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Background:Rapid eye movement sleep behaviour disorder (RBD) is considered to be one of the most frequent and important prodromal symptoms of Parkinson’s disease (PD). We aimed to study the neurophysiological abnormalities in patients of PD-RBD and PD without RBD (PD-nRBD) using transcranial magnetic stimulation (TMS).Methods:Twenty patients each of PD-RBD and PD-nRBD were included in the study in addition to 20 age and gender-matched healthy controls. RBD was identified using the RBD screening questionnaire (RBDSQ). All the subjects were evaluated with single and paired-pulse TMS and parameters such as resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded.Results:The mean age of the controls and PD patients with and without RBD was comparable. There were no significant differences in RMT, CMCT and silent period between the two patient groups. SICI was present in all the three groups with significant inhibition noted in PD-RBD group (p < 0.001). ICF was absent in patients of PD-RBD (0.19 ± 0.11) and PD-nRBD (0.7 ± 0.5) when compared to controls (1.88 ± 1.02) with profound impairment in patients with PD-RBD (p < 0.001). The mean MoCA score was found to be significantly different in all the three groups with a worse score in patients with RBD (23.10 ± 2.55; p < 0.001).Conclusions:PD-RBD patients have significantly greater inhibition and reduced intracortical facilitation suggesting enhanced GABAergic and reduced glutaminergic transmission. These abnormalities may underlie the different pathophysiological process observed in these patients.

BackgroundEmerging evidence support the view that brain stimulation might improve essential tremor (ET) by altering brain networks and facilitating plasticity. Yet, we are still missing a mechanistic explanation of the whole brain dynamics underlying these plasticity defining changes.MethodIn this study, we explored the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over left primary motor cortex (L-M1) on functional connectivity dynamics (FCD) in patients with ET. Resting-state fMRI (RsfMRI) was acquired before and after a single session of rTMS in 30 patients with ET and compared with RsfMRI of 20 age and gender matched healthy controls (HCs). We have measured the effect of brain stimulation using network topological re-organization through whole brain integration and segregation, brain stability and capacity of neural propagation through metastability and intrinsic ignition.ResultsPatients with ET had altered FCD measures compared to controls. After a single session rTMS, the brain connectivity measures approached normality and patients with ET revealed significantly higher integration, lower segregation with higher metastability and increased intrinsic ignition.ConclusionBrain metastability and intrinsic ignition measures could be valuable tools in appreciating mechanisms of brain stimulation in ET and other neurological diseases.

BACKGROUND AND PURPOSE: The corpus callosum (CC) consists of topographically arranged white matter (WM) fibers. Previous studies have indicated the CC to be discretely involved in WD. In this study, we strived to characterize the macrostructural properties of the CC using midsagittal cross-sectional area and thickness profile measurements. MATERIALS AND METHODS: This study was performed using archived magnetic resonance imaging (MRI) scans of 14 patients with WD and 14 age- and gender-matched healthy controls. Using an automated software pipeline for morphometric profiling, the midsagittal CC was segmented into five sub-regions (CC1–5) according to the Hofer–Frahm scheme. The mean thickness and area of different CC segments and their clinical and cognitive correlates were identified. RESULTS: The mean area was significantly different only in CC2 segment (94.2 ± 25.5 vs. 118.6 ± 19.7 mm2, corrected P < 0.05). The mean thickness was significantly different in CC1 (5.06 ± 1.15 vs. 6.93 ± 0.89 mm, corrected P < 0.05), CC2 (3.73 ± 0.96 vs. 4.87 ± 1.01 mm, corrected P < 0.05), and CC3 segments (3.42 ± 0.84 vs. 3.94 ± 0.72 mm, corrected P < 0.05). The age at onset of neurological symptoms and MMSE score was significantly correlated with the morphometric changes of CC1 and CC2 segments. CONCLUSION: Morphological changes of the CC are discrete in WD. Morphometric loss of CC was associated with an earlier onset of neurological symptoms and cognitive dysfunction in WD.

