Abstract Details

Title Decreased cerebral blood flow in the striatum is an early event in Huntington’s disease pathology

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-044

Objective This study was designed to investigate cerebral blood flow (CBF) changes in HD patients and premanifest HD gene carriers.

Background The ultimate cause of neuronal death in Huntington’s disease (HD) is still uncertain. Apart from impairment in systems for handling abnormal proteins, other mechanisms, such as inflammation, might contribute to neurodegeneration and progression of HD. Cerebral hypoperfusion has been described in neurodegenerative disorders such as Alzheimer’s disease, and in traumatic brain injury, and may play a role in HD.

Design/Methods 18 patients with genetically confirmed HD [11 manifest patients (48.6±10.9 y; 3M/8F), 7 premanifest HD gene carriers (47.3±9.4 y; 2M/5F)], and 13 controls (32.4±2.4 y; 7M/6F) underwent brain magnetic resonance imaging (MRI) at 3T with pseudo-continuous arterial spin labeling (pCASL) to quantify CBF, and 3D-MPRAGE for volumetric segmentation. pCASL images were analyzed with FMRIB Software Library (FSL) and FreeSurfer v5.3.0. Region of interest (ROI) analyses were performed to compare CBF in controls vs premanifest HD gene carriers vs manifest patients with HD (Kruskal-Wallis test followed by Dunn's multiple comparisons test).

Results Both premanifest HD gene carriers and manifest patients had a significant decrease in CBF in deep gray matter (DGM) in comparison with controls (p=0.037). There was a significant decrease in CBF in bilateral caudate and putamen of manifest patients with HD in comparison with controls. The same changes were observed in premanifest HD gene carriers with a mean of 8 years before the predicted onset of clinical symptoms (p=0.035 and p=0.003 for left and right caudate, respectively; and p=0.029 and p=0.012 for left and right putamen, respectively).

Conclusions Our preliminary results suggest that hypoperfusion may be an early event in HD and precedes motor symptom onset. Decreased CBF and oxygen supply could emerge as a link between neuroinflammation and neurodegeneration in HD. These findings may impact future therapeutic strategies.

Authors/Disclosures
Erin Furr-Stimming, MD, FAAN (University of Texas Health Science Center-Houston) PRESENTER	Dr. Furr-Stimming has received personal compensation for serving as an employee of Help4HD International. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedPage. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Life Sciences. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Latus Bio. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atalanta Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SkyHawk Therapeutics. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atalanta Therapeutics. The institution of Dr. Furr-Stimming has received research support from Roche/Genetech. The institution of Dr. Furr-Stimming has received research support from Uniqure. The institution of Dr. Furr-Stimming has received research support from CHDI. The institution of Dr. Furr-Stimming has received research support from Huntington Study Group/Neurocrine Bioscienes. The institution of Dr. Furr-Stimming has received research support from NIH/University of Iowa. The institution of Dr. Furr-Stimming has received research support from Sage Therapeutics. The institution of Dr. Furr-Stimming has received research support from HDSA. The institution of Dr. Furr-Stimming has received research support from Prilennia. Dr. Furr-Stimming has received publishing royalties from a publication relating to health care. Dr. Furr-Stimming has received publishing royalties from a publication relating to health care. Dr. Furr-Stimming has a non-compensated relationship as a Committee member with AAN UES Committee that is relevant to AAN interests or activities.
Natalia Pessoa Rocha	Natalia Pessoa Rocha has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gabriela Colpo	Gabriela Colpo has nothing to disclose.
Leorah A. Freeman, MD, PhD (Dell Medical School, The University of Texas at Austin)	Dr. Freeman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Hoffman La-Roche. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech, Inc. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Freeman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Dr. Freeman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Texas Neurological Society. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono/ Merck. The institution of Dr. Freeman has received research support from Genentech. The institution of Dr. Freeman has received research support from PCORI. The institution of Dr. Freeman has received research support from EMD Serono. The institution of Dr. Freeman has received research support from Sanofi. The institution of Dr. Freeman has received research support from MSAA. The institution of Dr. Freeman has received research support from National Multiple Sclerosis Society.
	No disclosure on file

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