01Approach to the Critical Patient/attcp49

Immediate priorities

›Airway and breathing threats

›Respiratory compromise from high cervical cord or severe brainstem lesion

›Bilateral phrenic nerve involvement

›Bulbar dysfunction with inability to protect airway

›Oxygenation failure

›SpO2 < 90% on room air

›If unable to protect airway, proceed to definitive airway

›Ventilation failure

›Rising PaCO2 with respiratory fatigue

›Early intubation planning for progressive cervical myelopathy

›Rapidly deteriorating neurologic status

›Fulminant demyelinating disease (Marburg variant)

›Progressive loss of consciousness

›Brainstem herniation signs

›If declining mental status, urgent MRI brain and neurology activation

›Rule out tumefactive MS, ADEM, CNS lymphoma

›Steroid initiation only after infection ruled out

›Pseudo-relapse versus true relapse — first branch point

›Pseudo-relapse features

›Fever or confirmed infection (UTI, URI, skin)

›Symptoms reproduce previously documented deficits

›Rapid resolution with antipyresis or antibiotic treatment

›True relapse features

›New or distinctly worse symptoms lasting more than 24 hours

›No infectious or metabolic trigger identified

›Development over hours to days with maximal deficit within 4 weeks

02History/hx75

Onset and symptom characterization

›Relapse definition

›New or worsening neurological symptoms lasting at least 24 hours

›Developing acutely or subacutely

›In absence of fever, infection, or metabolic derangement

›Symptom progression tempo

›Maximal deficit typically within 4 weeks of onset

›Faster than 4 hours raises concern for stroke or hemorrhage

Core symptoms

›Visual symptoms

›Blurred vision with eye pain on movement (optic neuritis)

›Typically monocular; bilateral suggests NMOSD

›Color desaturation and afferent pupillary defect

›Diplopia from internuclear ophthalmoplegia or cranial nerve palsy

›INO highly characteristic of MS when bilateral

›Motor and sensory symptoms

›Asymmetric limb weakness

›Corticospinal pattern with hyperreflexia

›Spastic gait disturbance

›Numbness or tingling

›Dermatomal or CNS-pattern sensory loss

›Lhermitte sign: electric sensation down spine with neck flexion

›Cerebellar and brainstem symptoms

›Gait ataxia and dysmetria

›Intention tremor

›Scanning dysarthria

›Vertigo, nausea, hiccups

›Area postrema involvement raises concern for NMOSD

›Intractable nausea/vomiting not typical of MS relapse

›Autonomic and bladder symptoms

›Urinary urgency, frequency, incontinence, or retention

›Most common persistent symptom cluster in MS

›Urinary retention may require catheterization

›Constipation or bowel incontinence

›Erectile dysfunction in males

Triggers and precipitants

›Infection as relapse trigger

›Upper respiratory tract infection (RR 2.07 for relapse within 4 weeks)

›Urinary tract infection most common pseudo-relapse trigger

›Skin and wound infections

›Postpartum period (RR 1.43 versus pre-pregnancy)

›Risk highest in first 3 months after delivery

›Heat exposure (Uhthoff phenomenon)

›Symptom worsening in 60–80% of MS patients with heat exposure

›Environmental heat, exercise, fever, hot bath

›Reversible with cooling; does not represent true relapse

›Stressful life events (RR 2.2 within 4 weeks of major stress)

›Psychological stressors in prospective cohort data

›Preceding adverse events associated with clinical relapses

›DMT nonadherence or discontinuation

›Abrupt fingolimod cessation: rebound severe relapses

›Abrupt natalizumab cessation: rebound disease activity

›Always review current DMT and adherence history

Alarm features in history

›Features suggesting NMOSD rather than MS

›Bilateral or severe unilateral optic neuritis with poor recovery

›Complete transverse myelopathy with bilateral involvement

›Intractable nausea/vomiting/hiccups (area postrema syndrome)

