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Reduction of Ritualistic Behavior in a Patient with Autism Spectrum Disordertreated with Antibiotics: A Case Report
... In an ASD patient, cefazolin was well known to significantly reduce the patient's repetitive behaviour aside from its antibacterial effect. 15 Before the procedure begins, the patient's behaviour needs to be taken care of. Knowing that the patient might not be communicative and to minimize disruption, the environment should be made less noisy and waiting time should not be prolonged. ...
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and the presence of restricted interests and repetitive behaviours. Comorbidities following ASD, such as seizure, intellectual disability, and sensory impairment worsen patients’ ability to care for themselves. We present the case of a 22-year-old man with autism, intellectual disability and visual impairment who had recurrent pain in his upper and lower left posterior teeth that had cavities. On the first visit, the patient was observed and had panoramic x-ray. Clinical examination could not be done properly due to lack of patient cooperation. Restoration, pulp capping, tooth extraction, and odontectomy were planned under general anaesthesia.
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.
Electronic supplementary material
The online version of this article (doi:10.1186/s13041-017-0292-0) contains supplementary material, which is available to authorized users.
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.
The author, a parent of a child with autism, describes an n=1 case in which his child's autism symptoms dramatically and rapidly improved following administration of a common antibiotic. The author asserts that this finding is not unusual in the autism population and that, when combined with prior recent medical research, suggests that a link between autism and the microbiome in some children is not just plausible, but in fact likely for some meaningful percentage of cases. The author argues for increased funding for a more thorough examination of links between autism and the microbiome and poses a series of questions to be further examined in future research.
Mammalian brain development is initiated in utero and internal and external environmental signals can affect this process all the way until adulthood. Recent observations suggest that one such external cue is the indigenous microbiota which has been shown to affect developmental programming of the brain. This may have consequences for brain maturation and function that impact on cognitive functions later in life. This review discusses these recent findings from a developmental perspective.
The authors assessed the effects of D-cycloserine on the core symptom of social impairment in subjects with autism.
Following a 2-week, single-blind placebo lead-in phase, drug-free subjects with autistic disorder were administered three different doses of D-cycloserine during each of three 2-week periods. Measures used for subject ratings included the Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist.
Significant improvement was found on the CGI and social withdrawal subscale of the Aberrant Behavior Checklist. d-Cycloserine was well tolerated at most of the doses used in this study.
In this pilot study, D-cycloserine treatment resulted in significant improvement in social withdrawal. Further controlled studies of D-cycloserine in autism appear warranted.
In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.
Objective:
Previous studies suggest that the unexplained sudden and severe onset of obsessive-compulsive disorder (OCD) and/or tics may be infection or immune precipitated. Beta lactam antibiotics may be neuroprotective beyond their antimicrobial efficacy. We examine the preliminary safety and efficacy of cefdinir in reducing obsessive-compulsive and/or tic severity in children with new-onset symptoms.
Method:
Twenty subjects were randomized to receive placebo or cefdinir for 30 days for the treatment of recent-onset OCD and/or tics. The placebo group received a comparable inactive treatment matched for taste, color, and consistency. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and Yale Global Tic Severity Scale (YGTSS) were the primary outcome measures utilized.
Results:
Subjects receiving cefdinir saw notable improvements in tic symptoms, with 44.4% showing at least a 25% reduction in YGTSS (mean decrease=9.5) scores compared with 9.1% of the placebo group (mean decrease=0.13). Despite improvements, significant group differences were not observed for YGTSS (F [1, 13]=4.03, p=0.066) although there were moderate differences between group treatment effects (d=0.72). For OCD symptoms, subjects receiving cefdinir saw improvements in OCD symptoms, with 33.3% showing at least a 25% reduction in CY-BOCS scores (mean decrease=7.8) compared with 27.3% of the placebo group (mean decrease=4.7), but there were also no significant differences for CY-BOCS (F [1, 13]=0.385, p=0.546; d=0.24).
Conclusions:
Subjects assigned to cefdinir exhibited notable, albeit nonstatistically significant, improvements in tic symptoms, compared with the placebo group. There were also some improvements in OCD symptoms, although these were not significant. Overall, cefdinir was well tolerated. Given these preliminary results, a fully powered study is warranted to explore the efficacy of cefdinir as a therapeutic tool for new-onset pediatric neuropsychiatric symptoms, particularly those that appear to be precipitated by infection.
Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.
