- Details
- Biju Hameed
- News
- Hits: 450
A study from Boston Children's Hospital published in BMC Medicine this week suggest a EEG coherence-based phenotype for childhood autism.
EEG coherence is a measure of the degree of association or coupling of frequency spectra between two EEG signals when compared over time.
The EEG coherence was studied by quantifying the degree to which any two EEG signals from multiple electrodes at different time points were synchronised.High coherence values for eg where two or more waves rise and fall together over time, are taken as a measure of strong connectivity between the brain regions that produce the compared EEG signals.
The investigators compared raw EEG data from 430 children with autism and 554 control subjects, ages 2 to 12, and found that those with autism had consistent EEG patterns indicating altered connectivity between brain regions.
Using computational techniques, the researchers generated coherence readings for more than 4,000 unique combinations of electrode signals, and looked for the ones that seemed to vary the most from child to child. From these, they identified 33 coherence "factors" that consistently distinguished the children with autism from the controls, across all age groups (2 to 4, 4 to 6, and 6 to 12 years).
The autistic children generally showing reduced connectivity compared to controls. The left hemisphere language areas in particular showed reduced connectivity in autistic children, consistent with neuroimaging findings suggesting altered connectivity in the arcuate fasciculus
There are several interesting aspects to the study methodology in that the researchers had included a mid-range cross section of childhood autism and pervasive developmental disorder while excluding the high functioning autism or Asperger's syndrome where the children are typically cooperative. The group at Boston children's also had at their disposal a large database of EEG data on typical neurologically normal children.
In addition they had also studied all the available scalp channels and spectral bands and using a technique called Principal Components Analysis the extensive spectral coherence data sets were reduced to a much small number of factors and these variables were studied among the cases and controls.
There are plans to repeat this study in children with Asperger's syndrome and also in autism associated with tuberous sclerosis, fragile x syndrome and extreme prematurity and see if its EEG patterns are similar to or different from that of classic autism.
The findings from this study are interesting since it explores potential diagnostic tests for autism particularly at younger ages when behavior-based measures are unreliable.
The full text of this study is available via open access at http://www.biomedcentral.com/1741-7015/10/64
Source: Children's Hospital Boston
Read More
- Details
- ICNA
- News
- Hits: 657
MINNEAPOLIS – The American Academy of Neurology has issued an updated guideline outlining the best treatments for infantile spasms. The guideline, which was co-developed with the Child Neurology Society, is published in the June 12, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.
The guideline found that the hormone therapy adrenocorticotropic hormone, also known as ACTH, may be effective for treatment of infantile spasms. The seizure drug [[vigabatrin]] may also be considered for treatment, although evidence suggests ACTH may be more effective than vigabatrin. For children with seizures caused by tuberous sclerosis complex, however, vigabatrin may be more effective.
The guideline, which is based on a review of all available evidence on treatment for infantile spasms and is an update of a guideline published in 2004, also found that low-dose ACTH is probably as effective as high-dose ACTH and it may lower the risk of side effects.
There is not enough evidence to know whether other treatments, alone or combined, are effective in treating infantile spasms, according to the guideline.
The guideline recommends that early diagnosis and early treatment may lead to better long-term outcomes for children's development and learning skills.
Guideline
Update: Medical Treatment of Infantile Spasms
Read More
- Details
- Biju Hameed
- News
- Hits: 468
An important work published in the May 24 issue of Neuron by, researchers from Dana-Farber Cancer Institute and Harvard Medical School helps toward the understanding of the molecular mechanisms of mitochondrial and metabolic control of seizures and helps to uncover how the ketogenic diet works in epilepsy.
The efficacy of the ketogenic diet in children with epilepsy has pointed to a role for metabolism as a component of the pathogenesis of seizures. However the molecular mechanisms behind the dependence of neuronal activity on metabolic substrates has not been fully understood2. In parallel to its role in apoptosis, the Bcl-2-associated death promoter (BAD) protein , a pro-apoptotic member of the Bcl-2 gene family, has been shown to have an important role in glucose metabolism and utilization.
In this respect the phosphorylation of BAD does not only prevent initiation of cell death, but it is also required for efficient mitochondrial utilization of glucose in liver. Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis.
