Multiple Sclerosis - Chronic Management¶
VERSION: 1.0 CREATED: January 27, 2026 STATUS: Draft - Pending Review
DIAGNOSIS: Multiple Sclerosis - Chronic Management
ICD-10: G35 (Multiple sclerosis)
SYNONYMS: MS maintenance, chronic MS, established MS, MS long-term care, relapsing-remitting MS maintenance, RRMS chronic, secondary progressive MS, SPMS, progressive MS management
SCOPE: Long-term management of established MS including disease-modifying therapy (DMT) monitoring, symptom management optimization, surveillance imaging, preventive care, and special populations (pregnancy planning). Excludes acute MS relapse (see "MS - Exacerbation") and initial diagnostic workup (see "MS - New Diagnosis"). Primary focus is outpatient management with guidance for ED/hospital presentation of established MS patients.
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
SECTION A: ACTION ITEMS¶
1. LABORATORY WORKUP¶
1A. Essential/Core Labs - Routine Monitoring (All MS Patients)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential | Baseline monitoring; DMT safety; infection assessment | Normal; ALC varies by DMT (see 1B) | STAT | STAT | ROUTINE | STAT |
| CMP | Metabolic panel; renal/hepatic function for DMT dosing | Normal | STAT | STAT | ROUTINE | STAT |
| LFTs (AST, ALT, ALP, bilirubin) | DMT hepatotoxicity monitoring (interferons, teriflunomide, S1P modulators) | AST/ALT <3x ULN | URGENT | ROUTINE | ROUTINE | URGENT |
| Urinalysis with culture | UTI common MS comorbidity; can trigger pseudorelapse | Negative | STAT | STAT | ROUTINE | STAT |
| TSH | Thyroid dysfunction (interferons, alemtuzumab) | Normal (0.4-4.0 mIU/L) | - | ROUTINE | ROUTINE | - |
| Vitamin D, 25-hydroxy | Deficiency associated with disease activity | >40 ng/mL (target >50) | - | ROUTINE | ROUTINE | - |
1B. DMT-Specific Monitoring Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| INTERFERONS (Avonex, Rebif, Betaseron, Plegridy) | ||||||
| CBC with differential | Leukopenia, thrombocytopenia monitoring | WBC >3000, ANC >1500, Plt >100K | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| TSH | Thyroid dysfunction | Normal | - | ROUTINE | ROUTINE | - |
| GLATIRAMER ACETATE (Copaxone, Glatopa) | ||||||
| No routine labs required | Minimal systemic toxicity | N/A | - | - | - | - |
| DIMETHYL/DIROXIMEL FUMARATE (Tecfidera, Vumerity) | ||||||
| CBC with differential | Lymphopenia (PML risk if ALC <500 for >6 months) | ALC >500/uL; discontinue if ALC <500 x6mo | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| TERIFLUNOMIDE (Aubagio) | ||||||
| CBC with differential | Leukopenia | WBC >3000, ANC >1500 | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity (black box warning) | ALT <3x ULN; discontinue if >3x with symptoms | - | ROUTINE | ROUTINE | - |
| Blood pressure | Hypertension | <140/90 mmHg | - | ROUTINE | ROUTINE | - |
| Pregnancy test | Teratogenic (Category X) | Negative | STAT | STAT | ROUTINE | - |
| FINGOLIMOD (Gilenya) | ||||||
| CBC with differential | Lymphopenia expected (therapeutic effect) | ALC 200-600/uL typical; concern if <200 | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| VZV IgG | Pre-treatment; vaccinate if negative | Positive (immune) | - | ROUTINE | ROUTINE | - |
| SIPONIMOD (Mayzent) | ||||||
| CBC with differential | Lymphopenia | ALC 200-600/uL typical | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| CYP2C9 genotype | Required before initiation; determines dosing | 1/3 or 2/3: 1 mg dose; 3/3: contraindicated | - | - | ROUTINE | - |
| OZANIMOD (Zeposia) / PONESIMOD (Ponvory) | ||||||
| CBC with differential | Lymphopenia | ALC 200-600/uL typical | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| NATALIZUMAB (Tysabri) | ||||||
| JCV antibody with index | PML risk stratification | Negative preferred; if positive, index <0.9 lower risk | URGENT | URGENT | ROUTINE | URGENT |
| CBC with differential | Infusion reactions; general monitoring | Normal | URGENT | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
| OCRELIZUMAB (Ocrevus) / OFATUMUMAB (Kesimpta) / UBLITUXIMAB (Briumvi) | ||||||
| Hepatitis B surface antigen, core antibody | Reactivation risk | Negative; if positive, HBV DNA and GI/ID consult | - | ROUTINE | ROUTINE | - |
| Quantitative immunoglobulins (IgG, IgA, IgM) | Hypogammaglobulinemia risk | IgG >400 mg/dL | - | ROUTINE | ROUTINE | - |
| CD19/CD20 B-cell count | Therapeutic monitoring | B-cell depletion expected | - | ROUTINE | ROUTINE | - |
| ALEMTUZUMAB (Lemtrada) | ||||||
| CBC with platelet count | ITP, neutropenia (monthly x 48 months after last dose) | Platelets >100K; report petechiae/bruising | STAT | STAT | ROUTINE | STAT |
| Serum creatinine, urinalysis | Anti-GBM nephropathy (monthly x 48 months) | Creatinine stable; UA negative for RBCs/protein | STAT | STAT | ROUTINE | STAT |
| TSH | Autoimmune thyroid disease (quarterly x 48 months) | Normal | - | ROUTINE | ROUTINE | - |
| CLADRIBINE (Mavenclad) | ||||||
| CBC with differential | Lymphopenia (target); timing critical | ALC >800 before year 2; monitoring at months 2 and 6 | - | ROUTINE | ROUTINE | - |
| LFTs | Hepatotoxicity | AST/ALT <3x ULN | - | ROUTINE | ROUTINE | - |
1C. Rare/Specialized Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| JCV PCR (CSF) | Suspected PML (focal neuro symptoms on natalizumab/DMF/fingolimod) | Negative (if positive, confirms PML) | STAT | STAT | - | STAT |
| Serum natalizumab antibodies | Suspected infusion reactions or loss of efficacy | Negative | - | - | EXT | - |
| Anti-drug antibodies (interferon) | Suspected neutralizing antibodies with breakthrough disease | Negative | - | - | EXT | - |
