amphiphysin | — | STAT | — | STAT |
| TPO antibodies | Hashimoto's encephalopathy | Document if elevated | — | ROUTINE | — | ROUTINE |
| Anti-thyroglobulin antibodies | Hashimoto's encephalopathy | Document if elevated | — | ROUTINE | — | ROUTINE |
| ANA, dsDNA | Autoimmune disease screen | Usually negative | — | ROUTINE | — | ROUTINE |
| ANCA | Vasculitis screen | Negative | — | ROUTINE | — | ROUTINE |
| Tumor markers (CEA, AFP, CA-125, CA 19-9, beta-hCG, PSA) | Occult malignancy | Normal | — | ROUTINE | — | ROUTINE |
| Serum protein electrophoresis | Paraproteinemia | Normal | — | ROUTINE | — | ROUTINE |
| Quantitative immunoglobulins | Pre-IVIg, immunodeficiency | IgA >7 mg/dL | — | URGENT | — | URGENT |
| Hepatitis B surface antigen | Pre-rituximab screening | Negative | — | ROUTINE | — | ROUTINE |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Cell-based assay for neuronal antibodies | More sensitive than commercial panels | Antibody confirmation | — | EXT | — | EXT |
| VGCC antibodies (P/Q and N-type) | LEMS, cerebellar degeneration | Negative unless paraneoplastic | — | EXT | — | EXT |
| SOX1 antibody | SCLC-associated | Document | — | EXT | — | EXT |
| DPPX antibody | GI symptoms + encephalopathy | Document | — | EXT | — | EXT |
| Neurexin-3 antibody | Encephalitis, seizures | Document | — | EXT | — | EXT |
| IgLON5 antibody | Sleep disorder, brainstem dysfunction | Document | — | EXT | — | EXT |
| Mitochondrial DNA testing | Mitochondrial encephalopathy | Normal | — | EXT | — | EXT |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with and without contrast | STAT | Medial temporal T2/FLAIR hyperintensity (limbic); may be normal in 50% | Hemodynamic instability, pacemaker | STAT | STAT | — | STAT |
| EEG (routine or continuous) | STAT if seizures or AMS | Extreme delta brush (NMDAR), temporal slowing, seizures | None | STAT | STAT | — | STAT |
| CT chest/abdomen/pelvis with contrast | Tumor search | Occult malignancy (lung, ovary, testes, thymus) | Contrast allergy, renal impairment | — | URGENT | — | URGENT |
MRI Findings: - Limbic encephalitis: Medial temporal lobe T2/FLAIR hyperintensity (uni- or bilateral) - Anti-NMDAR: Often normal; may show subtle cortical/subcortical changes - May be normal in up to 50%: Does NOT rule out autoimmune encephalitis
EEG Findings: - Extreme delta brush: Highly specific for anti-NMDAR encephalitis (seen in ~30%) - Temporal slowing: Common in limbic encephalitis - Subclinical seizures: Frequent; continuous EEG recommended
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Pelvic ultrasound (women) | If anti-NMDAR positive | Ovarian teratoma | None | — | URGENT | — | URGENT |
| MRI pelvis with contrast | If US equivocal | Ovarian teratoma | Pacemaker | — | URGENT | — | URGENT |
| Testicular ultrasound (men <50) | If anti-Ma2 or clinical concern | Testicular tumor | None | — | URGENT | — | URGENT |
| CT or PET-CT chest | Thymoma, lung cancer | Tumor identification | Contrast allergy | — | URGENT | — | URGENT |
| Whole body PET-CT | Occult malignancy search | Any FDG-avid tumor | Hemodynamic instability | — | URGENT | — | URGENT |
| Mammogram | Breast cancer screening | Normal | None | — | ROUTINE | — | ROUTINE |
| Continuous EEG (cEEG) | Refractory cases, coma | Nonconvulsive seizures | None | — | STAT | — | STAT |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Brain biopsy | Diagnostic uncertainty, refractory | Inflammatory infiltrate | Coagulopathy | — | EXT | — | EXT |
| FDG-PET brain | Clarify extent of involvement | Temporal hypermetabolism | Hemodynamic instability | — | EXT | — | EXT |
| Repeat whole body imaging | If initial negative, strong suspicion | Occult tumor | — | — | EXT | — | EXT |
LUMBAR PUNCTURE¶
Indication: ALL suspected autoimmune encephalitis
Timing: URGENT after CT (or proceed directly if no contraindications)
Volume Required: 15-20 mL (need adequate volume for antibody testing)
| Study | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Opening pressure | Usually normal | 10-20 cmH2O | URGENT | STAT | — | STAT |
| Cell count with differential | Lymphocytic pleocytosis | WBC 10-100 (lymphocyte predominant); may be normal | URGENT | STAT | — | STAT |
| Protein | Often mildly elevated | 45-100 mg/dL; may be normal | URGENT | STAT | — | STAT |
| Glucose | Usually normal | Normal | URGENT | STAT | — | STAT |
| Autoimmune encephalitis panel (CSF) | Critical for diagnosis | Identify neuronal antibodies; CSF more sensitive than serum for some (NMDAR) | STAT | STAT | — | STAT |
| Oligoclonal bands | Intrathecal synthesis | May be positive | — | ROUTINE | — | ROUTINE |
| IgG index | Intrathecal synthesis | May be elevated | — | ROUTINE | — | ROUTINE |
| HSV PCR | Exclude HSV encephalitis | Negative (but post-HSV autoimmune is possible) | STAT | STAT | — | STAT |
| VZV PCR | Exclude VZV encephalitis | Negative | STAT | STAT | — | STAT |
| Bacterial culture, Gram stain | Exclude bacterial infection | Negative | STAT | STAT | — | STAT |
| Cytology | Carcinomatous meningitis | Negative | — | ROUTINE | — | ROUTINE |
| BioFire ME Panel | Exclude infectious causes | Negative | STAT | STAT | — | STAT |
CSF Findings in Autoimmune Encephalitis:
| Parameter | Typical Finding |
|---|---|
| Opening pressure | Normal |
| WBC | Normal to mild pleocytosis (10-100, lymphocytes) |
| Protein | Normal to mildly elevated |
| Glucose | Normal |
| Oligoclonal bands | May be positive |
| Neuronal antibodies | Positive (CSF more sensitive for NMDAR) |
CRITICAL: CSF may be completely normal in autoimmune encephalitis. A normal CSF does NOT rule out the diagnosis.
Special Handling: Send adequate volume (15-20 mL). CSF autoimmune panel sent to reference lab; results may take 1-2 weeks.
3. TREATMENT¶
CRITICAL: Start immunotherapy empirically if clinical suspicion high. Do NOT wait for antibody results (may take 1-2 weeks).
When to Start Empiric Immunotherapy¶
Start empiric treatment when ALL of the following are met: 1. Clinical presentation meets criteria for "possible autoimmune encephalitis" (subacute onset, encephalopathy, plus seizures/CSF pleocytosis/MRI findings) 2. Infectious etiologies reasonably excluded (negative CSF bacterial culture/Gram stain, HSV PCR sent or negative) 3. Alternative diagnoses (toxic, metabolic, structural) reasonably excluded
Escalate urgency for empiric treatment if: - Severe presentation (ICU admission, status epilepticus, coma) - Rapidly progressive course - Classical syndrome (e.g., young woman with psychiatric symptoms + movement disorder → anti-NMDAR)
Reference: Canadian Consensus Guidelines; Cellucci et al. 2020
3A. First-Line Immunotherapy¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Methylprednisolone | IV | First-line immunotherapy | 1000 mg daily x 5 days :: IV :: daily x 5 days :: 1000 mg IV daily x 3-5 days; infuse over 1 hour | Active untreated infection, uncontrolled diabetes (relative) | Glucose, BP, psychiatric symptoms, GI bleeding | — | STAT | — | STAT |
| IVIg (immune globulin IV) | IV | First-line immunotherapy | 0.4 g/kg/day x 5 days :: IV :: daily x 5 days :: 0.4 g/kg/day IV for 5 days (total 2 g/kg); start slow day 1 | IgA deficiency with anti-IgA antibodies; severe renal impairment | Renal function, headache, infusion reactions | — | STAT | — | STAT |
| Plasmapheresis (PLEX) | — | First-line immunotherapy | 5-7 exchanges over 10-14 days :: — :: QOD :: 5-7 exchanges over 10-14 days; 1-1.5 plasma volumes per exchange | Hemodynamic instability, severe sepsis | BP, electrolytes, coagulation, fibrinogen | — | STAT | — | STAT |
