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Journal of Personalized Medicine May 2021Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.
PubMed: 34070826
DOI: 10.3390/jpm11060488 -
Arquivos Brasileiros de Cardiologia Jun 2014Diagnosis, prognosis and evaluation of death risk in Chagas cardiomyopathy still constitute a challenge due to the diversity of manifestations, which determine the... (Review)
Review
Diagnosis, prognosis and evaluation of death risk in Chagas cardiomyopathy still constitute a challenge due to the diversity of manifestations, which determine the importance of using echocardiography, tissue Doppler and biomarkers. To evaluate, within a systematic review, clinical and echocardiographic profiles of patients with chronic chagasic cardiomyopathy, which may be related to worse prognosis and major mortality risk. To perform the systematic review, we used Medline (via PubMed), LILACS and SciELO databases to identify 82 articles published from 1991 to 2012, with the following descriptors: echocardiography, mortality and Chagas disease. We selected 31 original articles, involving diagnostic and prognostic methods. The importance of Chagas disease has increased due to its emergence in Europe and United States, but most evidence came from Brazil. Among the predictors of worse prognosis and higher mortality risk are morphological and functional alterations in the left and right ventricles, evaluated by conventional echocardiography and tissue Doppler, as well as the increase in brain natriuretic peptide and troponin I concentrations. Recently, the evaluations of dyssynchrony, dysautonomia, as well as strain, strain rate and myocardial twisting were added to the diagnostic arsenal for the early differentiation of Chagas cardiomyopathy. Developments in imaging and biochemical diagnostic procedures have enabled more detailed cardiac evaluations, which demonstrate the early involvement of both ventricles, allowing a more accurate assessment of the mortality risk in Chagas disease.
Topics: Adult; Aged; Chagas Cardiomyopathy; Female; Humans; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Time Factors; Ultrasonography; Young Adult
PubMed: 25004422
DOI: 10.5935/abc.20140068 -
Parkinsonism & Related Disorders Nov 2022Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace amounts of αSyn oligomers in vivo.. Herein, we assessed the diagnostic accuracy of the αSyn-SAAs across biospecimens, diagnostic references, methods, and subtypes.
METHODS
A systematic literature search yielded 36 eligible studies for a meta-analysis of the sensitivity and specificity of αSyn-SAAs in patients with α-synucleinopathies(n = 2722) and controls(n = 2278). Pooled sensitivities and specificities with 95% confidence intervals (CIs) were calculated using bivariate random-effects models and a meta-regression analysis was performed.
RESULTS
The summary sensitivity and specificity of αSyn-SAAs positivity for the diagnosis of α-synucleinopathies were 0.88(95% CIs = 0.84-0.91) and 0.95(0.93-0.97), respectively. Two covariates (biospecimen and diagnostic reference) were significant in fitting the meta-regression model (likelihood-ratio test for sensitivity and specificity, p < 0.01, p = 0.01, respectively). Skin αSyn-SAAs exhibited the highest sensitivity 0.92(0.87-0.95), which was not different from that of cerebrospinal fluid (CSF)(0.90(0.86-0.93), p = 0.39). Olfactory mucosa αSyn-SAAs exhibited a lower sensitivity 0.64(0.49-0.76) than those of the other two specimens(p = 0.02, 0.01, compared to CSF and skin, respectively). Application of pathological diagnostic standards were associated with a higher specificity of αSyn-SAAs compared to clinical diagnosis (p < 0.01). The diagnostic sensitivity and specificity of CSF αSyn-SAAs were 0.91(0.87-0.94) and 0.96(0.93-0.98) for Lewy body disease, 0.90(0.79-0.95) and 0.96(0.90-0.98) for prodromal α-synucleinopathies, and 0.63(0.24-0.90) and 0.97(0.93-0.99) for multiple system atrophy.
CONCLUSIONS
αSyn-SAAs are promising in vivo detectors of abnormal αSyn aggregates and may aid the early diagnosis of α-synucleinopathies.
Topics: Humans; alpha-Synuclein; Synucleinopathies; Lewy Body Disease; Multiple System Atrophy; Sensitivity and Specificity
PubMed: 36289019
DOI: 10.1016/j.parkreldis.2022.10.007 -
Journal of Hypertension Oct 2016The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States.
METHODS
MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis.
RESULTS
Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)].
CONCLUSION
Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension.
REGISTRATION
PROSPERO ID CRD42015024612.
Topics: Antiparkinson Agents; Blood Pressure; Droxidopa; Humans; Hypotension, Orthostatic; Posture; Registries
PubMed: 27442791
DOI: 10.1097/HJH.0000000000001043 -
Journal of Neurology Apr 2024Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune... (Review)
Review
BACKGROUND
Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB.
