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Neuroscience and Biobehavioral Reviews Oct 2021Post-mortem studies allow for the direct investigation of brain tissue in those with autism and related disorders. Several review articles have focused on aspects of... (Review)
Review
Post-mortem studies allow for the direct investigation of brain tissue in those with autism and related disorders. Several review articles have focused on aspects of post-mortem abnormalities but none has brought together the entire post-mortem literature. Here, we systematically review the evidence from post-mortem studies of autism, and of related disorders that present with autistic features. The literature consists of a small body of studies with small sample sizes, but several remarkably consistent findings are evident. Cortical layering is largely undisturbed, but there are consistent reductions in minicolumn numbers and aberrant myelination. Transcriptomics repeatedly implicate abberant synaptic, metabolic, proliferation, apoptosis and immune pathways. Sufficient replicated evidence is available to implicate non-coding RNA, aberrant epigenetic profiles, GABAergic, glutamatergic and glial dysfunction in autism pathogenesis. Overall, the cerebellum and frontal cortex are most consistently implicated, sometimes revealing distinct region-specific alterations. The literature on related disorders such as Rett syndrome, Fragile X and copy number variations (CNVs) predisposing to autism is particularly small and inconclusive. Larger studies, matched for gender, developmental stage, co-morbidities and drug treatment are required.
Topics: Autism Spectrum Disorder; Autistic Disorder; Autopsy; Brain; Cerebellum; DNA Copy Number Variations; Humans
PubMed: 34273379
DOI: 10.1016/j.neubiorev.2021.07.014 -
Translational Psychiatry May 2016Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders... (Meta-Analysis)
Meta-Analysis Review
Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.
Topics: Animals; Cerebellum; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ibogaine; Illicit Drugs; Male; Motor Activity; Neurons; Self Administration; Substance-Related Disorders
PubMed: 27244235
DOI: 10.1038/tp.2016.71 -
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 -
The Laryngoscope Sep 2021Cerebellopontine angle (CPA) and internal auditory canal (IAC) lipomas are rare, benign tumors comprising 0.08% of all intracranial tumors and can be mistaken for other,... (Comparative Study)
Comparative Study
OBJECTIVES/HYPOTHESIS
Cerebellopontine angle (CPA) and internal auditory canal (IAC) lipomas are rare, benign tumors comprising 0.08% of all intracranial tumors and can be mistaken for other, more common lesions of the CPA/IAC such as vestibular schwannoma. The purpose of this study was to review the literature and assess the evolution of CPA/IAC lipoma diagnosis and management. In addition, we present 17 new lipomas, matching the largest known case series of this rare tumor.
STUDY DESIGN
Retrospective case series and systematic review.
METHODS
Systematic review of the literature was performed using PubMed and Google Scholar. References from identified articles were also reviewed to identify potential additional manuscripts. Manuscripts and abstracts were reviewed to identify unique cases. For the case series, the charts of all CPA/IAC lipoma patients seen at a single institution from 2006-2019 were manually reviewed. Logistic regression and chi-squared analysis were performed where appropriate.
RESULTS
A total of 219 unique lipomas have been reported in the literature, including 17 presented in this study. Surgical management has been performed in 46% of cases and has been conducted less often in recent decades, likely due to improved radiographic diagnostic capabilities and understanding of surgical outcomes. Surgical management is associated with worse neurologic outcomes (P = .002) and has become less common in recent decades. Although growth is unlikely, it has been demonstrated in patients into their 30s.
