UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

Abdel-Aziz, K; Schneider, T; Solanky, BS; Yiannakas, MC; Altmann, DR; Wheeler-Kingshott, CAM; Peters, AL; ... Ciccarelli, O; + view all (2015) Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis. Brain , 138 (6) pp. 1568-1582. 10.1093/brain/awv086. Green open access

[img]
Preview
Text
PPMS_Manuscript_Revised%2C Khaled Abdel_Aziz%2C Feb 2015.pdf

Download (301kB) | Preview

Abstract

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel 1H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = −0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = −3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = −4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability.

Type: Article
Title: Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awv086
Publisher version: http://dx.doi.org/10.1049/el.2015.390710.1093/brai...
Language: English
Additional information: his is a pre-copyedited, author-produced PDF of an article accepted for publication in Brain following peer review. The version of record Abdel-Aziz, K; Schneider, T; Solanky, BS; Yiannakas, MC; Altmann, DR; Wheeler-Kingshott, CAM; Peters, AL; (2015) Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis. Brain , 138 (6) pp. 1568-1582 is available online at:http://dx.doi.org/10.1093/brain/awv086
Keywords: multiple sclerosis imaging, biomarkers, cellular mechanisms
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1466168
Downloads since deposit
34Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item