Autism? Developmental Delay? Epilepsy? When to use Exome Sequencing - Now Official AAN Policy

Emerging in my practice in 2013, exome has now become an everyday child neurology practice tool like MRI.  - JR

Clinical Exome sequencing in neurologic disease

1. Brent L. Fogel, MD, PhD, 
2. Saty Satya-Murti, MD and 
3. Bruce H. Cohen, MD

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1. Correspondence to:
   bfogel@ucla.edu

1. Published online before print March 21, 2016doi:http:/​/​dx.​doi.​org/​10.​1212/​CPJ.​0000000000000239Neurol Clin Pract April 2016 vol. 6 no. 2 164-176

 

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ABSTRACT

Purpose of review: The landscape of genetic diagnostic testing has changed dramatically with the introduction of next-generation clinical exome sequencing (CES), which provides an unbiased analysis of all protein-coding sequences in the roughly 21,000 genes in the human genome. Use of this testing, however, is currently limited in clinical neurologic practice by the lack of a framework for appropriate use and payer coverage.

Recent findings: CES can be cost-effective due to its high diagnostic yield in comparison to other genetic tests in current use and should be utilized as a routine diagnostic test in patients with heterogeneous neurologic phenotypes facing a broad genetic differential diagnosis. CES can eliminate the need for escalating sequences of conventional neurodiagnostic tests.

Summary: This review discusses the role of clinical exome sequencing in neurologic disease, including its benefits to patients, limitations, appropriate use, and billing. We also provide a reference template policy for payer use when considering testing requests.

Clinical exome sequencing (CES) is a new state-of-the-art molecular diagnostic genetic test. It has the potential to rapidly and efficiently detect disease-causing genetic mutations within any gene in the human genome and is therefore becoming widely used in clinical practice. This template policy addresses the health benefits, limitations, and appropriate use of this type of testing in patients with neurologic disease.

Can Parkinsonian Symptoms Be Brought On by Traumatic Brain Injury?

TBI linked to Parkinson’s and Parkinson-related brain defects

Researchers at the Group Health Research Institute relates research to Muhammad Ali—and how we can prevent late-life injuries and falls for our families and ourselves.-JR

by Eric B. Larson, MD, MPH, executive director of Group Health Research Institute and vice president for research at Group Health

Traumatic brain injury (TBI), including concussion, is a big problem in older adulthood, the stage of life when accidents—especially falls—happen most often. Yet we hear a lot about TBI from sports, particularly football head injuries in younger people.

Muhammad Ali, who recently died, had a symptom complex called Parkinsonism. It’s very likely that multiple blows to the head from boxing set the stage for this condition. A new study that I helped to lead confirms concern over effects of TBI that threaten the structure and function of brain cells.

Here’s what we found—and didn’t find

With colleagues from the University of Washington (UW), Mt. Sinai School of Medicine, Cleveland Clinic, Rush University Medical Center, and the University of Utah, Paul Crane, MD, MPH, and I recently published “Association between Traumatic Brain Injury and Late Life Neurodegenerative Conditions and Neuropathological Findings" in JAMA Neurology. Dr. Crane is a professor of general internal medicine at the UW School of Medicine, an adjunct professor of health services at the UW School of Public Health, and an affiliate investigator at Group Health Research Institute (GHRI).

How to prevent falls

On a practical level, though, this research should remind us of just how important it is to prevent falls and other accidents. Here’s how you can prevent falls:

• Get regular exercise for general conditioning, strength, and balance training. 
• Avoid drugs that impair balance and judgment, such as narcotics, anticholinergics, and tranquilizers, and avoid over-treating high blood pressure and diabetes.
• Eliminate hazards in your environment—like inadequate lighting, rugs and cords that can cause tripping.
• Wear shoes or slippers with good soles that are not too thick. The ACT study has shown that older people are much more likely to fall in the home if they walk barefoot or in stocking feet.  
• At some point, consider using a cane or walker to avoid falls.

FULL ARTICLE HERE:

Helping Our School-Age Children Sleep Better when 23% have sleep problems!

Revisiting the importance of  healthy sleep habits in school-age children.
Common sleep problems and some strategies for resolving them... -JR

Helping Our School-Age Children Sleep Better
By Peri Klass, M.D.

"Everyone knows that getting a baby to sleep through the night can be a big challenge for parents. But sleep problems are common among preschool and school-age children, too. As we ask children to function in school, academically and socially, fatigue can affect their achievement and behavior.

