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BOSTON -- Multiple sclerosis patients with larger intracranial volumes -- a measure of maximal lifetime brain growth (MLBG) -- scored better on cognition and physical function tests than those with smaller skull sizes, a researcher said here.

MLBG, unadjusted for body size or other factors except for sex, was predictive of PASAT-3 cognition scores with a delta-R² value of 0.066 (P<0.001) -- with larger volume correlated with higher scores -- in a cross-sectional study of 352 MS patients, according to , senior research scientist at the Kessler Foundation in West Orange, N.J.

Values for MLBG were also significantly associated with faster times on the 25-foot walk test and higher scores on a finger-tapping test, he said during a poster session at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting, held jointly this year with its North American counterpart.

Sumowski said MLBG -- simply the largest brain size a person achieves in life, normally in late adolescence or young adulthood -- may reflect what could be called "brain reserve." That is, a certain brain volume, which does not vary much between individuals irrespective of their body size, is necessary for normal cognitive and neurophysical function.

Anything above that is a "reserve" that allows a person to continue to function without disability in the face of inevitable atrophy. But when brain volume declines below this threshold, clinical disability becomes manifest, he suggested.

The current study is the first to link brain reserve to physical motor function as well as cognition, Sumowski said.

"This is looking at brain reserve, so it actually had an effect on physical parameters, like mobility," said , who did not participate directly in the study but is the senior vice president for research at the Kessler Foundation. "It's a genetic perspective on how to predict decline in MS."

Sumowski and colleagues used a 3D T1 fast field echo to measure intracranial volume and normalized volumes of the total brain, grey matter, white matter, deep grey matter, and the thalamus. The researchers also quantified T2 lesion volume.

Disabilities were assessed by using a 25-foot walk, a nine-hole peg test, and the PASAT-3 (Paced Auditory Serial Addition Test, part of the Multiple Sclerosis Functional Composite scale) for cognitive results.

Patients included 255 with relapsing-remitting MS and 97 with secondary progressive disease. Mean age was 42 (SD 11) and about two-thirds were women. Mean disease duration was 13.5 years (SD 8.4). Participants scored a median of 2.5 and a mean of 3.2 (SD 2.0) on the Expanded Disability Status Scale.

MLBG correlated with finger-tapping scores with a delta-R² value of 0.060 (P<0.001); it predicted faster 25-foot walk times with a delta-R² value of 0.040 (P=0.01). It was not predictive of scores on the nine-hole peg test, however.

Other factors correlated with these outcome measures included age, sex, education, disease duration, and volumes of T2 lesions, thalamus, gray matter, and deep gray matter.

"This may help us understand another way in which susceptibility to progression in the disease is determined and further helps to motivate approaches for neurorehabilitation -- use it or lose it," said , professor of clinical neuroscience at Imperial College in London, who was not associated with the study.

Sumowski said that the results could be useful for trials and in clinics. "This has implications for predicting disability by using intracranial volume to identify people who are at greater risk," he told MedPage Today.

But ultimately MLBG might be a relatively small factor in determining the extent of disability, said Matthews in an email.

"Limiting progression of the disease itself by controlling inflammation still is the more powerful approach we have to limiting future disability," he said.

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