White matter degeneration revealed by fiber-specific analysis relates to recovery of hand function after stroke.

Recent developments of higher-order diffusion-weighted imaging models have enabled the estimation of specific white matter fiber populations within a voxel, addressing limitations of traditional imaging markers of white matter integrity. We applied fixel based analysis (FBA) to investigate the evolution of fiber-specific white matter changes in a prospective study of stroke patients and upper limb motor deficit over 1 year after stroke. We studied differences in fiber density and macrostructural changes in fiber cross-section. Motor function was assessed by grip strength. We conducted a whole-brain analysis of fixel metrics and predefined corticospinal tract (CST) region of interest in relation to changes in motor functions. In 30 stroke patients (mean age 62.3 years, SD ±16.9; median NIHSS 4, IQR 2-5), whole-brain FBA revealed progressing loss of fiber density and cross-section in the ipsilesional corticospinal tract and long-range fiber tracts such as the superior longitudinal fascicle and trans-callosal tracts extending towards contralesional white matter tracts. Lower FBA metrics measured at the brainstem section of the CST 1 month after stroke were significantly associated with lower grip strength 3 months (p = .009, adjusted R2  = 0.259) and 1 year (T4: p < .001, adj. R2  = 0.515) after stroke. Compared to FA, FBA metrics showed a comparably strong association with grip strength at later time points. Using FBA, we demonstrate progressive fiber-specific white matter loss after stroke and association with functional motor outcome. Our results promote the application of fiber-specific analysis to detect secondary neurodegeneration after stroke in relation to clinical recovery.

Cortical atrophy and transcallosal diaschisis following isolated subcortical stroke.

Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3-5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean -0.15 mm; 95% CI -0.23 to -0.07 mm) as well as homologous contralateral brain regions (mean -0.13 mm; 95% CI -0.07 to -0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis.

Altered topology of large-scale structural brain networks in chronic stroke.

Beyond disruption of neuronal pathways, focal stroke lesions induce structural disintegration of distant, yet connected brain regions via retrograde neuronal degeneration. Stroke lesions alter functional brain connectivity and topology in large-scale brain networks. These changes are associated with the degree of clinical impairment and recovery. In contrast, changes of large scale, structural brain networks after stroke are less well reported. We therefore aimed to analyse the impact of focal lesions on the structural connectome after stroke based on data from diffusion-weighted imaging and probabilistic fibre tracking. In total, 17 patients (mean age 64.5 ± 8.4 years) with upper limb motor deficits in the chronic stage after stroke and 21 healthy participants (mean age 64.9 ± 10.3 years) were included. Clinical deficits were evaluated by grip strength and the upper extremity Fugl-Meyer assessment. We calculated global and local graph theoretical measures to characterize topological changes in the structural connectome. Results from our analysis demonstrated significant alterations of network topology in both ipsi- and contralesional, primarily unaffected, hemispheres after stroke. Global efficiency was significantly lower in stroke connectomes as an indicator of overall reduced capacity for information transfer between distant brain areas. Furthermore, topology of structural connectomes was shifted toward a higher degree of segregation as indicated by significantly higher values of global clustering and modularity. On a level of local network parameters, these effects were most pronounced in a subnetwork of cortico-subcortical brain regions involved in motor control. Structural changes were not significantly associated with clinical measures. We propose that the observed network changes in our patients are best explained by the disruption of inter- and intrahemispheric, long white matter fibre tracts connecting distant brain regions. Our results add novel insights on topological changes of structural large-scale brain networks in the ipsi- and contralesional hemisphere after stroke.