Werring, David John; (2000) Mechanisms of central nervous system damage and recovery in demyelinating and oter neurological disorders: Structural and functional MRI studies. Doctoral thesis (Ph.D.), University College London (United Kingdom).

Text Mechanisms_of_central_nervous_.pdf Download (15MB)

Abstract

This thesis is concerned with multiple sclerosis (MS), a chronic, multifocal demyelinating disease of the central nervous system (CNS). In its early stages MS is characterised by reversible deficits, but with time recovery usually becomes incomplete, causing progressive disability. To understand this transition requires knowledge of mechanisms of recovery and fixed neurological deficit. Functional recovery from demyelination can occur despite irreversible conduction abnormalities and axon loss in affected pathways, suggesting that cortical adaptive mechanisms may contribute. To investigate this hypothesis, patients who had recovered from a single episode of optic neuritis were studied using functional magnetic resonance imaging (fMRI). Monocular visual stimulation to the recovered eye induced an anatomically and temporally abnormal response in areas outside the visual cortex, to which activation in control subjects was confined. The extra-occipital activation was most marked in those with delayed optic nerve conduction, suggesting a role in adaptation to persistently abnormal visual input. Mechanisms of tissue damage in MS were investigated using MR diffusion imaging, which quantifies water molecule mobility non-invasively and is sensitive to tissue structural integrity. Heterogeneous diffusion properties were demonstrated in MS lesions, and subtle abnormalities in the magnitude and directional restriction (anisotropy) of diffusion were found in widespread areas of normal-appearing white matter (NAWM). Diffusion in lesions correlated with that in NAWM, suggesting that the underlying pathogenic mechanisms are closely linked. In patients with ischaemic stroke, anisotropy changes were demonstrated in tracts distant to the lesion, indicating an ability to detect fibre degeneration. Finally, fMRI and diffusion imaging were combined to obtain complementary functional and structural information. In a traumatic CNS injury causing hemiplegia, excellent motor recovery was associated with a preservation of corticospinal tract structural integrity and motor cortex activation. In the human visual system, fibre tract structure and orientation, and cortical activation were demonstrated in single maps.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item