Innate structural biomarker to predict L-DOPA induced dyskinesia in Parkinson’s disease patients

Kumar, Aditya (2022) Innate structural biomarker to predict L-DOPA induced dyskinesia in Parkinson’s disease patients. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Aditya Kumar (17MS122)) 17MS122_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (8MB)

Abstract

The innate structural differences in the brain structures responsible for developing dyskinesia prior to starting L-DOPA medication have never been examined in Parkinson’s disease (PD) patients. PD is the second most commonly reported neurodegenerative disease after Alzheimer’s, and dopamine depletion in substantia nigra pars compacta (SNc) is considered its prominent characteristic. Since the dopaminergic neurons of the SNc project its axons to the striatum and further to the cortex, the whole circuit comprising the Thalamus, Caudate, Putamen, Nucleus-Accumbens, Globus pallidus, motor and somatosensory regions of the cortex gets affected. The most commonly used drug to compensate for dopamine depletion is L-DOPA. While L-DOPA remains the primary treatment for millions of PD patients, some PD patients develop dyskinesia (uncontrolled movements) due to L-DOPA medication, also called levodopa-induced dyskinesia (LID). Previous studies done on LID have involved a lesser sample size and were mostly focused on studying LID after L-DOPA medication (i.e. while ongoing treatment) has begun. However, no study has been done to explore if there already exist innate neuroanatomical differences in the brain of PD patients who develop LID. In this cross-sectional study, three groups comprising patients who develop dyskinesia in future (120 Dyskinetic), patients who do not develop dyskinesia in future (104 Non-Dyskinetic), and 100 Healthy controls subjects were compared on volumes of five subcortical regions (Caudate, Thalamus, Putamen, Globus pallidus, Nucleus-Accumbens) and cortical thickness, area, and volume of four cortical regions (Precentral, Paracentral, Postcentral, and Frontal middle). Using 3-Tesla T1-weighted MR images, volumes, cortical thickness, and area of the ROIs, as mentioned earlier, were calculated using the automated segmentation tool Freesurfer. Our results reveal a significant decrease in the volume of Left Putamen (p<0.0124) and Right Putamen (p<0.0337) in the Non-Dyskinetic group when compared to Healthy controls, and a significant increase in the volume of posterior cingulate and fusiform between the Dyskinetic and Healthy control groups even before starting the L-DOPA medication. However, no significant anatomical difference was observed between the Dyskinetic and Non-Dyskinetics groups in the aforementioned ROIs, suggesting no innate anatomical differences existed prior to starting L-DOPA medication between D and ND patients, and possibly there may exist other factors that may determine LID in PD patients.

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