Multiple Sclerosis - Chronic Management¶

VERSION: 1.0 CREATED: January 29, 2026 REVISED: January 29, 2026 STATUS: Approved

DIAGNOSIS: Multiple Sclerosis - Chronic Management

ICD-10: G35 (Multiple sclerosis)

CPT CODES: 85025 (CBC with differential), 80053 (CMP), 80076 (LFTs (AST, ALT, bilirubin)), 84443 (TSH), 81003 (Urinalysis), 82306 (Vitamin D (25-OH)), 80074 (Hepatitis B/C serology), 87389 (HIV), 87798 (JC virus antibody (anti-JCV)), 84703 (Pregnancy test), 70553 (MRI brain with and without contrast), 72156 (MRI cervical spine with and without contrast), 72157 (MRI thoracic spine (if indicated)), 92134 (OCT (optical coherence tomography)), 95930 (Evoked potentials (VEP, SSEP)), 96365 (Methylprednisolone IV), 36514 (Plasma exchange (PLEX))

SYNONYMS: Multiple sclerosis, MS, relapsing-remitting MS, RRMS, secondary progressive MS, SPMS, primary progressive MS, PPMS, demyelinating disease, chronic MS management, MS disease-modifying therapy, disseminated sclerosis, CNS demyelination

SCOPE: Long-term management of multiple sclerosis in adults including disease-modifying therapy (DMT) selection and monitoring, relapse management, symptom management, and pregnancy considerations. Excludes initial diagnosis workup (see MS New Diagnosis template) and acute relapse management as primary focus.

DEFINITIONS: - Relapsing-Remitting MS (RRMS): Most common form (~85%); discrete attacks with full or partial recovery - Secondary Progressive MS (SPMS): Progressive accumulation of disability after initial RRMS course - Primary Progressive MS (PPMS): Progressive accumulation from onset without discrete relapses (~15%) - Relapse (Exacerbation): New or worsening neurologic symptoms lasting >24 hours without fever/infection - NEDA (No Evidence of Disease Activity): No relapses, no disability progression, no new/enlarging MRI lesions - Highly Active MS: Frequent relapses (≥2/year), rapid disability progression, highly active MRI

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

1. LABORATORY WORKUP¶

1A. Baseline Labs (Before Starting DMT)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	-	ROUTINE	ROUTINE	-	Baseline; many DMTs affect counts	Normal
CMP (CPT 80053)	-	ROUTINE	ROUTINE	-	Hepatic/renal function	Normal
LFTs (AST, ALT, bilirubin) (CPT 80076)	-	ROUTINE	ROUTINE	-	Baseline for hepatotoxic DMTs	Normal
TSH (CPT 84443)	-	ROUTINE	ROUTINE	-	Alemtuzumab causes thyroid disease	Normal
Urinalysis (CPT 81003)	-	ROUTINE	ROUTINE	-	UTI causes pseudorelapse	Negative
Vitamin D (25-OH) (CPT 82306)	-	ROUTINE	ROUTINE	-	Deficiency common; may affect MS	>30 ng/mL (target 40-60)
Hepatitis B/C serology (CPT 80074)	-	ROUTINE	ROUTINE	-	Reactivation risk with some DMTs	Document status
HIV (CPT 87389)	-	ROUTINE	ROUTINE	-	Before immunosuppressive therapy	Negative
VZV IgG	-	ROUTINE	ROUTINE	-	Vaccinate if seronegative before DMTs	Document; vaccinate if negative
JC virus antibody (anti-JCV) (CPT 87798)	-	ROUTINE	ROUTINE	-	PML risk stratification for natalizumab	Document index
Pregnancy test (CPT 84703)	-	ROUTINE	ROUTINE	-	Most DMTs contraindicated in pregnancy	Negative before starting DMT

1B. Monitoring Labs (On DMT)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC (CPT 85025)	-	ROUTINE	ROUTINE	-	Lymphopenia (many DMTs), cytopenias	Per DMT thresholds
LFTs (CPT 80076)	-	ROUTINE	ROUTINE	-	Hepatotoxicity monitoring	Normal
Lymphocyte count	-	ROUTINE	ROUTINE	-	Critical for many DMTs	Per DMT; usually >200-500
JCV antibody (if on natalizumab) (CPT 87798)	-	ROUTINE	ROUTINE	-	PML risk; repeat q6 months	Monitor index
TSH (if on alemtuzumab) (CPT 84443)	-	ROUTINE	ROUTINE	-	Autoimmune thyroid disease	Normal; monthly × 48 months
Creatinine, urinalysis (alemtuzumab) (CPT 81003)	-	ROUTINE	ROUTINE	-	Autoimmune nephropathy	Normal; monthly × 48 months
Platelet count (alemtuzumab)	-	ROUTINE	ROUTINE	-	ITP risk	Normal; monthly × 48 months