OBJECTIVE White matter (WM) integrity of Spinocerebellar ataxia 2 (SCA2) is poorly understood, more so in the early stages of SCA2. In this study, we evaluated the microstructural integrity of the WM tracts with an emphasis on the nature of in vivo pathological involvement in early SCA2. MATERIALS AND METHODS We evaluated the MRI images of 26 genetically proven SCA2 patients with disease duration

Parkinson's disease (PD) with cognitive impairment (PDCI) is essentially diagnosed through clinical and neuropsychological examinations. There is a need to identify biomarkers to foresee cognitive decline in them. We performed label-free unbiased nontargeted proteomics (Q-TOF LC/MS-MS) on the CSF of non-neurological control; PDCI; PD; and normal pressure hydrocephalus (NPH) patients, followed by targeted ELISA for validation. Of the 281 proteins identified, 42 were differentially altered in PD, PDCI, and NPH. With a certain overlap, 28 proteins were altered in PDCI and 25 proteins were altered in NPH. Five significantly upregulated proteins in PDCI were fibrinogen, gelsolin, complement factor-H, and apolipoproteins A-I and A-IV, whereas carnosine dipeptidase-1, carboxypeptidase-E, dickkopf-3, and secretogranin-3 precursor proteins were downregulated. Those uniquely altered in NPH were the insulin-like growth factor-binding protein, ceruloplasmin, α-1 antitrypsin, VGF nerve growth factor, and neural cell adhesion molecule L1-like protein. The ELISA-derived protein concentrations correlated with neuropsychological scores of certain cognitive domains. In PDCI, the Wisconsin card sorting percentile correlated negatively with fibrinogen. Intraperitoneal injection of native fibrinogen caused motor deficits in C57BL/6J mice as assessed by the pole test. Thus, a battery of proteins such as fibrinogen-α-chain, CFAH, and APOA-I/APOA-IV alongside neuropsychological assessment could be reliable biomarkers to distinguish PDCI and NPH.

Objective Non-motor symptoms (NMSs) significantly contribute to increased morbidity and poor quality of life in patients with parkinsonian disorders. This study aims to explore the profile of NMSs in patients with progressive supranuclear palsy (PSP) using the validated Non-Motor Symptom Scale (NMSS). Methods Seventy-six patients with PSP were evaluated in this study. Motor symptoms and NMSs were evaluated using the PSP Rating Scale (PSPRS), Unified Parkinson's Disease Rating Scale-III, Montreal Cognitive Assessment, Hamilton Depression (HAM-D) and Anxiety Rating Scales, Parkinson's Disease Sleep Scale (PDSS) and NMSS. NMS severity and prevalence were also compared between patients with PSP-Richardson syndrome (PSP-RS) and those with PSP-parkinsonism. Results All subjects in this cohort reported at least 2 NMSs. The most prevalent NMSs in patients with PSP were in the domains of sleep/fatigue, mood/cognition, and sexual function. The least prevalent NMSs were in the domains of cardiovascular including falls, and perceptual problems/hallucinations. Significant correlations were observed between the NMSS scores and HAM-D, PDSS, PSPRS scores and PSPRS sub-scores. The severity of NMSs was unrelated to the duration of illness. Patients with PSP-RS reported a higher severity of drooling, altered smell/taste, depression and altered interest in sex and a higher prevalence of sexual dysfunction. Conclusion NMSs are commonly observed in patients with PSP, and the domains of sleep, mood and sexual function are most commonly affected. These symptoms contribute significantly to disease morbidity, and clinicians should pay adequate attention to identifying and addressing these symptoms.

Spinocerebellar ataxia type-12 (SCA12) is a rare form of SCA, most commonly reported from the IndianA retrospective chart-review of the genetically confirmed SCA12 patients from our centre. The demographic, clinical, and investigation findings were reviewed. Correlation of expanded repeats length with various demographic and clinical features were studied.A total of 49 patients (34 males, 42 families) were included of which 79.6% belonged toSCA12 is not confined to a single ethnicity. Upper limb tremor and ataxia were the most common presentation. Unusual presentation may cause diagnostic confusion especially when recorded in patients from non

Objective With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology.Methods This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia.Results Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1–58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years.Conclusion CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. We aimed to study the abnormalities in the retinal layers in patients with WD using optical coherence tomography (OCT).The study is a chart review of 16 patients with WD (six females) who underwent OCT at our hospital during follow-up visits. Spectral-domain OCT was performed in all subjects to assess the thickness of macula and retinal nerve fiber layer (RNFL) and the data was compared with 14 healthy controls (three females).The mean age of the patients was 20.81 ± 7.47 years and controls was 26.86 ± 9.95 years. The mean age at the onset of the illness was 16.25 ± 5.57 years (range 11-28 years) with the mean duration of illness being 4.81 ± 3.31 years at the final follow-up examination. The mean macular thickness was found to be significantly reduced in patients (232.13 ± 19.39) when compared to controls (271.30 ± 17.32 μm;Abnormalities of the retinal layers were observed in the patients with WD. OCT is a non-invasive tool to identify and quantify the abnormalities of the retinal layers.

