Ketan Jhunjhunwala

Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: A critical review.

Patients with Parkinsons disease (PD) may develop various non-motor symptoms (NMS) during the course of the illness and psychosis is one of the common NMS of PD. Visual hallucinations (VH) are the most common manifestation of psychosis in PD. The exact pathogenesis of VH in patients with PD is not clearly understood. Presence of VH has been described to be associated with rapid cognitive decline and increased nursing home placements in PD patients. A large number of structural and functional neuroimaging studies have been conducted to understand the cerebral basis of VH in PD. Structural imaging studies (Voxel Based Morphometry) have reported grey matter atrophy in multiple regions of the brain such as primary visual cortex, visual association cortex, limbic regions, cholinergic structures such as pedunculopontine nucleus and substantia innominata, which conclude possible alterations of brain regions associated with functions such as visuospatial-perception, attention control and memory. Most functional neuroimaging studies (functional MRI, positron emission tomography and single photon emission computerized tomography) have reported altered activation, blood flow, or reduced metabolism in both dorsal and ventral visual pathways, which probably indicates an alteration in the normal bottom-top visual processing and the presence of an aberrant top-down visual processing. This review critically analyzes the published studies on the structural and functional neuroimaging in PD patients with VH.

Interactions of visual hallucinations, rapid eye movement sleep behavior disorder and cognitive impairment in Parkinson's disease: A review

Patients with Parkinsons disease may develop various non-motor symptoms during the course of the illness. Visual hallucinations (VH) and cognitive impairment (CI) are two common non-motor symptoms of Parkinsons disease. Studies have reported association of both VH and CI with presence of rapid eye movement sleep behavior disorder (RBD). Presence of visual hallucinations and cognitive impairment has been described as risk factors for emergence of each other. There is marked overlap in the risk factors for development of RBD, VH and CI in patients with PD. Results of clinical and epidemiological studies as well as studies based on neuroimaging, electrophysiology especially transcranial magnetic stimulation and neuropsycholgical evaluations in PD patients have suggested presence of certain common neurobiological process leading to emergence of RBD, VH and CI. Structural neuroimaging studies using voxel-based morphometry have often reported grey matter atrophy of hippocampus and parahippocampal cortices in PD patients with RBD, VH and CI. Cholinergic dysfunction is common in PD patients with RBD, VH and CI. This review explores the complex interactions of RBD, VH and CI in patients with PD and their potential implications.

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).

Profile of extrapyramidal manifestations in 85 patients with spinocerebellar ataxia type 1, 2 and 3

This study aimed to determine the prevalence and type of extrapyramidal signs (EPS) in spinocerebellar ataxia (SCA) type 1, 2 and 3. Eighty-five patients with genetically confirmed SCA (SCA1=40, SCA2=28, SCA3=17) were evaluated for the prevalence and types of EPS. Forty-one SCA patients (48.2%) had one or more types of EPS. The prevalence of EPS was 60.7% in SCA2, 52.9% in SCA3, and 37.5% in SCA1. Among SCA2 patients, bradykinesia was the most frequent (35.3%), followed by reduced facial expression, postural tremor and dystonia (29.4% each), rest tremor, titubation and rigidity (23.5% each), and lip/jaw tremor and chorea (11.8% each). In SCA3 the common EPS were bradykinesia (44.4%), staring look, postural tremor and dystonia (33.3% each), and reduced facial expression and rigidity (22.2% each). In SCA1, staring look was the most common (53.3%), followed by dystonia and bradykinesia (33.3% each), and postural tremor (26.7%). In all three groups, there was no significant difference in the mean length of repeat of the abnormal allele between those with and without EPS. To conclude bradykinesia, staring look, dystonia and postural tremor were the most frequent EPS observed in SCA. In SCA1, these signs were seen more often in younger patients with early onset of symptoms.

