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neuro.ms-ppms.v1

Primary Progressive Multiple Sclerosis

neurologychronicadultoutpatientinpatientmixed
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro wave-10 (2026-05-15): authored at SCAFFOLDED — no PPMS-specific workup in clinical-tools-registry.ts. 8 phenotypes: classic_PPMS_men_40s / active_PPMS_lesion_or_relapse / non_active_PPMS / EDSS_4_to_6.5_ocrelizumab_eligible / cervical_cord_dominant / cognitive_dominant / progressive_paraparesis_dominant / NMOSD_mimic_pivot. 5 setting playbooks: home (symptomatic + pressure injury prevention) → outpatient (MS clinic + ocrelizumab + symptomatic + rehab) → ed (reversible precipitant triage) → icu (rare — pump, severe sepsis, dysreflexia, PML) → inpatient (IV abx, wound, infusion). 8 PMID evidence anchor: ORATORIO (28002688) + PROMISE rituximab (19847908) + Lublin (24871874) + McDonald (29275977) + NMOSD Wingerchuk (26092914) + EXPAND (29576505) + CLARITY (20089960) + OPERA (28002679). Schema-blocked: EDSS / MSSS / MSFC / PIRA / T25FW / 9HPT / SDMT / cervical cord lesion count — not in clinical-tools-registry; surfaced in depth bundle. Critical safety: ocrelizumab FDA label limits (age ≤55, EDSS ≤6.5, active disease); HBV/VZV/TB pre-DMT; hypogammaglobulinemia surveillance; infusion-reaction pre-medication; AVOID IFN/natalizumab if AQP4-IgG positive (NMOSD worsens). Sibling differentiation routes to neuro.ms-rrms.v1 (distinct relapsing, same-commit peer), neuro.ms-spms.v1 (secondary progressive, same-commit peer), neuro.ms-flare.core.v1 (rare acute pivot, PRODUCTION), neuro.transverse-myelitis.v1 (cord syndrome pivot). Promotion to INTEGRATED requires registered PPMS workup + ocrelizumab eligibility cascade in clinical-tools-registry.

Entry points (6)

  • symptom
    Progressive paraparesis or cord syndrome from onset ≥1 y without relapse (Lublin 2014 PMID 24871874 NEEDS_SOURCE_REVIEW)
    progressive_paraparesis_or_cord_syndrome_from_onset
  • symptom
    Cervical cord-dominant progressive syndrome — MRI shows cord atrophy + cord lesions, minimal brain
    cervical_cord_dominant_phenotype
  • symptom
    Cognitive-dominant PPMS — frontal/subcortical pattern without relapse
    cognitive_progressive_decline_from_onset
  • symptom
    Middle-age male with progressive neurological decline — typical PPMS demographic (M:F ~1:1, mean onset 40s)
    middle_age_male_progressive_neuro_decline
  • imaging
    MRI brain with few T2 lesions + cervical cord atrophy + occasional gad+ enhancement → PPMS pattern
    mri_pattern_supports_ppms
  • lab_abnormality
    CSF oligoclonal bands positive + progressive pattern without relapse → PPMS workup
    csf_ocb_positive_with_progressive_pattern

Required inputs (20)

  • agerequired
    demographic • used at CONTEXT
    Typical PPMS onset 40s; FDA ocrelizumab label age ≤55 for PPMS
  • sexrequired
    demographic • used at CONTEXT
    M:F ~1:1 in PPMS (vs 3:1 F in RRMS)
  • progression_duration_from_onsetrequired
    history • used at FRAME
    Lublin 2014 — ≥1 y progressive disability from onset without relapse defines PPMS
  • absence_of_prior_relapserequired
    history • used at DIFFERENTIAL
    PPMS by definition has no prior relapse history (rare exceptions: late relapse after years of PPMS)
  • edss_at_diagnosisrequired
    history • used at RISK_STRATIFICATION
    EDSS ≤6.5 required for ocrelizumab ORATORIO eligibility (FDA label); schema-blocked
  • active_vs_non_active_statusrequired
    history • used at DIFFERENTIAL
    Active PPMS = gad+ lesion OR new T2 in past 12 mo → ocrelizumab indicated (ORATORIO PMID 28002688)
  • mri_brain_with_gadrequired
    imaging • used at INITIAL_WORKUP
    Active PPMS = gad+ lesion OR new T2; annual MRI (AAN 2024)
  • mri_cervical_cordrequired
    imaging • used at INITIAL_WORKUP
    Cervical cord lesions + atrophy are PPMS hallmark; baseline + annual
  • csf_oligoclonal_bands
    lab • used at BRANCHING_WORKUP
    CSF OCB positive supports MS over alternative; required for McDonald 2017 (PMID 29275977)
  • aqp4_iggrequired
    lab • used at BRANCHING_WORKUP
    AQP4-IgG positive → NMOSD pivot (different DMT — eculizumab/satralizumab/inebilizumab/rituximab; AVOID IFN/natalizumab) (Wingerchuk 2015 PMID 26092914)
  • mog_igg
    lab • used at BRANCHING_WORKUP
    MOG-IgG positive → MOGAD (Banwell 2023)
  • b12_folate_copper_zincrequired
    lab • used at INITIAL_WORKUP
    Subacute combined degeneration mimic (B12 deficiency); copper deficiency myelopathy; treat reversible
  • rpr_or_treponemalrequired
    lab • used at INITIAL_WORKUP
    Tabes dorsalis / neurosyphilis mimic of progressive paraparesis
  • hiv_and_htlv1required
    lab • used at INITIAL_WORKUP
    HIV myelopathy + HTLV-1-associated myelopathy (TSP) mimic
  • cbc_lymphocyte_countrequired
    lab • used at MONITORING
    Lymphopenia surveillance on ocrelizumab
  • lft_baseline_and_q3_to_6_morequired
    lab • used at MONITORING
    Ocrelizumab LFT monitoring
  • hepatitis_b_screenrequired
    lab • used at BRANCHING_WORKUP
    HBV reactivation on anti-CD20 (AAN 2024)
  • igg_immunoglobulins
    lab • used at MONITORING
    Hypogammaglobulinemia on ocrelizumab — infection risk
  • spasticity_bladder_fatigue_dominantrequired
    history • used at TREATMENT
    Symptomatic phenotype drives baclofen / oxybutynin / amantadine / Nuedexta
  • depression_phq9required
    history • used at CONTEXT
    Depression highly comorbid in progressive MS

