Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus.
OBJECTIVE
The objective of this paper is to inform the pathophysiology of medial longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite structural-functional biomarker of axonal and myelin integrity in this tract.


METHODS
Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF and T2-visible brainstem lesions were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics.


RESULTS
eVOR onset latency was positively correlated with MLF lesion length (left: r = 0.66, p = 0.004; right: r = 0.75, p = 0.001). The mean conduction velocity (±SD) within MLF lesions was estimated at 2.72 (±0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = 0.66, p < 0.001) and fractional anisotropy (r = 0.44, p = 0.02) after exclusion of cases with ipsilateral vestibular root entry zone lesions.


CONCLUSIONS
Axonal conduction velocity through lesions involving the MLF was reduced below levels predicted for natively myelinated and remyelinated axons. Composite in vivo biomarkers enable delineation of axonal from myelin processes and may provide a crucial role in assessing efficacy of novel reparative therapies in MS.
Sydney Neuroimaging Analysis Centre, Sydney, Australia/Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
Chenyu
C
Wang
Royal Hallamshire Hospital, Sheffield, UK and Department of Neuroscience, University of Sheffield, Sheffield, UK.
David
D
Paling
Central Clinical School, University of Sydney, Sydney, Australia/Royal Prince Alfred Hospital, Sydney, Australia.
Luke
L
Chen
Sydney Neuroimaging Analysis Centre, Sydney, Australia/Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
Sean N
SN
Hatton
Sydney Neuroimaging Analysis Centre, Sydney, Australia/Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
Jim
J
Lagopoulos
Central Clinical School, University of Sydney, Sydney, Australia/Royal Prince Alfred Hospital, Sydney, Australia.
Swee T
ST
Aw
Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
Matthew C
MC
Kiernan
Sydney Neuroimaging Analysis Centre, Sydney, Australia/Brain and Mind Research Institute, University of Sydney, Sydney, Australia/Royal Prince Alfred Hospital, Sydney, Australia michael@sydneyneurology.com.au.
Michael H
MH
Barnett
D000328:Adult; D000368:Aged; D056324:Diffusion Tensor Imaging; D055724:Electrophysiological Phenomena; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009431:Neural Conduction / Q000502:physiology*; D015835:Ocular Motility Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012027:Reflex, Vestibulo-Ocular; D014795:Visual Pathways / Q000473:pathology / Q000503:physiopathology*
Multiple sclerosis; axonal conduction; demyelination; electrophysiology; magnetic resonance imaging; medial longitudinal fasciculus; remyelination