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Multiple sclerosis

Definition
MS is a chronic immune-mediated disease, characterized by demyelinating lesions in the brain and spinal cord.
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Pathophysiology
Demyelinating lesions are thought to result from migration of autoreactive lymphocytes across the blood-brain barrier, which triggers a cascade of inflammation with T- and B-cell clonal expansion and activation of microglia, leading to the development of characteristic plaque Genetic factors (HLA-DRB1 haplotype) and environmental factors (viruses, low vitamin D, distance from the equator) have been implicated.
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Epidemiology
The prevalence of MS varies markedly geographically. In the US, MS has an estimated prevalence of 149.2 persons per 100,000 population. Incidence has been estimated at 17.3 cases per 100,000 person-years in Western Europe.
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Disease course
The clinical manifestations of MS are wide ranging. Common presenting features include weakness, paresthesia or focal sensory loss, optic neuritis, diplopia, ataxia and vertigo. Autonomic dysfunction is common, and may manifest as bladder, bowel and sexual symptoms. Other manifestations can include painful muscle spasms, trigeminal neuralgia, fatigue and depression, subtle cognitive difficulties, psychiatric disturbances and seizures.
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Prognosis and risk of recurrence
MS typically follows a relapsing and remitting course, but it can be progressive from disease onset, or can become progressive after initial remissions. The interval between relapses is variable. The latent phase between the first manifestation of MS and the first relapse can be many years.
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Key sources
The following summarized guidelines for the evaluation and management of multiple sclerosis are prepared by our editorial team based on guidelines from the Canadian Expert Group on Cannabinoids Use in Chronic Pain (CCP-CEG 2023), the American College of Radiology (ACR 2021), the American Academy of Sleep Medicine (AASM 2021), the Infectious Diseases Society of America (IDSA/ACR/AAN 2021), the European Society for Neurogastroenterology and Motility (ESNM/UEG 2021), the Middle East North Africa Committee for Research and Treatment in Multiple Sclerosis (MENACTRIMS 2020), the European Academy of Neurology (EAN 2020), the Latin American Consensus Group on Neuromyelitis Optica Spectrum Disorder (LACG-NMOSD 2020), the American Academy of Neurology (AAN 2019; 2018; 2016; 2014; 2002), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/EAN 2018), the American College of Gastroenterology (ACG 2018), and the European Federation of Neurological Societies (EFNS 2010; 2005).
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Guidelines

1.Screening and diagnosis

Differential diagnosis, neuromyelitis optica: rule out MS in patients with suspected neuromyelitis optica spectrum disorder.
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  • Differential diagnosis (Lyme disease)

  • Associated comorbidities (Crohn's disease)

  • Associated comorbidities (gastroparesis)

2.Diagnostic investigations

Diagnostic imaging: obtain spinal cord MRI as initial imaging in patients with acute onset or chronic/progressive myelopathy.
B

3.Medical management

Management of clinically isolated syndrome: as per MENACTRIMS 2020 guidelines, obtain close follow-up for the development of a clinical event in patients with radiologically isolated syndrome. Do not initiate disease-modifying therapies in patients with radiologically isolated syndrome.
E

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  • Management of acute relapses (corticosteroids)

  • Management of acute relapses (plasma exchange)

  • Management of acute relapses (IVIG)

  • Disease-modifying therapies (indications)

  • Disease-modifying therapies (pretreatment counseling)

  • Disease-modifying therapies (choice of agent, relapsing-remitting MS)

  • Disease-modifying therapies (choice of agent, primary-progressive MS)

  • Disease-modifying therapies (choice of agent, secondary-progressive MS)

  • Disease-modifying therapies (switching to another agent)

  • Disease-modifying therapies (discontinuation)

  • Management of spasticity (exercise)

  • Management of spasticity (skeletal muscle relaxants)

  • Management of spasticity (cannabinoids)

  • Management of spasticity (botulinum toxin)

  • Management of spasticity (transcutaneous electrical nerve stimulation)

  • Management of pain (anticonvulsants and antidepressants)

  • Management of pain (opioids)

  • Management of pain (cannabinoids)

  • Management of pain (therapeutic procedures)

  • Management of fatigue (nonpharmacological management)

  • Management of fatigue (pharmacotherapy)

  • Management of urinary incontinence (antimuscarinic agents)

  • Management of urinary incontinence (desmopressin)

  • Management of urinary incontinence (cannabinoids)

  • Management of urinary incontinence (botulinum toxin)

  • Management of urinary incontinence (behavioral management)

  • Management of urinary incontinence (pelvic floor muscle training)

  • Management of urinary incontinence (catheterization)

  • Management of depressive symptoms

  • Management of pseudobulbar affect

  • Management of sleep disturbances (CEG-CCP)

  • Management of sleep disturbances

  • Palliative care

4.Nonpharmacologic interventions

Support programs: consider directing patients with MS eligible for disease-modifying therapies to support programs.
C

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  • Alternative and complementary therapies

5.Specific circumstances

Pregnant patients: as per AAN 2018 guidelines, monitor the reproductive plans of females of childbearing potential with MS, and counsel patients on DMT regarding reproductive risks and the use of contraception.
B
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6.Preventative measures

Routine immunizations: discuss the evidence regarding immunizations in MS with the patient and explore their opinions, preferences, and questions.
B
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7.Follow-up and surveillance

Assessment of treatment response: as per AAN 2018 guidelines, monitor for medication adherence, adverse effects, safety, and effectiveness of the DMT in patients with MS on disease-modifying therapies.
B
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