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neuro.encephalitis-autoimmune-other.v1

Other Autoimmune Encephalitis (surface + intracellular AB)

neurologyacutesubacuteadultpediatricgeriatricacuteinpatientmixed
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Phase C shard-3 neuro wave-13 (2026-05-15): authored at SCAFFOLDED — no AE-other-specific workup in clinical-tools-registry.ts (workup.encephalopathy covers shared scaffolding; CSF/serum AE antibody panel + paraneoplastic cancer-search workups schema-blocked). 12 phenotypes: CASPR2_Morvan / GABA-B_receptor_refractory_status_paraneoplastic_SCLC / AMPA_receptor_limbic_psychosis / DPPX_PERM_like / mGluR5_Ophelia_Hodgkin / IgLON5_sleep_parkinsonism_bulbar / anti-Hu_paraneoplastic_SCLC / anti-Ma2_paraneoplastic_testicular / anti-Ri_paraneoplastic_OMR / anti-CV2_CRMP5_SCLC_thymoma / refractory_to_first_line_immunotherapy / intracellular_AB_poor_response_cancer_directed_priority. 5 setting playbooks: home (slow taper + rituximab maintenance + AED + cancer surveillance + CPAP IgLON5) → outpatient (multidisciplinary neuro + onc + sleep clinic q3-6 mo) → ed (STAT MRI + LP + HSV PCR + AE panel + cancer search CT + empiric acyclovir + methylpred) → icu (GABA-B refractory status / DPPX hyperexcitability / IgLON5 respiratory failure / second-line refractory) → inpatient (complete first-line + cancer-directed therapy + steroid-sparing). 6 PMID evidence anchor: Graus 2016 IRCNS criteria (26906964) + Honnorat 2018 paraneoplastic (17480225) + NEJM 2018 AE review (29490181) + IgLON5 (28381508) + CASPR2 Morvan (20663977) + intracellular paraneoplastic (34006622). Schema-blocked: calc.edss / calc.mrs / calc.gcs / workup.autoimmune_encephalitis_panel / workup.paraneoplastic_panel / workup.cancer_search_ct_pet / workup.thymoma_chest_ct / workup.testicular_us_anti_ma2 — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: CRITICAL distinction between surface AB (immunotherapy priority) vs intracellular AB (CANCER-DIRECTED THERAPY PRIORITY — Honnorat 2018 PMID 17480225); full AE panel via CBA mandatory; HSV PCR MANDATORY; cancer search CT chest/abdomen/pelvis MANDATORY; testicular US in young male (anti-Ma2); PET/CT if initial negative + intracellular AB; GABA-B refractory status route to status engine + SCLC workup; IgLON5 PSG + CPAP for sleep-disordered breathing; HBV/VZV/TB pre-rituximab; cyclophosphamide CONTRAINDICATED pregnancy; cancer surveillance q3 mo first 2 y if paraneoplastic; slow 6-12 mo steroid taper. Sibling differentiation routes to neuro.encephalitis.hsv.v1 (HSV mimic - PCR mandatory), neuro.status-epilepticus.core.v1 (GABA-B refractory status), neuro.ms-flare.core.v1 (shared acute pulse; chronic DMT diverges), neuro.encephalitis-anti-nmdar.v1 (same-commit dedicated NMDAR engine), neuro.encephalitis-anti-lgi1.v1 (same-commit dedicated LGI1 engine). Promotion to INTEGRATED requires registered AE-panel workup (workup.autoimmune_encephalitis_panel, workup.paraneoplastic_panel, workup.cancer_search_ct_pet) + cancer-search cascade in clinical-tools-registry; calc.mrs/calc.gcs/calc.case for severity quantification.

