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Tremor and Other Hyperkinetic Movements... 2023Movement disorders are the commonest clinical presentation in patients with neurological Wilson's disease (NWD). There are very few studies evaluating the spectrum,...
INTRODUCTION
Movement disorders are the commonest clinical presentation in patients with neurological Wilson's disease (NWD). There are very few studies evaluating the spectrum, severity and their correlation with magnetic resonance imaging (MRI) changes of movement disorders in NWD.
OBJECTIVE
To study the spectrum, topographic distribution, radiological correlate, temporal course and outcome in our cohort of NWD patients.
METHODS
Retrospective chart review of the NWD patients having movement disorders was performed and analyzed.
RESULTS
Sixty-nine patients (males- 47) with NWD were analysed and the mean age at the onset of neurological symptoms was 13.6 ± 6.6 years (median 13 years; range 7-37 years). The first neurological symptom was movement disorder in 55 (79.7%) patients. Tremor (43.6%) and dystonia (41.8%) was the commonest movement disorder as the first neurological symptom. Dystonia (76.8%) was the most common overall movement disorder followed by parkinsonism (52.1%) and tremors (47.8%). Chorea (10.1%), myoclonus (1.4%) and ataxia (1.4%) were the least common movement disorder. Putamen was the most common affected site (95.6%) followed by caudate nucleus (73.9%), thalamus (60.8%), midbrain (59.4%), internal capsule (49.2%), pons (46.3%). Putamen was the most common area of abnormality in dystonia (98%), tremors (85%). Caudate (75%) and putamen (75%) was the most common areas of abnormality in parkinsonism. Favourable outcome was observed in 42 patients (60.8%) following treatment.
CONCLUSION
Dystonia is the most common movement disorder in NWD in isolation or in combination with parkinsonism and tremors. Putamen is the most common radiological site of lesions and more frequently affected in patients with dystonia and tremors. Favourable outcome does occur with appropriate medical and surgical treatment.
Topics: Male; Humans; Child; Adolescent; Young Adult; Adult; Hepatolenticular Degeneration; Tremor; Dystonia; Retrospective Studies; Movement Disorders; Dystonic Disorders; Parkinsonian Disorders
PubMed: 37840995
DOI: 10.5334/tohm.794 -
The Journal of Biological Chemistry Sep 2023Single-cell transcriptomics are powerful tools to define neuronal cell types based on co-expressed gene clusters. Limited RNA input in these technologies necessarily...
Single-cell transcriptomics are powerful tools to define neuronal cell types based on co-expressed gene clusters. Limited RNA input in these technologies necessarily compromises transcriptome coverage and accuracy of differential expression analysis. We propose that bulk RNA-Seq of neuronal pools defined by spatial position offers an alternative strategy to overcome these technical limitations. We report a laser-capture microdissection (LCM)-Seq method which allows deep transcriptome profiling of fluorescently tagged neuron populations isolated with LCM from histological sections of transgenic mice. Mild formaldehyde fixation of ZsGreen marker protein, LCM sampling of ∼300 pooled neurons, followed by RNA isolation, library preparation and RNA-Seq with methods optimized for nanogram amounts of moderately degraded RNA enabled us to detect ∼15,000 different transcripts in fluorescently labeled cholinergic neuron populations. The LCM-Seq approach showed excellent accuracy in quantitative studies, allowing us to detect 2891 transcripts expressed differentially between the spatially defined and clinically relevant cholinergic neuron populations of the dorsal caudate-putamen and medial septum. In summary, the LCM-Seq method we report in this study is a versatile, sensitive, and accurate bulk sequencing approach to study the transcriptome profile and differential gene expression of fluorescently tagged neuronal populations isolated from transgenic mice with high spatial precision.
PubMed: 37536628
DOI: 10.1016/j.jbc.2023.105121 -
BMC Neurology Jul 2023Migraine and depression are two of the most common and debilitating conditions. From a clinical perspective, they are mostly prevalent in women and manifest a partial...
BACKGROUND
Migraine and depression are two of the most common and debilitating conditions. From a clinical perspective, they are mostly prevalent in women and manifest a partial overlapping symptomatology. Despite the high level of comorbidity, previous studies hardly investigated possible common patterns in brain volumetric differences compared to healthy subjects. Therefore, the current study investigates and compares the volumetric difference patterns in sub-cortical regions between participants with migraine or depression in comparison to healthy controls.
METHODS
The study included data from 43 930 participants of the large UK Biobank cohort. Using official ICD10 diagnosis, we selected 712 participants with migraine, 1 853 with depression and 23 942 healthy controls. We estimated mean volumetric difference between the groups for the different sub-cortical brain regions using generalized linear regression models, conditioning the model within the levels of BMI, age, sex, ethnical background, diastolic blood pressure, current tobacco smoking, alcohol intake frequency, Assessment Centre, Indices of Multiple Deprivation, comorbidities and total brain volume.
