A high-fat, low-carbohydrate diet termed the ‘ketogenic diet’ has been found to be safe and effective in the management of drug-resistant epilepsy. Published in the June issue of Lancet Neurology, the diet showed impressive effects, with some patients reporting a greater than 90% reduction in seizure frequency whilst on the diet.
A total of 145 children aged between 2 and 16 years who had failed to respond to at least two antiepileptic drugs and who were still having at least seven fits per week participated in the study. None of the children had previously tried the ketogenic diet.
Following a 4-week baseline period during which seizure frequency was recorded in a diary by the children’s parents, the children were randomly assigned to either a standard diet or the ketogenic diet.
“The parents say the first 2 weeks are quite difficult, but then it becomes much easier because you can make foods in bulk and it especially helps if you can see the benefits from it,” explained Helen Cross, Professor of Pediatric Neurology at University College London and Great Ormond Street Hospital (London, UK) and lead author of the study.
After 3 months, those on the ketogenic diet had a reduction in seizure frequency of at least one third, while the seizure frequency of those on the standard diet actually increased. In addition, 38% of children on the ketogenic diet experienced a seizure frequency reduction of over 50%, compared with only 6% of children on the normal diet. A total of five children on the ketogenic diet had a reduction in seizure frequency of greater than 90%. Reported side effects of the diet included constipation, vomiting, lack of energy and hunger.
“If your epilepsy is easily controlled on one medication then I wouldn’t advocate the diet, but if at least two drugs have failed then it should be considered,” Cross suggested.
Source: Neal EG, Chaffe H, Schwartz RH et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. (2008) (Epub ahead of print).
Ibuprofen may reduce risk of Alzheimer’s disease
A recent study, published in the May 6 issue of Neurology, has demonstrated that regularly taking NSAIDs for at least 5 years may reduce the risk of developing Alzheimer’s disease (AD).
The researchers analyzed 5 years of prescription data of almost 250,000 patients from the Veterans Affairs healthcare system. The sample included people over the age of 55 years, approximately 49,000 of whom had a diagnosis of AD and approximately 200,000 without AD.
Regularly taking a NSAID for at least 5 years was associated with a 25% decrease in the risk of developing AD; for ibuprofen the risk was reduced by 40%.
“Some of these medications taken long-term decrease the risk of AD, but it’s very dependent on the exact drugs used. It doesn’t appear that all NSAIDs decrease the risk at the same rate,” commented lead author Steven Vlad of Boston University School of Medicine (MA, USA).
Although the results are impressive, they by no means suggest that ibuprofen, or NSAIDs in general, should be taken on a regular basis to reduce AD risk. NSAIDs are associated with severe renal and gastrointestinal side effects and it is currently unclear whether the benefit of possibly preventing AD is worth the risk of severe, potentially fatal side effects.
“The big issue is that ibuprofen looks like it prevents AD, but all these drugs have well-known side effects and significant side effects, so the risk–benefit ratio is not clear at this point. Patients shouldn’t go on ibuprofen to prevent AD,” explained Vlad.
“A clinical trial of ibuprofen for the prevention of AD would be reasonable to get the risks and benefits,” Vlad said. “There’s also going to be ongoing research into developing drugs like ibuprofen without the toxicities.”
Source: Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 70(19), 1672–1677 (2008).
Genetic variants associated with neuroblastoma discovered
Neuroblastoma is a relatively rare childhood cancer, with only 7% of childhood cancers being of this form. However, owing to its potentially aggressive nature, neuroblastoma causes 15% of all childhood cancer deaths. The cause of neuroblastoma had remained largely unknown. However, a chromosome region has recently been identified that is associated with the cancer.
“Until now we had very few clues as to what causes neuroblastoma,” explained study leader John Maris, Director of the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia (PA, USA). “Although there is much work to be done, understanding this cancer’s origin provides a starting point for developing novel treatments.”
