scholarly journals Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (11) ◽  
pp. 1141
Author(s):  
Daniel A. Rossignol ◽  
Richard E. Frye
Keyword(s):  
Systematic Review ◽  
Significant Variation ◽  
Folate Receptor ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Effect Sizes ◽  
Pooled Prevalence ◽  
Spectrum Disorders ◽  
The Brain ◽  
Cerebral Folate Deficiency

The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain; low 5-MTHF in the brain causes cerebral folate deficiency (CFD). CFD has been associated with autism spectrum disorders (ASD) and is treated with d,l-leucovorin (folinic acid). One cause of CFD is an autoantibody that interferes with the function of the FRα. FRα autoantibodies (FRAAs) have been reported in ASD. A systematic review was performed to identify studies reporting FRAAs in association with ASD, or the use of d,l-leucovorin in the treatment of ASD. A meta-analysis examined the prevalence of FRAAs in ASD. The pooled prevalence of ASD in individuals with CFD was 44%, while the pooled prevalence of CFD in ASD was 38% (with a significant variation across studies due to heterogeneity). The etiology of CFD in ASD was attributed to FRAAs in 83% of the cases (with consistency across studies) and mitochondrial dysfunction in 43%. A significant inverse correlation was found between higher FRAA serum titers and lower 5-MTHF CSF concentrations in two studies. The prevalence of FRAA in ASD was 71% without significant variation across studies. Children with ASD were 19.03-fold more likely to be positive for a FRAA compared to typically developing children without an ASD sibling. For individuals with ASD and CFD, meta-analysis also found improvements with d,l-leucovorin in overall ASD symptoms (67%), irritability (58%), ataxia (88%), pyramidal signs (76%), movement disorders (47%), and epilepsy (75%). Twenty-one studies (including four placebo-controlled and three prospective, controlled) treated individuals with ASD using d,l-leucovorin. d,l-Leucovorin was found to significantly improve communication with medium-to-large effect sizes and have a positive effect on core ASD symptoms and associated behaviors (attention and stereotypy) in individual studies with large effect sizes. Significant adverse effects across studies were generally mild but the most common were aggression (9.5%), excitement or agitation (11.7%), headache (4.9%), insomnia (8.5%), and increased tantrums (6.2%). Taken together, d,l-leucovorin is associated with improvements in core and associated symptoms of ASD and appears safe and generally well-tolerated, with the strongest evidence coming from the blinded, placebo-controlled studies. Further studies would be helpful to confirm and expand on these findings.

scholarly journals A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder

2021 ◽  
Vol 11 (6) ◽  
pp. 488
Author(s):  
Daniel A Rossignol ◽  
Richard E Frye
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Immunoglobulin G ◽  
Meta Analysis ◽  
Intravenous Immunoglobulins ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Effect Sizes ◽  
Aberrant Behavior ◽  
Children With Asd

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.

scholarly journals Autism Spectrum Disorder and Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Julio Vaquerizo-Serrano ◽  
Gonzalo Salazar de Pablo ◽  
Jatinder Singh ◽  
Paramala Santosh
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Literature Search ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Clinical High Risk ◽  
Psychotic Experiences ◽  
Attenuated Psychosis Syndrome ◽  
The Mean ◽  
Spectrum Disorders

AbstractPsychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.

scholarly journals Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies

2018 ◽  
Vol 21 (4) ◽  
pp. 146-154 ◽  
Author(s):  
Amparo Díaz-Román ◽  
Junhua Zhang ◽  
Richard Delorme ◽  
Anita Beggiato ◽  
Samuele Cortese
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorders ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Newcastle Ottawa Scale ◽  
Spectrum Disorders ◽  
Sleep Alterations ◽  
The Impact ◽  
Ottawa Scale

BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2 statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted using Review Manager and Comprehensive Meta-Analysis.FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.

scholarly journals Global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Kevin Phan ◽  
Olivia Charlton ◽  
Saxon D. Smith
Keyword(s):  
Systematic Review ◽  
Significant Variation ◽  
Hidradenitis Suppurativa ◽  
Meta Analysis ◽  
Asia Pacific ◽  
Cochrane Library ◽  
Prevalence Rates ◽  
Level Of Evidence ◽  
Pooled Prevalence ◽  
The Usa

Abstract Background There is a significant variation in the reported prevalence of hidradenitis suppurativa (HS), ranging from 0.03–4%. We hypothesized that this significant variation may be due to different prevalence rates of HS according to geographical location as well as sex. Objective We aimed to perform a meta-analysis to determine pooled overall prevalence of HS, prevalence stratified according to geographical region and sex. Materials and methods A systematic review was performed by searching Ovid Medline, PubMed, Cochrane Library, DARE, and Embase, from inception to August 2018. A systematic review and meta-analysis was performed according to PRISMA guidelines. A meta-analysis of proportions was performed to determined pooled prevalence rates, with meta-regression based on geographic region. Prevalence in males versus females was also performed according to region. Results The overall pooled prevalence rate was 0.3% (0.2–0.6%) based on 118,760,093 HS cases available. Subgroup analysis demonstrated prevalence differences, with the highest being in Europe 0.8% (0.5–1.3%), compared to the USA 0.2% (0.1–0.4%), Asia-Pacific 0.2% (0.01–2.2%), and South America 0.2% (0.01–0.9%). Prevalence in males was lower compared to females in the USA (OR 0.403, 95% CI 0.37–0.439, P < 0.001) as well as in Europe (OR 0.635, 95% CI 0.397–1.015, P = 0.08) but not in the Asia-Pacific region (OR 0.936, 95% CI 0.319–2.751, P = 0.78). Conclusion Prevalence of HS varies significantly according to the geographical population. This variation is likely attributed to different ethnicity distributions amongst different continents. Level of evidence III

Oral health status of children and young adults with autism spectrum disorders: systematic review and meta-analysis

2016 ◽  
Vol 27 (5) ◽  
pp. 388-398 ◽  
Author(s):  
Silvana Nunes da Silva ◽  
Thais Gimenez ◽  
Rafael Celestino Souza ◽  
Anna Carolina Volpi Mello-Moura ◽  
Daniela Prócida Raggio ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorders ◽  
Health Status ◽  
Oral Health ◽  
Meta Analysis ◽  
Oral Health Status ◽  
Autism Spectrum ◽  
Adults With Autism ◽  
Children And Young Adults ◽  
Spectrum Disorders
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