Bhavani Shankara Bagepally

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.

In vivo evaluation of white matter pathology in patients of progressive supranuclear palsy using TBSS.

IntroductionThe purpose of this research is to study white matter (WM) changes in patients of progressive supranuclear palsy (PSP) using automated analysis of diffusion tensor imaging (DTI) indices.MethodsThis was a prospective study comprising of 24 patients of PSP and 26 matched healthy controls. Fractional anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) changes were studied in the WM of the PSP patients using an automated analysis technique, tract-based spatial statistics (TBSS). Two subtypes of PSP, i.e., classic Richardson’s syndrome (PSP-RS) and parkinsonian type (PSP-P), were also compared among themselves to identify relative severity of WM changes as well as identify spatial distribution of the differences. Clinicoradiological correlation was done to determine the strength of correlation between WM abnormalities identified using TBSS and clinical scores.ResultsThere were areas of significant abnormality seen in the frontoparietal cerebral WM, thalamus, midbrain tectum, superior cerebellar peduncle, and cerebellar WM. The abnormalities were more spatially widespread on MD and RD maps. Compared to PSP-P, the patients of PSP-RS had more spatial abnormalities localized to the frontal WM. There was no correlation between the observed WM changes and clinical rating scales.ConclusionsThe TBSS analysis showed widespread WM abnormalities in PSP patients including areas which have been shown to be involved in previous pathological studies. PSP-RS showed more severe white matter abnormality compared to the PSP-P subtype.

Apolipoprotein E Polymorphism and Dementia: A Hospital-Based Study from Southern India

Background/Aims: To evaluate the ApoE gene polymorphism among patients with dementia from southern India. Methods: Persons with dementia attending a geriatric clinic in a hospital setting located in southern India and matched controls were recruited. All subjects were evaluated on standard assessments and were diagnosed according to the ICD-10; genotyping was done at the apolipoprotein E (ApoE) locus. Results: The study comprised 212 cases and 195 controls. The ApoE4 allele was significantly more prevalent in dementia (λ = 0.18 vs. λ = 0.07; p = 0.0018), especially in the Alzheimer’s disease subgroup (n = 137; λ = 0.21 vs. λ = 0.07; p < 0.001), with a trend in vascular dementia subtype (n = 31; λ = 0.17 vs. λ = 0.07) in comparison with the control group. ApoE4 carrier status did not differ between the other dementia group (n = 44) and controls (p > 0.20), or between the Alzheimer’s group and vascular dementia groups. Cognitive and functional deficits were not correlated to the presence ApoE4 polymorphism in the dementia group. Conclusion: The study confirmed the positive association of the ApoE4 polymorphism in dementia, both in the Alzheimer’s and vascular etiology subgroups. Influence of this polymorphism on various clinical phenotypes, including extent of cognitive and functional deficits, needs further evaluation.

Subcortical structures in progressive supranuclear palsy: vertex-based analysis

To study the abnormalities of deep grey matter (GM) structures in patients with progressive supranuclear palsy (PSP) using MR volumetry and shape analysis techniques.

Apolipoprotein E4 and brain white matter integrity in Alzheimer's disease: tract-based spatial statistics study under 3-Tesla MRI.

Introduction: Apolipoprotein E4 (ApoE ε4) polymorphism is a known genetic risk factor for Alzheimer’s disease (AD). Objectives: To evaluate the role of ApoE ε4 on white matter structural integrity in AD. Methods: Subjects were 32 patients with probable AD (ApoE ε4-positive: n = 15) and 18 matched controls (ApoE ε4-positive: n = 6). All subjects were right-handed, evaluated using standard scales and genotyped at the ApoE locus. Diffusion tensor imaging was performed with a 3-tesla MRI scanner and analyzed using the tract-based spatial statistics method. Results: AD patients had significantly lower fractional anisotropy (FA) in bilateral temporoparietal, limbic and parahippocampal regions in comparison to healthy comparison subjects. ApoE ε4 carriers among both AD and healthy comparison subjects showed lower FA in limbic and medial temporal regions. Conclusions: There is a modest association between ApoE ε4 carrier status and reduction in white matter tract integrity at medial temporal and limbic regions in both healthy and AD subjects.