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Monitoring MRI¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI brain with and without contrast (CPT 70553)	-	ROUTINE	ROUTINE	-	Baseline, 6 months, then annually	No new/enlarging lesions	Pacemaker, metal; gadolinium in renal disease
MRI cervical spine with and without contrast (CPT 72156)	-	ROUTINE	ROUTINE	-	Baseline, then PRN or q2-3 years	No new lesions	Same
MRI thoracic spine (if indicated) (CPT 72157)	-	-	EXT	-	If thoracic symptoms	No new lesions	Same

2B. Additional Studies¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
OCT (optical coherence tomography) (CPT 92134)	-	-	ROUTINE	-	Baseline, annually	Stable RNFL thickness	None
Evoked potentials (VEP, SSEP) (CPT 95930)	-	-	EXT	-	If clinical uncertainty	Baseline; monitor progression	None
Urodynamic studies	-	-	ROUTINE	-	If bladder symptoms	Characterize dysfunction	None

3. TREATMENT¶

3A. Disease-Modifying Therapies - Platform/Injectable (Moderate Efficacy)¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Glatiramer acetate (Copaxone)	SC	-	20 mg :: SC :: daily :: 20 mg SC daily or 40 mg SC 3×/week	-	Hypersensitivity	Injection site reactions; lipoatrophy	-	-	ROUTINE	-
Interferon beta-1a (Avonex)	IM	-	30 mcg :: IM :: - :: 30 mcg IM weekly	-	Depression, hepatic disease	CBC, LFTs q6 months; flu-like symptoms	-	-	ROUTINE	-
Interferon beta-1a (Rebif)	SC	-	44 mcg :: SC :: - :: 22 or 44 mcg SC 3×/week (titrate)	-	Same	Same	-	-	ROUTINE	-
Interferon beta-1b (Betaseron, Extavia)	SC	-	250 mcg :: SC :: - :: 250 mcg SC every other day	-	Same	Same	-	-	ROUTINE	-
Peginterferon beta-1a (Plegridy)	SC	-	125 mcg :: SC :: - :: 125 mcg SC q2 weeks	-	Same	Same	-	-	ROUTINE	-

3B. Disease-Modifying Therapies - Oral (Moderate-High Efficacy)¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dimethyl fumarate (Tecfidera)	PO	-	120 mg :: PO :: BID :: 120 mg BID × 7 days, then 240 mg BID	-	Lymphopenia (<500), PML risk	CBC q6 months; LFTs; GI symptoms, flushing	-	-	ROUTINE	-
Diroximel fumarate (Vumerity)	PO	-	231 mg :: PO :: BID :: 231 mg BID × 7 days, then 462 mg BID	-	Same	Same; less GI effects	-	-	ROUTINE	-
Monomethyl fumarate (Bafiertam)	PO	-	95 mg :: PO :: BID :: 95 mg BID × 7 days, then 190 mg BID	-	Same	Same	-	-	ROUTINE	-
Teriflunomide (Aubagio)	PO	-	14 mg :: PO :: daily :: 14 mg daily	-	Pregnancy (teratogenic), hepatic disease	LFTs monthly × 6mo; CBC; BP; pregnancy test; accelerated elimination available	-	-	ROUTINE	-
Fingolimod (Gilenya)	PO	-	0.5 mg :: PO :: daily :: 0.5 mg daily; first dose observation 6h	-	Recent MI, unstable angina, heart block, bradycardia	First-dose cardiac monitoring (6h); ophtho exam (macular edema); LFTs; varicella status; lymphocyte count	-	-	ROUTINE	-
Siponimod (Mayzent)	PO	-	2 mg :: PO :: daily :: Titration pack, then 2 mg daily (1 mg if CYP2C9 2/3); approved for active SPMS	-	Same as fingolimod; CYP2C9 testing required	Same as fingolimod; CYP2C9 genotype	-	-	ROUTINE	-
Ozanimod (Zeposia)	PO	-	0.23 mg :: PO :: daily :: Titration: 0.23 mg × 4d, 0.46 mg × 3d, then 0.92 mg daily	-	Same as fingolimod	Same; less first-dose effect	-	-	ROUTINE	-
Ponesimod (Ponvory)	PO	-	20 mg :: PO :: daily :: Titration over 14 days to 20 mg daily	-	Same as fingolimod	Same	-	-	ROUTINE	-
Cladribine (Mavenclad)	-	-	3.5 mg/kg :: - :: - :: 3.5 mg/kg total over 2 years (Year 1: 1.75 mg/kg in 2 cycles; Year 2: same); highly active RRMS	-	Pregnancy, HIV, active infection, malignancy	CBC q2 months Year 1, then q6 months; lymphocyte >500-800 to start	-	-	ROUTINE	-

