Spinal cord axonal loss in multiple sclerosis: a post-mortem study

There is increasing interest in the contribution that axonal damage may mak e to clinical disability in multiple sclerosis (MS). The present study repo rts a post-mortem examination of the area occupied by the lateral white mat ter columns of the spinal cord and nerve fibre density in the corticospinal tracts at C-3 and T-2 in 23 males and 20 females with MS, who lacked plaqu es at these levels, and in 31 controls who, although most had had some neur ological disease, showed no sign of cervical or spinal cord thoracic diseas e. The lateral column cross-sectional area, measured by low power image ana lysis of the outlined lateral columns, was reduced in MS by 17% at C-3 and 21% at T-2 in males and by 13% at C-3 and 18% at T-2 in females. These redu ctions were significant at both levels in males (P < 0.004 at C-3 and P < 0 .009 at T-2 ) but only at T-2 in females (P < 0.03). The nerve fibre densit y, measured by automatic image analysis of x200 microscopic fields in the r egion occupied by the crossed pyramidal tracts, was reduced by 41% at C-3 a nd 42% at T-2 in males and by 19% at both C-3 and T-2 in females. These red uctions were likewise significant at both levels in males (P < 0.003 and P < 0.000 at C-3 and T-2 , respectively) and T-2 only in females (P < 0.045). In MS, nerve fibre density was significantly lower at C-3 (P < 0.004) and T-2 (P < 0.000) in males than females. No differences were seen in these pa rameters between males and females in controls. The reductions in total ner ve fibre densities were entirely accounted for by reductions in small nerve fibres (cross sectional area less than 5 mu m(2) ). No significant reducti ons were seen in large fibre (cross sectional area 5 mu m(2) or more) densi ties. It is concluded that substantial axonal loss and spinal cord lateral column white matter atrophy occur at C-3 and T-2 in MS, and that these chan ges can be detected in some patients from early in the course of the diseas e.