Concurrent multiple sclerosis and amyotrophic lateral sclerosis: where inflammation and neurodegeneration meet?

Abstract

The concurrence of multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) is exceedingly rare and the pathological features have not been examined extensively. Here we describe the key pathological features of a 40 year old man with pathologically confirmed concurrent MS and ALS.This is the most pathologically illustrative case of coincident MS and ALS demonstrating inflammatory and neurodegenerative features characteristic of each disease, and is the first to exhibit the presence of TDP-43 inclusions in this clinical entity. The intricate relationship between neuroinflammation and neurodegeneration in these diseases is discussed.

Figure 1

Neuropathological features of concurrent MS and ALS. Left hemispheric leukocortical (within box) and periventricular lesions (arrow) (A). PLP staining of leukocortical plaque in A (inlay) demonstrating demyelination spanning grey and white matter (B), PG-M1 staining showing macrophage infiltration and microglia activation (C), and perivascular cuffing with cells resembling lymphocytes (D) within same lesion. Gross (E) and PLP-stained section (F) of pons (with cerebellum) demonstrating periventricular and parenchymal demyelination. PLP-stained section of demyelinated lesion in dorsal column of cervical spinal cord (arrow) (G) with diffuse microglia activation extending beyond lesional borders (PG-M1 staining) (H). Gross view of thinned and discolored ventral roots of lower cervical cord from case (I) compared to control (J). LBCV section of lumbar cord demonstrating significant loss of anterior horn cells in the case (K) compared to control (L). TDP-43 staining demonstrating intracytoplasmic neuronal inclusions in anterior horn cells in lumbar spinal cord (arrowheads) in case (M) compared to nuclear neuronal staining of the same area in a control (N).