Diet in Concussion & Brain Injury - What can you do?

A fair bit is known about how to use diet to enhance or ameliorate brain function after brain injury. - JR

J Child Neurol. 2013 Aug;28(8):983-8. doi: 10.1177/0883073813487594. 

Traumatic brain injury and diet

ARTICLE HERE

Greco T1, Prins ML.

Author information

• 1Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7039, USA.

Abstract

Increasing attention is being paid to nutritional and metabolic management of traumatic brain injury patients. The gross metabolic changes that occur after injury have been found to be influenced by both macronutrients, that is, dietary ratios of fat, carbohydrates, and protein, and micronutrients, for example, vitamins and minerals. Alterations in diet and nutritional strategies have been shown to decrease both morbidity and mortality after injury. Despite this knowledge, defining optimal nutritional support following traumatic brain injury continues to be an ongoing challenge. Keywords brain, injury, metabolism, ketones, substrate, pituitary

 April 1, 2013.

Brain Metabolism After Traumatic Brain Injury Traumatic Brain Injury

Traumatic brain injury occurs more than any other disease in the United States, with an annual incidence of 3.5 million new cases. It affects men and women of all age groups, with the greatest incidence among children under 4 years of age and 14 to 19 years old. Traumatic brain injury is caused by the rapid movement of the brain within the skull and does not require direct contact with an object for injury to occur. Although there are pathophysiological similarities between glutamate excitotoxicity and hypoxic and ischemic brain injuries, it is the movement of the brain during traumatic brain injury that produces its unique time course and complex dysfunction.

Chronic care in disability - Good Care Matters.

Important Editorial for Parents Pediatricians, Payors...and docs. JR

Good care matters

Authors

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• First published: 1 February 2017

...‘Cerebral palsy’ continues to be used as a diagnostic bucket into which any physically disabling condition is dumped, without the careful precision of diagnostic assessment advocated by the Surveillance of Cerebral Palsy in Europe's freely available Reference and Training Manual (2016; http://www.scpenetwork.eu). Different diagnoses bring different associated conditions, patterns of inheritance, and outcomes. Diagnostic precision matters....

ARTCLE HERE

Prevention of dislocation of the hip in children with cerebral palsy

20-year results of a population-based prevention programme

http://www.bjj.boneandjoint.org.uk/content/96-B/11/1546.long

Trump and Autism? Why the focus?

The attention to special education is appreciated yet there are many issues requiring his attention.  - JR

Trump Focus On ASD Misplaced, Advocates Say

by Michelle Diament | February 17, 2017

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At a White House gathering this week, President Donald Trump expressed concern about a “tremendous increase” in autism, but experts caution that his rhetoric doesn’t tell the whole story.

During what was billed as a “listening session” with parents and teachers, Trump inquired about autism after Jane Quenneville introduced herself as the principal of a Virginia special education center.

“So what’s going on with autism?” Trump asked. “When you look at the tremendous increase, it’s really — it’s such an incredible — it’s really a horrible thing to watch, the tremendous amount of increase. Do you have any idea? And you’re seeing it in the school?”...

Full article here

Smog, Sperm & other possible Environmental Links to Autism

Smog, Sperm and other possible environmental links to autism ... oh yes... BUT NOT VACCINES, MR. TRUMP.

Health Promot Chronic Dis Prev Can. 2017 Jan;37(1):1-23.

Environmental factors associated with autism spectrum disorder: a scoping review for the years 2003-2013.

[Article in English, French; Abstract available in French from the publisher]

Ng M1,2, de Montigny JG3, Ofner M1,2, Do MT1,2.

Author information

Abstract

in English, French

FULL ARTICLE HERE

INTRODUCTION:

The number of children diagnosed with autism spectrum disorder (ASD) has been rapidly rising in the past decade. The etiology of this disorder, however, is largely unknown, although the environmental relative to the genetic contribution is substantial. We conducted a scoping review to comprehensively assess the current state of knowledge of the environmental factors present from preconception to early life associated with ASD, and to identify research gaps.

METHODS:

We searched electronic databases MEDLINE, PsycINFO and ERIC for articles on potential risk factors or protective factors from the physical and social environments associated with ASD and its subclassifications published between 1 January, 2003, and 12 July, 2013. We categorized articles into broad themes: chemical, physiological, nutritional and social factors, based on environmental exposure.

RESULTS:

We identified over 50 000 publications, but after ineligible studies were screened out, 315 articles remained. Most of these studies examined physiological factors, followed closely by chemical factors, and to a much lesser extent, nutritional and social factors, associated with ASD. Despite a vast literature and many heterogeneous studies, several risk factors emerged consistently: chemical factors such as traffic-related air pollutants; physiological factors including advanced parental age, preterm birth, low birth weight, hyperbilirubinemia and clustering of pregnancy complications; and maternal immigrant status. Despite extensive research on vaccines, findings overwhelmingly demonstrate no support for an association with ASD.

