Neurofilament and glial alterations in the cerebral cortex in amyotrophic lateral sclerosis.

According to the literature, only minor nonspecific histopathological lesions are present in the motor cortex in up to 90% of the amyotrophic lateral sclerosis (ALS) patients. These observations, however, have so far been based mainly on conventional staining techniques. An exception to this is the focal glial reaction that has been reported following immunocytochemical staining for glial fibrillary protein (GFAP), which is reported to be distinctive for ALS in the cortex. Since perikarya of degenerating motor neurons in the spinal cord of ALS patients have been found to accumulate phosphorylated neurofilaments (PNF), an investigation was conducted to determine whether PNF was also a sensitive marker for alterations in the motor cortex in this condition. On large brain sections from 15 ALS patients, intense PNF immunoreactivity was found in the motor cortex from 11 patients. It was mainly localized in small pyramidal cells and basket cells, whereas only slight staining was observed in Betz cells. PNF-positive basket cells were also present in controls, but the basket cells staining for PNF were less numerous in controls than in ALS specimens. PNF-positive Betz cells were found in 47% of 15 ALS patients and in 10% of the controls. PNF accumulation was also found in swollen, probably degenerating, terminal boutons around perikarya of large pyramidal cells and Betz cells in the motor areas of ALS patients only. These observations suggest that the premotor innervation of the motor system is preferentially affected in ALS. Small brain sections, comprising the motor cortex, from 18 additional ALS patients demonstrated a similar PNF-staining pattern. However, differentiating ALS patients from controls was much easier when studying large brain sections. No ubiquitin-immunoreactive inclusions were found, except for sporadic tangles. The presence of a focal-GFAP positive astrocytosis as reported in the literature in the precentral cortex was confirmed. However, it was found to be nonspecific since it was also present outside the precentral cortex and in the cortex of normal control patients. No spatial relation was found between the distribution of the glial reaction in ALS and the areas containing neurons and boutons accumulating PNF.