Sunday, June 21, 2015

Study: Positive Genetic Testing Increases Maternal Quality of Life

Obtaining a Genetic Diagnosis in a Child with Disability: Impact on Parental Quality of Life


  • Developmental delay;
  • intellectual disability;
  • array-based comparative genomic hybridization;
  • chromosomal microaberration;
  • quality of life


Recent progress in genetic testing has facilitated obtaining an etiologic diagnosis in children with developmental delay/intellectual disability (DD/ID) or multiple congenital anomalies (MCA) or both. Little is known about the benefits of diagnostic elucidation for affected families. We studied the impact of a genetic diagnosis on parental quality of life (QoL) using a validated semiquantitative questionnaire in families with a disabled child investigated by array CGH. We received completed questionnaires from 95 mothers and 76 fathers of 99 families. We used multivariate analysis for adjustment of potential confounders. Taken all 99 families together maternal QoL score (percentile rank scale 51.05) was significantly lower than fathers' QoL (61.83, p = 0.01). Maternal QoL score was 20.17 (95% CI [5.49; 34.82]) percentile rank scales higher in mothers of children with diagnostic (n = 34) array CGH as opposed to mothers of children with inconclusive (n = 65) array CGH (Hedges' g 0,71). Comparison of these QoL scores with retrospectively recalled QoL before array CGH revealed an increase of maternal QoL after diagnostic clarification. Our results indicate a benefit for maternal QoL if a genetic test, here array CGH, succeeds to clarify the etiologic diagnosis in a disabled child.

Friday, June 19, 2015

Cannabidiol and Pediatric Epilepsy: What is the Evidence?

 2013 Dec;29(3):574-7. doi: 10.1016/j.yebeh.2013.08.037.

Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.


Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child's seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use ofcannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child's seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures.
© 2013.


Cannabidiol; Dravet syndrome; Epilepsy; Intractable; Medically refractory seizures; Pediatric; Side effects; Treatment-resistant

Biologic Plausibility

Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In VivoS⃞

Can Braces Cure Sleep Apnea? What is the evidence?

What is the evidence? Orthodontic Treatment of PEDIATRIC  Sleep Apnea with Rapid Maxillary Expansion 

Probably yes. - JR

Clipboard: 6

Remove all items
 2011 May;15(2):179-84. doi: 10.1007/s11325-011-0505-1. Epub 2011 Mar 25.

Efficacy of rapid maxillary expansion in children with obstructive sleep apnea syndrome: 36 months of follow-up.



In view of the positive outcome of orthodontic treatment using rapid maxillary expansion (RME) on sleep-disordered breathing, we generated data on RME in children with obstructive sleep apnea (OSA) by evaluating objective and subjective data over a 36-month follow-up period, to determine whether RME is effective in the long-term treatment of OSA. We selected all patients with dental malocclusions and OSA syndrome (OSAS) confirmed by polysomnography.


Ten of the 14 children who completed the 12-month therapeutic trial using RME were enrolled in our follow-up study. The study was performed 24 months after the end of the RME orthodontic treatment. We enrolled all children presented with deep, retrusive or crossbite at the orthodontic evaluation. All subjects underwent an overnight polysomnography at the baseline, after 1 year of treatment and 24 months after the end of the orthodontic treatment. The children's mean age was 6.6 ± 2.1 years at entry and 9.7 ± 1.6 years at the end of follow-up.


After treatment, the apnea hypopnoea index (AHI) decreased and the clinical symptoms had resolved by the end of the treatment period. Twenty-four months after the end of the treatment, no significant changes in the AHI or in other variables were observed.


RME may be a useful approach in children with malocclusion and OSAS, as the effects of such treatment were found to persist 24 months after the end of treatment.
[PubMed - indexed for MEDLINE]
Icon for Springer
 2011 May;15(2):173-7. doi: 10.1007/s11325-010-0419-3. Epub 2010 Sep 17.

Adeno-tonsillectomy and rapid maxillary distraction in pre-pubertal children, a pilot study.