Neuropsychological and imaging profile of patients with Parkinson's disease and freezing of gait

BACKGROUND Neuropsychological evaluation with advanced neuroimaging may be a useful tool to determine the anatomical substrates that play crucial role in freezing of gait (FOG) in patients with Parkinsons Disease (PD). OBJECTIVES To compare the cognitive profile and gray matter (GM) changes (using Voxel Based Morphometry - VBM) between patients with PD with and without FOG (FOG+ve and FOG-ve). METHODS Seventeen FOG+ve (M:F = 11:6) and 21 FOG-ve (M:F = 11:10) were evaluated clinically and with a structured neuropsychological battery. All patients underwent 3 T MRI. In order to determine areas of GM atrophy, T1W volumetric MRI data of the two groups were compared using VBM and Statistical Parametric Mapping 8. RESULTS The mean age of FOG+ve and FOG-ve patients were 56.9 ± 6.6 and 47.4 ± 9.1 years respectively. There was no significant difference in the duration (6.0 ± 4.9 vs 5.2 ± 3.5 years, p < 0.05) and stage of PD (Hoehn & Yahr stage: 1.96 ± 0.53 vs 1.78 ± 0.37) between the two groups. Compared to the FOG-ve group, the FOG+ve group had (i) significant impairment in memory, attention, executive and visuospatial functions on neuropsychological tests, and (ii) significant GM atrophy in the right cerebellum (pyramis, declive), left cerebrum (Brodmann area (BA) 21 and 22) and right cerebrum (BA 10 and 6) on VBM analysis. CONCLUSIONS The FOG+ve group showed widespread involvement of cognition localizing to frontal, temporal (especially left) and parietal areas. VBM analysis showed significant GM atrophy in FOG+ve group in left temporal, right frontal areas (coinciding with that observed in neuropsychological tests) and significant involvement of right cerebellum.

The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a Secondary Phenomenon?

Essential tremor (ET) is a pathologically heterogeneous neurodegenerative disorder with both motor and increasingly recognized non-motor features. It is debated whether the non-motor manifestations in ET result from widespread neurodegeneration or are merely secondary to impaired motor functions and decreased quality of life due to tremor. It is important to review these features to determine how to best treat the non-motor symptoms of patients and to understand the basic pathophysiology of the disease and develop appropriate pharmacotherapies. In this review, retrospective and prospective clinical studies were critically analyzed to identify possible correlations between the severities of non-motor features and tremor. We speculated that if such a correlation existed, the non-motor features were likely to be secondary to tremor. According to the current literature, the deficits in executive function, attention, concentration, and memory often observed in ET are likely to be a primary manifestation of the disease. It has also been documented that patients with ET often exhibit characteristic personality traits. However, it remains to be determined whether the other non-motor features often seen in ET, such as anxiety, depression, and sleep disturbances are primary or secondary to motor manifestations of ET and subsequent poor quality of life. Finally, there is evidence that patients with ET can also have impaired color vision, disturbances of olfaction, and hearing impairments, though there are few studies in these areas. Further investigations of large cohorts of patients with ET are required to understand the prevalence, nature, and true significance of the non-motor features in ET.

Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor

IntroductionEssential tremor (ET) is the most common movement disorder among adults. Although ET has been recognized as a mono-symptomatic benign illness, reports of non-motor symptoms and non-tremor motor symptoms have increased its clinical heterogeneity. The neural correlates of ET are not clearly understood. The aim of this study was to understand the neurobiology of ET using resting state fMRI.MethodsResting state functional MR images of 30 patients with ET and 30 age- and gender-matched healthy controls were obtained. The functional connectivity of the two groups was compared using whole-brain seed-to-voxel-based analysis.ResultsThe ET group had decreased connectivity of several cortical regions especially of the primary motor cortex and the primary somatosensory cortex with several right cerebellar lobules compared to the controls. The thalamus on both hemispheres had increased connectivity with multiple posterior cerebellar lobules and vermis. Connectivity of several right cerebellar seeds with the cortical and thalamic seeds had significant correlation with an overall score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) as well as the subscores for head tremor and limb tremor.ConclusionSeed-to-voxel resting state connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical network in patients with ET. These alterations correlated with the overall FTM scores as well as the subscores for limb tremor and head tremor in patients with ET. These results further support the previous evidence of cerebellar pathology in ET.

