Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants.

OBJECTIVE: Multiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis. MATERIALS AND METHODS: Twenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls. RESULTS: The early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score. CONCLUSION: In early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA. KEY POINTS: • Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging. • White matter was more affected than grey matter in early MSA. • Clinical variables did not correlate with early structural changes.

Hippocampal subfield atrophy in patients with Parkinson's disease and psychosis.

Psychosis, manifested through formed visual hallucinations or minor hallucinations, is a common non-motor symptom of Parkinson's disease (PD). The pathogenesis of psychosis in PD remains unclear; however, is possibly linked to structural and functional alterations in the hippocampus. To explore the role of hippocampus in psychosis, a detailed hippocampal subfield analysis was performed on PD patients with (PD-P) and without psychosis (PD-NP), and healthy controls (HC). An automated subfield parcellation was performed on T1 MRI images of 141 subjects (PD-P:42, PD-NP:51, and HC:48). The volumes of 12 subfields on each side were estimated and analyzed between the three groups and were corrected for multiple comparisons using false discovery rates. The volumes were also correlated to psychosis severity and specific neuropsychological tests and finally were employed to predict the psychosis severity in PD-P using a support vector regression (SVR) model. Compared to controls, PD-NP group did not demonstrate any significant differences; however, the PD-P group had significantly lower total hippocampal volume. Bilateral molecular layer, granule cell-dentate gyrus, left subiculum, and hippocampal tail and right CA3, CA4, and HATA illustrated significantly lower volumes, while bilateral hippocampal fissure demonstrated a significant widening. Compared to PD-NP, the PD-P group had higher volume of the bilateral hippocampal fissures. Finally, SVR could significantly predict the psychosis severity from all the subfield volumes. Our findings indicate a higher degeneration of specific hippocampal subfields in PD-P compared to controls and a trend of higher volume of hippocampal fissures in PD-P group than in PD-NP.

A preliminary study of the neuroanatomical correlates of primary writing tremor: role of cerebellum.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Unraveling Brain Functional Connectivity of encoding and retrieval in the context of education.

Human memory is an enigmatic component of cognition which many researchers have attempted to comprehend. Accumulating studies on functional connectivity see brain as a complex dynamic unit with positively and negatively correlated networks in perfect coherence during a task. We aimed to examine coherence of network connectivity during visual memory encoding and retrieval in the context of education. School Educated (SE) and College Educated (CE) healthy volunteers (n=60) were recruited and assessed for visual encoding and retrieval. Functional connectivity using seed to voxel based connectivity analysis of the posterior cingulate cortex (PCC) was evaluated. We noticed that there were reciprocal dynamic changes in both dorsolateral prefrontal cortex (DLPFC) region and PCC regions during working memory encoding and retrieval. In agreement with the previous studies, there were more positively correlated regions during retrieval compared to encoding. The default mode network (DMN) networks showed greater negative correlations during more attentive task of visual encoding. In tune with the recent studies on cognitive reserve we also found that number of years of education was a significant factor influencing working memory connectivity. SE had higher positive correlation to DLPFC region and lower negative correlation to DMN in comparison with CE during encoding and retrieval.

Understanding the pathophysiology of reflex epilepsy using simultaneous EEG-fMRI.

Measuring neuro-haemodynamic correlates in the brain of epilepsy patients using EEG-fMRI has opened new avenues in clinical neuroscience, as these are two complementary methods for understanding brain function. In this study, we investigated three patients with drug-resistant reflex epilepsy using EEG-fMRI. Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. The analysis of EEG-fMRI data was based on the visual identification of interictal epileptiform discharges on scalp EEG. The convolution of onset time and duration of these epilepsy spikes was estimated, and using these condition-specific effects in a general linear model approach, we evaluated activation of fMRI. Patients with startle myoclonus epilepsy experienced epilepsy in response to sudden sound or touch, in association with increased delta and theta activity with a spike-and-slow-wave pattern of interictal epileptiform discharges on EEG and fronto-parietal network activation pattern on SPECT and EEG-fMRI. Eating epilepsy was triggered by sight or smell of food and fronto-temporal discharges were noted on video-EEG (VEEG). Similarly, fronto-temporo-parietal involvement was noted on SPECT and EEG-fMRI. Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement. SPECT and EEG fMRI revealed a similar fronto-parietal-occipital involvement. From these results, we conclude that continuous EEG recording can improve the modelling of BOLD changes related to interictal epileptic activity and this can thus be used to understand the neuro-haemodynamic substrates involved in reflex epilepsy.

Utility of resting fMRI and connectivity in patients with brain tumor.

BACKGROUND: Resting state (task independent) Functional Magnetic Resonance Imaging (fMRI) has opened a new avenue in cognitive studies and has found practical clinical applications. MATERIALS AND METHODS: Resting fMRI analysis was performed in six patients with brain tumor in the motor cortex. For comparison, task-related mapping of the motor cortex was done. Connectivity analysis to study the connections and strength of the connections between the primary motor cortex, premotor cortex, and primary somatosensory cortex on the affected side was also performed and compared with the contralateral normal side and the controls. RESULTS: Resting fMRI in patients with brain tumor in the motor cortex mapped the motor cortex in a task-free state and the results were comparable to the motor task paradigm. Decreased connectivity on the tumor-affected side was observed, as compared to the unaffected side. CONCLUSION: Resting fMRI and connectivity analysis are useful in the presurgical evaluation of patients with brain tumors and may help in uncooperative or pediatric patients. They can also prognosticate the postoperative outcome. This method also has significant applications due to the ease of image acquisition.

