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CNS Neuroscience & Therapeutics Feb 2024Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron-chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta-analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients.
METHODS
A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS-III).
RESULTS
Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS-III score compared to placebo (Standardized mean difference -0.06, 95% CI [-0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*-weighted MRI (with high certainty evidence).
CONCLUSION
Current evidence does not support the use of DFP in PD patients. Future disease-modification trials with better population selection, adjustment for concomitant medications, and long-term follow up are recommended.
Topics: Humans; Deferiprone; Parkinson Disease; Iron Chelating Agents; Iron; Substantia Nigra
PubMed: 38334258
DOI: 10.1111/cns.14607 -
International Journal of General... 2023Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or... (Review)
Review
BACKGROUND
Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or MRI findings are inconsistent or clinical symptoms and imaging findings do not appear simultaneously. We aimed to compile the cases in which imaging findings appeared on MRI retests and to examine in a systematic review whether temporal differences in the appearance of imaging findings correlate with clinical characteristics.
CASE PRESENTATION
An 80-year-old man with type 2 diabetes mellitus came to a hospital with abnormal movements of the left upper and lower extremities. Two days after the first visit, his symptoms flared up, and his head MRI showed an old cerebral infarction and no new lesion. On day 14, he retested T1-weighted imaging and showed a high signal in the right putamen, which was considered diabetic chorea. Blood glucose was controlled with insulin, and the involuntary movements disappeared.
METHODS
PubMed and ICHUSHI were searched to identify patients with diabetic chorea who had undergone MRI retests. Patients grouped by the temporal change in the presence/absence of imaging findings were compared on age, sex, duration of diabetes mellitus, blood glucose level, HbA1c level, side of involuntary movement, time to first MRI, and follow-up MRI.
RESULTS
Of the 64 cases analyzed, 43 (67.2%) were female. The mean age was 69.0 years. 16 (25.0%) had worsening findings upon MRI retesting, 37 (57.8%) had improvement, and 10 (15.6%) had unchanged findings. There were no significant differences in age, sex, mean blood glucose level or HbA1c at onset among the groups.
CONCLUSION
There was no association between the pattern of appearance of imaging findings over time and clinical characteristics, including glucose levels. If initial MRI findings are negative, MRI retesting after a certain time may help diagnose diabetic chorea.
PubMed: 37808208
DOI: 10.2147/IJGM.S423400 -
Human Brain Mapping Dec 2023The present study employed a novel paradigm and functional magnetic resonance imaging (fMRI) to uncover the specific regulatory mechanism of time pressure and empathy...
The present study employed a novel paradigm and functional magnetic resonance imaging (fMRI) to uncover the specific regulatory mechanism of time pressure and empathy trait in prosocial decision-making, compared to self-decision making. Participants were instructed to decide whether to spend their own monetary interest to alleviate themselves (or another person) from unpleasant noise threats under high and low time pressures. On the behavioral level, results showed that high time pressure had a significant effect on reducing participants' willingness to spend money on relieving themselves from the noise, while there is a similar but not significant trend in prosocial decision-making. On the neural level, for self-concerned decision-making, low time pressure activated the bilateral insula more strongly than high time pressure. For prosocial decision-making, high time pressure suppressed activations in multiple brain regions related to empathy (temporal pole, middle temporal gyrus, and inferior frontal gyrus), valuation (medial orbitofrontal cortex), and emotion (putamen). The functional connectivity strength among these regions, especially the connectivity between the medial orbitofrontal cortex and putamen, significantly predicted the effect of time pressure on prosocial decision-making at the behavioral level. Additionally, we discovered the activation of the medial orbitofrontal cortex partially mediated the effect of empathy trait scores on prosocial decision-making. These findings suggest that (1) there are different neural underpinnings for the modulation of time pressure for self and prosocial decision-making, and (2) the empathy trait plays a crucial role in the latter.
Topics: Humans; Social Behavior; Brain Mapping; Brain; Cerebral Cortex; Emotions; Empathy; Magnetic Resonance Imaging
PubMed: 37771259
DOI: 10.1002/hbm.26499 -
Frontiers in Aging Neuroscience 2023Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide corroborative data on neurophysiological alterations in Huntington's disease...
