Abhishek Lenka

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.

Optical coherence tomography as a tool to evaluate retinal changes in Parkinson's disease.

BACKGROUND Though Parkinsons disease (PD) is primarily a disease of the basal ganglia, recent evidence suggests that PD affects the retina. OBJECTIVE The study was designed to evaluate the thickness of retinal nerve fiber layer (RNFL) and thickness and volume of the macula in PD and hence explore the utility of optical coherence tomography (OCT) in studying retinal changes in PD. METHODS A prospective, hospital based evaluation of 30 patients with PD and 30 healthy controls was carried out. Various parameters such as RNFL, central macular thickness (CMT), central and total macular volumes (TMV) and retinal thickness were analyzed using OCT. RESULTS (a) RNFL thickness was not significantly different between the patients and controls. A significant negative correlation was found between the RNFL thickness in the right nasal superior sector and the UPDRS motor score. (b) CMT was found to be significantly reduced in the right eye and a negative correlation with the UPDRS motor score was noted. (c) TMV was significantly greater in patients compared to the controls. (d) The outer retinal layer in the right nasal quadrant and the right inferior quadrants were found to be significantly thinner in patients with PD. CONCLUSIONS We did not find any significant abnormality in the RNFL thickness in patients with PD. Decreased CMT in patients with PD and a significant negative correlation of RNFL thickness and CMT with severity of PD suggest a remote possibility of dopaminergic depletion in the retina. However long term studies are warranted to validate our findings.

Genetic substrates of psychosis in patients with Parkinson's disease: A critical review

Patients with Parkinsons disease (PD) may develop several non-motor symptoms such as psychosis, depression, cognitive impairment, autonomic disturbances and sleep disturbances. Psychosis is one of the common non-motor symptoms, which commonly manifests as visual hallucinations and minor hallucinations such as sense of passage and presence. Though long-term dopaminergic therapy, longer duration of PD and cognitive impairment have been described as risk factors for emergence of psychosis in PD, predicting psychosis in PD remains challenging. Multiple studies have explored the genetic basis of psychosis in PD by studying polymorphisms of several genes. Most of the studies have focused on apolipoprotein E polymorphism followed by polymorphisms in cholecystokinin (CCK) system, dopamine receptors and transporters, HOMER gene, serotonin, catechol-o-methyltransferase, angiotensin converting enzyme and tau. Other than the studies on polymorphisms of CCK, most of the studies have reported conflicting results regarding association with psychosis in PD. Three out of four studies on CCK polymorphism have reported significant association of -45C>T polymorphism with the presence of hallucinations. The discrepancies in the results across the studies reviewed are possibly due to racial differences as well as differences in the patient characteristics. This review critically analyzes the published studies on genetic polymorphisms in patients with PD and psychosis.

Pattern of cognitive impairment in patients with Parkinson's disease and psychosis: A critical review

Psychosis is one of the debilitating non-motor symptoms (NMS) of Parkinsons disease (PD). Cognitive impairment is considered to be a risk factor for emergence of psychosis in PD. Early detection of relevant cognitive impairment may serve as a predictor for development of psychosis, with implications for prevention and early intervention. However, the exact pattern of cognitive impairment associated with psychosis is not clear. In this article, we aim to critically review the literature on case-control studies in PD patients with and without psychosis in order to understand the pattern of cognitive impairment in those with psychosis. Majority of studies conducted till date have focused on executive and visuospatial functions. Despite some inconsistencies, most of the studies found significant impairment in these domains in PD patients with psychosis compared to those without psychosis. Studies assessing for other cognitive functions such as attention, language and memory in PD patients have also found worse performance in those with psychosis. Although there is enough evidence to suggest that PD patients with psychosis have poor cognitive functioning, it is unclear if these deficits are generalized or specific. The available evidence, which is primarily in the form of cross-sectional studies assessing for specific cognitive deficits, is not adequate to indicate a clear demarcating pattern of cognitive deficits, which differentiates PD patients with and without psychosis. Longitudinal studies with extensive cognitive assessment are warranted.

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.

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.

Are patients with limb and head tremor a clinically distinct subtype of essential tremor

BACKGROUND Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-) are few. METHODS To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. RESULTS HT was present in 44.4% of the patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. CONCLUSIONS Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

Utilizing inspiratory airflows during standard polysomnography to assess pharyngeal function in children during sleep

Obstructive sleep apnea (OSA) is the result of pharyngeal obstruction that occurs predominantly during REM in children. Pathophysiologic mechanisms responsible for upper airway obstruction, however, are poorly understood. Thus, we sought to characterize upper airway obstruction in apneic compared to snoring children during sleep. We hypothesized that apneic compared to snoring children would exhibit an increased prevalence and severity of upper airway obstruction, that would be greater in REM compared to non‐REM, and would improve following adenotonsillectomy.

Psychosis in Parkinson's disease: From the soft signs to the hard science

Patients with Parkinsons disease (PD) may develop a wide spectrum of non-motor symptoms during the course of illness. Psychosis is one such commonly observed non-motor symptoms of PD. Although several studies based on neuroimaging, genetics, retinal imaging, and neuropsychological evaluations have explored the pathogenesis of psychosis in PD; exact neural correlates are yet to be understood. Identification of factors related to psychosis in PD is important, as psychosis has been reported to be associated with higher rates of mortality, caregiver distress, and nursing home placements. This review highlights the potential of the previous studies to gain further insights into the soft signs and hard science related to psychosis in PD. Studies based on neuropsychological evaluations have revealed significant dysfunction in attention, executive and visuospatial functions in patients with PD and psychosis. Neuroimaging studies reveal grey matter atrophy in regions of the brain corresponding to both dorsal and ventral visual pathways, hippocampus, and cholinergic structures. Meanwhile, functional imaging studies suggest existence of an aberrant top-to-bottom visual processing system, which dominates the normal bottom-to-top system in patients with PD and visual hallucinations. Although nucleotide polymorphisms of several genes have been studied in PD patients with psychosis, those on -45C>T polymorphisms of cholecystokinin gene (CCK) have shown the greatest promise because of its association with psychosis in PD. All these taken together, cohesively unfold the current status of research in patients with PD and psychosis. This paper also highlights the missing links and discusses the approach to future research in this field.