Posts Tagged surgery

[WEB PAGE] Individual frequency can be used to control brain activity – News

Reviewed by Emily Henderson, B.Sc.Aug 17 2020

Individual frequency can be used to specifically influence certain areas of the brain and thus the abilities processed in them – solely by electrical stimulation on the scalp, without any surgical intervention. Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences have now demonstrated this for the first time.

Stroke, Parkinson’s disease and depression – these medical illnesses have one thing in common: they are caused by changes in brain functions. For a long time, research has therefore been conducted into ways of influencing individual brain functions without surgery in order to compensate for these conditions.

Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, have taken a decisive step. They have succeeded in precisely influencing the functioning of a single area of the brain. For a few minutes, they inhibited exactly the area that processes the sense of touch by specifically intervening in its rhythm. As a result, the area that was less networked with other brain regions, its so-called functional connectivity, decreased, and thus also the exchange of information with other brain networks.

This was possible because the researchers had previously determined each participant’s individual brain rhythm that occurs when perceiving touch. With the personal frequency, they were able to modulate the targeted areas of the brain one at a time in a very precise manner using what is known as transcranial alternating current stimulation. “This is an enormous advance,” explains Christopher Gundlach, first author of the underlying study. “In previous studies, connectivity fluctuated extensively when the current was distributed in different areas of the brain. The electrical current randomly sought its own path in the brain and thus affected different brain areas simultaneously in a rather imprecise manner.

In a preliminary study, the neuroscientists had already observed that this form of stimulation not only reduces the exchange of the targeted brain networks with other networks, it also affects the brain’s ability to process information, in this case the sense of touch. When the researchers inhibited the responsible somatosensory network, the perception threshold increased. The study participants only perceived stimuli when they were correspondingly strong. When, on the other hand, they stimulated the region, the threshold value dropped and the study participants already felt very gentle electrical stimuli.

The deliberate change in brain rhythm lasted only briefly. As soon as the stimulation is switched off, the effect disappears again. Nevertheless, the results are an important step towards a targeted therapy for diseases or disorders caused by disturbed brain functions”.

Bernhard Sehm, Study Leader

Targeted brain stimulation could help to improve, direct and, if necessary, attenuate the flow of information.

Source: Max Planck Institute for Human Cognitive and Brain Sciences

Journal reference: Gundlach, C., et al. (2020) Reduction of somatosensory functional connectivity by transcranial alternating current stimulation at endogenous mu-frequency.  NeuroImage. doi.org/10.1016/j.neuroimage.2020.117175.

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[WEB PAGE] Treatments for Epilepsy | MyEpilepsyTeam

Article written by Kelly Crumrin

There is at present no cure for epilepsy, although some people with epilepsy do go into remission. The good news is that while epilepsy is not yet curable, it is treatable for most people.

There are a wide range of epilepsy treatments, with most falling into one of four categories: medication, diet, implanted devices, and surgeries. Before recommending a course of treatment, a physician will take into account age, overall health, medical history, severity of condition, and type or types of seizure. The goal of epilepsy treatment is to stop seizures, or at least decrease their frequency as much as possible.

There is no one treatment that works for all types of seizures and types of epilepsy.

Some epilepsies and seizure types are more difficult to treat because they are less responsive to most treatments.

In most cases, a medication will be the first treatment prescribed. On average, anti-epileptic drugs (AEDs) will work for 70 percent of people with epilepsy. In as many as 20 to 40 percent of epilepsy cases, seizures cannot be adequately controlled with any type of anticonvulsant medication. Drug-resistant epilepsy is also known as intractable or refractory epilepsy. In cases where AEDs are ineffective, doctors may recommend a special diet, an implanted device, or surgery.

Medication

AEDs work in different ways, but they are all believed to reduce excess electrical activity in the brain. There are an increasing number of AEDs on the market, and many of the newer medications offer more focused treatment with fewer side effects.

If a medication is ineffective at controlling seizures, or if its side effects are bothering you, contact your doctor. Finding the right medication and the right dosage can be a long process. In cases where AEDs are ineffective, the doctor may recommend diet changes or surgery.

Most AEDs are taken orally. Some may be given rectally, as an injection, or are designed to dissolve in the mouth rather than be swallowed. AEDs that can be administered as a nasal spray are under development.

Narrow-Spectrum AEDs

Narrow-spectrum AEDs treat specific types of seizures, such as focal (partial) or absence seizures. Drugs in this category include Briviact (Brivaracetum), Dilantin (Phenytoin), Lyrica (Pregabalin), Neurontin, (Gabapentin), PhenobarbitalTrileptal (Oxcarbazepine), Vimpat (Lacosamide), and Carbamazepine, which is sold under the brand names Tegretol and Carbatrol.