CONCLUSIONS
Accurate radiographic diagnosis is imperative for appropriate patient management, as CPA/IAC lipomas should typically be managed through observation and serial imaging whereas vestibular schwannomas and other CPA/IAC lesions may require microsurgical or radiosurgical intervention depending on growth and symptomatology. Laryngoscope, 131:2081-2087, 2021.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Cerebellopontine Angle; Child; Child, Preschool; Diagnosis, Differential; Disease Management; Ear Canal; Female; Humans; Lipoma; Logistic Models; Magnetic Resonance Imaging; Male; Meniere Disease; Microsurgery; Middle Aged; Neuroma, Acoustic; Outcome Assessment, Health Care; Radiography; Radiosurgery; Retrospective Studies; Tomography, X-Ray Computed; Young Adult
PubMed: 33567134
DOI: 10.1002/lary.29434 -
Cerebellum (London, England) Dec 2023To date, cerebellar contribution to language is well established via clinical and neuroimaging studies. However, the particular functional role of the cerebellum in... (Meta-Analysis)
Meta-Analysis Review
To date, cerebellar contribution to language is well established via clinical and neuroimaging studies. However, the particular functional role of the cerebellum in language remains to be clarified. In this study, we present the first systematic review of the diverse language symptoms in spoken language after cerebellar lesion that were reported in case studies for the last 30 years (18 clinical cases from 13 papers), and meta-analysis using cluster analysis with bootstrap and symptom co-occurrence analysis. Seven clusters of patients with similar language symptoms after cerebellar lesions were found. Co-occurrence analysis revealed pairs of symptoms that tend to be comorbid. Our results imply that the "linguistic cerebellum" has a multiform contribution to language function. The most possible mechanism of such contribution is the cerebellar reciprocal connectivity with supratentorial brain regions, where the cerebellar level of the language network has a general modulation function and the supratentorial level is more functionally specified. Based on cerebellar connectivity with supratentorial components of the language network, the "linguistic cerebellum" might be further functionally segregated.
Topics: Humans; Language; Cerebellum; Language Disorders; Linguistics; Brain; Magnetic Resonance Imaging
PubMed: 36205825
DOI: 10.1007/s12311-022-01482-5 -
Multiple Sclerosis and Related Disorders Dec 2022Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system,... (Review)
Review
INTRODUCTION
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. The features and outcomes of CLIPPERS remains uncertain. we conducted this comprehensive systematic review to summarize all the existing studies that described CLIPPERS in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome.
METHODS
A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. We only included the cases that clearly reported probable or definite diagnosis of CLIPPERS based on Taieb et al.'s criteria. The quality of the included studies was assessed using the JBI Critical Appraisal Tool. Descriptive statistics were performed to analyze the studies. Data were expressed as mean and standard deviation (SD) for continuous variables and proportions for categorical variables.
RESULTS
We identified 100 case reports and series including a total of 140 patients with CLIPPERS (mean age: 46±18 years and males were 60%). The average follow-up duration was 32.27±57.8 months. Ataxia was the most common presenting symptom. Sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. The overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, P = 0.04). The overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. In the case of steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse.
CONCLUSION
CLIPPERS is a rare clinical syndrome that affects mainly middle-aged males. Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. Therefore, neurologists should maintain a high index of suspicion for CLIPPERS in any patient presenting with symptoms and signs referrable to the brainstem. These patients should be screened for associated malignancies, especially hematological malignancies. The cases associated with malignancy tend to have worse outcomes. The relapse rate is relatively high. The relapse rate may be associated with worse mortality. Based on our findings, we recommend that CLIPPERS be treated with high-dose steroid therapy for at least ten days during the acute phase with a very slow taper. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.
Topics: Middle Aged; Male; Humans; Adult; Magnetic Resonance Imaging; Prospective Studies; Pons; Inflammation; Steroids; Syndrome; Chronic Disease
PubMed: 36029706
DOI: 10.1016/j.msard.2022.104112 -
Journal of Neurology Oct 2023With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar ataxia. Therefore, we conducted a systematic review and meta-analysis to investigate the efficacy and safety of NIBS in treating patients with cerebellar ataxia.
METHODS
Databases, including PubMed, Embase, Web of Science, Medline, and Cochrane Library, were retrieved for relevant randomized controlled trials (RCTs). Two researchers conducted literature screening, data extraction, literature quality assessment, and heterogeneity analysis between RCTs. According to the magnitude of heterogeneity I, an appropriate data analysis model was selected for meta-analysis.