First-Line Strategy: - High-dose steroids + IVIg: Most common initial approach - PLEX: Alternative or in combination with steroids - Combination: Steroids + IVIg OR Steroids + PLEX often used together - Response time: May take 2-4 weeks; if no improvement, proceed to second-line
3B. Second-Line Immunotherapy (If First-Line Fails)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Rituximab | IV | First-line failure, anti-NMDAR | 375 mg/m² weekly x 4 weeks; 1000 mg x 2 doses :: IV :: weekly x 4 or 1000 mg q2wk x 2 :: 375 mg/m² IV weekly x 4 OR 1000 mg IV x 2 doses (2 weeks apart); pre-medicate | Active infection, HBV (screen), live vaccines | Infusion reactions, B-cell counts, immunoglobulins | — | URGENT | — | URGENT |
| Cyclophosphamide | IV | First-line failure, paraneoplastic | 750 mg/m² monthly x 6 :: IV :: monthly :: 750 mg/m² IV monthly x 6 cycles; with mesna for bladder protection | Cytopenias, active infection, pregnancy | CBC weekly, renal function, hemorrhagic cystitis | — | URGENT | — | URGENT |
Second-Line Timing: - Standard: Consider at 2-4 weeks if no response to first-line - Critically ill (ICU, coma, refractory status epilepticus): Consider second-line agents at 1-2 weeks if no improvement, or sooner if rapidly deteriorating - Early escalation considerations: Disease severity, initial treatment response, and relapse risk - Practical note: Given delayed onset of rituximab effect (weeks), continue first-line therapies until clinical improvement observed - Earlier in severe/refractory cases (persistent coma, ICU-level care) - Rituximab preferred for anti-NMDAR encephalitis - Cyclophosphamide often preferred for paraneoplastic encephalitis
3C. Tumor Treatment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Tumor resection (ovarian teratoma) | Surgical | Anti-NMDAR with teratoma | N/A :: — :: :: Surgical removal of ovarian teratoma is CRITICAL for recovery; early surgery improves outcomes | Unstable patient | Post-op neuro status | — | URGENT | — | URGENT |
| Thymectomy | Surgical | Thymoma-associated encephalitis | N/A :: — :: :: Surgical resection of thymoma | Unstable patient | Post-op neuro status | — | ROUTINE | — | ROUTINE |
| Oncology treatment | Various | Tumor-associated encephalitis | Per oncology :: — :: :: Treat underlying malignancy per oncology recommendations | — | Per oncology | — | ROUTINE | — | ROUTINE |
CRITICAL: Tumor removal is essential for neurological recovery in paraneoplastic cases. Early surgery (especially teratoma removal) significantly improves outcomes.
3D. Seizure Management¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Levetiracetam | IV/PO | Seizures, seizure prophylaxis | 1000 mg BID; 1500 mg BID; 2000 mg BID :: IV/PO :: BID :: Load 1000-2000 mg IV, then 1000-1500 mg BID; may need higher doses | Severe renal impairment (adjust) | Seizure frequency, behavior | STAT | STAT | — | STAT |
| Lacosamide | IV/PO | Adjunctive seizure control | 200 mg BID; 300 mg BID :: IV/PO :: BID :: Load 200-400 mg IV, then 200-300 mg BID | PR prolongation, severe cardiac disease | ECG, PR interval | — | STAT | — | STAT |
| Valproate | IV/PO | Seizures | 20 mg/kg load; 500 mg BID; 750 mg BID :: IV/PO :: load then BID :: Load 20-30 mg/kg IV, then 500-750 mg BID; target level 50-100 | Liver disease, mitochondrial disease, pregnancy | LFTs, ammonia, levels | STAT | STAT | — | STAT |
| Lorazepam | IV | Acute seizure termination | 2 mg; 4 mg :: IV :: PRN :: 0.1 mg/kg IV (max 4 mg); may repeat x1 | Respiratory depression | RR, O2 sat | STAT | STAT | — | STAT |