›Longitudinally extensive cord lesion spanning 3 or more segments

›Features suggesting PML

›Patient on natalizumab, ocrelizumab, or other immunosuppressants

›Subacute progressive rather than relapsing-remitting course

›Cognitive, motor, or visual deficits not matching typical MS pattern

›Features suggesting alternative diagnosis

›Fever, headache, meningismus, or encephalopathy

›These are atypical for MS relapse

›Suggest CNS infection, ADEM, or non-demyelinating disease

Baseline and prior disease history

›MS subtype and disease course

›Relapsing-remitting MS (RRMS): most common

›Secondary progressive MS (SPMS)

›Primary progressive MS (PPMS): no discrete relapses

›Clinically isolated syndrome (CIS): first demyelinating event

›Prior relapse pattern

›Frequency, severity, and degree of recovery

›Residual deficits from prior relapses

›Baseline EDSS score (critical for measuring change)

›Current and prior DMTs with response and adherence

›Frequency of prior steroid courses

›Prior plasma exchange

03Physical Exam/exam55

Vital signs

›Temperature assessment

›Fever above 38.0 C suggests pseudo-relapse or concurrent infection

›Mandates infectious workup before steroid initiation

›Even low-grade fever can unmask prior deficits (Uhthoff)

›Blood pressure and heart rate

›Hypertension common with high-dose steroid use

›Autonomic dysreflexia in cervical cord lesions

Neurologic examination

›Visual system

›Visual acuity and color vision testing

›Red desaturation in optic neuritis

›Snellen chart and Ishihara plates

›Afferent pupillary defect (Marcus Gunn pupil)

›Present in optic neuritis

›Relative afferent pupillary defect with swinging flashlight test

›Fundoscopic examination

›Optic disc pallor in prior optic neuritis

›Papilledema would suggest alternative diagnosis

›Cranial nerve examination

›Internuclear ophthalmoplegia

›Impaired adduction ipsilateral eye with nystagmus contralateral

›Bilateral INO highly suggestive of MS

›Facial sensory loss

›Trigeminal distribution

›Facial weakness and dysarthria from brainstem lesion

›Motor system

›Upper motor neuron pattern weakness

04Differential Diagnosis/ddx52

Pseudo-relapse

›Pseudo-relapse (most common mimic of true relapse)

›Definition: worsening of prior deficits without new demyelination

›Triggered by infection, fever, heat, metabolic derangement

›Resolves when trigger is treated

›ICD-10: G35 (MS), differentiated by clinical assessment

›Urinary tract infection most frequent trigger

›Resolution within 24–48 hours of antipyresis or antibiotics

Demyelinating mimics

›NMOSD (neuromyelitis optica spectrum disorder)

›AQP4-IgG positive in 70–80% of cases

›Longitudinally extensive transverse myelitis spanning 3 or more segments

›Bilateral or severe unilateral optic neuritis with poor recovery

›Area postrema syndrome: intractable nausea, vomiting, hiccups

›ICD-10: G36.0

›MOGAD (myelin oligodendrocyte glycoprotein antibody disease)

›MOG-IgG positive by cell-based assay

›Optic neuritis often bilateral with disc edema

›ADEM-like presentation in younger patients

›ICD-10: G37.9

›ADEM (acute disseminated encephalomyelitis)

›Post-infectious or post-vaccination encephalopathy

›Typically monophasic with encephalopathy

›More common in children; ICD-10: G04.01

Vascular

›Ischemic stroke or TIA

›Sudden onset within seconds to minutes

›Vascular territory distribution

05Laboratory Tests/lt51

First-line workup

›Rule out pseudo-relapse

›Complete blood count

›Leukocytosis suggests active infection

›Lymphopenia may reflect current DMT effect

›Comprehensive metabolic panel

›Electrolyte derangements as relapse mimics

›Blood glucose pre-steroid baseline (hyperglycemia risk)

›Urinalysis with urine culture

›UTI most common pseudo-relapse trigger

›Pyuria alone insufficient without symptoms

›ESR and CRP

›Elevated in active infection or systemic inflammation

›Usually normal in true MS relapse

Diagnostic uncertainty workup

›CSF analysis (when diagnosis uncertain or atypical presentation)

›Oligoclonal bands

›Present in 80–90% of MS patients

›Absent in serum (intrathecal synthesis)

›IgG index

›Elevated (above 0.7) in MS

›Kappa free light chains as additional marker

›Cell count and protein

›Mild pleocytosis acceptable in MS

›Marked pleocytosis suggests infection or NMOSD

›Glucose (paired serum and CSF)

