Spinal cord repair in MS: does mitochondrial metabolism play a role?
OBJECTIVE
To investigate the mechanisms of spinal cord repair and their relative contribution to clinical recovery in patients with multiple sclerosis (MS) after a cervical cord relapse, using spinal cord (1)H-magnetic resonance spectroscopy (MRS) and volumetric imaging.


METHODS
Fourteen patients with MS and 13 controls underwent spinal cord imaging at baseline and at 1, 3, and 6 months. N-acetyl-aspartate (NAA) concentration, which reflects axonal count and metabolism in mitochondria, and the cord cross-sectional area, which indicates axonal count, were measured in the affected cervical region. Mixed effect linear regression models investigated the temporal evolution of these measures and their association with clinical changes. Ordinal logistic regressions identified predictors of recovery.


RESULTS
Patients who recovered showed a sustained increase in NAA after 1 month. In the whole patient group, a greater increase of NAA after 1 month was associated with greater recovery. Patients showed a significant decline in cord area during follow-up, which did not correlate with clinical changes. A worse recovery was predicted by a longer disease duration at study entry.


CONCLUSIONS
The partial recovery of N-acetyl-aspartate levels after the acute event, which is concurrent with a decline in cord cross-sectional area, may be driven by increased axonal mitochondrial metabolism. This possible repair mechanism is associated with clinical recovery, and is less efficient in patients with longer disease duration. These insights into the mechanisms of spinal cord repair highlight the need to extend spinal cord magnetic resonance spectroscopy to other spinal cord disorders, and explore therapies that enhance recovery by modulating mitochondrial activity.
Ciccarelli
O
O
Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. o.ciccarelli@ion.ucl.ac.uk
Altmann
D R
DR
McLean
M A
MA
Wheeler-Kingshott
C A
CA
Wimpey
K
K
Miller
D H
DH
Thompson
A J
AJ
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001369:Axons / Q000473:pathology / Q000502:physiology; D002574:Cervical Vertebrae; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D009929:Organ Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D017382:Reactive Oxygen Species; D001224:Aspartic Acid; C000179:N-acetylaspartate