Deep white matter in Huntington's disease

White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression

Deep White Matter in Huntington's Disease

White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression

White matter rather than gray matter damage characterizes essential tremor

We investigated changes in gray matter (GM) and white matter (WM) in the whole brain, including both cortical and subcortical structures, and their relationship with tremor severity, psychiatric symptoms, and cognitive impairment in patients affected by essential tremor (ET)

Individual Deep White Matter Tractography Group Comparisons.

<p>Legend. AF = Arcuate Fasciculus, SLF = Superior Longitudinal Fasciculus, Cing = Cingulate, ILF = Inferior Longitudinal Fasciculus, IFO = Inferior Frontal Occipital fasciculus, ATR = Anterior Thalamic Radiation, UF = Uncinate Fasciculus; Hemi DWM = total left and right Deep White Matter, it is the result of the individual white matter tracts combined for each hemisphere; FA = Fractional Anisotropy; AD = Axial Diffusivity; RD = Radial Diffusivity; R = Right; L = Left.</p><p>*Significant FDR corrected results are in <b>BOLD</b>.</p><p>Individual Deep White Matter Tractography Group Comparisons.</p

Sociodemographic and clinical characteristics of patients and control subjects.

<p>Legend. HD = Huntington's disease; Pre-HD = gene-positive, without motor symptoms; SD = standard deviation; df = degrees of freedom; CAG, trinucleotide repeat number; MMSE = Mini Mental State Examination; UHDRS = Unified Huntington's Disease Rating Scale; TFC = Total Functional Capacity; NA = Not Available;</p>††<p>T-student, Bonferroni correction.</p>a<p>Pre-HDb</p><p>Pre-HD>HD (when referred to a cognitive scale comparison, higher punctuations mean lesser impairment).</p><p>*MMSE: Missing data for 5 Pre-HD & 5 HD subjects.</p><p>*UHDRS Motor: Missing data for 2 Pre-HD & 2 HD subjects.</p><p>*UHDRS Cognitive: Missing data for 5 Pre-HD & 2 HD subjects.</p><p>*UHDRS Behavioral: Missing data for 4 Pre-HD & 2 HD subjects.</p><p>*UHDRS Functional: Missing data for 2 Pre-HD & 2 HD subjects.</p><p>*TFC: Missing data for 2 Pre-HD & 2 HD subjects.</p><p>Sociodemographic and clinical characteristics of patients and control subjects.</p

Total Deep White Matter Tractography Group Comparisons.

<p>Legend. FA = Fractional Anisotropy; AD = Axial Diffusivity; RD = Radial Diffusivity. (AD/RD Mean units: 10⁻³ mm²/s, R2* (10⁻³ mm¹/s).</p><p>*Significant FDR corrected results are in <b>BOLD</b>.</p><p>Total Deep White Matter Tractography Group Comparisons.</p

Deep White Matter Microstructure for Each Group.

<p>Tracts shown use colour to represent the overall microstructure for each tract within each group. White = Normal, Yellow = Abnormal, Red = Damaged. Tracts Legend. AF = Arcuate Fasciculus, SLF = Superior Longitudinal Fasciculus, Cing = Cingulate, ILF = Inferior Longitudinal Fasciculus, IFO = Inferior Frontal Occipital fasciculus, ATR = Anterior Thalamic Radiation, UF = Uncinate Fasciculus.</p

Total Deep White Matter Tractography and Group Comparison.

<p>Bar graphs show differences between Total Deep White Matter FA, AD, RD, and Iron. The error bars represent the Standard Error Mean (SEM). Legend. FA = Fractional Anisotropy; AD = Axial Diffusivity; RD = Radial Diffusivity. (AD/RD Mean units: 10⁻³ mm²/s, R2* (10⁻³ mm¹/s). * Significant difference between Pre-HD and Controls+ Significant difference between Pre-HD and HD.</p

Changes of peripheral TGF-β1 depend on monocytes-derived macrophages in Huntington disease.

Background: Huntington Disease (HD) is a neurodegenerative disorder resulting from the expansion of polyglutamine stretch in the huntingtin protein (Htt). Mutant HTT (mHtt) leads to progressive impairment of several molecular pathways that have been linked to disease pathogenesis. Defects in the production of a number of neurotrophic factors have been described as important determinants contributing to the development of HD. We have previously demonstrated that production of transforming growth factor-beta 1 (TGF-beta 1) is also deregulated in HD. Peripheral levels of TGF-beta 1 were markedly reduced early in the disease and returned to normal levels with disease severity. However, the cause and the biochemical origin of such abnormalities are still unclear. Results: We report here that the abnormal production of peripheral TGF-beta 1 depends on the changes in the percentage of TGF-beta 1-producing macrophages along disease course. Variation in the number of TGF-beta 1-producing macrophages resulted from differential activation state of the same cells, which displayed phenotypic and functional heterogeneity throughout the clinical course of HD. We further demonstrated that, similar to the periphery, the number of TGF-beta 1-immunoreactive cells in human post-mortem brain with HD, varied with neuropathological changes. Conclusions: Our data indicate that reduced bioavailability of TGF-beta 1 in the serum of HD subjects is attributable to the variation of the number of TGF-beta 1-producing macrophages. Macrophages display a differential ability to produce TGF-beta 1, which reflects diversity in cells polarization throughout the disease course. Besides elucidating the biochemical origin of TGF-beta 1 fluctuations in HD, our study highlights an interesting parallelism between periphery and central compartment and underlines the potential of TGF-beta 1 as a possible indicator suitable for prediction of disease onset in HD