Movement disorders of probable infectious origin.

Background: Movement disorders (MDs) associated with infections remains an important debilitating disorder in the Asian countries. Objectives: The objective of the following study is to report the clinical and imaging profile of a large cohort of patients with MDs probably associated with infection. Materials and Methods: This was a chart review of 35 patients (F:M-15:20) presenting with MD in the Neurology services of National Institute of Mental Health and Neurosciences, India. The demographic profile, type of infection, time from infection to MD, phenomenology of MD and magnetic resonance imaging (MRI) findings were reviewed. Results: The mean age at presentation was 22.6 ± 13.3 years, (5-60), age of onset of MD was 15.7 ± 15 years, and duration of symptoms was 6.9 ± 8.1 years (42 days to 32 years). The mean latency of onset of MD after the infection was 5.9 ± 4.2 weeks. The phenomenology of MD were: (1) Pure dystonia-28.6%, (2) dystonia with choreoathetosis-22.9%, (3) Parkinsonism-14.6%, (4) pure tremor, hemiballismus, myoclonus and chorea-2.9% each, and (5) mixed MD-22.9%. Most often the MD was generalized (60%), followed by right upper limb (31.4%) and left upper limb (8.6%). A viral encephalitic type of neuroinfection was the most common infection (85.7%), which was associated with MD. Abnormalities of brain MRI, seen in 79.2%, included signal changes in (1) thalamus-52.0%, (2) putamen and subcortical white matter-16% each, (3) pons-12%, (4) striatopallidum, striatum and grey matter-8% each, and (5) caudate, cerebellum, lentiform nucleus, midbrain and subthalamic nucleus-4.0% each. Conclusions: MDs associated with infection were the most often post-encephalitic. Dystonia was the most common MD, and thalamus was the most common anatomical site involved.

Imaging biomarker correlates with oxidative stress in Parkinson's disease

Background: While oxidative stress (OS) may be one of the crucial factors determining the initiation and progression of Parkinsons disease (PD), its correlation with gray matter (GM) atrophy is not known. Aims: To determine the GM volume (GMV) changes using voxel-based morphometry (VBM) and correlation with OS marker serum malondialdehyde (MDA) in PD. Materials and Methods: Seventy-two patients with PD were clinically evaluated and underwent magnetic resonance imaging (MRI) on a 3T MRI scanner using a 32-channel head coil. Lipid peroxidation product MDA levels were measured by spectrophotometry. MDA levels and regional GM differences using VBM were compared with 72 healthy controls. Results: The mean age of the patients was 51.3 ± 10.6 years and that of controls was 50.8 ± 10.4 years. The mean age of onset of symptoms in PD was 45.2 ± 11.3 years. In PD, serum MDA level was significantly higher than that in controls (0.592 ± 0.89 μmol/l vs. 0.427 ± 0.055 μmol/l; P < 0.0001). Compared to controls, patients had greater regional GM atrophy in all the brain lobes (P < 0.001, uncorrected). A significant positive correlation was found between GMV and MDA in the caudate nucleus (CN) and posterior cingulate gyrus (PC) in the patient group (P < 0.001, uncorrected). Conclusions: We observed GM atrophy in all major brain lobes of patients when compared to controls. Only in the patient group, a significant positive correlation was observed in CN and PC with MDA. These findings suggest that, even though the whole brain is affected in PD, some of the non-substantia nigra regions of the brain, such as CN, may have some differential compensatory mechanism, which are preserved from oxidative damage.