CONCLUSION:

The lack of consistency, temporality and specificity of associations between environmental factors and ASD remains the largest barrier to establishing causal relationships. More robust research is required to resolve inconsistencies in the literature. Future research should explore underlying mechanisms of associations between the risk factors that we identified and ASD.

KEYWORDS:

ASD; autism; autism spectrum disorder; environmental exposure; etiology

De novo missense variants in CACNA1A can cause congenital cerebellar ataxia with global developmental delay

More information about the early utitlity of genetic testing for children with delay. Gratified to be included with these colleagues. - JR

PgmNr 2385: Link to American Society Human Genetics

De novo missense variants in CACNA1A can cause congenital cerebellar ataxia with global developmental delay.

Authors:
J.A. Rosenfeld ¹ ; T. Harel ¹ ; X. Luo ¹ ; S. Yamamoto ¹ ; M. Hall ² ; K. Wierenga ² ; M. Pastore ³ ; D. Bartholomew ³ ; M. Delgado ⁴ ; Joshua Rotenberg ⁵ ; R.A. Lewis ¹ ; M. Almannai ¹ ; L. Emrick ¹ ; T. Lotze ¹ ; M. Ummat ¹ ; C.A. Bacino ¹ ; M. Eldomery ¹ ; Z. Coban Akdemir ¹ ; F. Xia ¹ ; H. Bellen ¹ ; J. Lupski ¹ ; Y. Yang ¹ ; B. Lee ¹ ; S.R. Lalani ¹ ; M. Wangler ¹ ; Members of the UDN 

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Institutes
1) Molecular & Human Genetics, Baylor College of Medicine, Houston, TX.; 2) University of Oklahoma Health Sciences Center, Oklahoma City, OK; 3) Nationwide Children's Hospital & The Ohio State University, Columbus, OH; 4) Texas Scottish Rite Hospital, Dallas, TX; 5) Houston Specialty Clinic, Houston, TX 

---

Abstract:

Variants in CACNA1A [MIM 601011], encoding the α-1A subunit of the neuronal P/Q type voltage-dependent Ca²⁺ channel, are known causes of ataxia: triplet repeat expansions extending a polyglutamine tract in the protein cause adult-onset spinocerebellar ataxia, type 6 [MIM 183086], and heterozygous variants (typically loss-of-function) cause childhood-onset episodic ataxia, type 2 [MIM 108500]. Additionally, missense variants in the gene cause autosomal dominant familial hemiplegic migraines [MIM 141500]. 

We report five individuals with congenital, non-fluctuating ataxia, hypotonia, ophthalmologic abnormalities, and global developmental delay. Four individuals had a recurrent, de novo c.4991G>A/p.R1664Q variant, which has been described previously in another individual with early-onset, persistent limb and trunk ataxia. The fifth individual has a de novo missense variant, c.5018G>C/p.R1673P. Both missense variants alter arginine residues within the fourth transmembrane domain, changing the pattern of positive charges within the voltage sensor. This pattern is also altered by other severe pathogenic alleles, suggesting that more severe clinical phenotypes could result from disruption of this specific domain. A sixth individual with a severe presentation of neonatal stroke and subsequent refractory epilepsy had a de novo variant within this transmembrane domain, c.5075T>A/p.L1692Q. 

To explore the functional consequences of these variants, we generated a loss-of-function (LOF) allele in the homologous gene (cac) in Drosophila that will allow expression of these human variant forms. This LOF allele recapitulates the lethal phenotypes previously observed in cac mutant flies. Human variants will be assessed through their ability to rescue the loss of cac in Drosophila photoreceptors, where conditional knockout causes neurodegeneration, synaptic transmission deficits and neuronal accumulation of autophagic vesicles.

 This cohort, combined with previous reports, shows that variants in CACNA1A can cause congenital non-fluctuating cerebellar ataxia and other severe neonatal presentations, thus expanding the spectrum of ataxia and other features associated with this important neuronal calcium channel gene. Functional studies in model organisms will provide further insight into this disease spectrum.

An antibiotic for autism, neurologic, psychiatric illness? New fad or New Tool?

Go to:

Abstract

An antibiotic for autism, neurologic, psychiatric illness? New fad or New Tool? Two articles - One treatment trial and a review. - JR

Mol Autism. 2016 Jan 14;7:2. doi: 10.1186/s13229-015-0062-8. eCollection 2016.

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders.

