Objectives
To test the hypothesis that irrecoverable Neurological deficit in Multiple Sclerosis is associated with Axonal loss.
Methods
Magnetic Resonance Spectroscopy (MRS) was carried out in a group of patients with Clinically Definite Multiple Sclerosis (n=31).
Using this technique, the apparent concentration of NA ([NA] the sum of N-AcetylAspartate (NAA), a Neuronal marker, and N-AcetylAspartyl Glutamate has been compared in four groups of patients with Multiple Sclerosis classified as Benign, Relapsing/Remitting, Secondary/Progressive, Primary/Progressive, and a control group.
Results
In the patients with Relapsing/Remitting disease (n=9) there was a highly significant reduction of apparent NA (median 8.73 mM, range 6.86 mM-10.74 mM, P=0.0008) from an area of high signal compared with the control group (median 11.97 mM, range 10.55 mM-14.5 mM).
In the patients with Secondary/Progressive disease (n=10), there was again a highly significant reduction of apparent NA (median 7.82 mM, range 3.5 mM-10.3 mM, P=0.0003) from an area of high signal compared with the control group.
In the patients with Primary/Progressive disease (n=6) there was once again a highly significant reduction of apparent NA (median 8.83 mM, range 6.95 mM-9.89 mM, P<0.002) from an area of high signal compared with the control group.
In the patients with Benign disease, however, there was no significant difference in the apparent NA (median 10.5 mM, range 8.53 mM-12.8 mM, P>0.05) from an area of high signal compared with the control group.
In the patients with Benign disease (n=5) there was also no significant difference in the apparent NA (median 10.74 mM, range 8.58 mM-13.4 mM, P>0.3) from an area of Normal-Appearing White Matter compared with the control group.
In the patients with Primary/Progressive disease, however, there was a significant reduction of apparent NA from an area of Normal Appearing White Matter (median 8.78 mM, range 8.7 mM-12.38 mM, P< 0.025) compared with the control group.
There was a significant inverse correlation between [NA] from lesions in the patients with Multiple Sclerosis and disability as measured on the Kurtzke Expanded Disability Status Scale Score (r= -0.364, 0.05>P>0.02).
Conclusion
These findings support the hypothesis that Axonal loss is important in the development of disability in Multiple Sclerosis. They also provide evidence for Axonal loss in Normal-Appearing White Matter in patients with Primary/Progressive disease.
