Clinical Commander

All dossiers
neuro.ms-spms.v1

Secondary Progressive Multiple Sclerosis

neurologychronicadultoutpatientinpatientmixed
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro wave-10 (2026-05-15): authored at SCAFFOLDED — no SPMS-specific workup in clinical-tools-registry.ts. 8 phenotypes: active_SPMS / non_active_SPMS / EDSS_progression_PIRA / pseudobulbar_affect / spasticity_dominant / neurogenic_bladder / fatigue_dominant / cognitive_decline. 5 setting playbooks: home (symptomatic Rx + pressure injury prevention) → outpatient (MS clinic + symptomatic + rehab) → ed (reversible precipitant triage) → icu (rare — pump malfunction, severe sepsis, dysreflexia, PML) → inpatient (IV abx, wound, IV pulse, infusion). 8 PMID evidence anchor: EXPAND (29576505) + OPERA (28002679) + ofatumumab (32757523) + ASCEND (29545067) + Lublin (24871874) + CLARITY (20089960) + McDonald (29275977) + Apoly DS (21242498). Schema-blocked: EDSS / MSSS / MSFC / PIRA / T25FW / 9HPT / SDMT — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: CYP2C9 *3/*3 contraindicates siponimod; first-dose 6-h ECG; OCT q3 mo initial (macular edema); HBV/VZV/TB pre-DMT; avoid abrupt baclofen cessation (withdrawal seizure / hyperthermia). Sibling differentiation routes to neuro.ms-rrms.v1 (prior phase, same-commit peer), neuro.ms-ppms.v1 (distinct primary progressive, same-commit peer), neuro.ms-flare.core.v1 (acute pivot, PRODUCTION). Promotion to INTEGRATED requires registered SPMS workup + symptomatic-axis cascade.

Entry points (6)

  • symptom
    RRMS patient with insidious progression ≥6 mo independent of relapses (Lublin 2014 PMID 24871874 NEEDS_SOURCE_REVIEW)
    progressive_disability_independent_of_relapse
  • symptom
    EDSS step progression confirmed at 3 + 6 mo without intervening relapse — PIRA
    edss_step_progression_without_relapse
  • imaging
    Disproportionate cord/brain atrophy on annual MRI — neurodegenerative pattern
    cord_atrophy_or_brain_atrophy
  • history
    Worsening spasticity / neurogenic bladder / cognitive decline without relapse
    spasticity_or_bladder_progression
  • imaging
    Active SPMS — new T2 or gad+ lesion (still relapse-eligible)
    new_t2_lesion_in_known_spms
  • symptom
    Pseudobulbar affect — uncontrolled laughing/crying (NEDA criteria — TRANSIT trial dextromethorphan-quinidine)
    pseudobulbar_affect

Required inputs (19)

  • agerequired
    demographic • used at CONTEXT
    SPMS typically 10-20 y after RRMS diagnosis; usually 40s-50s
  • rrms_diagnosis_date_and_phenotyperequired
    history • used at FRAME
    Confirm prior RRMS to establish SPMS conversion (vs PPMS primary progression)
  • progression_duration_independent_of_relapserequired
    history • used at FRAME
    Lublin 2014 — ≥6 mo progression without relapse defines SPMS conversion
  • edss_trajectory_3_to_5_yrequired
    history • used at RISK_STRATIFICATION
    EDSS upward trajectory marks progression; schema-blocked
  • active_vs_non_active_statusrequired
    history • used at DIFFERENTIAL
    Active SPMS (with relapse or new MRI lesion) qualifies for siponimod; non-active SPMS has limited DMT options
  • mri_brain_with_gadrequired
    imaging • used at INITIAL_WORKUP
    Active SPMS = new T2 / gad+; baseline + annual (AAN 2024)
  • mri_cervical_thoracic_cord
    imaging • used at INITIAL_WORKUP
    Cord atrophy strong disability predictor in progressive MS
  • cbc_lymphocyte_countrequired
    lab • used at MONITORING
    Lymphopenia surveillance on siponimod / cladribine
  • lft_baseline_and_q3_to_6_morequired
    lab • used at MONITORING
    Siponimod hepatotoxicity (1% LFT >3× ULN); ocrelizumab LFT monitoring
  • cyp2c9_genotyperequired
    lab • used at TREATMENT
    Siponimod CYP2C9 *3/*3 contraindicates (EXPAND PMID 29576505)
  • vzv_immunityrequired
    lab • used at BRANCHING_WORKUP
    VZV-naive → vaccinate before S1P modulator (AAN 2024)
  • hepatitis_b_screenrequired
    lab • used at BRANCHING_WORKUP
    HBV reactivation on anti-CD20 (AAN 2024)
  • tb_quantiferonrequired
    lab • used at BRANCHING_WORKUP
    TB screen before immunosuppressive DMT (AAN 2024)
  • cardiac_history_av_block_bradycardiarequired
    history • used at TREATMENT
    Siponimod contraindicates 2nd/3rd degree AV block, recent MI/stroke/HF (EXPAND PMID 29576505)
  • depression_phq9required
    history • used at CONTEXT
    Depression highly comorbid in progressive MS; suicide risk elevated
  • spasticity_severityrequired
    history • used at TREATMENT
    Spasticity dominant phenotype — drives baclofen / tizanidine / BTX / pump decisions
  • bladder_functionrequired
    history • used at TREATMENT
    Neurogenic bladder common — anticholinergic / BTX / catheterization
  • fatigue_severity
    history • used at TREATMENT
    Fatigue dominant phenotype — amantadine / modafinil
  • cognitive_screen_sdmt
    history • used at MONITORING
    SDMT preferred MS cognitive screen; schema-blocked

