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Published: 13 May 2012

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The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) trial results published in the NEJM suggest that IM midazolam is at least as safe and effective as IV lorazepam for prehospital termination of seizures in status epilepticus.

This double-blind, randomised, phase 3, noninferiority trial designed and conducted by the Neurological Emergencies Treatment Trials (NETT) network, a multidisciplinary clinical trials infrastructure funded by the National Institute of Neurological Disorders and Stroke (NINDS), compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics.

Subjects with seizures lasting for more than 5 minutes and continuing to convulsive on arrival of the paramedics were given either i.m midazolam via autoinjector or i.v lorazepam. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy and Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures.

At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P 0.001 for both noninferiority and superiority). Besides, there was no difference between the treatment groups with respect to need for intubation or seizure recurrence or incidence of adverse effects.

All adults and those children with an estimated body weight of more than 40 kg received either 10 mg of intramuscular midazolam followed by intravenous placebo or intramuscular placebo followed by 4 mg of intravenous lorazepam. In children with an estimated weight of 13 to 40 kg, the active treatment was 5 mg of intramuscular midazolam or 2 mg of intravenous lorazepam.

It is possible that this might mean some subjects were administered lorazepam doses below the recommended standard of 0.1mg/kg/dose. The study also did not compare the effects of autoinjector versus conventional IM treatments nor the efficacy of IM/IV lorazepam/midazolam.

However the study results seem to support the use of intramuscular midazolam by emergency medical personnel in the pre hospital setting for status epileptics. In addition midazolam has the advantage of better stability when not refrigerated, compared to lorazepam.

Citation: Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600. PubMed PMID: 22335736; PubMed Central PMCID: PMC3307101.

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Published: 12 May 2012

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Seizures in early life are associated with autism with about 40% of patients with autism also having epilepsy as comorbidity. A study from Boston Children's Hospital finds a reason for the link, and suggests that the mTOR inhibitor rapamycin ,already shown to be safe in children, could help prevent autism from developing in newborns who have seizures.

Frances Jensen (standing) with her postdoc Jocelyn Lippman BellFrances Jensen and colleagues at the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children's Hospital used a rat model to show that early seizures not only resulted in epilepsy later in life, but also produced autistic-like behaviour. They have shown that disabling the mTOR pathway – by giving the drug rapamycin before and after seizures – prevented development of abnormal patterns of connections (synapses) between brain cells, reduced later-life seizures and eased autistic-like symptoms.

Dr Jensen's group in a related study published last year has shown that seizures exaggerated excitation and synaptic strengthening too soon in a rat model, causing synapses to lose their plasticity -- their ability to reconfigure in response to input from the outside world and following administration of the drug NBQX, which blocks receptors associated with excitation, these problems were reversed.

The mTOR pathway is already known to be over-active in tuberous sclerosis complex (TSC) which often includes epilepsy and autism. Boston Children's Hospital is currently conducting a clinical trial of rapamycin in children with TSC.

This study suggests that even without tuberous sclerosis, seizures are inducing the mTOR pathway, and might on their own be contributing to the development of autism. The fields of epilepsy and autism may thus inform each other about new treatment targets.

SOURCE : Boston Children's Hospital

Citation: Talos DM, Sun H, Zhou X, Fitzgerald EC, Jackson MC, et al. (2012) The Interaction between Early Life Epilepsy and Autistic-Like Behavioral Consequences: A Role for the Mammalian Target of Rapamycin (mTOR) Pathway. PLoS ONE 7(5): e35885. doi:10.1371/journal.pone.003588

For further background, see this feature published last year in Nature Medicine

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Published: 11 May 2012

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The  Annual General Meeting of the ICNA Annual General Meeting will be held on Tuesday 29th May, 18.30-19.30 at the Brisbane Convention & Exhibition Centre , Brisbane. All ICNA members are welcome and encouraged to attend this meeting.

Agenda

1. Welcome - Harry Chugani , USA
2. Reports

President -Harry Chugani, USA
Secretary Jo Wilmshurst, South Africa
Treasurer - Orvar Eeg-Oloffson, Sweden
President elect - Ingrid Tein, Canada

3. 2014 Congress update and 2016 Congress announcements

4. Changes to the membership – the pros and cons

Ken Mack, USA
Robert Ouvrier, Australia

5. Motions for the membership (Hugo Arroyo, Argentina) Changes to the constitution and the Bylaws

6. Questions

7. Membership vote

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Published: 11 May 2012

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A group of scientists has found that video games such as Nintendo's Wii offer an enjoyable opportunity to promote light to moderate physical activity in children with CP, and may have a role to play in rehabilitation therapy. Their research is published online in the Archives of Physical Medicine and Rehabilitation.

According to the lead investigator Elaine Biddiss, PhD, of Toronto's Bloorview Research Institute at Holland Bloorview Kids Rehabilitation Hospital, and the University of Toronto, CanadA, active video games (AVG) provide a low-cost, commercially available system that can be strategically selected to address specific therapeutic goals

Seventeen children with CP were studied while playing four AVGs: Wii Bowling, Tennis, Boxing, and Dance Dance Revolution (DDR). Energy, motion, and muscle activity data were captured, and the children completed a survey to indicate their level of enjoyment playing the games. The researchers evaluated the intensity of the physical activity, the therapeutic potential of AVG play, and the practical considerations surrounding the use of AVGs for physical activity promotion.

They found that children with mild CP can attain moderate levels of physical activity during AVG play with games that require full body movements, such as Wii Boxing and DDR, but the activity is not vigorous enough to build endurance or strength. However, they did find that AVG play encourages repetitive movement and provides feedback to the user through on-screen avatars and game scores, which could promote neuroplastic change. The children reported high levels of enjoyment, which also enhances neuroplasticity.

Researchers found that certain games, such as Wii boxing, may be a good choice for encouraging and training faster wrist movements. This is important for children with CP as they commonly experience difficulty in extending their wrists. Children with hemiplegia, a form of CP that affects the limbs on one side of the body, frequently underutilize their affected limb regardless of their functional abilities. In the study, children engaged both upper limbs when playing Wii Boxing or DDR.

The range of motion of the dominant limb was well within the typical norms associated with upper limb movements in able-bodied individuals. While further safety studies are needed, this suggests that AVG should be a relatively low impact activity for children with CP. The researchers noted considerable variability in the participant's strategies to succeed in the game.

Participants may adapt a movement that minimizes physical effort to maximize in-game rewards. In a therapeutic setting, it may be necessary to train and provide rewards for appropriate movement styles. "While not a replacement for structured exercise and physical therapy, AVGs may encourage children with CP to be physically active and to practice complex motor activities.

There are many opportunities for further research. Future development and optimization of AVG technologies may usher in a new age in physical rehabilitation where virtual environments provide an arena for neuroplastic change in the comfort of one's home.

Citation: 

Active Video Game Play in Children With Cerebral Palsy: Potential for Physical Activity Promotion and Rehabilitation Therapies
Jennifer Howcroft, Sue Klejman, Darcy Fehlings, Virginia Wright, Karl Zabjek, Jan Andrysek, Elaine Biddiss. Archives of physical medicine and rehabilitation 9 May 2012 (Article in Press DOI: 10.1016/j.apmr.2012.02.033)

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