Published online in May in the New England Journal of Medicine, the researchers analyzed blood samples from 1032 neuroblastoma patients and 2043 healthy controls. Using a genome-wide association study, the group identified three single nucleotide polymorphisms (SNPs) from approximately 500,000 studied that were much more common in patients with neuroblastoma than in healthy controls. All three of the SNPs were located in the same region of chromosome 6, 6p22.
“We expected for decades that this cancer was a genetic disease…”
“This is the first paper that helps us understand what causes this childhood cancer,” commented Maris. “We expected for decades that this cancer was a genetic disease, but we have had a hard time understanding what abnormalities in our genetic make-up lead to this cancer.”
In addition, patients with all three of the SNPs were more likely to develop an aggressive form of neuroblastoma.
“Properly defining risk level helps us to avoid the twin pitfalls of under-treating or over-treating any given child with neuroblastoma,” Maris explained.
The group is now carrying out further work on the genetics of neuroblastoma. “We are doing further studies to understand how these relatively common genetic changes translate into increased risk of cancer,” commented Maris. “Ultimately, they probably cause subtle changes in gene expression during early development, interacting with other genes yet to be discovered. This suggests that neuroblastoma has complex causes, in which a series of genetic changes may occur at different sites to combine into a ‘perfect storm’ that results in this cancer.”
Source: Maris JM, Mosse YP, Bradfield JP et al. Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N. Engl. J. Med. (2008) (Epub ahead of print).
Fluoxetine may be beneficial for multiple sclerosis sufferers
Published online in May in the Journal of Neurology, Neurosurgery and Psychiatry, researchers from The Netherlands have found that fluoxetine reduces the number of new areas affected by inflammation in patients with relapsing–remitting multiple sclerosis (RRMS) compared with placebo.
A total of 38 patients completed the double-blind study, 19 of whom received 20 mg/day fluoxetine and 19 who received placebo. A MRI scan was performed on study participants every 4 weeks to assess the changes in neurological inflammation. After 8 weeks of treatment the scans started to show less new areas of inflammation in the fluoxetine-treated patients compared with placebo. This delay in effect matches the time that it takes for selective serotonin reuptake inhibitors, like fluoxetine, to become effective when treating depression.
From week 8 to 24, the average number of new areas of inflammation was 3.16 in the placebo-treated group and 1.21 in the fluoxetine-treated group.
During the last 16 weeks of treatment, an impressive 63% of those treated with fluoxetine had no new areas of inflammation on MRI, compared with only 26% of those on placebo.
The authors concluded that although this was only an exploratory study and that the sample sizes were small, the results are “sufficiently encouraging to justify further studies with fluoxetine in patients with MS.”
Source: Mostert JP, Admiraal-Behloul F, Hoogduin JM et al. Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study. J. Neurol. Neurosurg. Psychiatry (2008) (Epub ahead of print).
American Academy of Neurology develops new botulinum toxin guidelines
Following systematic reviews of approved and off-label use of botulinum toxin, the American Academy of Neurology (AAN) has developed a series of guidelines for the use of botulinum toxin.
Endorsed by the American Academy of Physical Medicine and Rehabilitation, the guidelines state that botulinum toxin is safe and effective for the treatment of cervical dystonia, and may also be used for a variety of other disorders, such as hemifacial spasm, focal limb dystonias and essential tremors.
However, based on the results of four studies in episodic migraine and four in tension-type headache, the guidelines concluded that the neurotoxin is probably not effective in the treatment of these disorders.
“Based on currently available data, botulinum toxin injections should not be offered to patients with episodic migraine and chronic tension-type headaches,” commented Markus Naumann, member of the AAN. “It is no better than placebo injections for these types of headache.”
The guidelines were developed to offer clinical guidance for the use of botulinum toxin, which will no doubt be invaluable, particularly in light of several recent reports highlighting concerns of the use of the neurotoxin.
Sources: Simpson DM, Gracies JM, Graham HK et al. Assessment: botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology
Assessment Subcommittee of the American Academy of Neurology. Neurology 70(19), 1691–1698 (2008). Simpson DM, Blitzer A, Brashear A et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70(19), 1699–1706 (2008).
Naumann M, So Y, Argoff CE et al. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70(19), 1707–1714 (2008).