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  • Updated 08.08.2023
  • Released 10.23.2014
  • Expires For CME 08.08.2026

Multiple sclerosis: presentation and course



Multiple sclerosis affects every part of the neuraxis and has replaced syphilis as the great mimicker in neurology. In this article, the author describes the entire spectrum of multiple sclerosis signs and symptoms, focal and diffuse brain lesions, look-alike diseases, the overactive immune response, the complex pathology of demyelination, death and dysfunction of oligodendroglia and neurons, MRI and CSF abnormalities, the effects of vitamin D, and other comorbidities in multiple sclerosis. This update contains new comments on the 2017 revised diagnostic criteria, the evolving understanding of the demographics of and racial differences in multiple sclerosis, the recently identified prodromal state, and the increasingly well-characterized demyelinating disease myelin oligodendrocyte glycoprotein, as well as more minor updates.

Key points

• The incidence of multiple sclerosis is increasing around the world.

• Although historically considered primarily a disease of white young and middle-aged females, those of African ancestry in the United States carry a higher risk of developing multiple sclerosis and appear to experience a particularly aggressive disease course (269)

• Multiple sclerosis lesions cause focal neurologic deficits. Problems with fatigue, cognition, and bladder control are common but often overlooked.

• Diagnosis is complex and requires neurologic history, clinical and MRI examination, and sometimes spinal fluid and evoked potential analysis.

• Demyelinating diseases that mimic multiple sclerosis include neuromyelitis optica, CNS Sjögren syndrome, and myelin oligodendrocyte glycoprotein antibody disease, as well as many other toxic, inflammatory, and metabolic disorders.

• The impact of COVID-19 infection on persons with multiple sclerosis.

Historical note and terminology

Greek and Roman physicians did not document multiple sclerosis, but it may have been mentioned in 13th century Icelandic sagas. Saint Lidwina of Holland appears to have developed multiple sclerosis in 1396 (170). The court physician was not optimistic after examining Lidwina, stating, "Believe me, there is no cure for this illness; it comes directly from God. Even Hippocrates and Gallenus would not be of any help here." The clinical description and prognosis of multiple sclerosis have improved in the intervening 500 years, but progress in understanding its etiology is debatable.

Elizabeth Foster of Coldingham, north of the Scottish/English/North Sea border, developed intermittent paralysis, sensory symptoms, and possible optic neuritis starting in 1742 at age 18 (156). Multiple sclerosis was clearly depicted in 1822 in the diary of Sir Augustus D' Este, grandson of King George III of England (76). One of his relapses is portrayed here:

At Florence, I began to suffer from a confusion of sight. About the 6th of November, the malady increased to the extent of my seeing all objects double. Each eye had its separate visions. Dr. Kissock supposed bile to be the cause. I was twice blooded from the temple by leeches. Purges were administered. One Vomit and twice I lost blood from the arm. The Malady in my eyes abated, again I saw all object naturally in their single state. I was able to go out and walk” (175).

Cruveilhier in Paris and Carswell in London illustrated CNS plaques and sclerosis in the 1840s, and Charcot characterized the demyelination in plaques and published detailed clinical descriptions of the disease. Rindfleisch described the perivascular inflammatory CNS lesions in the 1860s (42). These observers documented the intermittent and seemingly random neurologic symptoms of multiple sclerosis and the variable evolution of the disease. The history of multiple sclerosis is extensively reviewed by Murray (175).

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