Multiple sclerosis: Difference between revisions
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==Background==
==Background==
*CNS myelin destruction causes variable motor, sensory, visual and cerebellar dysfunction<ref>Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin, Volume 95, Issue 1, September 2010, Pages 79–104. https://doi.org/10.1093/bmb/ldq017</ref>
*CNS myelin destruction causes variable motor, sensory, visual and cerebellar dysfunction<ref>Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin, Volume 95, Issue 1, September 2010, Pages 79–104. https://doi.org/10.1093/bmb/ldq017</ref>
 
*Peak onset age 20-40 years, F:M ratio ~3:1
*More common in populations of Northern European descent and at higher latitudes
===Types===
===Types===
*'''Relapsing/remitting (most common)'''
*Clinically isolated syndrome (CIS)
**Single first episode of neurologic symptoms lasting ≥24 hours, caused by CNS demyelination
**May or may not progress to MS
*Radiologically isolated syndrome (RIS)
**Incidental MRI findings suggestive of MS in asymptomatic patients
*Relapsing/remitting (most common)
**Relapse (days-months) followed by remission
**Relapse (days-months) followed by remission
*'''Secondary progressive'''
*Secondary progressive  
**Relapses and partial recoveries occur, but disability does not fade away between cycles
**Relapses and partial recoveries occur, but disability does not fade away between cycles
*'''Primary progressive'''
*Primary progressive
**Symptoms progress slowly and steadily without remission
**Symptoms progress slowly and steadily without remission
*'''Progressive relapsing'''
*Progressive relapsing
**Similar to primary progressive but with superimposed flares
**Similar to primary progressive but with superimposed flares
==Clinical Features==
==Clinical Features==
*Classic patient has multiple presentations for neuro symptoms of different areas of pathology  
*Classic patient has multiple presentations for neuro symptoms of different areas of pathology  
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**[[numbness|Decrease]] in proprioception/pain/temperature sensation
**[[numbness|Decrease]] in proprioception/pain/temperature sensation
**Lhermitte sign
**Lhermitte sign
***Electric shock sensation radiating down back into arms/egs from neck flexion
***Electric shock sensation radiating down back into arms/legs from neck flexion
***If the discomfort is severe, carbamazepine or gabapentin may be beneficial for some patients.
***If the discomfort is severe, carbamazepine or gabapentin may be beneficial for some patients.
**Partial [[transverse myelitis]]
***Asymmetric motor/sensory deficits at a spinal cord level
***One of the most common acute presenting syndromes
**[[Trigeminal neuralgia]]
***Bilateral trigeminal neuralgia in a young patient should raise suspicion for MS
*[[Optic neuritis]]
*[[Optic neuritis]]
**Initial sign in 30% of patients
**Initial sign in 30% of patients
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**[[Diplopia]]
**[[Diplopia]]
*[[Internuclear ophthalmoplegia]]
*[[Internuclear ophthalmoplegia]]
**Abnormal eye adduction bilaterally and horizontal nystagmus
**Impaired adduction of the adducting eye with nystagmus of the abducting eye
**Bilateral INO is classic for MS
**Convergence (both eyes center medially) is preserved
**Convergence (both eyes center medially) is preserved
*Dysautonomia
*Dysautonomia
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**[[Constipation]] or incontinence
**[[Constipation]] or incontinence
**Sexual dysfunction (males)
**Sexual dysfunction (males)
 
