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, and MRI and CSF abnormalities. This revision includes new comments on clinical symptoms and on effects of vitamin D and other comorbidities in multiple sclerosis.
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• The incidence of multiple sclerosis is increasing around the world.
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• Multiple sclerosis lesions cause focal neurologic deficits. Problems with fatigue, cognition, and bladder control are common but often overlooked.
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• Diagnosis is complex and requires neurologic history, clinical and MRI examination, and sometimes spinal fluid and evoked potential analysis.
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• Demyelinating diseases that mimic multiple sclerosis include neuromyelitis optica and CNS Sjögren’s syndrome as well as many other toxic, inflammatory, and metabolic disorders.
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 (155). 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 (143). Multiple sclerosis was clearly depicted in 1822 in the diary of Sir Augustus D' Este, grandson of King George III of England (72). One of his relapses is portrayed here:
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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” (160).
Cruveilhier in Paris and Carswell in London clearly illustrated central nervous system plaques and sclerosis in the 1840s. Charcot published detailed clinical descriptions and characterized the demyelination in plaques, and Rindfleisch described the perivascular inflammatory CNS lesions in the 1860s (40). 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 (160).