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neuro.encephalitis-autoimmune-other.v1PRODUCTION
neuro.encephalitis-autoimmune-other.v1

Other Autoimmune Encephalitis (surface + intracellular AB)

neurologyacutesubacuteadultpediatricgeriatric
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Canonical 12-phase frame with authored status for this dossier.

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Detailed

Subacute neuropsychiatric / neurological syndrome with distinctive phenotype cluster (Morvan tetrad / refractory status / PERM / Ophelia / sleep+parkinsonism / sensory neuronopathy / diencephalic / OMR / chorea+optic) → suspect AE-other subtype (Graus 2016 IRCNS PMID 26906964)

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Patient inputs (20)

Demographics vary by AE subtype — CASPR2 younger male (~50), GABA-B older (~60), AMPA middle-aged, anti-Ma2 testicular if young male / lung if older, IgLON5 older (~60)

Sex distribution varies — CASPR2 male predominance ~80%; anti-Ma2 testicular in young men; anti-Ri breast in women

Each AE subtype has distinct phenotype cluster — Morvan tetrad (CASPR2), refractory status (GABA-B), limbic+psychosis (AMPA), PERM (DPPX), Ophelia (mGluR5), sleep+parkinsonism (IgLON5), sensory neuronopathy (Hu), diencephalic (Ma2), OMR (Ri), chorea+optic (CV2/CRMP5)

CSF + serum AE antibody panel via CBA — must include CASPR2, GABA-B, AMPA1/2, DPPX, mGluR5, IgLON5, Hu, Ma2, Ri, CV2/CRMP5; Graus 2016 IRCNS criteria (PMID 26906964)

HSV PCR MANDATORY to rule out HSV encephalitis mimic; empiric acyclovir until result

CSF — variable; often mild lymphocytic pleocytosis; OCB variable; intrathecal antibody synthesis supports diagnosis

Cancer search — CT chest (SCLC, thymoma, breast) + abdomen/pelvis (gonadal, GI); mandatory for ALL AE workup but ESSENTIAL for intracellular AB (Hu/Ma2/Ri/CV2-CRMP5) where cancer drives prognosis

MRI brain with gad — patterns vary: limbic encephalitis pattern (most), brainstem/diencephalic (Ma2), parkinsonism / bulbar atrophy (IgLON5)

EEG — refractory status (GABA-B), generalised slowing, epileptiform discharges; cEEG if persistent AMS

GABA-B → refractory status epilepticus (route to neuro.status-epilepticus.core.v1); other AE subtypes may have seizures variably

Required before cyclophosphamide / MMF initiation

Rituximab / B-cell depletion pre-screen

PET/CT for occult malignancy when CT negative + intracellular AB positive + clinical suspicion remains; whole-body imaging

Polysomnography for IgLON5 — parasomnia + sleep-disordered breathing + dream enactment; OSA frequently co-existing

EMG for CASPR2 — continuous motor unit activity (neuromyotonia); peripheral nerve hyperexcitability

IgLON5 distinctive — parasomnia + sleep-disordered breathing + dream enactment; sleep study confirms; anti-Ma2 also has sleep disorders

IgLON5 parkinsonism + chorea; anti-CV2/CRMP5 chorea; anti-Ri opsoclonus-myoclonus; phenotype clusters guide AB panel

CASPR2 Morvan — neuromyotonia (continuous muscle activity, fasciculations); EMG confirms; distinguishes from central AE

DPPX distinctive — severe diarrhea (often profound weight loss) + CNS hyperexcitability; rare clue

Testicular US for anti-Ma2 in young male — testicular germ cell tumor association

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Severity triggers (12)

