Autoimmune Encephalitis¶

VERSION: 1.0 CREATED: January 27, 2026 STATUS: Initial creation

DIAGNOSIS: Autoimmune Encephalitis

ICD-10: G04.81 (Other autoimmune encephalitis), G04.90 (Encephalitis and encephalomyelitis, unspecified)

CPT CODES: 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 84443 (TSH), 85652 (ESR), 86140 (CRP), 87040 (Blood cultures (x2 sets)), 82947 (Blood glucose), 83036 (HbA1c), 82140 (Ammonia), 83605 (Lactate), 83735 (Magnesium), 84100 (Phosphorus), 84145 (Procalcitonin), 84484 (Troponin), 82550 (CPK), 80307 (Urine drug screen), 80320 (Alcohol level), 81025 (Pregnancy test (females of childbearing age)), 83615 (LDH), 86255 (Anti-NMDAR antibody (serum AND CSF)), 86235 (Anti-LGI1 antibody (serum AND CSF)), 70450 (CT head without contrast), 70553 (MRI brain with and without contrast), 95816 (EEG (routine or continuous)), 93000 (ECG (12-lead)), 71046 (Chest X-ray), 78816 (FDG-PET/CT (whole body)), 89051 (Cell count with differential (tubes 1 and 4)), 84157 (Protein), 82945 (Glucose with paired serum glucose), 87529 (HSV 1/2 PCR), 87327 (Cryptococcal antigen), 86592 (VDRL (CSF)), 83916 (Oligoclonal bands (CSF AND paired serum)), 88104 (Cytology), 87116 (AFB culture and smear), 87102 (Fungal culture), 96365 (Methylprednisolone IV)

SYNONYMS: Autoimmune encephalitis, AE, anti-NMDA receptor encephalitis, anti-NMDAR encephalitis, limbic encephalitis, antibody-mediated encephalitis, paraneoplastic encephalitis, LGI1 encephalitis, CASPR2 encephalitis, rapid neurocognitive syndrome

SCOPE: Diagnostic workup, acute treatment, and long-term management of suspected or confirmed autoimmune encephalitis. Covers antibody-mediated encephalitis (anti-NMDAR, LGI1, CASPR2, GABA-B, AMPA, DPPX, IgLON5, GABA-A, GAD65), first-line immunotherapy, second-line escalation, seizure management, psychiatric symptom management, ICU considerations, tumor screening, and long-term immunosuppression. For infectious encephalitis, use "HSV Encephalitis" template. For paraneoplastic syndromes without encephalitis, use "Paraneoplastic Syndrome" template. For status epilepticus management, use "Status Epilepticus" template.

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Baseline; infection screen; pre-immunotherapy	Normal
CMP (BMP + LFTs) (CPT 80053)	STAT	STAT	ROUTINE	STAT	Metabolic screen; renal/hepatic baseline for immunotherapy	Normal
TSH (CPT 84443)	URGENT	ROUTINE	ROUTINE	URGENT	Thyroid encephalopathy mimic; Hashimoto encephalopathy screen	Normal
ESR (CPT 85652)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory/vasculitis screen	Normal (<20 mm/hr)
CRP (CPT 86140)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory marker; infection screen	Normal
Urinalysis with culture (CPT 81003+87086)	STAT	STAT	ROUTINE	STAT	UTI as encephalopathy trigger	Negative
Blood cultures (x2 sets) (CPT 87040)	STAT	STAT	-	STAT	Rule out septic encephalopathy	No growth
Blood glucose (CPT 82947)	STAT	STAT	ROUTINE	STAT	Metabolic encephalopathy screen; pre-steroid baseline	Normal
HbA1c (CPT 83036)	-	ROUTINE	ROUTINE	-	Glycemic status before high-dose steroids	<5.7%
Ammonia (CPT 82140)	STAT	STAT	-	STAT	Hepatic encephalopathy mimic	Normal
Lactate (CPT 83605)	STAT	STAT	-	STAT	Sepsis screen; metabolic screen	Normal (<2.0 mmol/L)
PT/INR, aPTT (CPT 85610+85730)	STAT	STAT	-	STAT	Coagulopathy screen pre-LP; DIC screen	Normal
Magnesium (CPT 83735)	STAT	STAT	ROUTINE	STAT	Seizure threshold; metabolic screen	Normal
Phosphorus (CPT 84100)	STAT	STAT	-	STAT	Metabolic screen	Normal
Procalcitonin (CPT 84145)	URGENT	URGENT	-	URGENT	Distinguish bacterial vs autoimmune etiology	Normal (<0.1 ng/mL)
Troponin (CPT 84484)	STAT	STAT	-	STAT	Cardiac involvement; autonomic instability assessment	Normal
CPK (CPT 82550)	URGENT	URGENT	-	URGENT	Rhabdomyolysis from prolonged seizures/catatonia	Normal
Urine drug screen (CPT 80307)	STAT	STAT	-	STAT	Toxic/drug-induced encephalopathy mimic	Negative
Alcohol level (CPT 80320)	STAT	STAT	-	STAT	Alcohol-related encephalopathy	Negative
Pregnancy test (females of childbearing age) (CPT 81025)	STAT	STAT	ROUTINE	STAT	Eclampsia mimic; treatment planning (teratogenicity)	As applicable
Peripheral blood smear	URGENT	URGENT	-	URGENT	TTP/HUS screen if thrombocytopenia	Normal
LDH (CPT 83615)	URGENT	ROUTINE	ROUTINE	URGENT	Hemolysis screen; tumor marker	Normal
Uric acid	-	ROUTINE	ROUTINE	-	Tumor lysis risk if malignancy suspected	Normal
Lipase	STAT	STAT	-	STAT	Pancreatitis-related encephalopathy	Normal

1B. Autoimmune Antibody Panel¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Anti-NMDAR antibody (serum AND CSF) (CPT 86255)	URGENT	URGENT	ROUTINE	URGENT	Most common autoimmune encephalitis; CSF more sensitive than serum; cell-based assay (CBA) preferred	Negative
Anti-LGI1 antibody (serum AND CSF) (CPT 86235)	URGENT	URGENT	ROUTINE	URGENT	Limbic encephalitis; faciobrachial dystonic seizures (FBDS); hyponatremia	Negative
Anti-CASPR2 antibody (serum AND CSF) (CPT 86235)	URGENT	URGENT	ROUTINE	URGENT	Limbic encephalitis; Morvan syndrome; neuromyotonia; neuropathic pain	Negative
Anti-GABA-B antibody (serum AND CSF)	URGENT	URGENT	ROUTINE	URGENT	Limbic encephalitis with prominent seizures; 50% associated with SCLC	Negative
Anti-AMPA antibody (serum AND CSF)	URGENT	URGENT	ROUTINE	URGENT	Limbic encephalitis; relapsing course; associated with thymoma, lung, breast	Negative
Anti-DPPX antibody (serum AND CSF)	URGENT	URGENT	ROUTINE	URGENT	Encephalitis with hyperexcitability, GI symptoms, PERM	Negative
Anti-IgLON5 antibody (serum AND CSF)	-	URGENT	ROUTINE	URGENT	Sleep disorder, bulbar dysfunction, gait instability, tau pathology	Negative
Anti-GABA-A antibody (serum AND CSF)	-	URGENT	ROUTINE	URGENT	Refractory seizures/status epilepticus; often with thymoma	Negative
Anti-GAD65 antibody (serum AND CSF)	URGENT	URGENT	ROUTINE	URGENT	Limbic encephalitis, stiff-person spectrum, cerebellar ataxia; high titers (>20 nmol/L) significant	Negative or low titer
Mayo Autoimmune Evaluation - Encephalopathy (serum)	URGENT	URGENT	ROUTINE	URGENT	Comprehensive panel: NMDAR, LGI1, CASPR2, GABA-B, AMPA, DPPX	All negative
Mayo Autoimmune Evaluation - Encephalopathy (CSF)	URGENT	URGENT	ROUTINE	URGENT	CSF panel: NMDAR, LGI1, CASPR2, GABA-B, AMPA, DPPX	All negative
ANA (CPT 86235)	URGENT	ROUTINE	ROUTINE	URGENT	Lupus cerebritis screen	Negative or low titer
Anti-dsDNA	-	ROUTINE	ROUTINE	-	If ANA positive; lupus evaluation	Negative
Anti-SSA/SSB (Ro/La)	-	ROUTINE	ROUTINE	-	Sjogren syndrome with CNS involvement	Negative
Anti-TPO antibodies	URGENT	ROUTINE	ROUTINE	URGENT	Hashimoto encephalopathy (SREAT)	Negative
Anti-thyroglobulin antibodies	URGENT	ROUTINE	ROUTINE	URGENT	Hashimoto encephalopathy (SREAT)	Negative
AQP4-IgG (NMO antibody)	-	ROUTINE	ROUTINE	-	NMOSD overlap; cell-based assay preferred	Negative
MOG-IgG	-	ROUTINE	ROUTINE	-	MOGAD overlap; ADEM-like presentation	Negative
Complement C3, C4	-	ROUTINE	ROUTINE	-	Lupus; complement-mediated disease	Normal
Quantitative immunoglobulins (IgG, IgA, IgM)	-	ROUTINE	ROUTINE	-	Baseline before immunotherapy; IgA deficiency (IVIG contraindication)	Normal

