emDOCs Podcast – Episode 99: Multiple Sclerosis in the ED

Background:

• MS is an autoimmune disease affecting oligodendrocytes, the nerve cell responsible for myelinating the axons of neurons. This results in demyelination and axonal loss within the central nervous system (CNS).
• MS typically affects women age 20-40 years. Risk factors include northern latitudes, vitamin D deficiency, EBV infection, smoking, genetics, and concomitant autoimmune diseases.

Presentation

• Most initially present with long tract signs or symptoms (46%) and less frequently with optic neuritis (21%) or brainstem syndromes (10%).
• 23% of patient will present with multifocal symptoms (worse prognosis).
• Long tract signs: upper motor myelopathy, asymmetric spastic paraplegia, and urinary or erectile dysfunction.
• Others: Lhermitte’s sign (an electric shock sensation when the neck is flexed), Brown-Sequard syndrome, and the “MS hug” (thoracic demyelination produces a sensation of having a band wrapped around the torso).
• Altered fine sensation, vibration sensation, or proprioception may occcur, and a sensory level may be present.
• Optic neuritis usually presents with painful visual loss and color vision changes.
• Bilateral internuclear ophthalmoplegia is that discoordination of lateral eye movements when looking to either side.
• May also find abducens palsy, dysarthria, dysphagia, facial numbness, and direction-changing nystagmus.

Diagnosis:

• Diagnosis based on McDonald Criteria, which were last revised in 2017. Patients can partially meet these criteria, and we refer to these patients as having “possible MS.”
• Can’t make the diagnosis until other differentials are excluded. The criteria are as follows:

Disease Progression:

• For CIS, the patient must have symptoms for at least 24 hours in the absence of any infection.
• To call a presentation CIS, the patient must have symptoms for at least 24 hours in the absence of any infection.
• RIS and CIS may or may not progress to RRMS, PPMS, or SPMS.
• Risk factors for MS development in RIS patients: spinal cord involvement, male sex, and age < 37 years at diagnosis.
• Risk factors for progression of CIS to RRMS, PPMS, or SPMS: age < 30 at time of presentation, non-Caucasian race, motor symptoms, multifocal symptoms, increased EBV antigen titer, smoking, and increased number or size of radiographic lesions on MRI.

Evaluation:

• For possible CIS, must exclude other causes of their symptoms.
• Most of these patients will receive extensive laboratory workup and imaging, including MRI, before receiving CIS diagnosis.
• Goal of evaluation: for patients with established MS, need to differentiate relapse/exacerbation from pseudo-relapse.
  • True relapse is worsening of baseline neurologic symptoms with a significant change in neurologic examination for at least 24 hours with 30 days of preceding clinical stability.
  • Pseudo-relapse like recrudescence in stroke patients. Symptoms may wax and wane and last less than 24 hours.
• Physical stress such as infection can be a trigger for relapse or pseudo-relapse, so sources of infection (particularly UTI) should be identified and treated, and heat, menstruation, or emotional stressors can bring on pseudo-relapse.
• ED workup for the established MS patient coming in with neurologic symptoms should include CBC, CMP, UA, ECG, and CXR.
  • For CIS, consult neurology
• Patients with new focal deficits should undergo CT head +/- CTA head and neck and perfusion scanning to exclude stroke or alternate causes of symptoms.
• MRI with contrast is the ideal strategy for diagnosing suspected CIS or MS flare.

Management:

• Steroids necessary for most patient. If possible, get the MRI before giving steroids in patients who present with CIS or MS relapse. However, don’t delay steroids if highly suspicious for MS flare and there will be a delay to obtaining MRI.
  • Standard therapy recommended for MS flares is high-dose methylprednisolone 1 g IV for 3-5 days, but oral steroids can be used as an alternative in consultation with neurology.
• For steroid refractory patients, plasmapheresis is second line therapy. Other treatments include ACTH, pooled antibody, immunoadsorption apheresis
• Treating any underlying infections that are triggering first-time presentation or relapse.
  • Patients on disease modifying therapy (DMT) – i.e. immunosuppressive agents – may be susceptible to infections that occur in other immunocompromised patients.
• Reducing fever is critically important in ill patients, since heat makes MS symptoms worse.

Disposition:

• If presenting with new neurologic symptoms lasting > 24 hours that are disabling, they need to be admitted.
• If they have non-disabling new neurologic symptoms lasting > 24 hours, precipitating causes should be identified, and need for admission vs. the possibility of outpatient management should be discussed with neurology.
• Pseudo-relapse with worsening of baseline exam should be worked up similarly to true relapse, and admission vs. discharge discussed with neurology.
• For pseudo-relapse with no significant change in baseline neurologic exam, or for MS patients coming in with non-neurologic issues, they should be treated similar to other ED patients, but with consideration that those on DMTs may be at risk for different types of infections than immunocompetent patients.

Summary:

• MS is an autoimmune disorder that targets the CNS and can cause severe disability. Clinical diagnosis based on the McDonald criteria.
• RIS and CIS patients may or may not subsequently develop chronic MS, which is broken into RRMS, PPMS, or SPMS.
• We need to make this diagnosis, Early diagnosis and treatment of CIS or MS relapse may delay the next relapse .
• Pseudo-relapse has a short duration (< 24 hours) with a waxing and waning course and there’s no new neurologic deficits.
• Base testing on the history, exam, and consideration of other conditions that may result in neurologic symptoms. Consult neurology early.
• If you can, get the MRI before giving steroids in patients who present with CIS or MS relapse. But if there’s going to be a significant delay, go ahead and give the steroid.
• You don’t necessarily need the MRI for patients who present with new neurologic symptoms that are non-disabling, they have a clear pseudo-relapse, or non-neurological medical complaints, but involve your neurologists.
• Don’t need MRI of the spinal cord if the symptoms don’t localize there.
• When it comes to therapy for CIS or MS relapse, the first line treatment is steroids.

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