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Radiology Case Reports May 2024Basal ganglia germinomas (BGGs) are rare lesions. Because of the atypical features of early-stage clinical symptoms and imaging characteristics, BGGs are easily...
Basal ganglia germinomas (BGGs) are rare lesions. Because of the atypical features of early-stage clinical symptoms and imaging characteristics, BGGs are easily misdiagnosed with non-tumorous conditions. This article presented cases of 2 young male patients who came to the hospital due to right arm weakness. Brain Magnetic Resonance Imaging (MRI) images in the first case revealed a lobulated mixed component mass on the left basal ganglia. The solid part showed restricted diffusion on diffusion-weighted imaging, heterogeneous strong enhancement, and no signal of calcification or bleeding. The second case in the left putamen showed hypointensity on T2*, mild enhancement, and atrophy of the ipsilateral cerebral peduncle, increased choline, and decreased n-acetyl-aspartate (NAA) on spectroscopy. Follow-up MRI after 6 months showed a mass increase in size and hypointensity part on T2*. BGGs have been confirmed on biopsy in both cases. With isolated chemotherapy application, there is no sign of remission in the first patient. The second patient was treated with chemotherapy and radiotherapy, and MRI images after treatment showed a complete response.
PubMed: 38523694
DOI: 10.1016/j.radcr.2024.02.047 -
Brain : a Journal of Neurology Mar 2024The most common genetic risk factors for Parkinson's disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD)...
The most common genetic risk factors for Parkinson's disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD) exhibit earlier age of onset and faster disease progression with more severe cognitive impairments, postural instability and gait problems. These GBA-PD features suggest more severe cholinergic system pathologies. PET imaging with the vesicular acetylcholine transporter ligand 18F-F-fluoroethoxybenzovesamicol (18F-FEOBV PET) provides the opportunity to investigate cholinergic changes and their relationship to clinical features in GBA-PD. The study investigated 123 newly diagnosed, treatment-naïve Parkinson's disease subjects-with confirmed presynaptic dopaminergic deficits on PET imaging. Whole-gene GBA1 sequencing of saliva samples was performed to evaluate GBA1 variants. Patients underwent extensive neuropsychological assessment of all cognitive domains, motor evaluation with the Unified Parkinson's Disease Rating Scale, brain MRI, dopaminergic PET to measure striatal-to-occipital ratios of the putamen and 18F-FEOBV PET. We investigated differences in regional cholinergic innervation between GBA-PD carriers and non-GBA1 mutation carriers (non-GBA-PD), using voxel-wise and volume of interest-based approaches. The degree of overlap between t-maps from two-sample t-test models was quantified using the Dice similarity coefficient. Seventeen (13.8%) subjects had a GBA1 mutation. No significant differences were found in clinical features and dopaminergic ratios between GBA-PD and non-GBA-PD at diagnosis. Lower 18F-FEOBV binding was found in both the GBA-PD and non-GBA-PD groups compared to controls. Dice (P < 0.05, cluster size 100) showed good overlap (0.7326) between the GBA-PD and non-GBA-PD maps. GBA-PD patients showed more widespread reduction in 18F-FEOBV binding than non-GBA-PD when compared to controls in occipital, parietal, temporal and frontal cortices (P < 0.05, FDR-corrected). In volume of interest analyses (Bonferroni corrected), the left parahippocampal gyrus was more affected in GBA-PD. De novo GBA-PD show a distinct topography of regional cholinergic terminal ligand binding. Although the Parkinson's disease groups were not distinguishable clinically, in comparison to healthy controls, GBA-PD showed more extensive cholinergic denervation compared to non-GBA-PD. A larger group is needed to validate these findings. Our results suggest that de novo GBA-PD and non-GBA-PD show differential patterns of cholinergic system changes before clinical phenotypic differences between carriers versus non-carrier groups are observable.
Topics: Humans; Parkinson Disease; Glucosylceramidase; Ligands; Gait; Corpus Striatum; Dopamine
PubMed: 37748026
DOI: 10.1093/brain/awad323 -
Brain : a Journal of Neurology Mar 2024Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e....
Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson's disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson's disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.
Topics: Humans; Parkinson Disease; Hypokinesia; Basal Ganglia; Corpus Striatum; Dopamine; Putamen
PubMed: 37757883
DOI: 10.1093/brain/awad325 -
Brain Communications 2023Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at...
Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at emotional, motivational, cognitive, behavioural or somatic levels. Evidence indicates that depression is caused by disruption of bio-aminergic fibre tracts between prefrontal and limbic or striatal brain regions comprising different functional networks. Voxel-based lesion-symptom mapping studies reported discrepant findings regarding the association between infarct locations and depression. Inconsistencies may be due to the usage of sum scores, thereby mixing different symptoms of depression. In this cross-sectional study, we used multivariate support vector regression for lesion-symptom mapping to identify regions significantly involved in distinct depressive symptom domains and global depression. MRI lesion data were included from 200 patients with acute first-ever ischaemic stroke (mean 0.9 ± 1.5 days of post-stroke). The Montgomery-Åsberg Depression Rating interview assessed depression severity in five symptom domains encompassing motivational, emotional and cognitive symptoms deficits, anxiety and somatic symptoms and was examined 8.4 days of post-stroke (±4.3). We found that global depression severity, irrespective of individual symptom domains, was primarily linked to right hemispheric lesions in the dorsolateral prefrontal cortex and inferior frontal gyrus. In contrast, when considering distinct symptom domains individually, the analyses yielded much more sensitive results in regions where the correlations with the global depression score yielded no effects. Accordingly, motivational deficits were associated with lesions in orbitofrontal cortex, dorsolateral prefrontal cortex, pre- and post-central gyri and basal ganglia, including putamen and pallidum. Lesions affecting the dorsal thalamus, anterior insula and somatosensory cortex were significantly associated with emotional symptoms such as sadness. Damage to the dorsolateral prefrontal cortex was associated with concentration deficits, cognitive symptoms of guilt and self-reproach. Furthermore, somatic symptoms, including loss of appetite and sleep disturbances, were linked to the insula, parietal operculum and amygdala lesions. Likewise, anxiety was associated with lesions impacting the central operculum, insula and inferior frontal gyrus. Interestingly, symptoms of anxiety were exclusively left hemispheric, whereas the lesion-symptom associations of the other domains were lateralized to the right hemisphere. In conclusion, this large-scale study shows that in acute stroke patients, differential post-stroke depression symptom domains are associated with specific structural correlates. Our findings extend existing concepts on the neural underpinnings of depressive symptoms, indicating that differential lesion patterns lead to distinct depressive symptoms in the first weeks of post-stroke. These findings may facilitate the development of personalized treatments to improve post-stroke rehabilitation.
PubMed: 37908237
DOI: 10.1093/braincomms/fcad275 -
Frontiers in Neurology 2023Brain gray matter alterations in patients with trigeminal neuralgia (TN) have been detected in prior neuroimaging studies, but the results are heterogeneous. The current... (Review)
Review
BACKGROUND
Brain gray matter alterations in patients with trigeminal neuralgia (TN) have been detected in prior neuroimaging studies, but the results are heterogeneous. The current study conducted coordinate-based meta-analyses across neuroimaging studies, aiming to find the pattern of brain anatomic and functional alterations in patients with TN.
METHODS
We performed a systematic literature search of PubMed, Embase, and Web of Science to identify relevant publications. A multimodal meta-analysis for whole-brain voxel-based morphometry (VBM) studies and functional imaging studies in TN was performed using anisotropic effect size-based signed differential mapping.
RESULTS
The meta-analysis comprised 10 VBM studies with 398 TN patients and 275 healthy controls, and 13 functional magnetic resonance imaging studies with 307 TN patients and 264 healthy controls. The multimodal meta-analysis showed conjoint structural and functional brain alterations in the right fusiform gyrus and inferior temporal gyrus, bilateral thalamus, left superior temporal gyrus, left insula, and inferior frontal gyrus. The unimodal meta-analysis showed decreased gray matter volume alone in the left putamen, left postcentral gyrus, and right amygdala as well as only functional abnormalities in the left cerebellum, bilateral precuneus, and left middle temporal gyrus.
CONCLUSION
This meta-analysis revealed overlapping anatomic and functional gray matter abnormalities in patients with TN, which may help provide new insights into the neuropathology and potential treatment biomarkers of TN.
PubMed: 37602249
DOI: 10.3389/fneur.2023.1179896 -
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 -
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 -
Proceedings of the National Academy of... Dec 2023The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting...
The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting brain function. However, their differential sensitivity to stimulant-induced dopamine (DA) increases, including the rate of DA rise and the relationship between them, have not been investigated. Here we used, simultaneous PET-fMRI to examine the association between dynamic changes in striatal DA and brain activity as assessed by ALFF and gFCD, following placebo, intravenous (IV), or oral methylphenidate (MP) administration, using a within-subject double-blind placebo-controlled design. In putamen, MP significantly reduced D receptor availability and strongly reduced ALFF and increased gFCD in the brain for IV-MP (Cohen's d > 1.6) but less so for oral-MP (Cohen's d < 0.6). Enhanced gFCD was associated with both the level and the rate of striatal DA increases, whereas decreased ALFF was only associated with the level of DA increases. These findings suggest distinct representations of neurovascular activation with ALFF and gFCD by stimulant-induced DA increases with differential sensitivity to the rate and the level of DA increases. We also observed an inverse association between gFCD and ALFF that was markedly enhanced during IV-MP, which could reflect an increased contribution from MP's vasoactive properties.
Topics: Brain; Dopamine; Magnetic Resonance Imaging; Methylphenidate; Double-Blind Method
PubMed: 38109535
DOI: 10.1073/pnas.2314596120