Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients

Axonal degeneration has been proposed as a cause of irreversible neurologic al disability in multiple sclerosis (MS) patients. The purpose of this stud y was to quantify axonal loss in spinal cord lesions from 5 paralyzed (Expa nded Disability Status Scale score r7.5) MS patients and to determine if ax onal number or volume correlated with levels of the neuronal marker N-acety l aspartate (NAA). Axonal loss in MS lesions ranged from 45 to 84% and aver aged 68%. NAA levels were significantly reduced (>50%) in cross sections of spinal cords containing MS lesions. Reduced NAA correlated with reduced ax onal numbers within lesion areas. In addition, NAA levels per axonal volume were significantly reduced in demyelinated axons (42%) and in myelinated a xons in normal-appearing white matter (30%). The data support axonal loss a s a major cause of irreversible neurological disability in paralyzed MS pat ients and indicate that reduced NAA as measured by magnetic resonance spect roscopy can reflect axonal loss and reduced NAA levels in demyelinated and myelinated axons.