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neuro.nmosd.v1

Neuromyelitis Optica Spectrum Disorder (NMOSD)

neurologychronicsubacuteadultpediatricpregnancyoutpatientinpatientmixed
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro wave-11 (2026-05-15): authored at SCAFFOLDED — no NMOSD-specific workup in clinical-tools-registry.ts (only workup.ms_flare registered for the shared MS-flare-style steroid + PLEX pulse). 10 phenotypes: aqp4_igg_positive_classic / aqp4_igg_negative_seronegative / area_postrema_syndrome / LETM / severe_bilateral_ON / brainstem / cerebral / diencephalic / pediatric / pregnancy_postpartum_relapse_risk. 5 setting playbooks: home (SC satralizumab self) → outpatient (MS-NMO clinic q3-6 mo) → ed (acute relapse + AQP4 sample BEFORE steroid) → inpatient (IV pulse + PLEX + DMT initiation incl mandatory pre-eculizumab meningococcal vaccination) → icu (cervical LETM with respiratory failure, area postrema crisis, meningococcal sepsis on eculizumab). 8 PMID evidence anchor: Wingerchuk IPND (26092914) + PREVENT eculizumab (31050279) + N-MOmentum inebilizumab (31495497) + SAkura satralizumab (31774956) + SAkuraStar (32333898) + Lyme CDC (33257476) + Apoly DS PLEX (21242498) + Banwell MOGAD (36706773). Schema-blocked: calc.edss / calc.opticospinal_severity / workup.aqp4_igg_index / workup.mog_igg / workup.ar_relapse_severity — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: MANDATORY meningococcal vaccination ≥2 wk before eculizumab initiation (PREVENT PMID 31050279; encapsulated organism risk); HBV/VZV/TB pre-rituximab/inebilizumab; AVOID IFN-β / fingolimod / natalizumab (worsen NMOSD); sample AQP4 BEFORE steroid pulse if feasible; postpartum relapse peak at 6 mo postpartum; slow steroid taper to prevent rebound. Sibling differentiation routes to neuro.ms-flare.core.v1 (acute pulse shared scaffolding but DMT diverges), neuro.transverse-myelitis.v1 (LETM pivot), neuro.ms-rrms.v1 (DMT pivot — wrong DMT causes harm), neuro.mogad.v1 (MOG-IgG distinct same-commit peer), neuro.adem.v1 (pediatric overlap same-commit peer). Promotion to INTEGRATED requires registered NMOSD workup (e.g., workup.aqp4_igg_index, workup.mog_igg) + eculizumab + meningococcal vaccination cascade in clinical-tools-registry.

Entry points (8)

  • symptom
    AQP4-IgG positive (cell-based assay) + ≥1 core clinical event per Wingerchuk 2015 (PMID 26092914)
    aqp4_igg_positive_with_core_event
  • symptom
    LETM ≥3 contiguous vertebral segments on MRI — cardinal NMOSD feature (Wingerchuk 2015 PMID 26092914)
    longitudinally_extensive_transverse_myelitis_LETM
  • symptom
    Severe ON — bilateral simultaneous, or severe unilateral with poor recovery + chiasmal lesion — NMOSD phenotype
    severe_optic_neuritis_bilateral_or_simultaneous
  • symptom
    Intractable hiccups + nausea/vomiting ≥48 h afebrile — area postrema dorsal medulla lesion (Wingerchuk 2015 PMID 26092914)
    area_postrema_syndrome
  • symptom
    Brainstem syndrome with characteristic lesion on MRI (e.g., periependymal 4th ventricle) — NMOSD core
    acute_brainstem_syndrome_with_lesion
  • symptom
    Diencephalic (narcolepsy / SIADH) or cerebral syndrome with AQP4-typical lesion (corticospinal / corpus callosum)
    diencephalic_or_cerebral_syndrome_aqp4_specific
  • history
    Pregnancy + known NMOSD — relapse risk peaks postpartum; DMT planning (azathioprine OK; rituximab caution; eculizumab Class B)
    pregnancy_in_known_nmosd
  • demographic
    Pediatric NMOSD — AQP4-IgG+ children rarer; ADEM overlap pattern; rituximab off-label
    pediatric_nmosd_under_18

Required inputs (16)

