TORONTO—Recent fMRI studies have shown altered cortical activation during cognitive tasks in patients with multiple sclerosis (MS), changes that appear to be adaptive responses to brain damage. Evidence of such neuroplastic changes at least opens the door for potentially stimulating recovery of function and creating new rehabilitation strategies for patients with MS, according to Robert K. Shin, MD.

“We’re making a lot of progress in terms of reducing attacks and reducing disability, but many of our patients still have attacks,” said Dr. Shin. “The question is, are there ways we can help them recover their function?” Dr. Shin is an Assistant Professor of Neurology and Ophthalmology at the University of Maryland School of Medicine in Baltimore. He addressed the 18th Annual Meeting of the Consortium of Multiple Sclerosis Centers.

Simply put, neuroplasticity refers to the brain’s ability to reorganize in response to injury, and “for a long time, we really didn’t think the brain had this capability,” said Dr. Shin. “But now there’s been an increasing understanding that that’s not true, that actually the brain can adapt, it can react.”

Dr. Shin said that particularly early on in the course of MS, patients will have an attack but will then improve afterward. Yet at the same time, these patients are also losing brain tissue. “As N-acetylaspartate goes down, brain volume decreases gradually over time,” he said. “The question you might ask yourself is, if the brain seems to be continually losing neurons, why do we get this relapsing-remitting course? Also, why, when you look at some of the brain MRIs, does the number of lesions or how bad it looks not necessarily correlate with how badly the patient is doing clinically? Is the brain somehow compensating for the injuries that are occurring in MS? Perhaps this is why you have preservation of function, despite progression on an MRI.”

THE CASE FOR CORTICAL PLASTICITY

Dr. Shin related the example of a 39-year-old woman who developed right hemiparesis from a relapse of MS. She became plegic but soon recovered. Reddy et al concluded that her improvement and the progressive reduction of her abnormally large fMRI cortical activation with movement demonstrated that dynamic reorganization of the motor cortex accompanied remission of MS.

Initially, as the patient got stronger, her contralateral activation became more robust, noted Dr. Shin. “In six months, the patient had fully recovered functionally, and the activation really wasn’t quite as robust as it was during that recovery period,” he said. “But an interesting phenomenon is that we are seeing changes in functional imaging in a patient with a brain lesion. Activation in the other hemisphere when she was asked to move her completely normal left hand was sort of as you would expect, and actually that didn’t change over the course of the study. It raises the possibility that there’s actually more of a dynamic cortical response than maybe we’re used to thinking of, not just in MS. There was also ipsilateral activation—the activation seemed to decrease as the patient recovered.”

Similarly, in 2003, Rocca and colleagues followed 16 patients with a clinically isolated syndrome suggestive of MS. The patients were compared with 15 age- and sex-matched controls during a finger flexion task. The patients had more significant activations of the contralateral primary somatomotor cortex, secondary somatosensory cortex, and inferior frontal gyrus.

Dr. Shin pointed out that in patients with relatively little evidence of brain damage, the activation is not much different from that in a healthy control. “But as there seems to be more evidence of general brain damage,” he said, “the activation that is seen during this simple motor task is increased. So again, is the brain responding to cortical pathology? Even when an MS patient has his or her first episode, there can already be evidence that there has been loss of neurons. The increase in activation seemed to correlate with that—the worse the brain seemed to be doing, the more activation was seen with the simple motor task.”

THE OPTIC NEURITIS IRONY

Optic neuritis is a common presenting complaint in MS, noted Dr. Shin. “You almost always get better from your optic neuritis,” he said. “Even when these patients get their vision back, they often continue to have delayed visual evoked potentials.... So it seems kind of a strange phenomenon—someone has optic neuritis, his or her vision gets better, yet by all of our other indicators, the optic nerve is worse. What’s going on? Is the brain actually somehow compensating with this impaired function in the optic nerve?”

Earlier this year, Mainero and colleagues used fMRI to look at attention and memory in patients with MS. “For a long time, this was not appreciated, that MS patients have cognitive functioning even early on in the course of disease,” Dr. Shin remarked. In a study of 22 patients with relapsing-remitting MS and controls, the investigators showed that patients exhibited significantly greater brain activation than did controls and recruited additional brain areas. “Overall, the average MS patient was still performing pretty well, close to normal,” said Dr. Shin.

“What I think is interesting about these functional studies is that [activation shown on] fMRI seems to be altered in MS patients, even those who are performing normally,” said Dr. Shin. “One argument would be that these are adaptive changes made in order to maintain function, which might go some way to explain the mystery of why patients with MS can do well for a while before they seem to decompensate in the later stages.”

STRATEGIES FOR REHABILITATION

Overall, rehabilitation of patients with MS is an area that has been somewhat neglected, according to Dr. Shin. In addition, he believes that proprioceptive stimulation, neurotrophic factors, and increased neurotransmitter release are potential means of enhancing cortical plasticity and are worthy of further research. “[Rehabilitation] is a fruitful area that we can look into,” he commented. “If there is evidence of adaptive changes, are there ways we could enhance that? It is very important to do what we are doing. We are preventing relapses; we are preventing disability. But we don’t have a 100% cure, so we are still going to have patients with disability.... Is there any way we can identify patients who might respond better to rehabilitation efforts than others? If you believe that these data show cortical plasticity, can this be enhanced? This is an area that is underresearched now but an area that we will hopefully see a lot more of in the future.”

NR

—Colby Stong

Suggested Reading
Mainero C, Caramia F, Pozzilli C, et al. fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage. 2004;21:858-867.
Reddy H, Narayanan S, Matthews PM, et al. Relating axonal injury to functional recovery in MS. Neurology. 2000;54:236-239.
Rocca MA, Mezzapesa DM, Falini A, et al. Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage. 2003;18:847-855.
Werring DJ, Bullmore ET, Toosy AT, et al. Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation. J Neurol Neurosurg Psychiatry. 2000;68:441-449.

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