3C. Disease-Modifying Therapies - Infusion (High Efficacy)¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Natalizumab (Tysabri)	IV	-	300 mg :: IV :: - :: 300 mg IV q4 weeks	-	PML risk (JCV+, prior immunosuppression, duration >2y)	JCV antibody q6 months; MRI q6-12 months; infusion reactions	-	-	ROUTINE	-
Ocrelizumab (Ocrevus)	IV	-	300 mg :: IV :: - :: 300 mg IV × 2 doses (2 weeks apart), then 600 mg IV q6 months	-	Active Hep B, active infection	Pre-infusion CBC, LFTs; HBV screening; infection monitoring; malignancy screening	-	-	ROUTINE	-
Ofatumumab (Kesimpta)	SC	-	20 mg :: SC :: monthly :: 20 mg SC weeks 0, 1, 2, then 20 mg SC monthly	-	Same as ocrelizumab	Same; self-administered SC	-	-	ROUTINE	-
Ublituximab (Briumvi)	IV	-	150 mg :: IV :: - :: 150 mg IV day 1, 450 mg IV day 15, then 450 mg IV q6 months	-	Same as ocrelizumab	Same	-	-	ROUTINE	-
Alemtuzumab (Lemtrada)	IV	-	12 mg :: IV :: daily :: Year 1: 12 mg IV daily × 5 days; Year 2: 12 mg IV daily × 3 days; highly active MS, REMS	-	Active infection, HIV, immunocompromised	CBC, LFTs, creatinine, urinalysis, TSH monthly × 48 months after last dose; REMS program	-	-	ROUTINE	-

3D. Treatment for Progressive MS¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Ocrelizumab (PPMS)	PO	-	300 mg :: PO :: - :: 300 mg × 2, then 600 mg q6 months	-	Per above	Per above; only approved for PPMS	-	-	ROUTINE	-
Siponimod (active SPMS)	-	-	N/A :: - :: per protocol :: Per above	-	Per above	Per above	-	-	ROUTINE	-

3E. Acute Relapse Treatment¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Methylprednisolone IV (CPT 96365)	IV	-	1000 mg :: IV :: daily :: 1000 mg IV daily × 3-5 days	Active infection (relative), uncontrolled DM	Glucose, BP, sleep, psychiatric	STAT	STAT	ROUTINE	-
Prednisone oral (alternative)	IV	-	1250 mg :: IV :: daily :: 1250 mg PO daily × 3-5 days (bioequivalent to IV)	Same	Same	-	ROUTINE	ROUTINE	-
Plasma exchange (PLEX) (CPT 36514)	-	-	N/A :: - :: once :: 5-7 exchanges over 2 weeks; severe relapse not responding to steroids	Hemodynamic instability	Electrolytes, coagulation	-	STAT	-	-
ACTH gel (Acthar)	IM	-	80-120 units :: IM :: daily :: 80-120 units IM daily × 2-3 weeks; alternative to steroids	Same as steroids	Same	-	-	ROUTINE	-