Note: ALWAYS send BOTH serum AND CSF for antibody testing. CSF is more sensitive for anti-NMDAR; serum is more sensitive for anti-LGI1 and anti-CASPR2. Cell-based assay (CBA) is gold standard -- avoid ELISA-only testing. Mayo panels preferred for comprehensive evaluation. Results may take 1-3 weeks; do NOT wait for results before starting empiric immunotherapy if clinical suspicion is high.

1C. Rare/Specialized (Refractory or Atypical)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Anti-neuronal nuclear antibody type 1 (ANNA-1/anti-Hu)	-	EXT	EXT	-	Paraneoplastic; SCLC, neuroblastoma	Negative
Anti-neuronal nuclear antibody type 2 (ANNA-2/anti-Ri)	-	EXT	EXT	-	Paraneoplastic; breast, SCLC	Negative
Anti-CV2/CRMP5	-	EXT	EXT	-	Paraneoplastic; SCLC, thymoma	Negative
Anti-amphiphysin	-	EXT	EXT	-	Paraneoplastic; breast, SCLC; stiff-person overlap	Negative
Anti-Ma2/Ta	-	EXT	EXT	-	Paraneoplastic limbic encephalitis; testicular germ cell tumor	Negative
Anti-SOX1	-	EXT	EXT	-	SCLC-associated; Lambert-Eaton overlap	Negative
Anti-Kelch-like protein 11 (KLHL11)	-	EXT	EXT	-	Testicular seminoma; brainstem/cerebellar syndrome	Negative
Anti-GlyR (glycine receptor)	-	EXT	EXT	-	Progressive encephalomyelitis with rigidity and myoclonus (PERM)	Negative
Anti-mGluR5	-	EXT	EXT	-	Ophelia syndrome; Hodgkin lymphoma	Negative
Anti-mGluR1	-	EXT	EXT	-	Cerebellar ataxia; Hodgkin lymphoma	Negative
Anti-neurexin-3-alpha	-	EXT	EXT	-	Rapid-onset encephalitis; seizures; confusion	Negative
Anti-D2R (dopamine-2 receptor)	-	EXT	EXT	-	Basal ganglia encephalitis; movement disorders	Negative
Paraneoplastic evaluation panel (comprehensive)	-	EXT	EXT	-	If standard panels negative and paraneoplastic suspected	All negative
14-3-3 protein (CSF)	-	EXT	EXT	-	Prion disease mimic; rapidly progressive dementia	Negative
RT-QuIC (CSF)	-	EXT	EXT	-	Prion disease exclusion in rapidly progressive cases	Negative
Next-generation sequencing (CSF metagenomics)	-	EXT	EXT	-	Occult infection when standard testing negative	No pathogens detected

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT head without contrast (CPT 70450)	STAT	STAT	-	STAT	Immediate (ED triage)	Rule out mass, hemorrhage, hydrocephalus	None significant
MRI brain with and without contrast (CPT 70553)	URGENT	URGENT	ROUTINE	URGENT	Within 24h	Mesial temporal T2/FLAIR hyperintensity (limbic encephalitis); cortical/subcortical signal changes; leptomeningeal enhancement	GFR <30, gadolinium allergy, pacemaker
EEG (routine or continuous) (CPT 95816)	URGENT	URGENT	ROUTINE	STAT	Within 24h; continuous if ICU or altered consciousness	Extreme delta brush (anti-NMDAR); focal/generalized slowing; epileptiform discharges; subclinical seizures	None significant
ECG (12-lead) (CPT 93000)	STAT	STAT	ROUTINE	STAT	Immediate	Autonomic dysfunction; arrhythmia; QTc prolongation (medication safety)	None
Chest X-ray (CPT 71046)	STAT	STAT	-	STAT	Immediate	Mediastinal mass (thymoma); pulmonary mass (SCLC)	Pregnancy (relative)
Continuous telemetry	-	STAT	-	STAT	Continuous in hospital	Arrhythmia from autonomic instability	None

2B. Extended¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI spine (cervical and thoracic) with and without contrast	-	ROUTINE	ROUTINE	ROUTINE	Within 48-72h	Concurrent myelitis; overlap syndromes	GFR <30, gadolinium allergy
CT chest/abdomen/pelvis with contrast (CPT 71260+74178)	-	URGENT	ROUTINE	URGENT	Within 48h	Occult malignancy: thymoma, lung cancer, ovarian teratoma, lymphoma	Contrast allergy, renal insufficiency
Pelvic/transvaginal ultrasound (females)	-	URGENT	ROUTINE	URGENT	Within 48h	Ovarian teratoma (anti-NMDAR)	None significant
Testicular ultrasound (males <50)	-	URGENT	ROUTINE	URGENT	Within 48h	Testicular germ cell tumor (anti-Ma2, KLHL11)	None significant
FDG-PET/CT (whole body) (CPT 78816)	-	ROUTINE	ROUTINE	-	Within 1-2 weeks	Occult malignancy not seen on CT; FDG-avid tumor	Uncontrolled diabetes, pregnancy
Video-EEG monitoring (prolonged)	-	ROUTINE	ROUTINE	STAT	As needed	Characterize seizure semiology; subclinical seizures; extreme delta brush pattern	None
FDG-PET brain	-	EXT	EXT	-	Within 1-2 weeks	Mesial temporal hypermetabolism (early) or hypometabolism (late); cortical metabolic changes	Same as PET/CT

2C. Rare/Specialized¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI brain with epilepsy protocol	-	EXT	EXT	-	If seizures refractory	Subtle cortical lesions; hippocampal sclerosis	Gadolinium contraindications
Brain biopsy	-	EXT	-	-	Last resort	Inflammatory infiltrate; exclusion of other pathology	Coagulopathy, inaccessible location
CT-guided biopsy (tumor)	-	EXT	EXT	-	After tumor identified	Histopathological confirmation	Coagulopathy, tumor location
Mammography/breast MRI	-	ROUTINE	ROUTINE	-	If AMPA, amphiphysin positive	Breast malignancy	Implants (relative for MRI)
Polysomnography	-	-	EXT	-	If IgLON5 suspected	REM/NREM parasomnias; sleep disordered breathing	None significant

LUMBAR PUNCTURE¶

Indication: Essential for diagnosis of autoimmune encephalitis; supports Graus 2016 criteria (CSF pleocytosis); CSF antibody testing more sensitive than serum for anti-NMDAR; rules out infectious encephalitis

Timing: STAT/URGENT -- perform as soon as safely possible after CT head; do NOT delay for MRI

Volume Required: 20-30 mL (large volume for comprehensive antibody and infectious testing)