RESULTS
We detected larger overall volume of the caudate (mean difference: 66, 95% CI [-3, 135]) and of the thalamus (mean difference: 103 mm, 95% CI [-2, 208]) in migraineurs than healthy controls. We also observed that individuals with depression appear to have also larger overall (mean difference: 47 mm, 95% CI [-7, 100]) and gray matter (mean difference: 49 mm, 95% CI [2, 95]) putamen volumes than healthy controls, as well as larger amygdala volume (mean difference: 17 mm, 95% CI [-7, 40]).
CONCLUSION
Migraineurs manifested larger overall volumes at the level of the nucleus caudate and of the thalamus, which might imply abnormal pain modulation and increased migraine susceptibility. Larger amygdala and putamen volumes in participants with depression than controls might be due to increased neuronal activity in these regions.
Topics: Humans; Female; Depression; Biological Specimen Banks; Magnetic Resonance Imaging; Brain; Migraine Disorders; United Kingdom
PubMed: 37507671
DOI: 10.1186/s12883-023-03336-x -
Neurourology and Urodynamics Nov 2023Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD...
INTRODUCTION
Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD patients with UI (UI-PD) compared to those PD patients without UI (nonUI-PD) with the expectation of demonstrating increased functional connectivity (FC) between areas in the striatum and limbic system and decreased FC in executive areas.
METHODS
rsfMRI and T1w data (n = 119) were retrieved from the Parkinson's Progression Markers Initiative (PPMI). Resting-state FC analyses assessed temporal covariance with anterior cingulate gyrus, precuneus, and putamen seed regions.
RESULTS
The UI-PD group (n = 32, 16 females) showed significantly greater positive FC between the bilateral putamen seed and the right caudate and right thalamus (p < 0.01), relative to individuals with PD but who did not have UI (n = 87, 18 females). The UI-PD group showed greater negative FC between the anterior cingulate seed and right angular gyrus (p < 0.01) relative to nonUI-PD.
CONCLUSION
Individuals with PD and UI display stronger FC within neural circuits likely affected by PD such as between the putamen and caudate, as well as within those associated with brain bladder control, compared to persons with PD and without UI. Clinical application based on this study's results can provide greater discernment of treatment strategies for UI-PD patients.
Topics: Female; Humans; Parkinson Disease; Magnetic Resonance Imaging; Brain; Brain Mapping; Urinary Incontinence
PubMed: 37528804
DOI: 10.1002/nau.25258 -
Journal of Neurology, Neurosurgery, and... Mar 2024Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully...
BACKGROUND
Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia.
METHODS
Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS).
RESULTS
The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (P<0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen.
CONCLUSIONS
GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.
Topics: Humans; Torticollis; Activation, Metabolic; Deep Brain Stimulation; Subthalamic Nucleus; Globus Pallidus; Treatment Outcome; Parkinson Disease
PubMed: 37758453
DOI: 10.1136/jnnp-2023-331668 -
Psychiatry Research. Neuroimaging Oct 2023Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive...
Striatal and thalamic automatic segmentation, morphology, and clinical correlates in Parkinsonism: Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.
Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.
Topics: Humans; Parkinson Disease; Supranuclear Palsy, Progressive; Multiple System Atrophy; Parkinsonian Disorders; Thalamus
PubMed: 37806261
DOI: 10.1016/j.pscychresns.2023.111719 -
Clinical Parkinsonism & Related... 2023Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar...
Most commonly, hemichorea associated with nonketotic and ketotic hyperglycemia resolves with normalization of blood glucose. Herein, we present a case of hyperosmolar hyperglycemic left hemichoreoathetosis-hemidystonia that has persisted for over 1 year. The subject presented to the emergency room with dysarthria and manifested left hemichoreoathetosis-hemidystonia within 36 h of admission. Initial computed tomography (CT) showed hyperdensity in the right putamen and left caudate. Magnetic resonance imaging (MRI) showed T1 hyperintensity within the right putamen. Failure to detect these classic imaging abnormalities during hospitalization resulted in a delayed etiologic diagnosis. Modest symptomatic improvement in the severity of hemichoreoathetosis-hemidystonia has been noted with low dose tetrabenazine.