3F. Symptom Management¶

Symptom	Treatment	Dosing	Monitoring
Fatigue	Amantadine	100 mg :: - :: BID :: 100 mg BID	Livedo reticularis
	Modafinil	100-200 mg :: - :: daily :: 100-200 mg AM	BP, sleep
	Armodafinil	150-250 mg :: - :: daily :: 150-250 mg AM	Same
Spasticity	Baclofen	5 mg :: - :: TID :: 5 mg TID, titrate to 20 mg TID	Sedation, weakness
	Tizanidine	2-4 mg :: - :: TID :: 2-4 mg TID	LFTs, sedation, hypotension
	OnabotulinumtoxinA	N/A :: - :: per protocol :: Injection for focal spasticity	Weakness
	Intrathecal baclofen	N/A :: - :: per protocol :: Pump for severe spasticity	Pump complications
Walking	Dalfampridine (Ampyra)	10 mg :: - :: BID :: 10 mg BID	Seizures (discontinue if occurs)
Bladder (OAB)	Oxybutynin	5 mg :: - :: TID :: 5 mg BID-TID	Dry mouth, cognitive effects
	Solifenacin	5-10 mg :: - :: daily :: 5-10 mg daily	Same (less cognitive)
	Mirabegron	25-50 mg :: - :: daily :: 25-50 mg daily	HTN
	OnabotulinumtoxinA (bladder)	100-200 units :: - :: per protocol :: 100-200 units injection	Retention
	Intermittent catheterization	N/A :: - :: PRN :: As needed	UTI
Bladder (retention)	Clean intermittent cath	N/A :: - :: per protocol :: Schedule-based	UTI prevention
Neuropathic pain	Gabapentin	300-1200 mg :: - :: TID :: 300-1200 mg TID	Sedation
	Pregabalin	75-300 mg :: - :: BID :: 75-300 mg BID	Same
	Duloxetine	30-60 mg :: - :: daily :: 30-60 mg daily	Nausea
	Carbamazepine (trigeminal)	200-400 mg :: - :: BID :: 200-400 mg BID	Rash, CBC, LFTs
Depression	SSRIs (sertraline, escitalopram)	N/A :: - :: per protocol :: Standard dosing	Per SSRI
Cognitive dysfunction	Cognitive rehabilitation	N/A :: - :: daily :: PT/OT/neuropsych referral	Progress
Tremor	Propranolol	40-160 mg/day :: - :: daily :: 40-160 mg/day	HR, BP
	Clonazepam	0.5-2 mg :: - :: QHS :: 0.5-2 mg QHS	Sedation
Sexual dysfunction	Sildenafil (male)	25-100 mg :: - :: PRN :: 25-100 mg PRN	BP with nitrates
	Refer to specialist	N/A :: - :: per protocol :: Female; multifactorial	Per evaluation

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU	Indication
MS specialist/Neurologist	-	ROUTINE	ROUTINE	-	All patients; DMT selection and monitoring
Neuro-ophthalmology	-	ROUTINE	ROUTINE	-	Optic neuritis, visual symptoms
Physical therapy	-	ROUTINE	ROUTINE	-	Gait, balance, strengthening, spasticity
Occupational therapy	-	ROUTINE	ROUTINE	-	ADLs, fatigue management, adaptive equipment
Speech therapy	-	ROUTINE	ROUTINE	-	Dysphagia, dysarthria, cognitive-communication
Neuropsychology	-	-	ROUTINE	-	Cognitive assessment, rehabilitation
Urology	-	-	ROUTINE	-	Bladder management, urodynamics
Psychiatry	-	ROUTINE	ROUTINE	-	Depression, anxiety, pseudobulbar affect
Maternal-fetal medicine	-	-	ROUTINE	-	Pregnancy planning, high-risk pregnancy
Social work	-	ROUTINE	ROUTINE	-	Disability services, resources

4B. Patient/Family Instructions¶

Recommendation	ED	HOSP	OPD
MS is a chronic condition requiring lifelong management	-	ROUTINE	ROUTINE
Take DMT as prescribed; do not stop without consulting neurologist	-	ROUTINE	ROUTINE
Report new symptoms promptly (may be relapse)	-	ROUTINE	ROUTINE
Avoid overheating (Uhthoff phenomenon); swimming and cooling vests help	-	ROUTINE	ROUTINE
Vaccination: Get flu and COVID vaccines; avoid live vaccines on most DMTs	-	ROUTINE	ROUTINE
Infections can trigger pseudorelapses; treat promptly	-	ROUTINE	ROUTINE
Pregnancy planning: Many DMTs contraindicated; discuss before conception	-	ROUTINE	ROUTINE
National MS Society (nationalmssociety.org) for resources	-	-	ROUTINE

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Regular exercise (aerobic + strength) improves fatigue, mood, function	-	ROUTINE	ROUTINE
Maintain vitamin D levels (40-60 ng/mL); supplement if low	-	ROUTINE	ROUTINE
No smoking (worsens progression)	-	ROUTINE	ROUTINE
Healthy diet (Mediterranean-style)	-	-	ROUTINE
Adequate sleep	-	ROUTINE	ROUTINE
Stress management	-	-	ROUTINE
Avoid excessive heat exposure	-	ROUTINE	ROUTINE