Study	ED	HOSP	OPD	Rationale	Target Finding
Opening pressure	URGENT	ROUTINE	ROUTINE	Elevated ICP assessment	10-20 cm H2O
Cell count with differential (tubes 1 and 4) (CPT 89051)	STAT	STAT	ROUTINE	Lymphocytic pleocytosis supports autoimmune	WBC 5-80 (lymphocyte-predominant); RBC 0
Protein (CPT 84157)	STAT	STAT	ROUTINE	Mildly elevated in autoimmune; markedly elevated suggests infection/GBS	Normal to mildly elevated (usually <100 mg/dL)
Glucose with paired serum glucose (CPT 82945)	STAT	STAT	ROUTINE	Low in infection/carcinomatous meningitis	Normal (>60% of serum)
Gram stain and bacterial culture (CPT 87205+87070)	STAT	STAT	ROUTINE	Rule out bacterial meningitis	No organisms
HSV 1/2 PCR (CPT 87529)	STAT	STAT	ROUTINE	Rule out HSV encephalitis (most important mimic)	Negative
VZV PCR	URGENT	URGENT	ROUTINE	Varicella encephalitis	Negative
EBV PCR	-	ROUTINE	ROUTINE	EBV-associated encephalitis; lymphoma screen	Negative
CMV PCR	-	ROUTINE	ROUTINE	Immunocompromised patients	Negative
HHV-6 PCR	-	ROUTINE	ROUTINE	Post-transplant; limbic encephalitis mimic	Negative
Enterovirus PCR	URGENT	URGENT	-	Viral meningitis/encephalitis	Negative
West Nile virus IgM/IgG	-	ROUTINE	-	Endemic areas; flaccid paralysis	Negative
Cryptococcal antigen (CPT 87327)	URGENT	ROUTINE	-	Immunocompromised; chronic meningitis	Negative
VDRL (CSF) (CPT 86592)	-	ROUTINE	ROUTINE	Neurosyphilis	Negative
Oligoclonal bands (CSF AND paired serum) (CPT 83916)	URGENT	ROUTINE	ROUTINE	Intrathecal IgG synthesis; MS/NMOSD overlap	May show CSF-specific bands
IgG index	URGENT	ROUTINE	ROUTINE	Intrathecal antibody synthesis	May be elevated
Cytology (CPT 88104)	-	ROUTINE	ROUTINE	Carcinomatous/lymphomatous meningitis	Negative
Flow cytometry	-	ROUTINE	ROUTINE	CNS lymphoma	Normal
Autoimmune encephalitis antibody panel (CSF)	URGENT	URGENT	ROUTINE	NMDAR, LGI1, CASPR2, GABA-B, AMPA, DPPX -- CBA method	All negative
Anti-NMDAR IgG (CSF)	URGENT	URGENT	ROUTINE	CSF more sensitive than serum for NMDAR	Negative
AFB culture and smear (CPT 87116)	-	ROUTINE	-	TB meningitis if risk factors	Negative
Fungal culture (CPT 87102)	-	ROUTINE	-	Immunocompromised	Negative

Special Handling: Send minimum 2 mL CSF to each reference lab. Anti-NMDAR CSF testing is more sensitive than serum -- ALWAYS send CSF. Antibody results take 1-3 weeks. Cytology requires rapid transport (<1 hour). Store extra CSF (frozen at -20C) for future testing.

Contraindications: Elevated ICP without imaging (get CT first), coagulopathy (INR >1.5, platelets <50K), skin infection at LP site, posterior fossa mass with risk of herniation

3. TREATMENT¶

3A. Acute/Emergent¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Empiric acyclovir IV (until HSV ruled out)	IV	-	10 mg/kg :: IV :: q8h :: 10 mg/kg IV q8h; continue until HSV PCR negative x2 (48h apart) or alternative diagnosis confirmed	Renal impairment (adjust dose); adequate hydration required	Renal function daily; hydration status; crystal nephropathy prevention	STAT	STAT	-	STAT
Empiric antibiotics (if bacterial meningitis not excluded)	IV	-	2g :: IV :: q12h :: Ceftriaxone 2g IV q12h + vancomycin 15-20 mg/kg IV q8-12h + dexamethasone 0.15 mg/kg q6h x 4 days	Per individual drug allergies	Cultures; clinical response; renal function; vancomycin troughs	STAT	STAT	-	STAT
Lorazepam (acute seizure)	IV	-	0.1 mg/kg :: IV :: - :: 0.1 mg/kg IV (max 4 mg/dose); may repeat x1 in 5 minutes	Respiratory depression; acute narrow-angle glaucoma	Respiratory status; sedation level; airway patency	STAT	STAT	-	STAT
Midazolam (if no IV access)	IV	-	10 mg :: IM :: - :: 10 mg IM (adults >40 kg) or 0.2 mg/kg intranasal	Respiratory depression	Same as lorazepam	STAT	STAT	-	STAT
Lorazepam (catatonia challenge)	IV	-	1-2 mg :: IV :: - :: 1-2 mg IV; observe 15-30 min for response; if improvement, continue 1-2 mg IV/PO q4-8h (up to 8-24 mg/day)	Respiratory compromise; prior paradoxical response	Bush-Francis Catatonia Rating Scale; respiratory status; sedation	STAT	STAT	-	STAT

Note: Initiate empiric acyclovir and antibiotics IMMEDIATELY. Do NOT delay antimicrobials for LP. Start immunotherapy as soon as autoimmune encephalitis is clinically suspected -- do NOT wait for antibody results.

3B. First-Line Immunotherapy¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Methylprednisolone IV (CPT 96365)	IV	-	1000 mg :: IV :: daily :: 1000 mg IV daily x 5 days; infuse over 1-2 hours	Active untreated infection; uncontrolled diabetes; psychosis from steroids	Glucose q6h (target <180); BP; mood/sleep; I/O; GI prophylaxis	URGENT	STAT	-	STAT
Omeprazole (GI prophylaxis during steroids)	IV	-	40 mg :: IV :: daily :: 40 mg IV/PO daily during steroid course	PPI allergy	None routine	URGENT	STAT	-	STAT
Insulin sliding scale	-	-	180 mg :: - :: - :: Per protocol if glucose >180 mg/dL	Hypoglycemia risk	Glucose q6h; adjust per response	URGENT	STAT	-	STAT
IVIG (intravenous immunoglobulin) (CPT 96365)	IV	-	0.4 g/kg :: IV :: daily x 5 days :: 0.4 g/kg/day IV x 5 days (total 2 g/kg); infuse per weight-based protocol; premedicate with acetaminophen, diphenhydramine	IgA deficiency (anaphylaxis risk); recent thromboembolic event; renal failure	Renal function daily; headache (aseptic meningitis); thrombosis; volume overload; check IgA level before first dose	-	STAT	-	STAT
Plasmapheresis (PLEX)	-	-	N/A :: - :: once :: 5-7 exchanges over 10-14 days; 1-1.5 plasma volumes per exchange; albumin replacement	Hemodynamic instability; sepsis; coagulopathy; poor vascular access	BP during exchanges; electrolytes (Ca, K, Mg); coagulation (fibrinogen); line site; citrate reactions	-	STAT	-	STAT

Note: Methylprednisolone is typically started first (often in combination with IVIG or PLEX). IVIG and PLEX are considered equivalent first-line therapies and should be started concurrently or within days of steroids if clinical suspicion is high. For anti-NMDAR encephalitis, combination of all three first-line agents is common. PLEX may be preferred if rapid deterioration; IVIG may be preferred if hemodynamic instability or vascular access issues.

