TY - JOUR
T1 - Multimodal Imaging and Visual Evoked Potentials Reveal Key Structural and Functional Features That Distinguish Symptomatic from Presymptomatic Huntington's Disease Brain
AU - Thota, Sai Manohar
AU - Chan, Kimberly L.
AU - Pradhan, Sai Sanwid
AU - Nagabushana, Bhavana
AU - Priyanka, G. B.
AU - Sunil, H. V.
AU - Kanneganti, Vidyasagar
AU - Vasoya, Pavan
AU - Vinnakote, Krishna Murthy
AU - Viswamitra, Sanjaya
AU - Thambisetty, Madhav
AU - Kumar, Dileep
AU - Tiwari, Vivek
AU - Joshy, E. V.
AU - Sivaramakrishnan, Venketesh
N1 - Funding Information:
We acknowledge the support of the Science and Engineering Research Board, Department of Science and Technology (EMR/2017/005381); Basic Scientific Research, University Grants commission (F.25.1/2013.14(BSR)/7.164/2007(BSR)); Bioinformatics Infrastructure Facility, Department of Biotechnology (BT/BI/25/063/2012); Fund for Improvement of S and T Infrastructure, Department of Science and Technology (SR/FST/LSI.616/2014); Special Assistance Programme, University Grants Commission (F.3.19/2018/DRS.III (SAP.II)); and Basic Research in Modern Biology, Department of Biotechnology (BT/PR8226/BRB/10/1224/2013).
Publisher Copyright:
© 2021 Wolters Kluwer Medknow Publications. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background: Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric abnormalities. Currently, matched analyses of structural and functional differences in the brain from the same study cohort and, specifically, in HD patients from an ethnically diverse Indian population are lacking. Such findings aid in identifying noninvasive and sensitive imaging biomarkers. Objective: The aim of the study was to understand the structural and functional differences between HD and control brain, and presymptomatic and symptomatic HD brain in the Indian population. Materials and Methods: Seventeen HD (11 symptomatic HD [S-HD] and six presymptomatic HD [P-HD], with comparable CAG repeats), and 12 healthy controls were examined. Macrostructural (volume), microstructural (diffusivity), and functional (neurochemical levels and glucose metabolism) imaging of the brain was done along with the determination of visual latencies. Results: HD brain showed increased intercaudate distance; significant subcortical volumetric loss; reduced fractional anisotropy; increased mean, axial, and radial diffusivity; lower levels of total N-acetyl aspartate; elevated total choline levels; and reduced glucose metabolism compared with control brain. Interestingly, compared with P-HD, S-HD patients demonstrated a strong inverse correlation between age at onset and CAG repeat length, and prolonged P100 latency. In addition, caudate and putamen in S-HD brain showed significant volumetric loss and increased diffusivity compared with P-HD brain. Conclusions: HD brain showed distinct macrostructural, microstructural, and functional differences compared with control brain in the Indian population. Interestingly, patients with S-HD had a significant volumetric loss, increased diffusivity, altered neurochemical profile, and delayed P100 latency compared with P-HD patients. Examining these alterations clinically could aid in monitoring the progression of HD.
AB - Background: Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric abnormalities. Currently, matched analyses of structural and functional differences in the brain from the same study cohort and, specifically, in HD patients from an ethnically diverse Indian population are lacking. Such findings aid in identifying noninvasive and sensitive imaging biomarkers. Objective: The aim of the study was to understand the structural and functional differences between HD and control brain, and presymptomatic and symptomatic HD brain in the Indian population. Materials and Methods: Seventeen HD (11 symptomatic HD [S-HD] and six presymptomatic HD [P-HD], with comparable CAG repeats), and 12 healthy controls were examined. Macrostructural (volume), microstructural (diffusivity), and functional (neurochemical levels and glucose metabolism) imaging of the brain was done along with the determination of visual latencies. Results: HD brain showed increased intercaudate distance; significant subcortical volumetric loss; reduced fractional anisotropy; increased mean, axial, and radial diffusivity; lower levels of total N-acetyl aspartate; elevated total choline levels; and reduced glucose metabolism compared with control brain. Interestingly, compared with P-HD, S-HD patients demonstrated a strong inverse correlation between age at onset and CAG repeat length, and prolonged P100 latency. In addition, caudate and putamen in S-HD brain showed significant volumetric loss and increased diffusivity compared with P-HD brain. Conclusions: HD brain showed distinct macrostructural, microstructural, and functional differences compared with control brain in the Indian population. Interestingly, patients with S-HD had a significant volumetric loss, increased diffusivity, altered neurochemical profile, and delayed P100 latency compared with P-HD patients. Examining these alterations clinically could aid in monitoring the progression of HD.
KW - Atrophy
KW - chorea
KW - diffusivity
KW - Huntington's disease
KW - visual evoked potentials
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U2 - 10.4103/0028-3886.329528
DO - 10.4103/0028-3886.329528
M3 - Article
C2 - 34747792
AN - SCOPUS:85119049299
SN - 0028-3886
VL - 69
SP - 1247
EP - 1258
JO - Neurology India
JF - Neurology India
IS - 5
ER -