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The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study.

ABSTRACT: Recently, hyperbaric oxygen therapy (HBOT) has increased in popularity as a treatment for autism. Numerous studies document oxidative stress and inflammation in individuals with autism; both of these conditions have demonstrated improvement with HBOT, along with enhancement of neurological function and cognitive performance. In this study, children with autism were treated with HBOT at atmospheric pressures and oxygen concentrations in current use for this condition. Changes in markers of oxidative stress and inflammation were measured. The children were evaluated to determine clinical effects and safety.Eighteen children with autism, ages 3-16 years, underwent 40 hyperbaric sessions of 45 minutes duration each at either 1.5 atmospheres (atm) and 100% oxygen, or at 1.3 atm and 24% oxygen. Measurements of C-reactive protein (CRP) and markers of oxidative stress, including plasma oxidized glutathione (GSSG), were assessed by fasting blood draws collected before and after the 40 treatments. Changes in clinical symptoms, as rated by parents, were also assessed. The children were closely monitored for potential adverse effects.At the endpoint of 40 hyperbaric sessions, neither group demonstrated statistically significant changes in mean plasma GSSG levels, indicating intracellular oxidative stress appears unaffected by either regimen. A trend towards improvement in mean CRP was present in both groups; the largest improvements were observed in children with initially higher elevations in CRP. When all 18 children were pooled, a significant improvement in CRP was found (p = 0.021). Pre- and post-parental observations indicated statistically significant improvements in both groups, including motivation, speech, and cognitive awareness (p < 0.05). No major adverse events were observed.In this prospective pilot study of children with autism, HBOT at a maximum pressure of 1.5 atm with up to 100% oxygen was safe and well tolerated. HBOT did not appreciably worsen oxidative stress and significantly decreased inflammation as measured by CRP levels. Parental observations support anecdotal accounts of improvement in several domains of autism. However, since this was an open-label study, definitive statements regarding the efficacy of HBOT for the treatment of individuals with autism must await results from double-blind, controlled trials.clinicaltrials.gov NCT00324909.

SUBMITTER: Rossignol DA

PROVIDER: S-EPMC2244616 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study.

Rossignol Daniel A DA Rossignol Lanier W LW James S Jill SJ Melnyk Stepan S Mumper Elizabeth E

BMC pediatrics 20071116

<h4>Background</h4>Recently, hyperbaric oxygen therapy (HBOT) has increased in popularity as a treatment for autism. Numerous studies document oxidative stress and inflammation in individuals with autism; both of these conditions have demonstrated improvement with HBOT, along with enhancement of neurological function and cognitive performance. In this study, children with autism were treated with HBOT at atmospheric pressures and oxygen concentrations in current use for this condition. Changes i ...[more]

PMID: 18005455

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Project description:Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression.Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation.Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P?=?0.042) and hepatic growth factor (HGF) (P?=?0.028) in CSF. In serum, the ratio of the truncated BDNF form and ?-2 macroglobulin (?-2 M), was also significantly lower (P?=?0.028) while the mature BDNF/?-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P?=?0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-?, CD40L, IL-6, IFN-? and IL-1? when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline.Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration.NCT00409747.

Project description:Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects millions worldwide. Suggested pathophysiology includes cerebral hypoperfusion, inflammation, mitochondrial and immune dysregulation, and oxidative stress. Debate exists concerning the benefit of hyperbaric oxygen therapy (HBOT) in treating ASD and its impacts on verbal behavior. The present study directly assesses the impacts of HBOT treatments on verbal behavior using a novel and unique manner. Materials and methods A two-group quasi-experimental trial using a pretest and a posttest was designed to retrospectively assess (n = 65) any association between HBOT and change in verbal scores in children (n = 65) with ASD. All children completed two verbal tests six months apart, either the Verbal Behavior Milestones Assessment and Placement Program (VBMAPP) or the Assessment of Basic Language and Learning Skills (ABLLS), based on their developmental age. The control cohort received applied behavior analysis (ABA) without HBOT. The experimental cohort received ABA and a minimum of 40 HBOT treatments, breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 60 minutes. Results Sixty-five children were included, of which 32 received HBOT (mean (M) = 5.1, standard deviation (SD) = 2.93), with an age range of two to 17 years. More than 63% of the subjects had an autism severity level of three. The 23 children administered VBMAPP who received HBOT showed substantial mean differences with high effect sizes (ESs) (-0.743 to -1.65) and a total score (TS) ES equal to -1.23 as measured by Cohen's d. There was a statistically significant improvement (p < 0.05) in all VBMAPP milestone domains and TS. TS change from baseline versus those in the non-HBOT (Control-ABA) group (n=12) was 46.41 ± 20.14 vs 14.42 ± 6.99; p < 0.0001, ES = -1.23. The 30 children administered the ABLLS showed substantial mean difference (TS) change from baseline 268.89 ± 182.05 vs 190.81 ± 135.26 and exhibited small to medium (-.114 to -.773) ESs with a TS ES = -0.487. Due to the high within-group variability (low statistical power) within the ABLLS cohort, there was a non-significant mean difference between the control (ABA) and experimental (ABA + HBO2) groups' difference scores (p > 0.2024), despite the medium (TS) ES. Conclusions The child cohorts administered the VBMAPP and the ABLLS demonstrated substantial improvements between the non-HBOT (control-ABA) and HBOT (experimental-ABA + HBO2) groups as measured by the significant mean differences and small to large ESs. Simply put, the children in the experimental cohort acquired more verbal skills than their counterparts in the control group.

Project description:BackgroundAutism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.ResultsMTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).ConclusionsThis exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.Trial registrationThis trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.

Project description:Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS.An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes.Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females.Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment. Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true.

Project description:BackgroundMinocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder.MethodsParticipants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p < 0.05 using ANOVA and partial eta squared (η(2)) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett's post hoc testing.ResultsSignificant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period.ConclusionThe clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted.Trial registrationNCT01531582 - clinicaltrials.gov.

Dataset Information

The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study.

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The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study.

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