| Midazolam infusion | IV | Refractory status epilepticus | 0.1-0.4 mg/kg/hr :: IV :: continuous :: 0.2 mg/kg bolus, then 0.1-0.4 mg/kg/hr infusion; for refractory seizures | — | EEG, sedation, respiratory | — | — | — | STAT |
3E. Symptomatic/Supportive Care¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Haloperidol | IV/IM | Agitation, psychosis | 2-5 mg q4-6h PRN :: IV/IM :: q4-6h PRN :: 2-5 mg IV/IM q4-6h PRN for severe agitation; avoid in movement disorders | QT prolongation, movement disorders, Parkinson | QTc, EPS | STAT | STAT | — | STAT |
| Quetiapine | PO | Agitation, psychosis (milder) | 25 mg BID; 50 mg BID; 100 mg BID :: PO :: BID :: Start 25 mg BID; titrate as needed; lower EPS risk | QT prolongation | QTc, sedation | — | ROUTINE | — | ROUTINE |
| Lorazepam | IV/PO | Catatonia, agitation | 1 mg q6h; 2 mg q6h :: IV/PO :: q6h :: 1-2 mg IV/PO q6h; often effective for catatonia | Respiratory depression | RR, sedation | STAT | STAT | — | STAT |
| Propranolol | PO | Autonomic instability (tachycardia) | 10 mg TID; 20 mg TID :: PO :: TID :: 10-20 mg PO TID for tachycardia | Bradycardia, hypotension, asthma | HR, BP | — | ROUTINE | — | ROUTINE |
| Clonidine | PO/transdermal | Autonomic instability | 0.1 mg BID; 0.1 mg patch weekly :: PO/TD :: BID :: 0.1 mg PO BID or 0.1 mg/24h patch; for hypertension/tachycardia | Hypotension | BP, HR | — | ROUTINE | — | ROUTINE |
| Enoxaparin | SC | DVT prophylaxis | 40 mg daily :: SC :: daily :: 40 mg SC daily | Active bleeding, coagulopathy | Platelet count | — | STAT | — | STAT |
| Famotidine | IV/PO | Stress ulcer prophylaxis | 20 mg BID :: IV/PO :: BID :: 20 mg BID if on steroids or intubated | None | GI bleeding | — | ROUTINE | — | ROUTINE |
| Insulin | IV/SC | Steroid-induced hyperglycemia | Per sliding scale :: IV/SC :: per protocol :: Target glucose <180 mg/dL | Hypoglycemia | Glucose q4-6h | — | ROUTINE | — | STAT |
3F. Long-Term/Maintenance Immunotherapy¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Mycophenolate mofetil | PO | Maintenance immunosuppression | 500 mg BID; 1000 mg BID; 1500 mg BID :: PO :: BID :: Start 500 mg BID; increase to 1000-1500 mg BID over 2-4 weeks | Pregnancy, cytopenias | CBC q2wk x 2 mo, then monthly | — | ROUTINE | ROUTINE | — |
| Azathioprine | PO | Maintenance immunosuppression | 50 mg daily; 100 mg daily; 150 mg daily :: PO :: daily :: Start 50 mg daily; increase by 50 mg q2-4wk to 2-3 mg/kg/day; check TPMT first | TPMT deficiency, pregnancy | CBC weekly x 4, then monthly; LFTs | — | ROUTINE | ROUTINE | — |
| Prednisone (oral taper) | PO | Steroid taper | 60 mg daily; 40 mg daily; 20 mg daily; 10 mg daily :: PO :: daily :: Taper over weeks to months; individualize based on response | — | Glucose, BP, bone density | — | ROUTINE | ROUTINE | — |
| Rituximab (maintenance) | IV | Relapse prevention (NMDAR) | 500-1000 mg q6mo :: IV :: q6 months :: 500-1000 mg IV q6 months for 2 years or longer; recheck antibodies | Active infection | B-cell counts, immunoglobulins | — | — | ROUTINE | — |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurology consult for diagnosis confirmation, immunotherapy guidance, and antibody interpretation | STAT | STAT | — | STAT |
| Neuro-immunology consult for complex cases, second-line therapy decisions, and long-term management | — | URGENT | ROUTINE | URGENT |
| Oncology consult for tumor workup and treatment if paraneoplastic syndrome identified | — | URGENT | — | URGENT |
| Gynecologic oncology for ovarian teratoma removal which is critical for anti-NMDAR encephalitis recovery | — | URGENT | — | URGENT |
| Critical care consult for ICU admission given autonomic instability, coma, or need for sedation/ventilation | STAT | STAT | — | STAT |