When both narrow maxilla and moderately enlarged tonsils are present in children with obstructive sleep apnea, the decision of which treatment to do first is unclear. A preliminary randomized study was done to perform a power analysis and determine the number of subjects necessary to have an appropriate response. Thirty-one children, 14 boys, diagnosed with OSA based on clinical symptoms and polysomnography (PSG) findings had presence of both narrow maxillary complex and enlarged tonsils. They were scheduled to have both adeno-tonsillectomy and RME for which the order of treatment was randomized: group 1 received surgery followed by orthodontics, while group 2 received orthodontics followed by surgery. Each child was seen by an ENT, an orthodontist, and a sleep medicine specialist. The validated pediatric sleep questionnaire and PSG were done at entry and after each treatment phase at time of PSG. Statistical analyses were ANOVA repeated measures and t tests.


The mean age of the children at entry was 6.5 ± 0.2 years (mean ± SEM). Overall, even if children presented improvement of both clinical symptoms and PSG findings, none of the children presented normal results after treatment 1, at the exception of one case. There was no significant difference in the amount of improvement noted independently of the first treatment approach. Thirty children underwent treatment 2, with an overall significant improvement shown for PSG findings compared to baseline and compared to treatment 1, without any group differences.


This preliminary study emphasizes the need to have more than subjective clinical scales for determination of sequence of treatments.
[PubMed - indexed for MEDLINE]
Icon for Springer
 2009 Apr;10(4):471-8. doi: 10.1016/j.sleep.2008.04.003. Epub 2008 Aug 26.

NREM sleep instability changes following rapid maxillary expansion in children with obstructive apnea sleep syndrome.



To evaluate NREM sleep microstructure in children with obstructive sleep apnea syndrome (OSAS) before and after one year of rapid maxillary expander (RME) treatment by means of the cyclic alternating pattern (CAP).


Nine children with OSAS aged 4-8 years (6 males, mean age 6.4+/-1.97 years) and age-matched normal controls were included. All subjects underwent an overnight polysomnography in the sleep laboratory after one adaptation night, as a baseline evaluation; children with OSAS were recorded again after one year of RME treatment.


After one year of treatment the OSAS group showed a longer duration of time in bed and sleep period time, a reduction in number of stage shifts compared to baseline recordings, and the apnea-hypopnea index decreased significantly. At baseline, the OSAS group had a higher CAP rate during slow-wave sleep and an increased A2 index compared to normal controls. After one year of RME application, children with OSAS showed an increase in CAP rate associated with an increase of A1 index during slow-wave sleep.


RME treatment almost normalized sleep architecture and improved sleep respiratory disturbances; however, sleep microstructure and respiratory parameters did not completely recover. The persistence of increased CAP rate in slow-wave sleep associated with an increase of A1 index might reflect a partial failure of orthodontic treatment. On the other hand, the rebound of A1 subtypes might be an indirect sign of an attempt to normalize sleep that has been disturbed by the respiratory events.
[PubMed - indexed for MEDLINE]
Icon for Elsevier Science
 2008 Jul;31(7):953-7.

Orthodontic expansion treatment and adenotonsillectomy in the treatment of obstructive sleep apnea in prepubertal children.

Erratum in

  • Sleep. 2009 Jan 1;32(1):table of contents.



Rapid maxillary expansion and adenotonsillectomy are proven treatments of obstructive sleep apnea (OSA) in children. Our goal was to investigate whether rapid maxillary expansion should be offered as an alternative to surgery in select patients. In addition, if both therapies are required, the order in which to perform these interventions needs to be determined.


Prepubertal children with moderate OSA clinically judged to require both adenotonsillectomy and orthodontic treatment were randomized into 2 treatment groups. Group 1 underwent adenotonsillectomy followed by orthodontic expansion. Group 2 underwent therapies in the reverse sequence.


Thirty-two children (16 girls) in an academic sleep clinic.


Clinical evaluation and polysomnography were performed after each stage to assess efficacy of each treatment modality.


The 2 groups were similar in age, symptoms, apnea-hypopnea index, and lowest oxygen saturation. Two children with orthodontic treatment first did not require subsequent adenotonsillectomy. Thirty children underwent both treatments. Two of them were still symptomatic and presented with abnormal polysomogram results following both therapies. In the remaining 28 children, all results were significantly different from those at entry (P = 0.001) and from single therapy (P = 0.01), regardless of the order of treatment. Both therapies were necessary to obtain complete resolution of OSA.


