Clinical Commander

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neuro.ms-rrms.v1

Relapsing-Remitting Multiple Sclerosis (chronic DMT)

neurologychronicadultpediatricpregnancyoutpatientinpatientmixed
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro wave-10 (2026-05-15): authored at SCAFFOLDED — no MS-subtype-specific workup in clinical-tools-registry.ts (only workup.ms_flare registered for acute relapse). 8 phenotypes: active_RRMS / highly_active_RRMS / classic_RRMS / CIS / pregnancy_RRMS / pediatric_RRMS / breakthrough_on_DMT / PML_risk_natalizumab. 5 setting playbooks: home (DMT injection + adherence) → outpatient (primary MS clinic q3-6 mo) → ed (relapse triage + PML rule-out) → icu (rare — PML, severe relapse, sepsis on immunosuppressive) → inpatient (IV pulse + PLEX + mAb infusion). 8 PMID evidence anchor: OPERA (28002679) + HERMES (18272891) + DEFINE (22992073) + CLARITY (20089960) + ASCLEPIOS (32757523) + ULTIMATE (36001711) + McDonald 2017 (29275977) + ONTT (1734247). Schema-blocked: EDSS / MSSS / MSFC / NEDA-3 / NEDA-4 / ARR / JCV-Ab index slot — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: JCV-Ab q6 mo on natalizumab (PML risk); HBV/VZV/TB pre-DMT; CYP2C9 for siponimod; teriflunomide cholestyramine washout pre-pregnancy; cladribine 6 mo washout; cardiac monitoring first-dose fingolimod; alemtuzumab secondary autoimmunity surveillance. Sibling differentiation routes to neuro.ms-flare.core.v1 (acute pivot, PRODUCTION), neuro.ms-spms.v1 (same-commit peer), neuro.ms-ppms.v1 (same-commit peer), neuro.transverse-myelitis.v1 (cord lesion pivot). Promotion to INTEGRATED requires registered chronic-MS workup (e.g., workup.ms_dmt_chronic) + first JCV/MRI cascade in clinical-tools-registry.

Entry points (7)

  • symptom
    Established RRMS per McDonald 2017 (Thompson Lancet Neurol PMID 29275977) — DIS + DIT confirmed
    rrms_established_diagnosis
  • symptom
    Clinically Isolated Syndrome (CIS) — first demyelinating event + MRI with risk → start DMT per McDonald 2017
    first_demyelinating_event_cis
  • imaging
    New T2 lesion or gad+ enhancing lesion on surveillance MRI — disease activity (AAN 2024)
    new_t2_or_gad_enhancing_lesion
  • symptom
    Confirmed relapse despite ≥6 mo on DMT → escalation candidate (ECTRIMS 2024)
    breakthrough_relapse_on_dmt
  • history
    RRMS patient planning pregnancy — DMT washout discussion (AAN 2024)
    pregnancy_planning_in_rrms
  • demographic
    Pediatric-onset MS — different DMT pharmacokinetics; PARADIGMS fingolimod NEJM 2018 (PMID 30207920 NEEDS_SOURCE_REVIEW)
    pediatric_ms_under_18
  • lab_abnormality
    JCV-Ab positivity on natalizumab — PML risk → switch DMT class (AAN 2024)
    jcv_seroconversion_on_natalizumab

Required inputs (17)

  • agerequired
    demographic • used at CONTEXT
    Younger patients have higher relapse rate; pregnancy alters DMT eligibility (AAN 2024)
  • sex_and_pregnancy_statusrequired
    demographic • used at TREATMENT
    Pregnancy excludes most DMTs; planning required for washout (cladribine 6 mo, teriflunomide cholestyramine washout) (AAN 2024)
  • symptom_onset_date_and_initial_phenotyperequired
    history • used at FRAME
    Anchor for relapse counting + DIT per McDonald 2017 (PMID 29275977)
  • annualized_relapse_raterequired
    history • used at RISK_STRATIFICATION
    ARR drives high vs moderate efficacy decision (ECTRIMS 2024) — schema-blocked, captured in required_assessments
  • edss_baseline_score
    history • used at RISK_STRATIFICATION
    EDSS pre-DMT anchors NEDA-3 + progression-independent-of-relapse (PIRA) tracking — schema-blocked
  • mri_brain_with_gad_baselinerequired
    imaging • used at INITIAL_WORKUP
    Active disease = new T2 / gad+ lesion since prior MRI; NEDA-3 target on DMT (AAN 2024)
  • mri_cervical_cord
    imaging • used at INITIAL_WORKUP
    Cervical cord lesions strong disability predictor; baseline + annual (AAN 2024)
  • jcv_antibody_index
    lab • used at TREATMENT
    JCV-Ab index gates natalizumab eligibility; recheck q6 mo on natalizumab (PML risk) (AAN 2024)
  • cbc_lymphocyte_countrequired
    lab • used at MONITORING
    Lymphopenia surveillance on DMF / cladribine / siponimod / fingolimod (AAN 2024)
  • lft_baseline_and_q3_to_6_morequired
    lab • used at MONITORING
    DMT hepatotoxicity surveillance (DMF, teriflunomide, ocrelizumab) (AAN 2024)
  • igg_immunoglobulins
    lab • used at MONITORING
    Hypogammaglobulinemia on anti-CD20 (ocre/ofa/ublitux) — infection risk (AAN 2024)
  • hepatitis_b_screenrequired
    lab • used at BRANCHING_WORKUP
    HBV reactivation risk on anti-CD20 — screen pre-DMT (AAN 2024)
  • vzv_immunityrequired
    lab • used at BRANCHING_WORKUP
    VZV-naive → vaccinate before S1P modulator or anti-CD20 (AAN 2024)
  • tb_screen_quantiferonrequired
    lab • used at BRANCHING_WORKUP
    Latent TB screen before DMT, especially anti-CD20 + S1P (AAN 2024)
  • pregnancy_testrequired
    lab • used at TREATMENT
    Required before DMT initiation in reproductive-age females (AAN 2024)
  • cyp2c9_for_siponimod
    lab • used at TREATMENT
    CYP2C9 *3/*3 contraindicates siponimod (genotype-driven dose) (AAN 2024)
  • cardiac_history_for_s1p_modulatorsrequired
    history • used at TREATMENT
    AV block, bradycardia, recent MI/stroke contraindicate fingolimod/siponimod first-dose (AAN 2024)