Identifying elders with neuropsychiatric problems in a clinical setting

Objective: Multiple health problems among the elderly necessitate a comprehensive enquiry to detect problems early and also initiate treatment. We utilized available validated instruments to comprehensively identify older persons with neuro-psychiatric problems including dementia and comorbid medical ailments in the screening desk of the geriatric clinic. Materials and Methods: Individuals aged 60 years and above seeking outpatient care at NIMHANS during a 2-year period (October 2008-September 2010) participated. We used General Health Questionnaire (12-item), AD8, questions to identify psychoses and neurological problems and a checklist of common medical ailments. A probable clinical diagnosis was made at the end by medical personnel based on ICD-10. Results: A total of 5,260 individuals were screened and more than one-third (36.7%) were women. About 50% had psychological distress (≥2 on GHQ-12), 20.1% had probable cognitive impairment (≥2 on AD8) and about 17% had symptoms suggestive of psychoses (≥1 on Psychoses screener). More than 65% had either a neurological or neurosurgical problems (≥1 on Neurological screener) and headache was the commonest complaint. At probable diagnosis, more than 50% had a neurological problem and over 30% had psychiatric disorders. Of these the most common psychiatric illnesses were psychotic disorders (22.0%), mood disorders (21.4%) and dementia (14.4%). The most common medical comorbidity included hypertension (36.4%), visual impairment (31.8%) and joint pains (30.5%). Nearly 80% had one or more medical comorbidity in addition to psychiatric illness. The overall set of instruments took about 15-20 minutes. It systematically and comprehensively guided in evaluating the elderly for neuropsychiatric problems and hence was collated to constitute the Instruments for Comprehensive Evaluation of the Elderly (ICE-E). Conclusions: ICE-E was brief, easy to administer and improved decision making even by personnel from a non-medical background. The instrument aided in systematically detecting neuro-psychiatric problems among the elderly (including psychological distress and cognitive changes) and other medical comorbidities.

Dementia and diabetes mellitus: association with apolipoprotein e4 polymorphism from a hospital in southern India.

Objective. To evaluate the association of Apolipoprotein E4 (ApoE4) in Alzheimers dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimers dementia (AD) (n = 209), individuals with non-Alzheimers dementia (nAD) (n = 122), individuals with parental history of AD (f/hAD) (n = 70), and control individuals who had normal cognitive functions and no parental history of dementia (NC) (n = 193). Dementia was diagnosed using International Classification of Diseases-10 revision (ICD-10) criteria. DM was assessed on the basis of self-report and/or use of antidiabetic medications. ApoE genotyping was done using sequence-specific primer polymerase chain reaction. Results. ApoE4 allele frequencies were highest among AD with comorbid DM (0.35) followed by AD without DM (0.25), nAD with DM (0.13), nAD without comorbid DM (0.12), and NC (0.08). Frequency of ApoE4 in persons with f/hAD was 0.13. The association of AD with co-morbid DM in ApoE4 carriers was more in comparison to NC with DM (OR = 5.68, P = 0.04). Conclusion. There is a significant association between AD with co-morbid DM and ApoE4 genotype.

Catatonia and mania in patient with AIDS: treatment with lorazepam and risperidone

A 30-year-old woman presented with psychiatric symptoms and was found to be HIV positive prior to admission to the hospital. We present the first case report of catatonia and mania in an HIV-positive subject unrelated to infectious processes. The catatonic symptoms were alleviated by intravenous lorazepam, and manic symptoms were adequately treated with risperidone. Clinicians need to be aware that HIV infection should be considered in all patients with new-onset mania alternating with catatonia or in those with HIV risk factors.

Childhood autism in India: A case-control study using tract-based spatial statistics analysis

Context: Autism is a serious behavioral disorder among young children that now occurs at epidemic rates in developing countries like India. We have used tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) measures to investigate the microstructure of primary neurocircuitry involved in autistic spectral disorders as compared to the typically developed children. Objective: To evaluate the various white matter tracts in Indian autistic children as compared to the controls using TBSS. Materials and Methods: Prospective, case-control, voxel-based, whole-brain DTI analysis using TBSS was performed. The study included 19 autistic children (mean age 8.7 years ± 3.84, 16 males and 3 females) and 34 controls (mean age 12.38 ± 3.76, all males). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were used as outcome variables. Results: Compared to the control group, TBSS demonstrated multiple areas of markedly reduced FA involving multiple long white matter tracts, entire corpus callosum, bilateral posterior thalami, and bilateral optic tracts (OTs). Notably, there were no voxels where FA was significantly increased in the autism group. Increased RD was also noted in these regions, suggesting underlying myelination defect. The MD was elevated in many of the projections and association fibers and notably in the OTs. There were no significant changes in the AD in these regions, indicating no significant axonal injury. There was no significant correlation between the FA values and Childhood Autism Rating Scale. Conclusion: This is a first of a kind study evaluating DTI findings in autistic children in India. In our study, DTI has shown a significant fault with the underlying intricate brain wiring system in autism. OT abnormality is a novel finding and needs further research.