KS has been supported by a Higher Education Funding Council for England
Clinical Senior Lectureship. This work was supported by Barts Charity (grant code 468/1506)

Abdel-Fahim

Abercrombie

Albert

Andrews

Artacho-Perula

Brownell

Calabrese

Charil

Coleman

Compston

Dawson

DeLuca

Dinkler

Dutta

Fabricius

Ferguson

Filippi

Fischer

Fisniku

Geurts

Goldschmidt

Gundersen

Henstridge

Howell

Jurgens

Klaver

Korbo

Kuhlmann

Lassmann

Leray

Levin

Lucchinetti

Magliozzi

Mandolesi

Marburg

Michailidou

Pakkenberg

Pelvig

Peterson

Petrova

Pomeroy

Popescu

Reynolds

Roosendaal

Ruckh

Sailer

Sander

Scalfari

Schmierer

Schob

Sormani

Steenwijk

Tillema

Trapp

Vercellino

Vollmer

Watkins

Wegner

West

Zivadinov

Neuropathology and Applied Neurobiology

AIMS: Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology and demyelination. METHODS: Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (× 60) following stereological principles. Grey and WM demyelination was outlined on myelin basic protein immunostained sections, and expressed as percentages of cortex and WM respectively. RESULTS: In MS, the mean number of neurons was 14.9 ± 1.9 billion vs. 24.4 ± 2.4 billion in controls (P < 0.011), a 39% difference. The density of neurons was smaller by 28% (P < 0.001) and cortical volume by 26% (P = 0.1). Strong association was detected between number of neurons and cortical volume (P < 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the WM, however, neither correlated with neuronal loss. Only weak association was detected between number of neurons and WM volume. CONCLUSION: Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS

Carassiti, D

Altmann, DR

Petrova, N

Pakkenberg, B

Scaravilli, F

Schmierer, K

LSHTM Research Online

Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex.

AIMS: Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology and demyelination.METHODS: Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (× 60) following stereological principles. Grey and WM demyelination was outlined on myelin basic protein immunostained sections, and expressed as percentages of cortex and WM respectively.RESULTS: In MS, the mean number of neurons was 14.9 ± 1.9 billion vs. 24.4 ± 2.4 billion in controls (P &lt; 0.011), a 39% difference. The density of neurons was smaller by 28% (P &lt; 0.001) and cortical volume by 26% (P = 0.1). Strong association was detected between number of neurons and cortical volume (P &lt; 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the WM, however, neither correlated with neuronal loss. Only weak association was detected between number of neurons and WM volume.CONCLUSION: Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS.</p

Altmann, D R

Copenhagen University Research Information System

English

Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex

Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology and demyelination. 

 Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (× 60) following stereological principles. Grey and WM demyelination was outlined on myelin basic protein immunostained sections, and expressed as percentages of cortex and WM respectively. 

 In MS, the mean number of neurons was 14.9 ± 1.9 billion vs. 24.4 ± 2.4 billion in controls (P &lt; 0.011), a 39% difference. The density of neurons was smaller by 28% (P &lt; 0.001) and cortical volume by 26% (P = 0.1). Strong association was detected between number of neurons and cortical volume (P &lt; 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the WM, however, neither correlated with neuronal loss. Only weak association was detected between number of neurons and WM volume. 

 Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS

Queen Mary Research Online

D. Carassiti

D. R. Altmann

N. Petrova

B. Pakkenberg

F. Scaravilli

K. Schmierer

Crossref

http://researchonline.lshtm.ac.uk/4121188/1/Neuronal%20loss%2C%20demyelination_GREEN%20AAM.pdf

Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex

Abstract

Similar works

Full text

Available Versions

LSHTM Research Online

Copenhagen University Research Information System

LSHTM Research Online

Queen Mary Research Online

Crossref