PubMed: 37927362
DOI: 10.1016/j.prdoa.2023.100221 -
NeuroImage Nov 2023Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can assess the magnetic properties of cerebral iron in vivo. Although... (Review)
Review
Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can assess the magnetic properties of cerebral iron in vivo. Although brain iron is necessary for basic neurobiological functions, excess iron content disrupts homeostasis, leads to oxidative stress, and ultimately contributes to neurodegenerative disease. However, some degree of elevated brain iron is present even among healthy older adults. To better understand the topographical pattern of iron accumulation and its relation to cognitive aging, we conducted an integrative review of 47 QSM studies of healthy aging, with a focus on five distinct themes. The first two themes focused on age-related increases in iron accumulation in deep gray matter nuclei versus the cortex. The overall level of iron is higher in deep gray matter nuclei than in cortical regions. Deep gray matter nuclei vary with regard to age-related effects, which are most prominent in the putamen, and age-related deposition of iron is also observed in frontal, temporal, and parietal cortical regions during healthy aging. The third theme focused on the behavioral relevance of iron content and indicated that higher iron in both deep gray matter and cortical regions was related to decline in fluid (speed-dependent) cognition. A handful of multimodal studies, reviewed in the fourth theme, suggest that iron interacts with imaging measures of brain function, white matter degradation, and the accumulation of neuropathologies. The final theme concerning modifiers of brain iron pointed to potential roles of cardiovascular, dietary, and genetic factors. Although QSM is a relatively recent tool for assessing cerebral iron accumulation, it has significant promise for contributing new insights into healthy neurocognitive aging.
Topics: Humans; Aged; Iron; Healthy Aging; Neurodegenerative Diseases; Brain; Brain Mapping; Magnetic Resonance Imaging; Cognition; Gray Matter
PubMed: 37802405
DOI: 10.1016/j.neuroimage.2023.120401 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2023Inhibition is a core executive cognitive function. However, the neural correlates of non-motor inhibitory control are not well understood. We investigated this question...
Inhibition is a core executive cognitive function. However, the neural correlates of non-motor inhibitory control are not well understood. We investigated this question using functional Magnetic Resonance Imaging (fMRI) and a simple Count Go/NoGo task (n = 23), and further explored the causal relationships between activated brain regions. We found that the Count NoGo task activated a distinct pattern in the subcortical basal ganglia, including bilateral ventral anterior/lateral nucleus of thalamus (VA/VL), globus pallidus/putamen (GP/putamen), and subthalamic nucleus (STN). Stepwise regressions and mediation analyses revealed that activations in these region(s) were modulated differently by only 3 cortical regions i.e. the right inferior frontal gyrus/insula (rIFG/insula), along with left IFG/insula, and anterior cingulate cortex/supplementary motor area (ACC/SMA). The activations of bilateral VA/VL were modulated by both rSTN and rIFG/insula (with rGP/putamen as a mediator) independently, and the activation of rGP/putamen was modulated by ACC/SMA, with rIFG/insula as a mediator. Our findings provide the neural correlates of inhibitory control of counting and causal relationships between them, and strongly suggest that both indirect and hyperdirect pathways of the basal ganglia are involved in the Count NoGo condition.
Topics: Magnetic Resonance Imaging; Brain Mapping; Brain; Subthalamic Nucleus; Executive Function
PubMed: 37724423
DOI: 10.1093/cercor/bhad336 -
Neurobiology of Disease Jul 2024Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload... (Observational Study)
Observational Study
BACKGROUND
Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD. Whether brain iron deposition is causal or secondary to the neurodegenerative processes in the general population is unclear.
METHODS
We analysed 39,533 UK Biobank participants of European genetic ancestry with brain MRI data. We studied brain iron estimated by R2* and quantitative susceptibility mapping (QSM) in 8 subcortical regions: accumbens, amygdala, caudate, hippocampus, pallidum, putamen, substantia nigra, and thalamus. We performed genome-wide associations studies (GWAS) and used Mendelian Randomization (MR) methods to estimate the causal effect of brain iron on grey matter volume, and risk of AD, non-AD and PD. We also used MR to test whether genetic liability to AD or PD causally increased brain iron (R2* and QSM).
FINDINGS
In GWAS of R2* and QSM we replicated 83% of previously reported genetic loci and identified 174 further loci across all eight brain regions. Higher genetically predicted brain iron, using both R2* and QSM, was associated with lower grey matter volumes in the caudate, putamen and thalamus (e.g., Beta-putamenQSM: -0.37, p = 2*10-46). Higher genetically predicted thalamus R2* was associated with increased risk of non-AD dementia (OR 1.36(1.16;1.60), p = 2*10-4) but not AD (p > 0.05). In males, genetically predicted putamen R2* increased non-AD dementia risk, but not in females. Higher genetically predicted iron in the caudate, putamen, and substantia nigra was associated with an increased risk of PD (Odds Ratio QSM ∼ substantia-nigra 1.21(1.07;1.37), p = 0.003). Genetic liability to AD or PD was not associated with R2* or QSM in the dementia or PD-associated regions.
INTERPRETATION
Our genetic analysis supports a causal effect of higher iron deposition in specific subcortical brain regions for Parkinson's disease, grey matter volume, and non-Alzheimer's dementia.
Topics: Humans; Parkinson Disease; Magnetic Resonance Imaging; Male; Dementia; Female; Iron; Gray Matter; United Kingdom; Aged; Genome-Wide Association Study; Middle Aged; Cohort Studies; Biological Specimen Banks; Brain; UK Biobank
PubMed: 38789058
DOI: 10.1016/j.nbd.2024.106539