Background: Substantial grey matter (GM) demyelination occurs in both the cerebral cortex and spinal cord in multiple sclerosis (MS). GM demyelination also occurs in the cerebellar cortex and the deep GM nuclei of the brain. However, no study has made a direct ''within subject'' comparison of the extent of GM pathology between these regions. Aim: To examine the extent and pattern of GM demyelination in the motor cortex, cingulate gyrus, cerebellum, thalamus and spinal cord in MS. Methods: Postmortem study using material from 14 MS cases and three controls. Sections were taken from the five predetermined areas and stained for proteolipid protein. The extent of GM and white matter (WM) demyelination was assessed in each region. Results and conclusion: Overall, 28.8% of the GM was demyelinated compared with 15.6% of the WM (p,0.001), with demyelination being greater in the GM than in the WM at each of the anatomical sites. There was substantial variation in the extent of demyelination between the different CNS regions. GM demyelination was most extensive in the spinal cord and cerebellum while WM demyelination was most prominent in the spinal cord.The factors influencing plaque topography in multiple sclerosis (MS) are not fully understood. The majority of white matter (WM) plaques occur in a perivenular distribution, with areas containing a high density of small veins and venules-such as the periventricular WM, leucocortical junction and the WM tracts of the brainstem and spinal cordshowing a preponderance for demyelination. 1 While it has been recognised that MS also involves grey matter (GM) structures, the conventional myelin stains used in these studies grossly underestimate the true extent of this GM pathology. [2][3][4] In comparison, myelin protein immunohistochemistry is more sensitive for detecting GM demyelination, demonstrating extensive demyelination in the cerebral cortex and spinal cord GM in MS.4-6 However, it is unclear whether GM demyelination is more prominent in the spinal cord, the cerebral cortex or other GM structures; comparisons between studies are likely to be confounded by differences in MS subtype, disease duration, age, gender, etc. Therefore, in this study, we used autopsy material to quantify GM and WM demyelination in the cerebral cortex, cerebellum, spinal cord and thalamus, allowing us to make ''within subject'' comparisons of the extent of demyelination in these regions.
MATERIALS AND METHODS Clinical materialFormalin fixed, paraffin embedded autopsy material was obtained from 14 pathologically confirmed MS cases and three controls (MS Brain Bank, London, UK). Patients with MS (one man, 13 women) were aged 44-81 years (mean 56.6, median 56) with disease durations of 6-32 years (mean 23.7, median 22). Eleven cases had secondary progressive MS (SPMS), two primary progressive MS (PPMS) and one relapsing remitting MS (RRMS). The controls (two women aged 69 and 78 years, one man aged 35 years) had no clinical or pathological evidence of neurological disease. The local research...