12 need judgement
  • informationallife_threateninggaba_b_receptor_refractory_status_paraneoplastic_sclc
    GABA-B receptor encephalitis: refractory status epilepticus + paraneoplastic SCLC ~60% — both engines apply (neuro.status-epilepticus.core.v1)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecaspr2_morvan_syndrome
    CASPR2 Morvan syndrome: neuromyotonia + insomnia + amnesia + dysautonomia tetrad; thymoma ~20%; younger male predominance (PMID 20663977)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereampa_receptor_limbic_psychosis
    AMPA receptor encephalitis: limbic + psychosis; paraneoplastic SCLC / breast / thymoma ~70%
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveredppx_perm_like
    DPPX PERM-like: CNS hyperexcitability + severe diarrhea + tremor + profound weight loss; rare
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremglur5_ophelia_hodgkin
    mGluR5 Ophelia syndrome: limbic encephalitis + psychiatric + Hodgkin lymphoma paraneoplastic
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereiglon5_sleep_parkinsonism_bulbar
    IgLON5: parasomnia + sleep-disordered breathing + parkinsonism + bulbar features + chorea + tauopathy; HLA-DRB1*10:01+DQB1*05:01 (PMID 28381508)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereanti_hu_paraneoplastic_sclc
    Anti-Hu paraneoplastic SCLC ~80%: sensory neuronopathy + brainstem + cerebellum + limbic; INTRACELLULAR — cancer-directed PRIORITY (Honnorat 2018 PMID 17480225)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereanti_ma2_paraneoplastic_testicular_cancer
    Anti-Ma2 paraneoplastic testicular germ cell (young men) / lung (older): diencephalic + brainstem + hypothalamic + sleep disorders; INTRACELLULAR — cancer-directed PRIORITY
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereanti_ri_paraneoplastic_omr
    Anti-Ri paraneoplastic breast / SCLC: opsoclonus-myoclonus + brainstem (OMR spectrum); INTRACELLULAR — cancer-directed PRIORITY
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereanti_cv2_crmp5_sclc_thymoma
    Anti-CV2/CRMP5 SCLC / thymoma: chorea + optic neuritis + sensorimotor + uveitis; INTRACELLULAR — cancer-directed PRIORITY
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_to_first_line_immunotherapy
    No improvement at 4 wk on first-line steroid + IVIG + PLEX (surface AB) → second-line rituximab + cyclophosphamide
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereintracellular_ab_poor_response_cancer_directed_priority
    Intracellular AB (Hu/Ma2/Ri/CV2-CRMP5) — antibodies are markers; T-cell mediated pathology; CANCER-DIRECTED THERAPY IS PRIORITY (chemo + surgery + radiation per cancer type); immunotherapy adjunct (Honnorat 2018 PMID 17480225)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONoptionalDrives severity classification
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Recommended regimen

AE-other surface vs intracellular AB treatment — surface immunotherapy priority; intracellular cancer-directed priority + immunotherapy adjunct (Graus 2016 PMID 26906964; Honnorat 2018 PMID 17480225)
axis: ae_other_surface_vs_intracellular_treatmentstep 1 - Step 1 — Surface AB first-line immunotherapy (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5)
Selected step "Step 1 — Surface AB first-line immunotherapy (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5)" — Surface antibody positive (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5) on CSF + serum CBA
  • methylprednisolone
    first line
    corticosteroid_pulse
    1 g IV daily × 5 d • IV • daily × 5 d (max: 5 g cumulative)
    triggers: acute_surface_ae_other
    First-line acute pulse for surface AB; Graus 2016 PMID 26906964
    rxcui 6902
  • IVIG
    first line
    pooled_human_IgG
    0.4 g/kg/day × 5 d (2 g/kg total) • IV • daily × 5 d
    triggers: acute_surface_ae_other
    First-line combo with steroid
    rxcui 1426680
  • plasmapheresis (PLEX)
    first line
    apheresis
    5 cycles q48h • IV/large-bore • q2 days × 5
    triggers: severe_surface_ae_or_ivig_alternative
    Alternative to IVIG for severe presentation
  • prednisone
    add on
    corticosteroid_oral_taper
    60 mg PO daily × 2-4 wk then slow taper over 6-12 mo • PO • daily slow taper
    triggers: post_pulse_taper_ae_other
    Maintenance after IV pulse; slow taper to prevent relapse
    rxcui 8640

outpatient playbook — drug actions (7)

  1. 1. rituximab maintenance
    1 g IV q6 mo × 2 y • IV • q6 mo
    trigger: Refractory or chronic
    Long-term DMT
  2. 2. prednisone slow taper
    Per taper down to 5-10 mg/d then off • PO • daily taper
    trigger: Post-acute
    Slow taper
  3. 3. azathioprine or MMF steroid-sparing
    AZA 2-3 mg/kg/d OR MMF 1-3 g/d • PO • daily / BID
    trigger: Steroid-sparing
    Maintenance
  4. 4. cancer-directed maintenance
    Per onc plan • per regimen • per regimen
    trigger: Paraneoplastic
    Priority for intracellular AB
  5. 5. levetiracetam (continued)
    1000-1500 mg BID • PO • BID
    trigger: Seizure history
    Long-term AED
  6. 6. levodopa-carbidopa (IgLON5)
    25/100 mg PO TID titrate • PO • TID
    trigger: IgLON5 parkinsonism
    Symptomatic
  7. 7. sertraline (post-AE depression)
    25-200 mg PO daily • PO • daily
    trigger: PHQ-9 ≥10
    Common sequelae