›Low ratio suggests bacterial meningitis

›Antibody serology

06Diagnostic Tests/dt83

Scoring Systems

›EDSS (Expanded Disability Status Scale)

›Validated 0–10 scale measuring MS-related disability

›EDSS 0: normal neurologic exam

›EDSS 4.0: significant disability, walks 500 m unaided

›EDSS 6.0: requires unilateral assistance for 100 m

›EDSS 7.0: unable to walk more than 5 m with aid; wheelchair dependent

›Record before and after relapse to quantify change

›Functional system scores (FSS)

›Seven systems: pyramidal, cerebellar, brainstem, sensory, bowel/bladder, visual, cerebral

›EDSS derives from worst FSS combination

›MS Functional Composite (MSFC)

›Quantitative outcome measure combining three domains

›Timed 25-foot walk (25FW) for ambulation

›Nine-hole peg test (9HPT) for upper extremity function

›Symbol digit modalities test (SDMT) for cognition

›More sensitive to change than EDSS in clinical trials

›Used in research; less practical at bedside

›McDonald Criteria (2017, updated 2024)

›Dissemination in space and time requirements

›Lesions in at least 2 of 4 characteristic locations: periventricular, juxtacortical/cortical, infratentorial, spinal cord

›New T2 or gadolinium-enhancing lesion on follow-up MRI

›2024 update incorporates central vein sign and paramagnetic rim lesions

›Central vein sign in at least 6 lesions supports MS diagnosis

›Paramagnetic rim lesions highly specific for MS

MRI

›MRI brain without and with gadolinium

›First-line imaging for all patients with suspected or confirmed MS relapse

›Active demyelination found in approximately 88% of confirmed exacerbations on emergency MRI

›New or enlarging T2/FLAIR lesions indicate active disease

›Gadolinium-enhancing lesions

›Indicate active blood-brain barrier breakdown

›Enhancement typically resolves within 4–8 weeks

›Incomplete ring (open ring) enhancement distinguishes MS from abscess or tumor

›Characteristic lesion locations (McDonald criteria)

›Periventricular: ovoid, perpendicular to ventricles (Dawson fingers)

›Juxtacortical and cortical lesions

›Infratentorial: pons, middle cerebellar peduncle, medulla

›Spinal cord lesions (isolated cord activity in only 10% without brain lesions)

›2024 McDonald biomarkers on MRI

›Central vein sign: vein visible at center of lesion

›Paramagnetic rim lesion: iron-laden microglia at lesion edge

›Highly specific for MS; reduces misdiagnosis

›MRI spinal cord (cervical and thoracic) with gadolinium

›Indicated when symptoms suggest cord involvement or brain MRI nondiagnostic

›Short (less than 3 segments), peripheral, asymmetric cord lesions typical of MS

›Long cord lesion (3 or more segments) suggests NMOSD

›MAGNIMS-CMSC-NAIMS 2021 recommendations

›Gadolinium contrast for all new neurologic symptoms

›Short-tau inversion recovery (STIR) sequence for cord lesions

›Sagittal and axial T2 sequences required

›MRI for PML exclusion

›Natalizumab-treated patients with atypical progressive symptoms

›DWI (diffusion-weighted imaging): PML shows restricted diffusion at lesion edge

›PML lesions non-enhancing, confluent, without mass effect

›T2 lesions involving subcortical U-fibers (spares periventricular white matter)

CT

›CT head (non-contrast)

›Not the preferred modality for MS diagnosis

›CT insensitive for demyelinating lesions

›Use when MRI contraindicated or unavailable

›Indications in MS relapse context

›Acute exclusion of hemorrhage or mass lesion

›Rapidly deteriorating mental status before MRI

›Metallic implants or pacemaker precluding MRI

›Limitations

›Misses most white matter lesions

›Normal CT does not exclude MS relapse or serious pathology

›ACR Appropriateness Criteria: MRI without and with contrast is usually appropriate; CT head is rarely appropriate for initial workup