| Psychiatry consult for severe psychiatric symptoms, catatonia, or behavioral management in acute phase | — | URGENT | — | URGENT |
| Epilepsy consult for refractory seizures and continuous EEG monitoring guidance | — | URGENT | — | URGENT |
| Physical therapy for mobility assessment and fall prevention given fluctuating weakness and dyskinesias | — | ROUTINE | ROUTINE | ROUTINE |
| Occupational therapy for ADL assessment and cognitive rehabilitation to maximize functional recovery | — | ROUTINE | ROUTINE | ROUTINE |
| Speech therapy for swallow evaluation and communication strategies given dysarthria and aphasia | — | URGENT | ROUTINE | URGENT |
| Neuropsychology for formal cognitive assessment to document deficits and guide rehabilitation | — | — | ROUTINE | — |
| Social work for discharge planning and family support given prolonged recovery and potential disability | — | ROUTINE | ROUTINE | ROUTINE |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately if worsening confusion, seizures, or new symptoms develop (may indicate relapse requiring treatment escalation) | STAT | — | STAT |
| Continue immunotherapy as prescribed even when feeling better; stopping early increases relapse risk | — | STAT | STAT |
| Report fever or signs of infection promptly as immunosuppression increases infection risk | — | STAT | STAT |
| Follow seizure precautions including no driving, swimming alone, or heights due to unpredictable seizure risk | — | STAT | STAT |
| Attend all follow-up appointments as relapses can occur months to years after initial presentation | — | ROUTINE | ROUTINE |
| Expect that recovery may take months to years; improvement often continues for 2+ years | — | ROUTINE | ROUTINE |
| Participate in cognitive rehabilitation as this is essential for optimizing recovery from memory and executive deficits | — | ROUTINE | ROUTINE |
| Contact Autoimmune Encephalitis Alliance (www.aealliance.org) for patient support and educational resources | — | ROUTINE | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Use fall precautions including walker and supervision due to movement disorders and cognitive impairment | STAT | STAT | STAT |
| Aspiration precautions including thickened liquids and upright positioning if swallow impaired | STAT | STAT | — |
| DVT prophylaxis with SCDs and/or anticoagulation given prolonged immobility risk | — | STAT | — |
| Avoid live vaccines while on immunosuppression; inactivated vaccines are safe and recommended | — | ROUTINE | ROUTINE |
| Practice infection prevention including hand hygiene and avoiding sick contacts while on immunosuppression | — | STAT | STAT |
| Continue regular cancer screening for paraneoplastic cases as tumor recurrence can trigger relapse | — | — | ROUTINE |
| Use cognitive pacing with scheduled rest periods to manage post-encephalitis fatigue | — | ROUTINE | ROUTINE |
| Do not drive until cleared by neurology due to seizure risk and cognitive impairment | — | STAT | STAT |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| HSV encephalitis | Acute, temporal lobe predominant, hemorrhagic | MRI temporal, HSV PCR |
| Other viral encephalitis | Fever, CSF pleocytosis, specific epidemiology | Viral PCRs |
| Bacterial meningitis | Acute, toxic, PMN predominant CSF | CSF Gram stain, culture |
| Tuberculous meningitis | Subacute, basilar, low glucose | CSF AFB, PCR, ADA |
| Neurosyphilis | Risk factors, varied presentations | RPR, CSF VDRL, FTA-ABS |
| Primary CNS lymphoma | Immunocompromised, periventricular | MRI pattern, CSF cytology |
| Glioblastoma | Focal deficits, ring-enhancing mass | MRI, biopsy |
| Creutzfeldt-Jakob disease | Rapid dementia, myoclonus, DWI restriction | MRI pattern, 14-3-3, RT-QuIC |
| Hashimoto's encephalopathy (SREAT) | Elevated TPO, responds to steroids | TPO antibodies, exclusion |
