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neuro.nmosd.v1PRODUCTION
neuro.nmosd.v1

Neuromyelitis Optica Spectrum Disorder (NMOSD)

neurologychronicsubacuteadultpediatricpregnancy
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12/12 authored

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

Current phase

Frame

Detailed

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

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NMOSD phenotype assigned (AQP4+, AQP4-, or pending)

Patient inputs (16)

Distinguish from MOGAD — different DMT; MOG-IgG live cell-based assay (Banwell 2023 PMID 36706773)

NMOSD highly comorbid with SLE / Sjögren / autoimmune thyroid; document concurrent autoimmunity

Exclude infectious LETM mimics — HIV myelopathy, neurosyphilis, Lyme myelitis (CDC PMID 33257476); HTLV-1 if endemic exposure

Adult NMOSD peaks 30s-40s; pediatric phenotype overlaps with ADEM; older onset suggests paraneoplastic mimic (Wingerchuk 2015 PMID 26092914)

AQP4-IgG+ NMOSD female:male 9:1 in adults; seronegative more balanced; pediatric 3:1

Prior IFN-β / natalizumab / fingolimod may have WORSENED disease before NMOSD diagnosis — document for DMT history; avoid re-exposure

NMOSD is a relapsing disease (60% relapse in 1 y untreated per Wingerchuk 2015 PMID 26092914); document ARR + most severe event

AQP4-IgG via cell-based assay (CBA) — gold standard; ELISA lower sensitivity; sample BEFORE steroid pulse if possible (steroid lowers titer)

STAT MRI cervical + thoracic cord with gadolinium — LETM ≥3 vertebral segments cardinal NMOSD feature; cord swelling (Wingerchuk 2015 PMID 26092914)

Brain + orbits — optic nerve gad enhancement (chiasmal involvement specific); area postrema dorsal medulla; periependymal 4th ventricle / 3rd ventricle / corpus callosum NMOSD-typical lesions

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

High cervical LETM (C3-C5) → diaphragm; FVC < 20 mL/kg or NIF magnitude < 30 → intubate; ICU threshold

Required before DMT initiation in reproductive-age females; impacts DMT selection

Eculizumab MANDATES meningococcal vaccination ≥2 wk before initiation (anti-C5 → encapsulated organism risk; PREVENT PMID 31050279)

Rituximab/inebilizumab need HBV / VZV / TB screen pre-initiation

SLE / Sjögren / MG / autoimmune thyroid frequently coexist with NMOSD; influences immunosuppression strategy

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (10)

10 need judgement
  • informationalsevereaqp4_igg_positive_classic_nmosd
    AQP4-IgG positive with ≥1 core clinical event (ON / LETM / area postrema / brainstem / diencephalic / cerebral) per Wingerchuk 2015 (PMID 26092914)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverearea_postrema_syndrome_aqp4_specific
    Intractable hiccups + nausea/vomiting ≥48 h afebrile + dorsal medulla lesion — area postrema syndrome (Wingerchuk 2015 PMID 26092914)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverelongitudinally_extensive_transverse_myelitis_LETM
    Acute myelitis with LETM ≥3 contiguous vertebral segments — strongly suggests NMOSD vs MS (Wingerchuk 2015 PMID 26092914)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_optic_neuritis_bilateral_simultaneous
    Severe ON — bilateral simultaneous or severe unilateral with NLP / chiasmal involvement / poor recovery — NMOSD phenotype
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebrainstem_clinical_syndrome_nmosd
    Brainstem syndrome with characteristic NMOSD lesion (periependymal 4th ventricle, dorsal medulla)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepediatric_nmosd_under_18
    Pediatric NMOSD — overlaps with ADEM phenotype; AQP4-IgG+ children rarer; rituximab off-label first-line
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_with_nmosd_postpartum_relapse_risk
    Pregnancy in known NMOSD — relapse rate increases in postpartum window (first 6 mo); plan DMT continuity (eculizumab Cat B preferred; AZA Cat D but used)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateaqp4_igg_negative_seronegative_nmosd
    AQP4-IgG-negative + ≥2 core clinical events + MRI features + alternative diagnosis excluded (Wingerchuk 2015 PMID 26092914)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatecerebral_syndrome_extensive_nmosd
    Cerebral syndrome with AQP4-typical lesion (corticospinal, corpus callosum, periependymal) — Wingerchuk 2015 core
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatediencephalic_syndrome_aqp4_specific
    Diencephalic syndrome — narcolepsy, SIADH, hypothalamic dysfunction with periependymal 3rd ventricle lesion
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