Australian research on sleep problems in children has included work aimed at the “school transition” year in which children adjust to a school schedule. In a study of 4,460 children, 22.6 percent had sleep problems, according to their parents, at that transition age of 6 to 7 years. “We were surprised, we thought it was all baby sleep” that was the problem, said Dr. Harriet Hiscock, a pediatrician who is a senior research fellow at the Murdoch Childrens Research Institute at the Royal Children’s Hospital in Melbourne who was one of the authors of the study.

The most common sleep issues for children around the age of school entry, Dr. Hiscock said, definitely include limit-setting issues — that is, some of them need their parents to make the rules and routines clear. But there are also children with what sleep specialists call “sleep onset association disorder,” in which a child has become habituated to falling asleep only in a certain context, requiring the presence of a parent, or needing to have the TV on, to cite two common examples. Very anxious children are also often problem sleepers. And then there are children beset by nightmares, night terrors and early morning waking.

Many parts of the brain work less well when children are tired. “The prefrontal cortex is very sensitive to sleep deprivation, and it is key to the brain mechanisms which underlie executive function and some of the attention  processes,” she said. “The amygdala is affected by sleep deprivation and is essential for emotional processes.”"

FULL ARTICLE HERE:

Are Pregnant Women Suffering From a Form of Sleep Apnea?

Israeli-US research: Pregnant women may suffer from sleep apnea

New research suggests that pregnant women may commonly suffer from gestational sleep apnea.

Researchers say that further investigation will determine therapy and criteria for the condition. - JR

Overweight adults aren’t the only ones to suffer from potentially dangerous obstructive sleep apnea (OSA); about a quarter of pregnant women have the condition, according to sleep-medicine researchers in Jerusalem and St. Louis.

Just as pregnant women may be at risk for gestational diabetes and gestational hypertension that develop while carrying their fetuses, they may also develop gestational OSA, in which one stops breathing for several seconds during sleep, the researchers said. The obese most commonly suffer from OSA, putting them at higher risk for high blood pressure, heart disease and type 2 diabetes.

Now, in an editorial in the International Journal of Obstetric Anesthesia, sleep researchers from Israel and the US recommend a new diagnosis, “Gestational Sleep Apnea” (GSA). This would allow health professionals to properly describe, diagnose and treat OSA in pregnant women.

FULL ARTICLE HERE:

“Currently there is a lack of uniform criteria to diagnose, treat and classify OSA in the pregnant population, which in turn complicates efforts to determine the risk factors for, and complications of, gestational sleep apnea,” said Prof. Yehuda Ginosar, director of the mother and child anesthesia unit at Hadassah-University Medical Center in Jerusalem’s Ein Kerem who is on the faculty of the Hebrew University’s Faculty of Medicine.

Does early botox in the arm have LONG LASTING effects on the brain and motor learning? Maybe.

Was injecting botox today (under sedation) to kids so its on my mind.....

In the 13 years of practice, I have observed  motor learning and even language to rapidly  improve if I treat spasticity early. Other illnesses show that cortical reorganization changes with improved use of a limb.  I recognize that it takes a team, yet  I was not surprised to see kids "take off".  JR

Dev Neurorehabil. 2015 Jun;18(3):145-8. doi: 10.3109/17518423.2013.796018. Epub 2013 Jul 19.

Quantification of long-term effects of botulinum injection in a case of cerebral palsy affecting the upper limb movement.

Molteni E1, Rigoldi C, Morante M, Rozbaczylo C, Haro M, Albertini G, Galli M, Bianchi AM.

Author information

Abstract

OBJECTIVE:

The aim of this work was to put into evidence the long-lasting modification induced by botulinum toxin injection and rehabilitative treatment on motor control.

METHODS:

In this contribution, we report the case of a female child showing hemiplegia, due to cerebral palsy. She underwent botulinum injection, followed by physical and occupational therapy. We quantified the biomechanical, cerebral and occupational aspects of her impaired upper limb, also dynamically, with respect to her pre- and post-treatment condition.

RESULTS:

Small long-lasting improvements--induced on biomechanics by botulinum injection--triggered wide cerebral modification, well reflected in improved contextual movements and motor strategy.

CONCLUSION:

These results provide evidences that small modifications in the end-effector performance often imply cerebral modifications and improvement in finalized motor strategy.

KEYWORDS:

Botulinum injection; EEG analysis; cerebral palsy; movement analysis; upper limb

Doctor, can botox be used for excess sweating in teens.. Read on...