Broad-Spectrum AEDs

Broad spectrum AEDs can be effective for multiple seizure types. Broad-spectrum anticonvulsants include Depakote (Valproic acid), Keppra (Levetiracetum), Lamictal (Lamotrigine), Topamax (Topiramate), and Zonegran (Zonisamide).

Apart from AEDs, other classes of drugs may be prescribed to control seizures. For instance, Klonopin (Clonazepam) is a sedative of the benzodiazepine class used to treat Lennox-Gastaut syndrome, and Phenobarbital is a barbiturate.

All AEDs have side effects, especially during the first few weeks of treatment. Common side effects of AEDs include drowsiness, dizziness, problems with memory or attention, vision changes, mood changes, and increase or decrease in appetite.

All AEDs are required by the U.S. Food and Drug Administration (FDA) to carry a suicide warning. The risk for suicide due to AEDs is quite low, but anyone taking an AED should be aware of and report any serious depression or suicidal thoughts to their doctor.

Some AEDs can interfere with hormonal birth control methods, and some birth control pills can interfere with the effectiveness of AEDs. Certain AEDs are known to have a higher risk of birth defects if either the father or mother is taking them.

Never change your dose or stop your medication without consulting with your doctor. Withdrawal must be done with close supervision. Suddenly stopping a medication can cause more severe seizures.

Diet

In cases where epilepsy is refractory (resistant to medication), doctors may recommend adopting a specific diet to help control seizures. Research shows that in combination with AEDs, a diet high in fat and low in carbohydrates can help some people control their epilepsy.

The ketogenic diet, used to treat children with refractory epilepsy, is an extreme diet involving fasting and monitoring by a physician and a nutritionist. The purpose of the diet is to force the body to burn fat for energy instead of carbohydrates, increasing the level of molecules called ketones in the blood. For some children, a high level of ketones reduces seizure activity.

For adults, a less extreme version of the ketogenic diet is the modified Atkins diet. The modified Atkins diet lowers seizure activity in nearly half of the adults who follow it for several months.

Diet changes should be made with your doctor’s knowledge and guidance.

Implanted Devices

Some people with intractable epilepsy may be candidates for an implanted device such as a vagus nerve stimulator (VNS) or a responsive neurostimulation system (RNS). To be eligible, people must generally be 12 years or older and have tried several AEDs.

vagus nerve stimulator is a device similar to a pacemaker that is implanted under the skin near the collarbone. The device uses a lead, or thin wire, to connect to the vagus nerve in the neck. It then stimulates the nerve at regular intervals, which can reduce the intensity and frequency of seizures. VNS may be more effective in treating focal seizures than other types of seizures.

responsive neurostimulation system is a small, electronic device that is implanted inside the skull. One or two thin wires from the device are connected to the seizure targets. The device is then programmed to detect and record brain activity patterns and respond with electrical stimulation when abnormal patterns are detected. Stimulation cannot be felt. When you go home, you will receive a brain activity monitor that will record data and send it to the neurologist.

People generally continue taking AEDs after receiving an implanted device.

Surgery

Surgical treatment may be recommended for people whose seizures are severe or frequent enough to be life-threatening or significantly impact quality of life. Candidates for epilepsy surgery must have failed several epilepsy drugs and have seizures with a known focus.

Epilepsy surgeries fall into two general categories: resection and disconnection. The most common type of neurosurgery for epilepsy is resection, in which the portion of the brain causing seizures is removed. If successful, the surgery can provide long-term remission from seizures. Names of resection procedures often end in ‘-ectomy,’ which means removal by cutting. Temporal lobectomy, also known as temporal lobe resection, is the most frequently performed of all epilepsy surgeries and has the highest rate of success. Other resection surgeries include extratemporal cortical resectionfrontal lobectomylesionectomyoccipital lobectomyparietal lobectomy, and right frontal lobectomy.

Disconnection surgeries attempt to limit the spread of seizure activity and reduce seizure frequency. Disconnection surgeries are known as palliative treatments because they can improve quality of life, but do not cure epilepsy. The most common type of disconnection surgery is the corpus callosotomy, in which the fibers connecting the two hemispheres, or sides of the brain, are severed to prevent the spread of seizures from one side to the other. Corpus callosotomy surgery is usually performed on children who have debilitating seizures that cause injuries and falls. Multiple subpial transection is another surgery designed to disconnect the seizure focus, limiting the spread of seizures.

Functional hemispherectomy combines the resection of a seizure focus in one hemisphere with corpus callosotomy.

Other Treatments

Some people with epilepsy try natural or alternative treatments. Some report improvements when they use medical cannabis, melatonin, or complementary therapies such as acupuncture, herbal or nutritional supplements, chiropractic treatments, and mind-body practices such as meditation.

