Monitoring epilepsy in the brain with a wireless system

Wed, 02/11/2015 - 12:56pm Laure-Anne Pessina, EPFL   Source: Thinkstock/EPFLThe large majority of the 50 million people around the world who suffer from epilepsy can be treated by anticonvulsant drugs. Yet a handful of patients do not respond to the standard treatment. More and more of them are turning to surgery to give them back a normal life. The principle is to locate, with the help of electrodes, the region in the brain that is the source of the epilepsy and, in the most serious cases, remove it. The current presurgical phase is complex and highly invasive. Patients undergo a cranial operation to have electrodes implanted on the surface of their cortex. Once the wound is closed, the patients must remain in bed in intensive care for several weeks with wires passing through their cranium. The electrodes are connected the entire time to a recording machine, which is used to identify the source of the epilepsy during seizures. Researchers at EPFL are now developing a network of wireless microelectrodes that will monitor the patients' brain activity with great precision, without requiring them to remain confined to their hospital bed. Gürkan Yilmaz presented this research as part of his doctoral thesis, conducted in collaboration with doctors and researchers from Inselspital (University Hospital of Bern). A number of in vivo tests have been carried out successfully. Greater precision and less damage to the brain The new wireless method still needs a cranial operation, but it offers a number of advantages. In addition to suppressing cumbersome wires and sparing patients the ordeal of staying in intensive care during the presurgical phase, it extends the monitoring time, thanks to the reduced risk of infection. The source of the epilepsy can also be identified more precisely. "We are developing electrodes that are less than 100 micrometers in diameter, versus 10 millimeters for electrodes used in traditional intracranial electroencephalograms," says Yilmaz. "As a result, measurements are much more precise, and the fewest possible neurons are removed during the operation. This allows us to minimise the damage that can result from this type of operation." With the new system, which consists of a network of electrodes, a microchip and an antenna, the electric signals are captured and processed under the skin in a miniaturised station. The internal device is powered from the outside by wireless power transfer, more specifically by electromagnetic induction. Thanks to this energy, the internal system can process a large amount of data, and then transfer the results to an external unit. "We could use a mobile phone to receive the data, but for reasons of data security, it is not the preferred method," says Gürkan Yilmaz. At this stage, in vivo tests have been successfully run on laboratory mice. Innovative, less invasive therapies Medical doctors are showing a significant interest in this technology. Claudio Pollo, a neurosurgeon in charge of epilepsy surgery at Bern University Hospital, explains the potential represented by such a system. "We would be able to observe epileptogenesis at the level of a few cells rather than tens of thousands of cells," he notes. "This would enable us to remove smaller epileptogenic zones, and to develop innovative therapies. For example, when a given region cannot be removed, we could deliver electrical stimulation to the lesions to prevent seizures." And this type of surgery produces excellent results. "The recovery rate is nearly 80%, when talking about temporal lobe epilepsy. More and more children are operated on, and this drastically changes their future." In the laboratory, the researchers continue their work. Their goals include adjusting the size of the electrodes so that they can measure the activity of a single neuron. Source: EPFL

Low carb, high fat diets may reduce seizures in tough-to-treat epilepsy

 

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Diets high in fat and low in carbohydrates, such as the ketogenic or modified Atkins diet, may reduce seizures in adults with tough-to-treat epilepsy, according to a review of the research published in the October 29, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Epilepsy is a nervous system disorder in which the nerve cells in the brain work abnormally, causing seizures. About 50 million people have epilepsy worldwide, according to the World Health Organization.

"We need new treatments for the 35 percent of people with epilepsy whose seizures are not stopped by medications," said study author Pavel Klein, M.B.,B. Chir., of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md., and a member of the American Academy of Neurology. "The ketogenic diet is often used in children, but little research has been done on how effective it is in adults."

The ketogenic and modified Atkins diets include items such as bacon, eggs, heavy cream, butter, leafy green vegetables and fish. The ketogenic diet consists of a ratio of fat to protein/carbohydrates of three or four to one by weight. The modified Atkins diet has a one-to-one fat to carbohydrate/protein ratio by weight.