Ultrasound

›Bladder ultrasound

›Post-void residual volume measurement

›Post-void residual above 100 mL indicates significant urinary retention

›Retention may require intermittent or indwelling catheterization

›Guides acute management of neurogenic bladder

›Serial assessments

›Repeat after void if retention suspected

›Correlate with patient symptoms of incomplete emptying

›Optic nerve ultrasound

›Optic nerve sheath diameter measurement

›Not used for MS diagnosis

›Can assess for elevated intracranial pressure if papilledema suspected

›ONSD above 5 mm suggests raised ICP

›General utility

›No established primary diagnostic role for MS relapse

›Ancillary use for bladder retention and ICP screening

›Transcranial doppler not routinely indicated

07Disposition/dispo35

Admission criteria

›Indications for inpatient admission

›Severe neurologic deficits requiring close monitoring

›Inability to ambulate or care for self

›Significant visual loss affecting function

›Bulbar dysfunction or dysphagia

›Need for plasma exchange

›5–7 exchanges over approximately 2 weeks

›Requires inpatient coordination with nephrology

›Respiratory compromise from high cervical cord lesion

›Intensive care level monitoring

›Ventilatory support planning

›Diagnostic uncertainty requiring urgent inpatient workup

›LP, urgent MRI, or brain biopsy consideration

›Concern for PML, CNS lymphoma, or serious alternative diagnosis

Observation indications

›Moderate relapse with IV steroid treatment

›Reassess functional status after 1–3 days of IV methylprednisolone

›Ability to ambulate and perform ADLs

›Response to treatment guides transition to outpatient care

Discharge criteria

›Mild to moderate relapse with preserved function

›Able to ambulate and perform ADLs independently

›Oral steroid regimen feasible as outpatient

›Reliable neurology follow-up arranged within 1–2 weeks

›Safe home environment with adequate support

›Caregiver or support system available

›Return precautions clearly communicated

08Treatment/t79

Acute relapse treatment — steroids

›IV methylprednisolone (first-line)

›1,000 mg/day intravenously for 3–5 days

›Infuse over 60–90 minutes

›Accelerates recovery without changing long-term relapse outcome

›Pre-treatment measures

›Screen for active infection before initiation

›Blood glucose baseline (diabetic patients)

›Avoid in active untreated infection

›Oral methylprednisolone alternative

›1,000 mg/day orally for 3 days

›Noninferior to IV in COPOUSEP randomized controlled trial

›ACEP supports oral as equivalent when IV access difficult

›Oral prednisone alternative

›1,250 mg/day orally for 5 days

›Randomized data support noninferiority

›No routine oral taper required after pulse steroid course

›Adverse effects monitoring

›Hyperglycemia: glucose checks every 4–6 hours

›Insomnia: counsel patient at discharge

›Psychiatric effects: agitation, mood lability, rarely psychosis

›Hypertension: monitor BP every 30 minutes during infusion

›Bradycardia risk with rapid infusion (infuse over at least 60 minutes)

Steroid-refractory relapse

›Plasma exchange (therapeutic plasma exchange, TPE)

›Indication: no meaningful improvement after 2 weeks of steroids

›5–7 exchanges over approximately 2 weeks

›Each exchange processes 1–1.5 plasma volumes

›Efficacy data

›Response rate approximately 77% in RRMS in observational series

›TPE superior to escalated IV methylprednisolone in direct comparison (good recovery 60.9% TPE vs 15.2% escalated IVMP)

›Meta-analysis supports TPE and immunoadsorption in demyelinating disease

›Contraindications and precautions

›Hypofibrinogenemia or active bleeding

›Hemodynamic instability

›Requires central venous access

›IVIG as alternative

›2 g/kg total dose over 2–5 days

›Particularly in pediatric patients or when TPE unavailable

›Limited randomized data in adults; Class IIb recommendation

Disease-modifying therapy review

›Breakthrough relapse on current DMT

›Neurology consultation for escalation planning

›Consider switch to higher-efficacy agent

›Review adherence and injection technique

›DMT rebound syndromes

›Fingolimod cessation: severe rebound relapses within weeks

›Natalizumab cessation: rebound activity at 3–6 months

›Bridging therapy may be required

›DMT adverse effect management

›Fingolimod: first-dose bradycardia and AV block

›6-hour cardiac monitoring post first dose

›Macular edema screening at 3–4 months

›Natalizumab: PML risk stratification

›JCV antibody index and prior immunosuppression

›MRI monitoring every 6 months if JCV index above 1.5

›Ocrelizumab: infusion reactions and immunosuppression

›Premedicate with methylprednisolone, antihistamine, acetaminophen

Supportive care

›Bladder management

›Intermittent catheterization for post-void residual above 100 mL

›Indwelling catheter if retention severe or patient unable to self-catheterize

›Oxybutynin or solifenacin for urinary urgency (avoid in retention)