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Resources

External resources

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FAQs

Can I get assistance paying for my AEDs?
Anti-epileptic drugs can be costly. Many people with private or employer-sponsored health insurance are eligible for copay assistance programs – many with a $0 copay – through drug manufacturers. Some people without health insurance who meet low-income criteria may qualify for free AEDs through non-profit organizations or drug manufacturers.

What is the difference between brand-name and generic drugs?
Some medications are available as either brand-name or generic products. Generic drugs are almost always less expensive than brand-name drugs. Both products have the same active ingredient at the same dosage. However, some people with epilepsy notice differences between branded drugs and generics in the level of effectiveness, how quickly drugs become active, and how long they stay active between brand and generic medications. Side effects may also differ, or differ in intensity, between generic and brand-name AEDs. Generic versions may also differ between manufacturers. When switching to a generic, or if switching to a different manufacturer, inform your doctor about any breakthrough seizures or changes in side effects.

How can a service animal help someone with epilepsy?
Seizure response dogs are specially trained to support people with epilepsy when they have seizures. Seizure dogs can alert caregivers, activate an alarm system, retrieve a cell phone or medication, and act as a physical support by lying down next to a person having a seizure or helping them up. Rarely, after many years with a person, some service dogs can learn to recognize an oncoming seizure and warn the person before it happens.

via Treatments for Epilepsy | MyEpilepsyTeam

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[WEB PAGE] International researchers propose new classification system of seizures

Epilepsy is a wide-spread neurological disorder that affects around 50 million people worldwide. It is characterized by recurrent epileptic seizures, which are sudden bursts of electrical activity in the brain. There are many different types of seizures, and a person with epilepsy can experience more than one type.

Clinicians today use EEG measurements, with electrodes either placed on a patient’s scalp or inside the brain, to identify when and where a seizure begins. But these measurements alone do not always provide enough information to understand the type of seizure and make optimal decisions regarding treatment.

Now, an international team of researchers led by Aix-Marseille University in France and the University of Michigan has proposed a new classification system of seizures based on a deep understanding and mathematical modelling of brain oscillations. “It represents the first objective and unbiased taxonomy of its kind”, says one of the lead authors, HBP-scientist Prof. Viktor Jirsa from Aix-Marseille University.

The researchers used “bifurcation theory” – a method commonly used in fields such as physics and engineering – to analyze data from over a hundred patients across the globe. Researchers from the University of Melbourne and Monash University, both in Australia, the University of Freiburg in Germany, and Kyoto University in Japan also contributed to the work. Seizures with similar properties were categorized into groups.

They found sixteen types of seizure dynamics – or ‘dynamotypes’ – with distinct characteristics. “Similar to the periodic table of elements in chemistry, we demonstrated the existence of a clear classification system of seizures”, says Jirsa.

The system could lead clinicians to a better understanding of seizures and how they should be treated. “Seizure types react differently to treatments. For instance, some seizures can be stopped through electric stimulation, others not, dependent on their dynamotype. The systems scientific basis is theory work developed around the Epileptor, a central epilepsy model we developed in the Human Brain Project that is also at the heart of a large clinical trial running now”, the researcher explains.

Classification, however, is not explanation. There is much work ahead of us to better understand epilepsy mechanisms. This is where EBRAINS will play a key role, as it provides the tools connecting cellular, network and brain imaging signals aiding in mechanism discovery. ”

Prof. Viktor Jirsa, HBP-Scientist from Aix-Marseille University

EBRAINS is a new shared digital brain research infrastructure for the European Union that the Human Brain Project (HBP) is building.

Within the HBP, Jirsa and his team had first begun adapting the open network simulator The Virtual Brain towards applications in epilepsy. The work has laid the foundations for project EPINOV (“Improving EPilepsy surgery management and progNOsis using Virtual brain technology”) a multi-year project involving more than a dozen French hospitals that is funded by the French state. EPINOV tests whether the use of the personalized HBP modeling technology for epilepsy networks can improve surgery preparation in drug-resistant patients.

via International researchers propose new classification system of seizures

 

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[NEWS] Novel artificial intelligence algorithm helps detect brain tumor

 

A brain tumor is a mass of abnormal cells that grow in the brain. In 2016 alone, there were 330,000 incident cases of brain cancer and 227,000 related-deaths worldwide. Early detection is crucial to improve patient prognosis, and thanks to a team of researchers, they developed a new imaging technique and artificial intelligence algorithm that can help doctors accurately identify brain tumors.

 

Image Credit: create jobs 51 / Shutterstock.com

Image Credit: create jobs 51 / Shutterstock.com

Published in the journal Nature Medicine, the study reveals a new method that combines modern optical imaging and an artificial intelligence algorithm. The researchers at New York University studied the accuracy of machine learning in producing precise and real-time intraoperative diagnosis of brain tumors.

