The Global Neocortical Loss Of Neurons In Multiple Sclerosis (P1.190)

OBJECTIVE: To estimate the total neuronal loss in the neocortex of people with MS (pwMS) BACKGROUND: Total neuronal loss in the MS neocortex is unknown. Accurate quantification of cortical neurons is important to understand (i) MS pathophysiology and (ii) in vivo substrates of neuronal loss such as brain atrophy indices derived from magnetic resonance imaging (MRI) DESIGN/METHODS: Formalin fixed brain hemispheres of three pwMS and one reference case were used. Hemispheres were dissected into 1.1 cm thick coronal slabs, and spatially referenced images obtained of each slab at dissection and after embedding in wax to calculate tissue shrinkage. Neurons were identified on Giemsa stained sections using a x60 oil objective on a microscope equipped with a motorized stage. The cortical area of interest (AOI) was outlined on 40μm-thick sections and disectors were cast randomly on a grid with measures X= 3455μm, Y= 4655μm. Number of neurons in each slab was calculated according to N V x V REF stereology method: N V = total neurons counted/volume of all disectors and V REF = AOI x cortical thickness adjusted for tissue shrinkage RESULTS: The total number (mean ± SD) of neocortical neurons in pwMS was 11.3 ± 5.3 billion whilst the total number of cortical neurons in control brain was 19.8 billion CONCLUSIONS: The total number of neocortical neurons in control brain was similar to figures reported elsewhere. The detected 43% loss of neocortical neurons in pwMS underpins the devastating character of MS. Confirmation of this data in a larger cohort is underway. Further future work will include (i) assessing cortical demyelination to explore its relationship with neuronal loss and (ii) investigating the association between cortical and spinal cord pathology to explore whether a tract specific pattern of neuro-axonal degeneration contributes to chronic disease progression in MS Study Supported by: Disclosure: Dr. Carassiti has nothing to disclose. Dr. Papachatzaki has nothing to disclose. Dr. Scaravilli has nothing to disclose. Dr. Schmierer has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Novartis and Merck Serono.