  • agerequired
    demographic • used at CONTEXT
    Adult NMOSD peaks 30s-40s; pediatric phenotype overlaps with ADEM; older onset suggests paraneoplastic mimic (Wingerchuk 2015 PMID 26092914)
  • sexrequired
    demographic • used at CONTEXT
    AQP4-IgG+ NMOSD female:male 9:1 in adults; seronegative more balanced; pediatric 3:1
  • symptom_onset_and_relapse_historyrequired
    history • used at FRAME
    NMOSD is a relapsing disease (60% relapse in 1 y untreated per Wingerchuk 2015 PMID 26092914); document ARR + most severe event
  • aqp4_igg_serum_cell_based_assayrequired
    lab • used at INITIAL_WORKUP
    AQP4-IgG via cell-based assay (CBA) — gold standard; ELISA lower sensitivity; sample BEFORE steroid pulse if possible (steroid lowers titer)
  • mog_igg_serum_cell_based_assayrequired
    lab • used at BRANCHING_WORKUP
    Distinguish from MOGAD — different DMT; MOG-IgG live cell-based assay (Banwell 2023 PMID 36706773)
  • mri_cord_with_gad_for_letmrequired
    imaging • used at INITIAL_WORKUP
    STAT MRI cervical + thoracic cord with gadolinium — LETM ≥3 vertebral segments cardinal NMOSD feature; cord swelling (Wingerchuk 2015 PMID 26092914)
  • mri_brain_orbit_with_gadrequired
    imaging • used at INITIAL_WORKUP
    Brain + orbits — optic nerve gad enhancement (chiasmal involvement specific); area postrema dorsal medulla; periependymal 4th ventricle / 3rd ventricle / corpus callosum NMOSD-typical lesions
  • lp_csf_cell_count_protein_ocb_igg_indexrequired
    lab • used at INITIAL_WORKUP
    CSF — pleocytosis often >50 cells (vs MS <50); neutrophils + eosinophils may be present (vs MS lymphocyte-dominant); OCB+ in only 15-30% of NMOSD (vs MS 90%+); GFAP if seronegative
  • autoimmune_panel_ana_dsdna_ss_a_ss_b_anti_rorequired
    lab • used at BRANCHING_WORKUP
    NMOSD highly comorbid with SLE / Sjögren / autoimmune thyroid; document concurrent autoimmunity
  • hiv_rpr_lymerequired
    lab • used at BRANCHING_WORKUP
    Exclude infectious LETM mimics — HIV myelopathy, neurosyphilis, Lyme myelitis (CDC PMID 33257476); HTLV-1 if endemic exposure
  • pregnancy_testrequired
    lab • used at TREATMENT
    Required before DMT initiation in reproductive-age females; impacts DMT selection
  • meningococcal_vaccination_statusrequired
    lab • used at TREATMENT
    Eculizumab MANDATES meningococcal vaccination ≥2 wk before initiation (anti-C5 → encapsulated organism risk; PREVENT PMID 31050279)
  • hepatitis_b_vzv_tb_screenrequired
    lab • used at TREATMENT
    Rituximab/inebilizumab need HBV / VZV / TB screen pre-initiation
  • prior_dmt_exposurerequired
    history • used at CONTEXT
    Prior IFN-β / natalizumab / fingolimod may have WORSENED disease before NMOSD diagnosis — document for DMT history; avoid re-exposure
  • comorbid_autoimmune_disease
    history • used at CONTEXT
    SLE / Sjögren / MG / autoimmune thyroid frequently coexist with NMOSD; influences immunosuppression strategy
  • respiratory_status_in_cervical_letmrequired
    symptom • used at RED_FLAGS
    High cervical LETM (C3-C5) → diaphragm; FVC < 20 mL/kg or NIF magnitude < 30 → intubate; ICU threshold

12-phase flow (12)

