Familial multiple sclerosis appears more severe than non-familial

Magnetic resonance images (MRI) of a large group of patients with multiple sclerosis has provided the first evidence that those with a history of MS in their families show more severe brain damage than patients who have no close relatives with the disease.

The results, based on brain MRIs of 759 consecutive MS patients, support the hypothesis that a patient's genetic make-up plays a role not only in development but also in severity of the disease.

A University at Buffalo team of neurologists and imaging experts headed by Robert Zivadinov, M.D., Ph.D., professor of neurology, conducted the research at the Buffalo Neuroimaging Analysis Center (BNAC), which Zivadinov directs. The BNAC is an arm of the Jacobs Neurology Institute, UB's Department of Neurology in the School of Medicine and Biomedical Sciences. Patients were recruited at the Baird MS Center, also part of the Jacobs Neurological Institute.

The research findings were presented at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis in Prague, Czech Republic.

"From the early 1980s on," said Zivadinov, "MS researchers thought that genetic factors likely played a role in the disease, that its traits were determined by several different genes, and our findings support this hypothesis.

"Our MRI analysis showed a difference between the severity of disease characteristics in familial MS patients versus what we call sporadic, or non-familial, MS patients," he said. "These differences may be related to some disease-modifying genes, but to prove this, we must do further investigation."

MS destroys myelin, the fatty sheath that protects nerve fibers carrying message traffic from various muscles to and from the central nervous system. For reasons currently unknown, in some people the myelin sheath breaks down, resulting in destruction of the nerve fibers and the symptoms of MS.

This demyelization process leads to mild to serious disability, from slight numbness of the limbs to loss of vision and paralysis.

The cohort of 759 patients involved in the study ranged in age from 36-56, with an average disability score of 3.4 on a scale of 0-10. A higher number indicates more disability.

Of these patients, 478 had relapsing-remitting MS, involving acute attacks with full or partial recovery; 222 had secondary-progressive MS, characterized by occasional attacks and sustained progression; 30 had primary-progressive MS with steady worsening from onset, and 29 had experienced their first attack.

Twenty-six percent, or 198, had a positive family history of MS. The breakdown between first-, second- or third-degree relatives with MS was 81/35/82. All patients obtained full clinical and quantitative MRI evaluations.

Using MRI, researchers measured the number and volume of lesions (plaques), which represent areas of demeylination; atrophy of the whole brain, white matter (the neural pathways), grey matter (brain regions) and the cortex, as well as employing additional imaging techniques.

There were no significant differences between familial and sporadic cases based on age, disease duration, disease course, disability score and total lifetime use of disease-modifying drugs.

Analysis showed that compared to patients with no family history of MS, familial MS patients had significantly more destructed lesions, and significantly lower volume of whole brain, white matter and gray matter, as well as other indications of greater brain degradation.

"Patients whose parents, children or siblings [first-degree relatives] had MS showed more damage than patients who had cousins with MS," Zivadinov said. "This indicates that the closer the relationship, the greater the risk of MS.

"Of particular interest is the finding of more severe gray matter damage and more lesions, particularly in those with MS in first-degree relatives. These findings are very interesting and we will be investigating them further."

Additional researchers on the study from the BNAC and the JNI, were Frederick E. Munschauer, M.D., Nadir Abdelrahman, M.D., Sara Hussein, Jackie Durfee, Barbara E. Teter, Ph.D., David Hojnacki, M.D., Michael G. Dwyer, Jennifer L. Cox, Ph.D., Marlieke De Brujin, Milena Stosic, M.D., Fernando Nussenbaum and Bianca Weinstock-Guttman, M.D.

Murali Ramanathan, Ph.D., from the UB School of Pharmacy and Pharmaceutical Sciences, also contributed to the research.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The School of Medicine and Biomedical Sciences and School of Pharmacy and Pharmaceutical Sciences are two of five schools that constitute UB's Academic Health Center. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

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