Freezing of gait and white matter changes: a tract-based spatial statistics study

Abstract

BackgroundWe hypothesized that the integrity of white matter might be related to the severity of freezing of gait in age-related white matter changes.MethodsTwenty subjects exhibiting excessive hyperintensities in the periventricular and deep white matter were recruited. The subjects underwent the Freezing of Gait Questionnaire, computerized gait analyses, and diffusion tensor magnetic resonance imaging. Images of axial, radial and mean diffusivity, and fractional anisotropy were calculated as indices of white matter integrity and analyzed with tract-based spatial statistics.ResultsThe fractional anisotropy, mean, axial and radial diffusivity averaged across the whole white matter structure were all significantly correlated with Freezing of Gait Questionnaire scores. Regionally, a negative correlation between Freezing of Gait Questionnaire scores and fractional anisotropy was found in the left superior longitudinal fasciculus beneath the left premotor cortex, right corpus callosum, and left cerebral peduncle. The scores of the Freezing of Gait Questionnaire were positively correlated with mean diffusivity in the left corona radiata and right corpus callosum, and with both axial and radial diffusivity in the left corona radiata. The white matter integrity in these tracts (except the corpus callosum) showed no correlation with cognitive or other gait measures, supporting the specificity of those abnormalities to freezing of gait.ConclusionDivergent pathological lesions involved neural circuits composed of the cerebral cortex, basal ganglia and brainstem, suggesting that freezing of gait has a multifactorial nature.

Association between Various Brain Pathologies and Gait Disturbance

“…Among 429 non-demented later middle-aged adults (mean age=65) with cerebral small vessel disease, lower FA and higher MD of the corpus callosum was associated with slower gait speed, reduced stride length and cadence, and increased stride width [23]. In a smaller study of 20 older adults (range=65–84) with significant cerebrovascular pathology, lower FA and higher MD, and axial and radial diffusivity across all WM were associated with freezing of gait [24]. Another study that examined the effect of FA within the context of WMHs found that FA measures throughout WM regions significantly moderated the association between WMH volume and gait speed among 265 community-dwelling older adults (mean age=83) [25].…”

White matter integrity and cognitive dysfunction: Radiological and neuropsychological correlations

“…34,35 Principally, freezing of gait is found in patients with WM lesions, and has been associated with disintegration of microstructures in the striato-frontal WM. 36,37…”

“…On the other hand, parkinsonian gait disorder has been attributed to frontal WM lesions . Principally, freezing of gait is found in patients with WM lesions, and has been associated with disintegration of microstructures in the striato‐frontal WM …”

Clinical features of freezing of gait in Parkinson's disease patients

“…The pathogenesis of FOG is complicated and involves multiple mechanisms, including disordered limbic system and cognitive functions regulated by the basal ganglia, supplementary motor area, and cerebral cortex (Iseki et al., ; Okuma, ; Snijders et al., ; Teramoto, Morita, Ninomiya, Shiota, & Kamei, ). The association of FOG with these systems has not yet been investigated in detail.…”