Giménez-Cassina et al. (2012) investigating the potential role of BAD in seizures, found the existence of a phosphodependent regulatory switch in BAD that reduces neuronal excitability upon kainic acid-induced seizures. Similar to what occurs in the liver they showed that cortical neurons and astrocytes from Bad−/− mice display lower glucose utilization for mitochondrial respiration.
This showed an interesting connection between BAD deficient mice or mice with nonphosphorylable BAD and ketogenic diet which reduces seizures in terms of glucose utilization by mitochondria.
The authors therefore investigated whether BAD might also influence seizure sensitivity in vivo. They found that BAD deficient as well as BadS155A(mice bearing a phosphodeficient knockin allele of Bad at serine 155) mice were significantly protected from the proconvulsant drug kainic acid. Moreover, seizure resistance was specific for BAD and independent from its proapoptotic function, pointing therefore to its role in metabolism.
BAD Phosphorylation Controls Mitochondrial Fuel Utilization to Switch Neuronal ExcitabilityThe proapoptotic BH3-only protein BAD can be viewed as a relay: its phosphorylation on Ser 155 switches the preferred source of reducing equivalents for mitochondria from glucose to ketones. Plasma membrane KATP channels are closed in neurons with “glycolytic” mitochondria, as opposed to the ones where mitochondria use ketone bodies and that are less susceptible to seizures. (source: Neuron Volume 74, Issue 4, 24 May 2012, Pages 600–602)The Ketogenic diet has been shown to increases the activity of KATP channels. KATP channels are activated following decreased intracellular ATP, in a negative feedback loop that is believed to help neurons to overcome excitotoxicity during seizure. Giménez-Cassina et al. also found that the dentate granule neurons (DGNs) of hippocampal slices from BAD deficient (Bad−/− ) mice showed increased single KATP channels, while ablation of KATP channels expression in BAD deficient (Bad−/− ) mice diminished their resistance to seizures .
The study thus linked BAD phosphorylation and KATP channels activity to the attenuation of seizures, a hitherto unknown signalling pathway The study, funded by Harvard Catalyst, Citizens United for Research in Epilepsy, and the NIH has contributed significantly to the understanding of the molecular mechanisms of mitochondrial and metabolic control of seizures with potential implications for future therapeutic strategies.
Citations
1. Elena Ziviani, Luca Scorrano. Neuron, Volume 74, Issue 4, 24 May 2012, Pages 600-602
2. Giménez-Cassina et al. Neuron, 74 (2012), pp. 719–730
Read More
- Details
- ICNA
- News
- Hits: 519
The next few years will be exciting for the ICNA and its members. In the current report we move away from activities in Europe (for now) and cover the ICNA meeting in Uganda on “Children with Epilepsy”, the build-up to the imminent Brisbane ICNC and address the next ICNC in 2014 which will be in Brazil.
This Newsletter is timed to come out just before the 12th ICNC in Brisbane. In future, editions will continue to be mid-year and towards the end of the year, or just prior to major meetings. The ICNA AGM agenda is available in this edition included, it itemises one of the important proposals for the membership to vote on, namely that of whether the association should move to free membership! The board discussed this and voted in favour of the proposal but the final decision will lie with the membership - read on if you want to know more.
A number of bursaries and awards will be received at the 12th ICNC in Brisbane - these are summarised in this issue.
Crossing the globe further the dynamic Pratibha Singhi continues her work in her country and has provided a report on the meeting on “Childhood Epilepsy in Office Practice” in India which she was part of.
Enjoy this issue - please remember to send me suggestions of topics you would like included and any interesting photos. Also any brave vignettes you would share with the readers.
Jo Wilmshurst
Editor
Read More
- Details
- ICNA
- News
- Hits: 519
In a study published in the Annals of Neurology, researchers at Georgetown University Medical Center (GUMC) report that the anti-epilepsy drug phenobarbital given to rat pups about a week old changed the way the animals' brains were wired, causing cognitive abnormalities later in life. The results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult.
Using patch-clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal learning at weaning.
Synaptic maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine, but not levetiracetam. Interestingly melatonin pretreatment which prevents drug induced neurodevelopmental apoptosis, prevented this disruption in maturation.
The study raises new questions about using phenobarbitone as the first-line drug to treat epilepsy in neonates.
Citation: Forcelli, P. A., Janssen, M. J., Vicini, S. and Gale, K. (2012), Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Ann Neurol.. doi: 10.1002/ana.23600 [abstract]
Read More