| Psychiatric illness (primary) | No CSF/MRI changes, prior history | Normal workup, psychiatric evaluation |
| Toxic/metabolic encephalopathy | Drug/toxin exposure, metabolic derangement | Toxicology, metabolic panel |
| ADEM | Post-infectious, multifocal white matter | MRI pattern (multifocal), monophasic |
| CNS vasculitis | Multifocal strokes, systemic symptoms | Angiography, vessel wall MRI |
| Wernicke encephalopathy | Alcoholism, classic triad, mammillary bodies | Thiamine trial, MRI |
| Seizure-related (postictal) | Seizure witnessed, resolves with time | EEG, observation |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurological exam (GCS, MMSE) | q4-8h initially | Improving | Re-evaluate treatment, escalate | STAT | STAT | ROUTINE | STAT |
| Seizure activity | Continuous if cEEG; q4h assessment | No seizures | Escalate antiepileptic therapy | STAT | STAT | — | STAT |
| Vital signs (autonomic function) | q1-4h | Stable HR, BP, temp | Supportive care, ICU if unstable | STAT | STAT | — | STAT |
| Blood glucose | q6h if on steroids | <180 mg/dL | Insulin adjustment | — | ROUTINE | — | STAT |
| Renal function | q24-48h during IVIg | Cr stable | Hydration, adjust IVIg rate | — | ROUTINE | — | ROUTINE |
| Serum sodium | q12-24h (especially LGI1) | 135-145 mEq/L | Fluid restriction if hyponatremic | STAT | STAT | — | STAT |
| Antibody titers (serum/CSF) | q3-6 months | Decreasing | Consider treatment escalation | — | — | ROUTINE | — |
| Tumor surveillance | Per oncology | No recurrence | Oncology management | — | — | ROUTINE | — |
| B-cell counts (if on rituximab) | Before each infusion | Adequate depletion | Adjust dosing interval | — | — | ROUTINE | — |
| CBC (if on immunosuppression) | q1-4 weeks | Normal counts | Hold medication, infection workup | — | ROUTINE | ROUTINE | ROUTINE |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| ICU admission | GCS <12; refractory seizures; autonomic instability; need for intubation; coma; severe psychiatric symptoms requiring restraint |
| Step-down/telemetry | GCS 12-14; controlled seizures; stable autonomic function; receiving immunotherapy |
| General floor | GCS 15; stable; no seizures; able to participate in therapies; can complete immunotherapy |
| Acute rehabilitation | Significant cognitive or motor deficits; requires intensive therapy; medically stable |
| Discharge home | Significant improvement; safe swallow; adequate support; outpatient immunotherapy arranged; neurology follow-up scheduled |
| Long-term care | Severe persistent deficits; unable to live independently |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| First-line immunotherapy (steroids, IVIg, PLEX) | Class II, Level B | Titulaer et al. Lancet Neurol 2013 |
| Early immunotherapy improves outcomes | Class II, Level B | Titulaer et al. Lancet Neurol 2013 |
| Second-line therapy (rituximab, cyclophosphamide) | Class III, Level C | Dalmau et al. Lancet Neurol 2019 |
| Tumor removal essential for recovery | Class II, Level B | Titulaer et al. Lancet Neurol 2013 |
| CSF more sensitive than serum for NMDAR | Class II, Level B | Gresa-Arribas et al. Lancet Neurol 2014 |
| Extreme delta brush in anti-NMDAR | Class III, Level C | Schmitt et al. Neurology 2012 |
| LGI1 associated with hyponatremia and FBDS | Class II, Level B | Irani et al. Brain 2010 |
| Diagnostic criteria for autoimmune encephalitis | Consensus Guidelines | Graus et al. Lancet Neurol 2016 |
| Long-term outcomes and relapse risk | Class II, Level B | Titulaer et al. Lancet Neurol 2013 |
CHANGE LOG¶
v1.0 (January 24, 2026) - Initial template creation - Comprehensive antibody syndrome table - First and second-line immunotherapy protocols - Tumor screening guidance - Seizure and autonomic management - Long-term maintenance therapy