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: CASPR2 Morvan syndrome: neuromyotonia + insomnia + amnesia + dysautonomia tetrad (PMID 20663977); GABA-B receptor encephalitis: refractory status epilepticus + early-onset seizures + paraneoplastic SCLC ~60% (Graus 2016 PMID 26906964); AMPA receptor encephalitis: limbic + psychosis; paraneoplastic SCLC / breast / thymoma ~70%.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Other Autoimmune Encephalitis (surface + intracellular AB)** (neuro.encephalitis-autoimmune-other.v1).
Phenotype framing: AE-other (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5 surface; Hu / Ma2 / Ri / CV2-CRMP5 intracellular paraneoplastic) / HSV encephalitis / anti-NMDAR / anti-LGI1 / Hashimoto encephalopathy / CJD / Alzheimer / vascular dementia / paraneoplastic without identifiable antibody / sarcoid / SLE / Behçet / Susac / Whipple / drug-induced encephalopathy / metabolic encephalopathy
Scope: Subacute neuropsychiatric / neurological syndrome with distinctive phenotype cluster (Morvan tetrad / refractory status / PERM / Ophelia / sleep+parkinsonism / sensory neuronopathy / diencephalic / OMR / chorea+optic) → suspect AE-other subtype (Graus 2016 IRCNS PMID 26906964)

No severity triggers fired against current inputs.

Plan

Regimen axis: **AE-other surface vs intracellular AB treatment — surface immunotherapy priority; intracellular cancer-directed priority + immunotherapy adjunct (Graus 2016 PMID 26906964; Honnorat 2018 PMID 17480225)** — step "Step 1 — Surface AB first-line immunotherapy (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5)".
1. methylprednisolone 1 g IV daily × 5 d IV daily × 5 d (corticosteroid_pulse, first line) — First-line acute pulse for surface AB; Graus 2016 PMID 26906964
2. IVIG 0.4 g/kg/day × 5 d (2 g/kg total) IV daily × 5 d (pooled_human_IgG, first line) — First-line combo with steroid
3. plasmapheresis (PLEX) 5 cycles q48h IV/large-bore q2 days × 5 (apheresis, first line) — Alternative to IVIG for severe presentation
4. prednisone 60 mg PO daily × 2-4 wk then slow taper over 6-12 mo PO daily slow taper (corticosteroid_oral_taper, add on) — Maintenance after IV pulse; slow taper to prevent relapse

Setting playbook (outpatient) — Primary neurology + oncology + sleep medicine multidisciplinary — relapse surveillance + DMT + cancer surveillance (paraneoplastic) + IgLON5 sleep follow-up + cognitive rehab
5. rituximab maintenance 1 g IV q6 mo × 2 y IV q6 mo — Refractory or chronic (Long-term DMT)
6. prednisone slow taper Per taper down to 5-10 mg/d then off PO daily taper — Post-acute (Slow taper)
7. azathioprine or MMF steroid-sparing AZA 2-3 mg/kg/d OR MMF 1-3 g/d PO daily / BID — Steroid-sparing (Maintenance)
8. cancer-directed maintenance Per onc plan per regimen per regimen — Paraneoplastic (Priority for intracellular AB)
9. levetiracetam (continued) 1000-1500 mg BID PO BID — Seizure history (Long-term AED)
10. levodopa-carbidopa (IgLON5) 25/100 mg PO TID titrate PO TID — IgLON5 parkinsonism (Symptomatic)
11. sertraline (post-AE depression) 25-200 mg PO daily PO daily — PHQ-9 ≥10 (Common sequelae)

Non-pharmacologic actions:
- Multidisciplinary tumor board if paraneoplastic
- Cognitive rehab + memory aids
- PT/OT for parkinsonism / ataxia / neuromyotonia
- Speech / swallow therapy
- CPAP for IgLON5
- Pre-DMT vaccinations
- Bone health
- Mental health referral if PHQ-9 ≥10
- Vocational rehab

AVOID / contraindication checks:
- Surface_vs_intracellular_AB_distinction_critical (intracellular = cancer directed priority)
- Full_autoimmune_AE_panel_via_CBA (CSF + serum; CASPR2/GABA B/AMPA/DPPX/mGluR5/IgLON5/Hu/Ma2/Ri/CV2 CRMP5)
- HSV_PCR_MANDATORY_to_rule_out_HSV_mimic
- Cancer_search_CT_chest_abdomen_pelvis_MANDATORY (paraneoplastic association)
- Testicular_US_in_young_male_with_anti_Ma2
- PET_CT_if_initial_negative_cancer_search_with_intracellular_AB
- Cancer_directed_therapy_PRIORITY_for_intracellular_AB (Hu/Ma2/Ri/CV2 CRMP5 — Honnorat 2018 PMID 17480225)
- GABA_B_refractory_status_route_to_status_epilepticus_engine + SCLC workup
- IgLON5_PSG_and_CPAP_for_sleep_disordered_breathing
- HBV_VZV_TB_screen_before_rituximab
- Cyclophosphamide_CONTRAINDICATED_in_pregnancy
- Cancer_surveillance_q3_mo_first_2_years_if_paraneoplastic
- Slow_6_to_12_mo_steroid_taper_to_prevent_relapse

