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Harry Chugani

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Published: 01 June 2011

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It is my distinct honor, on behalf of the International Child Neurology Association, to invite you to register for the 12th International Child Neurology Congress to be held in Brisbane, Australia during May 2012.

The Congress will be held jointly with the 11th Asian and Oceanian Congress of Child Neurology, and promises to attract a large international audience. As in the past congresses, the Scientific Program will be of the highest caliber, emphasizing not only the latest developments and advances in child neurology, but also a review of current standard of care in the practice of child neurology. Participants from all over the world will be able to engage in collegial exchange of ideas in a friendly and warm atmosphere.

An attractive socio-cultural program is also being planned, and participants and their families will be able to enjoy both the diversity and uniqueness that Australia has to offer. Therefore, it is with great enthusiasm that we urge you to join us in Brisbane, May 2012 in what we anticipate to be a memorable scientific, academic and social experience.

Harry T. Chugani, M.D.

President, The International Child Neurology Association (ICNA)
Bruce and Rosalie Rosen Professor of Pediatrics and Neurology
Director, Positron Emission Tomography Center
Children's Hospital of Michigan, Detroit Medical Center
Wayne State University School of Medicine, Detroit, Michigan, USA

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ICNA

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Published: 18 May 2011

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Use of newer-generation antiepileptic drugs, which are also prescribed for bipolar mood disorders and migraine headaches, during the first trimester of pregnancy was not associated with an increased risk of major birth defects in the first year of life among infants in Denmark, according to a study in the May 18 issue of JAMA. Older-generation antiepileptic drugs are associated with an increased risk of birth defects. 

"Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on first-trimester use of newer-generation antiepileptic drugs and birth defects are limited," according to background information in the article. 

Ditte Molgaard-Nielsen, M.Sc., and Anders Hviid, M.Sc., Dr.Med.Sci., of the Statens Serum Institut, Copenhagen, Denmark, conducted a study to analyze the association between the use of lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam (newer-generation antiepileptic drugs) during the first trimester of pregnancy and the risk of any major birth defects. The study included data on 837,795 live-born infants in Denmark from January 1996 through September 2008. Individual-level information on dispensed antiepileptic drugs to mothers, birth defect diagnoses, and potential confounders (factors that can influence outcomes) were ascertained from nationwide health registries.

Among the live births included in the study (837,795), 19,960 were diagnosed with a major birth defect (2.4 percent) during the first year of life. Among 1,532 pregnancies exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester, 49 infants were diagnosed with a major birth defect (3.2 percent) compared with 19,911 infants (2.4 percent) among 836,263 unexposed pregnancies. After adjusting for various factors, the authors found that exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester was not associated with an increased risk of major birth defects. Gabapentin and levetiracetam exposure during the first trimester was uncommon.

The prevalence odds ratios for any major birth defects after exposure to any newer-generation antiepileptic drugs during the first trimester were not statistically different for mothers with epilepsy, mood affective disorder or migraine, or without a diagnosis.

"Our study, to our knowledge, is the largest analytic cohort study on this topic and provides comprehensive safety information on a class of drugs commonly used during pregnancy. The use of lamotrigine and oxcarbazepine during the first trimester was not associated with moderate or greater risks of major birth defects like the older-generation antiepileptic drugs, but our study cannot exclude a minor excess in risk of major birth defects or risks of specific birth defects. Topiramate, gabapentin, and levetiracetam do not appear to be major teratogens [an agent that can cause malformations in an embryo or fetus], but our study cannot exclude minor to moderate risks of major birth defects," the authors conclude.

JAMA. 2011;305[19]1996-2002.
Abstract: http://jama.ama-assn.org/content/305/19/1996.short

Note:

In 2008, a 200-patient study in Neurology found that topiramate in the first trimester of pregnancy carries a higher-than-usual rate of congenital malformations — especially when taken with valproate. [Article link: http://www.neurology.org/content/71/4/272.abstract ]

In March 2011, the FDA warned against use of topiramate during pregnancy because of its association with cleft lip and cleft palate; the FDA had  classified topiramate in pregnancy category D. [FDA MedWatch alert]

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ICNA

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Published: 18 May 2011

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Researchers including members from the Niels Bohr Institute at the University of Copenhagen have developed a new method for making detailed X-ray images of brain cells. The method, called SAXS-CT, can map the myelin sheaths of nerve cells, which are important for conditions such as multiple sclerosis and Alzheimer's disease. The results have been published in the scientific journal, NeuroImage.

The myelin sheaths of nerve cells are lamellar membranes surrounding the neuronal axons. The myelin layers are important to the central nervous system as they ensure the rapid and uninterrupted communication of signals along the neuronal axons. Changes in the myelin layers are associated with a number of neurodegenerative disorders such as cerebral malaria, multiple sclerosis, and Alzheimer's disease.

The development of these diseases are still not fully understood, but are thought to be related to the damage of the myelin layers, so that messages from the brain reach the various parts of the body poorly or not at all. It is like an electric cord where the insulating material has been damaged and the current short circuits. In order to find methods to prevent or treat the diseases it is important to understand the connection between the diseases and the changes in the myelin.