In our study, 87.5% of the children with sleep-disordered breathing had both treatments. In terms of treatment order, 2 of 16 children underwent orthodontic treatment alone, whereas no children underwent surgery alone to resolve OSA. Two children who underwent both treatments continued to have OSA.
[PubMed - indexed for MEDLINE] 
Free PMC Article
Icon for PubMed Central
 2008 Dec;122(12):1318-24. doi: 10.1017/S002221510800279X. Epub 2008 Jun 25.

Down syndrome: otolaryngological effects of rapid maxillary expansion.



Phenotypical Down syndrome includes pharyngeal and maxillary hypoplasia and, frequently, constricted maxillary arch with nasal obstruction.


This clinical trial assessed the effects of rapid maxillary expansion on ENT disorders in 24 children with Down syndrome randomly allocated to receive either rapid maxillary expansion or not. Each group received ENT and speech therapy assessments before expansion and after the device had been removed.


In the rapid maxillary expansion group, the yearly ENT infection rate was reduced when assessed after device removal (p < 0.01). The parents of rapid maxillary expansion children reported a reduction in respiratory obstruction symptoms. Audiological assessment revealed improvements in the rapid maxillary expansion group (p < 0.01). Cephalometry showed increased maxillary width in the rapid maxillary expansion group.


Rapid maxillary expansion resulted in a reduction in hearing loss, yearly rate of ENT infections and parentally assessed symptoms of upper airway obstruction, compared with no treatment. These findings are probably related to expanded oronasal space, due to rapid maxillary expansion.
[PubMed - indexed for MEDLINE]
Icon for Cambridge University Press
 1998 Dec 15;21(8):831-5.

Treatment of obstructive sleep apnea syndrome by rapid maxillary expansion.


The precise role of maxillary constriction in the pathophysiology of obstructive sleep apnea (OSA) is unclear. However, it is known that subjects with maxillary constriction have increased nasal resistance and resultant mouth-breathing, features typically seen in OSA patients. Maxillary constriction is also associated with alterations in tongue posture which could result in retroglossal airway narrowing, another feature of OSA. Rapid maxillary expansion (RME) is an orthodontic treatment for maxillary constriction which increases the width of the maxilla and reduces nasal resistance. The aim of this pilot study was to investigate the effect of rapid maxillary expansion in OSA. We studied 10 young adults (8 male, 2 female, mean age 27 +/- 2 [sem] years) with mild to moderate OSA (apnea/hypopnea index-AHI 19 +/- 4 and minimum SaO2 89 +/- 1%), and evidence of maxillary constriction on orthodontic evaluation. All patients underwent treatment with RME, six cases requiring elective surgical assistance. Polysomnography was repeated at the completion of treatment. Nine of the 10 patients reported improvements in snoring and hypersomnolence. There was a significant reduction in AHI (19 +/- 4 vs 7 +/- 4, p < 0.05) in the entire group. In seven patients, the AHI returned to normal (i.e., = < 5); only one patient showed no improvement. These preliminary data suggest that RME may be a useful treatment alternative for selected patients with OSA.
[PubMed - indexed for MEDLINE]

Thursday, June 11, 2015

More than 13% of boys in America have ADHD

This article claims that over 13% of American boys have ADHD.

A total of 9.5% of children aged 4-17 in the US have at some point been diagnosed with ADHD, according to statistics from the US Centers for Disease Control. While prevalence statistics often rely on the administration of mental health screening tests, the latest statistics reflect actual diagnoses given to the children by physicians or mental health care providers. The CDC also identified significant trends based on gender and income levels.
The latest statistics came from the National Health Interview Survey of the National Center for Health Statistics. Between 2011-13, information was collected for 29,968 children aged 4–17. Respondents were asked, “Has a doctor or health professional ever told you that [sample child] had attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD)?”
There were differences based on age, gender and income.
"For those aged 4–5, prevalence was 2.7%, 9.5% for those aged 6–11, and 11.8% for those aged 12–17," stated a CDC data brief. "13.3% of boys and 5.6% of girls aged 4–17 had ever been diagnosed with ADHD."
The ADHD rates were highest among children with public insurance at 11.7%, and lowest among uninsured children at 5.7%. Among children with private insurance, the rate was 8.6%.
Of families with incomes below 200% of the federal poverty threshold, 10.4% of children had been diagnosed with ADHD, compared with 8.8% of children in families with incomes at or above 200% of the poverty threshold.
Read more here

Nerve cells discovered that act like a speedometer

Scientists have identified nerve cells in mice's brains that provide information like a speedometer. It is thought that these cells also exist in humans, and their existence may have implications for Parkinson's disease.