›Treat UTI promptly (pseudo-relapse trigger)

›Urine culture-directed antibiotics

›Spasticity management

›Baclofen 5–10 mg orally three times daily, titrate to effect

›Maximum 80 mg/day

›Physiotherapy as adjunct

›Tizanidine 2–4 mg orally at bedtime or up to three times daily

›Monitor LFTs

›Neuropathic pain

›Gabapentin 100–300 mg orally three times daily, titrate

›Maximum 3,600 mg/day

›Pregabalin 75 mg twice daily as alternative

›Fatigue

›Amantadine 100 mg orally twice daily

›Modafinil 200 mg orally daily (off-label)

›Heat avoidance and cooling strategies

›Depression and anxiety

›High prevalence comorbidity in MS (up to 50%)

›SSRIs preferred; avoid medications that worsen fatigue

›Psychiatry referral for moderate-severe depression

09Special Populations/sp71

Pregnancy

›Relapse risk during pregnancy

›Relapse rate decreases during pregnancy (RR 0.56 vs pre-pregnancy)

›Most significant reduction in third trimester

›Protective effect attributed to immune tolerance mechanisms

›Postpartum relapse risk (RR 1.43 vs pre-pregnancy)

›Highest risk in first 3 months postpartum

›Planning breastfeeding and DMT restart timing is critical

›Treatment of relapse in pregnancy

›IV methylprednisolone acceptable in second and third trimester

›Short course pulse steroids (3–5 days) preferred

›First trimester: relative avoidance due to cleft palate risk

›Consult neurology and maternal-fetal medicine

›Plasma exchange

›Safe in pregnancy for severe steroid-refractory relapse

›Coordinate with obstetrics

›IVIG 2 g/kg over 2–5 days

›Safe in pregnancy; used for severe relapse when steroids contraindicated

›DMT management during pregnancy

›Most DMTs discontinued before or at conception

›Interferon-beta and glatiramer acetate relatively safer (Category B)

›Natalizumab: case-by-case late pregnancy continuation

›Fingolimod, teriflunomide, cladribine: contraindicated in pregnancy

›Breastfeeding considerations

›Exclusive breastfeeding may prolong postpartum protection

›Most DMTs incompatible with breastfeeding

›Discuss timing of DMT restart with neurology

Geriatric

›Age-related diagnostic challenges

›Late-onset MS (symptom onset after age 50) less common

›Broader differential including stroke, cervical spondylosis, B12 deficiency

›Hua et al. 2024 JAMA Neurology: expanded differential for late-onset presentation

›Comorbidities confounding examination

›Degenerative joint disease, peripheral neuropathy, vestibular dysfunction

›Vascular disease may coexist and confound MRI interpretation

›Treatment modifications in elderly

›High-dose corticosteroids: heightened risk of adverse effects

›Glucose dysregulation in diabetes or prediabetes

›Osteoporosis risk with frequent steroid use (calcium and vitamin D supplementation)

›Psychiatric effects and delirium risk

›Fall risk with neurologic deficits

›Inpatient physiotherapy assessment

›Home safety evaluation before discharge

›DMT selection in older patients

›Lower-efficacy agents may be preferred for tolerability

›Increased infection risk with highly immunosuppressive DMTs

›Renal function monitoring for drug clearance adjustments

Pediatrics

›Pediatric MS characteristics

›MS onset before age 18 accounts for 3–5% of all MS cases

›Pediatric MS is predominantly relapsing-remitting

›Higher relapse rate than adult MS; better recovery between relapses

›Differential diagnosis broader in children

›ADEM more common and may precede MS

›MOGAD and NMOSD must be excluded

›Mitochondrial disease and metabolic disorders in differential

›Diagnostic considerations in pediatrics

›McDonald criteria require modification for children under 11

›ADEM-like first attack does not preclude subsequent MS diagnosis

›Fadda et al. 2021 Lancet Neurology: pediatric MS and antibody-associated demyelination