3C. Second-Line Immunotherapy¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Rituximab	IV	-	375 mg/m2 :: IV :: - :: 375 mg/m2 IV weekly x 4 doses OR 1000 mg IV x 2 doses (day 0 and day 14); premedicate with methylprednisolone 100 mg, acetaminophen, diphenhydramine	Active hepatitis B; severe active infection; live vaccines within 4 weeks	Hepatitis B serology (before first dose); CBC with differential q2-4 weeks; immunoglobulin levels q3 months; CD19/CD20 B-cell counts; infusion reactions; PML surveillance	-	URGENT	ROUTINE	URGENT
Cyclophosphamide	IV	-	750 mg/m2 :: IV :: monthly :: 750 mg/m2 IV monthly x 6 cycles; pre-hydrate with 1L NS; administer with MESNA (uroprotection)	Pregnancy; active infection; bone marrow failure; bladder outlet obstruction	CBC weekly x 4 weeks after each cycle (nadir day 10-14); urinalysis; BMP; LFTs; fertility counseling; hemorrhagic cystitis prevention	-	URGENT	ROUTINE	URGENT
Tocilizumab (third-line)	IV	-	8 mg/kg :: IV :: - :: 8 mg/kg IV every 4 weeks (max 800 mg/dose)	Active infection; hepatic impairment (ALT >5x ULN); diverticulitis; concurrent live vaccines	CBC, LFTs, lipids q4-8 weeks; infection surveillance; GI perforation risk; neutropenia	-	EXT	EXT	EXT
Bortezomib (third-line)	IV	-	1.3 mg/m2 :: IV :: - :: 1.3 mg/m2 SC/IV on days 1, 4, 8, 11 of 21-day cycles x 4-6 cycles	Severe hepatic impairment; peripheral neuropathy grade 2+	CBC; peripheral neuropathy assessment (dose-reduce or hold if worsens); herpes zoster prophylaxis (acyclovir 400 mg BID)	-	EXT	EXT	EXT
Repeated IVIG or PLEX cycles	PO	-	0.4 g/kg :: PO :: daily x 5 days :: IVIG 0.4 g/kg/day x 5 days (repeat q4 weeks) or PLEX 5 exchanges (repeat as needed)	Same as first-line	Same as first-line	-	URGENT	ROUTINE	URGENT
Oral prednisone taper (following IV methylprednisolone)	IV	-	1 mg/kg :: PO :: - :: 1 mg/kg/day (max 60 mg) x 2 weeks; taper by 10 mg/week to 20 mg; then taper by 5 mg/week to discontinuation OR low-dose maintenance	Active infection; uncontrolled diabetes; avascular necrosis	Glucose; BP; bone density if prolonged; mood; weight; adrenal insufficiency on taper	-	ROUTINE	ROUTINE	-

Note: Second-line therapy should be initiated if no improvement within 2 weeks of first-line therapy OR if clinically worsening despite first-line treatment. For anti-NMDAR encephalitis, early escalation to rituximab is associated with improved outcomes. Rituximab is generally preferred over cyclophosphamide given better safety profile. Third-line agents (tocilizumab, bortezomib) reserved for refractory cases failing rituximab/cyclophosphamide.

3D. Seizure Management¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam (first-line ASM)	IV	-	1000-1500 mg :: IV :: BID :: Load: 1000-1500 mg IV; Maintenance: 500-1500 mg IV/PO BID (max 3000 mg/day)	-	Renal impairment (adjust dose per CrCl)	Behavioral changes (rage, irritability); suicidality; renal function	STAT	STAT	ROUTINE	STAT
Lacosamide (second-line ASM)	IV	-	200-400 mg :: IV :: BID :: Load: 200-400 mg IV; Maintenance: 100-200 mg IV/PO BID (max 400 mg/day)	-	Second/third degree AV block; severe hepatic impairment	ECG (PR prolongation); dizziness; cardiac monitoring during load	URGENT	URGENT	ROUTINE	URGENT
Valproic acid	IV	-	20-40 mg/kg :: IV :: q8h :: Load: 20-40 mg/kg IV (max rate 6 mg/kg/min); Maintenance: 250-500 mg IV/PO q8h (target level 50-100 mcg/mL)	-	Pregnancy (teratogenic -- Category X); hepatic disease; urea cycle disorders; mitochondrial disease (POLG)	LFTs; ammonia; CBC (thrombocytopenia); drug level; pancreatitis	URGENT	URGENT	ROUTINE	URGENT
Brivaracetam	IV	-	100 mg :: IV :: BID :: Load: 100 mg IV; Maintenance: 50-100 mg IV/PO BID (max 200 mg/day)	-	Hepatic impairment (reduce dose)	Behavioral changes; sedation	-	URGENT	ROUTINE	URGENT
Clobazam	PO	-	5-10 mg :: PO :: BID :: Start 5-10 mg BID; titrate to 20-40 mg/day in divided doses	-	Severe hepatic impairment; myasthenia gravis	Sedation; CYP2C19 poor metabolizers (reduce dose); tolerance; dependence	-	ROUTINE	ROUTINE	ROUTINE
Phenytoin/fosphenytoin (refractory)	IV	-	20 mg :: IV :: BID :: Fosphenytoin: 20 mg PE/kg IV (max rate 150 mg PE/min); Maintenance: 5-7 mg/kg/day divided BID-TID (target level 10-20 mcg/mL)	-	AV block; bradycardia	Continuous cardiac monitoring during load; drug level; purple glove syndrome (peripheral IV); gingival hyperplasia	STAT	STAT	-	STAT
Phenobarbital (refractory)	IV	-	15-20 mg/kg :: IV :: - :: Load: 15-20 mg/kg IV (max rate 60 mg/min); Maintenance: 1-3 mg/kg/day (target level 15-40 mcg/mL)	-	Severe respiratory depression; porphyria	Respiratory depression; sedation; hypotension; drug level	-	URGENT	-	URGENT
Midazolam infusion (refractory SE)	IV	-	0.2 mg/kg :: IV :: once :: Bolus: 0.2 mg/kg IV; Infusion: 0.1-2.0 mg/kg/hr; titrate to EEG burst suppression	-	Unprotected airway (requires intubation)	Continuous EEG; respiratory status; hemodynamics; tachyphylaxis	-	-	-	STAT
Propofol infusion (refractory SE)	IV	-	1-2 mg/kg :: IV :: once :: Bolus: 1-2 mg/kg IV; Infusion: 20-80 mcg/kg/min (max 5 mg/kg/hr to avoid PRIS)	-	Propofol infusion syndrome risk (prolonged use >48h at high doses); egg/soy allergy	Continuous EEG; triglycerides q48h; CPK; lactate; hemodynamics; PRIS surveillance	-	-	-	STAT
Ketamine infusion (super-refractory SE)	IV	-	1-3 mg/kg :: IV :: once :: Bolus: 1-3 mg/kg IV; Infusion: 0.5-5 mg/kg/hr	-	Uncontrolled hypertension; raised ICP (relative)	Continuous EEG; BP; HR; hepatic function; laryngospasm risk	-	-	-	STAT

Note: Seizures in autoimmune encephalitis are driven by antibody-mediated mechanisms -- immunotherapy is the definitive seizure treatment. ASMs control acute seizures but will not resolve the underlying cause. Avoid carbamazepine/oxcarbazepine in LGI1 encephalitis (may worsen hyponatremia). Levetiracetam and lacosamide are preferred first-line ASMs given favorable drug interaction profiles with immunotherapy.

3E. Psychiatric Symptom Management¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Haloperidol (acute agitation)	IV	-	0.5-2 mg :: IV :: PRN :: 0.5-2 mg IV/IM q4-6h PRN (lowest effective dose); max 20 mg/day	QTc >500 ms; Parkinson disease; prior NMS	ECG (QTc); EPS; NMS surveillance; temperature; CPK if NMS suspected	STAT	STAT	-	STAT
Olanzapine (agitation/psychosis)	IM	-	2.5-5 mg :: IM :: BID :: 2.5-5 mg PO/IM BID (start low); max 20 mg/day	QTc prolongation; metabolic syndrome	Glucose; lipids; QTc; weight; sedation; EPS	-	ROUTINE	ROUTINE	ROUTINE
Quetiapine (psychosis/insomnia)	PO	-	25-50 mg :: PO :: qHS :: Start 25-50 mg qHS; titrate to 200-400 mg/day in divided doses	QTc prolongation; severe hepatic impairment	QTc; metabolic parameters; orthostatic BP; sedation	-	ROUTINE	ROUTINE	-
Lorazepam (catatonia -- first-line)	IV	-	1-2 mg :: IV :: - :: Start 1-2 mg IV/PO; if response, 1-2 mg q4-8h (escalate to 8-24 mg/day as needed for catatonia)	Respiratory compromise (high doses)	Bush-Francis Catatonia Rating Scale; respiratory rate; sedation; airway	STAT	STAT	ROUTINE	STAT
Dexmedetomidine (agitation in ICU)	IV	-	1 mcg/kg :: IV :: - :: Load: 1 mcg/kg IV over 10 min (optional); Infusion: 0.2-0.7 mcg/kg/hr (max 1.5 mcg/kg/hr)	Severe bradycardia; advanced heart block	HR (bradycardia); BP (hypotension); sedation level (RASS)	-	-	-	STAT
Valproic acid (mood stabilization/agitation)	PO	-	250-500 mg :: PO :: BID :: 250-500 mg PO BID; titrate to level 50-100 mcg/mL (dual benefit: mood + seizure)	Pregnancy; hepatic disease	LFTs; ammonia; CBC; drug level	-	ROUTINE	ROUTINE	ROUTINE
Melatonin (sleep-wake disturbance)	PO	-	3-10 mg :: PO :: qHS :: 3-10 mg PO qHS	None significant	Sleep quality; no significant drug interactions	-	ROUTINE	ROUTINE	ROUTINE
Trazodone (insomnia)	PO	-	25-100 mg :: PO :: qHS :: 25-100 mg PO qHS	Concurrent MAOIs; QTc prolongation	Orthostatic hypotension; priapism (rare); sedation	-	ROUTINE	ROUTINE	-
Electroconvulsive therapy (ECT) (refractory catatonia)	-	-	N/A :: - :: per protocol :: Per psychiatry protocol; typically 3x/week	Pheochromocytoma; raised ICP (relative)	Anesthesia monitoring; cognitive function; post-procedure seizure threshold	-	EXT	EXT	EXT

