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Clinically Isolated Syndromes in Multiple Sclerosis

By Edited Jun 13, 2016 0 0

Multiple sclerosis is a relatively common chronic nervous system disease that can have serious sequelae. It likely autoimmune in origin, where proteins called antibodies attack other cells in the body. Younger adults, typically females, are often more likely to be affected. Multiple sclerosis also tends to affect those of European lineage and those living in cooler climates. Symptoms of multiple sclerosis can include fatigue, weakness, numbness, tingling, optic neuritis, double vision, and urinary incontinence. They often occur in "attacks," which resolve.


Multiple sclerosis can be diagnosed using a combination of clinical symptoms, imaging with Magnetic Resonance Imaging (MRI), and analysis of cerebral spinal fluid that is obtained by a spinal tap. Sometimes, the diagnosis, especially in the early stages of multiple sclerosis, is not always clear. For example, a patient may experience an attack but not have enough findings on MRI to meet criteria for diagnosis. This is called a clinically isolated syndrome. Similarly, a patient may have no symptoms but have findings on MRI suggestive of multiple sclerosis. This is called a radiologically isolated syndrome. It is important to identify these patients since early treatment is thought to be beneficial.

Radiologically Isolated Syndrome

MRI findings that are suggestive of multiple sclerosis include circular white lesions that are commonly seen around the ventricles of the brain and the spinal cord. In a 2009 study by Lebrun et. al., 5.2 years after discovery of these lesions, 33% of patients began having clinical symptoms of multiple sclerosis.

Acute Transverse Myelitis

This clinically isolated syndrome is an inflammatory disorder that can present as symmetric or asymmetric involvement of the spinal cord. Symptoms include rapid-onset weakness, sensory alterations, bowel dysfunction, or bladder dysfunction. If both sides of the body are affected, there is a 5-10% risk of progression to multiple sclerosis. If only one side is affected, there is a larger risk of 10-30%. If one side is affected, and there are MRI findings, the risk of progression is 60-90% in 3-5 years.

Optic Neuritis

Optic neuritis is also an inflammatory condition that can cause sudden painful but transient vision loss in one eye. This symptom is highly associated with multiple sclerosis. In the 1997 Optic Neuritis Treatment Trial (ONTT), 30% of people with an episode of optic neuritis developed multiple sclerosis after five years. 40% developed it after twelve years.

Treatment for Clinically Isolated Syndromes

  • β-interferons - Data from the CHAMPS, ETOMS, and BENEFIT trials show that these delay the occurence of a second attack for up to five years
  • Glatiramer acetate - In the PreCISe trial, treatment with glatiramer acetate prolonged the time to conversion and reduced the frequency of conversion to multiple sclerosis
  • IVIG - This is intravenous immunotherapy that also decreases the probability of converting to multiple sclerosis.

Although early treatment may delay the onset of multiple sclerosis, it is unknown if early treatment prevents long-term disability. For the radiologically isolated syndrome, there is no indication for disease-modifying treatment.


For the clinically isolated syndrome, the first step toward diagnosis is to get an MRI. If abnormal, it is recommended to start therapy. If normal, an MRI should be repeated in three to six months. If abnormal, therapy should be started. However, if this second MRI is normal, no further work-up is indicated.


•Hauser Stephen L, Goodin Douglas S, "Chapter 375. Multiple Sclerosis and Other Demyelinating Diseases" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2906445.
•Lebrun C, Bensa C, Debouverie M, Wiertlevski S, Brassat D, de Seze J, Rumbach L, Pelletier J, Labauge P, Brochet B, Tourbah A, Clavelou P, Club Francophone de la Sclerose en Plaques. “Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients.”(2009) Arch. Neurol. 66(7): 841-6.
•Miller D, Barkhof F, Montalban X, Thompson A, and Filippi M. (2005). “Clinically isolated syndromes suggestive of multiple sclerosis, part 1: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol. 4(5): 281-8.
•Miller D, Barkhof F, Montalban X, Thompson A, and Filippi M. (2005). “Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management. Lancet Neurol. 4(6): 341-8.
•"Multiple Sclerosis." Quick Answers to Medical Diagnosis and Therapy: http://www.accessmedicine.com/quickam.aspx.
•Olek, MJ. “Clinically isolated syndromes suggestive of multiple sclerosis.” UptoDate, last updated Jun 2011.
•Olek, MJ. “Diagnosis of multiple sclerosis in adults.” UptoDate, last updated Jun 2011.
•“The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial. Optic Neuritis Study Group.” (1997). Neurology. 49(5):1404-13.


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