Kate Johnson

June 07, 2011

June 7, 2011 (Montreal, Quebec, Canada) — Fatigue is a solitary symptom in almost one third of patients who go on to develop multiple sclerosis (MS), sometimes years later, according to a study presented here at the annual meeting of the Consortium of Multiple Sclerosis Centers.

"A careful history and physical examination for features suggestive of multiple sclerosis is mandated in any patient presenting with unexplained fatigue," concluded Joseph R. Berger, MD, professor and chairman of the Department of Neurology and Director of the Multiple Sclerosis Clinic and the Neuro-AIDS Program at the University of Kentucky College of Medicine in Lexington, Kentucky.

Claims Data

The study used claims data from the MS Marketscan Database to identify patients with clinically definite MS, defined as 2 or more MS claims (International Classification of Diseases, 9th revision [ICD-9], diagnostic code 340); or 1 MS claim plus a prescription claim for disease-modifying therapy.

For each patient, the 3 years preceding the index MS claim were analyzed for diagnoses of chronic fatigue syndrome or malaise (ICD-9 diagnostic codes 780.71 or 780.79), as well as fatigue-related prescriptions, other diagnoses, and MS-associated symptoms.

A total of 5305 patients were identified with an index MS claim made between January 1, 2005, and September 30, 2009. Three quarters of the patients were female, and "an overwhelming majority" (67%) were between the ages of 40 and 59 years, said Dr. Berger.

In 1534 (29%) of the identified patients, at least 1 diagnosis of fatigue or malaise preceded their MS diagnosis, and 42% presented with more than 2 such claims.

"To me that's somewhat astonishing because I seldom put fatigue down as a diagnostic code, and I suspect that's true of many of us," said Dr. Berger. "So my belief is that this is probably an under-representation of the number of people that actually have fatigue in advance of the diagnosis of clinically definite MS."

… my belief is that this is probably an under-representation of the number of people that actually have fatigue in advance of the diagnosis of clinically definite MS.

Among those with a diagnosis of fatigue or malaise, a third received the diagnosis 2 to 3 years before their MS diagnosis, and a quarter received it 1 to 2 years before. For the remainder, the fatigue diagnosis came within the year leading up to the diagnosis of MS.

One third of patients with fatigue/malaise had no other neurologic symptoms suggestive of MS, and 38% of the patients with a cluster of symptoms had fatigue present as the first symptom in the cluster. Other symptoms included visual and movement disorders, muscle and speech disorders, facial neuralgia, dizziness, paralysis, and disturbance of skin sensation.

Although fatigue preceded the diagnosis of MS by an average of 501 days, only 10% of patients received such medications as amantadine, pemoline, modafinil, dexamphetamine, methylphenidate, or dextroamphetamine, said Dr. Berger.

A Unique Precursor?

Mark S. Freedman, MD, professor and director of Multiple Sclerosis Research at the University of Ottawa in Ottawa, Ontario, Canada, was somewhat cautious in interpreting these results.

"I think he’s probably right, I think the data is tantalizing, but the simple question is, how common is the diagnosis of fatigue in the general population?" he told Medscape Medical News. "It’s probably an extremely common complaint. Without that denominator it is hard to say that fatigue is a unique precursor to MS."

"I think fatigue probably does predate MS…but when it becomes the debilitating fatigue that he described — I have a hard time believing it reaches that stage without all the other evidence of MS."

Dr. Berger has received consulting fees from Asphelia, Astellas, Bayer, Biogen Idec, Genentech, GlaxoSmithKline, Millenium, Pfizer, and Perseid; honoraria from Bayer, Biogen Idec, Teva, and EMD Serono; and other financial benefits from EMD Serono, Bayer, and Biogen Idec. Dr. Berger’s coauthors are employees of Bayer HealthCare Pharmaceuticals. Dr. Freedman has received consulting fees from Biogen Idec, Bayer HealthCare, Celgene, Sanofi-Aventis, Novartis, Merck Serono, and Genzyme. He is also an uncompensated member of the editorial advisory board for Medscape.

The 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers. Abstract #18. Presented June 2, 2011.

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