APPENDIX A: Graus 2016 Diagnostic Criteria for Autoimmune Encephalitis¶
Possible Autoimmune Encephalitis (all 3 required): 1. Subacute onset (<3 months) of working memory deficits, altered mental status, or psychiatric symptoms 2. At least ONE of: - New focal CNS findings - Seizures not explained by prior seizure disorder - CSF pleocytosis (>5 WBC/μL) - MRI features suggestive of encephalitis 3. Reasonable exclusion of alternative causes
Definite Autoimmune Encephalitis: - Possible autoimmune encephalitis PLUS - Positive neuronal antibody (serum or CSF)
Probable Anti-NMDAR Encephalitis (all 3 required): 1. Rapid onset (<3 months) of at least 4 of: - Abnormal behavior or cognitive dysfunction - Speech dysfunction - Seizures - Movement disorder, dyskinesias, or rigidity - Decreased level of consciousness - Autonomic dysfunction or central hypoventilation 2. At least ONE of: - Abnormal EEG - CSF pleocytosis or oligoclonal bands 3. Reasonable exclusion of alternative causes
APPENDIX B: Tumor Screening by Antibody¶
| Antibody | Primary Tumor | Screening |
|---|---|---|
| Anti-NMDAR | Ovarian teratoma (women) | Pelvic US → MRI pelvis if negative; repeat q6mo x 2 years |
| Anti-LGI1 | Thymoma (rare) | CT chest |
| Anti-CASPR2 | Thymoma (~20%) | CT chest |
| Anti-GABA-B | SCLC (~50%) | CT chest; PET-CT if negative |
| Anti-AMPA | SCLC, thymoma, breast | CT chest/abdomen; mammogram; PET-CT |
| Anti-Hu (ANNA-1) | SCLC (~80%) | CT chest; PET-CT if negative |
| Anti-Yo | Ovarian, breast | Pelvic US, mammogram, CT |
| Anti-Ma2/Ta | Testicular (young men), SCLC | Testicular US, CT chest |
| Anti-CV2/CRMP5 | SCLC, thymoma | CT chest |
| Anti-amphiphysin | Breast, SCLC | Mammogram, CT chest |
If initial screening negative but paraneoplastic suspected: - Repeat imaging in 3-6 months - Consider whole-body PET-CT - Continue surveillance for at least 5 years
APPENDIX C: Treatment Algorithm¶
SUSPECTED AUTOIMMUNE ENCEPHALITIS
│
▼
┌─────────────────────────────┐
│ 1. Exclude infections (HSV, │
│ bacterial, etc.) │
│ 2. Send antibody panels │
│ (serum AND CSF) │
│ 3. MRI brain, EEG │
│ 4. CT body for tumor │
└─────────────────────────────┘
│
▼
High clinical suspicion?
/ \
YES NO
│ │
▼ ▼
┌──────────────┐ Wait for
│ START │ antibody
│ FIRST-LINE: │ results
│ • IV steroids│
│ • IVIg │
│ • ± PLEX │
└──────────────┘
│
▼
Response at 2-4 weeks?
/ \
YES NO
│ │
▼ ▼
┌──────────────┐ ┌──────────────┐
│ Continue │ │ SECOND-LINE: │
│ maintenance │ │ • Rituximab │
│ therapy │ │ • ± Cyclophos│
└──────────────┘ └──────────────┘
│ │
▼ ▼
TUMOR FOUND? TUMOR FOUND?
│ │
YES YES
│ │
▼ ▼
┌─────────────────────┐
│ TUMOR TREATMENT │
│ (Surgery, chemo, │
│ radiation) │
│ ESSENTIAL FOR │
│ NEUROLOGICAL │
│ RECOVERY │
└─────────────────────┘
APPENDIX D: Prognosis by Antibody Type¶
| Antibody | Outcome | Relapse Rate | Notes |
|---|---|---|---|
| Anti-NMDAR | Good with treatment (80% significant recovery) | 12-25% | Better if teratoma removed; relapses respond to treatment |
| Anti-LGI1 | Good (70-80% respond) | 20-35% | Cognitive deficits may persist; hyponatremia improves |
| Anti-CASPR2 | Moderate to good | Variable | May have associated neuromyotonia |
| Anti-GABA-B | Moderate (depends on tumor) | Low if tumor controlled | Prognosis linked to tumor |
| Anti-AMPA | Moderate to poor | High (>50%) | Often paraneoplastic; tumor treatment important |
| Anti-Hu | Poor | Low (progressive) | Usually paraneoplastic; neurological deficits often irreversible |
| Anti-Yo | Poor | Low (progressive) | Cerebellar degeneration usually irreversible |
| Anti-Ma2 | Moderate | Variable | Better if testicular tumor found and treated |