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide corroborative data on neurophysiological alterations in Huntington's disease (HD). However, the alterations in EEG and fMRI resting-state functional connectivity (rsFC), as well as their interrelations, at different stages of HD remain insufficiently investigated. This study aimed to identify neurophysiological alterations in individuals with preclinical HD (preHD) and early manifest HD (EMHD) by analyzing EEG and fMRI rsFC and examining their interrelationships. We found significant differences in EEG power between preHD individuals and healthy controls (HC), with a decrease in power in a specific frequency range at the theta-alpha border and slow alpha activity. In EMHD patients, in addition to the decrease in power in the 7-9 Hz range, a reduction in power within the classic alpha band compared to HC was observed. The fMRI analysis revealed disrupted functional connectivity in various brain networks, particularly within frontal lobe, putamen-cortical, and cortico-cerebellar networks, in individuals with the HD mutation compared to HC. The analysis of the relationship between EEG and fMRI rsFC revealed an association between decreased alpha power, observed in individuals with EMHD, and increased connectivity in large-scale brain networks. These networks include putamen-cortical, DMN-related and cortico-hippocampal circuits. Overall, the findings suggest that EEG and fMRI provide valuable information for monitoring pathological processes during the development of HD. A decrease in inhibitory control within the putamen-cortical, DMN-related and cortico-hippocampal circuits, accompanied by a reduction in alpha and theta-alpha border oscillatory activity, could potentially contribute to cognitive decline in HD.
PubMed: 38161585
DOI: 10.3389/fnagi.2023.1270226 -
Molecular Psychiatry Feb 2024Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited....
Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation.
Topics: Humans; Female; Male; Adult; Depressive Disorder, Major; Magnetic Resonance Imaging; Middle Aged; Psychomotor Disorders; Psychomotor Agitation; Brain; Depression; Neural Pathways; Motor Cortex; Brain Mapping; Nerve Net
PubMed: 38036604
DOI: 10.1038/s41380-023-02327-1 -
NeuroImage Sep 2023Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated...
Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.
Topics: Humans; Brain; Parietal Lobe; Gravity, Altered; Somatosensory Cortex; Space Flight
PubMed: 37422277
DOI: 10.1016/j.neuroimage.2023.120261 -
Quantitative Imaging in Medicine and... Oct 2023The diagnosis of Parkinson's disease (PD) is challenging because the clinical symptoms overlap with other neurodegenerative diseases. The discovery of reliable...
BACKGROUND
The diagnosis of Parkinson's disease (PD) is challenging because the clinical symptoms overlap with other neurodegenerative diseases. The discovery of reliable biomarkers is highly expected to facilitate clinical diagnosis. Through the analysis of the H magnetic resonance spectroscopy (H-MRS) in the putamen, the purpose of the study was to discuss the possibility of the difference in metabolite concentrations between the left and right putamen as biomarkers for patients with severe PD.
METHODS
We collected H-MRS of unilateral or bilateral putamen from 41 patients and used the independent sample -test and paired -test to analyze 4 metabolite concentrations, including choline (Cho), total N-acetyl aspartate (tNAA), total creatine (tCr), and combined glutamate and glutamine; Bonferroni correction was used to correct P values for multiple comparisons. We designed 4 controlled experiments as follows: (I) PD patients versus healthy controls (HCs) in the left putamen; (II) PD patients versus HCs in the right putamen; (III) the left putamen versus the right putamen for PD patients; and (IV) the left putamen versus the right putamen for HCs.
RESULTS
No statistically significant differences (P>0.05) were detected among 4 metabolites in the ipsilateral and bilateral putamen for the PD and HCs groups, except for tCr in the left putamen (PD 6.426±0.557, HCs 6.026±0.460, P=0.046) for ipsilateral comparisons.
CONCLUSIONS
In the bilateral putamen of severe PD patients, there was no statistically significant difference in the 4 metabolites. The difference (P<0.05) in tCr in the left putamen might be a potential biomarker to distinguish HCs from severe patients in clinic. This might provide a reference for the clinical diagnosis and acquisition strategy of 1H-MRS in severe PD.
PubMed: 37869290
DOI: 10.21037/qims-23-231 -
Neurological Sciences : Official... Dec 2023Dopamine dysregulation syndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk...
BACKGROUND
Dopamine dysregulation syndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk factors for DDS are poorly known, and it is critical to identify them in the early stages of PD.