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Recommended regimen

NMOSD acute relapse + chronic AQP4+ DMT (PREVENT eculizumab PMID 31050279 / N-MOmentum inebilizumab PMID 31495497 / SAkura satralizumab PMID 31774956)
axis: nmosd_acute_and_chronic_treatmentstep 1 - Step 1 — Acute relapse: IV methylprednisolone pulse (ONTT/MS-flare scaffolding; Wingerchuk 2015 PMID 26092914)
Selected step "Step 1 — Acute relapse: IV methylprednisolone pulse (ONTT/MS-flare scaffolding; Wingerchuk 2015 PMID 26092914)" — Acute NMOSD core event (ON / LETM / area postrema / brainstem / diencephalic / cerebral) with neuro deficit
  • methylprednisolone
    first line
    corticosteroid_pulse
    1 g IV daily × 3-5 d (typically 5 d) • IV • daily × 3-5 d (max: 5 g cumulative)
    triggers: acute_nmosd_relapse
    First-line acute pulse; reduces inflammation; same scaffolding as MS-flare ONTT-style; sample AQP4 BEFORE steroid if feasible (steroid lowers titer)
    rxcui 6902
  • prednisone
    add on
    corticosteroid_oral_taper
    60 mg PO daily × 2 wk then taper over 4-8 wk • PO • daily taper
    triggers: post_pulse_taper
    Slow oral taper after IV pulse to bridge to DMT initiation; NMOSD relapses often rebound during steroid taper
    rxcui 8640

outpatient playbook — drug actions (8)

  1. 1. eculizumab (infusion suite)
    1200 mg IV q2 wk • IV • q2 wk
    trigger: AQP4+ NMOSD chronic DMT
    PREVENT PMID 31050279; meningococcal vaccination MANDATORY ≥2 wk before initiation
  2. 2. inebilizumab (infusion suite)
    300 mg IV q6 mo • IV • q6 mo
    trigger: AQP4+ NMOSD chronic DMT alt
    N-MOmentum PMID 31495497; HBV/VZV/TB pre-screen
  3. 3. satralizumab (clinic-administered or self)
    120 mg SC q4 wk • SC • q4 wk
    trigger: AQP4+ NMOSD chronic DMT SC alt
    SAkura PMID 31774956
  4. 4. rituximab (off-label)
    1 g IV × 2 doses q6 mo • IV • q6 mo
    trigger: Biologic-unavailable / cost-constrained AQP4+
    HERMES-style; off-label widely used; HBV/VZV/TB screen first
  5. 5. azathioprine (oral steroid-sparing)
    2-3 mg/kg PO daily • PO • daily
    trigger: Biologic-unavailable / pregnancy planning
    TPMT + CBC + LFT monitoring
  6. 6. mycophenolate mofetil (oral steroid-sparing)
    1 g PO BID titrate to 2-3 g/day • PO • BID
    trigger: Biologic-unavailable / AZA-intolerant
    CONTRAINDICATED in pregnancy
  7. 7. baclofen (spasticity)
    10-20 mg PO TID • PO • TID
    trigger: Spasticity
    AAN symptomatic; max 80-120 mg/day; renal adjust
  8. 8. oxybutynin or mirabegron (bladder)
    targeted • PO • daily-TID
    trigger: Neurogenic detrusor overactivity
    Urology-managed

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: AQP4-IgG positive (cell-based assay) + ≥1 core clinical event per Wingerchuk 2015 (PMID 26092914); LETM ≥3 contiguous vertebral segments on MRI — cardinal NMOSD feature (Wingerchuk 2015 PMID 26092914); Severe ON — bilateral simultaneous, or severe unilateral with poor recovery + chiasmal lesion — NMOSD phenotype.

Objective

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

Assessment

**Neuromyelitis Optica Spectrum Disorder (NMOSD)** (neuro.nmosd.v1).
Phenotype framing: 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
Scope: 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

No severity triggers fired against current inputs.