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Neuromyelitis optica spectrum disorder	AQP4-IgG+, longitudinally extensive myelitis, bilateral optic neuritis	AQP4-IgG, MOG-IgG; MRI pattern
MOG antibody disease	MOG-IgG+, optic neuritis, myelitis, ADEM-like	MOG-IgG
CNS vasculitis	Progressive, multifocal; systemic symptoms	Angiography, biopsy
Neurosarcoidosis	Leptomeningeal enhancement, systemic sarcoid	ACE level, chest imaging, biopsy
Lyme disease	Endemic area, systemic symptoms	Lyme serology
B12 deficiency myelopathy	Subacute combined degeneration, macrocytic anemia	B12 level, MMA
Migraine with MRI lesions	Headache predominant; non-specific white matter lesions	Clinical; lesion pattern different

6. MONITORING PARAMETERS¶

Parameter	ED	HOSP	OPD	ICU	Frequency	Target/Threshold	Action if Abnormal
EDSS score	-	-	ROUTINE	-	q6-12 months	Stable or improving	Assess treatment efficacy
MRI brain	-	-	ROUTINE	-	Baseline, 6mo, then annually	No new/enlarging lesions	Treatment escalation
Relapse count	-	ROUTINE	ROUTINE	-	Ongoing	≤1 per year (ideally 0)	Treatment escalation
CBC (most DMTs)	-	ROUTINE	ROUTINE	-	q3-6 months	Normal; lymphocyte count per DMT	Hold DMT if low
LFTs (hepatotoxic DMTs)	-	ROUTINE	ROUTINE	-	q3-6 months	Normal	Hold DMT if elevated
JCV antibody (natalizumab)	-	-	ROUTINE	-	q6 months	Monitor index; PML risk stratification	Switch if high-risk
Vitamin D	-	-	ROUTINE	-	Annually	40-60 ng/mL	Supplement
Urinalysis	-	ROUTINE	ROUTINE	-	If relapse suspected	Negative (rule out UTI)	Treat UTI

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Outpatient management	Stable MS, on appropriate DMT, routine monitoring
Admit to hospital	Acute relapse requiring IV steroids, severe relapse, functional decline
MS specialist follow-up	q3-6 months while adjusting DMT; q6-12 months once stable
Urgent follow-up	New relapse, DMT side effects, significant progression

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
High-efficacy DMTs reduce relapses/progression	Class I, Level A	Multiple RCTs
Ocrelizumab effective for PPMS	Class I, Level A	ORATORIO trial
Early high-efficacy treatment improves long-term outcomes	Class II, Level B	Observational data
IV steroids for acute relapse	Class I, Level A	Multiple RCTs
Vitamin D supplementation may reduce relapse	Class II, Level B	Observational data; RCTs ongoing
Exercise improves fatigue and quality of life	Class I, Level A	Multiple RCTs
Natalizumab PML risk stratification	Class I	JCV antibody testing; risk algorithms
Siponimod for active SPMS	Class I, Level A	EXPAND trial

NOTES¶

MS is a heterogeneous disease requiring individualized treatment
"Treat early, treat effectively" philosophy - high-efficacy therapy increasingly used first-line
NEDA (No Evidence of Disease Activity) is aspirational goal: no relapses, no progression, no MRI activity
DMT escalation indicated for breakthrough disease (relapses, new MRI lesions, progression)
PML risk with natalizumab: JCV+, prior immunosuppression, and duration >2 years are major risk factors
S1P receptor modulators (fingolimod, siponimod, ozanimod, ponesimod) require first-dose cardiac monitoring (less for ozanimod)
Anti-CD20 therapies (ocrelizumab, ofatumumab, ublituximab) very effective but infection risk
Alemtuzumab highly effective but requires 4+ years of monthly monitoring for autoimmune complications
Pregnancy: Most DMTs contraindicated; glatiramer acetate considered safest; natalizumab continued in high-risk cases
Many symptoms (fatigue, bladder, spasticity, pain) significantly impact quality of life and are treatable

CHANGE LOG¶

v1.0 (January 29, 2026) - Initial template creation - Comprehensive DMT list with monitoring requirements - Symptom management section - Pregnancy considerations noted - PML risk stratification for natalizumab - Progressive MS treatment (ocrelizumab, siponimod)