Current issues of ACP Journal Club are published in Annals of Internal Medicine


Younger age, paresthesia at onset, and remitting clinical course predicted longer survival in multiple sclerosis

ACP J Club. 1995 Nov-Dec;123:75. doi:10.7326/ACPJC-1995-123-3-075

Source Citation

Midgard R, Albrektsen G, Riise T, Kvåle G, Nyland H. Prognostic factors for survival in multiple sclerosis: a longitudinal, population based study in Møre and Romsdal, Norway. J Neurol Neurosurg Psychiatr. 1995 Apr;58:417-21.



To determine the effect of multiple sclerosis (MS) on survival, with specific attention to age at onset, sex, initial clinical course, and initial symptoms.


Inception cohort followed for a mean of 18.1 years.


Community-based study in Norway.


251 patients (141 women) had onset of MS between 1950 and 1984. Patients were classified according to the McAlpine clinical criteria as definite (n = 142), probable (n = 43), and possible (n = 66) MS and were grouped according to clinical course as remitting or primary progressive.

Assessment of prognostic factors

Age at onset of disease, age at diagnosis, clinical manifestations (including optic neuritis, diplopia, vertigo, ataxia, dysarthria, paresthesia, motor weakness, and bladder dysfunction), and clinical course were assessed using the primary clinical records of local general practitioners and attending neurologists and the patient files of county hospitals, the local MS society, the national insurance administration, and the government statistics department.

Main outcome measures

Total and MS-specific mortality.

Main results

Univariate analysis for total mortality showed a longer survival in women (hazard ratio [HR] 0.50, 95% CI 0.28 to 0.87) and in patients with paresthesia at onset (HR 0.37, CI 0.20 to 0.67) and a shorter survival in patients with a progressive clinical course (HR 3.60, CI 1.87 to 7.11), in patients with ataxia at onset (HR 1.77, CI 1.01 to 3.09), and in older patients (HR 1.07, CI 1.04 to 1.10). The same factors were associated with MS-specific mortality. Patients classified as possible MS were excluded from the multivariate analysis. Risk factors associated with shorter survival for total mortality were progressive clinical course (adjusted HR 3.44, CI 1.68 to 7.06) and older age at onset (adjusted HR 1.06, CI 1.03 to 1.09); paresthesia at onset was associated with longer survival (adjusted HR 0.46, CI 0.24 to 0.87). The same factors were associated with MS-specific mortality.


Remitting course of disease, paresthesia at onset, and younger age at onset were the strongest predictors for longer survival in a cohort of patients with multiple sclerosis.

Sources of funding: Norwegian MS Society; Odd Fellow Order; Legacy of Ingrid and Fritz Nilsen; Norwegian Research Council for Science and the Humanities.

For article reprint: Dr. R. Midgard, Department of Neurology, Molde Hospital, N-6407, Molde, Norway. FAX 47-7121-7021.


Patients with MS face a lifetime of uncertainty. Most are told that their prognosis depends on their ability to recover from repeated attacks of the disease and that continued progression may develop later in the course of their illness. Neurologists and MS clinical trialists are cognizant of the need to identify patients at risk for severe disability so that these patients can be considered for early intervention with experimental treatments.

Midgard and colleagues have confirmed that several clinical features identifiable at or shortly after onset of MS influence survival. This supports previous observations that male sex, older age at onset, progressive disease, and cerebellar dysfunction worsen prognosis and that relapsing patients with MS who have initial sensory dysfunction may have a more benign disease course. Because most deaths from MS result from advanced chronic disability and not from acute attacks of the disease, it is not surprising that measures of advanced disability and mortality have similar predictors.

The finding of increasing mortality in recent decades and the marked difference in the numbers of patients identified by decade suggest that ascertainment was incomplete in the past. Suicide was not addressed in this study (1). Crude mortality rate and age- and sex-adjusted mortality rate were not reported and, therefore, the authors' experience cannot be compared with that in other series (2).

New therapies favorably alter the natural history of this disease. If so, men with MS and all persons with ataxia or progressive disease may be uniquely targeted for early intervention with these therapies.

John Noseworthy, MD
Brian Weinshenker, MDMayo Clinic and Mayo Medical SchoolRochester, Minnesota, USA


1. Sadovnick AD, Ebers GC, Wilson RW, Paty DW. Life expectancy in patients attending multiple sclerosis clinics. Neurology. 1992;42:991-4.

2. Bronnum-Hansen H, Koch-Henriksen N, Hyllested K. Survival of patients with multiple sclerosis in Denmark: a nationwide, long-term epidemiologic survey. Neurology. 1994;44:1901-7.