DIR-visible grey matter lesions and atrophy in multiple sclerosis: partners in crime?
BACKGROUND
The extent and clinical relevance of grey matter (GM) pathology in multiple sclerosis (MS) are increasingly recognised. GM pathology may present as focal lesions, which can be visualised using double inversion recovery (DIR) MRI, or as diffuse pathology, which can manifest as atrophy. It is, however, unclear whether the diffuse atrophy centres on focal lesions. This study aimed to determine if GM lesions and GM atrophy colocalise, and to assess their independent relationship with motor and cognitive deficits in MS.


METHODS
Eighty people with MS and 30 healthy controls underwent brain volumetric T1-weighted and DIR MRI at 3 T, and had a comprehensive neurological and cognitive assessment. Probability mapping of GM lesions marked on the DIR scans and voxel- based morphometry (assessing GM atrophy) were carried out. The associations of GM lesion load and GM volume with clinical scores were tested.


RESULTS
DIR-visible GM lesions were most commonly found in the right cerebellum and most apparent in patients with primary progressive MS. Deep GM structures appeared largely free from lesions, but showed considerable atrophy, particularly in the thalamus, caudate, pallidum and putamen, and this was most apparent in secondary progressive patients with MS. Very little co-localisation of GM atrophy and lesions was seen, and this was generally confined to the cerebellum and postcentral gyrus. In both regions, GM lesions and volume independently correlated with physical disability and cognitive performance.


CONCLUSIONS
DIR-detectable GM lesions and GM atrophy do not significantly overlap in the brain but, when they do, they independently contribute to clinical disability.
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK.
Steven H P
SH
van de Pavert
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK School of Psychology and Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, Glamorgan, UK.
Nils
N
Muhlert
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK.
Varun
V
Sethi
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK.
Claudia A M
CA
Wheeler-Kingshott
Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, UK Nuffield Department of Clinical Neurosciences, FMRIB Centre, University of Oxford, Oxford, UK.
Gerard R
http://orcid.org/0000-0002-7676-7860
GR
Ridgway
Department Anatomy & Neurosciences, Section of Clinical Neuroscience, VU University Medical Centre, Amsterdam, The Netherlands.
Jeroen J G
JJ
Geurts
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK.
Maria
M
Ron
Sara Koe PSP Research Centre, UCL Institute of Neurology, London, UK.
Tarek A
TA
Yousry
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK NIHR UCL/UCLH Biomedical Research Centre, London, UK.
Alan J
AJ
Thompson
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK NIHR UCL/UCLH Biomedical Research Centre, London, UK.
David H
DH
Miller
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK NIHR UCL/UCLH Biomedical Research Centre, London, UK.
Declan T
DT
Chard
NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK NIHR UCL/UCLH Biomedical Research Centre, London, UK.
Olga
O
Ciccarelli
D000328:Adult; D001284:Atrophy / Q000473:pathology*; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000473:pathology*; D059906:Neuroimaging
IMAGE ANALYSIS; MRI; MULTIPLE SCLEROSIS; PATHOLOGY