Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

OBJECTIVES: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. METHODS: We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. RESULTS: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. CONCLUSION: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial Number: R000016846.

Agrypnia excitata.

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.

Pre-treatment of BALB/c mice with a centrally acting serotonin antagonist (cyproheptadine) reduces mortality from Boophone disticha poisoning.

INTRODUCTION: Crude extracts of Boophone disticha are used in Southern African traditional medical practice for the management of various illnesses and conditions and have also been abused for their claimed euphoric and hallucinogenic effects. Unfortunately, ingestion of Boophone disticha has resulted in toxicity and death. The results of a recent acute toxicity study in a rat model insinuated that central nervous system (CNS) serotonin overdrive could be the cause of toxicity in B. disticha poisoning. The present work sought to test that hypothesis by investigating whether pre-treatment of B. disticha poisoned BALB/c mice with the CNS acting serotonin antagonist, cyproheptadine, has a dose-dependent protective effect on toxicity and mortality. METHODS: A hydroethanolic extract of B. disticha was used in all the experiments. Five groups each with 10 animals were constituted as follows; a negative control group (received 10 ml/kg Normal Saline), a positive control group (received 375 mg/kg of the B. disticha extract), and three test groups each receiving 10 mg/kg, 15 mg/kg and 20 mg/kg cyproheptadine intraperitoneally 15 minutes before oral gavage administration of 375 mg/kg B. disticha extract respectively. The Functional Observational Battery was used to evaluate neurobehavioral and physiological changes resulting from toxicity of the plant extract. The mice were then placed in an open field for another five minutes and the number of rearings and border crossings were counted and recorded. Gait abnormalities, involuntary motor movements, mobility, arousal and stereotypical behavior were also scored according to predefined criteria. All open field investigations were recorded electronically using a LABTEC Webcam(®) and results were later analysed and recorded by one of the group members. All results were entered on data collection forms. Time to death (survival time) was considered as the time period from dosage with Boophone disticha to time of death. The study follow up period was 7 days and those mice that were alive at the end of the 7 day follow-up period were considered as having survived the poisoning episode. The Kaplan Meier plot and Log-rank test were used to compare differences in mortality and median time to death for mice in the 5 treatment groups. RESULTS: We found that cyproheptadine pre-treatment led to a dose-dependent decrease in mortality from 80% in the group not pre-treated with cyproheptadine, to 30% in the 15 and 20 mg/kg cyproheptadine pre-treated groups (n = 10 per group, p < 0.05). There was also a dose-dependent increase in median survival times amongst the groups (p < 0.0001). Pre-treatment with cyproheptadine also resulted in a decrease of other toxic symptoms associated with Boophone disticha. CONCLUSIONS: We conclude that cyproheptadine has a dose-dependent protective effect on mortality and toxicity produced by exposure to Boophone disticha in our mouse model of toxicity.

Kata techniques training consistently decreases stereotypy in children with autism spectrum disorder.

The effects of 14 weeks of Kata techniques training on stereotypic behaviors of children with autism spectrum disorders (ASD) were investigated. The study included 30 eligible (diagnosed ASD, school age) children with ages ranging from 5 to 16 years whom they assigned to an exercise (n=15) or a no-exercise control group (n=15). Participants of the exercise group received Kata techniques instruction four times per week for 14 weeks (56 sessions). Stereotypy was assessed at baseline (pre-intervention), week 14 (post-intervention), and at one month follow up in both groups. Results showed that Kata techniques training significantly reduced stereotypy in the exercise group. Following participation in Kata techniques training, stereotypy decreased from baseline levels by a M of 42.54% across participants. Interestingly, after 30 days of no practice, stereotypy in the exercise group remained significantly decreased compared to pre-intervention time. The participants of the control group did not show significant changes in the stereotypy. Teaching martial arts techniques to children with ASD for a long period of time consistently decreased their stereotypic behaviors.

Effects of three types of noncontingent auditory stimulation on vocal stereotypy in children with autism.

We evaluated the effects of 3 types of noncontingent auditory stimulation (music, white noise, recordings of vocal stereotypy) on 2 children with autism who engaged in high rates of vocal stereotypy. For both participants, the music condition was the most effective in decreasing vocal stereotypy to near-zero levels, resulted in the highest parent social validity ratings, and was selected as most preferred in treatment preference evaluations.

Electroacupuncture for children with autism spectrum disorder: pilot study of 2 cases.

OBJECTIVE: The objective of this study was to observe for efficacy, safety, and compliance of electroacupuncture for autism spectrum disorder (ASD). METHODS: Two (2) children with ASD received electroacupuncture for 24 sessions over 8 weeks and were assessed pre- and postacupuncture. We defined a positive or negative change as an improvement or deterioration of 25%, respectively, in total score or any subscales of Aberrant Behavioral Checklist (ABC), Ritvo-Freeman Real Life Scale (RFRLS), WeeFIM, and as a rating of much improved or much worse on the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: For ABC, positive changes in "Irritability" and "Stereotypy" was noted in case 1 but no changes occurred for case 2. For RFRLS, positive changes were found for both cases in "Sensory motor," "Sensory response," and "Total score," although negative change was noted for case 2 in "Affectual response." For WeeFIM, there were no positive or negative changes in both cases. For CGI-I, positive change in case 1 with much improved in "Social relatedness, Communication, and Stereotypy behavior" was reported. CONCLUSIONS: A short intensive course of electroacupuncture might improve some core features of children with ASD.