In the past, the only way to diagnose brain tumors is through hematoxylin and eosin staining of processed tissue in time. Plus, interpretation of the findings relies on pathologists who examine the specimen. The researchers hope the new method will provide a better and more accurate diagnosis, which can help initiate effective treatments right away.

In cancer treatment, the earlier cancer has been diagnosed, the earlier the oncologists can start the treatment. In most cases, early detection improves health outcomes. The researchers have found that their novel method of detection yielded a 94.6 percent accuracy, compared to 93.9 percent for pathology-based interpretation.

The imaging technique

The researchers used a new imaging technique called stimulated Raman histology (SRH), which can reveal tumor infiltration in human tissue. The technique collects scattered laser light and emphasizes features that are not usually seen in many body tissue images.

With the new images, the scientists processed and studied using an artificial intelligence algorithm. Within just two minutes and thirty seconds, the researchers came up with a brain tumor diagnosis. The fast detection of brain cancer can help not only in diagnosing the disease early but also in implementing a fast and effective treatment plan. With cancer caught early, treatments may be more effective in killing cancer cells.

The team also utilized the same technology to accurately identify and remove undetectable tumors that cannot be detected by conventional methods.

“As surgeons, we’re limited to acting on what we can see; this technology allows us to see what would otherwise be invisible, to improve speed and accuracy in the OR, and reduce the risk of misdiagnosis. With this imaging technology, cancer operations are safer and more effective than ever before,” Dr. Daniel A. Orringer, associate professor of Neurosurgery at NYU Grossman School of Medicine, said.

Study results

The study is a walkthrough of various ideas and efforts by the research team. First off, they built the artificial intelligence algorithm by training a deep convolutional neural network (CNN), containing more than 2.5 million samples from 415 patients. The method helped them group and classify tissue samples into 13 categories, representing the most common types of brain tumors, such as meningioma, metastatic tumors, malignant glioma, and lymphoma.

For validation, the researchers recruited 278 patients who are having brain tumor resection or epilepsy surgery at three university medical centers. The tumor samples from the brain were examined and biopsied. The researchers grouped the samples into two groups – control and experimental.

The team assigned the control group to be processed traditionally in a pathology laboratory. The process spans 20 to 30 minutes. On the other hand, the experimental group had been tested and studied intraoperatively, from getting images and processing the examination through CNN.

There were noted errors in both the experimental and control groups but were unique from each other. The new tool can help centers detect and diagnose brain tumors, particularly those without expert neuropathologists.

“SRH will revolutionize the field of neuropathology by improving decision-making during surgery and providing expert-level assessment in the hospitals where trained neuropathologists are not available,” Dr. Matija Snuderl, associate professor in the Department of Pathology at NYU Grossman School of Medicine, explained.

Journal references:

Patel, A., Fisher, J, Nichols, E., et al. (2019). Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30468-X/fulltext#%20

Hollon, T., Pandian, B, Orringer, D. (2019). Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks. Nature Medicine. https://www.nature.com/articles/s41591-019-0715-9

 

via Novel artificial intelligence algorithm helps detect brain tumor

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[WEB PAGE] Study offers possibility of squelching a focal epilepsy seizure before symptoms appear

Patients with focal epilepsy that does not respond to medications badly need alternative treatments.

In a first-in-humans pilot study, researchers at the University of Alabama at Birmingham have identified a sentinel area of the brain that may give an early warning before clinical seizure manifestations appear. They have also validated an algorithm that can automatically detect that early warning.

These two findings offer the possibility of squelching a focal epilepsy seizure — before the patient feels any symptoms — through neurostimulation of the sentinel area of the brain. This is somewhat akin to the way an implantable defibrillator in the heart can staunch heart arrhythmias before they injure the heart.

In the pilot study, three epilepsy patients undergoing brain surgery to map the source of their focal epilepsy seizures also gave consent to add an investigational aspect to their planned surgeries.

As neurosurgeons inserted long, thin, needle-like electrodes into the brain to map the location of the electrical storm that initiates an epileptic seizure, they also carefully positioned the electrodes to add one more task — simultaneously record the electrical activity at the anterior nucleus of the thalamus.

The thalamus is a structure sitting deep in the brain that is well connected with other parts of the brain. The thalamus controls sleep and wakefulness, so it often is called the “pacemaker” of the brain. Importantly, preclinical studies have shown that focal sources of seizures in the cortex can recruit other parts of the brain to help generate a seizure. One of these recruited areas is the anterior thalamic nucleus.

The UAB team led by Sandipan Pati, M.D., assistant professor of neurology, found that nearly all of the epileptic seizures detected in the three patients — which began in focal areas of the cortex outside of the thalamus — also recruited seizure-like electrical activity in the anterior thalamic nucleus after a very short time lag. Importantly, both of these initial electrical activities appeared before any clinical manifestations of the seizures.