  1. 1FRAME
    Confirm NMOSD per Wingerchuk 2015 IPND criteria (PMID 26092914) — AQP4-IgG+ with ≥1 core clinical event OR AQP4-IgG-negative with ≥2 core + MRI features + alternative diagnosis exclusion
    inputs: symptom_onset_and_relapse_history
    advance: NMOSD phenotype assigned (AQP4+, AQP4-, or pending)
  2. 2ENTRY
    Acute core event (ON / LETM / area postrema / brainstem / diencephalic / cerebral) → acute pathway; established NMOSD on DMT → chronic management; pregnancy / pediatric → specialty routing
    inputs: age, sex
    advance: Pathway selected (acute vs chronic vs specialty)
  3. 3CONTEXT
    Capture pregnancy status, comorbid autoimmunity (SLE/Sjögren/MG/thyroid), prior DMT exposure (esp IFN-β which worsens), vaccination status (meningococcal critical for eculizumab), HBV/VZV/TB
    inputs: comorbid_autoimmune_disease, prior_dmt_exposure
    advance: NMOSD-relevant context captured
  4. 4RED_FLAGS
    High cervical LETM → respiratory failure (FVC < 20 mL/kg or NIF magnitude < 30 → intubate); area postrema crisis → aspiration risk; severe bilateral ON → permanent blindness if untreated; rapid LETM ascent → ICU
    inputs: respiratory_status_in_cervical_letm
    actions: workup.ms_flare
    advance: Critical airway / vision / cord-level escalation triaged
  5. 5INITIAL_WORKUP
    AQP4-IgG (CBA) + MOG-IgG (CBA) — BEFORE steroid if feasible; STAT MRI brain + orbits + cervical + thoracic cord with gad (LETM ≥3 segments cardinal); LP (cell count, protein, OCB, IgG index, GFAP); CBC + CMP + LFT + glucose + pregnancy test; ESR + CRP
    inputs: aqp4_igg_serum_cell_based_assay, mri_cord_with_gad_for_letm, mri_brain_orbit_with_gad, lp_csf_cell_count_protein_ocb_igg_index
    actions: panel.csf, panel.cbc, panel.renal, panel.lft, panel.inflammation
    advance: AQP4 status pending or returned + MRI complete + LP done
  6. 6BRANCHING_WORKUP
    If AQP4-IgG-negative — send MOG-IgG (MOGAD pivot to neuro.mogad.v1), GFAP-IgG (autoimmune GFAP astrocytopathy), repeat AQP4 in 3 mo; autoimmune panel ANA/dsDNA/SS-A/SS-B; infectious panel HIV/RPR/Lyme (CDC PMID 33257476)/HTLV-1; paraneoplastic if older + atypical
    inputs: mog_igg_serum_cell_based_assay, autoimmune_panel_ana_dsdna_ss_a_ss_b_anti_ro, hiv_rpr_lyme
    advance: Etiology classified (AQP4+ / MOG+ pivot / seronegative NMOSD / mimic)
  7. 7DIFFERENTIAL
    NMOSD AQP4+ classic / NMOSD AQP4- seronegative / MOGAD (pivot to neuro.mogad.v1) / MS LETM-variant (rare; route to neuro.ms-flare.core.v1) / sarcoid LETM / SLE TM / Sjögren TM / paraneoplastic (anti-CRMP5/amphiphysin) / Lyme myelitis / HTLV-1 TSP / B12/copper / spinal cord infarct / dural AV fistula
    advance: Final phenotype assigned with confidence
  8. 8RISK_STRATIFICATION
    Severity of index event (ASIA, visual acuity); annualized relapse rate; AQP4-IgG titer; LETM length; respiratory involvement; vaccination + DMT-eligibility screen (PREVENT eculizumab PMID 31050279 / N-MOmentum PMID 31495497 / SAkura PMID 31774956)
    advance: DMT-eligibility tier assigned
  9. 9TREATMENT
    ACUTE: IV methylprednisolone 1 g/d × 3-5 d + PLEX 5 sessions q48h for severe / steroid-refractory (Apoly DS PMID 21242498); IVIG alternative if PLEX contraindicated. CHRONIC AQP4+: eculizumab (PREVENT PMID 31050279) — meningococcal vaccination first; OR satralizumab SC (SAkura PMID 31774956); OR inebilizumab anti-CD19 IV q6 mo (N-MOmentum PMID 31495497); rituximab 1 g IV × 2 q6 mo (off-label, widely used). AZA / MMF less effective. AVOID IFN-β / fingolimod / natalizumab (worsen NMOSD).
    inputs: pregnancy_test, meningococcal_vaccination_status, hepatitis_b_vzv_tb_screen
    advance: Acute pulse + DMT selected with shared decision
  10. 10DISPOSITION
    Admit neurology for any acute relapse with deficit (steroid + monitoring + PLEX trigger); ICU if cervical LETM with respiratory or aspiration risk; outpatient infusion suite for chronic DMT; MS-NMO specialty clinic q3-6 mo
    advance: Disposition documented
  11. 11MONITORING
    Daily neuro exam + ASIA (schema-blocked) in acute phase; bowel/bladder + pressure ulcer surveillance; CBC + CD19/CD20 + IgG q3-6 mo on B-cell depletion; meningococcal booster q3-5 y on eculizumab; LFT/CBC on AZA/MMF; AQP4 titer not routinely re-tested but may correlate; annual MRI
    actions: panel.cbc, panel.lft, panel.renal
    advance: Monitoring schedule active
  12. 12FOLLOWUP
    Rehab (PT/OT/SLP); ophthalmology q3-6 mo if ON; urology for neurogenic bladder; PCP for vaccinations + bone health; mental health screen (depression highly comorbid); pregnancy planning + postpartum surveillance (60% relapse peak); MS-NMO specialty clinic q3-6 mo
    advance: Long-term plan + specialty referrals documented