Attention deficit hyperactivity disorder (ADHD) is a frequent behavioral problem in young boys with fragile X syndrome (FXS), and its treatment is critical for improving social ability. The short-term efficacy of stimulant medications like methylphenidate (MPH) is well established in children with ADHD. FXS boys treated with MPH have improved attention span and socialization skills; however their mood becomes unstable at higher doses. Therefore, alternative pharmacological treatment of ADHD symptoms is desirable. A recent study showed that carnitine has a beneficial effect on the hyperactive-impulsive behavior in boys with ADHD without side effects. Our previous placebo-controlled trial indicated that L-acetylcarnitine (LAC) reduces hyperactivity in FXS boys. The objective of this study was to determine the efficacy of LAC in a larger sample of FXS boys with ADHD. The study design was randomized, double blind placebo controlled, parallel, and multicenter (with eight centers involved in Italy, France, and Spain). Sixty-three FXS males with ADHD (aged 6-13 years) were enrolled; 7 patients dropped out, 56 completed the one-year treatment, and 51 were included in the statistical analysis. Both groups improved their behavior, showing that psychosocial intervention has a significant therapeutic effect. However, we observed a stronger reduction of hyperactivity and improvement of social behavior in patients treated with LAC, compared with the placebo group, as determined by the Conners' Global Index Parents and the Vineland Adaptive Behavior Scale. Our results show that LAC (20-50 mg/kg/day) represents a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children. Copyright 2008 Wiley-Liss, Inc.

ETHNOPHARMACOLOGICAL RELEVANCE:Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.

AIM OF THE REVIEW:This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.

MATERIALS AND METHODS:All the information and data was collected on Ashwagandha using keywords"Ashwagandha"along with"Phytoconstituents","Ayurvedic, Unani and Homeopathy marketed formulation","Brain disorders","Mechanism"and"Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.

RESULTS:Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.

CONCLUSION:The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

OBJECTIVE:This study presents a case series of 157 children with developmental delay syndromes, including the conditions such as dyspraxia, dyslexia, attention-deficit hyperactivity disorder, and learning disabilities who received chiropractic care.

CLINICAL FEATURES:A consecutive sample of 157 children aged 6 to 13 years (86 boys and 71 girls) with difficulties in reading, learning, social interaction, and school performance who met these inclusion criteria were included.

INTERVENTION AND OUTCOMES:Each patient received a multimodal chiropractic treatment protocol, applied kinesiology chiropractic technique. The outcome measures were a series of 8 standardized psychometric tests given to the children by a certified speech therapist pre- and posttreatment, which evaluate 20 separate areas of cognitive function, including patient- or parent-reported improvements in school performance, social interaction, and sporting activities. Individual and group data showed that at the end of treatment, the 157 children showed improvements in the 8 psychometric tests and 20 areas of cognitive function compared with their values before treatment. Their ability to concentrate, maintain focus and attention, and control impulsivity and their performance at home and school improved.

CONCLUSIONS:This report suggests that a multimodal chiropractic method that assesses and treats motor dysfunction reduced symptoms and enhanced the cognitive performance in this group of children.

BACKGROUND: For children with attention deficit/hyperactivity disorder (ADHD), a reduction of inattention, impulsivity and hyperactivity by neurofeedback (NF) has been reported in several studies. But so far, unspecific training effects have not been adequately controlled for and/or studies do not provide sufficient statistical power. To overcome these methodological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite randomised controlled study using a computerised attention skills training as a control condition. METHODS: 102 children with ADHD, aged 8 to 12 years, participated in the study. Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each (randomised group assignment). The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training. Pre-training, intermediate and post-training assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents and teachers. Evaluation ('placebo') scales were applied to control for parental expectations and satisfaction with the treatment. RESULTS: For parent and teacher ratings, improvements in the NF group were superior to those of the control group. For the parent-rated FBB-HKS total score (primary outcome measure), the effect size was .60. Comparable effects were obtained for the two NF protocols (theta/beta training, SCP training). Parental attitude towards the treatment did not differ between NF and control group. CONCLUSIONS: Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD. Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD.

In a multicentre randomised controlled trial, we evaluated the clinical efficacy of neurofeedback (NF) training in children with ADHD and investigated the mechanisms underlying a successful training. We used an attention skills training, coupled with the training setting and demands made upon participants, as the control condition. At the behavioural level, NF was superior to the control group concerning core ADHD symptomatology as well as associated domains. For the primary outcome measure (improvement in the FBB-HKS total score), the effect size was .60. The same pattern of results was obtained at the 6-month follow-up. Thus, NF may be seen as a clinically effective module in the treatment of children with ADHD. At the neurophysiological level (EEG, ERPs), specific effects for the two NF protocols, theta/beta training, and training of slow cortical potentials were demonstrated. For example, for theta/beta training, a decrease of theta activity in the EEG was associated with a reduction of ADHD symptomatology. SCP training was accompanied inter alia by an increase in the contingent negative variation in the attention network test; thus, children were able to allocate more resources for preparation. EEG- and ERP-based predictors were also found. The present article reviewed the findings of the original papers related to the trial and outlines future research topics.

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD). Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results. This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.

BACKGROUND:Characterized with hyperactivity, inattention and impulsivity, attention-deficit/hyperactivity disorder (ADHD) has a prevalence in children, ranging from 2.6% to 11.4%. The medical approach is multimodal, with combination therapies of behavioral modification and pharmacotherapy. With growing concerns regarding the safety of both short-term and long-term use of psychotropic medications, the need for investigating alternative approaches to the care of children is warranted.

OBJECTIVE:The aim of this review was to describe the chiropractic care of children with medically diagnosed ADHD.

DESIGN:Retrospective case series were reviewed.

SETTING:The review was conducted in a private practice of chiropractic with a solo practitioner.

PATIENTS/PARTICIPANTS:Pediatric patients (aged

INTERVENTION:The intervention was chiropractic spinal manipulative therapy augmented by nutritional supplements.

RESULTS:Our review found four patient files satisfying the inclusion criteria. All patients were males, ranging in age from nine to 13 years (mean age, 10 years), with three patients having a history of medication use and two patients having prescribed medication at the start of chiropractic care. Using a 15-item parent/teacher ADHD questionnaire, the patients' responses to chiropractic care were monitored. Using the Friedman test to compare observations repeated on the same subjects, our findings found improvement in ADHD symptoms (ie, hyperactivity, impulsivity, and inattentiveness, as well as behavioral, social, or emotional difficulties) and provide supporting evidence on the effectiveness of chiropractic in the treatment of children with ADHD.

CONCLUSION:A retrospective case series of ADHD patients under chiropractic care is described. This provides supporting evidence on the benefits of chiropractic spinal manipulative therapy. We encourage further research in this area.