The current review covers extant literature on pharmacotherapy for core symptoms of autism. The core symptoms of autism include impairments in social interaction and communication, as well as the presence of restricted and repetitive behaviors. There are no known efficacious treatments for the core social symptoms, although effects on repetitive behaviors are indicated with some data. While studies of fenfluramine, secretin, opiates, and mood stabilizers generally find no effect, mixed results suggest more research is needed on antidepressants and atypical antipsychotics. Newer lines of research, including cholinergic and glutamatergic agents and oxytocin, will be of considerable interest in the future. However, research on the treatment of core symptoms is plagued by limitations in study design, statistical power, and other issues inherent to the study of treatments for autism (e.g., heterogeneity of the disorder) that continue to prevent the elucidation of efficacious treatments.
There has been a marked decline in mortality due to rheumatic fever in the United States. We present evidence for the important role of penicillin in changing the severity of rheumatic carditis, beginning about 1946. Since that year, mortality due to rheumatic carditis has rapidly decreased to zero at the hospital we studied (House of the Good Samaritan, Boston), the rate of loss of all murmurs in patients at the study hospital accelerated simultaneously and exceeded 40 percent by 1970, and the rates of decline in national mortality due to rheumatic carditis accelerated fourfold with the advent of antibiotics. These data, together with reports of recent outbreaks of rheumatic fever, emphasize the importance of continued efforts to diagnose and treat Group A streptococcal pharyngitis.
The current diagnostic criteria for pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) are pediatric onset, neuropsychiatric disorder (obsessive-compulsive disorder [OCD]) and/or tic disorder; abrupt onset and/or episodic course of symptoms; association with group A beta-hemolytic streptococcal (GABHS) infection; and association with neurological abnormalities (motoric hyperactivity or adventitious movements, including choreiform movements or tics).
To assess new-onset PANDAS cases in relation to acute GABHS tonsillopharyngitis.
Prospective PANDAS case identification and follow-up.
Over a 3-year period (1998-2000), we identified 12 school-aged children with new-onset PANDAS. Each patient had the abrupt appearance of severe OCD behaviors, accompanied by mild symptoms and signs of acute GABHS tonsillopharyngitis. Throat swabs tested positive for GABHS by rapid antigen detection and/or were culture positive. The GABHS serologic tests, when performed (n = 3), showed very high antideoxyribonuclease antibody titers. Mean age at presentation was 7 years (age range, 5-11 years). In children treated with antibiotics effective in eradicating GABHS infection at the sentinel episode, OCD symptoms promptly disappeared. Follow-up throat cultures negative for GABHS were obtained prospectively after the first PANDAS episode. Recurrence of OCD symptoms was seen in 6 patients; each recurrence was associated with evidence of acute GABHS infection and responded to antibiotic therapy, supporting the premise that these patients were not GABHS carriers. The OCD behaviors exhibited included hand washing and preoccupation with germs, but daytime urinary urgency and frequency without dysuria, fever, or incontinence were the most notable symptoms in our series (58% of patients). Symptoms disappeared at night, and urinalysis and urine cultures were negative.
To our knowledge, this is the first prospective study to confirm that PANDAS is associated with acute GABHS tonsillopharyngitis and responds to appropriate antibiotic therapy at the sentinel episode.
The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) describes a subgroup of children with obsessive-compulsive disorder and/or tic disorder that experience symptom exacerbations following streptococcal infections. We hypothesized that the prevention of streptococcal infections among children in the PANDAS subgroup would decrease neuropsychiatric symptom exacerbations.
Twenty-three subjects with PANDAS were enrolled in a double blind, randomized controlled trial. Antibiotic prophylaxis with penicillin or azithromycin was administered for 12 months. Rates of streptococcal infections and neuropsychiatric symptom exacerbations were compared between the study year and the baseline year prior to entry.
Significant decreases in streptococcal infections during the study year were found with a mean of .1 (.3 SD) per subject, compared to the baseline year with 1.9 (1.2 SD) in the penicillin group and 2.4 (1.1 SD) in the azithromycin group [p<.01]. Significant decreases in neuropsychiatric exacerbations during the study year were also found with a mean of .5 (.5 SD) per subject in the penicillin group and .8 (.6 SD) in the azithromycin group, compared to the baseline year with 2.0 (.9 SD) in the penicillin group and 1.8 (.6 SD) in the azithromycin group [p<.01].
Penicillin and azithromycin prophylaxis were found to be effective in decreasing streptococcal infections and neuropsychiatric symptom exacerbations among children in the PANDAS subgroup.