Plan

Regimen axis: **NMOSD acute relapse + chronic AQP4+ DMT (PREVENT eculizumab PMID 31050279 / N-MOmentum inebilizumab PMID 31495497 / SAkura satralizumab PMID 31774956)** — step "Step 1 — Acute relapse: IV methylprednisolone pulse (ONTT/MS-flare scaffolding; Wingerchuk 2015 PMID 26092914)".
1. methylprednisolone 1 g IV daily × 3-5 d (typically 5 d) IV daily × 3-5 d (corticosteroid_pulse, first line) — First-line acute pulse; reduces inflammation; same scaffolding as MS-flare ONTT-style; sample AQP4 BEFORE steroid if feasible (steroid lowers titer)
2. prednisone 60 mg PO daily × 2 wk then taper over 4-8 wk PO daily taper (corticosteroid_oral_taper, add on) — Slow oral taper after IV pulse to bridge to DMT initiation; NMOSD relapses often rebound during steroid taper

Setting playbook (outpatient) — Primary MS-NMO clinic — comprehensive NMOSD management q3-6 mo with relapse + MRI + DMT + comorbidity + pregnancy + symptomatic care; meningococcal booster surveillance; vaccination + infection prevention (Wingerchuk 2015 PMID 26092914; PREVENT PMID 31050279)
3. eculizumab (infusion suite) 1200 mg IV q2 wk IV q2 wk — AQP4+ NMOSD chronic DMT (PREVENT PMID 31050279; meningococcal vaccination MANDATORY ≥2 wk before initiation)
4. inebilizumab (infusion suite) 300 mg IV q6 mo IV q6 mo — AQP4+ NMOSD chronic DMT alt (N-MOmentum PMID 31495497; HBV/VZV/TB pre-screen)
5. satralizumab (clinic-administered or self) 120 mg SC q4 wk SC q4 wk — AQP4+ NMOSD chronic DMT SC alt (SAkura PMID 31774956)
6. rituximab (off-label) 1 g IV × 2 doses q6 mo IV q6 mo — Biologic-unavailable / cost-constrained AQP4+ (HERMES-style; off-label widely used; HBV/VZV/TB screen first)
7. azathioprine (oral steroid-sparing) 2-3 mg/kg PO daily PO daily — Biologic-unavailable / pregnancy planning (TPMT + CBC + LFT monitoring)
8. mycophenolate mofetil (oral steroid-sparing) 1 g PO BID titrate to 2-3 g/day PO BID — Biologic-unavailable / AZA-intolerant (CONTRAINDICATED in pregnancy)
9. baclofen (spasticity) 10-20 mg PO TID PO TID — Spasticity (AAN symptomatic; max 80-120 mg/day; renal adjust)
10. oxybutynin or mirabegron (bladder) targeted PO daily-TID — Neurogenic detrusor overactivity (Urology-managed)

Non-pharmacologic actions:
- PT/OT referral for gait + ADL
- Mental health referral if PHQ-9 ≥10
- Ophthalmology q3-6 mo if ON history
- Urology q-y for neurogenic bladder
- Vitamin D 2000-4000 IU/d
- Smoking cessation counseling
- Mediterranean diet
- Pelvic floor PT for bladder
- Pre-DMT vaccinations (live MMR / VZV / yellow fever 4-6 wk before B-cell depletion; meningococcal MANDATORY pre-eculizumab)
- Bone health (DEXA, vitamin D, calcium)
- Pregnancy planning + postpartum surveillance (60% relapse peak)

AVOID / contraindication checks:
- AQP4_BEFORE_steroid_if_feasible (CBA assay titer lowered by steroid pulse)
- AVOID_IFN_beta_fingolimod_natalizumab_in_NMOSD (documented disease worsening)
- MANDATORY_meningococcal_vaccination_2wk_before_eculizumab (PREVENT PMID 31050279; encapsulated organism risk)
- HBV_VZV_TB_screen_before_rituximab_inebilizumab (B cell depletion + reactivation risk)
- Cyclophosphamide_CONTRAINDICATED_in_pregnancy
- Mycophenolate_CONTRAINDICATED_in_pregnancy
- Rituximab_caution_in_pregnancy (Cat C; eculizumab preferred biologic)
- Postpartum_relapse_peak_6mo_window_continue_DMT
- Steroid_taper_slow_to_prevent_rebound_relapse
- Meningococcal_booster_q3_to_5_y_on_eculizumab
- Hypogammaglobulinemia_surveillance_on_b_cell_depletion