Scientists reviewed five studies on the ketogenic diet with a total of 47 people included in the analysis and five studies on the modified Atkins diet with 85 people included.

Researchers found that across all studies, 32 percent of people treated with the ketogenic diet and 29 percent of those treated with the modified Atkins diet experienced a 50 percent or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5 percent in the modified Atkins group had a greater than 90 percent reduction in seizures.

The positive results occurred quickly with both diets, within days to weeks. The effect persisted long-term, but, unlike in children, the results did not continue after participants stopped following the diet. Side effects of both diets were similar and not serious, with weight loss the most common side effect.

Fifty-one percent of the ketogenic diet group and 42 percent of the modified Atkins group stopped the diet before the study was completed.

"Unfortunately, long-term use of these diets is low because they are so limited and complicated. Most people eventually stop the diet because of the culinary and social restrictions," said Klein. "However, these studies show the diets are moderately to very effective as another option for people with epilepsy."

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Story Source:

The above story is based on materials provided by American Academy of Neurology (AAN). Note: Materials may be edited for content and length.

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Journal Reference:

1. Pavel Klein, Ivana Tyrlikova, and Gregory C. Mathews. Dietary treatment in adults with refractory epilepsy: A review. Neurology, October 2014 DOI: 10.1212/WNL.0000000000001004

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Combining Epilepsy Drug, Morphine Can Result in Less Pain, Lower Opioid Doses

 

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Adding a common epilepsy drug to a morphine regimen can result in better pain control with fewer side effects. Moreover, the combination can reduce the dosage of the opioid needed to be effective, according to a team of pain researchers at Indiana University.

The result could bring significant relief to many patients with neuropathic pain, a difficult-to-treat condition often felt in the arms and legs and associated with nerve tissue damage.

"There is a huge unmet need for better treatments for neuropathic pain," said Fletcher A. White, Ph.D., the Vergil K. Stoelting Professor of Anesthesia at the Indiana University School of Medicine.

In laboratory tests using rodents, White and his colleagues found that while morphine lost its pain-relieving effectiveness three weeks after nerve injury, a combination therapy of morphine and carbamazepine -- used to prevent epileptic seizures -- could effectively reverse this loss of drug action. Their findings were reported in the journal PLOS ONE.

Although morphine and related opioid drugs are effective in treating pain, they can result in dependence and produce side effects including respiratory depression, nausea, constipation and other problems. In addition, such drugs can, paradoxically, actually cause pain, a condition called opioid-induced hyperalgesia.

"People immediately think, 'Oh, it's tolerance, the patient needs more of the drug for pain control,'" Dr. White said.

In fact, research indicates that the pain of hyperalgesia occurs because the morphine latches on not only to cellular targets that reduce pain sensation but to other "non-opioid" targets that result in activation of pain-sensing neurons. Dr. White and his colleagues had previously identified a key cellular factor -- known to be a specific voltage-gated sodium ion channel -- involved in that non-opioid process of pain nerve stimulation. Meanwhile another IU School of Medicine researcher, Theodore Cummins, Ph.D., professor of pharmacology and toxicology, had previously determined that carbamazepine alone has the opposite effect on the same ion channel.

Combining the two drugs could prevent the escalating doses of opioids that are sometimes prescribed to provide pain relief in the clinic.

"We know that opioids have benefits," Dr. White said. "If we can diminish the off-target effects, that's good. If we can diminish the opioid dosages required for pain relief, then you've really got something."

Because both drugs are approved for use by the Food and Drug Administration, physicians have tested the combination with patients, resulting in anecdotal reports of significantly improved pain management, Dr. White said. More formally, Dr. White and physician-researchers have begun testing the combination of morphine and a close relative of carbamazepine with patients in a small clinical trial at the Indiana University Melvin and Bren Simon Cancer Center.

