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 ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1247--1258

Multimodal Imaging and Visual Evoked Potentials Reveal Key Structural and Functional Features That Distinguish Symptomatic From Presymptomatic Huntington's Disease Brain


1 Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, India
2 Advanced Imaging Research Center, UT Southwestern Medical Center, Texas, USA
3 Department of Radiology, Sri Sathya Sai Institute of Higher Medical Sciences, Bengaluru, Karnataka, India
4 FDI + Care, Department of Nuclear Medicine and PET CT, Mazumdar Shaw Cancer Centre, Bengaluru, Karnataka, India
5 Department of Neurosurgery, Sri Sathya Sai Institute of Higher Medical Sciences, Bengaluru, Karnataka, India
6 Department of Neurology, Sri Sathya Sai Institute of Higher Medical Sciences, Bengaluru, Karnataka, India
7 Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, USA
8 Siemens Healthcare Private Limited, Indian Institute of Science, Bengaluru, Karnataka, India
9 Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka, India

Correspondence Address:
E V Joshy
MBBS, MD, DM (NIMHANS), Neuromuscular Fellowship (USA) Dr. Joshy's Holistic Neurology – Joshy's Medical Center, Senior Consultant Neurologist, Brains Hospital; Former Chief of Neurology, Department of Neurology, Sri Sathya Sai Institute of Higher Medical Sciences, Bengaluru, Karnataka
India
Venketesh Sivaramakrishnan
Associate Professor, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh
India
Vivek Tiwari
Assistant Professor, Centre for Brain Research, Indian Institute of Science, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.329528

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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.






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