Note: CAUTION with antipsychotics in autoimmune encephalitis -- patients (especially anti-NMDAR) are highly susceptible to neuroleptic malignant syndrome (NMS) and EPS. Use LOWEST effective doses. Benzodiazepines (lorazepam) are first-line for catatonia and agitation. Catatonia may be present in up to 40% of anti-NMDAR cases. If catatonia does not respond to lorazepam, consider ECT before escalating antipsychotics. Psychiatric symptoms in AE are driven by antibody-mediated mechanisms -- immunotherapy is the definitive treatment.

3F. ICU-Specific Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Intubation and mechanical ventilation	-	-	N/A :: - :: once :: RSI: avoid succinylcholine if hyperkalemia risk; maintain normocapnia	As per standard airway management	Ventilator parameters; ABG; daily SBT when appropriate	-	-	-	STAT
Labetalol IV (autonomic hypertensive crisis)	IV	-	10-20 mg :: IV :: PRN :: 10-20 mg IV q10-15min PRN; or infusion 0.5-2 mg/min; target SBP <180	Severe bradycardia; AV block; decompensated CHF; asthma	Continuous BP; HR; I/O	-	-	-	STAT
Esmolol IV (autonomic tachycardia)	IV	-	500 mcg/kg :: IV :: once :: Bolus: 500 mcg/kg over 1 min; Infusion: 50-200 mcg/kg/min	Severe bradycardia; decompensated CHF; cardiogenic shock	Continuous HR/BP; ECG	-	-	-	STAT
Atropine (autonomic bradycardia)	IV	-	0.5-1 mg :: IV :: - :: 0.5-1 mg IV q3-5min (max 3 mg total)	Tachycardia; thyrotoxicosis	HR; rhythm	-	-	-	STAT
Isoproterenol drip (severe autonomic bradycardia)	IV	-	2-10 mcg :: IV :: - :: 2-10 mcg/min IV infusion; titrate to HR >60	Tachyarrhythmia; digoxin toxicity	Continuous ECG; HR; BP	-	-	-	STAT
Temporary transvenous pacemaker	-	-	N/A :: - :: continuous :: Per cardiology if pharmacologic measures fail	Active infection at insertion site	Capture; sensing; threshold checks	-	-	-	STAT
Norepinephrine (autonomic hypotension)	IV	-	0.1-0.5 mcg/kg :: IV :: - :: 0.1-0.5 mcg/kg/min IV; titrate to MAP >65	Peripheral ischemia risk at high doses	Arterial line; MAP; lactate; urine output	-	-	-	STAT
DVT prophylaxis (enoxaparin)	SC	-	40 mg :: SC :: daily :: 40 mg SC daily (adjust for renal function: 30 mg SC daily if CrCl <30)	Active bleeding; HIT; severe thrombocytopenia	Platelet count; anti-Xa if renal impairment; bleeding signs	-	STAT	-	STAT
Temperature management (hyperthermia)	IV	-	1g :: IV :: q6h :: Targeted temperature: 36-37C; cooling blankets; acetaminophen 1g IV/PO q6h PRN	Avoid overcooling; avoid shivering (increases metabolic demand)	Continuous temperature; shivering assessment (BSAS)	-	-	-	STAT
Sodium correction (hyponatremia -- LGI1)	IV	-	100-150 mL :: IV :: - :: If Na <125: 3% NaCl 100-150 mL IV over 10-20 min (repeat up to 3x); Target correction: 4-6 mEq/L in first 6h, max 8 mEq/L in 24h	Avoid overcorrection (osmotic demyelination risk)	Sodium q2-4h during correction; urine output; neurologic status	URGENT	URGENT	ROUTINE	URGENT
Fludrocortisone (chronic hyponatremia -- LGI1)	PO	-	0.05-0.2 mg :: PO :: daily :: 0.05-0.2 mg PO daily	CHF; hypertension	Sodium; potassium; BP; edema	-	ROUTINE	ROUTINE	-
Fluid restriction (SIADH-related hyponatremia)	-	-	N/A :: - :: per protocol :: Restrict to 1-1.2 L/day if SIADH suspected (LGI1)	Dehydration risk	Sodium; I/O; daily weight; urine osmolality	-	ROUTINE	-	ROUTINE

Note: Central hypoventilation occurs in anti-NMDAR encephalitis and may require prolonged mechanical ventilation (weeks to months). Autonomic instability (tachycardia/bradycardia alternating, blood pressure lability, central hyperthermia, cardiac dysrhythmias) is a hallmark of severe anti-NMDAR encephalitis. LGI1 encephalitis frequently causes SIADH-related hyponatremia. Do NOT over-correct sodium (risk of osmotic demyelination).

3G. Long-Term Immunosuppression / Maintenance¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Mycophenolate mofetil (CellCept)	PO	-	500 mg :: PO :: BID :: Start 500 mg PO BID; increase to 1000 mg PO BID over 2-4 weeks (target 1500-3000 mg/day)	Pregnancy (Category D -- teratogenic); active infection	CBC q2 weeks x 3 months, then monthly; LFTs; GI symptoms; infection surveillance; pregnancy prevention	-	-	ROUTINE	-
Azathioprine (Imuran)	PO	-	50 mg :: PO :: daily :: Start 50 mg PO daily; increase by 50 mg every 2 weeks to target 2-3 mg/kg/day	TPMT deficiency (check before starting); pregnancy (relative)	TPMT genotype/activity before starting; CBC q2 weeks x 2 months, then monthly; LFTs; pancreatitis	-	-	ROUTINE	-
Rituximab (maintenance)	IV	-	500-1000 mg :: IV :: - :: 500-1000 mg IV every 6 months; re-dose based on CD19/CD20 B-cell repopulation or clinical relapse	Active hepatitis B; severe active infection	CD19/CD20 counts q3 months; immunoglobulin levels q3-6 months; hepatitis B surveillance; infection monitoring; PML surveillance	-	-	ROUTINE	-
Oral prednisone (low-dose maintenance)	PO	-	5-10 mg :: PO :: daily :: 5-10 mg PO daily; aim to taper off within 3-6 months if on steroid-sparing agent	Poorly controlled diabetes; active infection; avascular necrosis	Glucose; BP; bone density (DEXA if >3 months); weight; mood; cataracts; adrenal assessment on taper	-	-	ROUTINE	-
IVIG (maintenance)	IV	-	0.4 g/kg :: IV :: - :: 0.4 g/kg IV every 4 weeks OR 1-2 g/kg IV every 4-6 weeks (adjust per response)	IgA deficiency; thromboembolic history	Renal function; headache; IgG trough levels; infusion reactions	-	-	ROUTINE	-
Calcium + Vitamin D (bone protection with steroids)	-	-	1000-1200 mg/day :: PO :: - :: Calcium 1000-1200 mg/day + Vitamin D 1000-2000 IU/day	Hypercalcemia; kidney stones	25-OH Vitamin D level; calcium; DEXA baseline if anticipated steroid use >3 months	-	ROUTINE	ROUTINE	-

Note: Long-term immunosuppression is guided by antibody subtype, relapse risk, and tumor status. Anti-NMDAR encephalitis has ~12-20% relapse rate. Rituximab maintenance is most commonly used for relapse prevention. Mycophenolate and azathioprine are steroid-sparing alternatives. Monitor for immunosuppression-related complications (infection, malignancy). Duration of maintenance therapy is individualized -- typically minimum 2 years; some patients require indefinite treatment.