Introduction: Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder caused by mutations in theNPC 1or2genes. Movement disorders can occur as the first symptom and as predominant symptom mainly in juvenile-onset. The frequency and heterogeneity of movement disorders in NPC are not well described. We studied the frequency and spectrum of movement disorders in patients with NPC of different age of onset.Methods: Retrospective chart review of patients with NPC diagnosed based on the Suspicion Index tool and demonstration of foamy macrophages/sea-blue histiocytes in bone marrow aspirate.Results: We report 9 cases of NPC with 2 patients of late-infantile, 4 juvenile-onset and 3 of adult-onset. The mean age at onset of symptoms was 11.7 ± 10.4 (range 4–38 years) and the median duration of illness was 4 years. Vertical supranuclear gaze palsy (VSGP) was noted in 8 patients and VSGP with slowing of saccade in 1 patient. Splenomegaly was seen in 5 patients. Movement disorders as the first symptom occurred in 4 patients. Dystonia was the first symptom in 2 patients and cerebellar ataxia in 2 patients. Cerebellar ataxia occurred during the course of illness in 5 patients, dystonia in 6 patients. One patient with late-infantile NPC had stimulus-sensitive myoclonus.Conclusion: Movement disorders are common in NPC and occur as a presenting symptom. Cerebellar ataxia and dystonia are the most common movement disorder in NPC. Vertical supranuclear gaze palsy along with the movement disorders should lead to clinical suspicion of NPC.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson’s disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.

Cognitive impairment is a debilitating non-motor symptom of Parkinsons disease (PD). The diagnosis of PD with cognitive impairment (PDCI) is essentially through clinical and neuropsychological examinations. There is an emerging need to identify biomarker(s) to foresee cognitive decline in PD patients, at an early stage. We performed label-free unbiased non-targeted proteomics (Q-TOF LC/MS-MS) in CSF of non-neurological control (NNC); PDCI; PD and normal pressure hydrocephalus (NPH), followed by targeted ELISA for validation. The diagnosis was confirmed by neuropsychological and MRI assessments prior to CSF collection. Of the 282 proteins identified by mass spectrometry, 42 were differentially altered in PD, PDCI and NPH. Further, 28 proteins were altered in PDCI and 25 in NPH. An interesting overlap of certain proteins was noted both in PDCI and NPH. Five significantly upregulated proteins in PDCI were fibrinogen, gelsolin, complement factor-H, apolipoprotein A-IV and apolipoprotein A-I. Whereas carnosine dipeptidase 1, carboxypeptidase E, dickkpof 3 and secretogranin 3 precursor proteins were down-regulated. NPH also had few uniquely altered proteins viz. insulin-like growth factor-binding protein, ceruloplasmin, -1 antitrypsin, VGF nerve growth factor, neural cell adhesion molecule L1 like protein. Interestingly, the ELISA-derived protein concentrations correlated well with the neuropsychological scores of certain cognitive domains. Executive function was affected both in PDCI and NPH. In PD, Wisconsin card sorting test (WCST) percentile correlated positively with ApoA-IV and negatively with the ratio of ApoA-I:ApoA-IV. Thus assessment of a battery of proteins like fibrinogen--chain, CFAH and ApoA-I:ApoA-IV ratio alongside neuropsychological could be reliable biomarkers to distinguish PDCI and NPH. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/436097v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@18b0dbaorg.highwire.dtl.DTLVardef@323e83org.highwire.dtl.DTLVardef@a63cd2org.highwire.dtl.DTLVardef@1e3285b_HPS_FORMAT_FIGEXP M_FIG C_FIG

INTRODUCTION: Cognitive impairment (CI) is reported but is poorly explored in spinocerebellar ataxia 2 (SCA2). This study was undertaken to evaluate and classify cognitive impairment in patients with SCA2 and to identify their grey matter (GM) correlates. METHODS: We evaluated the neurocognitive profile of 35 SCA2 and 30 age-, gender- and education-matched healthy controls using tests for attention, executive functions, learning and memory, language and fluency, and visuomotor constructive ability. Patients were classified into SCA2 with and without CI based on normative data from population and healthy controls. Furthermore, patients with CI were sub-classified based on the number of impaired domains into multi-domain CI (≥3 domains; MDCI) and limited domain CI (≤2 domains; LDCI). The underlying GM changes were identified using voxel based morphometry. RESULTS: The mean age at onset, duration of disease, and ataxia score was 28.7 ± 8.51 years, 66.7 ± 44.1 months, and 16.1 ± 4.9 points, respectively. CI was present in 71.4% of SCA2 subjects (MDCI: 42.7%; LDCI: 28.5%). Patients with CI had significant atrophy of the posterior cerebellum, sensorimotor cortex, and superior frontal gyrus (FWE p-value