Entry points (12)

  • symptom
    CASPR2 Morvan syndrome: neuromyotonia + insomnia + amnesia + dysautonomia tetrad (PMID 20663977)
    caspr2_morvan_syndrome
  • symptom
    GABA-B receptor encephalitis: refractory status epilepticus + early-onset seizures + paraneoplastic SCLC ~60% (Graus 2016 PMID 26906964)
    gaba_b_receptor_refractory_status_paraneoplastic_sclc
  • symptom
    AMPA receptor encephalitis: limbic + psychosis; paraneoplastic SCLC / breast / thymoma ~70%
    ampa_receptor_limbic_psychosis
  • symptom
    DPPX (PERM-like): CNS hyperexcitability + severe diarrhea + tremor + weight loss; rare
    dppx_perm_like
  • symptom
    mGluR5 Ophelia syndrome: limbic + psychiatric + Hodgkin lymphoma paraneoplastic
    mglur5_ophelia_hodgkin
  • symptom
    IgLON5: sleep disorder (parasomnia + sleep-disordered breathing) + parkinsonism + bulbar features + chorea; tauopathy (PMID 28381508)
    iglon5_sleep_parkinsonism_bulbar
  • symptom
    Anti-Hu paraneoplastic SCLC ~80%: sensory neuronopathy + brainstem + cerebellum + limbic; intracellular
    anti_hu_paraneoplastic_sclc
  • symptom
    Anti-Ma2 paraneoplastic testicular cancer (young men) / lung (older): diencephalic + brainstem + hypothalamic + sleep
    anti_ma2_paraneoplastic_testicular
  • symptom
    Anti-Ri paraneoplastic breast / SCLC: opsoclonus-myoclonus + brainstem; OMS spectrum
    anti_ri_paraneoplastic_omr
  • symptom
    Anti-CV2/CRMP5 SCLC / thymoma: chorea + optic neuritis + sensorimotor neuropathy + uveitis
    anti_cv2_crmp5_sclc_thymoma
  • history
    No response to first-line immunotherapy → second-line rituximab + cyclophosphamide; for intracellular AB cancer-directed priority
    refractory_to_first_line_immunotherapy
  • history
    Intracellular AB (Hu/Ma2/Ri/CV2-CRMP5) — antibodies are markers; T-cell mediated pathology; cancer-directed therapy PRIORITY (chemo + surgery + radiation); immunotherapy adjunct
    intracellular_ab_poor_response_cancer_directed_priority

Required inputs (20)