›CSF analysis more often required

›Oligoclonal bands less frequent than in adults (50–70%)

›MOG-IgG and AQP4-IgG testing mandatory in pediatric demyelination

›Treatment in pediatrics

›IV methylprednisolone 20–30 mg/kg/day (maximum 1,000 mg) for 3–5 days

›Oral equivalent for mild-moderate relapse

›Monitor glucose closely in younger children

›IVIG 2 g/kg over 2–5 days

›Preferred alternative for steroid-refractory relapse in children

›Better tolerated than plasma exchange in young children

›DMT selection in pediatric MS

›Interferon-beta approved for pediatric use

›Natalizumab and fingolimod have pediatric data

›Consult pediatric neurology for all cases

10Background/b74

Epidemiology

›Global MS prevalence and incidence

›Approximately 2.8 million people affected globally (2020 estimate)

›Prevalence 35.9 per 100,000 worldwide

›Highest prevalence in North America and Northern Europe

›Incidence approximately 2–3 per 100,000 person-years in high-prevalence regions

›Female-to-male ratio approximately 3:1 for RRMS

›Age of onset typically 20–50 years; peak in third decade

›Relapse epidemiology

›Untreated RRMS relapse rate approximately 1–2 per year

›DMT reduces relapse rate by 30–70% depending on agent

›Relapse triggers: infection (RR 2.07), postpartum (RR 1.43), stress (RR 2.2)

›85% of MS patients begin with relapsing-remitting course

›50% of untreated RRMS patients convert to SPMS within 10–15 years

›Progressive MS: steady neurologic decline without discrete relapses

›Disability outcomes

›EDSS 6.0 (requires walking aid) reached by 50% of patients at 15 years without DMT

›Modern high-efficacy DMTs significantly reduce disability progression

›Beiki et al. 2019 JAMA Neurology: declining disability milestone rates with contemporary treatment

Pathophysiology

›Immune-mediated demyelination

›Autoreactive T cells and B cells target myelin antigens

›CD4+ T helper 1 and T helper 17 cells drive inflammation

›CD8+ T cells contribute to tissue destruction

›B cells produce autoantibodies and present antigen (Bar-Or and Li, Lancet Neurology 2021)

›Blood-brain barrier breakdown allows inflammatory infiltrate

›Gadolinium enhancement on MRI marks active BBB disruption

›Inflammatory lesions cause conduction block and demyelination

›Relapse mechanism

›Focal inflammatory plaque causes acute conduction failure

›Reversible with remyelination or resolution of inflammation

›Incomplete recovery leaves residual axonal injury

›Axonal loss begins early in disease course

›Serum NfL reflects degree of ongoing neuro-axonal damage

›Accumulating axonal loss underlies progressive disability

›Lesion distribution

›Periventricular white matter: perivenular inflammation along medullary veins

›Infratentorial: brainstem, cerebellum, pons

›Spinal cord: short, peripheral, asymmetric lesions

›Cortical/juxtacortical: meningeal inflammation drives cortical demyelination

›Remyelination

›Spontaneous remyelination occurs early in disease

›Shadow plaques indicate partial remyelination

›Remyelination capacity declines with disease duration

›Active area of therapeutic research

Therapeutic Considerations

›Steroid mechanism of action

›High-dose corticosteroids reduce BBB inflammation and edema

›Accelerate recovery from individual relapse by days to weeks

›Do not alter long-term relapse outcome or disability trajectory

›Oral and IV routes are bioequivalent at equivalent doses (COPOUSEP trial)

›Plasma exchange mechanism

›Removes circulating antibodies and inflammatory mediators

›Particularly effective in antibody-mediated attack (NMOSD, MOGAD)

›Response rate approximately 77% in RRMS; 60.9% superior to escalated IVMP

›Immunoadsorption as alternative to plasma exchange

›Disease-modifying therapy classes

›Platform therapies (lower efficacy)