Background The spectrum of symptoms exhibited by patients with essential tremor (ET) extends far beyond the classical tremor. This study aims to explore and establish the presence of subtle balance abnormalities in ET using dynamic posturography (DP). Methods DP was performed on 18 patients with ET and 26 controls. Diagnosis of ET was based on the Consensus Statement of the Movement Disorder Society on Tremor. Dynamic stability which included the overall balance index, anterior-posterior index and mediolateral index, and limits of stability were measured. Results Patients with ET had significantly impaired balance indices. Impairment of dynamic stability revealed poor static balance control in all directions. Lower limits of stability scores indicated a smaller range of motion prior to which patients have to shift foot balance. No correlations were observed between age at evaluation, age at onset, duration of illness and the balance indices. Conclusions Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET.

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB).This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (HY) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB.The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and HY stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5).Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up.

To determine the diagnostic characteristics of poor visualisation of nigrosome-1 as a neuroimaging biomarker in Parkinson’s disease (PD) and to explore the relationship of poor visualisation of nigrosome-1 and clinical asymmetry. High-resolution gradient-echo sequences of 67 patients with PD and 63 healthy controls were reviewed by two radiologists blinded to the clinical details. A three-tier classification system was used to categorise the scans based on the visualisation of nigrosome-1, and inter-rater reliability was calculated at each level of classification. Other diagnostic properties such as sensitivity, specificity and predictive values were calculated. The relationship between poor visualisation of nigrosome-1 and clinical asymmetry was also assessed. Poor visualisation of nigrosome-1 had high sensitivity (98.5%), specificity (93.6%), positive-predictive value (94.3%), negative-predictive value (98.3%), accuracy (96%) and inter-rater reliability (k = 0.75–0.92). Poorly visualised nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side in 64.8% of subjects (p = 0.004). Poor visualisation of nigrosome-1 in PD had good diagnostic properties as a neuroimaging biomarker in PD. There was also a significant agreement on clinical asymmetry and poor visualisation of nigrosome-1. • Nigrosome-1 represents the largest collection of dopaminergic neurons in dorso-lateral substantia nigra. • Loss of nigrosome-1 is being studied as a biomarker in Parkinson’s disease. • Visualisation of nigrosome-1 had good diagnostic properties as a biomarker. • There was a contralateral relationship between nigrosome-1 lateralisation and clinical asymmetry. • We also highlight the potential limitations of nigrosome-1 visualisation as a biomarker.

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinson’s disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results suggest that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.

To determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson's disease using voxel based morphometry (VBM).Clinical and imaging data of 10 patients (all male, mean age 16.0 ± 6.3years) with Wilson's Disease were analyzed. T1W volumetric MRI data of patients without obvious cortical atrophy or signal changes on conventional MRI was compared with MRI of 11 matched control subjects using VBM analysis with Statistical Parametric Mapping 8. Results were expressed at statistical threshold of p 0.05 (FWE corrected) and p 0.001 (uncorrected). Multiple regression analysis was done to analyze possible relation between GM atrophy, duration of disease and biochemical abnormalities.Compared to controls, patients showed scattered areas of reduced GM volume in bilateral caudate head, medial part of right globus pallidus and body of right caudate (FWE corrected p 0.05). At p 0.001(uncorrected) widespread areas of cortical atrophy were also noted involving the frontal and temporal lobes, lentiform nuclei, cerebellum and thalamus. Significant positive correlation (uncorrected p 0.001) were noted between (i) duration of disease and cortical GM volume of frontal, parietal and temporal lobes and cerebellum (ii) serum copper levels and GM volume of right medial frontal gyrus and paracentral lobule.To the best of our knowledge, this is the first VBM study in patients with Wilson's disease. In spite of apparently normal cortex on visual inspection of MRI, decreased cortical GM volume was detected using VBM. In addition, serum copper may act as surrogate marker of cortical abnormalities in Wilson's disease.

