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Neuroscience and Biobehavioral Reviews Jan 2021Pupillometry, measuring pupil size and reactivity, has been proposed as a measure of autonomic nervous system functioning, the latter which might be altered in... (Meta-Analysis)
Meta-Analysis Review
Pupillometry, measuring pupil size and reactivity, has been proposed as a measure of autonomic nervous system functioning, the latter which might be altered in individuals with autism spectrum disorder (ASD). This study aims to evaluate if pupillary responses differ in individuals with and without ASD. After performing a systematic literature search, we conducted a meta-analysis and constructed a qualitative synthesis. The meta-analysis shows a longer latency of the pupil response in the ASD-group as a substantial group difference, with a Hedges' g of 1.03 (95% CI 0.49-1.56, p = 0.008). Evidence on baseline pupil size and amplitude change is conflicting. We used the framework method to perform a qualitative evaluation of these differences. Explanations for the group differences vary between studies and are inconclusive, but many authors point to involvement of the autonomous nervous system and more specifically the locus coeruleus-norepinephrine system. Pupillometry reveals differences between people with and without ASD, but the exact meaning of these differences remains unknown. Future studies should align research designs and investigate a possible effect of maturation.
Topics: Attention; Autism Spectrum Disorder; Humans; Locus Coeruleus; Norepinephrine
PubMed: 33172600
DOI: 10.1016/j.neubiorev.2020.09.032 -
Neuroscience and Biobehavioral Reviews Jan 2022Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve... (Meta-Analysis)
Meta-Analysis Review
Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.
Topics: Humans; Magnetic Resonance Imaging; Melanins; Schizophrenia; Substantia Nigra
PubMed: 34718049
DOI: 10.1016/j.neubiorev.2021.10.028 -
Qatar Medical Journal 2021The central nervous system is an unusual location of sarcoidosis, which commonly affects the cranial nerves, meninges, hypothalamus, and pituitary gland. Involvement of...
BACKGROUND
The central nervous system is an unusual location of sarcoidosis, which commonly affects the cranial nerves, meninges, hypothalamus, and pituitary gland. Involvement of the pineal region is extremely rare. This systematic review focused on the diagnosis and management of pineal region sarcoidosis, dorsal mesencephalon, and periaqueductal region.
OBJECTIVES
This study aimed to discuss diagnostic modalities and best management tools of the aforementioned pathology.
METHODS
ScienceDirect, PubMed, and Google Scholar databases were searched for English or French articles about sarcoidosis of the pineal region, dorsal mesencephalon, and periaqueductal region. The clinical case of a patient managed at our department that we believe is directly relevant to this review is also presented. Patients' demographics, clinical presentations, presence of hydrocephalus, other sarcoidosis locations in the central nervous system, and medical treatment were collected. Surgical management, surgical approach, and outcomes and complications of each procedure were also obtained. This study was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
RESULTS
Fifteen cases were examined. The study sample consisted of nine (60%) male and six (40%) female, and the mean age was 32 years. Eight (53%) patients had hydrocephalus, and the predominant clinical presentations were signs of increasing intracranial pressure (headaches, vomiting, and papilledema). Six (40%) patients had diplopia, and convergence-retraction nystagmus was noted in three (20%) patients. Argyll Robertson sign was present in one patient and suspected in another patient (13%). Medical treatment consisted mainly of steroids (93% of cases). Open surgery on the pineal region was performed in five patients, and four of them reported to have serious complications (such as ophthalmoplegia, hemianopsia, hemiparesis, bilateral third cranial nerve paresis, and cerebellar syndrome). Endoscopic management was performed in two patients without complications.
CONCLUSION
To treat hydrocephalus, brain imaging is mandatory in patients with sarcoidosis if intracranial hypertension is suspected. In pineal region sarcoidosis, management of hydrocephalus is the priority, followed by medical treatment of the lesion. Open surgery of any approach presents a high risk of complications; thus, an endoscopic approach is the preferred management, as it treats hydrocephalus and makes biopsy possible with minimal risk.