OBJECTIVE
To explore the incidence of and risk factors for DDS in patients with early PD.
METHODS
A retrospective cohort study was conducted on the general data, clinical features, and imaging data of patients with early PD in the PPMI database. Multivariate Cox regression analysis was performed to analyze the risk factors for the development of DDS in patients with early PD, and Kaplan‒Meier curves examined the frequency and predictors of incident DDS symptoms.
RESULTS
At baseline, 2.2% (n = 6) of patients with early PD developed DDS, and the cumulative incidence rates of DDS during the 5-year follow-up period were 2.8%, 6.4%, 10.8%, 15.5%, and 18.7%, respectively. In the multivariate Cox regression model controlling for age, sex, and drug use, hypersexuality (HR = 3.088; 95% CI: 1.416~6.732; P = 0.005), compulsive eating (HR = 3.299; 95% CI: 1.665~6.534; P = 0.001), compulsive shopping (HR = 3.899; 95% CI: 1.769~8.593; P = 0.001), anxiety (HR = 4.018; 95% CI: 2.136~7.599; P < 0.01), and lower Hoehn-Yahr (H-Y) stage (HR = 0.278; 95% CI: 0.152~0.509; P < 0.01) were independent risk factors for DDS in patients with early PD. PD patients with DDS had lower DAT uptake values than those patients without DDS.
CONCLUSION
Early PD patients with hypersexuality, compulsive eating, compulsive shopping, anxiety, and lower H-Y stage were at increased risk for DDS. The occurrence of DDS may be related to the decrease in the average DAT uptake of the caudate and putamen.
Topics: Humans; Dopamine; Parkinson Disease; Retrospective Studies; Disruptive, Impulse Control, and Conduct Disorders; Quality of Life; Syndrome
PubMed: 37452260
DOI: 10.1007/s10072-023-06956-w -
Genes Sep 2023Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the...
Aromatic L-Amino-Acid Decarboxylase Deficiency Screening by Analysis of 3-O-Methyldopa in Dried Blood Spots: Results of a Multicentric Study in Neurodevelopmental Disorders.
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd.
Topics: Humans; Infant, Newborn; Carboxy-Lyases; Malnutrition; Muscle Hypotonia; Neurodevelopmental Disorders
PubMed: 37761968
DOI: 10.3390/genes14091828 -
Molecular Neurobiology Aug 2023The present study, employing a comparative proteomic approach, analyzes the protein profile of pig claustrum (CLA), putamen (PU), and insula (IN). Pig brain is an...
The present study, employing a comparative proteomic approach, analyzes the protein profile of pig claustrum (CLA), putamen (PU), and insula (IN). Pig brain is an interesting model whose key translational features are its similarities with cortical and subcortical structures of human brain. A greater difference in protein spot expression was observed in CLA vs PU as compared to CLA vs IN. The deregulated proteins identified in CLA resulted to be deeply implicated in neurodegenerative (i.e., sirtuin 2, protein disulfide-isomerase 3, transketolase) and psychiatric (i.e., copine 3 and myelin basic protein) disorders in humans. Metascape analysis of differentially expressed proteins in CLA vs PU comparison suggested activation of the α-synuclein pathway and L1 recycling pathway corroborating the involvement of these anatomical structures in neurodegenerative diseases. The expression of calcium/calmodulin-dependent protein kinase and dihydropyrimidinase like 2, which are linked to these pathways, was validated using western blot analysis. Moreover, the protein data set of CLA vs PU comparison was analyzed by Ingenuity Pathways Analysis to obtain a prediction of most significant canonical pathways, upstream regulators, human diseases, and biological functions. Interestingly, inhibition of presenilin 1 (PSEN1) upstream regulator and activation of endocannabinoid neuronal synapse pathway were observed. In conclusion, this is the first study presenting an extensive proteomic analysis of pig CLA in comparison with adjacent areas, IN and PUT. These results reinforce the common origin of CLA and IN and suggest an interesting involvement of CLA in endocannabinoid circuitry, neurodegenerative, and psychiatric disorders in humans.
Topics: Humans; Animals; Swine; Claustrum; Endocannabinoids; Proteomics; Neurons; Brain
PubMed: 37095366
DOI: 10.1007/s12035-023-03347-2