To explore the neuroanatomical correlates of primary writing tremor (PWT) and the role of cerebellum, using advanced structural neuroimaging. Till date, there are no studies exploring the gray and white matter changes using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in PWT. Ten male patients with PWT were evaluated clinically and with magnetic resonance imaging. VBM and DTI images of patients were compared with that of 10 healthy male subjects. Spatially unbiased infra-tentorial template (SUIT) analysis was done to investigate the alterations of cerebellar gray matter. Region-of-interest analysis was performed on regions observed to be significantly different on DTI analysis. The mean duration of illness and mean age of the patients were 3.5 ± 1.9 and 51.7 ± 8.6 years, respectively. On VBM analysis, the cluster of gray matter atrophy was found in bilateral cerebellar areas of culmen and left declive, right superior and medial frontal gyrus, bilateral middle frontal gyrus, bilateral anterior cingulate gyrus, and bilateral parahippocampal gyrus. DTI showed significantly reduced fractional anisotrophy of the anterior thalamic radiation, cingulum, and inferior fronto-occipital fasciculus in PWT patients compared to controls. The axial diffusivity, mean diffusivity, and radial diffusivity maps did not reveal any significant differences. On SUIT analysis, significant atrophy was found in right uvula and semilunar lobule in patients with PWT compared to controls. Our study found that patients with PWT had predominant gray matter atrophy in parts of cerebellum and frontal lobe along with white matter changes of the cingulum and frontal lobe connections.

Sleep disturbance is one of the commonly reported non-motor symptoms in patients with Parkinson's disease (PD) as well as in Parkinson plus disorders such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). Although there is a wealth of literature on sleep disturbances in PD, the same is not robust on the Parkinson plus disorders. This article aims to comprehensively review the sleep disturbances in Parkinson plus disorders. The literature review was as per the guidelines of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). We searched PubMed and MEDLINE till December 2019 using a combination of words - "Sleep disturbance" with additional search terms such as: "synucleinopathy", "tauopathy", "multiple system atrophy", "dementia with Lewy bodies", "progressive supranuclear palsy", and "corticobasal syndrome". A wide range of sleep disorders that include insomnia, rapid eye movement (REM) sleep behaviour disorder (RBD), periodic limb movement disorder, excessive daytime sleepiness, and sleep apneas, may complicate the course of the Parkinson plus disorders. Pathophysiology of these sleep disorders remains elusive, thus making targeted pharmacotherapy challenging. We describe the cardinal features and the management options of these sleep disorders in the context of Parkinson plus disorders.

Background: The occurrence of impulse control disorders (ICDs) in Parkinson's disease (PD) is frequently attributed to dopamine replacement therapy. However, not all patients who receive medication develop ICDs. Recent imaging studies have suggested specific neuroanatomical abnormalities in patients with PD and ICD. Objectives: This study aims to identify changes in volumes of subcortical structures and cortical thickness specific to patients with PD and ICDs. Methodology: A total of 11 patients with PD and ICD (PDICD(+)), 15 patients with PD without ICD (PDICD(−)), and 15 healthy controls were analyzed in this study. ICDs were diagnosed and quantified using the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). Structural imaging was performed on a 3T scanner; volumes of subcortical structures and cortical thickness were obtained using first in FSL and FreeSurfer. Results: Significant volume loss of the nucleus accumbens was observed in the PDICD(+) group. Several areas of significant cortical thinning were observed in the PDICD(+) group in comparison PDICD(−) group. Thinning of the left middle temporal gyrus, transverse temporal gyrus, and bilateral temporal poles was observed in the PDICD(+) group. No correlations were observed between QUIP-RS scores and areas of cortical thinning. Conclusions: The PDICD(+) group has specific neuroanatomical variations in the nucleus accumbens and temporal lobes, which may contribute to the development of ICD and perhaps predispose a patient to ICDs on exposure to dopamine replacement therapy.

To evaluate the non-ataxic clinical manifestations in genetically proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and predictors.Seventy-three subjects with genetically proven SCA2 were evaluated clinically for the common non-ataxic manifestations. Based on the presence or absence of non-ataxic manifestations, patients were classified into groups and then compared for significant differences in the CAG repeat length, age at onset (AAO), duration of disease, and ataxia rating score. Predictors of non-ataxic symptoms were identified using multivariable binary logistic regression.The most common non-ataxic clinical manifestations were peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive impairment and lower motor neuron signs. The CAG repeat length was inversely related to the AAO of symptoms (r = -0.46, p .001). Patients with peripheral neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive impairment and extrapyramidal symptoms had higher CAG repeat length whereas presence of lower motor neuron signs was more common in patients with lower CAG repeat length.The lower strength of association between CAG repeat length and AAO in our cohort suggests the presence of additional factors underlying the variability in AAO. Both CAG repeat length and AAO were identified as significant determinants and predictors of non-ataxic symptoms.