  • agerequired
    demographic • used at CONTEXT
    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)
  • sexrequired
    demographic • used at CONTEXT
    Sex distribution varies — CASPR2 male predominance ~80%; anti-Ma2 testicular in young men; anti-Ri breast in women
  • phenotype_cluster_identificationrequired
    symptom • used at FRAME
    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)
  • new_onset_seizures_statusrequired
    symptom • used at RED_FLAGS
    GABA-B → refractory status epilepticus (route to neuro.status-epilepticus.core.v1); other AE subtypes may have seizures variably
  • sleep_disorder_parasomnia
    symptom • used at CONTEXT
    IgLON5 distinctive — parasomnia + sleep-disordered breathing + dream enactment; sleep study confirms; anti-Ma2 also has sleep disorders
  • movement_disorder_parkinsonism_chorea_myoclonus
    symptom • used at CONTEXT
    IgLON5 parkinsonism + chorea; anti-CV2/CRMP5 chorea; anti-Ri opsoclonus-myoclonus; phenotype clusters guide AB panel
  • neuromyotonia_peripheral_nerve_hyperexcitability
    symptom • used at CONTEXT
    CASPR2 Morvan — neuromyotonia (continuous muscle activity, fasciculations); EMG confirms; distinguishes from central AE
  • severe_diarrhea_weight_loss
    symptom • used at CONTEXT
    DPPX distinctive — severe diarrhea (often profound weight loss) + CNS hyperexcitability; rare clue
  • csf_serum_autoimmune_ae_panel_cbarequired
    lab • used at INITIAL_WORKUP
    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_csfrequired
    lab • used at INITIAL_WORKUP
    HSV PCR MANDATORY to rule out HSV encephalitis mimic; empiric acyclovir until result
  • csf_cell_count_protein_ocbrequired
    lab • used at INITIAL_WORKUP
    CSF — variable; often mild lymphocytic pleocytosis; OCB variable; intrathecal antibody synthesis supports diagnosis
  • ct_chest_abdomen_pelvis_cancer_searchrequired
    imaging • used at INITIAL_WORKUP
    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
  • pet_scan_cancer_search_refractory
    imaging • used at BRANCHING_WORKUP
    PET/CT for occult malignancy when CT negative + intracellular AB positive + clinical suspicion remains; whole-body imaging
  • testicular_us_anti_ma2_young_male
    imaging • used at INITIAL_WORKUP
    Testicular US for anti-Ma2 in young male — testicular germ cell tumor association
  • mri_brain_with_gadrequired
    imaging • used at INITIAL_WORKUP
    MRI brain with gad — patterns vary: limbic encephalitis pattern (most), brainstem/diencephalic (Ma2), parkinsonism / bulbar atrophy (IgLON5)
  • eeg_routine_and_continuousrequired
    imaging • used at INITIAL_WORKUP
    EEG — refractory status (GABA-B), generalised slowing, epileptiform discharges; cEEG if persistent AMS
  • sleep_study_polysomnography_iglon5
    lab • used at BRANCHING_WORKUP
    Polysomnography for IgLON5 — parasomnia + sleep-disordered breathing + dream enactment; OSA frequently co-existing
  • emg_caspr2_neuromyotonia
    lab • used at BRANCHING_WORKUP
    EMG for CASPR2 — continuous motor unit activity (neuromyotonia); peripheral nerve hyperexcitability
  • pregnancy_testrequired
    lab • used at TREATMENT
    Required before cyclophosphamide / MMF initiation
  • hbv_vzv_tb_screenrequired
    lab • used at TREATMENT
    Rituximab / B-cell depletion pre-screen

12-phase flow (12)