| Serum neurofilament light chain (NfL) | Research/emerging; monitor subclinical disease activity | Low/stable (no established threshold) | - | - | EXT | - |
| Pregnancy test (urine or serum) | Before DMT initiation or if pregnancy suspected | Negative before teratogenic DMTs | STAT | STAT | ROUTINE | - |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line - Surveillance Imaging¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with and without contrast (MS protocol) | Annual surveillance; 3-6 months after DMT change | No new/enlarging T2 lesions; no new enhancing lesions (NEDA-3) | GFR <30; gadolinium allergy; pacemaker | URGENT | URGENT | ROUTINE | URGENT |
| MRI C-spine with and without contrast | Annual or with new symptoms; baseline if not done | No new cord lesions | GFR <30; gadolinium allergy; pacemaker | URGENT | URGENT | ROUTINE | URGENT |
| MRI T-spine with and without contrast | Baseline; repeat if new lower extremity symptoms | No new cord lesions | GFR <30; gadolinium allergy; pacemaker | URGENT | ROUTINE | ROUTINE | URGENT |
2B. Extended - DMT-Specific and Symptom-Directed¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain for PML surveillance (natalizumab, DMF, fingolimod) | q3-6 months if high JCV risk; q12 months if low risk | No new periventricular or subcortical lesions without enhancement | Standard MRI contraindications | URGENT | URGENT | ROUTINE | URGENT |
| OCT (optical coherence tomography) | Annual; baseline; after optic neuritis | Stable RNFL thickness (>5 micron/year loss is pathological) | None | - | - | ROUTINE | - |
| Visual evoked potentials | Baseline; suspected subclinical optic nerve involvement | Stable P100 latency | None | - | - | ROUTINE | - |
| ECG | S1P modulators (fingolimod, siponimod) first dose; baseline and annually | Normal sinus rhythm; PR <200 ms; QTc <500 ms | None | URGENT | ROUTINE | ROUTINE | - |
| Ophthalmology exam (macular OCT) | S1P modulators at 3-4 months; then annually | No macular edema | None | - | - | ROUTINE | - |
| Pulmonary function tests | If respiratory symptoms; alemtuzumab monitoring | FVC >80% predicted | None | - | ROUTINE | ROUTINE | - |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| PET-CT | Suspected malignancy (lymphoma risk with immunosuppression) | No FDG-avid lesions | Pregnancy; uncontrolled diabetes | - | EXT | EXT | - |
| Urodynamic studies | Refractory bladder symptoms | Defines neurogenic bladder type (hyperreflexic vs hyporeflexic) | Active UTI | - | - | EXT | - |
| Video swallow study | Dysphagia or recurrent aspiration | Safe swallow; define texture modifications | None | - | ROUTINE | ROUTINE | - |
| Sleep study (polysomnography) | Severe fatigue; suspected sleep apnea | AHI <5/hour | None | - | - | ROUTINE | - |
| DEXA scan | Long-term steroid exposure; mobility impairment; menopause | T-score >-2.5 | None | - | - | ROUTINE | - |
3. TREATMENT¶
3A. Acute/Emergent (MS Patient Presenting to ED/Hospital)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Continue home DMT | Various | Established MS patient on DMT | Home dose :: Home route :: per home schedule :: Verify home DMT and continue unless contraindicated; consult neurology for infusion therapies | Varies by DMT | Per DMT | STAT | STAT | - | STAT |
| Methylprednisolone IV | IV | Acute MS relapse | 1000 mg :: IV :: daily x 3-5 days :: 1000 mg IV daily for 3-5 days; infuse over 1 hour | Active infection; uncontrolled diabetes; psychosis | Glucose q6h; BP; mood | STAT | STAT | - | STAT |
| Omeprazole | PO | GI prophylaxis during steroids | 20 mg daily; 40 mg daily :: PO :: daily :: 20-40 mg PO daily during steroids | PPI allergy | None | STAT | STAT | - | STAT |
| Insulin sliding scale | SC | Steroid-induced hyperglycemia | Per protocol :: SC :: PRN :: Per protocol if glucose >180 mg/dL | Hypoglycemia risk | Glucose q6h | STAT | STAT | - | STAT |
3B. Symptomatic Treatments - Fatigue¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Amantadine | PO | MS-related fatigue (first-line) | 100 mg qAM; 100 mg BID :: PO :: :: Start 100 mg every morning; may add 100 mg early afternoon (before 2 PM to avoid insomnia); max 200 mg/day | Renal impairment (adjust dose CrCl <50); seizure history; uncontrolled glaucoma | Livedo reticularis; ankle edema; hallucinations; insomnia | - | ROUTINE | ROUTINE | - |
| Modafinil | PO | MS-related fatigue (second-line); Schedule IV | 100 mg qAM; 200 mg qAM :: PO :: :: Start 100 mg every morning; may increase to 200 mg; max 200 mg daily; take early AM | Cardiac arrhythmia; left ventricular hypertrophy; mitral valve prolapse | BP; HR; may reduce hormonal contraception efficacy | - | - | ROUTINE | - |
| Armodafinil | PO | MS-related fatigue; longer half-life; Schedule IV | 150 mg qAM :: PO :: :: 150 mg every morning; longer duration than modafinil | Same as modafinil | Same as modafinil | - | - | ROUTINE | - |
| Methylphenidate | PO | Refractory fatigue; Schedule II | 5 mg BID; 10 mg BID; 20 mg BID :: PO :: :: Start 5 mg morning and noon; titrate by 5-10 mg/week; max 60 mg/day; avoid afternoon dosing | Marked anxiety; glaucoma; motor tics; MAOIs; severe hypertension | BP; HR; appetite; mood; growth (rare in adults) | - | - | ROUTINE | - |
3B. Symptomatic Treatments - Spasticity¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Baclofen | PO | Spasticity (first-line) | 5 mg TID; 10 mg TID; 20 mg TID; 25 mg TID :: PO :: :: Start 5 mg TID; increase by 5 mg/dose every 3 days; max 80 mg/day divided TID-QID | Renal impairment (reduce dose); avoid abrupt withdrawal | Sedation; weakness; AVOID ABRUPT DISCONTINUATION (withdrawal seizures, hallucinations) | - | ROUTINE | ROUTINE | ROUTINE |