PubMed: 34466394
DOI: 10.5339/qmj.2021.29 -
Movement Disorders : Official Journal... Nov 2021Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review... (Review)
Review
Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review explores the epidemiology, clinical and prognostic associations, radiological features, and pathological findings associated with MPS in older adults free from neurodegenerative disease. We find that MPS as currently defined are strongly associated with increasing age and increased risk of development of Parkinson's disease (PD), all-cause dementia, disability, and death. Positive associations with later PD are found mainly in younger populations and those with other features of prodromal PD. There are currently no consistent radiological findings for MPS, and pathological studies have shown that MPS, at least in the oldest old, are often underpinned by mixed neuropathologies, including those associated with Alzheimer's disease, cerebrovascular disease, nigral neuronal loss, and Lewy bodies. Different subcategories of MPS appear to convey varying risk and specificity for PD and other outcomes. MPS overall are not specific for parkinsonian disorders and, although associated with increased risk of PD, can reflect multiple pathologies, particularly in older individuals. "Mild motor signs" appears a more appropriate term to avoid prognostic and pathological implications, and larger future studies to prospectively examine outcomes and associations of specific MPS subcategories are required. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Aged; Aged, 80 and over; Humans; Lewy Bodies; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Substantia Nigra
PubMed: 34562045
DOI: 10.1002/mds.28777 -
European Journal of Neurology Mar 2021Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD. However, the results on cerebrospinal (CSF) and serum/plasma iron levels in PD patients have been controversial. The aim of this systematic review and meta-analysis was to establish the CSF and serum/plasma levels of iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, and hepcidine) levels, and the urine levels of iron, in patients with PD.
METHODS
Four databases (PubMed, EMBASE, MedLine, and Web of Science - Core Collection) were reviewed for studies published from 1966 to October 5, 2020. References of interest were identified. A meta-analysis of eligible studies was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, using the R software package meta.
RESULTS
A non-significant trend towards higher CSF iron levels and marginally significantly lower serum/plasma iron levels was observed in patients with PD compared with age- and sex-matched controls. CSF and serum/plasma ferritin and transferrin concentrations, and serum/plasma lactoferrin and haptoglobin concentrations did not differ significantly between PD patients and controls.
CONCLUSION
The findings of this study suggest an association between decreased serum/plasma iron levels and, possibly, higher CSF iron levels with risk of PD.
Topics: Ferritins; Humans; Iron; Parkinson Disease; Substantia Nigra
PubMed: 33098743
DOI: 10.1111/ene.14607 -
European Radiology Mar 2021To determine the diagnostic performance of neuromelanin-sensitive magnetic resonance imaging discriminating between patients with Parkinson's disease and normal healthy... (Meta-Analysis)
Meta-Analysis
Diagnostic performance of neuromelanin-sensitive magnetic resonance imaging for patients with Parkinson's disease and factor analysis for its heterogeneity: a systematic review and meta-analysis.
OBJECTIVE
To determine the diagnostic performance of neuromelanin-sensitive magnetic resonance imaging discriminating between patients with Parkinson's disease and normal healthy controls and to identify factors causing heterogeneity influencing the diagnostic performance.
METHODS
A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before February 17, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Subgroup and meta-regression analyses were also performed to determine factors influencing heterogeneity.
RESULTS
Twelve articles including 403 patients with Parkinson's disease and 298 control participants were included in this systematic review and meta-analysis. Neuromelanin-sensitive magnetic resonance imaging showed a pooled sensitivity of 89% (95% confidence interval, 86-92%) and a pooled specificity of 83% (95% confidence interval, 76-88%). In the subgroup and meta-regression analysis, a disease duration longer than 5 and 10 years, comparisons using measured volumes instead of signal intensities, a slice thickness in terms of magnetic resonance imaging parameters of more than 2 mm, and semi-/automated segmentation methods instead of manual segmentation improved the diagnostic performance.
CONCLUSION
Neuromelanin-sensitive magnetic resonance imaging had a favorable diagnostic performance in discriminating patients with Parkinson's disease from healthy controls. To improve diagnostic accuracy, further investigations directly comparing these heterogeneity-affecting factors and optimizing these parameters are necessary.
KEY POINTS
• Neuromelanin-sensitive MRI favorably discriminates patients with Parkinson's disease from healthy controls. • Disease duration, parameters used for comparison, magnetic resonance imaging slice thickness, and segmentation methods affected heterogeneity across the studies.
Topics: Factor Analysis, Statistical; Humans; Magnetic Resonance Imaging; Melanins; Parkinson Disease; Substantia Nigra
PubMed: 32886201
DOI: 10.1007/s00330-020-07240-7 -
Biology of Sex Differences Nov 2022In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in Parkinson's disease as epidemiological and clinical features differ between males and females.
METHODS
To study sex bias in Parkinson's disease, we conducted a systematic review to select sex-labeled transcriptomic data from three relevant brain tissues: the frontal cortex, the striatum, and the substantia nigra. We performed differential expression analysis on each study chosen. Then we summarized the individual differential expression results with three tissue-specific meta-analyses and a global all-tissues meta-analysis. Finally, results from the meta-analysis were functionally characterized using different functional profiling approaches.