RESULTS
A total of 14 RCTs including 406 patients with cerebellar ataxia met the inclusion criteria. The included RCTs had an overall low-risk bias and an intermediate level of evidence recommendation for key outcome indicators, such as the scale for the assessment and rating of ataxia (SARA) and international cooperative ataxia rating scale (ICARS). The results of meta-analysis showed that cerebellar NIBS, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), was effective in reducing the SARA scores (MD = - 3.45, 95%CI = [- 4.85, - 2.50], P < 0.05) and ICARS scores (MD = - 10.87, 95%CI = [- 14.46, - 7.28], P < 0.05) in patients with cerebellar ataxia compared to controls. Subgroup analysis showed that the efficacy of tDCS and rTMS was statistically different in patients with cerebellar ataxia as assessed by the SARA scores, but not by the ICARS scores. There was statistically significant difference in the efficacy of NIBS for the treatment of cerebellar ataxia caused by different etiologies. As for safety, 8 of 14 included studies documented the adverse effects of NIBS, and only two studies reported the mild adverse events of NIBS.
CONCLUSIONS
Cerebellar NIBS was safe and effective in improving the motor coordination of patients with cerebellar ataxia, and tDCS was better than rTMS in the treatment of cerebellar ataxia. In addition, the efficacy of NIBS was different in the treatment of different types of cerebellar ataxia.
Topics: Humans; Cerebellar Ataxia; Randomized Controlled Trials as Topic; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cerebellum
PubMed: 37460852
DOI: 10.1007/s00415-023-11799-8 -
JAMA Oct 2019The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.
OBJECTIVE
To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.
DESIGN, SETTING, AND PARTICIPANTS
Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).
EXPOSURE
Surgical hematoma evacuation vs conservative treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH.
RESULTS
Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).
CONCLUSIONS AND RELEVANCE
Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.
Topics: Aged; Cerebellar Diseases; Cerebellum; Cerebral Hemorrhage; Conservative Treatment; Female; Hematoma; Humans; Male; Observational Studies as Topic; Treatment Outcome
PubMed: 31593272
DOI: 10.1001/jama.2019.13014 -
Cerebellum (London, England) Oct 2023The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for... (Meta-Analysis)
Meta-Analysis
The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.
Topics: Humans; Cerebellum; Emotions; Cerebellar Vermis; Magnetic Resonance Imaging; Neuroimaging; Brain Mapping
PubMed: 35999332
DOI: 10.1007/s12311-022-01459-4 -
BMC Neurology Mar 2022Study the cognitive profile of individuals with Friedreich ataxia (FRDA) and seek evidence for correlations between clinical, genetic and imaging characteristics and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Study the cognitive profile of individuals with Friedreich ataxia (FRDA) and seek evidence for correlations between clinical, genetic and imaging characteristics and neuropsychological impairments.
METHODS
Based on PRISMA guidelines, a meta-analysis was realized using the Pubmed and Scopus databases to identify studies (1950-2021) reporting neuropsychological test results in genetically confirmed FRDA and control participants in at least one of the following cognitive domains: attention/executive, language, memory and visuo-spatial functions as well as emotion. Studies using identical outcomes in a minimum of two studies were pooled. Pooled effect sizes were calculated with Cohen's d.
RESULTS
Eighteen studies were included. Individuals with FRDA displayed significantly lower performance than individuals without FRDA in most language, attention, executive function, memory visuospatial function, emotion regulation and social cognitive tasks. Among the included studies, thirteen studies examined the relationship between neuropsychological test results and clinical parameters and reported significant association with disease severity and six studies reviewed the relationship between neuroimaging measures and cognitive performance and mainly reported links between reduced cognitive performance and changes in cerebellar structure.
CONCLUSIONS
Individuals with FRDA display significantly lower performances in many cognitive domains compared to control participants. The spectrum of the cognitive profile alterations in FRDA and its correlation with disease severity and cerebellar structural parameters suggest a cerebellar role in the pathophysiology of FRDA cognitive impairments.
Topics: Cerebellum; Cognition; Executive Function; Friedreich Ataxia; Humans; Neuropsychological Tests
PubMed: 35300598
DOI: 10.1186/s12883-022-02615-3