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Key Clinical Updates in Multiple Sclerosis

Patients without a typical clinical attack may be diagnosed with radiologically isolated syndrome if a brain MRI incidentally demonstrates findings consistent with multiple sclerosis. Teriflunomide and dimethyl fumarate were shown to delay time to first clinical attack compared to placebo in such patients.

Lebrun-Frénay C et al. JAMA Neurol. [PMID: 37603328]

Okuda DT et al. Ann Neurol. [PMID: 36401339]

ESSENTIALS OF DIAGNOSIS

  • Episodic neurologic symptoms.

  • Patient usually < 55 years of age at onset.

  • Single pathologic lesion cannot explain clinical findings.

  • Multiple foci best visualized by MRI.

GENERAL CONSIDERATIONS

This common neurologic disorder, which probably has an autoimmune basis, has its greatest incidence in young adults. Epidemiologic studies indicate that multiple sclerosis is much more common in persons who live in temperate zones. Environmental factors hypothesized to increase risk for multiple sclerosis include reduced sunlight exposure, low vitamin D level, and infection with Epstein-Barr virus. A genetic susceptibility to the disease is present. Pathologically, focal—often perivenular—areas of demyelination with reactive gliosis (fibrous proliferation of glial cells in injured areas of the CNS) are found scattered in the white matter of the brain and spinal cord and in the optic nerves. Axonal damage also occurs.

CLINICAL FINDINGS

A. Symptoms and Signs

The common initial presentation is weakness, numbness, tingling, or unsteadiness in a limb; spastic paraparesis; retrobulbar optic neuritis; diplopia; dysequilibrium; or a sphincter disturbance such as urinary urgency or hesitancy. Symptoms may disappear after a few days or weeks, although examination often reveals a residual deficit (eFigure 26–13).

eFigure 26–13.

Bilateral internuclear ophthalmoplegia due to multiple sclerosis. (A) Reduced adduction of the left eye on rightward gaze. (B) Reduced adduction of the right eye on leftward gaze. (Reproduced with permission from Riordan-Eva P, Augsburger JJ. Vaughan & Asbury's General Ophthalmology, 19th ed. McGraw Hill, 2018.)

Several forms of the disease are recognized. In most patients, there is an interval of months or years after the initial episode before new symptoms develop or the original ones recur (relapsing-remitting disease). Eventually, however, relapses and usually incomplete remissions lead to increasing disability, with weakness, spasticity, and ataxia of the limbs, impaired vision, and urinary incontinence. The findings on examination at this stage commonly include optic atrophy; nystagmus; dysarthria; and pyramidal, sensory, or cerebellar deficits in some or all of the limbs. In some of these patients, the clinical course changes so that a steady deterioration occurs, unrelated to acute relapses (secondary progressive disease). Less commonly, symptoms are steadily progressive from their onset, and disability develops at a relatively early stage (primary progressive disease). The diagnosis cannot be made with confidence unless the total clinical ...

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