12-phase flow (12)

  1. 1FRAME
    Confirm RRMS per McDonald 2017 (DIS + DIT) with active or stable disease; distinguish from SPMS (progression independent of relapses) and PPMS (steady accumulation from onset) (PMID 29275977)
    inputs: symptom_onset_date_and_initial_phenotype
    advance: RRMS subtype confirmed and active/non-active status assigned
  2. 2ENTRY
    Established RRMS / CIS with risk → DMT pathway; breakthrough relapse on DMT → escalation pathway (AAN 2024; ECTRIMS 2024)
    inputs: age
    advance: DMT pathway activated
  3. 3CONTEXT
    Pregnancy planning, comorbidities (cardiac for S1P, hepatic for DMF/teriflunomide), JCV status, vaccination history, last relapse date (AAN 2024)
    inputs: sex_and_pregnancy_status, cardiac_history_for_s1p_modulators
    advance: Full DMT-relevant context captured
  4. 4RED_FLAGS
    Acute relapse → route to neuro.ms-flare.core.v1; suspected PML on natalizumab (JCV+ with new MRI lesion + cognitive/focal deficit) → STAT MRI + neurology; bowel/bladder + cord syndrome → admit
    inputs: jcv_antibody_index
    actions: workup.ms_flare
    advance: Acute pathways routed; chronic DMT pathway preserved
  5. 5INITIAL_WORKUP
    MRI brain + cervical cord with gad (baseline + annual); CBC, CMP, LFT; HBV/HCV/HIV; VZV serology; TB QuantiFERON; pregnancy test (AAN 2024)
    inputs: mri_brain_with_gad_baseline, cbc_lymphocyte_count, lft_baseline_and_q3_to_6_mo, hepatitis_b_screen, vzv_immunity, tb_screen_quantiferon
    actions: panel.cbc, panel.lft, panel.renal
    advance: Baseline labs + MRI + pre-DMT infection screen complete
  6. 6BRANCHING_WORKUP
    JCV-Ab if natalizumab considered; CYP2C9 if siponimod (off-label in RRMS but applies if breakthrough); CSF OCB if McDonald not yet met; AQP4-IgG / MOG-IgG if atypical features pivot to NMOSD/MOGAD (AAN 2024)
    inputs: jcv_antibody_index, cyp2c9_for_siponimod
    advance: DMT eligibility branches resolved
  7. 7DIFFERENTIAL
    Confirm RRMS vs CIS vs SPMS conversion (insidious progression ≥6 mo independent of relapse) vs PPMS vs NMOSD vs MOGAD vs ADEM (AAN 2024)
    advance: Phenotype assigned with confidence
  8. 8RISK_STRATIFICATION
    Disease activity (relapses + new lesions); high vs moderate efficacy stratification per ARR + lesion burden + EDSS trajectory; pregnancy planning timeline (AAN 2024; ECTRIMS 2024)
    inputs: annualized_relapse_rate, edss_baseline_score
    advance: Activity tier + efficacy ladder selected
  9. 9TREATMENT
    Moderate efficacy first-line (IFN-β / glatiramer / teriflunomide / DMF) for low-activity OR high efficacy first-line (ocrelizumab / ofatumumab / natalizumab / cladribine / alemtuzumab) for highly active; escalate on breakthrough; ublituximab newer (AAN 2024; ECTRIMS 2024)
    inputs: pregnancy_test
    advance: DMT selected with shared decision + pre-screen complete
  10. 10DISPOSITION
    Outpatient MS clinic q3-6 mo; infusion suite for IV DMTs (ocrelizumab/natalizumab/ublituximab); admit only for acute relapse / PML / severe ARI (AAN 2024)
    advance: Care setting documented
  11. 11MONITORING
    CBC + LFT q3-6 mo; annual brain MRI (NEDA-3 target); JCV-Ab q6 mo on natalizumab; IgG annually on anti-CD20; lymphocyte nadir on DMF/cladribine/siponimod; ARR + EDSS at each visit (AAN 2024)
    inputs: cbc_lymphocyte_count, lft_baseline_and_q3_to_6_mo, igg_immunoglobulins
    actions: panel.cbc, panel.lft
    advance: Monitoring schedule active
  12. 12FOLLOWUP
    Rehab/PT/OT; symptomatic Rx (spasticity, fatigue, bladder); pregnancy planning + washout when applicable; vaccinations before next DMT cycle; annual MRI; cognitive screen (AAN 2024)
    advance: Follow-up bundle scheduled