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU	Indication
Neurology (autoimmune/neuroimmunology)	STAT	STAT	ROUTINE	STAT	All suspected autoimmune encephalitis cases; immunotherapy management
Epilepsy/EEG service	STAT	STAT	ROUTINE	STAT	Seizure management; continuous EEG monitoring; extreme delta brush interpretation
Psychiatry	URGENT	URGENT	ROUTINE	URGENT	Psychiatric manifestations (psychosis, catatonia, agitation); antipsychotic management; NMS risk
Critical care/ICU	URGENT	URGENT	-	-	Autonomic instability; respiratory failure; refractory status epilepticus; altered consciousness
Gynecologic oncology (females with anti-NMDAR)	-	URGENT	URGENT	URGENT	Ovarian teratoma screening and surgical resection
Oncology	-	URGENT	ROUTINE	URGENT	Any identified malignancy; tumor screening guidance; chemotherapy planning
Urology (males <50 with anti-Ma2/KLHL11)	-	URGENT	ROUTINE	-	Testicular germ cell tumor screening
Hematology/apheresis	-	URGENT	-	URGENT	PLEX coordination; catheter placement
Physical therapy	-	ROUTINE	ROUTINE	ROUTINE	Motor rehabilitation; gait training; fall prevention
Occupational therapy	-	ROUTINE	ROUTINE	ROUTINE	ADL assessment; cognitive rehabilitation; adaptive strategies
Speech-language pathology	-	ROUTINE	ROUTINE	ROUTINE	Swallowing evaluation; language/communication rehabilitation; cognitive-linguistic therapy
Neuropsychology	-	-	ROUTINE	-	Formal cognitive assessment; rehabilitation planning; serial monitoring
Social work	-	ROUTINE	ROUTINE	-	Family support; insurance navigation; disability resources; long-term care planning
Rehabilitation medicine	-	ROUTINE	ROUTINE	-	Comprehensive inpatient or outpatient rehab program coordination
Palliative care	-	EXT	EXT	EXT	Refractory cases; prolonged ICU stay; family support; goals of care discussion
Infectious disease	URGENT	URGENT	-	URGENT	Rule out infection; antimicrobial guidance; post-immunosuppression infection management
Endocrinology	-	ROUTINE	ROUTINE	-	Steroid-induced hyperglycemia management; thyroid evaluation if Hashimoto suspected

4B. Patient/Family Instructions¶

Recommendation	ED	HOSP	OPD
Return to ED immediately for new seizures, sudden behavioral changes, fever, difficulty breathing, or loss of consciousness	Y	Y	Y
Autoimmune encephalitis is a treatable condition -- recovery may be slow (months to years) but significant improvement is expected with appropriate immunotherapy	Y	Y	Y
Do NOT drive until seizure-free for state-mandated period AND cleared by neurology	Y	Y	Y
Keep seizure diary (date, time, type, duration, triggers)	-	Y	Y
Behavioral and psychiatric symptoms are part of the disease, not a primary psychiatric disorder -- immunotherapy is the treatment	Y	Y	Y
Report any signs of infection (fever >100.4F, cough, dysuria, rash) immediately while on immunotherapy	-	Y	Y
Avoid live vaccines while on immunosuppressive therapy (inform all physicians of immunosuppression status)	-	Y	Y
Do not stop anti-seizure medications abruptly	-	Y	Y
Avoid alcohol and recreational drugs (lower seizure threshold, interact with medications)	-	Y	Y
Pregnancy must be avoided during immunotherapy; discuss contraception with neurology and OB/GYN	-	Y	Y
Expect gradual improvement -- anti-NMDAR recovery typically occurs in reverse order of symptom onset (psychiatric symptoms resolve last)	-	Y	Y
Cognitive rehabilitation exercises as directed by speech and occupational therapy	-	Y	Y
Safety modifications at home (remove sharp objects, secure stairways, fall prevention)	-	Y	Y
Medical alert bracelet recommended (autoimmune encephalitis, seizure risk, immunosuppressed)	-	Y	Y
Follow-up appointments are critical -- relapse monitoring requires regular visits	-	Y	Y

4C. Tumor Screening Protocols by Antibody¶

Antibody	Associated Tumor(s)	Screening Protocol	Frequency
Anti-NMDAR	Ovarian teratoma (females, especially 12-45 years); rarely other tumors	Pelvic MRI or transvaginal US; CT chest/abdomen/pelvis	At diagnosis; repeat q6 months x 2 years if initially negative
Anti-LGI1	Thymoma (~5-10%)	CT chest with contrast	At diagnosis; repeat if relapse
Anti-CASPR2	Thymoma (~20-30%)	CT chest with contrast	At diagnosis; repeat if relapse
Anti-GABA-B	Small cell lung cancer (~50%)	CT chest; FDG-PET/CT if CT negative	At diagnosis; q6 months x 4 years
Anti-AMPA	Thymoma, lung cancer, breast cancer	CT chest/abdomen/pelvis; mammography; FDG-PET/CT	At diagnosis; q6 months x 4 years
Anti-DPPX	B-cell lymphoma (rare)	CT chest/abdomen/pelvis; FDG-PET if suspected	At diagnosis
Anti-Ma2/Ta	Testicular germ cell tumor (young males); lung cancer (older patients)	Testicular US (males <50); CT chest; FDG-PET/CT	At diagnosis; q6 months x 4 years
Anti-Hu (ANNA-1)	Small cell lung cancer (>90%)	CT chest; FDG-PET/CT	At diagnosis; q6 months x 4 years
Anti-CV2/CRMP5	SCLC; thymoma	CT chest; FDG-PET/CT	At diagnosis; q6 months x 4 years
Anti-amphiphysin	Breast cancer; SCLC	Mammography/breast MRI; CT chest	At diagnosis; q6 months x 4 years
Anti-KLHL11	Testicular seminoma	Testicular US; FDG-PET/CT	At diagnosis; repeat if relapse

Note: Tumor resection is critical for treatment response -- immunotherapy alone may be insufficient if underlying tumor is not removed. If initial tumor screen is negative but paraneoplastic antibody is positive, repeat imaging q6 months x 4 years. Consider FDG-PET/CT if CT is negative and clinical suspicion remains high.

