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Parkinsonism & Related Disorders May 2024Chorea is primarily due to an imbalance of basal ganglia output pathways, often due to dysfunction or degeneration of the caudate nucleus and putamen, and can be due to... (Review)
Review
INTRODUCTION
Chorea is primarily due to an imbalance of basal ganglia output pathways, often due to dysfunction or degeneration of the caudate nucleus and putamen, and can be due to many causes.
METHODS
We reviewed the recent literature to identify newly-recognized causes of chorea, including auto-immune, metabolic, and genetic. We also focused upon developments in mechanisms relating to underlying pathophysiology of certain genetic choreas and advances in therapeutics.
RESULTS
Novel autoantibodies continue to be identified as causes of chorea. Both COVID-19 infection and vaccination are reported to result rarely in chorea, although in some cases causality is not clearly established. Advances in genetic testing continue to find more causes of chorea, and to expand the phenotype of known genetic disorders. Deep brain stimulation can be successful in certain circumstances.
CONCLUSION
Our understanding of mechanisms underlying this movement disorder continues to advance, however much remains to be elucidated.
Topics: Humans; Chorea; COVID-19; Deep Brain Stimulation; Autoantibodies
PubMed: 38378310
DOI: 10.1016/j.parkreldis.2024.106045 -
Movement Disorders : Official Journal... Aug 2023Chorea-acanthocytosis (ChAc) is associated with mutations of VPS13A, which encodes for chorein, a protein implicated in lipid transport at intracellular membrane contact...
BACKGROUND
Chorea-acanthocytosis (ChAc) is associated with mutations of VPS13A, which encodes for chorein, a protein implicated in lipid transport at intracellular membrane contact sites.
OBJECTIVES
The goal of this study was to establish the lipidomic profile of patients with ChAc.
METHODS
We analyzed 593 lipid species in the caudate nucleus (CN), putamen, and dorsolateral prefrontal cortex (DLPFC) from postmortem tissues of four patients with ChAc and six patients without ChAc.
RESULTS
We found increased levels of bis(monoacylglycerol)phosphate, sulfatide, lysophosphatidylserine, and phosphatidylcholine ether in the CN and putamen, but not in the DLPFC, of patients with ChAc. Phosphatidylserine and monoacylglycerol were increased in the CN and N-acyl phosphatidylserine in the putamen. N-acyl serine was decreased in the CN and DLPFC, whereas lysophosphatidylinositol was decreased in the DLPFC.
CONCLUSIONS
We present the first evidence of altered sphingolipid and phospholipid levels in the brains of patients with ChAc. Our observations are congruent with recent findings in cellular and animal models, and implicate defects of lipid processing in VPS13A disease pathophysiology. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Animals; Humans; Neuroacanthocytosis; Phospholipids; Phosphatidylserines; Vesicular Transport Proteins; Brain
PubMed: 37307400
DOI: 10.1002/mds.29445 -
Nature Communications Jul 2023The ability to use blood to predict the outcomes of Parkinson's disease, including disease progression and cognitive and motor complications, would be of significant...
The ability to use blood to predict the outcomes of Parkinson's disease, including disease progression and cognitive and motor complications, would be of significant clinical value. We undertook bulk RNA sequencing from the caudate and putamen of postmortem Parkinson's disease (n = 35) and control (n = 40) striatum, and compared molecular profiles with clinical features and bulk RNA sequencing data obtained from antemortem peripheral blood. Cognitive and motor complications of Parkinson's disease were associated with molecular changes in the caudate (stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset Parkinson's disease were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence), respectively. Transcriptome patterns in the postmortem Parkinson's disease brain were also evident in antemortem peripheral blood, and correlated with clinical features of the disease. Together, these findings identify molecular signatures in Parkinson's disease patients' brain and blood of potential pathophysiologic and prognostic importance.
Topics: Humans; Parkinson Disease; Transcriptome; Brain; Corpus Striatum; Putamen
PubMed: 37407548
DOI: 10.1038/s41467-023-39652-6 -
The Journal of Clinical Endocrinology... Jul 2023Hemichorea associated with nonketotic hyperglycemia (HC-NH) is a rare diabetic complication for which the pathogenesis remains unclear.
CONTEXT
Hemichorea associated with nonketotic hyperglycemia (HC-NH) is a rare diabetic complication for which the pathogenesis remains unclear.
OBJECTIVE
This study reported 16 cases of HC-NH to improve the understanding of the disease and avoid misdiagnosis and missed diagnosis.
METHODS
Data of 16 patients with HC-NH in a single center from 2000 to 2021 were analyzed retrospectively, and the relevant literature was reviewed.
RESULTS
The participants (8 men and 8 women) had a mean age of 67.6 ± 16.4 years. Bilateral limbs were involved in 2 cases, and the others had hemichorea (6 in the left side and 8 in the right side). The average random blood glucose level was 17.51 ± 7.67 mmol/L, and the glycated hemoglobin A1c level was 11.9%±3.1% at admission. Eleven patients had a history of diabetes, and the other 5 patients were diagnosed with new-onset diabetes mellitus, but no remarkable differences were observed in the presentation or treatment of chorea. Ketonuria was detected in 7 patients. The basal ganglia (putamen, globus pallidus, and caudate nucleus) of 9 cases had typical hyperdensity on computed tomography and/or hyperintensity signals from magnetic resonance imaging. The chorea symptoms of 15 patients improved within 5.0 ± 1.9 days after treatment.
