-
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 -
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 -
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 -
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 -
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 -
The Laryngoscope Mar 2017To report two patients with a history of microvascular decompression (MVD) for hemifacial spasm who presented with Teflon granulomas (TG) mimicking cerebellopontine... (Review)
Review
OBJECTIVES/HYPOTHESIS
To report two patients with a history of microvascular decompression (MVD) for hemifacial spasm who presented with Teflon granulomas (TG) mimicking cerebellopontine angle (CPA) tumors and to perform a systematic review of the English-language literature.
STUDY DESIGN
Case series at a single tertiary academic referral center and systematic review.
METHODS
Retrospective chart review with analysis of clinical, radiological, and histopathological findings. Systematic review using PubMed, Embase, MEDLINE, and Web of Science databases.
RESULTS
Two patients with large skull base TGs mimicking CPA tumors clinically and radiographically were managed at the authors' institution. The first presented 4 years after MVD with asymmetrical sensorineural hearing loss, multiple progressive cranial neuropathies, and brainstem edema due to a growing TG. Reoperation with resection of the granuloma confirmed a foreign-body reaction consisting of multinucleated giant cells containing intracytoplasmic Teflon particles. The second patient presented 11 years after MVD with asymmetrical sensorineural hearing loss and recurrent hemifacial spasm. No growth was noted over 2 years, and the patient has been managed expectantly. Only one prior case of TG after MVD for hemifacial spasm has been reported in the English literature.
CONCLUSIONS
TG is a rare complication of MVD for hemifacial spasm. The diagnosis should be suspected in patients presenting with a new-onset enhancing mass of the CPA after MVD, even when performed decades earlier. A thorough clinical and surgical history is critical toward establishing an accurate diagnosis to guide management and prevent unnecessary morbidity. Surgical intervention is not required unless progressive neurologic complications ensue.
LEVEL OF EVIDENCE
4 Laryngoscope, 127:715-719, 2017.
Topics: Academic Medical Centers; Adult; Biopsy, Needle; Cerebellar Neoplasms; Cerebellopontine Angle; Diagnosis, Differential; Female; Follow-Up Studies; Granuloma, Foreign-Body; Hemifacial Spasm; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Microvascular Decompression Surgery; Middle Aged; Polytetrafluoroethylene; Postoperative Complications; Reoperation; Retrospective Studies; Sampling Studies; Treatment Outcome
PubMed: 27320780
DOI: 10.1002/lary.26126 -
World Neurosurgery Mar 2021Lesioning the Forel field or the subthalamic region is considered a possible treatment for tremoric patients with Parkinson disease, essential tremor, and other...
BACKGROUND
Lesioning the Forel field or the subthalamic region is considered a possible treatment for tremoric patients with Parkinson disease, essential tremor, and other diseases. This surgical treatment was performed in the 1960s to 1970s and was an alternative to thalamotomy. Recently, there has been increasing interest in the reappraisal of stimulating and/or lesioning these targets, partly as a result of innovations in imaging and noninvasive ablative technologies, such as magnetic resonance-guided focused ultrasonography.
OBJECTIVE
We wanted to perform a thorough review of the subthalamic region, both from an anatomic and a surgical standpoint, to offer a comprehensive and updated analysis of the techniques and results reported for patients with tremor treated with different techniques.
METHODS
We performed a systematic review of the literature, gathering articles that included patients who underwent ablative or stimulation surgical techniques, targeting the pallidothalamic pathways (pallidothalamic tractotomy), cerebellothalamic pathway (cerebellothalamic tractotomy), or subthalamic area.
RESULTS
Pallidothalamic tractotomy consists of a reduced area that includes pallidofugal pathways. It may be considered an interesting target, given the benefit/risk ratio and the clinical effect, which, compared with pallidotomy, involves a lower risk of injury or involvement of vital structures such as the internal capsule or optic tract. Cerebellothalamic tractotomy and/or posterior subthalamic area are other alternative targets to thalamic stimulation or ablative surgery.
CONCLUSIONS
Based on the significant breakthrough that magnetic resonance-guided focused ultrasonography has meant in the neurosurgical world, some classic targets such as the pallidothalamic tract, Forel field, and posterior subthalamic area may be reconsidered as surgical alternatives for patients with movement disorders.
Topics: Cerebellum; Deep Brain Stimulation; Essential Tremor; Globus Pallidus; Humans; Implantable Neurostimulators; Neural Pathways; Parkinson Disease; Prosthesis Implantation; Radiofrequency Ablation; Subthalamus; Thalamus; Tremor; Ultrasonic Surgical Procedures
PubMed: 33276174
DOI: 10.1016/j.wneu.2020.11.143 -
Cerebellum (London, England) Jun 2016Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts... (Review)
Review
Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks.
Topics: Cerebellum; Emotions; Functional Neuroimaging; Humans; Schizophrenia; Schizophrenic Psychology; Theory of Mind
PubMed: 26155761
DOI: 10.1007/s12311-015-0696-2 -
World Neurosurgery Feb 2017Synchronous tumors of the cerebellopontine angle (CPA) are very rare and inconsistently described. We present 2 cases of contiguous vestibular schwannoma (VS) and... (Review)
Review
BACKGROUND
Synchronous tumors of the cerebellopontine angle (CPA) are very rare and inconsistently described. We present 2 cases of contiguous vestibular schwannoma (VS) and meningioma and a systematic literature review of all multiple CPA tumors.
METHODS
Retrospective chart review and systematic literature review were performed.
RESULTS
A 64-year-old woman and a 42-year-old man presented with symptoms referable to the CPA. Magnetic resonance imaging in both patients revealed 2 separate contiguous tumors. Retrosigmoid craniotomy and tumor removal in each case confirmed VS and meningioma. Systematic literature review identified 42 previous English-language publications describing 46 patients with multiple CPA tumors. Based on Frassanito criteria, there were 4 concomitant tumors (8%), 16 contiguous tumors (33%), 3 collision tumors (6%), 13 mixed tumors (27%), and 11 tumor-to-tumor metastases (23%). Extent of resection was gross total in 16 cases and subtotal in 16 cases (50% each). Unfavorable House-Brackmann grade III-VI function was documented in 27% overall and in 33% of patients with VS and meningioma, a marked increase from the observed range in isolated VS.
CONCLUSIONS
Multiple CPA tumors are rare, heterogeneous lesions with a marked predisposition toward poor facial nerve outcomes, potentially attributable to a paracrine mechanism that simultaneously drives multiple tumor growth and increases invasiveness or adhesiveness at the facial nerve-tumor interface. Preceding nomenclature has been confounding and inconsistent; we recommend classifying all multiple CPA tumors as "synchronous tumors," with "schwannoma with meningothelial hyperplasia" or "tumor-to-tumor metastases" reserved for rare, specific circumstances.
Topics: Adult; Cerebellar Neoplasms; Cerebellopontine Angle; Craniotomy; Female; Humans; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasms, Multiple Primary; Neuroma, Acoustic; Retrospective Studies
PubMed: 27836701
DOI: 10.1016/j.wneu.2016.11.002 -
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