Decrease in neuronal density in the cerebral cortex in multiple system atrophy

Abstract

The presence of argyrophilic oligodendroglial cytoplasmic inclusions (GCIs) is a pathognomonic feature of multiple system atrophy (MSA), which has established MSA as a nosological entity, and serves as a diagnostic criterion. As a neurodegenerative disease, MSA exhibits neuronal degeneration and loss from several regions of the central nervous system. Recent mapping studies of the distribution of GCIs have shown their presence in regions of the brain previously thought not to be affected in MSA, for example the cerebral cortex. This study has used stereological techniques to establish whether neuronal loss is related to the presence of GCIs in three regions of the cerebral cortex. In the prefrontal cortex, in which GCIs are sparse, there is no significant difference in either neuronal or glial cell numerical density in MSA cases compared to controls. However in two cortical regions which are both GCI rich, the anterior central gyrus and the supplementary motor cortex, there is a marked reduction in neuronal density of 18.7% and 21.4% respectively, which is statistically significant only in the supplementary motor cortex. In both of these regions there is a concomitant increase in glial cell numerical density which results in a significant change in the ratio of neurons to glial cells. These results indicate that there is a regional reduction in the neuronal density in the cortex in multiple system atrophy which is associated with the presence of GCIs.

The neuropathology, pathophysiology and genetics of multiple system atrophy

“…Scale bar = 15 mm. neuronal loss showed an approximately 20% reduction in neurones in the motor and supplementary motor cortex [21], which was later confirmed by other studies [22], one of which indicated it was related to involvement of the StrN system [23]. It is of note that a recent study has shown that 10-32% of MSA patients suffer from cognitive dysfunction [24], with an imaging study correlating this with frontal atrophy [25].…”

“…Loss of neurones in autonomic system nuclei of the hypothalamus, brainstem and spinal cord is thought to be responsible for the autonomic dysfunction seen in MSA patients [20]. Although cortical involvement in MSA was considered rare in earlier studies, a robust method of quantifying neuronal loss showed an approximately 20% reduction in neurones in the motor and supplementary motor cortex [21], which was later confirmed by other studies [22], one of which indicated it was related to involvement of the StrN system [23]. It is of note that a recent study has shown that 10–32% of MSA patients suffer from cognitive dysfunction [24], with an imaging study correlating this with frontal atrophy [25].…”

Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy

“…Pathological changes in the cerebrum of MSAp are most consistent and severe in motor areas such as M1 and SMA [Dickson, ; Mochizuki et al, ; Papp and Lantos, ; Spargo et al, ; Su et al, ]. VBM has revealed reduced volume in cortical motor areas of MSAp [Brenneis et al, ; Minnerop et al, ; Tir et al, ; Tzarouchi et al, ], and suggests that cortical atrophy is more prominent in the later stages of disease [Brenneis et al, ].…”