Biology subjects

Kolbe, S.

Publications and source records attributed to Kolbe, S..

3 recordsLinked to original sources

bioRxiv2020

Evaluation of cerebellar function scores in relation to cerebellar axonal loss in multiple sclerosis

BackgroundCerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are hampered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS. ObjectiveExamine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMS MethodsWe recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle. ResultsLoss of cerebellar FDC was associated with increased SARA (r=-0.42, p<0.01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p<0.01) and tremor severity (rho=0.41, p=0.01). ConclusionFibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression.

neuroscience↗

bioRxiv2020

Modulation of white matter bundle connectivity in the presence of axonal truncation pathologies

Endpoint-to-endpoint fibre bundle connectivity estimated using spherical deconvolution & streamlines tractography in diffusion MRI may be excessive in the presence of pathologies that involve truncation of axons within the white matter. Here we propose a simple modification to an existing method that directly quantifies and corrects for this over-estimation.

neuroscience↗

bioRxiv2017

White matter haemodynamics: basic physiology and disruption in neuroinflammatory disease

The white matter is highly vascularised by the cerebral venous system. The neuroinflammatory disease multiple sclerosis is associated with infiltration of peripheral immune cells into the brain via these vessels. Understanding venous pathophysiology in multiple sclerosis is thus critical for understanding early disease aetiology. In this paper, we describe a unique blood oxygen-level dependent (BOLD) signal within the white matter using functional MRI and spatial independent components analysis, a blind signal source separation method. The signal was characterised by a narrow peak frequency band between 0.05 and 0.1 Hz. Hypercapnia (transient breath holds), known to alter venous calibre in cortex, induced transient increases in white matter BOLD that disrupted the oscillation indicative of a vasodilatory/contractile mechanism. Comparison of the white matter BOLD oscillations between age and sex matched groups of 18 multiple sclerosis and 14 healthy participants revealed a loss of power in the white matter BOLD signal in the peak frequency band (patients = 6.70{+/-}0.94 dB/Hz vs controls = 7.64{+/-}0.71 dB/Hz; p=0.006). In multiple sclerosis patients, lower power was associated with greater levels of neuroinflammatory activity (R=-0.64, p=0.006) but not neurodegenerative disease markers. Using a signal modelling technique, we assessed the anatomical distribution of white matter BOLD signal abnormalities and detected reduced power in the periventricular white matter, a region of known venous damage in multiple sclerosis patients. These results demonstrate a novel link between neuroinflammation and vascular physiological dysfunction in the cerebral white matter, and could indicate enduring loss of vascular compliance associated with imperfect repair of blood-brain barrier damage after resolution of acute neuroinflammation.

neuroscience↗