Rose Dawn Bharath

Decrease in Cerebral and Cerebellar Gray Matter in Essential Tremor: A Voxel-Based Morphometric Analysis under 3T MRI

Though routine neuroimaging is usually normal in essential tremor (ET) there is clinical evidence of widespread involvement of central nervous system. This study aimed at determining morphological changes in brain of patients with ET using voxel‐based morphometry (VBM) analysis and also compare the subtypes of ET.

Diffusion tensor imaging: Tract based spatial statistics study in essential tremor

INTRODUCTION Essential tremor (ET) is a common movement disorder with motor and non-motor symptoms. We aimed to investigate the neurodegenerative changes in the brain white matter of patients with ET using Diffusion Tensor Imaging (DTI). METHODS Clinical and MRI data from 20 patients (5 women and 15 men; age-38.2 ± 16.5 yrs) with ET and 17 controls (3 women and 14 men; age-40.7 ± 16.5 yrs) were collected prospectively. The DTI data were analyzed using tract based spatial statistics (TBSS) software for tract wise analysis. Further region of interest (ROI) analysis was carried out in the genu of corpus callosum, anterior limb of internal capsule (ALIC), corticospinal tract (CS), and cerebellar peduncles. Effect of tremor severity, disease duration and age of onset on DTI metrics was also studied. RESULTS Patients with ET in comparison to controls showed significant (P(corrected) < 0.05) increase of mean diffusivity and radial diffusivity in right frontoparietal white matter. Axial diffusivity increase was seen in bilateral cerebral hemispheres, thalamus, brainstem and cerebellar hemisphere white matter. No significant change in fractional anisotropy of the white matter was seen. ROI analysis also revealed abnormalities in the ALIC and cerebellar peduncles. There was no correlation between the severity of white matter changes and clinical tremor severity score as well as disease duration. CONCLUSIONS This study provides in vivo evidence for axonal disintegration of the cerebral and cerebellar white matter fibres in patients with ET.

Recovery of resting brain connectivity ensuing mild traumatic brain injury

Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

Hyperemesis gravidarum induced Wernicke's encephalopathy: Serial clinical, electrophysiological and MR imaging observations

Wernickes encephalopathy (W.E.), a potentially reversible condition caused by thiamine deficiency, is usually suspected in the setting of chronic alcoholism and might not be recognized when associated with other conditions. We describe a young pregnant woman who presented with rapidly evolving ataxia, diplopia and irrelevant speech following repeated vomiting. Characteristic brain MRI and rapid response to thiamine suggested that she had W.E. possibly due to hyperemesis gravidarum. A high index of suspicion is required, since delayed or lack of treatment may lead to high morbidity and mortality.

Clinical and Imaging Observations in Isolated Sulfite Oxidase Deficiency

Isolated sulfite oxidase deficiency is a rare neurometabolic disorder that closely mimics hypoxic ischemic encephalopathy both clinically and radiologically. Phenotypic and imaging observations in 2 children (aged 14 months and 8 years) with this disease are described. Both had profound mental retardation, microcephaly, spastic quadriparesis, and uncontrolled seizures from the neonatal period. Diagnosis was established by demonstrating the presence of sulfites in urine and genetic analysis. Magnetic resonance imaging of the brain revealed severe cystic leukomalacia, cortical atrophy with ulegyric pattern, and cerebellar hypoplasia that progressed over time in both the patients. Early diagnosis of this devastating disorder will provide an opportunity for genetic counseling and prenatal testing.

Freezing of gait in Parkinson's disease is associated with altered functional brain connectivity

BACKGROUND Patients with Parkinsons disease (PD) may develop several gait disturbances during the course of illness and Freezing of gait (FOG) is one of them. Several neuroimaging studies have been conducted to identify the neural correlates of FOG but results have not been uniform. Resting state functional MRI (rs-fMRI) is relatively less explored in PD patients with FOG. This study aims to compare the whole brain resting state connectivity of PD patients with and without FOG using rs-fMRI. METHODS rs-fMRI was obtained for 28 PD patients (15 with and 13 patients without FOG) who were matched for various demographic and clinical characteristics. Seed to voxel analysis was performed at whole brain level and compared between the two groups. RESULTS When compared to patients without FOG, the patients with FOG had reduced functional connectivity across multiple seeds. Major finding was reduced inter-hemispheric connectivity of left parietal opercular cortex with multiple regions of the brain primarily involving the primary somatosensory and auditory areas, which also negatively correlated with the FOGQ scores. CONCLUSION Our findings suggest that alterations in the resting state functional connectivity of the opercular parietal cortex may be one of the substrates of FOG. Reduced interhemispheric connectivity probably is the reason for impairment of control and coordination in bilateral leg movements while walking.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

Writers cramp (WC) is a focal task‐specific dystonia of the hand which is increasingly being accepted as a network disorder. Non‐invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI).

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.

Electro-clinical features and magnetic resonance imaging correlates in Menkes disease

BACKGROUND Epilepsy is an early and important feature in Menkes disease (MD), an X-linked recessive neurodegenerative disorder of childhood with defect in copper metabolism. There are only few reports on the electro-clinical and magnetic resonance imaging correlates in Menkes disease. The current study describes the electro-clinical features in MD in relation with the structural findings on MRI. PATIENTS AND METHODS Six patients from five families were evaluated between 2005 and 2011. Their diagnosis was based on the characteristic morphological features, microscopic evidence of pili torti and low copper and ceruloplasmin levels. All the patients underwent MRI and EEG as part of the evaluation. RESULTS All patients had classical form of MD with typical morphological features. All but one patient had refractory seizures. Seizure types included multifocal clonic seizures (n=3), myoclonic jerks (n=4) and tonic spasms (n=1). EEG was markedly abnormal in all except in the patient without clinical seizures. While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter. MR Imaging revealed abnormalities in all patients, with cerebral atrophy and delayed myelination being the most common observations. Other features noted were subdural effusion (n=3), leukoencephalopathy (n=3) and basal ganglia signal changes (n=1). Follow up imaging in three patients showed resolution of white matter signal intensity changes. CONCLUSIONS Electro-clinical features in Menkes disease are age dependent and evolve sequentially. White matter changes coincided with acute exacerbation of seizures. There was fair correlation between the electro-clinical features and structural findings on MRI.

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.