Early Axonal Injury in Multiple Sclerosis

Abstract & Commentary

Source: Filippi M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003;126:433-437.

Filippi and colleagues performed conventional brain MRIs and whole-brain N-acetylaspartate (WBNAA) measurements with proton magnetic resonance spectroscopy in 31 patients presenting with clinically isolated syndromes suggestive of multiple sclerosis (MS). This was compared with 16 normal controls. Patients were rescanned by conventional MRI 4-6 months later to detect dissemination of lesions in time. The average WBNAA concentration was significantly lower (P < .0001) in this early MS population (10.09, SE 0.43) compared to controls (12.98, SE 0.58). The reduction in WBNAA in MS patients did not correlate with other brain MRI parameters, such as gadolinium enhancement, T2 lesion load, brain atrophy, or dissemination of lesions. Based on this 20% reduction in WBNAA in early MS patients, Filippi et al concluded that axonal and neuronal injury occurs early in the course of MS, somewhat independent of the more obvious MRI measurements.

Commentary

It is unclear what such sensitive measures of WBNAA at early stages of MS truly reflect about brain pathology (ie, axonal transection with cell death vs impaired neuronal physiology with mitochondrial dysregulation). Some simple questions were not addressed in this study. How did WBNAA measures vary over time? How were they affected by corticosteroid or interferon-beta treatment? Are WBNAA changes seen in "pure" spinal or optic nerve forms of demyelination (ie, the monosymptomatic transverse myelitis or optic neuritis patient)? If WBNAA measures are obtained on "normal" individuals with a strong family pedigree for MS, what is the earliest discernable alteration that can be detected—perhaps many years before more obvious clinical or paraclinical measures evolve? It remains to be seen what this sensitive brain spectroscopy measure clearly reflects about early brain pathology in MS, but it supports the concept of early treatment intervention. — Brian R. Apatoff

Dr. Apatoff is Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus.