EM@3AM: Multiple Sclerosis

Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 33-year-old female presents with blurry vision. She has also experienced intermittent paresthesias in her extremities and weakness. Her symptoms seem to worsen in the heat but improve in the cold.

Your motor and sensory exam is normal, but you find internuclear ophthalmoplegia and an afferent pupillary defect. With these intermittent neurologic symptoms and ocular findings, what is the likely diagnosis, and what is your next step in evaluation?

AnswerMultiple Sclerosis (MS)

Background: MS is an immune-mediated disease due to inflammation with destruction of myelinated axons in the CNS. This results in axon and myelin destruction and a variety of signs and symptoms involving the neurologic system. Demyelinating lesions are known as plaques.

  • Currently no definitive underlying etiology, but current thoughts include combination of genetic and non-genetic causes (low vitamin D, infection, environmental). Autoimmune disorders are related to MS.
  • Women are more commonly affected (female-to-male 1.4/2.3 to 1), as are Caucasians.
  • Most common age group affected is 15-45 years.
  • Geography may play a role: incidence is lower in equatorial regions and higher with greater latitudes, though there are exceptions.



  • Relapsing/remitting (most common, 80-85%): Relapse for days to months and then improvement. 50% progress to secondary progressive form within 15 years.
  • Secondary progressive: Relapse with partial recovery between episodes.
  • Primary progressive (10%): Symptoms worsen steadily with no remission or improvement.
  • Progressive relapsing: Like primary progressive, but associated with flares.


History and Exam

  • Focused history and exam are essential. Evaluate motor, sensory, cerebellar, cranial nerves, cognition, mood, gait, and potential triggers of exacerbation (infection).
  • Patients classically have multiple presentations with different neurologic symptoms that may affect different anatomic regions. Attacks/deficits are separated by “time and space”.
  • In early stages, symptoms will often resolve.
  • Neurologic symptoms worsen with increased body temperature (Uhthoff’s phenomenon) and exercise.
  • Early complaints include paresthesias. Sensation changes include proprioception, pain, and temperature.
  • Pain affects 30-50% and fatigue affects 75% of patients with MS.
  • Spasticity and cramping may occur with spinal cord involvement, which affects up to 75% of patients. Patients may have upper motor signs with hyperreflexia.
  • Cerebellar symptoms include nystagmus, dysarthria, and intention tremor.
  • Trigeminal neuralgia.
  • Lower motor weakness is usually worse than upper extremity weakness
  • Lhermitte’s sign includes electric shock sensation that travels down the back into the extremities with neck flexion.
  • Cognitive difficulties with attention, concentration, memory.
  • Optic neuritis:
    • May be the first sign in 15-30% of patients. 50% of those with optic neuritis go on to develop MS.
    • Patients often experience retrobulbar pain followed by blurry vision and visual loss.
    • Nystagmus and diplopia may be present.
    • Red desaturation test (affected eye sees a red object as a lighter red/pink).
    • Afferent pupillary defect but normal intraocular pressures.
    • Ocular ultrasound often demonstrates increased optic nerve sheath diameter.
  • Internuclear ophthalmoplegia: Both eyes can center medially, but abnormal eye adduction with horizontal nystagmus.
  • Dysautonomia: Bladder spasms and urinary retention increase risk of UTI, constipation/incontinence, and sexual dysfunction.
  • Evaluate for any exacerbating condition such as ischemia or infection.
  • Patients are at significant risk for depression and suicide.


Laboratory Assessment

  • CBC, renal and liver function, electrolytes, urinalysis.
  • Inflammatory markers: ESR and CRP.
  • LP can be obtained if MRI not available; however, LP is now not routinely required for diagnosis. Send CSF for cell count, protein, glucose, gram stain, IgG (70-90% of cases), albumin, oligoclonal bands (90-95% of cases), myelin basic protein.
    • CSF typically demonstrates elevated protein and gamma-globulin, oligoclonal bands/myelin basic protein.