*Other common symptoms
**Fatigue — most common symptom overall; frequent reason for ED presentation
**Cognitive dysfunction (up to 50% of patients)
==Differential Diagnosis==
==Differential Diagnosis==
{{Weakness DDX}}
{{Weakness DDX}}
==Evaluation==
==Evaluation==
[[File:MS_MRI_1.jpg|thumb|MRI brain with contrast of a patient in her mid-20s with new onset MS. Large lesion in left parietal area.]]
[[File:MS_MRI_1.jpg|thumb|MRI brain with contrast of a patient in her mid-20s with new onset MS. Large lesion in left parietal area.]]
[[File:MS_MRI_2.jpg|thumb|MRI brain with contrast of same patient with new onset MS with another lesion in the left cerebellum.]]
[[File:MS_MRI_2.jpg|thumb|MRI brain with contrast of same patient with new onset MS with another lesion in the left cerebellum.]]
===Known MS Patient with Exacerbation===
*[[Urinalysis]] — rule out occult [[UTI]] as pseudorelapse trigger (very common in MS)
*CBC, Chemistry
*Consider [[chest X-ray|CXR]] or other infectious workup based on presentation
*Temperature — fever suggests pseudorelapse or infection
*[[brain MRI|MRI]] with GAD generally not needed emergently unless diagnostic uncertainty or concern for [[PML]]
*LP is generally not needed for exacerbation of known MS — defer to neurology
===Suspected New Diagnosis===
*[[brain MRI|MRI]] with GAD of brain (+/- spine) and orbits (if [[optic neuritis]] suspected)
**Multiple lesions in supratentorial white matter, paraventricular area, spinal cord
*[[LP|CSF]]
*[[LP|CSF]]
**Elevated protein and gamma-globulin (increased oligoclonal bands)
**Elevated protein and gamma-globulin (increased oligoclonal bands)
*[[brain MRI|MRI]]
**Generally can be deferred to neurology
**Multiple lesions in supratentorial white matter, paraventricular area, spinal cord
*[[brain MRI|MRI]] with GAD of brain (+/- spine) and orbits (if [[optic neuritis]] suspected)
*CBC, Chemistry
*CBC, Chemistry
*[[Urinalysis]]
*[[Urinalysis]]
*TSH, B12, RPR/VDRL — rule out MS mimics
*Consider NMO/aquaporin-4 antibody testing (especially if longitudinally extensive transverse myelitis or bilateral optic neuritis)<ref>Pelletier J, et al. "Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review." J Emerg Med. 2024;66(4):e441-e456.</ref>


==Management==
==Management==
===Pseudorelapse vs True Relapse===
{| class="wikitable"
|-
! !! '''True Relapse''' !! '''Pseudorelapse'''
|-
| '''Definition''' || New inflammatory demyelinating event || Temporary worsening of old symptoms from an external trigger
|-
| '''Duration''' || >24 hours, evolves over hours to days, persists days to weeks || Typically <24 hours; resolves when trigger is removed
|-
| '''Triggers''' || None (not explained by fever or infection) || Infection (especially UTI), fever, heat, stress, dehydration, medication changes
|-
| '''Symptoms''' || New neurologic symptoms OR worsening in a new distribution || Recurrence of prior/known deficits; symptoms may fluctuate
|-
| '''MRI''' || Often shows new gadolinium-enhancing lesion || No new lesion
|-
| '''Treatment''' || High-dose corticosteroids || Treat the underlying trigger; steroids are '''not''' indicated
|}
<ref>Mellen Center Approaches: Management of MS Relapses. Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research. https://my.clevelandclinic.org/departments/neurological/depts/multiple-sclerosis/ms-approaches/relapse-management-ms</ref><ref>Defined by Thompson AJ, et al. "Diagnosis of multiple sclerosis: 2017 revisions of the McDonald Criteria." Lancet Neurol. 2018;17(2):162-173.</ref>
*Always check UA and infectious workup before initiating steroids — occult UTI is a very common pseudorelapse trigger in MS patients
*If symptoms are identical to a prior relapse, pseudorelapse is more likely (MS rarely causes repeated inflammation in the same CNS location)
*Symptoms that fluctuate or resolve completely and then return favor pseudorelapse<ref>Amin A, et al. "Triaging Patients with Multiple Sclerosis in the Emergency Department: Room for Improvement." Proc Bayl Univ Med Cent. 2022;36(2):186-189.</ref>
===Fever and Infection===
*Fever must be reduced to minimize weakness associated with elevated temperature
*Fever must be reduced to minimize weakness associated with elevated temperature
===Infection Treatment===
*Antibiotics or surgical control of any infectious sources
*Antibiotics or surgical control of any infectious sources
===Steroids and Immunomodulators===
 