OBJECTIVES
To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB.
METHODS
We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term "IgLON5". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB.
RESULTS
We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM-sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%.
CONCLUSIONS
We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease.
Topics: Humans; Middle Aged; Lewy Body Disease; Cognitive Dysfunction; Sleep Apnea, Obstructive; REM Sleep Behavior Disorder; Sleep Wake Disorders; Encephalitis; Hashimoto Disease
PubMed: 38195895
DOI: 10.1007/s00415-023-12145-8 -
Autonomic Neuroscience : Basic &... Dec 2023To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination.
METHODS
We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series.
RESULTS
We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05).
CONCLUSION
Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Postural Orthostatic Tachycardia Syndrome; Demography
PubMed: 38000119
DOI: 10.1016/j.autneu.2023.103132 -
Tropical Medicine & International... Oct 2021Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality...
Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.
Topics: Anticonvulsants; Humans; Magnesium Sulfate; Tetanus
PubMed: 34403179
DOI: 10.1111/tmi.13667 -
Journal of Neurology Mar 2022To investigate the retina thickness assessed using optical coherence tomography in atypical parkinsonism in comparison with health controls (HC) and patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
To investigate the retina thickness assessed using optical coherence tomography in atypical parkinsonism in comparison with health controls (HC) and patients with Parkinson's disease (PD).
METHODS
PubMed and EMBASE were searched for potentially eligible studies that reported retina thickness in atypical parkinsonism [including progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration] in comparison with that of HC and PD patients from their dates of inception to Jan 24, 2021. Mean difference (μm) of the thickness of peripapillary retinal nerve fiber layer (pRNFL) and central macular thickness (CMT) were pooled with random effects model.
RESULTS
We included ten studies eligible for inclusion criteria. Average pRNFL thickness and average CMT were thinner in PSP [pooled mean difference (μm) of - 4.71, 95% CI (- 7.15, - 2.27); - 15.12, 95% CI (- 16.93, - 13.30)] and in MSA [- 5.37, 95% CI (- 6.59, - 4.15); - 5.93, 95% CI (- 11.00, - 0.87)] compared with HC, and were thinner in PSP [- 5.81, 95% CI (- 8.92, - 2.69); - 10.63, 95% CI (- 20.29, - 0.98)] and in MSA [- 0.35 μm, 95% CI (- 5.72, 5.01); - 7.42 μm [95% CI (- 12.46, - 2.38)] compared with PD. The pRNFL thickness was thinning in superior, inferior and nasal quadrants, and CMT was thinning in outer sectors in MSA compared with HC.
CONCLUSIONS
The retina thickness was significantly thinner in PSP and MSA than those in HC and PD. The specific patterns of retina thinning in MSA could be clinical importance for differentiation among atypical parkinsonism.
Topics: Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Retina; Tomography, Optical Coherence
PubMed: 34245345
DOI: 10.1007/s00415-021-10703-6 -
International Journal of Environmental... Mar 2022Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV.... (Meta-Analysis)
Meta-Analysis Review
Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV. Design: A systematic review and meta-analysis on the impact of hyperthyroidism on HRV. Methods: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hyperthyroidism and healthy controls. Random-effects meta-analysis was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals (or Normal-to-Normal intervals—NN), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. Results: We included 22 studies with 10,811 patients: 1002 with hyperthyroidism and 9809 healthy controls. There was a decrease in RR (effect size = −4.63, 95% CI −5.7 to −3.56), SDNN (−6.07, −7.42 to −4.71), RMSSD (−1.52, −2.18 to −0.87), pNN50 (−1.36, −1.83 to −0.88), TP (−2.05, −2.87 to −1.24), HFnu (−3.51, −4.76 to −2.26), and VLF power (−2.65, −3.74 to −1.55), and an increase in LFnu (2.66, 1.55 to 3.78) and LF/HF ratio (1.75, 1.02 to 2.48) (p < 0.01). Most parameters had ES that was twice as high in overt compared to subclinical hyperthyroidism. Increased peripheral thyroid hormones and decreased TSH levels were associated with lower RR intervals. Conclusions: Hyperthyroidism is associated with a decreased HRV, which may be explained by the deleterious effect of thyroid hormones and TSH. The increased sympathetic and decreased parasympathetic activity may have clinical implications.
Topics: Cardiovascular System; Heart; Heart Rate; Humans; Hyperthyroidism; Thyrotropin
PubMed: 35329294
DOI: 10.3390/ijerph19063606 -
Clinical Cardiology Jul 2023Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitamin D-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.
Topics: Humans; Tilt-Table Test; Syncope, Vasovagal; Syncope; Vitamin D Deficiency; Vitamin D
PubMed: 37226313
DOI: 10.1002/clc.24035