12-phase flow (12)

  1. 1FRAME
    Confirm SPMS conversion from RRMS — ≥6 mo progression independent of relapse (Lublin 2014); active vs non-active classification
    inputs: rrms_diagnosis_date_and_phenotype, progression_duration_independent_of_relapse
    advance: SPMS confirmed with active/non-active status
  2. 2ENTRY
    RRMS with progression OR established SPMS for chronic management
    inputs: age
    advance: SPMS pathway activated
  3. 3CONTEXT
    Comorbidities (cardiac for siponimod), depression, spasticity severity, bladder function, fatigue, cognitive baseline, vaccination history
    inputs: cardiac_history_av_block_bradycardia, depression_phq9, spasticity_severity, bladder_function
    advance: Symptomatic + DMT-relevant context captured
  4. 4RED_FLAGS
    Acute relapse in active SPMS → route to neuro.ms-flare.core.v1; rapid EDSS jump → admit + neurology; severe spasticity with autonomic dysreflexia → ED; severe pressure injury → admit
    actions: workup.ms_flare
    advance: Acute concerns routed; chronic SPMS pathway preserved
  5. 5INITIAL_WORKUP
    MRI brain + cord with gad annually; CBC + CMP + LFT q3-6 mo; CYP2C9 if siponimod considered; VZV/HBV/TB pre-DMT; PHQ-9 (AAN 2024)
    inputs: mri_brain_with_gad, cbc_lymphocyte_count, lft_baseline_and_q3_to_6_mo, cyp2c9_genotype, vzv_immunity, hepatitis_b_screen, tb_quantiferon
    actions: panel.cbc, panel.lft, panel.renal
    advance: Baseline labs + MRI + pre-DMT screen complete
  6. 6BRANCHING_WORKUP
    CYP2C9 genotype for siponimod; cardiac eval (ECG + echo if cardiac history); urodynamics for bladder; SLP for dysphagia; PT/OT eval for function
    inputs: cyp2c9_genotype
    advance: DMT + symptomatic axes resolved
  7. 7DIFFERENTIAL
    Active SPMS (relapse / new MRI) vs non-active SPMS; RRMS-still vs SPMS-conversion (often retrospective); PIRA tracking; consider PPMS misclassification (rare after established RRMS)
    inputs: active_vs_non_active_status
    advance: Subtype + activity classified
  8. 8RISK_STRATIFICATION
    EDSS step progression at 3 + 6 mo confirms PIRA; cord atrophy + brain atrophy; CYP2C9 stratification for siponimod dose
    inputs: edss_trajectory_3_to_5_y
    advance: PIRA + DMT eligibility documented
  9. 9TREATMENT
    Siponimod 2 mg PO daily (after titration) for active SPMS (EXPAND PMID 29576505); ocrelizumab off-label active SPMS; cladribine for active SPMS; symptomatic (baclofen/tizanidine for spasticity, oxybutynin/BTX for bladder, amantadine/modafinil for fatigue, SSRI for depression, dextromethorphan-quinidine for PBA)
    inputs: cyp2c9_genotype
    advance: DMT + symptomatic regimen set
  10. 10DISPOSITION
    Outpatient MS clinic q3-6 mo + neurorehab; admit for acute relapse / severe pressure injury / aspiration / suspected PML
    advance: Care setting documented
  11. 11MONITORING
    CBC + LFT q3-6 mo; annual MRI; EDSS / SDMT / T25FW / 9HPT (schema-blocked) at each visit; pressure injury surveillance; UA + bladder scan q6 mo; depression + cognitive screen annually (AAN 2024)
    inputs: cbc_lymphocyte_count, lft_baseline_and_q3_to_6_mo
    actions: panel.cbc, panel.lft
    advance: Monitoring schedule active
  12. 12FOLLOWUP
    PT/OT/SLP; spasticity clinic + intrathecal baclofen pump consideration if refractory; pulmonary surveillance (FVC); palliative + advance directives at EDSS ≥7; caregiver support (AAN 2024)
    advance: Multidisciplinary follow-up scheduled