Sometimes I'm asked to help. Frankly, I am not sure why more do not ask me in Texas .... JR

Summary:

80-93% have a 75% plus response that lasts 4-6 months.
5.6% with mild/moderate adverse response

JR

A Prospective, Nonrandomized, Open-Label Study of the Efficacy and Safety of OnabotulinumtoxinA in Adolescents with Primary Axillary Hyperhidrosis.

Glaser DA1, Pariser DM2,3, Hebert AA4, Landells I5, Somogyi C6, Weng E6, Brin MF6,7, Beddingfield F6,8.

Author information

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of onabotulinumtoxinA in adolescents with primary axillary hyperhidrosis.

METHODS:

This 52-week, multicenter, nonrandomized, open-label study was conducted in 141 adolescents ages 12 to 17 years with severe primary axillary hyperhidrosis. Patients could receive up to six treatments with onabotulinumtoxinA (50 U per axilla), with re-treatment occurring no sooner than 8 weeks after the prior treatment cycle and no later than 44 weeks after the initial treatment cycle. The primary efficacy measure was treatment response, based on self-assessed hyperhidrosis severity following the first two treatments using the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Other efficacy measures included spontaneous resting sweat production and health outcomes.

RESULTS:

Fifty-six (38.9%) participants underwent one treatment, 59 (41.0%) underwent two, 20 (13.9%) underwent three, 6 (4.2%) underwent four, and 3 (2.1%) underwent five. OnabotulinumtoxinA significantly improved HDSS scores and decreased sweat production compared with treatment cycle baselines. Seventy-nine patients (54.9%) responded to treatment based on HDSS criteria. From 56.6% to 72.3% of patients experienced a two-grade or more improvement at 4 and 8 weeks after each of the first two treatments. The majority (79.4%-93.2%) had a 75% or greater reduction in sweat production at week 4 (treatments 1-3). The median duration of effect for responders ranged from 134 to 152 days. Using quality of life measures, health outcomes improved markedly. Eight patients (5.6%) had mild or moderate treatment-related adverse events. No unexpected safety signals were observed in this study. Neutralizing antibodies to onabotulinumtoxinA did not develop.

CONCLUSION:

OnabotulinumtoxinA injections provided beneficial effects in adolescents with primary axillary hyperhidrosis.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00168415.

© 2015 The Authors. Pediatric Dermatology Published by Wiley Periodicals, Inc.

PMID:

 

26059781

 

PMCID:

 

PMC4744704

 

DOI:

 

10.1111/pde.12620

Botox for headaches in children, teen and adults? 82% returned in year-2!

Common questions for me include response rate to botox and how much might it help?

A very useful article about the use of botox for migraine. 

Response rate was 82% in year-one!

In responders, consumption of medication reduced by 53%, er visits reduced 61%.

Adverse events were uncommon (14%) and transient

JR

Cephalalgia. 2015 Sep;35(10):864-8. doi: 10.1177/0333102414561873. Epub 2014 Nov 27.

Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: What happens after one year?

Cernuda-Morollón E1, Ramón C1, Larrosa D1, Alvarez R1, Riesco N1, Pascual J2.

Author information

Abstract

BACKGROUND:

OnabotulinumtoxinA (onabotA) has shown its efficacy over placebo in chronic migraine (CM), but clinical trials lasted only up to one year.

OBJECTIVE:

The objective of this article is to analyse our experience with onabotA treatment of CM, paying special attention to what happens after one year.

PATIENTS AND METHODS:

We reviewed the charts of patients with CM on onabotA. Patients were injected quarterly during the first year but the fifth appointment was delayed to the fourth month to explore the need for further injections.

RESULTS:

We treated 132 CM patients (mean age 47 years; 119 women). A total of 108 (81.8%) showed response during the first year. Adverse events, always transient and mild-moderate, were seen in 19 (14.4%) patients during the first year; two showed frontotemporal muscle atrophy after being treated for more than five years. The mean number of treatments was 7.7 (limits 2-29). Among those 108 patients with treatment longer than one year, 49 (45.4%) worsened prior to the next treatment, which obliged us to return to quarterly injections and injections were stopped in 14: in 10 (9.3%) due to a lack of response and in four due to the disappearance of attacks. In responders, after an average of two years of treatment, consumption of any acute medication was reduced by 53% (62.5% in triptan overusers) and emergency visits decreased 61%.