The UAB researchers also used electroencelphalography, or EEG, brain recordings from the patients to develop and validate an algorithm that was able to automatically detect initiation of that seizure-like electrical activity in the anterior thalamic nucleus.

“This exciting finding opens up an avenue to develop brain stimulation therapy that can alter activities in the cortex by stimulating the thalamus in response to a seizure,” Pati said. “Neurostimulation of the thalamus, instead of the cortex, would avoid interference with cognition, in particular, memory.”

“In epilepsy, different aspects of memory go down,” Pati explained. “Particularly long-term memory, like remembering names, or remembering events. The common cause is that epilepsy affects the hippocampus, the structure that is the brain’s memory box.”

Pati said these first three patients were a feasibility study, and none of the patients had complications from their surgeries. The UAB team is now extending the study to another dozen patients to confirm the findings.

“Hopefully, after the bigger group is done, we can consider stimulating the thalamus,” Pati said. That next step would have the goals of improved control of seizures and improved cognition, vigilance and memory for patients.

For epilepsy patients where medications have failed, the surgery to map the source of focal seizures is a prelude to two current treatment options — epilepsy surgery to remove part of the brain or continuous, deep-brain stimulation. If the UAB research is successful, deep brain stimulation would be given automatically, only as the seizure initiates, and it would be targeted at the thalamus, where the stimulation might interfere less with memory.

 

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[WEB SITE] Surgery for Epilepsy – What Do You Need to Know?

Surgery for Epilepsy – What Do You Need to Know?

Epilepsy is one of the most common neurological disorders that can affect anyone irrespective of their age and gender. Marked by recurrent seizures causing a disturbance in the normal functioning of the body, epilepsy takes a toll on the patient’s overall normal life. Therefore, it is crucial that the patient must seek medical consultation from the best neurologist in India for accurate and timely treatment.

Thanks to the advancements in the medical field, epilepsy can be controlled by using various treatment options. Approximately 70% of people who suffer from epilepsy can control this condition through medications prescribed by a neurologist. In case medications are not enough to manage the condition, the patients can opt for surgery or other alternatives.

Now, deciding to undergo neurosurgery is a big step. Hence, it is very important to gather all the information about the surgery and find the best neurosurgeon in India for a successful result. For anyoneplanning to undergo a surgery for epilepsy, here is what they need to know.

Types of Epilepsy Surgery

Usually, the main aim of an epilepsy surgery is either to remove the part of the brain which causes seizures orcontrol the nerves to stop the seizures. Depending on the patient’s condition, the neurosurgeon can opt for different types of epilepsy surgery, including:

  • Resective Surgery

It is the most common type of surgery that is performed to treat epilepsy. In resective surgery, the neurosurgeons remove the part of the brain that causes seizures. It is helpful in reducing the number of seizures and limiting the risk of permanent brain damage.

  • Multiple Subpial Transection

It is a rare procedure that is performedonly when the patient suffers from severe and frequent seizures. During this surgery, the neurosurgeoncreates small incisions in the brain to stop the seizures.

  • Hemispherectomy

In this type of surgery, the neurosurgeon removes, disconnects or disables half of the brain (cerebral hemisphere). It is usually performed in cases where children suffer from a damaged hemisphere and have intractable seizures.

  • Corpus Callosotomy

Unlike other epilepsy surgeries, it focuses on decreasing the severity of the seizures rather than stopping them. Neurosurgeon cuts the nerve fiberswhich helps in preventing the seizures from spreading from one side of the hemisphere to the other.

The Surgery

Before making the surgical decision, the neurosurgeon ensures that the patient is eligible for the surgery by performing various tests and evaluating the results. It is only after a thorough examination that the neurosurgeon begins with the procedure.

The surgery is performed by neurosurgeons trained in this field. Hospitals like Max Healthcare have teams consisting of thebest neurosurgeon in India. Before the surgery, the neurosurgeon informs the patient about all the procedures, risks and benefits.

In an anterior temporal lobectomy, that is the most common type of Resective Surgery.The neurosurgeons make an opening in the skin of the head andmake a circular opening in the skull, known as a craniotomy. Using special equipment, they perform brain mapping to locate the areas of the brain that cause seizures. Once the area is identified, neurosurgeons remove that area while carefully looking through an operative microscope. After the surgery, the bone flap is replaced and secured with titanium plates and screws. The skin of the head is also sutured back together.

Usually, the surgery takes three to four hours,and the patient is shifted to the neuroscience intensive care unit (NSICU) for observation and monitoring. The hospital stay can vary from three to four days.

The Road to Recovery

After the surgery, the patient needs to take at least three to four weeks of rest before resuming to normal activities. If the patient keeps following the advice of doctors and adopts a healthy lifestyle, the recovery process can accelerate significantly. Moreover, there are various precautions that are needed to be takenin order to avoid any complications. Doctors also recommend speech or physical therapy if there are any issues after the surgery.