CONCLUSION
This study provides additional valuable information about the clinical and neuroimaging features of HC-NH. We hypothesize that chronic ischemia of the basal ganglia due to cerebral atherosclerosis combined with hyperglycemia is associated with HC-NH.
Topics: Male; Humans; Female; Middle Aged; Aged; Aged, 80 and over; Chorea; Retrospective Studies; Hyperglycemia; Diabetes Mellitus; Magnetic Resonance Imaging
PubMed: 36800278
DOI: 10.1210/clinem/dgad077 -
Human Brain Mapping Dec 2023Atrophy related to multiple sclerosis (MS) has been found at the early stages of the disease. However, the archetype dynamic trajectories of the neurodegenerative...
Atrophy related to multiple sclerosis (MS) has been found at the early stages of the disease. However, the archetype dynamic trajectories of the neurodegenerative process, even prior to clinical diagnosis, remain unknown. We modeled the volumetric trajectories of brain structures across the entire lifespan using 40,944 subjects (38,295 healthy controls and 2649 MS patients). Then, we estimated the chronological progression of MS by assessing the divergence of lifespan trajectories between normal brain charts and MS brain charts. Chronologically, the first affected structure was the thalamus, then the putamen and the pallidum (around 4 years later), followed by the ventral diencephalon (around 7 years after thalamus) and finally the brainstem (around 9 years after thalamus). To a lesser extent, the anterior cingulate gyrus, insular cortex, occipital pole, caudate and hippocampus were impacted. Finally, the precuneus and accumbens nuclei exhibited a limited atrophy pattern. Subcortical atrophy was more pronounced than cortical atrophy. The thalamus was the most impacted structure with a very early divergence in life. Our experiments showed that lifespan models of most impacted structures could be an important tool for future preclinical/prodromal prognosis and monitoring of MS.
Topics: Humans; Multiple Sclerosis; Longevity; Magnetic Resonance Imaging; Brain; Atrophy; Gray Matter
PubMed: 37615064
DOI: 10.1002/hbm.26464 -
Movement Disorders : Official Journal... Sep 2023It has been suggested that the loss of nigrostriatal dopaminergic axon terminals occurs before the loss of dopaminergic neurons in the substantia nigra (SN) in...
BACKGROUND
It has been suggested that the loss of nigrostriatal dopaminergic axon terminals occurs before the loss of dopaminergic neurons in the substantia nigra (SN) in Parkinson's disease (PD). This study aimed to use free-water imaging to evaluate microstructural changes in the dorsoposterior putamen (DPP) of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) patients, which is considered a prodromal stage of synucleinopathies.
METHODS
Free water values in the DPP, dorsoanterior putamen (DAP), and posterior SN were compared between the healthy controls (n = 48), iRBD (n = 43) and PD (n = 47) patients. In iRBD patients, the relationships between baseline and longitudinal free water values and clinical manifestations or dopamine transporter (DAT) striatal binding ratio (SBR) were analyzed.
RESULTS
Free water values were significantly higher in the DPP and posterior substantia nigra (pSN), but not in the DAP, in the iRBD and PD groups than in controls. In iRBD patients, free water values in the DPP were progressively increased and correlated with the progression of clinical manifestations and the striatal DAT SBR. Baseline free water in the DPP was negatively correlated with striatal DAT SBR and hyposmia and positively correlated with motor deficits.
CONCLUSIONS
This study demonstrates that free water values in the DPP are increased cross-sectionally and longitudinally and associated with clinical manifestations and the function of the dopaminergic system in the prodromal stage of synucleinopathies. Our findings indicate that free-water imaging of the DPP has the potential to be a valid marker of early diagnosis and progression of synucleinopathies. © 2023 International Parkinson and Movement Disorder Society.
Topics: Humans; REM Sleep Behavior Disorder; Putamen; Synucleinopathies; Prodromal Symptoms; Parkinson Disease; Dopamine; Water
PubMed: 37342973
DOI: 10.1002/mds.29499 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2024Lead poisoning in childhood remains an important public health concern. We highlight the radiological findings in a patient with a high blood lead concentration.
INTRODUCTION
Lead poisoning in childhood remains an important public health concern. We highlight the radiological findings in a patient with a high blood lead concentration.
CASE SUMMARY
A 7-year-old girl presented to hospital with abdominal pain, nausea, and asthenia. Laboratory tests showed severe hypochromic microcytic anemia, punctate basophilic stippling of erythrocytes, and a blood lead concentration of 880 µg/L (4.3 µmol/L).
IMAGES
Radiographs of the femur, tibia, and fibula demonstrated dense metaphyseal bands ("lead lines"). On cranial computed tomography, we observed multiple speck-like and curvilinear hyperdensities involving subcortical regions, putamen, and left cerebellar hemisphere.
CONCLUSION
In patients with lead poisoning, imaging of the brain and bones may show characteristic features. These imaging findings may point to the diagnosis of lead toxicity when these radiographic findings are discovered during the evaluation of vague complaints such as abdominal pain or mental status changes or when a blood lead concentration is not readily available.
PubMed: 38899783
DOI: 10.1080/15563650.2024.2342928 -
BioRxiv : the Preprint Server For... Aug 2023Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous...
Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer's disease and Parkinson's disease genome-wide association studies (GWAS), such as apolipoprotein E (), and leucine-rich repeat kinase 2 () in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website, https://brainexp-hykyffa56a-uc.a.run.app/.
PubMed: 37577533
DOI: 10.1101/2023.07.31.551097