| Tizanidine | PO | Spasticity (alternative to baclofen; less weakness) | 2 mg qHS; 4 mg TID; 8 mg TID :: PO :: :: Start 2 mg qHS or TID; increase by 2-4 mg every 3-4 days; max 36 mg/day divided TID | Hepatic impairment; concurrent ciprofloxacin or fluvoxamine (CYP1A2 inhibitors) | LFTs at baseline, 1, 3, 6 months; hypotension; sedation | - | ROUTINE | ROUTINE | ROUTINE |
| Cyclobenzaprine | PO | Spasticity with muscle spasm component | 5 mg TID; 10 mg TID :: PO :: :: 5-10 mg TID; max 30 mg/day; short-term use preferred | Cardiac arrhythmia; heart block; CHF; MAOIs; hyperthyroidism | Anticholinergic effects; sedation; cardiac | - | ROUTINE | ROUTINE | - |
| Dantrolene | PO | Spasticity refractory to baclofen/tizanidine | 25 mg daily; 25 mg TID; 50 mg TID; 100 mg TID :: PO :: :: Start 25 mg daily; increase by 25 mg every 4-7 days; max 100 mg QID | Active liver disease; concurrent hepatotoxic drugs | LFTs monthly x 6 months, then periodically; hepatotoxicity (black box) | - | ROUTINE | ROUTINE | - |
| OnabotulinumtoxinA | IM | Focal spasticity (upper or lower extremity) | 100-400 units total :: IM :: q12 weeks :: Dose varies by muscle group; 100-400 units total; repeat every 12 weeks | Infection at injection site; myasthenia gravis; ALS | Systemic weakness (rare); local weakness | - | - | ROUTINE | - |
| Intrathecal baclofen pump | IT | Severe refractory spasticity affecting quality of life | Continuous infusion :: IT :: :: Trial 50-100 mcg bolus; maintenance typically 100-400 mcg/day; pump refill q1-3 months | Active infection; pump site not suitable | Pump alarm; reservoir level; overdose symptoms (sedation); withdrawal symptoms | - | ROUTINE | ROUTINE | ROUTINE |
3B. Symptomatic Treatments - Neuropathic Pain¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Gabapentin | PO | Neuropathic pain (first-line); dysesthesias; Lhermitte sign | 300 mg qHS; 300 mg TID; 600 mg TID; 900 mg TID :: PO :: :: Start 300 mg qHS; increase by 300 mg every 1-3 days; target 900-1800 mg TID; max 3600 mg/day | Renal impairment (adjust dose per CrCl) | Sedation; dizziness; peripheral edema; ataxia | - | ROUTINE | ROUTINE | ROUTINE |
| Pregabalin | PO | Neuropathic pain (first-line alternative); Schedule V | 75 mg BID; 150 mg BID; 225 mg BID; 300 mg BID :: PO :: :: Start 75 mg BID; increase to 150 mg BID after 1 week; max 300 mg BID | Renal impairment (adjust per CrCl) | Sedation; weight gain; peripheral edema | - | ROUTINE | ROUTINE | - |
| Duloxetine | PO | Neuropathic pain with comorbid depression | 30 mg daily; 60 mg daily; 90 mg daily :: PO :: :: Start 30 mg daily x 1 week; increase to 60 mg daily; max 120 mg/day | Hepatic impairment; MAOIs; uncontrolled narrow-angle glaucoma | Nausea (transient); BP; discontinuation syndrome (taper) | - | ROUTINE | ROUTINE | - |
| Amitriptyline | PO | Neuropathic pain; nocturnal pain; insomnia | 10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: :: Start 10-25 mg qHS; increase by 10-25 mg weekly; max 150 mg qHS | Cardiac conduction abnormality; recent MI; urinary retention; narrow-angle glaucoma | Anticholinergic effects; ECG if dose >100 mg/day; weight gain | - | ROUTINE | ROUTINE | - |
| Nortriptyline | PO | Neuropathic pain; less sedating than amitriptyline | 10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: :: Start 10-25 mg qHS; increase by 10-25 mg weekly; max 150 mg qHS | Cardiac conduction abnormality; recent MI; urinary retention; narrow-angle glaucoma | Anticholinergic effects; ECG if dose >100 mg/day | - | ROUTINE | ROUTINE | - |
| Carbamazepine | PO | Trigeminal neuralgia in MS | 100 mg BID; 200 mg BID; 400 mg BID :: PO :: :: Start 100 mg BID; increase by 200 mg/day every 3-7 days; max 1200 mg/day | AV block; bone marrow suppression; MAOIs | CBC; LFTs; sodium; HLA-B*1502 in Asian ancestry (SJS risk) | - | ROUTINE | ROUTINE | - |
| Oxcarbazepine | PO | Trigeminal neuralgia (better tolerated than carbamazepine) | 300 mg BID; 600 mg BID; 900 mg BID :: PO :: :: Start 300 mg BID; increase by 300 mg every 3 days; max 1200 mg BID | Hypersensitivity to carbamazepine | Sodium (hyponatremia more common); HLA-B*1502 screening | - | ROUTINE | ROUTINE | - |
3B. Symptomatic Treatments - Bladder Dysfunction¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Oxybutynin IR | PO | Detrusor hyperreflexia; urinary urgency/frequency | 5 mg BID; 5 mg TID :: PO :: :: Start 5 mg BID-TID; max 5 mg QID | Urinary retention; uncontrolled narrow-angle glaucoma; GI obstruction | Dry mouth; constipation; COGNITIVE IMPAIRMENT (avoid in elderly) | - | ROUTINE | ROUTINE | - |
| Oxybutynin ER | PO | Urinary urgency (fewer CNS effects than IR) | 5 mg daily; 10 mg daily; 15 mg daily :: PO :: :: Start 5-10 mg daily; max 30 mg daily | Same as IR | Same but less cognitive impairment | - | - | ROUTINE | - |
| Solifenacin | PO | Urinary urgency (better CNS profile) | 5 mg daily; 10 mg daily :: PO :: :: Start 5 mg daily; may increase to 10 mg daily | Urinary retention; gastric retention; uncontrolled narrow-angle glaucoma | Dry mouth; constipation; preferred if cognitive concerns | - | - | ROUTINE | - |
| Mirabegron | PO | Urinary urgency (beta-3 agonist; no anticholinergic effects) | 25 mg daily; 50 mg daily :: PO :: :: Start 25 mg daily; may increase to 50 mg daily | Uncontrolled hypertension; severe hepatic impairment | BP monitoring; well-tolerated; fewer cognitive effects | - | - | ROUTINE | - |
| Vibegron | PO | Urinary urgency (newer beta-3 agonist) | 75 mg daily :: PO :: :: 75 mg once daily; no titration needed | Severe hepatic impairment | BP; well-tolerated | - | - | ROUTINE | - |