CONCLUSIONS:

Our results confirm the long-term response to onabotA in three-quarters of CM patients. After one year, lack of response occurs in about one out of 10 patients and injections can be delayed, but not stopped, to four months in around 40% of patients. Except for local muscle atrophy in two cases treated more than five years, adverse events are comparable to those already described in short-term clinical trials.

© International Headache Society 2014.

KEYWORDS:

Chronic migraine; onabotulinumtoxinA

PMID:

 

25431141

 

DOI:

 

10.1177/0333102414561873

Gratified to be Named a Top Pediatric Neurology Doc for Houston 2016 .

Always nice to  be recognized for my work. Thanks to all. JR

Top Doc 2016  - Pediatric Neurology Epilepsy Sleep Medicine

http://www.houstoniamag.com/doctors/joshua-simon-rotenberg

How to Keep The Kids Busy In the Dog Days Of Summer

Kids stuck at home this summer? Here's how to keep them busy

Dr Arif Khan, consultant pediatric neurologist and epileptologist, describes healthy and effective ways to keep your children busy this summer without excessive use of technology. -JR

Here are some tips to physically and mentally engage your children this summer while keeping a balance between entertainment and creative engagement:

1.) Structure the day or week with activities: Create a schedule each day so your child knows what to expect. For example, 9 to 10am: Bike riding or dog walk to the park. This type of structure works particularly well with children who have a lot of energy.  By creating plenty of activities in advance, you will reduce distractions, impulses, boredom, and ultimately depression and accidents.

2.) Encourage children to keep track of their activity: For children who spend several hours in front of a computer or TV screen, activity trackers might be the motivator they need to get moving. Activity trackers such as iBitz or the TupeloLife offer an 8-week after school programme where children can track of their steps and learn about the importance of being active every day.

3.) Keep children active and take advantage of summer camps: With so many different summer camps available for children during the school holidays, enrolling your child in a camp based on their preference, skills and interest is an option that can be very rewarding. Summer camps can help children build self-confidence and self-esteem by removing the kind of academic, athletic and social competition that shapes their lives in school. You can choose a camp that's focused on a sport or a special interest one that covers a broad spectrum of activities, including arts and crafts, social aspects and team games, encouraging children to socialize.

4.) Exercise their minds and get involved: Introducing children to creative activities that they might not necessarily have the time to do during the school year can be equally rewarding. From reading to cooking, here are some activities that can be explored by children and parents:
- Engage in Kitchen fun
- Set up free play games
- Organize family activity days
- Set a Bedtime

Read Full Article Here:

Ever Wonder What Drives Hardcore Sports Fandom?

Interesting neurological perspective to remember when you can't understand why your friend or loved one is yelling at the TV during the Olympics....and....

Go Team Canada!-JR

The Unique Neurology of the Sports Fan’s Brain

Brian J. Barth

"Sports fans aren’t typically in the mood for academic research in the minutes before a big game. But Paul Bernhardt, an aspiring young behavioral scientist at Georgia State University, was determined. Armed with a bag of sterile vials, Bernhardt inched through the crowd at Atlanta’s Omni arena, politely asking anyone decked out in either University of Georgia or Georgia Tech basketball garb—the teams that were set to battle that evening—for a bit of saliva.

The year was 1991. Fans of the Bulldogs and the Yellow Jackets, the state’s two most renowned collegiate sports institutions, had been hating each other’s guts since 1893, a rivalry affectionately known as COFH: Clean, Old-Fashioned Hate. (Yes, sports rivalries can have names; COFH is historically significant enough to have a 5,000-plus word entry in Wikipedia with 50 citations.) Bernhardt wasn’t there to celebrate a century of feuding, however; he was hoping to break new ground on the scientific understanding of such fandemonium—“highly identified” fans would be the proper psychology term—to explain why being a sports nut, bitter hatred and all, feels soooo gooooood.

The fact that athletes experience a tidal rush of testosterone, a hormone associated not just with male sexuality but with self-esteem, upon winning a big game was well established. But there was a hypothesis floating around among social psychologists at the time that fans ride a similar hormonal high. Bernhardt just needed a little spit, which offers a reliable approximation of the body’s biochemistry at any given moment, to find out."

FULL ARTICLE HERE:

Give your dog a belly rub to activate the caudate, but some dogs just prefer the food.

The caudate is activated.