 

via Surgery for Epilepsy – What Do You Need to Know? » Northeast Today

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[NEWS] Surgery, precision medicine: the big hopes for epilepsy

19 March 2018

Αποτέλεσμα εικόνας για Surgery, precision medicine: the big hopes for epilepsy

PRECISION therapies targeting the molecular mechanisms of the disease are the shining hope for patients with uncontrolled, drug-resistant epilepsy, according to the authors of a narrative review published by the MJA.

The review was written in the wake of a new classification of epileptic seizures released by the International League Against Epilepsy (ILEA) in March 2017, which emphasises the importance of aetiology in allowing “optimisation of management”, as well as the importance of identifying comorbidities, such as learning, psychiatric and behavioural problems.

“The treatment of epilepsy relies primarily on antiepileptic drug (AED) therapy, which fully controls seizures in about two-thirds of patients,” wrote the authors – Dr Piero Perucca, consultant neurologist at the Royal Melbourne Hospital and Monash University, Professor Ingrid Scheffer, paediatric neurologist at Austin Health and the Florey Institute, and Dr Michelle Kiley, the director of Epilepsy Services at the Royal Adelaide Hospital.

“Second generation AEDs have expanded opportunities for tailoring treatment, but the burden of drug-resistant epilepsy, with its associated risks of disability, morbidity and mortality, has remained substantially unchanged for several decades.”

Over 15 second-generation AEDs have been developed since the 1990s and although they offer greater choice, and therefore more targeted options for patients, they have not significantly altered seizure-free outcomes.

Patients with drug-resistant epilepsy – defined by ILEA as “failure of adequate trials of two tolerated, appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure-freedom” – should be considered for surgery at the earliest opportunity, the review authors wrote.

“Epilepsy surgery involves resection or, less commonly, disconnection or destruction of epileptic tissue, and it is the most effective therapy for selected patients with drug-resistant epilepsy,” they wrote.

Despite that, and official recommendations from the American Academy of Neurology, the American Epilepsy Society and the American Association of Neurological Surgeons, delayed uptake of the surgical option remains “of concern”.

“These recommendations have not translated to increased use of epilepsy surgery,” Perucca and colleagues wrote.

“Consideration of epilepsy surgery still occurs typically 20 years after epilepsy onset, despite evidence of its effectiveness after failure of two adequate AED trials, and despite data suggesting that longer epilepsy duration adversely affects surgical outcome.”

Other non-pharmacological therapies – including vagus nerve stimulation, transcutaneous stimulation of the vagus or trigeminal nerve, deep brain stimulation of the anterior nucleus of the thalamus and responsive cortical stimulation, ketogenic diet and a modified Atkins diet – are also evaluated by the review authors as hopeful paths for research.

Perucca and colleagues were cautious in their hopes for medicinal cannabis.

“Scientifically sound evidence on the effectiveness of cannabinoids in epilepsy was provided only recently [in cases of Dravet and Lennox–Gastaut syndromes] … Overall, more evidence is required before cannabidiol can be considered further for the treatment of most individuals with epilepsy,” they wrote.

Precision medicine provides perhaps the brightest hope for patients battling resistant epilepsy, the review authors wrote.

“The advent of next-generation sequencing has fuelled renewed hope, especially following successful models developed in oncology.

“Epilepsy offers a promising opportunity for precision medicine, due to the myriad of gene discoveries, availability of experimental in vitro and in vivo models for drug screening, and the feasibility of conducting small, cost-effective trials of novel agents.

“For some genetic epilepsies, precision medicine is already a reality,” they said.

“A prime example is glucose transporter type 1 deficiency syndrome, in which dominant mutations in SLC2A1 result in impaired brain uptake of glucose. These patients respond to the ketogenic diet, which provides the brain with an alternative energy substrate.

“Identifying the molecular cause of epilepsy also allows the prevention or minimisation of AED adverse effects. In SCN1A-related epilepsies, sodium channel-blocking AEDs, such as carbamazepine, may aggravate seizures. In epilepsies due to POLG mutations, avoidance of valproate is recommended due to increased risk of hepatic failure.”

The review authors concluded by emphasising surgery and precision medicine as the areas of greatest potential for patients with epilepsy seeking to lead a seizure-free life.

“A subset of drug-resistant individuals can be rendered seizure-free by epilepsy surgery, which should be considered as soon as two AEDs have failed.

“In other individuals, seizure control can be improved by using alternative AEDs or non-pharmacological therapies, but they rarely result in seizure freedom.