| Tamsulosin | PO | Urinary retention; hesitancy (detrusor-sphincter dyssynergia) | 0.4 mg daily :: PO :: :: 0.4 mg daily 30 minutes after same meal each day | Severe sulfonamide allergy (caution) | Orthostatic hypotension; retrograde ejaculation | - | ROUTINE | ROUTINE | - |
| Intermittent self-catheterization | — | Urinary retention (PVR >100-200 mL) | Per protocol :: — :: 4-6x daily :: Clean technique; frequency based on PVR and symptoms | Unable to perform; urethral stricture | UTI frequency; bladder diary; PVR | - | ROUTINE | ROUTINE | - |
| OnabotulinumtoxinA (bladder) | Cystoscopic | Refractory detrusor hyperreflexia | 100-200 units :: Cystoscopic :: q6-12 months :: 100 units (start); may increase to 200 units; cystoscopic injection | UTI; urinary retention not willing to catheterize | PVR (may require ISC); UTI | - | - | ROUTINE | - |
3B. Symptomatic Treatments - Depression and Anxiety¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Sertraline | PO | Depression in MS (first-line) | 50 mg daily; 100 mg daily; 150 mg daily; 200 mg daily :: PO :: :: Start 50 mg daily; increase by 25-50 mg every 1-2 weeks; max 200 mg daily | Concurrent MAOIs; pimozide | Suicidality monitoring weeks 1-4; serotonin syndrome | - | ROUTINE | ROUTINE | - |
| Escitalopram | PO | Depression; anxiety in MS | 10 mg daily; 20 mg daily :: PO :: :: Start 10 mg daily; may increase to 20 mg after 1 week; max 20 mg daily | Concurrent MAOIs; QT prolongation | QTc if risk factors or dose >10 mg; suicidality monitoring | - | ROUTINE | ROUTINE | - |
| Bupropion SR/XL | PO | Depression; fatigue; no sexual side effects | 150 mg daily; 150 mg BID; 300 mg XL daily :: PO :: :: Start 150 mg SR daily; increase to 150 mg SR BID or 300 mg XL daily; max 400 mg/day | Seizure disorder; eating disorders; abrupt alcohol/benzo withdrawal | Seizure risk; insomnia; agitation | - | ROUTINE | ROUTINE | - |
| Venlafaxine XR | PO | Depression with pain component; anxiety | 75 mg daily; 150 mg daily; 225 mg daily :: PO :: :: Start 37.5-75 mg daily; increase by 75 mg every 4-7 days; max 225 mg daily | Uncontrolled hypertension; MAOIs | BP monitoring; discontinuation syndrome (taper slowly) | - | ROUTINE | ROUTINE | - |
| Duloxetine | PO | Depression with neuropathic pain | 30 mg daily; 60 mg daily :: PO :: :: Start 30 mg daily x 1 week; increase to 60 mg daily; max 120 mg/day | Hepatic impairment; MAOIs; narrow-angle glaucoma | Nausea; BP; discontinuation syndrome | - | ROUTINE | ROUTINE | - |
3B. Symptomatic Treatments - Gait/Mobility¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Dalfampridine | PO | Walking impairment in MS (improves walking speed) | 10 mg q12h :: PO :: :: 10 mg every 12 hours (MUST be exactly 12 hours apart); do NOT exceed 20 mg/day; swallow whole | Seizure history; CrCl <50 mL/min; history of seizure on dalfampridine | Seizure risk (dose-dependent); UTI; dizziness; insomnia | - | - | ROUTINE | - |
3B. Symptomatic Treatments - Cognitive Impairment¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Cognitive rehabilitation therapy | — | MS-related cognitive impairment | Per protocol :: — :: 1-2x weekly :: Referral to neuropsychology or speech therapy for structured cognitive exercises | None | Compliance; functional outcomes | - | - | ROUTINE | - |
| Donepezil | PO | Cognitive impairment (off-label; limited evidence) | 5 mg qHS; 10 mg qHS :: PO :: :: Start 5 mg qHS; may increase to 10 mg after 4-6 weeks | GI bleeding; cardiac conduction disease | Nausea; diarrhea; bradycardia; vivid dreams | - | - | EXT | - |
3B. Symptomatic Treatments - Other¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Dextromethorphan-quinidine (Nuedexta) | PO | Pseudobulbar affect (PBA) | 20/10 mg daily; 20/10 mg q12h :: PO :: :: Start 20/10 mg daily x 7 days; then 20/10 mg every 12 hours | QT prolongation; MAOIs; concurrent quinidine/quinine | ECG at baseline; QTc monitoring; drug interactions (CYP2D6) | - | - | ROUTINE | - |
| Propranolol | PO | Action tremor in MS | 20 mg BID; 40 mg BID; 80 mg BID :: PO :: :: Start 20 mg BID; increase by 20-40 mg every 3-7 days; max 320 mg/day | Asthma/COPD; bradycardia; heart block; decompensated CHF | HR; BP; fatigue; depression | - | ROUTINE | ROUTINE | - |
| Primidone | PO | Tremor refractory to propranolol | 25 mg qHS; 50 mg TID; 125 mg TID :: PO :: :: Start 25 mg qHS; increase by 25 mg weekly; usual 50-250 mg TID | Porphyria; phenobarbital hypersensitivity | Severe sedation initially; ataxia; cognitive effects | - | - | ROUTINE | - |
| Polyethylene glycol 3350 | PO | Constipation (common with immobility, anticholinergics) | 17 g daily; 17 g BID :: PO :: :: 17 g (1 capful) in 8 oz liquid daily; adjust to effect; may take 1-3 days | Bowel obstruction; ileus | Electrolytes if prolonged use | - | ROUTINE | ROUTINE | - |
3C. Second-line/Refractory Acute Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Plasmapheresis (PLEX) | — | Steroid-refractory acute relapse | 5-7 exchanges :: — :: over 10-14 days :: 5-7 exchanges over 10-14 days; 1-1.5 plasma volumes per exchange | Hemodynamic instability; sepsis; central line contraindication | BP; electrolytes; coagulation; fibrinogen; line infection | - | URGENT | - | URGENT |
| IVIG | IV | Steroid-refractory relapse (alternative to PLEX) | 0.4 g/kg/day :: IV :: x 5 days :: 0.4 g/kg/day x 5 days (total 2 g/kg) | IgA deficiency; renal failure; thrombosis history | Renal function; headache; aseptic meningitis; thrombosis | - | URGENT | - | URGENT |
3D. Disease-Modifying Therapies - Monitoring Protocols¶
DMT monitoring is critical for chronic MS management. See Section 1B for specific lab requirements. Below are monitoring schedules by DMT class.
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| INJECTABLE DMTs | ||||||||||
| Interferon beta (any formulation) | IM/SC | RRMS; established patient on therapy | Per product labeling :: IM/SC :: :: Continue established regimen | CBC, LFTs, TSH at baseline | Decompensated liver disease; depression (relative) | CBC, LFTs q3-6 months; TSH annually; depression screening | - | - | ROUTINE | - |
| Glatiramer acetate (any formulation) | SC | RRMS; established patient | 20 mg daily or 40 mg TIW :: SC :: :: Continue established regimen | None required | Hypersensitivity | Injection site reactions; post-injection reaction (self-limited) | - | - | ROUTINE | - |
| ORAL DMTs - MODERATE EFFICACY | ||||||||||
| Dimethyl fumarate (Tecfidera) | PO | RRMS; established patient | 240 mg BID :: PO :: :: Continue 240 mg BID with food | CBC, LFTs | ALC <500 for >6 months (discontinue); PML risk | CBC q6 months; LFTs periodically; MRI surveillance for PML | - | - | ROUTINE | - |
| Diroximel fumarate (Vumerity) | PO | RRMS; less GI side effects than Tecfidera | 462 mg BID :: PO :: :: Continue 462 mg BID with food | CBC, LFTs | ALC <500 for >6 months (discontinue); PML risk | CBC q6 months; LFTs periodically; MRI surveillance for PML | - | - | ROUTINE | - |
| Teriflunomide (Aubagio) | PO | RRMS; established patient | 7 mg or 14 mg daily :: PO :: :: Continue established dose | LFTs monthly x 6 months; TB test; BP; pregnancy test | Pregnancy (Category X); severe hepatic impairment | LFTs monthly x 6 months, then periodically; BP; pregnancy test PRN | - | - | ROUTINE | - |
| ORAL DMTs - S1P MODULATORS (HIGH EFFICACY) | ||||||||||
| Fingolimod (Gilenya) | PO | RRMS; established patient | 0.5 mg daily :: PO :: :: Continue 0.5 mg daily | First-dose observation completed; VZV immune; macular OCT; ECG | Cardiac conduction issues; recent MI/stroke; macular edema | Macular OCT annually; CBC q6-12 months; LFTs annually; MRI for PML surveillance | - | - | ROUTINE | - |
| Siponimod (Mayzent) | PO | SPMS or RRMS; established patient | 1 mg or 2 mg daily (per CYP2C9) :: PO :: :: Continue established dose per genotype | CYP2C9 genotype; first-dose observation; macular OCT | CYP2C9 3/3; cardiac conduction issues; macular edema | Macular OCT annually; CBC q6-12 months; LFTs annually | - | - | ROUTINE | - |
| Ozanimod (Zeposia) | PO | RRMS; established patient | 0.92 mg daily :: PO :: :: Continue 0.92 mg daily | Macular OCT; ECG (no first-dose observation required) | Cardiac conduction issues; recent MI/stroke; MAOIs | Macular OCT at 3-4 months then annually; CBC; LFTs | - | - | ROUTINE | - |
| Ponesimod (Ponvory) | PO | RRMS; established patient | 20 mg daily :: PO :: :: Continue 20 mg daily | Macular OCT; ECG (no first-dose observation required) | Cardiac conduction issues; recent MI/stroke | Macular OCT at 3-4 months then annually; CBC; LFTs | - | - | ROUTINE | - |
| ORAL DMTs - HIGH EFFICACY OTHER | ||||||||||
| Cladribine (Mavenclad) | PO | RRMS/SPMS; induction therapy | 1.75 mg/kg/year x 2 years :: PO :: :: Year 1 and Year 2 only; no treatment years 3-4 | ALC >800 before each year; LFTs; HIV; Hep B/C | Active infection; HIV; malignancy; pregnancy | CBC at months 2 and 6 each treatment year; malignancy screening | - | - | ROUTINE | - |
| INFUSION DMTs - HIGH EFFICACY | ||||||||||
| Natalizumab (Tysabri) | IV | RRMS; established patient | 300 mg q4 weeks or extended q6 weeks :: IV :: :: Standard interval q4 weeks; extended interval dosing (EID) q6 weeks if stable and JCV negative | JCV antibody q6 months; REMS enrollment | JCV+ with index >1.5 and prior immunosuppression (high PML risk) | JCV q6 months; MRI q3-6 months (high risk) or q6-12 months (low risk) for PML surveillance | - | - | ROUTINE | - |
| Ocrelizumab (Ocrevus) | IV | RRMS/PPMS; established patient | 600 mg q6 months :: IV :: :: 600 mg IV every 6 months; premedicate | Hepatitis B screening; TB test; immunoglobulins | Active Hepatitis B; active infection | IgG annually; infection monitoring; infusion reactions | - | - | ROUTINE | - |
| Ofatumumab (Kesimpta) | SC | RRMS; established patient | 20 mg monthly :: SC :: :: 20 mg SC monthly; self-administered at home | Hepatitis B screening; TB test; immunoglobulins | Active Hepatitis B; active infection | IgG annually; infection monitoring | - | - | ROUTINE | - |
| Ublituximab (Briumvi) | IV | RRMS; established patient | 450 mg q6 months :: IV :: :: 450 mg IV every 24 weeks (after initial doses); 1-hour infusion | Hepatitis B screening; TB test; immunoglobulins | Active Hepatitis B; active infection | IgG annually; infection monitoring; infusion reactions | - | - | ROUTINE | - |
| Alemtuzumab (Lemtrada) | IV | RRMS; established patient post-induction | No further dosing unless rebound :: IV :: :: Monitoring continues 48 months after last infusion even without additional dosing | REMS enrollment; extensive baseline labs | Active infection; ongoing autoimmune disease | CBC monthly x 48 months; TSH q3 months x 48 months; creatinine/UA monthly x 48 months | - | - | ROUTINE | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| MS specialist/Neuroimmunology for annual comprehensive review and DMT optimization | - | ROUTINE | ROUTINE | - |
| Neuro-ophthalmology for visual complaints, OCT monitoring, or suspected optic neuritis | - | ROUTINE | ROUTINE | - |
| Physical therapy for gait training, balance exercises, and fall prevention given progressive mobility decline | - | ROUTINE | ROUTINE | ROUTINE |
| Occupational therapy for ADL assessment, energy conservation strategies, and adaptive equipment | - | ROUTINE | ROUTINE | - |
| Speech therapy for dysphagia evaluation given brainstem involvement or swallowing concerns | - | URGENT | ROUTINE | URGENT |
| Neuropsychology for formal cognitive testing if subjective or objective cognitive decline | - | - | ROUTINE | - |
| Cognitive rehabilitation (speech therapy or neuropsychology) for documented cognitive impairment | - | - | ROUTINE | - |
| Urology for refractory bladder symptoms, recurrent UTIs, or urodynamic testing consideration | - | - | ROUTINE | - |