Monitoring

Regimen monitoring:
- Daily neuro exam + ASIA grading (schema-blocked) during acute admission
- AQP4-IgG titer baseline + serial (correlation soft)
- CBC + CD19/CD20 + IgG q3-6 mo on B-cell depletion (rituximab/inebilizumab)
- LFT + CBC monthly first 6 mo on AZA/MMF
- Meningococcal booster q3-5 y on eculizumab
- Annual MRI brain + cord
- Ophthalmology q3-6 mo if ON history
- Bowel + bladder log if cord involvement; urology q-mo
- Pressure ulcer surveillance + DEXA
- Pregnancy / postpartum surveillance (60% relapse peak postpartum)

Setting (outpatient) monitoring:
- Annual MRI brain + orbits + cord
- CBC + LFT q3-6 mo
- IgG annually on B-cell depletion
- Meningococcal booster q3-5 y on eculizumab
- AQP4 titer (not routine)
- Pregnancy intent each visit

Follow-up plan: 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
- Close-out criterion: Long-term plan + specialty referrals documented

Monitoring phase: 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

Disposition

Current setting: outpatient — Primary MS-NMO clinic — comprehensive NMOSD management q3-6 mo with relapse + MRI + DMT + comorbidity + pregnancy + symptomatic care; meningococcal booster surveillance; vaccination + infection prevention (Wingerchuk 2015 PMID 26092914; PREVENT PMID 31050279)

Disposition criteria:
- Continue indefinite MS-NMO clinic q3-6 mo
- Admit for any acute relapse with deficit
- Hospice + palliative if severe disability + recurrent complications

Escalation triggers (move to higher acuity):
- Breakthrough relapse on DMT → consider switch to higher-efficacy biologic
- New ON / LETM / area postrema → ED + steroid pulse + PLEX trigger
- IgG <500 + recurrent infection on B-cell depletion → IVIG / pause
- Hepatotoxicity (LFT >3× ULN) on AZA/MMF → pause + workup
- Severe lymphopenia on biologic → pause + workup
- Pregnancy confirmed → MS-NMO + MFM coordination
- Fever / systemic infection on eculizumab → urgent w/u (meningococcal sepsis)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] AQP4-IgG positive with ≥1 core clinical event (ON / LETM / area postrema / brainstem / diencephalic / cerebral) per Wingerchuk 2015 (PMID 26092914)
- [SEVERE] Intractable hiccups + nausea/vomiting ≥48 h afebrile + dorsal medulla lesion — area postrema syndrome (Wingerchuk 2015 PMID 26092914)
- [SEVERE] Acute myelitis with LETM ≥3 contiguous vertebral segments — strongly suggests NMOSD vs MS (Wingerchuk 2015 PMID 26092914)

Citations

- Wingerchuk 2015 IPND criteria (PMID 26092914) + PREVENT (Pittock NEJM 2019 PMID 31050279) + N-MOmentum (Cree Lancet 2019 PMID 31495497) + SAkura (Yamamura NEJM 2019 PMID 31774956) + AAN 2024 NMOSD [PMID:26092914](https://pubmed.ncbi.nlm.nih.gov/26092914/)
- Cited evidence (PMID 31050279) [PMID:31050279](https://pubmed.ncbi.nlm.nih.gov/31050279/)
- Cited evidence (PMID 31495497) [PMID:31495497](https://pubmed.ncbi.nlm.nih.gov/31495497/)
- Cited evidence (PMID 31774956) [PMID:31774956](https://pubmed.ncbi.nlm.nih.gov/31774956/)
- Cited evidence (PMID 32333898) [PMID:32333898](https://pubmed.ncbi.nlm.nih.gov/32333898/)

Last reconciled with current guidelines: 2026-05-22.
References
  • Wingerchuk 2015 IPND criteria (PMID 26092914) + PREVENT (Pittock NEJM 2019 PMID 31050279) + N-MOmentum (Cree Lancet 2019 PMID 31495497) + SAkura (Yamamura NEJM 2019 PMID 31774956) + AAN 2024 NMOSD — PMID:26092914
  • Cited evidence (PMID 31050279) — PMID:31050279
  • Cited evidence (PMID 31495497) — PMID:31495497
  • Cited evidence (PMID 31774956) — PMID:31774956
  • Cited evidence (PMID 32333898) — PMID:32333898