Minshawi NF1, Wink LK2, Shaffer R2, Plawecki MH1, Posey DJ3, Liu H4, Hurwitz S5, McDougle CJ6, Swiezy NB1, Erickson CA2.

Author information

Abstract

BACKGROUND:

Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD.

METHODS:

A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio.

RESULTS:

No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures.

CONCLUSIONS:

The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed.

TRIAL REGISTRATION:

ClinicalTrials.govNCT01086475.

D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review

Sebastian Schade, MD and Walter Paulus, MD

Int J Neuropsychopharmacol. 2016 Apr; 19(4): pyv102.

Published online 2015 Sep 12. doi:  10.1093/ijnp/pyv102

Abstract

D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits.

© The Author 2015. Published by Oxford University Press on behalf of CINP.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851259/

Case reports or just that 1 case. B6 is fairly innocuous but can have side effects. Consult your specialist physician. -JR

Seizure. 2017 Jan 3;45:189-191. doi: 10.1016/j.seizure.2016.12.020. [Epub ahead of print]

Dramatic response to pyridoxine in a girl with absence epilepsy with ataxia caused by a de novo CACNA1A mutation.

Du X1, Chen Y2, Zhao Y1, Luo W2, Cen Z3, Hao W4.

Author information

PMID:

 

28088730

 

DOI:

 

10.1016/j.seizure.2016.12.020

Trial of 4-aminopyridine in Episodic Ataxia

Neurology. 2011 Jul 19;77(3):269-75. doi: 10.1212/WNL.0b013e318225ab07. Epub 2011 Jul 6.

A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.

Strupp M1, Kalla R, Claassen J, Adrion C, Mansmann U, Klopstock T, Freilinger T, Neugebauer H, Spiegel R, Dichgans M, Lehmann-Horn F, Jurkat-Rott K, Brandt T, Jen JC, Jahn K.

Author information

Abstract

OBJECTIVE:

The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus.

METHODS:

After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis.

RESULTS:

The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated.

CONCLUSIONS:

This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life.

LEVEL OF EVIDENCE:

This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.

Comment in

• A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias. [Neurology. 2011]
• News on ion channels: erythromelalgia, treatment of episodic ataxia and faciobrachial dystonic seizures. [J Neurol. 2011]

PMID:

 

21734179

 

PMCID:

 

PMC3136055

 

DOI:

 

10.1212/WNL.0b013e318225ab07

[PubMed - indexed for MEDLINE] 

Free PMC Article

VNS may be more effective in children WITHOUT intellectual disability.

In specialty epilepsy treatment, a common clinical question is: who might benefit from earlier vns? VNS may be more effective in children WITHOUT intellectual disability.  -JR

Eur J Paediatr Neurol. 2017 Jan 30. pii: S1090-3798(17)30071-5. doi: 10.1016/j.ejpn.2017.01.011. [Epub ahead of print]

Vagus Nerve Stimulation in children: A focus on intellectual disability.

Sourbron J1, Klinkenberg S2, Kessels A3, Schelhaas HJ4, Lagae L5, Majoie M6.

Author information

Abstract

INTRODUCTION:

Vagus Nerve Stimulation (VNS) can be an efficacious add-on treatment in patients with drug-resistant epilepsy, who are not eligible for surgery. Evidence of VNS efficacy in children with intellectual disability (ID) is scarce.

OBJECTIVES:

The purpose of this study was to review all available VNS data in the pediatric population (≤18 years old) and focus on the subpopulation with ID since appropriate treatment of these children is often challenging and complex.

METHODS:

Cochrane, EMBASE, PubMed and MEDLINE were used to collect all research associated to VNS and ID (or synonyms) leading to a total of 37 studies. Seven studies showed the results of patients with ID and those without separately; thereby only these studies were included in the VNS meta-analysis.

RESULTS:

Our meta-analysis showed that VNS was less effective in pediatric epilepsy patients with ID compared to those without ID (Mantel-Haenszel meta-analysis; p = 0.028, OR 0.18 (CI 95% 0.039-0.84)). However, there were no prospective controlled studies. Numerous studies reported quality of life (QoL) improvements in this subpopulation. The most common adverse events were transient and well tolerated. Side effects on cognition and behavior were not reported.

DISCUSSION:

These results might be a reason to consider VNS early on in the treatment of this subgroup. The significantly greater amount of retrospective studies, differences in follow-up (FU), lack of control data, heterogeneous series and limited number of patients could have biased the outcome measurements. Hence, current data do not exclude VNS for children with drug-resistant epilepsy and ID but should be interpreted with caution.

Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

Alternative treatment; Drug-resistant epilepsy; Meta-analysis; Neurostimulation; Quality of life; VNS