  • Head CT can be obtained but is usually normal.
  • Obtain chest x-ray if respiratory signs/symptoms are present.
  • MRI with gadolinium contrast of the brain and spine is the imaging modality of choice, which may demonstrate multiple lesions (supratentorial white matter, paraventricular region, and spinal cord).
    • 90-95% of MS patients will have MRI findings, and spinal cord lesions are present in up to 75%.


Diagnosis: McDonald’s Criteria

Treatment: Goals include stabilize life-threatening conditions, begin supportive care, and evaluate/monitor for increased ICP.

  • Treat any associated infection and fever.
  • Provide steroids for relapses.
    • Provide 1 g IV methylprednisolone for serious symptoms, including optic neuritis.
  • Plasmapheresis may be utilized for severe attacks if steroids are contraindicated.
  • Other medications for suppression include interferon beta, glatiramer, natalizumab, and estriol.



  • Consult neurology.
  • Hospitalize patients experiencing exacerbation with severe symptoms for IV steroids and antibiotics.



  • Severe physical disability occurs within 20-25 years in over a quarter of patients.
  • Males with primary progressive form have the worst prognosis.
  • Greater spinal cord involvement is a poor prognostic finding.
  • Death usually occurs due to secondary complications such as infection.
  • Increased risk of mood disorders and attempted suicide.

A 44-year-old woman with a history of multiple sclerosis presents with progressively worsening fatigue and leg weakness. Her vital signs are T 99°F, HR 102 beats/minute, RR 18 breaths/minute, BP 118/76 mm Hg, and oxygen saturation 99% on room air. Her bilateral leg strength is 3 out of 5, her rectal tone is normal, and she has nystagmus. Which of the following is the most appropriate intervention at this time?

A) Dexamethasone

B) Lumbar puncture

C) MRI brain

D) Natalizumab



Answer: A

Multiple sclerosis (MS) is an autoimmune demyelination disease of the brain and spinal cord with subsequent axonal damage. Patients are typically young females with a Caucasian predominance. The clinical presentation may vary, but typically there are neurologic deficits separated by time and space (i.e., anatomic location). Patients may experience ocular symptoms such as painful vision loss (e.g., optic neuritis); cerebellar or brainstem findings such as diplopia, ataxia, scanning speech, nystagmus, or intention tremor; motor weakness; electric shock-like sensation with neck flexion (Lhermitte phenomenon); bladder incontinence; paresthesias; and sensory deficits. Symptoms may be exacerbated by activities that increase body temperature, such as exercise. The clinical course is classically relapsing and remitting. Analysis of cerebrospinal fluid reveals increased levels of immunoglobulin G and myelin basic protein. Oligoclonal bands are diagnostic. The gold standard of diagnosis is with MRI of the brain and spinal cord, which demonstrates periventricular white matter plaques, which represent loss of oligodendrocytes with reactive gliosis. Acute exacerbations are treated with IV corticosteroids such as dexamethasone. Disease-modifying therapies (e.g., beta-interferon, natalizumab, glatiramer) are used to stop relapses and slow progression. Other symptomatic therapies for neurogenic bladder, spasticity, and pain are also recommended.

Lumbar puncture (B) and MRI brain (C) are diagnostic studies used in the initial workup of MS but are not immediately indicated during acute exacerbations. Disease-modifying drugs such as natalizumab (D) are not part of the emergency department management of acute MS flares.

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Further Reading:





  1. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb. 17 (2):162-173.
  2. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul. 50(1):121-7.
  3. Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, et al. Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS: Report of the Guideline Development Subcommittee of the American Academy of Neurology.Neurology. 2013 Dec 27. [
  4. Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.Neurology. 2018 Apr 24. 90 (17):777-788.
  5. Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.Neurology. 2018 Apr 24. 90 (17):789-800.
  6. Wattjes MP, Rovira À, Miller D, Yousry TA, Sormani MP, de Stefano MP, et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis–establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015 Oct. 11 (10):597-606.


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