*High-dose [[Corticosteroids|steroid]] therapy for relapses in the form of oral or intravenous methylprednisolone (1000 mg)<ref>Le Page et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2016 Jan 23;387(10016):340. https://core.ac.uk/download/pdf/52993687.pdf</ref>
===Steroids===
*Suppression therapies
*High-dose [[Corticosteroids|steroid]] therapy for true relapses in the form of oral or intravenous methylprednisolone (1000 mg daily x 3-5 days)<ref>Le Page et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2016 Jan 23;387(10016):340. https://core.ac.uk/download/pdf/52993687.pdf</ref>
**IFN B, Glatiramer, Estriol (usually not in ED)
**Oral methylprednisolone at equivalent doses is non-inferior to IV and allows for outpatient treatment
*Do not initiate steroids until infection has been ruled out as the cause of symptom worsening
 
===Plasma Exchange (PLEX)===
*Second-line treatment for severe relapses refractory to high-dose corticosteroids<ref>Ehler J, et al. "Therapeutic Plasma Exchange in Multiple Sclerosis and Autoimmune Encephalitis." J Clin Med. 2019;8(10):1793.</ref>
*~20-35% of patients may not fully respond to steroids alone
*Typically 5-7 sessions over 10-14 days
*Consult neurology early if relapse is severe or not responding to steroids
 
===Disease-Modifying Therapies (DMTs)===
*Suppression therapies (IFN-β, Glatiramer, etc.) — initiation is generally not in ED
*However, ED physicians should be aware of complications of DMTs in patients already on treatment:
 
{| class="wikitable"
|-
! '''DMT''' !! '''ED-Relevant Complications'''
|-
| '''Natalizumab (Tysabri)''' || Risk of '''[[PML]]''' (progressive multifocal leukoencephalopathy) — any new neurologic worsening warrants urgent MRI and JC virus testing
|-
| '''Fingolimod / Siponimod''' || [[Bradycardia]], cardiac conduction abnormalities, macular edema
|-
| '''Ocrelizumab, Rituximab''' (anti-CD20) || Increased infection risk, infusion reactions, reactivation of hepatitis B
|-
| '''Interferons (Avonex, Rebif)''' || Flu-like symptoms (may mimic infection), hepatotoxicity, cytopenias
|-
| '''Dimethyl fumarate (Tecfidera)''' || Lymphopenia (increased infection risk); rare PML risk
|}
<ref>Pelletier J, et al. "Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review." J Emerg Med. 2024;66(4):e441-e456.</ref>


==Disposition==
==Disposition==
*Hospitalization indicated for:
===Discharge===
**Any disease exacerbation associated with significant morbidity
*Mild relapse in a patient who can ambulate safely
**IV antibiotics or steroid therapy required
*Able to tolerate oral medications (oral methylprednisolone non-inferior to IV)
**Depression and significant risk of suicide
*Has reliable follow-up with neurology (ideally within 1-3 days)
*No untreated infection
*Adequate social support
 
===Admission===
*Any disease exacerbation associated with significant morbidity or functional impairment
*IV antibiotics or steroid therapy required
*Inability to ambulate safely or care for self
*[[Urinary retention]] requiring catheterization
*Concern for [[PML]] or other serious DMT complication
*Depression and significant risk of suicide
*Need for plasma exchange


===Neurology Consultation===
*New suspected MS diagnosis
*Severe relapse with significant functional impairment
*Steroid-refractory symptoms (discuss PLEX)
*Concern for PML or other DMT-related complication
*Diagnostic uncertainty
===Return Precautions===
*Worsening weakness or new weakness
*New or worsening visual symptoms
*Inability to urinate or new incontinence
*Difficulty breathing or swallowing
*[[Fever]]
==See Also==
==See Also==
*[[Optic Neuritis]]
*[[Optic Neuritis]]
 
*[[Transverse myelitis]]
*[[Internuclear ophthalmoplegia]]
==References==
==References==
<references/>
<references/>
[[Category:Neurology]]
[[Category:Neurology]]

Latest revision as of 09:26, 22 March 2026

Background

  • CNS myelin destruction causes variable motor, sensory, visual and cerebellar dysfunction[1]
  • Peak onset age 20-40 years, F:M ratio ~3:1
  • More common in populations of Northern European descent and at higher latitudes