“Hope to reduce the proportion of patients with uncontrolled seizures rests on future therapeutic advances, including precision therapies targeting underlying molecular mechanisms.”

via Surgery, precision medicine: the big hopes for epilepsy – MJA InSight 10, 19 March 2018 | doctorportal

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[WEB SITE] New method uses advanced noninvasive neuroimaging to localize and identify epileptic lesions

Epilepsy affects more than 65 million people worldwide. One-third of these patients have seizures that are not controlled by medications. In addition, one-third have brain lesions, the hallmark of the disease, which cannot be located by conventional imaging methods. Researchers at the Perelman School of Medicine at the University of Pennsylvania have piloted a new method using advanced noninvasive neuroimaging to recognize the neurotransmitter glutamate, thought to be the culprit in the most common form of medication-resistant epilepsy. Their work is published today in Science Translational Medicine.

Glutamate is an amino acid which transmits signals from neuron to neuron, telling them when to fire. Glutamate normally docks with the neuron, gives it the signal to fire and is swiftly cleared. In patients with epilepsy, stroke and possibly ALS, the glutamate is not cleared, leaving the neuron overwhelmed with messages and in a toxic state of prolonged excitation.

In localization-related epilepsy, the most common form of medication-resistant epilepsy, seizures are generated in a focused section of the brain; in 65 percent of patients, this occurs in the temporal lobe. Removal of the seizure-generating region of the temporal lobe, guided by preoperative MRI, can offer a cure. However, a third of these patients have no identified abnormality on conventional imaging studies and, therefore, more limited surgical options.

“Identification of the brain region generating seizures in location-related epilepsy is associated with significantly increased chance of seizure freedom after surgery,” said the new study’s lead author, Kathryn Davis, MD, MSTR, an assistant professor of Neurology at Penn. “The aim of the study was to investigate whether a novel imaging method, developed at Penn, could use glutamate to localize and identify the epileptic lesions and map epileptic networks in these most challenging patients.”

“We theorized that if we could develop a technique which allows us to track the path of and make noninvasive measurements of glutamate in the brain, we would be able to better identify the brain lesions and epileptic foci that current methods miss,” said senior author Ravinder Reddy, PhD, a professor of Radiology and director of Penn’s Center for Magnetic Resonance and Optical Imaging.

Reddy’s lab developed the glutamate chemical exchange saturation transfer (GluCEST) imaging method, a very high resolution magnetic resonance imaging contrast method not available before now, to measure how much glutamate was in different regions of the brain including the hippocampi, two structures within the left and right temporal lobes responsible for short- and long-term memory and spatial navigation and the most frequent seizure onset region in adult epilepsy patients.

The study tested four patients with medication-resistant epilepsy and 11 controls. In all four patients, concentrations of glutamate were found to be higher in one of the hippocampi, and confirmatory methods (electroencephalography and magnetic resonance spectra) verified independently that the hippocampus with the elevated glutamate was located in the same hemisphere as the epileptic focus/lesion. Consistent lateralization to one side was not seen in the control group.

While preliminary, this work indicates the ability of GluCEST to detect asymmetrical hippocampal glutamate levels in patients thought to have nonlesional temporal lobe epilepsy. The authors say this approach could reduce the need for invasive intracranial monitoring, which is often associated with complications, morbidity risk, and added expense.

“This demonstration that GluCEST can localize small brain hot spots of high glutamate levels is a promising first step in our research,” Davis said. “By finding the epileptic foci in more patients, this approach could guide clinicians toward the best therapy for these patients, which could translate to a higher rate of successful surgeries and improved outcomes from surgery or other therapies in this difficult disease.”

Source: Penn Medicine

Source: New method uses advanced noninvasive neuroimaging to localize and identify epileptic lesions

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[WEB SITE] Research provides insights for why some epilepsy patients continue to experience postoperative seizures

New research from the University of Liverpool, published in the journal Brain, has highlighted the potential reasons why many patients with severe epilepsy still continue to experience seizures even after surgery.

Epilepsy continues to be a serious health problem and is the most common serious neurological disorder. Medically intractable temporal lobe epilepsy (TLE) remains the most frequent neurosurgically treated epilepsy disorder.

Many people with this condition will undergo a temporal lobe resection which is a surgery performed on the brain to control seizures. In this procedure, brain tissue in the temporal lobe is resected, or cut away, to remove the seizure focus.

Unfortunately, approximately one in every two patients with TLE will not be rendered completely seizure free after temporal lobe surgery, and the reasons underlying persistent postoperative seizures have not been resolved.

Reliable biomarkers

Understanding the reasons why so many patients continue to experience postoperative seizures, and identifying reliable biomarkers to predict who will continue to experience seizures, are crucial clinical and scientific research endeavours.

Researchers from the University’s Institute of Translational Medicine, led by Neuroimaging Lead Dr Simon Keller and collaborating with Medical University Bonn (Germany), Medical University of South Carolina (USA) and King’s College London, performed a comprehensive diffusion tensor imaging (DTI) study in patients with TLE who were scanned preoperatively, postoperatively and assessed for postoperative seizure outcome.

