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Neuropsychology Review Jun 2023Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but... (Meta-Analysis)
Meta-Analysis Review
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but may cause a decline in specific cognitive domains. The aim of this systematic review and meta-analysis was to assess the long-term (1-3 years) effects of STN or GPi DBS on four cognitive functions: (i) memory (delayed recall, working memory, immediate recall), (ii) executive functions including inhibition control (Color-Word Stroop test) and flexibility (phonemic verbal fluency), (iii) language (semantic verbal fluency), and (iv) mood (anxiety and depression). Medline and Web of Science were searched, and studies published before July 2021 investigating long-term changes in PD patients following DBS were included. Random-effects model meta-analyses were performed using the R software to estimate the standardized mean difference (SMD) computed as Hedges' g with 95% CI. 2522 publications were identified, 48 of which satisfied the inclusion criteria. Fourteen meta-analyses were performed including 2039 adults with a clinical diagnosis of PD undergoing DBS surgery and 271 PD controls. Our findings add new information to the existing literature by demonstrating that, at a long follow-up interval (1-3 years), both positive effects, such as a mild improvement in anxiety and depression (STN, Hedges' g = 0,34, p = 0,02), and negative effects, such as a decrease of long-term memory (Hedges' g = -0,40, p = 0,02), verbal fluency such as phonemic fluency (Hedges' g = -0,56, p < 0,0001), and specific subdomains of executive functions such as Color-Word Stroop test (Hedges' g = -0,45, p = 0,003) were observed. The level of evidence as qualified with GRADE varied from low for the pre- verses post-analysis to medium when compared to a control group.
Topics: Adult; Humans; Parkinson Disease; Deep Brain Stimulation; Subthalamic Nucleus; Globus Pallidus; Cognition; Neuropsychological Tests
PubMed: 35318587
DOI: 10.1007/s11065-022-09540-9 -
Movement Disorders : Official Journal... Feb 2021The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to... (Review)
Review
BACKGROUND
The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico-striato-thalamocortical circuit.
METHODS
Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single-photon emission computed tomography were included.
RESULTS
The severity of anxiety was associated with changes in the fear circuit and the cortico-striato-thalamocortical limbic circuit. In the fear circuit, a reduced gray-matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico-striato-thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported.
CONCLUSION
To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico-striato-thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Amygdala; Anxiety; Anxiety Disorders; Humans; Magnetic Resonance Imaging; Neuroimaging; Parkinson Disease
PubMed: 33289195
DOI: 10.1002/mds.28404 -
Expert Opinion on Emerging Drugs Dec 2020Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered....
INTRODUCTION
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities.
AREAS COVERED
We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients.
EXPERT OPINION
Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.
Topics: Adult; Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cognition; Drug Design; Drug Development; Humans
PubMed: 32938246
DOI: 10.1080/14728214.2020.1820481 -
Neurological Sciences : Official... Apr 2021Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in... (Review)
Review
BACKGROUND
Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies.
OBJECTIVE
This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis.
METHODS
We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-D-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed.
DISCUSSION
The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.
Topics: Basal Ganglia; Encephalitis; Humans; Tic Disorders; Tics; Tourette Syndrome
PubMed: 33486621
DOI: 10.1007/s10072-021-05065-w -
Neurosurgical Review Jun 2023Bilateral basal ganglia hemorrhages (BBGHs) represent rare accidents, with no clear standard of care currently defined. We reviewed the literature on BBGHs and analyzed... (Review)
Review
Bilateral basal ganglia hemorrhages (BBGHs) represent rare accidents, with no clear standard of care currently defined. We reviewed the literature on BBGHs and analyzed the available conservative and surgical strategies. PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies reporting patients with BBGHs. Clinical characteristics, management, and outcomes were analyzed. We included 64 studies comprising 75 patients, 25 (33%) traumatic and 50 (67%) non-traumatic. Traumatic cases affected younger patients (mean age 35 vs. 46 years, p=0.014) and males (84% vs. 71%, p=0.27) and were characterized by higher proportion of normal blood pressures at admission (66% vs. 13%, p=0.0016) compared to non-traumatic cases. Most patients were comatose at admission (56%), with a mean Glasgow Coma Scale (GCS) score of 7 and a higher proportion of comatose patients in the traumatic than in the non-traumatic group (64% vs. 52%, p=0.28). Among the traumatic group, motor vehicle accidents and falls accounted for 79% of cases. In the non-traumatic group, hemorrhage was most associated with hypertensive or ischemic (54%) and chemical (28%) etiologies. Management was predominantly conservative (83%). Outcomes were poor in 56% of patients with mean follow-up of 8 months. Good recovery was significantly higher in the traumatic than in the non-traumatic group (48% vs. 17%, p=0.019). BBGHs are rare occurrences with dismal prognoses. Standard management follows that of current intracerebral hemorrhage guidelines with supportive care and early blood pressure management. Minimally invasive surgery is promising, though substantial evidence is required to outweigh the potentially increased risks of bilateral hematoma evacuation.
