The Role of Functional Plasticity and Adaptive Reorganization in the Multiple Sclerosis Disease Process

Multiple sclerosis (MS) is a heterogeneous disorder in several respects. The initial presentation of symptoms and signs, the clinical course of the disease, and its pathology can vary widely from patient to patient. There is growing evidence that MS is characterized by features other than the classic focal T2 lesions. These include diffuse damage to the gray matter and deleterious effects on the spinal cord. However, the brain has an extraordinary capacity for recovery from various disease states, including MS, and from trauma.

Maria Rocca, MD, is a faculty member in the Department of Neurology, and Professor of Clinical Neurology, at the Università Vita-Salute San Raffaele, Milan, Italy. She spoke at the Plenary Session on March 20^th, at the American Academy of Neurology (AAN) 2013 Annual Meeting, on the topic of “Functional Plasticity in MS.”

Rocca’s presentation focused on the role of functional plasticity and adaptive reorganization in the multiple sclerosis disease process. Cortical reorganization leads to recovery of function and, subsequently, clinical improvement and recovery. There may be maladaptive reorganization as is seen, for example, in association with fatigue in MS. Cortical recruitment tends to be more bilateral in MS patients compared to controls. Research has shown that there may be an impaired functional reserve, as well as within-network abnormalities and inter-network abnormalities in MS. Rocca alluded to her research into default-mode network (DMN) dysfunction and its association with cognitive impairment in patients with progressive MS. Conversely, several studies, including work by Rocca and her colleagues, have shown that training patients in cognitive (or other) functional activities appears to induce restoration of the DMN in the cerebral cortex.

Rocca used an individual female patient’s case history to illustrate several clinical points. She and her colleagues were fortunate to be able to perform quantitative functional MRI (fMRI) scans on this patient. Modern fMRI is a sophisticated technique allowing the brain to be scanned dynamically, following some conscious activity on the part of the patient, such as simple (or complex) standardized hand movements. This procedure was followed by a conventional MRI carried out at the same resolution. Rocca said that certain brain activity associated with the patient’s movements indicated recruitment from unaffected areas.

After the initial episode, the patient’s clinical condition remained stable for several years until she developed optical neuritis. Inflammation of the optic nerve and other changes were observed. The patient achieved a complete recovery after being put on steroids. From the course of this patient’s disease, a diagnosis of relapsing MS was made.

Rocca summed up her talk by observing that functional plasticity is a common phenomenon in diseases of the brain, including MS. There is variability in cortical rewiring and maladaptive plasticity may result in deterioration of the patient’s condition. With the increasing understanding of these mechanisms, Rocca said she looks forward to the development of new treatments which might enable intervention in these processes.