Scientists at the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn led by Prof. Stefan Remy report on this in the journal Neuron. Their investigations give new insights into the workings of spatial memory. Furthermore, they could also help improve our understanding of movement related symptoms associated with Parkinson's disease.
In a familiar environment our movements are purposeful. For example, if we leave our office desk for a coffee break, we naturally follow a predefined route that has been stored in our memory: Through the office door, left into the hall, past the windows. To keep us on track, our brain has to process varying sensory impressions quickly. "This is a fundamental issue our brain has to deal with. Not just on our way to the coffee machine, but any time we move in space. For example when we are on a bike or in a car," explains Remy. With increasing speed, the data rate also increases, he emphasizes: "The faster we move, the less time the brain has to take in environmental cues and to associate them with a location on our memorized spatial map. Our perception therefore has to keep pace with the speed of movement so that we remember the right way to go. Otherwise we end up at the copy machine instead of the coffee machine."
Rhythmic fluctuations
It has been known for some time that the hippocampus -- the part of the brain that controls memory, particularly spatial memory -- adjusts to the speed of locomotion. "The electrical activity of the hippocampus undergoes rhythmic fluctuations. The faster we move, the faster certain nerve cells are activated," says Remy. "This increased activation rate sensitizes the brain. It becomes more receptive to the changing sensory impressions that have to be processed when moving."
But how does the brain actually know how fast a movement is? Previously there was no answer to this question. Now, Remy and his colleagues have decoded the mechanism. For this, they stimulated specific areas within the mouse brain and recorded the ensuing brain activity and the mice's locomotion. "We have identified the neural circuits in mice that link their spatial memory to the speed of their movement. This interplay is an important foundation for a functioning spatial memory," says Remy. "We assume that humans have similar nerve cells, as the brains of mice and humans have a very similar structure in these regions."
Small cell group
The cells in question are located in the "medial septum," a part of the brain directly connected to the hippocampus. They make up a relatively small group comprising a few thousand cells. "They gather information from sensory and locomotor systems, determine the speed of movement and transmit this information to the hippocampus. In this way, they tune the spatial memory systems for optimized processing of sensory stimuli during locomotion," explains Remy. However, these circuits have even more functions. "We have found that they also give the start signal for locomotion and that they actively control its speed. Until now, this control function was almost exclusively ascribed to the motor cerebral cortex."
These newly discovered nerve cells are linked with areas of the brain that are affected by Parkinson's in humans. This disease is associated with movement-related symptoms and can cause dementia. "In this respect, our results go beyond the workings of spatial memory; they also have the potential to provide new insights into how memory systems and the execution of movements are affected in Parkinson's disease," says Remy.
Read more here

In autistic children, poor sleep linked to impaired intelligence

A study indicates that poor sleep is linked to impaired intelligence in autistic children.

