ECTRMS: Family History Worsens MS Severity

PRAGUE, Czech Republic, Oct. 12 -- A multiple sclerosis patient who has close relatives with the disease is likely to suffer more severely than one without a family history, results of a brain imaging study show.

MS patients with a family history of the disease had significantly more brain lesions (P=0.006), brain atrophy (P=0.014), and other aspects of brain damage than patients with nonfamilial (or sporadic) disease, researchers reported here at the Congress of the European Committee for the Treatment and Research in Multiple Sclerosis.

"From the early 1980s onward, it was supposed that both genetic and environmental factors play a role in the etiology of MS," said Robert Zivadinov, M.D., Ph.D., of the State University of New York at Buffalo, and colleagues.

These findings suggest that genetics play a role not just in who will get the disease, as previous studies have shown, but also in how severe that disease will be, they said.

The researchers prospectively studied 759 consecutive MS patients seen at a single center. The patients ranged in age from 36 to 56, with an average disease duration of 13.6 years. The average disability score was 3.4 on a 10-point scale.

Among them, 478 had relapsing-remitting MS, 222 had secondary-progressive disease, 30 had primary-progressive MS, and 29 had experienced their first clinically isolated attack.

Overall, 26.1% of the patients (198) had a close relative with MS. For most, it was a parent, sibling, or child (81) or a first cousin (82). Another 35 patients had a second-degree relative -- an aunt, uncle, grandparent, niece, or nephew -- with MS.

Familial and sporadic cases did not differ significantly in average age, disease duration, disease course, Expanded Disability Status Scale score, or total lifetime use of disease-modifying drugs.

All patients underwent full clinical and quantitative magnetic resonance imaging (MRI) evaluation.

The researchers found that patients with a family history of MS had significantly higher T1-hypointense lesion volumes (3.3 mL versus 2.2, P=0.006) than non-familial cases, although T2-hypointense and gadolinium lesion volumes were not significantly different between groups.

Brain atrophy measures also indicated more severe disease in familial cases than in sporadic cases, despite similar clinical characteristics.

Normalized whole brain volume was significantly lower in familial versus sporadic cases (1458.3 mL versus 1478 mL, P=0.014). Likewise, patients with a family history of MS had lower normalized cortex volume (543.8 versus 553.9, P=0.036) and gray matter volume (729.8 versus 742.2, P=0.044).

Furthermore, a family history of MS in first-degree relatives was associated with significantly greater damage seen on MRI than a family history of MS in third-degree relatives. This was seen in higher T1-hypointense lesion volume (P=0.046) and a trend for lower normalized gray matter volume (P=0.07).

The researchers also measured magnetization transfer ratio as a measure of demyelination of nerve fibers.

All measures were similar between groups except for magnetization transfer ratio of T1-hypointense lesions (32.5 versus 33.9, P=0.049) and whole brain entropy (3.45 versus 3.22, P=0.03), which both were better for sporadic than familial cases.

Severity of MRI damage seen in familial cases was significantly correlated in a regression analysis with normalized whole brain volume (P=0.004), normalized cortex volume (P=0.01) and whole brain entropy (P=0.021).

"This study supports the hypothesis that familial and sporadic MS might have different disease severity characteristics that are related to the influence of some disease-modifying genes," Dr. Zivadinov and colleagues concluded.

However, they noted, further investigation is needed to determine the link with disease-modifying genes.