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Neurodegeneration in Multiple Sclerosis: Relationship to Neurological Disability

Departments of Neurosciences, The Cleveland Clinic Foundation Cleveland, Ohio

Richard M. Ransohoff

Departments of Neurosciences, Lerner Research Institute and the Mellen Center for Multiple Sclerosis Treatment and Research (RMR, RAR) The Cleveland Clinic Foundation Cleveland, Ohio

Elizabeth Fisher

Biomedical Engineering, The Cleveland Clinic Foundation Cleveland, Ohio

Richard A. Rudick

Departments of Neurosciences, Lerner Research Institute and the Mellen Center for Multiple Sclerosis Treatment and Research (RMR, RAR) The Cleveland Clinic Foundation Cleveland, Ohio

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Most MS patients follow a relapsing-remitting course (RR-MS) for 8 to 15 years that transforms into a secondary progressive disease course (SP-MS). In this review, we discuss current data that describe MS as a neurodegenerative disease in which axonal loss is the major cause of irreversible neurological disability in MS patients. Neurological deficits in MS patients have two pathogeneses: acute inflammatory demyelination and axonal degeneration. Disability caused by inflammatory demyelination clinically dominates the early stages of RR-MS and is reversible. Axonal transection occurs at sites of inflammation and begins at disease onset but is clinically silent in RR-MS because the CNS compensates for neuronal loss. Once a threshold of axon loss is ex ceeded, MS patients enter an irreversible secondary progressive stage. In SP-MS, axonal degeneration is caused by chronic demyelination and may be irreversibly progressive. This view of MS provides a concep tional framework that explains conversion of RR-MS to SP-MS and provides a rationale for early aggressive anti-inflammatory and neuroprotective therapies. NEUROSCIENTIST 5:48-57, 1999

Key Words: KEY WORDS Multiple Sclerosis • Brain atrophy • Axonal degeneration • Neuroprotection • Demyelination

The Neuroscientist, Vol. 5, No. 1, 48-57 (1999)
DOI: 10.1177/107385849900500107


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