For children with autism, there are differences in brain activity during sleep in comparison with typically developing children, say Canadian researchers, whose findings underline the relationship between sleep quality and cognitive performance in all children and adolescents.
The researchers found that stage 2 sleep spindles, which are important for taking sleep into deeper phases and have been linked to learning potential, are shorter and of lesser frequency among autistic children, even when these children do not have overt sleep problems.
The investigators believe that the results, which showed a differential effect on subsequent performance on IQ tests, could result from differences in cortical organization and information processing in children affected by the condition.
"This is an important discovery that confirms the major role of sleep in consolidating cognitive abilities," said Roger Godbout, PhD, director of the Sleep Research Laboratory at the Hôpital Rivière-des-Prairies, who is also a professor at Université de Montréal, Canada, in a release.
"This study establishes beyond a doubt that children and adolescents are particularly affected by a lack of sleep, especially because they are in an important developmental period. This is also an important finding given that 10% to 25% of Canadian children and adolescents — and 45% to 85% of autistic children — have sleep problems."
The research was published in the July issue of the International Journal of Psychophysiology.
New Insight
The researchers studied 13 typically developing and 13 high-functioning autistic children who did not complain of poor sleep. They slept two consecutive nights in a sleep laboratory. Non–rapid eye movement sleep, sleep spindles, and sigma activity were measured using electroencephalography (EEG).
Stage 2 sleep spindles were identified visually on C3, C4 (central), and Fp1, Fp2 (frontal) leads. They were defined as bursts of EEG activity at 12-16 Hz lasting 0.5-2.0 seconds. Sigma activity was also recorded on the C3, C4, Fp1, and Fp2 EEG leads during stage 2 sleep, with total sigma (12-15.75 Hz), slow sigma (12-13 Hz), and fast sigma (13.25-15.75 Hz) frequencies determined.
The children also completed the French–Canadian version of the Wechsler Intelligence Scale for Children–IV test on the morning after each of the sleep recording nights.
Although autistic and typically developing children spent the same length of time in stage 2 sleep, for the autistic children, sleep spindle density was significantly lower and sleep spindles were of shorter duration at the Fp1 electrode for both the total and second quarter of the night (< .05 for all).
In the last 2 hours of the night, fast sigma EEG activity was significantly lower at the C3 and C4 electrode in autistic than in typically developing children (< .05 for both).
There was a negative correlation between verbal IQ and sleep spindle density at the Fp2 electrode in typically developing children. In contrast, there was a negative correlation between verbal and full-scale IQ scores with C3 sleep spindle density in autistic children.
The duration of sleep spindles at C4 was positively correlated with verbal IQ, but only in typically developing children. There was a positive correlation between performance IQ and fast sigma activity at C4 during the latter part of the night, again only in typically developing children.
Lead author Sophie Tessier, a student in the Sleep Laboratory and Clinic, Hôpital Rivière-des-Prairies, in Montreal, said that it was important that they studied children without sleep difficulties.
She explained that differences in the density and duration of sleep spindles suggest that autistic children have differences in cortical functioning, even when their sleep appears to be unaffected.
The findings also raise questions about the nature of autism.
"Our aim is really to understand what autism is and what its consequences are," Tessier said. "We are still wondering about the etiology and what it affects, and so we're still understanding how the brain network is connected and how it works."
She said that it is clear that the learning and cognitive processing are different between autistic and unaffected children during the day, and now it is known that their sleep patterns are "completely different."
"We also see that sleep doesn't support cognition, and the resources for learning are not available in the same way, so we are trying to understand what is autism and where it has find the target of intervention eventually," Tessier told Medscape Medical News.
A Good First Step
Commenting on the findings for Medscape Medical News, Shalini Paruthi, MD, fellow of the American Academy of Sleep Medicine and director of the Pediatric Sleep and Research Center at SSM Cardinal Glennon Children's Medical Center, in St. Louis, Missouri, said that the study was a "very interesting" descriptive study.
Although noting that the children included in the study were not typical of the autistic population, in whom sleep problems are extremely common, she added: "I think it's definitely a good first start at trying to understand their EEG sleep patterns and see if that correlates with their cognitive processing."
Dr Paruthi would like to see the study repeated in a larger group of children.
"Once you have a larger sample size, you can really see if those differences are becoming significant and something that can distinguish the typically developing normal children vs those children who have autism," she told Medscape Medical News.
She explained that it will also be important to look at different groups of children with autism, including those who are low functioning, and determine how EEG differences relate to daytime functioning.
If the impact of sleep is replicated in further studies, Dr Paruthi believes that it may help identify which specific types of services a child would benefit from to improve their functioning at a faster rate.
"The best outcome that we can hope for by doing any kind of research in kids who do have autism is how closely can we get them to learn how to communicate better, communicate more effectively, and communicate more frequently, and how we get them to really function in life.
"I think it's really important that we continue to do research on children who have autism. Everything takes time, so starting with small groups, starting with the kids who are more high functioning...I think that is totally an appropriate step, because we know that so many children are diagnosed with autism," she said.
Read more here