═══════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
HSV encephalitis	Acute fever, temporal lobe hemorrhagic necrosis, CSF lymphocytic pleocytosis with RBCs	HSV PCR (CSF); MRI temporal lobe changes; often more acute onset
Other viral encephalitis (EBV, CMV, HHV-6, enterovirus, West Nile)	Fever, CSF pleocytosis, specific exposure/season, immunocompromised status	Specific viral PCR/serology; CSF studies
Bacterial meningitis/encephalitis	Acute fever, meningismus, CSF neutrophilic pleocytosis, low glucose	CSF Gram stain, culture, procalcitonin, bacterial PCR
Neurosyphilis	Cognitive decline, psychiatric symptoms, Argyll Robertson pupils, positive serology	RPR/VDRL; CSF VDRL; FTA-ABS
Prion disease (CJD)	Rapidly progressive dementia, myoclonus, akinetic mutism; cortical ribboning on MRI (DWI)	14-3-3 protein; RT-QuIC; MRI DWI cortical ribboning; EEG periodic discharges
CNS lymphoma	Progressive encephalopathy, mass lesion, periventricular enhancement, immunocompromised	CSF cytology/flow cytometry; FDG-PET; brain biopsy
CNS vasculitis	Headache, stroke-like episodes, multifocal infarcts, elevated ESR/CRP	Angiography; brain/leptomeningeal biopsy; ESR/CRP
Neurosarcoidosis	Cranial neuropathies, hypothalamic dysfunction, leptomeningeal enhancement	ACE level; chest CT (hilar adenopathy); biopsy
Hashimoto encephalopathy (SREAT)	Encephalopathy with very high anti-TPO; steroid-responsive; diagnosis of exclusion	Anti-TPO; anti-thyroglobulin; dramatic steroid response
Acute disseminated encephalomyelitis (ADEM)	Post-infectious/post-vaccination, multifocal large white matter lesions, encephalopathy	MRI pattern; MOG-IgG; monophasic course
NMO spectrum disorder (NMOSD)	Optic neuritis, longitudinally extensive myelitis, area postrema syndrome	AQP4-IgG; MRI pattern
Drug/toxin-induced encephalopathy	Temporal correlation with drug exposure; resolves with discontinuation	Urine drug screen; medication review; drug levels
Metabolic encephalopathy	Hepatic, uremic, thyroid, electrolyte disturbances	CMP; LFTs; ammonia; TSH; specific metabolic panels
Psychiatric disorder (new-onset psychosis, catatonia)	No CSF pleocytosis; normal MRI/EEG; isolated psychiatric symptoms (caution: AE can present as pure psychiatric)	LP mandatory to differentiate; EEG; MRI; antibody testing before assuming primary psychiatric
Seizure-related encephalopathy (post-ictal/non-convulsive SE)	Prolonged post-ictal confusion; non-convulsive status on EEG	Continuous EEG monitoring; resolves with ASM treatment
Neuro-Behcet disease	Oral/genital ulcers; brainstem predominance; CSF neutrophilic pleocytosis	Clinical criteria; pathergy test; HLA-B51

6. MONITORING PARAMETERS¶

6A. Acute Phase Monitoring (Inpatient)¶

Parameter	Frequency	Target/Threshold	Action if Abnormal
Neurologic examination (GCS, orientation, cranial nerves, motor, reflexes)	Q4-6h (ICU); Q8-12h (floor)	Stable or improving	If worsening: urgent re-imaging; escalate immunotherapy; consider ICU transfer
Modified Rankin Scale (mRS)	Baseline, then weekly	Improvement over weeks-months	Document trajectory; guide treatment escalation; long-term disability tracking
Bush-Francis Catatonia Rating Scale	Daily if catatonia features	Score decreasing with treatment	If not responding to lorazepam: increase dose; consider ECT; escalate immunotherapy
Blood glucose	Q6h during IV steroids	<180 mg/dL	Insulin sliding scale; endocrine consult if persistent >250
Blood pressure	Q1h (ICU); Q4h (floor)	SBP 100-180 mmHg; MAP >65	Autonomic dysregulation: labetalol/esmolol for hypertension; norepinephrine for hypotension
Heart rate and rhythm	Continuous telemetry (ICU/floor)	HR 60-100; sinus rhythm	Autonomic instability: treat per protocol (3F); cardiology consult if sustained arrhythmia
Temperature	Q4h; continuous in ICU	36.0-37.5 C	Central hyperthermia: cooling measures; acetaminophen; rule out infection
Respiratory rate and NIF	Q4h (ICU); Q shift (floor)	RR <20; NIF >-30 cm H2O	NIF worsening toward -20: intubation; ICU transfer; evaluate for neuromuscular respiratory failure
Seizure log	Continuous	Decreasing frequency/severity	If increasing: escalate ASMs; re-assess immunotherapy; continuous EEG
EEG (continuous)	24-72h minimum; longer if ICU	Resolving extreme delta brush; no subclinical seizures	If persistent seizures: escalate per Section 3D
Sodium (Na)	Q6-12h (if LGI1 or hyponatremia)	Na >130 mEq/L	Correct per protocol (3F); fluid restriction if SIADH
I/O and daily weight	Daily	Euvolemic	Adjust fluids; diuretics if fluid overload; free water restriction if SIADH
Renal function (BUN/Cr)	Daily during IVIG; q48h otherwise	Stable	Hold IVIG if Cr rising; hydration; nephrology consult
CBC with differential	Q48h during immunotherapy; daily if on cyclophosphamide	WBC >3.0; ANC >1.5; Plt >100	Hold immunotherapy if critically low; growth factor support; hematology consult
LFTs	Q48-72h during acute treatment	ALT/AST <3x ULN	Dose adjustment or hold hepatotoxic medications
Fibrinogen (during PLEX)	Before each exchange	>100 mg/dL	Hold PLEX if <100; FFP replacement

6B. Outpatient/Long-Term Monitoring¶

Parameter	Frequency	Target/Threshold	Action if Abnormal
Neurologic examination (cognition, behavior, seizures, motor)	Monthly x 6 months; then q3 months x 2 years; then q6 months	Sustained improvement; no new symptoms	If relapse: repeat LP/MRI; resume or escalate immunotherapy; re-screen for tumor
Modified Rankin Scale (mRS)	Each visit	Improving toward mRS 0-1	Document trajectory; adjust rehab goals; consider treatment escalation if plateau or decline
CASE score (Clinical Assessment Scale in Autoimmune Encephalitis)	Each visit	Improving score over time	Standardized outcome measure; guide treatment decisions
MRI brain with and without contrast	3-6 months post-treatment; then annually x 3 years	Stable or improved signal changes	New/worsening lesions: relapse workup; repeat antibody testing; escalate treatment
EEG (routine)	3-6 months post-treatment; as needed for seizure management	Improved background; no epileptiform activity	If persistent abnormality: continue/adjust ASMs; consider repeat immunotherapy
Serum antibody titers	q3-6 months x 2 years; then annually	Decreasing or negative	Rising titers may precede clinical relapse; increase surveillance; consider preemptive treatment
CBC with differential	Q2-4 weeks on mycophenolate/azathioprine; then monthly	WBC >3.0; ANC >1.5; Plt >100	Hold/reduce immunosuppression; growth factor support
LFTs	Monthly x 3 months on azathioprine/mycophenolate; then q3 months	ALT/AST <3x ULN	Dose reduction or switch agent
Immunoglobulin levels (IgG, IgA, IgM)	Q3-6 months on rituximab or other B-cell depletion	IgG >400 mg/dL	Immunoglobulin replacement if recurrent infections with hypogammaglobulinemia
CD19/CD20 B-cell counts	Q3 months on rituximab	Depleted (<1% B-cells) during active treatment	Guide re-dosing interval; B-cell repopulation may trigger relapse
TPMT activity/genotype	Once before starting azathioprine	Normal enzyme activity	Dose reduce or avoid azathioprine if intermediate/low TPMT
Tumor surveillance (per antibody type -- Section 4C)	Per protocol: q6 months x 2-4 years	No tumor identified	If tumor found: urgent oncology referral and surgical resection
Neuropsychological testing	Baseline (when able); 6 months; 12 months; annually	Improving cognitive domains	Guide cognitive rehabilitation; inform return to work/school planning
DEXA scan (bone density)	Baseline if steroids >3 months; repeat q1-2 years	T-score >-2.5	Bisphosphonate therapy; calcium/vitamin D optimization
ASM drug levels (if applicable)	Per drug-specific schedule; after dose changes	Therapeutic range	Adjust dose; assess adherence