  1. 1FRAME
    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)
    inputs: phenotype_cluster_identification
    advance: AE-other pathway activated
  2. 2ENTRY
    ED / neurology / oncology / sleep medicine — phenotype-driven entry (e.g., refractory status → GABA-B suspect; sleep+parkinsonism → IgLON5 suspect; sensory neuronopathy with cancer → anti-Hu suspect)
    inputs: age, sex
    advance: Pathway selected
  3. 3CONTEXT
    Capture known malignancy, cancer risk factors (smoking → SCLC), prior immunotherapy, autoimmune comorbidity, sleep disturbance, peripheral nerve symptoms, GI symptoms, baseline cognition
    inputs: sleep_disorder_parasomnia, movement_disorder_parkinsonism_chorea_myoclonus, neuromyotonia_peripheral_nerve_hyperexcitability, severe_diarrhea_weight_loss
    advance: AE-other-relevant context captured
  4. 4RED_FLAGS
    GABA-B refractory status epilepticus (route to neuro.status-epilepticus.core.v1); severe AMS / coma → ICU; respiratory failure (IgLON5 bulbar / sleep-disordered breathing) → NIV or intubate; severe DPPX hyperexcitability → ICU sedation; OMR with severe ataxia falls
    inputs: new_onset_seizures_status
    actions: workup.encephalopathy
    advance: Critical airway / status / autonomic triaged
  5. 5INITIAL_WORKUP
    CSF + serum AUTOIMMUNE AE PANEL via CBA (CASPR2 / GABA-B / AMPA1/2 / DPPX / mGluR5 / IgLON5 / Hu / Ma2 / Ri / CV2-CRMP5; Graus 2016 PMID 26906964); CSF cell count + protein + OCB + IgG index + HSV PCR; STAT MRI brain with gad; EEG (cEEG if status); CT chest/abdo/pelvis cancer search (MANDATORY); testicular US if young male (anti-Ma2); CBC + CMP + LFT + glucose + UA; CRP + ESR; sleep study (IgLON5 suspect); EMG (CASPR2 suspect)
    inputs: csf_serum_autoimmune_ae_panel_cba, csf_cell_count_protein_ocb, hsv_pcr_csf, mri_brain_with_gad, eeg_routine_and_continuous, ct_chest_abdomen_pelvis_cancer_search
    actions: panel.csf, panel.cbc, panel.renal, panel.lft, panel.inflammation, panel.coag
    advance: AE panel + cancer search + HSV PCR pending or returned
  6. 6BRANCHING_WORKUP
    If HSV PCR+ → route to neuro.encephalitis.hsv.v1; if NMDAR+ → route to neuro.encephalitis-anti-nmdar.v1; if LGI1+ → route to neuro.encephalitis-anti-lgi1.v1; if surface AB (CASPR2/GABA-B/AMPA/DPPX/mGluR5/IgLON5) → immunotherapy priority; if intracellular AB (Hu/Ma2/Ri/CV2-CRMP5) → CANCER-DIRECTED THERAPY PRIORITY + onc consult + PET/CT if CT negative; if all negative + clinical syndrome strong → repeat CSF panel + seronegative AE workup
    inputs: pet_scan_cancer_search_refractory, testicular_us_anti_ma2_young_male, sleep_study_polysomnography_iglon5, emg_caspr2_neuromyotonia
    advance: AE subtype confirmed + surface vs intracellular distinction made + cancer search complete
  7. 7DIFFERENTIAL
    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
    advance: Final phenotype + antibody + cancer association assigned
  8. 8RISK_STRATIFICATION
    Surface vs intracellular AB distinction (CRITICAL — intracellular worse prognosis, cancer-directed therapy priority); severity at presentation; cancer stage + treatability; time to immunotherapy + cancer therapy; refractory vs responsive
    actions: calc.nihss
    advance: Severity tier + treatment priority (cancer vs immunotherapy) stratified
  9. 9TREATMENT
    SURFACE AB (CASPR2 / GABA-B / AMPA / DPPX / mGluR5 / IgLON5) — first-line: IV methylpred 1 g/d × 5 d + IVIG 0.4 g/kg/d × 5 d ± PLEX 5 cycles q48h; second-line refractory: rituximab 1 g × 2 (days 0+14) + cyclophosphamide 750 mg/m² monthly × 6 mo. INTRACELLULAR AB (Hu / Ma2 / Ri / CV2-CRMP5) — CANCER-DIRECTED THERAPY IS THE PRIORITY (oncology consult + surgery / chemo / radiation per cancer type and stage) + immunotherapy adjunct (methylpred + IVIG modest benefit; rituximab + cyclophosphamide for severe). IgLON5 — chronic immunotherapy + PSG for sleep + CPAP for sleep-disordered breathing + symptomatic Rx for parkinsonism. GABA-B refractory status → midazolam infusion + AED + lung cancer workup. AED for seizures (LEV first-line). Cancer treatment per onc (chemotherapy for SCLC, surgery for thymoma, orchiectomy for testicular germ cell, mastectomy for breast)
    inputs: pregnancy_test, hbv_vzv_tb_screen
    advance: Immunotherapy + cancer-directed therapy active
  10. 10DISPOSITION
    Admit neurology + oncology coordination; ICU if refractory status (GABA-B) / severe AMS / coma / respiratory failure (IgLON5 bulbar) / cardiac instability (autonomic AE); outpatient onc clinic for chemo cycles; sleep medicine for IgLON5; multidisciplinary tumor board for paraneoplastic
    advance: Disposition + onc coordination documented
  11. 11MONITORING
    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
    actions: panel.cbc, panel.lft
    advance: Monitoring schedule documented
  12. 12FOLLOWUP
    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
    actions: calc.phq9
    advance: Long-term plan + multidisciplinary follow-up documented