Topics: Male; Humans; Adult; Coma; Basal Ganglia Hemorrhage; Cerebral Hemorrhage; Minimally Invasive Surgical Procedures; Accidents, Traffic; Glasgow Coma Scale; Treatment Outcome
PubMed: 37273079
DOI: 10.1007/s10143-023-02044-x -
Journal of Clinical Movement Disorders 2017Chorea is a hyperkinetic movement disorder consisting of involuntary irregular, flowing movements of the trunk, neck or face. Although Huntington's disease is the most... (Review)
Review
Chorea is a hyperkinetic movement disorder consisting of involuntary irregular, flowing movements of the trunk, neck or face. Although Huntington's disease is the most common cause of chorea in adults, chorea can also result from many other neurodegenerative, metabolic, and autoimmune conditions. While the pathophysiology of these different conditions is quite variable, recent advances in functional imaging have enabled the development of new methods for analysis of brain activity and neuronal dysfunction. In this paper we review the growing body of functional imaging data that has been performed in chorea syndromes and identify particular trends, which can be used to better understand the underlying network changes within the basal ganglia. While it can be challenging to identify whether changes are primary, secondary, or compensatory, identification of these trends can ultimately be useful in diagnostic testing and treatment in many of the conditions that cause chorea.
PubMed: 28649394
DOI: 10.1186/s40734-017-0056-0 -
Neuropsychology Review Sep 2017Several brain imaging markers have been studied in the development of post-stroke depression (PSD) and post-stroke apathy (PSA), but inconsistent associations have been... (Meta-Analysis)
Meta-Analysis Review
Several brain imaging markers have been studied in the development of post-stroke depression (PSD) and post-stroke apathy (PSA), but inconsistent associations have been reported. This systematic review and meta-analysis aims to provide a comprehensive and up-to-date evaluation of imaging markers associated with PSD and PSA. Databases (Medline, Embase, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews) were searched from inception to July 21, 2016. Observational studies describing imaging markers of PSD and PSA were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to examine the association between PSD or PSA and stroke lesion laterality, type, and location, also stratified by study phase (acute, post-acute, chronic). Other imaging markers were reviewed qualitatively. The search retrieved 4502 studies, of which 149 studies were included in the review and 86 studies in the meta-analyses. PSD in the post-acute stroke phase was significantly associated with frontal (OR 1.72, 95% CI 1.34-2.19) and basal ganglia lesions (OR 2.25, 95% CI 1.33-3.84). Hemorrhagic stroke related to higher odds for PSA in the acute phase (OR 2.58, 95% CI 1.18-5.65), whereas ischemic stroke related to higher odds for PSA in the post-acute phase (OR 0.20, 95% CI 0.06-0.69). Frequency of PSD and PSA is modestly associated with stroke type and location and is dependent on stroke phase. These findings have to be taken into consideration for stroke rehabilitation programs, as this could prevent stroke patients from developing PSD and PSA, resulting in better clinical outcome.
Topics: Apathy; Biomarkers; Brain; Depression; Humans; Observational Studies as Topic; Stroke
PubMed: 28831649
DOI: 10.1007/s11065-017-9356-2 -
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 -
Movement Disorders : Official Journal... Mar 2021Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned... (Review)
Review
Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Movement Disorders; Pallidotomy; Treatment Outcome
PubMed: 33215750
DOI: 10.1002/mds.28384 -
Journal of Translational Medicine Sep 2023Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.
METHODS
We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.
RESULTS
The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the 'off' state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6-100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the 'off' state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.
CONCLUSIONS
This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760.
Topics: Humans; Parkinson Disease; Levodopa; Transplantation, Autologous; Transplantation, Homologous; Allogeneic Cells
PubMed: 37679754
DOI: 10.1186/s12967-023-04484-x