Getting 3-D X-ray images

"We have combined two well-known medical examination methods: SAXS (Small-Angle X-ray Scattering) and CT-scanning (computed tomography scanning). Combined with a specially developed programme for data processing, we have been able to examine the variations of the myelin sheaths in a rat brain all the way down to the molecular level without surgery", explains PhD Torben Haugaard Jensen, Niels Bohr Institute at the University of Copenhagen. The method is called 'Molecular X-ray CT', because you use X-ray CT to study myelin at the molecular level.

The research has been carried out in collaboration with researchers in Switzerland, France and Germany. The experiments took place at the Paul Scherrer Institute in Switzerland, where they have a powerful X-ray source that can measure Small-Angle X-Ray Scattering, SAXS at a high resolution. Normally such experiments would give two-dimensional X-ray images that are sharp and precise, but without information on depth. But by incorporating the method from CT-scanning, where you image from different angles, the researchers have managed to get 3D X-ray images.

This has not only required the development of new X-ray methods and experiments, but has also required the development of new methods for processing data. The extremely detailed measurements of cross sections from different angles meant that there were 800,000 images to be analysed. So the researchers have also developed an image-processing programme for the SAXS-CT method. The result is that they can see all of the detailed information from SAXS in spatially resolved.

From point samples to total samples

"We can see the myelin sheaths of the neuronal axons and we can distinguish the layers which have a thickness of 17.6 nanometers", explains Torben Haugaard Jensen. "Up until now, you had to cut out a little sample in order to examine the layers in one area and get a single measuring point. With the new method we can examine 250,000 points at once without cutting into the sample. We can get a complete overview over the concentration and thickness of the myelin and this gives of the ability to determine whether the destruction of the myelin is occurring in spots or across the entire sample", he explains.

The research provides new opportunities for collaboration with doctors at Copenhagen University Hospital and the Panum Institute, who they already have close contact with. The method cannot be used to diagnose living persons. But the doctors can obtain new knowledge about the diseases, what kind of damage is taking place? - and where? They will be able to follow the development of the diseases and find out how the brain is being attacked. This knowledge could perhaps be used to develop a treatment.

Source:
Gertie Skaarup
University of Copenhagen

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ICNA

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Published: 20 April 2011

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Researchers from the CHUM Research Centre (CRCHUM) have identified a new gene that predisposes people to both autism and epilepsy.

Led by the neurologist Dr. Patrick Cossette, the research team found a severe mutation of the synapsin gene (SYN1) in all members of a large French-Canadian family suffering from epilepsy, including individuals also suffering from autism. This study also includes an analysis of two cohorts of individuals from Quebec, which made it possible to identify other mutations in the SYN1 gene among 1% and 3.5% of those suffering respectively from autism and epilepsy, while several carriers of the SYN1 mutation displayed symptoms of both disorders. 

"The results show for the first time the role of the SYN1 gene in autism, in addition to epilepsy, and strengthen the hypothesis that a deregulation of the function of synapse because of this mutation is the cause of both diseases," notes Cossette, who is also a professor with the Faculty of Medicine at the Université de Montréal. He adds that "until now, no other genetic study of humans has made this demonstration."

The different forms of autism are often genetic in origin and nearly a third of people with autism also suffer from epilepsy. The reason for this comorbidity is unknown. The synapsin gene plays are crucial role in the development of the membrane surrounding neurotransmitters, also referred to as synaptic vesicles. These neurotransmitters ensure communication between neurons. Although mutations in other genes involved in the development of synapses (the functional junction between two neurons) have previously been identified, this mechanism has never been proved in epilepsy in humans until the present study.

The results of the present study were published in the latest online edition of Human Molecular Genetics.They provide the key to a common cause of epilepsy and autism and will make it possible to gain a better understanding of the pathophysiology of these devastating diseases that seriously perturb brain development. They will also contribute to the development of new treatment strategies.

Facts and figures relating to autism and epilepsy in Canada

Invasive development disorders, also called the autism spectrum, include five diagnoses: autism, the most well known; RETT syndrome; childhood disintegrative disorder; Asperger syndrome; and unspecified pervasive developmental disorder. It is estimated that 60 to 70 people (including 10 children) out of every 10,000 people are affected by pervasive development disorders in Canada.

Epilepsy affects around 85 out 10,000 people in Canada. There are several kinds of epileptic seizures and syndromes.

About the study

SYN1 loss-of-function mutations in ASD and partial epilepsy cause impaired synaptic function. Anna Fassio, Lysanne Patry, Sonia Congia, Franco Onofi, Amélie Piton, Julie Gauthier, Davide Pozzi, Mirko Messa, Enrico Defranci, Manuela Fadda, Anna Corradi, Pietro Baldelli, Line Lapointe, Judith St-Onge, Caroline Meloche, Laurent Mottron, Flavia Valtorta, Dang Khoa Nguyen, Guy A. Rouleau, Fabio Benfenati. Human Molecular Genetics.

Source:
Centre hospitalier de l'Université de Montréal