Types

  • Clinically isolated syndrome (CIS)
    • Single first episode of neurologic symptoms lasting ≥24 hours, caused by CNS demyelination
    • May or may not progress to MS
  • Radiologically isolated syndrome (RIS)
    • Incidental MRI findings suggestive of MS in asymptomatic patients
  • Relapsing/remitting (most common)
    • Relapse (days-months) followed by remission
  • Secondary progressive
    • Relapses and partial recoveries occur, but disability does not fade away between cycles
  • Primary progressive
    • Symptoms progress slowly and steadily without remission
  • Progressive relapsing
    • Similar to primary progressive but with superimposed flares

Clinical Features

  • Classic patient has multiple presentations for neuro symptoms of different areas of pathology
    • Patient often has resolution of the earlier symptoms
  • Symptoms worsen with increases in body temperature, classically after hot showers (Uhthoff's phenomenon[2])
  • Muscle/sensory signs:
    • Lower extremity weakness usually worse than upper extremity
    • Upper motor neuron signs:
      • Hyperreflexia
      • Positive Babinski
    • Decrease in proprioception/pain/temperature sensation
    • Lhermitte sign
      • Electric shock sensation radiating down back into arms/legs from neck flexion
      • If the discomfort is severe, carbamazepine or gabapentin may be beneficial for some patients.
    • Partial transverse myelitis
      • Asymmetric motor/sensory deficits at a spinal cord level
      • One of the most common acute presenting syndromes
    • Trigeminal neuralgia
      • Bilateral trigeminal neuralgia in a young patient should raise suspicion for MS
  • Optic neuritis
  • Internuclear ophthalmoplegia
    • Impaired adduction of the adducting eye with nystagmus of the abducting eye
    • Bilateral INO is classic for MS
    • Convergence (both eyes center medially) is preserved
  • Dysautonomia
  • Other common symptoms
    • Fatigue — most common symptom overall; frequent reason for ED presentation
    • Cognitive dysfunction (up to 50% of patients)

Differential Diagnosis

Weakness

Evaluation

MRI brain with contrast of a patient in her mid-20s with new onset MS. Large lesion in left parietal area.
MRI brain with contrast of same patient with new onset MS with another lesion in the left cerebellum.

Known MS Patient with Exacerbation

  • Urinalysis — rule out occult UTI as pseudorelapse trigger (very common in MS)
  • CBC, Chemistry
  • Consider CXR or other infectious workup based on presentation
  • Temperature — fever suggests pseudorelapse or infection
  • MRI with GAD generally not needed emergently unless diagnostic uncertainty or concern for PML
  • LP is generally not needed for exacerbation of known MS — defer to neurology

Suspected New Diagnosis

  • MRI with GAD of brain (+/- spine) and orbits (if optic neuritis suspected)
    • Multiple lesions in supratentorial white matter, paraventricular area, spinal cord
  • CSF
    • Elevated protein and gamma-globulin (increased oligoclonal bands)
    • Generally can be deferred to neurology
  • CBC, Chemistry
  • Urinalysis
  • TSH, B12, RPR/VDRL — rule out MS mimics
  • Consider NMO/aquaporin-4 antibody testing (especially if longitudinally extensive transverse myelitis or bilateral optic neuritis)[3]

Management

Pseudorelapse vs True Relapse

True Relapse Pseudorelapse
Definition New inflammatory demyelinating event Temporary worsening of old symptoms from an external trigger
Duration >24 hours, evolves over hours to days, persists days to weeks Typically <24 hours; resolves when trigger is removed
Triggers None (not explained by fever or infection) Infection (especially UTI), fever, heat, stress, dehydration, medication changes
Symptoms New neurologic symptoms OR worsening in a new distribution Recurrence of prior/known deficits; symptoms may fluctuate
MRI Often shows new gadolinium-enhancing lesion No new lesion
Treatment High-dose corticosteroids Treat the underlying trigger; steroids are not indicated

[4][5]


  • Always check UA and infectious workup before initiating steroids — occult UTI is a very common pseudorelapse trigger in MS patients
  • If symptoms are identical to a prior relapse, pseudorelapse is more likely (MS rarely causes repeated inflammation in the same CNS location)
  • Symptoms that fluctuate or resolve completely and then return favor pseudorelapse[6]

Fever and Infection

  • Fever must be reduced to minimize weakness associated with elevated temperature
  • Antibiotics or surgical control of any infectious sources

Steroids

  • High-dose steroid therapy for true relapses in the form of oral or intravenous methylprednisolone (1000 mg daily x 3-5 days)[7]
    • Oral methylprednisolone at equivalent doses is non-inferior to IV and allows for outpatient treatment
  • Do not initiate steroids until infection has been ruled out as the cause of symptom worsening

Plasma Exchange (PLEX)

  • Second-line treatment for severe relapses refractory to high-dose corticosteroids[8]
  • ~20-35% of patients may not fully respond to steroids alone
  • Typically 5-7 sessions over 10-14 days
  • Consult neurology early if relapse is severe or not responding to steroids

Disease-Modifying Therapies (DMTs)

  • Suppression therapies (IFN-β, Glatiramer, etc.) — initiation is generally not in ED
  • However, ED physicians should be aware of complications of DMTs in patients already on treatment:
DMT ED-Relevant Complications
Natalizumab (Tysabri) Risk of PML (progressive multifocal leukoencephalopathy) — any new neurologic worsening warrants urgent MRI and JC virus testing
Fingolimod / Siponimod Bradycardia, cardiac conduction abnormalities, macular edema
Ocrelizumab, Rituximab (anti-CD20) Increased infection risk, infusion reactions, reactivation of hepatitis B
Interferons (Avonex, Rebif) Flu-like symptoms (may mimic infection), hepatotoxicity, cytopenias
Dimethyl fumarate (Tecfidera) Lymphopenia (increased infection risk); rare PML risk

[9]

Disposition

Discharge

  • Mild relapse in a patient who can ambulate safely
  • Able to tolerate oral medications (oral methylprednisolone non-inferior to IV)
  • Has reliable follow-up with neurology (ideally within 1-3 days)
  • No untreated infection
  • Adequate social support

Admission

  • Any disease exacerbation associated with significant morbidity or functional impairment
  • IV antibiotics or steroid therapy required
  • Inability to ambulate safely or care for self
  • Urinary retention requiring catheterization
  • Concern for PML or other serious DMT complication
  • Depression and significant risk of suicide
  • Need for plasma exchange

Neurology Consultation

  • New suspected MS diagnosis
  • Severe relapse with significant functional impairment
  • Steroid-refractory symptoms (discuss PLEX)
  • Concern for PML or other DMT-related complication
  • Diagnostic uncertainty

Return Precautions

  • Worsening weakness or new weakness
  • New or worsening visual symptoms
  • Inability to urinate or new incontinence
  • Difficulty breathing or swallowing
  • Fever

See Also

References

  1. ↑ Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin, Volume 95, Issue 1, September 2010, Pages 79–104. https://doi.org/10.1093/bmb/ldq017
  2. ↑ Flensner G, et al. "Sensitivity to heat in MS patients: a factor strongly influencing symptomology-an explorative survey". BMC Neurol. 2011. 11:27.
  3. ↑ Pelletier J, et al. "Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review." J Emerg Med. 2024;66(4):e441-e456.
  4. ↑ Mellen Center Approaches: Management of MS Relapses. Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research. https://my.clevelandclinic.org/departments/neurological/depts/multiple-sclerosis/ms-approaches/relapse-management-ms
  5. ↑ Defined by Thompson AJ, et al. "Diagnosis of multiple sclerosis: 2017 revisions of the McDonald Criteria." Lancet Neurol. 2018;17(2):162-173.
  6. ↑ Amin A, et al. "Triaging Patients with Multiple Sclerosis in the Emergency Department: Room for Improvement." Proc Bayl Univ Med Cent. 2022;36(2):186-189.
  7. ↑ Le Page et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2016 Jan 23;387(10016):340. https://core.ac.uk/download/pdf/52993687.pdf
  8. ↑ Ehler J, et al. "Therapeutic Plasma Exchange in Multiple Sclerosis and Autoimmune Encephalitis." J Clin Med. 2019;8(10):1793.
  9. ↑ Pelletier J, et al. "Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review." J Emerg Med. 2024;66(4):e441-e456.
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