›Interferon-beta (IM or SC): reduces relapse rate 30%

›Glatiramer acetate SC: reduces relapse rate 30%

›Teriflunomide oral: reduces relapse rate 31–36%

›Moderate-efficacy therapies

›Dimethyl fumarate oral: reduces relapse rate 49–53%

›Fingolimod oral: reduces relapse rate 54%

›High-efficacy therapies

›Natalizumab IV monthly: reduces relapse rate 68%

›Ocrelizumab IV every 6 months: reduces relapse rate 46–47%

›Alemtuzumab IV: reduces relapse rate 49–54%

›Cladribine oral: reduces relapse rate 58%

›Vitamin D and lifestyle

›Low 25-OH vitamin D associated with increased relapse risk

›Target 25-OH vitamin D above 75 nmol/l

›No standardized supplementation dose established

›Smoking accelerates disability progression approximately 4.7% per year of continued smoking

›Smoking cessation counseling at every visit

›Heat avoidance for Uhthoff phenomenon

›Cooling strategies (cooling vest, cold fluids, air conditioning)

11Patient Discharge Instructions/pdi34

copy discharge instructions

›What is an MS relapse?

›A relapse means new or returning neurological symptoms that last more than 24 hours

›It is caused by inflammation in the brain or spinal cord

›Steroids help speed your recovery but do not change the long-term outcome

›Your steroid treatment

›Take your steroid medication exactly as prescribed

›Do not stop suddenly without your doctor's advice

›Check your blood sugar if you have diabetes

›Common side effects to expect

›Difficulty sleeping (take steroids in the morning if possible)

›Increased appetite and blood sugar

›Mood changes or feeling irritable

›Stomach upset (take with food)

›Activity and heat avoidance

›Avoid hot environments, hot baths, and excessive exercise until symptoms improve

›Heat can temporarily worsen your symptoms (Uhthoff phenomenon)

›Cooling strategies: cool fluids, fan, air conditioning

›Falls prevention

›Use assistive devices if your balance is affected

›Clear walkways at home and use grab bars

›Follow-up

›See your neurologist within 1–2 weeks

›A follow-up MRI may be scheduled within 1–3 months

›Report any medication side effects to your MS team

›Continue your disease-modifying therapy as directed

›Do not stop your MS medication without consulting your neurologist

›Stopping certain MS medications abruptly can trigger severe relapses

12References/r49

Guidelines and key sources

›McGinley MP, Goldschmidt CH, Rae-Grant AD — Diagnosis and Treatment of Multiple Sclerosis: A Review

›JAMA 2021

›First-line IV methylprednisolone and oral equivalence evidence

›DMT classification and relapse management overview

›Gavoille A, Rollot F, Casey R, et al — Acute Clinical Events Identified as Relapses With Stable MRI in Multiple Sclerosis

›JAMA Neurology 2024

›Alarm features distinguishing true relapse from alternatives

›Relapse definition and diagnostic criteria

›Le Page E, Veillard D, Laplaud DA, et al — COPOUSEP Randomized Controlled Trial

›Lancet 2015

›Oral versus IV high-dose methylprednisolone: noninferior for relapse treatment

›Wattjes MP, Ciccarelli O, Reich DS, et al — 2021 MAGNIMS-CMSC-NAIMS Consensus MRI Recommendations

›Lancet Neurology 2021

›MRI protocol standards for MS monitoring

›Gadolinium use and surveillance intervals

›Solomon AJ, Arrambide G, Brownlee WJ, et al — Differential Diagnosis of Suspected MS

›Lancet Neurology 2023

›Updated consensus differential diagnosis approach

›Red flags for NMOSD, MOGAD, and other mimics

›Bunganic R, Blahutova S, Revendova K, et al — Therapeutic Plasma Exchange in MS Aggressive Relapse

›Scientific Reports 2022

›TPE response rate approximately 77% in RRMS

›Pfeuffer S, Rolfes L, Bormann E, et al — Comparing Plasma Exchange to Escalated Methylprednisolone

›Journal of Clinical Medicine 2019

›TPE superior to escalated IVMP in refractory relapse (60.9% vs 15.2% good recovery)

›Jakimovski D, Bittner S, Zivadinov R, et al — Multiple Sclerosis

›Lancet 2024

Evidence & Review

Evidence & Review