Multiple Sclerosis: Neurofilament Pathology in Spinal Motor Neurons

Abstract

Objective: While traditionally a disorder of myelin, in multiple sclerosis (MS) neuronal and axonal damage has in recent years become an important topic of clinical relevance. To address this, alterations in neurofilament phosphorylation, known markers of neuronal health, were investigated in anterior horn cells in MS spinal cord tissue for signs of motor neuron damage. Methods: Spinal cord tissue was examined from 13 MS and 6 control patients. Fresh frozen sections were labelled with antibodies against phosphorylated and non-phosphorylated epitopes of neurofilament H (NF-H) and analyzed by light microscopy. Results: In MS, increased expression of phosphorylated NF-H in spinal motor neuron perikarya (abnormal for neurons) occurred in 61.5% of cases, mostly in chronic active lesions, with the strongest immunoreactivity at the lumbar level. Inflammatory activity was common in chronic active but rare in chronic silent lesions. In one case with an acute lesion, we saw swollen axons positive for non-phosphorylated NF-H, a pathologic marker in axons, but no signs of perikaryal damage. Expression of non-phosphorylated NF-H in spinal motor neuron perikarya was similar in both MS and controls. Conclusion: In line with previous studies, our findings implicate anterior horn cell damage as a common feature in MS. We propose that underlying mechanisms may involve reduced synaptic input and/or retrograde degeneration, subjects which remain to be investigated.