| Psychiatry for depression, anxiety, or adjustment disorders not responding to first-line treatment | - | ROUTINE | ROUTINE | - |
| Pain management for refractory neuropathic pain not responding to multiple first-line agents | - | - | ROUTINE | - |
| Physiatry/Rehabilitation medicine for comprehensive rehabilitation planning and spasticity management | - | ROUTINE | ROUTINE | - |
| Social work for disability planning, insurance navigation, and community resource connection | - | ROUTINE | ROUTINE | - |
| Genetic counseling if considering pregnancy with strong family history or known genetic mutations | - | - | ROUTINE | - |
| High-risk OB for pregnancy planning discussion in women on DMTs | - | - | ROUTINE | - |
| Infusion center for DMT administration and monitoring | - | ROUTINE | ROUTINE | - |
| Palliative care for advanced MS with significant symptom burden or goals of care discussions | - | ROUTINE | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately if rapid vision loss, new weakness, numbness, or difficulty walking develops (may indicate relapse requiring steroids) | ROUTINE | ROUTINE | ROUTINE |
| Report fever or signs of infection promptly as immunomodulatory DMTs increase infection risk | ROUTINE | ROUTINE | ROUTINE |
| Continue DMT as prescribed unless instructed otherwise by neurology - do not stop without discussing | - | ROUTINE | ROUTINE |
| Avoid live vaccines while on immunosuppressive DMTs (fingolimod, siponimod, cladribine, anti-CD20 therapies, alemtuzumab) | - | ROUTINE | ROUTINE |
| Heat may temporarily worsen symptoms (Uhthoff phenomenon) - use cooling strategies; this is NOT a new relapse | ROUTINE | ROUTINE | ROUTINE |
| Maintain symptom diary noting new symptoms, fatigue levels, and bladder/bowel patterns | - | ROUTINE | ROUTINE |
| Do not stop baclofen or tizanidine abruptly - taper under medical supervision to avoid withdrawal | - | ROUTINE | ROUTINE |
| Report any skin changes, new moles, or suspicious lesions given increased malignancy risk with some DMTs | - | - | ROUTINE |
| Women of childbearing potential: discuss pregnancy plans with MS specialist before conception given DMT-specific washout requirements | - | ROUTINE | ROUTINE |
| Report unusual fatigue, shortness of breath, chest pain, or palpitations if on S1P modulators (cardiac effects) | ROUTINE | ROUTINE | ROUTINE |
| If on natalizumab: report any new neurological symptoms, especially if subtle (confusion, personality change, clumsiness) as may indicate PML | URGENT | URGENT | ROUTINE |
| Take dalfampridine exactly 12 hours apart and never exceed 2 doses per day (seizure risk) | - | ROUTINE | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Smoking cessation - smoking accelerates MS progression, increases relapse rate, and worsens disability | ROUTINE | ROUTINE | ROUTINE |
| Vitamin D supplementation 2000-5000 IU daily to maintain serum 25-OH vitamin D >40 ng/mL (target >50 ng/mL) | - | ROUTINE | ROUTINE |
| Regular aerobic exercise 150 minutes per week as tolerated - improves fatigue, mood, mobility, and may slow progression | - | ROUTINE | ROUTINE |
| Aquatic therapy/swimming - allows exercise with built-in cooling and reduced fall risk | - | ROUTINE | ROUTINE |
| Resistance training 2-3 times weekly for strength maintenance and bone health | - | - | ROUTINE |
| Stress management techniques as stress may trigger pseudorelapses and worsen fatigue | - | ROUTINE | ROUTINE |
| Sleep hygiene - ensure 7-8 hours nightly; address sleep disorders contributing to fatigue | - | ROUTINE | ROUTINE |
| Avoid excessive heat exposure (hot tubs, saunas, exercising in heat) - use cooling vests for outdoor activities | - | ROUTINE | ROUTINE |
| Fall prevention: remove loose rugs, ensure adequate lighting, use assistive devices (cane, walker) as needed | - | ROUTINE | ROUTINE |
| Complete recommended vaccinations before starting immunosuppressive DMTs - inactivated vaccines safe on most DMTs | - | ROUTINE | ROUTINE |
| Annual influenza vaccine (inactivated) and COVID-19 vaccines per current guidelines (timing around infusions for anti-CD20) | - | ROUTINE | ROUTINE |
| Limit alcohol intake as it can worsen balance, cognitive symptoms, and interact with medications | - | - | ROUTINE |
| Mediterranean diet pattern may have anti-inflammatory benefits based on observational data | - | - | ROUTINE |
| DEXA scan for bone density monitoring if prolonged steroid exposure, immobility, or menopause | - | - | ROUTINE |
4D. Vaccination Guidance¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| LIVE vaccines (MMR, varicella, zoster live, yellow fever) contraindicated on fingolimod, siponimod, ozanimod, ponesimod, cladribine, anti-CD20 therapies, alemtuzumab | - | ROUTINE | ROUTINE |
| Recombinant zoster vaccine (Shingrix) - 2 doses recommended for patients >50 years; safe on most DMTs | - | - | ROUTINE |
| Ensure VZV immunity (IgG) before starting S1P modulators - vaccinate and wait 4 weeks if non-immune | - | - | ROUTINE |
| Hepatitis B vaccination if non-immune before starting anti-CD20 therapies (ocrelizumab, ofatumumab, ublituximab) | - | - | ROUTINE |
| Pneumococcal vaccination (PCV20 or PCV15 + PPSV23) recommended especially before immunosuppressive DMTs | - | - | ROUTINE |
| COVID-19 vaccination: complete primary series and boosters; for anti-CD20 therapies, time 2-4 weeks before next infusion or 12+ weeks after last infusion | - | ROUTINE | ROUTINE |
| HPV vaccination for eligible patients <45 years, especially before cladribine or alemtuzumab (malignancy screening required) | - | - | ROUTINE |
| Influenza vaccine annually (inactivated) - safe on all DMTs; for anti-CD20, optimize timing but do not delay if timing not ideal | - | ROUTINE | ROUTINE |
4E. Pregnancy Planning¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Discuss pregnancy plans with MS specialist before conception - most DMTs require washout period | - | - | ROUTINE |
| Teriflunomide: Category X - requires accelerated elimination procedure (cholestyramine or activated charcoal) before conception; verify undetectable levels | - | - | ROUTINE |
| Fingolimod: discontinue 2 months before conception; rebound risk after stopping | - | - | ROUTINE |
| Siponimod, ozanimod, ponesimod: discontinue 7-10 days before conception (shorter half-lives than fingolimod) | - | - | ROUTINE |
| Natalizumab: can continue until pregnancy confirmed; some continue through pregnancy in high-activity disease with shared decision-making | - | - | ROUTINE |
| Anti-CD20 therapies: discontinue 6-12 months before conception; B-cell recovery variable | - | - | ROUTINE |
| Cladribine: recommend effective contraception for 6 months after last dose (men and women) | - | - | ROUTINE |
| Alemtuzumab: recommend contraception for 4 months after last infusion | - | - | ROUTINE |
| Glatiramer acetate and interferon-beta: no evidence of harm; may continue during pregnancy if needed (glatiramer preferred) | - | - | ROUTINE |
| High-risk OB referral for all MS pregnancies given increased complication risk and postpartum relapse risk | - | - | ROUTINE |
| Plan for early postpartum DMT restart (relapses increase 3-6 months postpartum) | - | - | ROUTINE |
SECTION B: REFERENCE (Expand as Needed)¶
5. DIFFERENTIAL DIAGNOSIS¶
For established MS patients presenting with new symptoms, consider:
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| MS relapse vs pseudorelapse | True relapse: new neuroinflammation; Pseudorelapse: symptom worsening from infection, heat, stress without new inflammation | MRI with contrast (new enhancing lesions = true relapse); infection workup (UTI, URI) |
| Progressive multifocal leukoencephalopathy (PML) | Subacute cognitive/behavioral change, visual, motor symptoms; on natalizumab, DMF, fingolimod | MRI (subcortical non-enhancing lesions); CSF JCV PCR |
| CNS infection | Fever, meningeal signs, rapid deterioration; immunosuppressed | Lumbar puncture; blood cultures; imaging |
| Comorbid stroke/TIA | Sudden onset; vascular risk factors; non-MS territory | MRI DWI; vascular imaging |
| Medication side effect | Temporal relationship to new medication or dose change | Medication review; trial discontinuation |
| Functional neurological disorder | Inconsistent exam; non-anatomical patterns; psychiatric comorbidity | Clinical assessment; normal MRI |
| B12 deficiency myelopathy | Progressive; dorsal column signs; may coexist with MS | B12, MMA, homocysteine |
| Secondary malignancy | Progressive; atypical pattern; on immunosuppressive DMT | PET-CT; biopsy if indicated |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| CLINICAL | |||||||
| Neurologic examination (EDSS) | Every visit; minimum annually | Stable or improved | If worsening: MRI, DMT optimization discussion | - | ROUTINE | ROUTINE | - |
| Relapse frequency | Continuous; review at each visit | Zero relapses (NEDA goal) | Any relapse triggers MRI and DMT reassessment | - | - | ROUTINE | - |
| Walking speed (T25FW) | Annually | Stable or improved | If worsening: PT referral, dalfampridine consideration | - | - | ROUTINE | - |
| Cognition (SDMT or MoCA) | Annually | Stable (>4 point decline on SDMT significant) | Cognitive rehab referral; medication review | - | - | ROUTINE | - |
| Depression screening (PHQ-9) | Annually; more often if symptoms | Score <10 | Antidepressant; psychiatry referral | - | ROUTINE | ROUTINE | - |
| Fatigue (MFIS or FSS) | Each visit | Stable or improving | Fatigue management optimization | - | - | ROUTINE | - |
| IMAGING | |||||||
| MRI brain with contrast | Annually; 3-6 months after DMT switch | No new/enlarging T2 lesions; no enhancing lesions | New activity: DMT escalation discussion | URGENT | URGENT | ROUTINE | URGENT |
| MRI spine | Annually or with new symptoms | No new cord lesions | New lesions: DMT reassessment | URGENT | ROUTINE | ROUTINE | - |
| Macular OCT | Baseline; 3-4 months on S1P modulators; then annually | No macular edema; stable RNFL | Macular edema: discontinue S1P modulator; ophthalmology | - | - | ROUTINE | - |
| LABORATORY | |||||||
| CBC with differential | q6 months on lymphocyte-depleting DMTs; annually others | Per DMT-specific thresholds (see Section 1B) | Adjust or discontinue DMT per protocol | - | ROUTINE | ROUTINE | - |
| LFTs | Per DMT schedule; more frequent early on | AST/ALT <3x ULN | Hold DMT if >3x; resume if resolves | - | ROUTINE | ROUTINE | - |
| JCV antibody with index | q6 months on natalizumab | Negative preferred; monitor index if positive | Rising index: risk counseling; consider DMT switch | URGENT | URGENT | ROUTINE | - |
| Immunoglobulins (IgG) | Annually on anti-CD20 therapies | IgG >400 mg/dL | If low: infection precautions; consider IVIG replacement | - | ROUTINE | ROUTINE | - |
| Vitamin D, 25-OH | Annually | >40 ng/mL (target >50) | Increase supplementation if low | - | - | ROUTINE | - |
| ALEMTUZUMAB-SPECIFIC (48 months after last infusion) | |||||||
| CBC with platelets | Monthly x 48 months | Platelets >100K | If low: hold; hematology consult for ITP | STAT | STAT | ROUTINE | STAT |
| TSH | q3 months x 48 months | Normal | If abnormal: endocrine consult | - | ROUTINE | ROUTINE | - |
| Serum creatinine + UA | Monthly x 48 months | Stable creatinine; no RBCs/protein in UA | If abnormal: nephrology consult for anti-GBM disease | STAT | STAT | ROUTINE | STAT |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Discharge home | Mild symptom worsening attributable to pseudorelapse (infection treated, heat exposure resolved); stable neurologic exam; able to care for self or adequate caregiver support; reliable follow-up |
| Admit to floor | Moderate-severe acute relapse requiring IV steroids; functional decline preventing safe discharge; diagnostic workup for suspected PML or CNS infection; severe medication side effect requiring monitoring |
| Admit to ICU | Severe myelitis with respiratory compromise (NIF declining toward -20 cm H2O); brainstem involvement with airway risk; severe infusion reaction; suspected PML with rapid deterioration |