RESULTS
The tissue-specific meta-analyses linked Parkinson's disease to the enhanced expression of MED31 in the female frontal cortex and the dysregulation of 237 genes in the substantia nigra. The global meta-analysis detected 15 genes with sex-differential patterns in Parkinson's disease, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein-protein interaction networks, and transcription factors that differed by sex. While male patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. All results generated during this study are readily available by accessing an open web resource ( http://bioinfo.cipf.es/metafun-pd/ ) for consultation and reuse in further studies.
CONCLUSIONS
Our in silico approach has highlighted sex-based differential mechanisms in typical Parkinson Disease hallmarks (inflammation, mitochondrial dysfunction, and oxidative stress). Additionally, we have identified specific genes and transcription factors for male and female Parkinson Disease patients that represent potential candidates as biomarkers to diagnosis.
Topics: Humans; Male; Female; Parkinson Disease; Transcriptome; Substantia Nigra; Inflammation; Transcription Factors; Mediator Complex
PubMed: 36414996
DOI: 10.1186/s13293-022-00477-5 -
Neurosurgical Review Apr 2022Pediatric tectal gliomas generally have a benign clinical course with the majority of these observed radiologically. However, patients often need treatment for... (Review)
Review
Pediatric tectal gliomas generally have a benign clinical course with the majority of these observed radiologically. However, patients often need treatment for obstructive hydrocephalus and occasionally require cytotoxic therapy. Given the lack of level I data, there is a need to further characterize management strategies for these rare tumors. We have therefore performed the first systematic review comparing various management strategies. The literature was systematically searched from January 1, 2000, to July 30, 2020, to identify studies reporting treatment strategies for pediatric tectal gliomas. The systematic review included 355 patients from 14 studies. Abnormal ocular findings-including gaze palsies, papilledema, diplopia, and visual field changes-were a common presentation with between 13.6 and 88.9% of patients experiencing such findings. CSF diversion was the most performed procedure, occurring in 317 patients (89.3%). In individual studies, use of CSF diversion ranged from 73.1 to 100.0%. For management options, 232 patients were radiologically monitored (65.4%), 69 received resection (19.4%), 30 received radiotherapy (8.4%), and 19 received chemotherapy (5.4%). When examining frequencies within individual studies, chemotherapy ranged from 2.5 to 29.6% and radiotherapy ranged from 2.5 to 28.6%. Resection was the most variable treatment option between individual studies, ranging from 2.3 to 100.0%. Most tectal gliomas in the pediatric population can be observed through radiographic surveillance and CSF diversion. Other forms of management (i.e., chemotherapy and radiotherapy) are warranted for more aggressive tumors demonstrating radiological progression. Surgical resection should be reserved for large tumors and/or those that are refractory to other treatment modalities.
Topics: Brain Stem Neoplasms; Child; Glioma; Humans; Hydrocephalus; Radiography; Tectum Mesencephali
PubMed: 34609665
DOI: 10.1007/s10143-021-01653-8 -
Journal of Neurology Dec 2021To evaluate the diagnostic performance of iron-sensitive sequences targeting the substantia nigra for distinguishing patients with Parkinson's disease from control... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the diagnostic performance of iron-sensitive sequences targeting the substantia nigra for distinguishing patients with Parkinson's disease from control participants and to identify factors causing heterogeneity.
METHODS
A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before March 6, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Subgroup and meta-regression analyses were also performed to determine factors influencing heterogeneity affecting the diagnostic performance among the clinical, MRI, and analytic characteristics.
RESULTS
A total of 22 articles including 1126 patients with Parkinson's disease and 933 control participants were enrolled in this systematic review and meta-analysis. Of those, 12 studies used objective analyses of quantitative susceptibility measurements, and 10 visually assessed the nigrosome-1 in subjective analyses. Iron-sensitive nigral magnetic resonance imaging showed a pooled sensitivity of 92% (95% confidence interval 88-95%) and a pooled specificity of 90% (95% confidence interval 81-95%). According to subgroup and meta-regression analyses, a longer mean disease duration in patients with Parkinson's disease (≥ 5 years), subjective analysis, a smaller size of pixel (< 0.6 mm), a larger flip angle (> 15°), a smaller slice thickness (≤ 1 mm), and specific targeting of the substantia nigra pars compacta improved the diagnostic performance.
CONCLUSION
Iron-sensitive nigral magnetic resonance imaging had a favorable diagnostic performance in discriminating patients with Parkinson's disease from control participants. Subjective analytic methods remain superior to objective approaches. Further improvements of the spatial resolution and contrast-to-noise ratio to specifically target the nigrosome-1 with objective analytic methods will be needed.
Topics: Humans; Iron; Magnetic Resonance Imaging; Parkinson Disease; Sensitivity and Specificity; Substantia Nigra
PubMed: 33914142
DOI: 10.1007/s00415-021-10582-x -
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