Abnormalities in the white matter tracts in patients with Parkinson disease and psychosis.

OBJECTIVE: The objective of the current study was to compare the microstructural integrity of the white matter (WM) tracts in patients having Parkinson disease (PD) with and without psychosis (PD-P and PD-NP) through diffusion tensor imaging (DTI). METHODS: This cross-sectional study involved 48 PD-NP and 42 PD-P who were matched for age, sex, and education. Tract-based spatial statistics (TBSS) was used to compare several DTI metrics from the diffusion-weighted MRIs obtained through a 3-Tesla scanner. A set of neuropsychological tests was used for the cognitive evaluation of all patients. RESULTS: The severity and stage of PD were not statistically different between the groups. The PD-P group performed poorly in all the neuropsychological domains compared with the PD-NP group. TBSS analysis revealed widespread patterns of abnormality in the fractional anisotropy (FA) in the PD-P group, which also correlated with some of the cognitive scores. These tracts include inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, right parieto-occipital WM, body of the corpus callosum, and corticospinal tract. CONCLUSION: This study provides novel insights into the putative role of WM tract abnormalities in the pathogenesis of PD-P by demonstrating significant alterations in several WM tracts. Additional longitudinal studies are warranted to confirm the findings of our research.

Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early?

INTRODUCTION: Psychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis. METHODOLOGY: In this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics. RESULTS: Compared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP. CONCLUSION: Presence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD.

A Study on Utilization and Evaluation of Antiemetics in Chemotherapy-induced Nausea and Vomiting.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are the major adverse effects of cancer chemotherapy. The objectives of this study are to evaluate the utilization of antiemetics in CINV and to assess the emetogenicity of chemotherapy and to investigate the incidence of acute and delayed CINV. METHODS: A prospective observational study was carried out in patients undergoing chemotherapy. A suitable data collection form was designed to collect data regarding patient's demographics, cancer type, chemotherapy regimen, antiemetic prescribed, and incidence of CINV according to the standard methods utilizing morrow assessment of nausea and emesis form. RESULTS: Among 200 patients enrolled in the study, with age range of 18-83 (52 ± 11.65; mean ± standard deviation) of both sexes (44% of male and 56% of female), 38.5% of patients received highly emetogenic chemotherapy and 46.5% received moderate emetogenic chemotherapy. Among the patients, 88% received 5HT3-RA in combination with corticosteroid (99%) and NK1-RA (40.5%). Despite the administration of antiemetic, the incidence of acute and delayed nausea after chemotherapy treatment was reported by 54% and 15.5%, respectively. The comparable figures for acute and delayed vomiting were 36.5% and 14.5%. CONCLUSION: The incidence of CINV among the patients was relatively high and it indicates that more attention is needed for the treatment of both acute and delayed CINV. It also gives an idea for implementation of more efficient antiemesis guideline in the clinical practice.

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

INTRODUCTION: 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). METHODOLOGY: 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 (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. RESULTS: 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 H&Y 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, p<0.01). 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). CONCLUSION: 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.

Role of Corpus Callosum Volumetry in Differentiating the Subtypes of Progressive Supranuclear Palsy and Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder. Classic PSP or Richardson-Steele phenotype (PSP-RS) and parkinsonian phenotype (PSP-P) are the common subtypes of PSP. At the early stage, differentiating the subtypes of PSP as well as differentiating PSP from other parkinsonian disorders, especially Parkinson's disease (PD) is challenging. Microstructural abnormalities of corpus callosum (CC) have been reported both in PSP and PD. The objective of this study was to compare the volumes of various segments of CC between patients with PSP-P, PSP-RS, and early PD. METHODOLOGY: This study included 32 patients with PSP (RS: 18, P: 14), 20 patients with early PD, and 25 controls. All subjects underwent 3-Tesla MRI. An automated surface-based analysis package (FreeSurfer) was used to divide CC into five segments: anterior (CC1), midanterior (CC2), central (CC3), midposterior (CC4), and posterior (CC5). Volumes of these segments were compared among the four groups. RESULTS: The PSP-RS group had significantly lower CC volume in all segments except in CC1 and CC5, whereas the volumes of the five segments of CC were comparable among PSP-P, PD and controls. The PSP-RS group had lower CC3 volume compared to the PSP-P group, and the PSP-RS group had lower volume of both CC2 and CC3 compared to the PD group. CONCLUSIONS: The lower volume of the central segment of CC (CC3) might help in differentiating PSP-RS from PSP-P. There is no significant difference in the pattern of CC atrophy in PSP-P and early PD. Studies with higher sample sizes are warranted to confirm the results of our study.

Exploring cortical atrophy and its clinical and biochemical correlates in Wilson's disease using voxel based morphometry.

OBJECTIVES: To determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson's disease using voxel based morphometry (VBM). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.