Diffusion tensor imaging (DTI) is a MRI-based neuroimaging technique that provides insights into brain network connectivity.

The results of these scans allowed the researchers to examine regional tissue characteristics along the length of temporal lobe white matter tract bundles. White matter is mainly composed of axons of nerve cells, which form connections between various grey matter areas of the brain, and carry nerve impulses between neurons allowing communication between different brain regions.

Through their analysis the researchers could determine how abnormal the white matter tracts were before surgery and how the extent of resection had affected each tract from the postoperative MRI scans.

Surgery outcomes

The researchers identified preoperative abnormalities of two temporal lobe white matter tracts that are not included in standardised temporal lobe surgery in patients who had postoperative seizures but not in patients with no seizures after surgery.

The two tracts were in the ‘fornix’ area on the same side as surgery, and in the white matter of the ‘parahippocampal’ region on the opposite side of the brain.

The tissue characteristics of these white matter tracts enabled researchers to correctly identify those likely to have further seizures in 84% of cases (sensitivity) and those unlikely to have further seizures in 89% of cases (specificity). This is significantly greater than current estimates.

The researchers also found that a particular temporal lobe white matter tract called the ‘uncinate fasciculus’ was abnormal – and potentially involved in the generation of seizures – in patients with excellent and suboptimal postoperative outcomes.

However, it was found that significantly more of this tract was surgically resected/removed in the patients with an excellent outcome.

New insights

Dr Simon Keller, said: “There is scarce information on the prediction of postoperative seizure outcome using preoperative imaging technology, and this study is the first to rigorously investigate the tissue characteristics of temporal lobe white matter tracts with respect to future seizure classifications.

“Although there is some way to go before this kind of data can influence routine clinical practice, these results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures.”

Source: Research provides insights for why some epilepsy patients continue to experience postoperative seizures

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[WEB SITE] Brain surgery helps remove scar tissue causing seizures in epilepsy patients

By the time epilepsy patient Erika Fleck came to Loyola Medicine for a second opinion, she was having three or four seizures a week and hadn’t been able to drive her two young children for five years.

“It was no way to live,” she said.

Loyola epileptologist Jorge Asconapé, MD, recommended surgery to remove scar tissue in her brain that was triggering the seizures. Neurosurgeon Douglas Anderson, MD, performed the surgery, called an amygdalohippocampectomy. Ms. Fleck hasn’t had a single seizure in the more than three years since her surgery.

“I’ve got my life back,” she said. “I left my seizures at Loyola.”

Surgery can be an option for a minority of patients who do not respond to medications or other treatments and have epileptic scar tissue that can be removed safely. In 60 to 70 percent of surgery patients, seizures are completely eliminated, and the success rate likely will improve as imaging and surgical techniques improve, Dr. Anderson said.

Traditionally, patients would have to try several medications with poor results for years or decades before being considered for surgery, according to the Epilepsy Foundation. “More recently, surgery is being considered sooner,” the foundation said. “Studies have shown that the earlier surgery is performed, the better the outcome.” (Ms. Fleck is a service coordinator for the Epilepsy Foundation North/Central Illinois Iowa and Nebraska.)

Dr. Asconapé said Ms. Fleck was a perfect candidate for surgery because the scar tissue causing her seizures was located in an area of the brain that could be removed without damaging critical structures.

Ms. Fleck experienced complex partial seizures, characterized by a deep stare, unresponsiveness and loss of control for a minute or two. An MRI found the cause: A small area of scar tissue in a structure of the brain called the hippocampus. The subtle lesion had been overlooked at another center.

Epilepsy surgery takes about three hours, and patients typically are in the hospital for two or three days. Like all surgery, epilepsy surgery entails risks, including infection, hemorrhage, injury to other parts of the brain and slight personality changes. But such complications are rare, and they pose less risk to patients than the risk of being injured during seizures, Dr. Asconapé said.

Loyola has been designated a Level Four Epilepsy Center by the National Association of Epilepsy Centers. Level Four is the highest level of specialized epilepsy care available. Level Four centers have the professional expertise and facilities to provide the highest level of medical and surgical evaluation and treatment for patients with complex epilepsy.

Loyola’s comprehensive, multidisciplinary Epilepsy Center offers a comprehensive multidisciplinary approach to epilepsy and seizure disorders for adults and children as young as two years old. Pediatric and adult epileptologist consultation and state-of-the-art neuroimaging and electrodiagnostic technology are used to identify and assess complex seizure disorders by short- and long-term monitoring.

Source: Loyola University Health System

Source: Brain surgery helps remove scar tissue causing seizures in epilepsy patients

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