12-phase flow (12)

  1. 1FRAME
    Confirm PPMS — ≥1 y progressive disability from onset + no prior relapse; rule out mimics; active vs non-active classification per Lublin 2014 (PMID 24871874)
    inputs: progression_duration_from_onset, absence_of_prior_relapse
    advance: PPMS confirmed; active vs non-active classified
  2. 2ENTRY
    Progressive neurological decline + paraparesis / cord syndrome from onset → PPMS workup
    inputs: age, sex
    advance: PPMS pathway activated
  3. 3CONTEXT
    Symptomatic phenotype, depression, vaccination history, comorbidities; cervical cord-dominant or cognitive-dominant phenotype identified
    inputs: spasticity_bladder_fatigue_dominant, depression_phq9
    advance: Clinical phenotype + DMT-relevant context captured
  4. 4RED_FLAGS
    Acute decline → rule out reversible cause (UTI, pressure injury sepsis, aspiration); rare relapse on PPMS → route to neuro.ms-flare.core.v1; suspected NMOSD/MOGAD (LETM > 3 segments, bilateral optic neuritis) → AQP4/MOG urgent
    inputs: aqp4_igg
    actions: workup.ms_flare
    advance: Acute pathways routed
  5. 5INITIAL_WORKUP
    MRI brain + cervical/thoracic cord with gad (baseline + annual); B12 + folate + copper + RPR + HIV + HTLV-1; CBC + CMP + LFT (AAN 2024)
    inputs: mri_brain_with_gad, mri_cervical_cord, b12_folate_copper_zinc, rpr_or_treponemal, hiv_and_htlv1, cbc_lymphocyte_count, lft_baseline_and_q3_to_6_mo
    actions: panel.cbc, panel.lft, panel.renal
    advance: Baseline labs + MRI + mimics screen complete
  6. 6BRANCHING_WORKUP
    AQP4-IgG (NMOSD mimic — different DMT); MOG-IgG; CSF OCB + IgG index; HBV/VZV/TB pre-ocrelizumab; spinal angiogram if vascular myelopathy suspected
    inputs: aqp4_igg, csf_oligoclonal_bands, hepatitis_b_screen
    advance: NMOSD/MOGAD ruled in or out; pre-DMT screen complete
  7. 7DIFFERENTIAL
    PPMS vs NMOSD vs MOGAD vs HTLV-1 TSP vs B12/copper deficiency vs hereditary spastic paraparesis vs ALS vs cervical spondylotic myelopathy vs vascular myelopathy (AAN 2024)
    inputs: active_vs_non_active_status
    advance: PPMS diagnosis assigned with confidence
  8. 8RISK_STRATIFICATION
    EDSS ≤6.5 + age ≤55 + active disease (gad+ or new T2 in 12 mo) → ocrelizumab ORATORIO-eligible (PMID 28002688); cervical cord atrophy as prognostic
    inputs: edss_at_diagnosis
    advance: Ocrelizumab eligibility + prognosis documented
  9. 9TREATMENT
    Ocrelizumab 600 mg IV q6 mo for active PPMS age ≤55 EDSS ≤6.5 (ORATORIO PMID 28002688); rituximab off-label younger inflammatory; cyclophosphamide for highly active refractory; symptomatic identical to SPMS (baclofen/tizanidine/oxybutynin/amantadine/SSRI/Nuedexta/dalfampridine) (AAN 2024)
    inputs: active_vs_non_active_status, edss_at_diagnosis
    advance: DMT + symptomatic regimen set
  10. 10DISPOSITION
    Outpatient MS clinic q3-6 mo + neurorehab; admit for acute relapse / severe pressure injury / aspiration / suspected PML (rare on ocrelizumab)
    advance: Care setting documented
  11. 11MONITORING
    CBC + LFT q3-6 mo; IgG annually; annual MRI brain + cord; 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, igg_immunoglobulins
    actions: panel.cbc, panel.lft
    advance: Monitoring schedule active
  12. 12FOLLOWUP
    PT/OT/SLP; spasticity clinic + intrathecal baclofen pump; pulmonary FVC surveillance; palliative + advance directives at EDSS ≥7; caregiver support (AAN 2024)
    advance: Multidisciplinary follow-up scheduled