Monitoring

Regimen monitoring:
- Daily neuro exam + GCS
- cEEG if refractory status (GABA-B)
- PSG for IgLON5 + repeat at 6-12 mo
- CBC + CMP + LFT + glucose during steroid + chemotherapy
- CD19/CD20 + IgG q3-6 mo on rituximab
- Cancer surveillance imaging q3 mo first 2 y if paraneoplastic
- Tumor markers per cancer type
- CSF AE panel re-test at 6 wk if no improvement
- AED levels
- Pregnancy test before each cyclophosphamide cycle
- PHQ-9 + cognitive battery at follow-up

Setting (outpatient) monitoring:
- CBC + LFT + IgG q3-6 mo on DMT
- Cancer imaging q3 mo first 2 y
- PSG repeat for IgLON5
- AED levels
- Cognitive battery q6 mo
- PHQ-9 each visit

Follow-up plan: Long-term coordination — neurology + oncology + sleep medicine for IgLON5 + neuropsych + cognitive rehab; PHQ-9 + cognitive battery at 3 + 6 + 12 + 24 mo; cancer surveillance long-term; AED management; pre-DMT vaccinations; goals of care discussion if intracellular AB + advanced cancer + poor prognosis
- Close-out criterion: Long-term plan + multidisciplinary follow-up documented

Monitoring phase: Daily neuro + GCS during acute; cEEG if status (GABA-B); CBC + LFT + glucose during steroid + chemotherapy; tumor response markers; cancer surveillance imaging q3 mo for first 2 y if paraneoplastic; PSG repeat for IgLON5; CD19/CD20 + IgG q3-6 mo on rituximab; PHQ-9 / cognitive battery long-term; surveillance for second malignancy

Disposition

Current setting: outpatient — Primary neurology + oncology + sleep medicine multidisciplinary — relapse surveillance + DMT + cancer surveillance (paraneoplastic) + IgLON5 sleep follow-up + cognitive rehab

Disposition criteria:
- Continue indefinite multidisciplinary follow-up
- Admit for relapse or cancer recurrence
- Discharge from chronic DMT after 2-5 y stable + cancer remission

Escalation triggers (move to higher acuity):
- Breakthrough symptoms on DMT → escalate (rituximab / cyclophosphamide)
- Cancer recurrence → onc urgent + neuro coordination
- New neurological deficit → ED + repeat workup
- IgG <500 → IVIG / pause rituximab
- Severe depression / suicidality → urgent psych

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] GABA-B receptor encephalitis: refractory status epilepticus + paraneoplastic SCLC ~60% — both engines apply (neuro.status-epilepticus.core.v1)
- [SEVERE] CASPR2 Morvan syndrome: neuromyotonia + insomnia + amnesia + dysautonomia tetrad; thymoma ~20%; younger male predominance (PMID 20663977)
- [SEVERE] AMPA receptor encephalitis: limbic + psychosis; paraneoplastic SCLC / breast / thymoma ~70%

Citations

- Graus 2016 IRCNS Position Paper Autoimmune Encephalitis Criteria + Honnorat 2018 Lancet Neurol Paraneoplastic Neurological Syndromes + NEJM 2018 AE review + IgLON5 + CASPR2 Morvan + intracellular paraneoplastic 2020 [PMID:26906964](https://pubmed.ncbi.nlm.nih.gov/26906964/)
- Cited evidence (PMID 17480225) [PMID:17480225](https://pubmed.ncbi.nlm.nih.gov/17480225/)
- Cited evidence (PMID 29490181) [PMID:29490181](https://pubmed.ncbi.nlm.nih.gov/29490181/)
- Cited evidence (PMID 28381508) [PMID:28381508](https://pubmed.ncbi.nlm.nih.gov/28381508/)
- Cited evidence (PMID 20663977) [PMID:20663977](https://pubmed.ncbi.nlm.nih.gov/20663977/)

Last reconciled with current guidelines: 2026-05-22.
References
  • Graus 2016 IRCNS Position Paper Autoimmune Encephalitis Criteria + Honnorat 2018 Lancet Neurol Paraneoplastic Neurological Syndromes + NEJM 2018 AE review + IgLON5 + CASPR2 Morvan + intracellular paraneoplastic 2020 — PMID:26906964
  • Cited evidence (PMID 17480225) — PMID:17480225
  • Cited evidence (PMID 29490181) — PMID:29490181
  • Cited evidence (PMID 28381508) — PMID:28381508
  • Cited evidence (PMID 20663977) — PMID:20663977