In addition to Dr. White, researchers contributing to the study were Michael R. Due, Xiao-Fang Yang, Yohance M. Allette, Aaron L. Randolph, Matthew S. Ripsch, Sarah M. Wilson and Erik T. Dustrude of the IU School of Medicine; and Rajesh Khanna of the College of Medicine, University of Arizona.

The research was funded by National Institutes of Health grants NIDDK DK100905 and NIDA DA026040 and the Indiana Spinal Cord and Brain Injury Research Fund.

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Story Source:

The above story is based on materials provided by Indiana University. Note: Materials may be edited for content and length.

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Journal Reference:

1. Michael R. Due, Xiao-Fang Yang, Yohance M. Allette, Aaron L. Randolph, Matthew S. Ripsch, Sarah M. Wilson, Erik T. Dustrude, Rajesh Khanna, Fletcher A. White. Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain. PLoS ONE, 2014; 9 (9): e107399 DOI: 10.1371/journal.pone.0107399

Biologists pave the way for improved epilepsy treatments

 

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University of Toronto biologists leading an investigation into the cells that regulate proper brain function, have identified and located the key players whose actions contribute to afflictions such as epilepsy and schizophrenia. The discovery is a major step toward developing improved treatments for these and other neurological disorders.

“Neurons in the brain communicate with other neurons through synapses, communication that can either excite or inhibit other neurons,” said Professor Melanie Woodin in the Department of Cell and Systems Biology at the University of Toronto (U of T), lead investigator of a study published today in Cell Reports. “An imbalance among the levels of excitation and inhibition – a tip towards excitation, for example – causes improper brain function and can produce seizures. We identified a key complex of proteins that can regulate excitation-inhibition balance at the cellular level.”

This complex brings together three key proteins – KCC2, Neto2 and GluK2 – required for inhibitory and excitatory synaptic communication. KCC2 is required for inhibitory impulses, GluK2 is a receptor for the main excitatory transmitter glutamate, and Neto2 is an auxiliary protein that interacts with both KCC2 and GluK2. The discovery of the complex of three proteins is pathbreaking as it was previously believed that KCC2 and GluK2 were in separate compartments of the cell and acted independently of each other.

“Finding that they are all directly interacting and can co-regulate each other’s function reveals for the first time a system that can mediate excitation-inhibition balance among neurons themselves,” said Vivek Mahadevan, a PhD candidate in Woodin’s group and lead author of the study.

Mahadevan and fellow researchers made the discovery via biochemistry, fluorescence imaging and electrophysiology experiments on mice brains. The most fruitful technique was the application of an advanced sensitive gel system to determine native protein complexes in neurons, called Blue Native PAGE. The process provided the biochemical conditions necessary to preserve the protein complexes that normally exist in neurons. Blue Native PAGE is advantageous over standard gel electrophoresis, where proteins are separated from their normal protein complexes based on their molecular weights.

“The results reveal the proteins that can be targeted by drug manufacturers in order to reset imbalances that occur in neurological disorders such as epilepsy, autism spectrum disorder, schizophrenia and neuropathic pain,” said Woodin. “There is no cure for epilepsy; the best available treatments only control its effects, such as convulsions and seizures. We can now imagine preventing them from occurring in the first place.”

“It was the cellular mechanisms that determine the excitation-inhibition balance that needed to be identified. Now that we know the key role played by KCC2 in moderating excitatory activity, further research can be done into its occasional dysfunction and how it can also be regulated by excitatory impulses,” said Mahadevan.

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Story Source:

The above story is based on materials provided by University of Toronto. Note: Materials may be edited for content and length.

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Journal Reference:

1. Vivek Mahadevan, Jessica C. Pressey, Brooke A. Acton, Pavel Uvarov, Michelle Y. Huang, Jonah Chevrier, Andrew Puchalski, Caiwei M. Li, Evgueni A. Ivakine, Matti S. Airaksinen, Eric Delpire, Roderick R. McInnes, Melanie A. Woodin. Kainate Receptors Coexist in a Functional Complex with KCC2 and Regulate Chloride Homeostasis in Hippocampal Neurons. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.05.022