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home	Mild symptoms; stable or improving on established immunotherapy; no active seizures; able to perform basic ADLs; reliable follow-up within 1-2 weeks; no significant autonomic instability; family/caregiver education completed; outpatient infusion arranged if needed
Admit to floor (medical/neurology)	New-onset encephalitis requiring workup and immunotherapy initiation; seizures requiring medication adjustment; moderate behavioral symptoms manageable on floor; needs IV steroids/IVIG; diagnostic uncertainty requiring expedited workup
Admit to ICU	Refractory status epilepticus; altered consciousness (GCS <12); severe autonomic instability (hemodynamic swings, arrhythmias, central hypoventilation); need for continuous EEG monitoring; requirement for mechanical ventilation; severe catatonia unresponsive to lorazepam; frequent or prolonged seizures requiring IV anesthetic infusions
Transfer to higher level of care	PLEX or continuous EEG not available; neurology/neuroimmunology specialist not available; need for tumor resection (gynecologic oncology for teratoma); requires ICU care not available at current facility
Inpatient rehabilitation	Medically stable; significant functional deficits requiring intensive therapy (cognitive, motor, speech); unable to safely return home; expected to benefit from structured rehabilitation program
Long-term acute care (LTAC)	Prolonged ventilator dependence (common in severe anti-NMDAR); medically complex care needs; ongoing immunotherapy requirements; unable to participate in intensive rehab
Skilled nursing facility	Stable but unable to perform ADLs independently; requires ongoing nursing care; awaiting rehabilitation bed; chronic disability
Outpatient follow-up	All discharged patients: neurology follow-up within 1-2 weeks; infusion center for ongoing immunotherapy; neuropsychology referral; rehab services; tumor surveillance per protocol
Readmission criteria	New seizures after period of control; behavioral/cognitive regression; fever or signs of infection on immunotherapy; suspected relapse (any new neurologic/psychiatric symptoms)

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
Graus 2016 diagnostic criteria for autoimmune encephalitis	Expert Consensus, Class III	Graus F et al. Lancet Neurol 2016;15:391-404
CSF antibody testing more sensitive than serum for anti-NMDAR	Class II	Dalmau J et al. Lancet Neurol 2008;7:1091-1098
Cell-based assay (CBA) is gold standard for antibody detection	Class II	Waters P et al. J Neurol Neurosurg Psychiatry 2014
First-line immunotherapy: IV steroids + IVIG or PLEX	Class III, Expert Consensus	Titulaer MJ et al. Lancet Neurol 2013;12:157-165
Early immunotherapy improves outcomes	Class II	Titulaer MJ et al. Lancet Neurol 2013;12:157-165
Rituximab as second-line therapy	Class III, Retrospective	Lee WJ et al. Neurology 2016;86:1683-1691
Early second-line (rituximab) improves anti-NMDAR outcomes	Class III	Titulaer MJ et al. Lancet Neurol 2013;12:157-165
Cyclophosphamide as second-line therapy	Class III, Expert Consensus	Dalmau J & Graus F. N Engl J Med 2018;378:840-851
Tocilizumab for refractory autoimmune encephalitis	Class IV, Case Series	Lee WJ et al. Neurotherapeutics 2016;13:824-832
Bortezomib for refractory autoimmune encephalitis	Class IV, Case Series	Scheibe F et al. Neurology 2017;88:366-370
Ovarian teratoma resection is essential in anti-NMDAR	Class II	Titulaer MJ et al. Lancet Neurol 2013
Tumor screening by antibody type	Expert Consensus	Graus F et al. Lancet Neurol 2016
Extreme delta brush on EEG in anti-NMDAR	Class III	Schmitt SE et al. Neurology 2012;79:1094-1100
Faciobrachial dystonic seizures precede LGI1 encephalitis	Class III	Irani SR et al. Ann Neurol 2011;69:892-900
Hyponatremia in LGI1 encephalitis (SIADH mechanism)	Class III	Lai M et al. Lancet Neurol 2010;9:776-785
GABA-B encephalitis and SCLC association (~50%)	Class III	Lancaster E et al. Lancet Neurol 2010;9:67-76
Anti-NMDAR encephalitis staging and recovery pattern	Class II	Dalmau J et al. Lancet Neurol 2019;18:1045-1057
Modified Rankin Scale for outcome tracking	Validated Scale	van Swieten JC et al. Stroke 1988;19:604-607
CASE score for autoimmune encephalitis assessment	Validated Scale	Lim JA et al. Ann Neurol 2019;85:352-358
Catatonia in anti-NMDAR encephalitis (~40%)	Class III	Al-Diwani A et al. Lancet Psychiatry 2019;6:235-246
Lorazepam challenge for catatonia	Expert Consensus	Bush G et al. Acta Psychiatr Scand 1996;93:129-136
NMS risk with antipsychotics in anti-NMDAR	Class IV, Case Reports	Lejuste F et al. Neurol Neuroimmunol Neuroinflamm 2016;3:e280
Levetiracetam as preferred ASM in autoimmune encephalitis	Expert Consensus	Britton J. Handb Clin Neurol 2016;133:219-245
Avoid carbamazepine in LGI1 (worsens hyponatremia)	Expert Consensus	Irani SR et al. Brain 2010;133:2734-2748
Long-term rituximab maintenance prevents relapse	Class III	Nosadini M et al. Expert Rev Neurother 2015;15:1391-1419
Anti-NMDAR relapse rate 12-20%	Class II	Titulaer MJ et al. Lancet Neurol 2013
Mycophenolate as steroid-sparing agent	Class IV	Expert practice; no large trials
Autonomic instability management in anti-NMDAR	Expert Consensus	Dalmau J & Graus F. N Engl J Med 2018
Repeat tumor screening q6 months x 2-4 years	Expert Consensus	Graus F et al. Lancet Neurol 2016
Central hypoventilation in severe anti-NMDAR requiring prolonged ventilation	Class III	Florance NR et al. Ann Neurol 2009;66:11-18
Neuropsychological recovery trajectory in autoimmune encephalitis	Class III	Finke C et al. JAMA Neurol 2017;74:50-59

CLINICAL DECISION SUPPORT NOTES¶

Graus 2016 Diagnostic Criteria -- Possible Autoimmune Encephalitis¶

All three of the following must be met: - [ ] Subacute onset (rapid progression of <3 months) of working memory deficits, altered mental status, or psychiatric symptoms - [ ] At least one of: (a) new focal CNS findings, (b) seizures not explained by prior seizure disorder, (c) CSF pleocytosis (WBC >5), (d) MRI features suggestive of encephalitis - [ ] Reasonable exclusion of alternative causes

Anti-NMDAR Encephalitis Clinical Staging¶

Prodromal phase (days to 2 weeks): Fever, headache, URI-like symptoms
Psychiatric phase (weeks 1-2): Psychosis, paranoia, agitation, bizarre behavior, hallucinations, anxiety, insomnia
Unresponsive phase (weeks 2-4): Decreased consciousness, catatonia, mutism
Hyperkinetic phase (weeks 2-8): Orofacial dyskinesias, choreoathetosis, dystonic posturing, autonomic instability
Recovery phase (months to years): Gradual improvement in reverse order of symptom onset; prolonged cognitive/behavioral deficits

Red Flags for Autoimmune Encephalitis¶

CHANGE LOG¶

v1.0 (January 27, 2026) - Initial creation - Section 1: 24 core labs (1A), 20 antibody panel tests (1B), 16 rare/specialized tests (1C) - Section 2: 6 essential imaging/studies (2A), 7 extended (2B), 5 rare (2C), 22 LP/CSF studies - Section 3: Expanded to 7 subsections: - 3A: 5 acute/emergent treatments (empiric acyclovir, antibiotics, benzodiazepines, catatonia challenge) - 3B: 5 first-line immunotherapy agents (methylprednisolone, omeprazole, insulin, IVIG, PLEX) - 3C: 6 second-line immunotherapy agents (rituximab, cyclophosphamide, tocilizumab, bortezomib, repeated IVIG/PLEX, oral prednisone taper) - 3D: 10 anti-seizure medications including refractory/super-refractory status epilepticus protocols - 3E: 9 psychiatric symptom management agents (antipsychotics, lorazepam for catatonia, ICU sedation, mood stabilization, ECT) - 3F: 12 ICU-specific treatments (ventilation, autonomic instability, DVT prophylaxis, temperature management, sodium correction) - 3G: 6 long-term immunosuppression/maintenance agents (mycophenolate, azathioprine, rituximab maintenance, prednisone, IVIG maintenance, bone protection) - Section 4: 17 referrals (4A), 15 patient/family instructions (4B), 11 tumor screening protocols by antibody type (4C) - Section 5: 16 differential diagnoses with distinguishing features - Section 6: 16 acute monitoring parameters (6A), 15 outpatient/long-term monitoring parameters (6B) - Section 7: 9 disposition criteria - Section 8: 30 evidence references with evidence levels - Clinical Decision Support Notes: Graus 2016 diagnostic criteria checklist, anti-NMDAR clinical staging (5 phases), 10 red flags checklist