| Transfer to higher level | PLEX needed but unavailable; MS specialist not available for complex decision-making (PML management, severe breakthrough); MRI unavailable for urgent imaging |
| Outpatient follow-up | Every 3-6 months for stable patients; q1-3 months during DMT transition or active disease; annually minimum for established stable patients |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Annual MRI surveillance for subclinical disease activity | Class II, Level B | Wattjes MP et al. Lancet Neurol 2021 (MAGNIMS-CMSC-NAIMS) |
| NEDA (No Evidence of Disease Activity) as treatment target | Class II, Level B | Giovannoni G et al. Neurology 2017 |
| JCV antibody monitoring for PML risk stratification | Class I, Level A | Bloomgren G et al. NEJM 2012 |
| Extended interval dosing of natalizumab reduces PML risk | Class II, Level B | Zhovtis Ryerson L et al. Ann Neurol 2019 |
| Anti-CD20 therapies effective in RRMS and PPMS | Class I, Level A | Hauser SL et al. NEJM 2017 (OPERA) |
| Vitamin D supplementation reduces relapse rate | Class I, Level B | Hupperts R et al. Neurology 2019 (SOLAR) |
| Dalfampridine improves walking speed | Class I, Level A | Goodman AD et al. Lancet 2009 |
| Exercise improves fatigue and quality of life | Class I, Level B | Heine M et al. Cochrane 2015 |
| Smoking cessation slows disability progression | Class II, Level B | Hedstrom AK et al. Brain 2013 |
| Cognitive rehabilitation improves cognitive outcomes | Class II, Level B | Chiaravalloti ND et al. Neurology 2013 |
| S1P modulators: macular edema and cardiac monitoring required | Class I, Level A | FDA label; Cohen JA et al. NEJM 2010 (fingolimod) |
| Alemtuzumab: secondary autoimmunity monitoring for 48 months | Class I, Level A | CAMMS223 investigators NEJM 2008 |
| Pregnancy planning with DMT washout periods | Class III, Level B | Bove R et al. Nat Rev Neurol 2014 |
| Vaccinations before immunosuppressive DMTs | Expert consensus | Farez MF et al. Neurology 2019 (AAN guidelines) |
CHANGE LOG¶
v1.0 (January 27, 2026) - Initial template creation for MS chronic management - Comprehensive DMT monitoring protocols by drug class - Symptom management for fatigue, spasticity, pain, bladder, depression, cognition, gait - Vaccination guidance and live vaccine contraindications - Pregnancy planning section with DMT-specific washout requirements - PML surveillance protocols for natalizumab and other high-risk DMTs - Structured dosing format for order sentence generation - Full setting coverage (ED, HOSP, OPD, ICU) for monitoring and treatment
APPENDIX A: DMT Monitoring Schedule Summary¶
| DMT | Labs | Lab Frequency | Imaging | Other |
|---|---|---|---|---|
| Interferons | CBC, LFTs, TSH | q3-6 months; TSH annually | Annual MRI | Depression screening |
| Glatiramer | None routine | N/A | Annual MRI | Injection site monitoring |
| Dimethyl/Diroximel fumarate | CBC (ALC), LFTs | q6 months | Annual MRI + PML surveillance | Discontinue if ALC <500 x 6 months |
| Teriflunomide | LFTs, CBC, BP | Monthly x 6 mo, then periodic | Annual MRI | Pregnancy test PRN; teratogenic |
| Fingolimod | CBC, LFTs | q6-12 months | Annual MRI + PML surveillance | Macular OCT; first-dose cardiac monitoring |
| Siponimod | CBC, LFTs | q6-12 months | Annual MRI | CYP2C9 genotype; macular OCT |
| Ozanimod/Ponesimod | CBC, LFTs | q6-12 months | Annual MRI | Macular OCT at 3-4 mo then annually |
| Cladribine | CBC | Months 2 and 6 each treatment year | Annual MRI | ALC >800 before year 2; malignancy screen |
| Natalizumab | JCV Ab, CBC, LFTs | JCV q6 months | MRI q3-6 mo (high risk) or q6-12 mo | REMS; extended dosing option |
| Anti-CD20s | Hep B, IgG, CBC | IgG annually; others periodic | Annual MRI | Infection monitoring |
| Alemtuzumab | CBC monthly, TSH q3mo, Cr/UA monthly | x 48 months after last dose | Annual MRI | REMS; autoimmunity monitoring |
APPENDIX B: PML Risk Stratification (Natalizumab)¶
| Risk Factor | PML Risk | Monitoring Recommendation |
|---|---|---|
| JCV antibody NEGATIVE | Very low (<0.1 per 1000) | JCV q6 months; annual MRI |
| JCV antibody POSITIVE, index <0.9, no prior IS | Low (~0.5 per 1000) | JCV q6 months; MRI q6-12 months |
| JCV antibody POSITIVE, index 0.9-1.5, no prior IS | Moderate (~2 per 1000) | JCV q6 months; MRI q6 months; consider EID |
| JCV antibody POSITIVE, index >1.5, no prior IS | High (~5-6 per 1000) | JCV q6 months; MRI q3-6 months; consider DMT switch |
| JCV antibody POSITIVE + prior immunosuppression | Very high (~10+ per 1000) | Strong consideration for DMT switch |
| >24 months treatment duration | Increases risk | Factor into overall risk assessment |
EID = Extended Interval Dosing (q6 weeks instead of q4 weeks) - associated with ~90% reduction in PML risk
PML Warning Signs: - Subtle cognitive changes, confusion - Personality or behavioral changes - Visual disturbances (homonymous hemianopia) - Hemiparesis, ataxia - New speech difficulties
If PML suspected: STOP natalizumab immediately; STAT MRI brain; CSF JCV PCR; neurology consultation
APPENDIX C: DMT Washout Periods for Pregnancy¶
| DMT | Washout Required | Notes |
|---|---|---|
| Glatiramer acetate | None | May continue if needed; preferred in pregnancy |
| Interferon-beta | None to minimal | Limited data; can continue if high activity |
| Dimethyl/Diroximel fumarate | Minimal (short half-life) | Stop when pregnancy confirmed |
| Teriflunomide | Accelerated elimination required | Cholestyramine 8g TID x 11 days; verify level <0.02 mg/L |
| Fingolimod | 2 months | Rebound risk; monitor closely |
| Siponimod | 10 days | Shorter half-life than fingolimod |
| Ozanimod | 7 days | Includes active metabolites |
| Ponesimod | 7 days | Short half-life |
| Cladribine | 6 months | Applies to both partners |
| Natalizumab | Until pregnancy confirmed | Can continue through pregnancy in high-activity MS (shared decision) |
| Ocrelizumab | 6-12 months | B-cell recovery variable; check CD19 count |
| Ofatumumab | 6 months | B-cell recovery variable |
| Ublituximab | 6 months | B-cell recovery variable |
| Alemtuzumab | 4 months | After last infusion |