Am Fam Physician. 2022;106(2):173-183
Author disclosure: No relevant financial relationships.
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system and the most common cause of nontraumatic neurologic disability in young adults. Types of MS include relapsing-remitting (most common), secondary progressive, and primary progressive. Clinically isolated syndrome and radiologically isolated syndrome are additional categories for patients with findings concerning for MS who do not yet meet the diagnostic criteria for the disease. Symptoms of MS depend on the areas of neuronal involvement. Common symptoms include sensory disturbances, motor weakness, impaired gait, incoordination, optic neuritis, and Lhermitte sign. A patient history, neurologic examination, and application of the 2017 McDonald Criteria are needed to diagnose MS accurately. Patients with MS should be treated by a multidisciplinary team that may include physical and occupational therapists, speech and language therapists, mental health professionals, pharmacists, dietitians, neurologists, and family physicians. Steroids are the mainstay of treatment for the initial presentation of MS and relapses. Patients who do not adequately respond to steroids may benefit from plasmapheresis. Patients with MS who smoke tobacco should be strongly encouraged to quit. Disease-modifying therapy has been shown to slow disease progression and disability; options include injectable agents, infusions, and oral medications targeting different sites in the inflammatory pathway. Symptom-based care is important to address the bowel and bladder dysfunction, depression, fatigue, movement disorders, and pain that often complicate MS.
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system and the most common cause of nontraumatic neurologic disability in young adults.1 Prevalence differs by latitude, with higher rates among those living further from the equator. The prevalence of MS is 40 per 100,000 people in Lubbock, Tex., compared with 191 per 100,000 people in Olmstead County, Minn.2 An estimated 1 million people in the United States live with MS.1 Risk factors include smoking and a history of infectious mononucleosis. Women are twice as likely as men to have MS, and there is a modest genetic influence.3,4
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| The 2017 McDonald Criteria should be used in the diagnosis of MS.25 | C | Clinical practice guideline |
| There is no difference in effectiveness between oral and intravenous steroids in treating acute relapses of MS.28,29 | A | Cochrane review and a separate systematic review and meta-analysis of good-quality clinical trials |
| Patients with MS who smoke tobacco should be encouraged to quit to decrease disability progression and development of secondary progressive MS.34,35 | B | Cohort study and cross-sectional study |
| Disease-modifying therapy should be initiated in patients with active MS.36,37 | A | Clinical practice guidelines supported by randomized controlled trials and systematic review and meta-analyses |
| Patients with MS benefit from a comprehensive program addressing overall wellness, symptom management, and comorbid mental health and physical conditions.38 | C | Clinical practice guideline |
A woman with MS diagnosed at 35 years of age has an average life expectancy of seven to eight years less than that of the general population. Because MS has a relatively high prevalence and patients have a long life span after diagnosis, many family physicians care for patients with the disease.5
Pathophysiology
Types of MS include relapsing-remitting (RRMS; most common), secondary progressive, and primary progressive (Table 16–13). There are also classifications for people with first episodes concerning for MS who do not meet the diagnostic criteria for MS (clinically isolated syndrome) and those with incidental radiologic findings concerning for MS in the absence of clinical symptoms (radiologically isolated syndrome).13
| Type | Disease course |
|---|---|
| Clinically isolated syndrome | First episode of symptoms characteristic of MS, with acute or subacute onset and lasting at least 24 hours; does not yet meet diagnostic criteria for MS; 80% of patients with clinically isolated syndrome and abnormal MRI findings progress to MS within 20 years compared with 20% of those with normal MRI findings |
| Radiologically isolated syndrome | Radiography shows evidence of inflammatory demyelination without clinical manifestations (i.e., incidental findings on radiography performed for other purposes); 30% to 40% of patients with radiologically isolated syndrome later meet criteria for clinically isolated syndrome or MS |
| Relapsing-remitting MS* | Episodes of acute neurologic dysfunction (relapses) followed by partial or complete improvement, with a stable clinical course between relapses; 85% of MS cases |
| Secondary progressive MS* | Progressive worsening of neurologic function following initial relapsing-remitting disease; acute exacerbations may occur during progressive phase; develops in 50% of patients with relapsing-remitting MS |
| Primary progressive MS* | Progressive worsening of neurologic function from onset of symptoms; acute exacerbations may also occur; 15% of MS cases |
MS is characterized by focal areas of inflammation, demyelination, gliosis (proliferation and activation of glial cells), and degeneration (axonal loss) secondary to immune-mediated attacks.10 There is debate about whether the inflammation leading to MS is initiated within or outside the central nervous system; however, T cells, B cells, macrophages (including central nervous system microglia), astrocytes, inflammatory mediators, and blood-brain barrier permeability are all involved in a response that is associated with myelin sheath destruction, axonal injury, and clinical symptoms.4,10,14–16 In RRMS, clinical lesions may resolve through mechanisms such as axonal changes, neuroplasticity, and remyelination.13 Progressive forms of MS are associated with cumulative axonal loss and increasing neurologic deficits.10
Clinical Presentation
Symptoms and signs of MS depend on the areas of neuronal involvement17 (Table 21,18–22). Common presenting symptoms include sensory disturbances, motor weakness, impaired gait, incoordination, optic neuritis (unilateral vision loss with pain worsened by extraocular movements), and Lhermitte sign (an electric shock–like sensation down the spine on neck flexion).18–20 Other symptoms include urinary, bowel, and sexual dysfunction.
| Cognitive dysfunction (e.g., learning, memory, processing speed) Decreased sensation (e.g., vibration, position, pain) Depressed mood Dysarthria Fatigue Focal sensory disturbances (e.g., numbness, tingling) Focal weakness Hearing loss or tinnitus Heat sensitivity | Lhermitte sign (an electric shock–like sensation down the spine on neck flexion) Motor disturbances (e.g., ataxia, imbalance, incoordination, tremor, weakness) Nystagmus Pain Sexual dysfunction (e.g., erectile dysfunction; problems with arousal, lubrication, pain, orgasm) Urinary or bowel disturbances Vertigo Visual disturbances (e.g., blurring, diplopia, optic neuritis) and defects |
Diagnosis
Multiple diseases may mimic MS clinically and radiologically (Table 3).13,18,23,24 The differential diagnosis includes genetic, infectious, inflammatory, metabolic, and neoplastic processes. Psychiatric diseases, ingestions, and nutritional deficiencies may also be mistaken for MS.13,18,23,24 Table 4 lists tests that may help differentiate MS from other diseases.18
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