OK. I love dogs...Awkward to start doing this in schools, though.,  :-)  JR

Dogs would rather get a belly rub than a treat

When training dogs, a pat on the head may be more effective than a treat. A new study suggests that most dogs respond more positively to praise than to food. Researchers scanned (pictured) the brains of 15 dogs of various breeds while presenting objects paired with rewards. 

For example, after the scientists showed the canines a toy car, their owners would praise them. In other tests, the researchers gave the dogs a toy horse and a piece of hot dog. The scans revealed that when praised, 13 of the dogs showed equal or greater levels of brain activity in the region that controls decision-making and signals rewards than when they received food, the scientists will report in an upcoming issue of Social Cognitive and Affective Neuroscience. 

In a follow-up test, the team set up a Y-shaped maze with the dogs’ owners on one side and a bowl of treats on the other. Although most of the canines preferred to go the direction of their owner for a belly rub, the dogs that showed a greater reaction to food in the scanner consistently chose food in the maze

Therapy jobs with close human contact might better suit dogs that have a higher preference for praise, whereas dogs that don’t could succeed in more independent roles like search and rescue, where receiving a treat after a job well done would keep them motivated. At the very least, the study supports how important social interaction is to dogs—and provides a healthier alternative to treats, too. 

The Importance of Nutrition During Pregnancy for Brain Development

The Lifelong Importance of Nutrition in Pregnancy for Brain Development

Susanne D. Rooij

How drastic is the effect of nutrition during pregnancy on infant brain development? -JR

The importance of a healthy diet for proper functioning of the brain is increasingly being recognized. Week in, week out studies appear recommending a high intake of certain foods in order to achieve optimal brain function and prevent brain diseases. Although it is definitely no punishment for the most of us to increase our chocolate consumption to boost brain function, the most important period during which nutrition affects our brain may already be behind us.

Nutrition affects the brain throughout life, but it is potentially most important during the critical prenatal period, during which the lion’s share of our brain development takes place. During the time we spend in the womb, our brains undergo dramatic changes. The fetal nervous system from which the brain and spinal cord progress is one of the first systems to develop. Its foundations are laid down during the very first days of pregnancy. At the end of pregnancy, the brain has grown exponentially and is capable of learning and forming memories. It is actually not very hard to imagine that to lay a good foundation for the brain it is of utmost importance to receive the best building blocks through proper nutrition of the mother.

A very dramatic illustration of the consequences of not receiving adequate nutrition was shown in a study from the seventies in which Zena Stein and colleagues investigated the effects of prenatal exposure to the Dutch famine on the development of babies. The Dutch ‘Hungerwinter’ was a period of severe famine that struck the Western part of the Netherlands at the end of World War II. There was so little food available that even pregnant women suffered from severe undernutrition. Stein and her colleagues found that babies that had been exposed to the famine during the first trimester of pregnancy had increased rates of birth defects of the central nervous system.

FULL ARTICLE HERE:

Why being bilingual works wonders for your brain

Gaia Vince

Cartoon depiction of the Tower of Babel

Interesting article discussing bilingualism and why you should pick up a language or two more than you already know. -JR

In a cafe in south London, two construction workers are engaged in cheerful banter, tossing words back and forth. Their cutlery dances during more emphatic gesticulations and they occasionally break off into loud guffaws. They are discussing a woman, that much is clear, but the details are lost on me. It’s a shame, because their conversation sounds fun and interesting, especially to a nosy person like me. But I don’t speak their language.

Out of curiosity, I interrupt them to ask what language they are speaking. They both switch easily to English, explaining that they are South Africans and had been speaking Xhosa. In Johannesburg, where they are from, most people speak at least five languages, says one of them, Theo Morris. For example, Morris’s mother’s tongue is Sotho, his father’s is Zulu; he learned Xhosa and Ndebele from his friends and neighbours and English and Afrikaans at school. “I went to Germany before I came here, so I also speak German,” he adds.

Was it easy to learn so many languages? “Yes, it’s normal,” he laughs.

He’s right. Around the world, more than half of people – estimates vary from 60-75% – speak at least two languages. Many countries have more than one official national language – South Africa has 11. People are increasingly expected to speak, read and write at least one of a handful of “super” languages, such as English, Chinese, Hindi, Spanish or Arabic, as well. So to be monolingual, as many native English speakers are, is to be in the minority and perhaps to be missing out.

Multilingualism has been shown to have many social, psychological and lifestyle advantages. Moreover, researchers are finding a swath of health benefits from speaking more than one language, including faster stroke recovery and delayed onset of dementia.

FULL ARTICLE HERE: