Epileptic seizure

‘Determination’ can be induced by electrical brain stimulation.

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Applying an electric current to a particular part of the brain makes people feel a sense of determination, say researchers

The men were having a routine procedure to locate regions in their brains that caused epileptic seizures when they felt their heart rates rise, a sense of foreboding, and an overwhelming desire to persevere against a looming hardship.

The remarkable findings could help researchers develop treatments fordepression and other disorders where people are debilitated by a lack of motivation.

One patient said the feeling was like driving a car into a raging storm. When his brain was stimulated, he sensed a shaking in his chest and a surge in his pulse. In six trials, he felt the same sensations time and again.

Comparing the feelings to a frantic drive towards a storm, the patient said: “You’re only halfway there and you have no other way to turn around and go back, you have to keep going forward.”

When asked by doctors to elaborate on whether the feeling was good or bad, he said: “It was more of a positive thing, like push harder, push harder, push harder to try and get through this.”

A second patient had similar feelings when his brain was stimulated in the same region, called the anterior midcingulate cortex (aMCC). He felt worried that something terrible was about to happen, but knew he had to fight and not give up, according to a case study in the journal Neuron.

Both men were having an exploratory procedure to find the focal point in their brains that caused them to suffer epileptic fits. In the procedure, doctors sink fine electrodes deep into different parts of the brain and stimulate them with tiny electrical currents until the patient senses the “aura” that precedes a seizure. Often, seizures can be treated by removing tissue from this part of the brain.

“In the very first patient this was something very unexpected, and we didn’t report it,” said Josef Parvizi at Stanford University in California. But then I was doing functional mapping on the second patient and he suddenly experienced a very similar thing.”

“Its extraordinary that two individuals with very different past experiences respond in a similar way to one or two seconds of very low intensity electricity delivered to the same area of their brain. These patients are normal individuals, they have their IQ, they have their jobs. We are not reporting these findings in sick brains,” Parvizi said.

The men were stimulated with between two and eight milliamps of electrical current, but in tests the doctors administered sham stimulation too. In the sham tests, they told the patients they were about to stimulate the brain, but had switched off the electical supply. In these cases, the men reported no changes to their feelings. The sensation was only induced in a small area of the brain, and vanished when doctors implanted electrodes just five millimetres away.

Parvizi said a crucial follow-up experiment will be to test whether stimulation of the brain region really makes people more determined, or simply creates the sensation of perseverance. If future studies replicate the findings, stimulation of the brain region – perhaps without the need for brain-penetrating electrodes – could be used to help people with severe depression.

The anterior midcingulate cortex seems to be important in helping us select responses and make decisions in light of the feedback we get. Brent Vogt, a neurobiologist at Boston University, said patients with chronic pain and obsessive-compulsive disorder have already been treated by destroying part of the aMCC. “Why not stimulate it? If this would enhance relieving depression, for example, let’s go,” he said.

FDA Approves Implantable Neurostimulator for Epilepsy.

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The US Food and Drug Administration (FDA) today approved an implantable neurostimulator to reduce the frequency of seizures in patients with epilepsy whose condition is not successfully managed with medication.

The device, called the RNS System (Neuropace, Inc), detects abnormal electrical activity and delivers a remedial dose of electricity before the patient experiences seizures. It contrasts with neurostimulators for other conditions that provide continuous or scheduled stimulation.

The RNS System is implanted inside the skull under the scalp. Its 1 or 2 electrodes are situated near the patient’s seizure focus or foci in the brain.

The FDA based its decision on a clinical trial involving 191 patients with drug-resistant epilepsy who received the implanted device. However, the device was turned on in only half the patients. After 3 months, patients with activated neurostimulators experienced almost a median 34% reduction in the average number of seizures per month. For patients with unactivated devices, the median reduction was 19%. Twenty-nine percent of patients with activated devices had at least a 50% reduction in the overall number of seizures, compared with 27% with turned-off devices.

In February, a 13-member FDA advisory panel recommended approval of the RNS System. The majority of panelists found that the device beneficial, and that the benefits outweighed the risks. There was unanimous agreement that the RNS System was safe.

Implant site infection and premature battery depletion were the most common adverse events reported during the clinical trials.

The FDA cautioned that patients with the RNS System must avoid MRI procedures, diathermy procedures, electroconvulsive therapy, and transcranial magnetic stimulation.

“The energy created from these procedures can be sent through the neurostimulator and cause permanent brain damage, even if the device is turned off,” the agency said in a news release.

Vagus Nerve Stimulation for Children With Epilepsy.

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The Vagus Nerve Stimulator

The first vagus nerve stimulator (VNS) was implanted in 1988.[1]Since then, more than 70,000 have been implanted for epilepsy worldwide.[2]

The VNS consists of a generator, typically implanted in the chest, and an electrode surgically fastened to the left vagus nerve. In addition, an external handheld magnet may be used if the patient senses an aura or to stop a seizure already in progress.

US Food and Drug Administration Approval

In 1997, VNS received US Food and Drug Administration (FDA) approval for the adjunctive treatment of refractory seizures in patients older than 12 years.[3] In 2005, the VNS was approved for the treatment of chronic or recurrent depression in patients older than 18 years.

VNS may also have a beneficial effect on mood in patients with epilepsy in addition to its antiepileptic effect.[1] The mechanism of action of VNS is uncertain, but may be related to metabolic activation of brain stem, limbic, or thalamic structures.[4]

To date, the VNS is the only FDA-approved medical device for the treatment of epilepsy. However, other approaches, such as deep-brain stimulation of the anterior nucleus of the thalamus, responsive neurostimulation, trigeminal nerve stimulation, and transcranial magnetic stimulation, are in development.

Phase 3 Trials for Epilepsy

A randomized, multicenter, clinical trial (Study E03) of 114 patients with partial seizures demonstrated a mean seizure reduction of 31% and a 50% seizure reduction in 39% of patients.[5] A second randomized trial (Study E05) of 254 patients with intractable partial seizures demonstrated an average reduction in seizure frequency of 28% in the high-stimulation group vs a 15% reduction in the low-stimulation (pseudo-placebo) group (P = .04).[4] These results are modest, but similar to those obtained with new antiepileptic drugs in phase 3 trials. Unlike antiepileptic drugs, VNS efficacy appears to improve over time.[3]

Adverse Effects of VNS

Compared with antiepileptic drugs, VNS has a completely different side effect profile. Adverse effects are related to the surgical implantation of the generator, which may result in discomfort and deep or superficial infection. The lead attached to the vagus nerve is subject to breakage. In addition, the electrical stimulation in the neck may be uncomfortable and result in cough, hoarseness, or a feeling of shortness of breath.[4] On the other hand, VNS does not cause sedation or adverse cognitive effects, which are often limiting factors with antiepileptic drug treatment.[6]

Magnet Activation of VNS

Neurostimulation by the VNS occurs at prespecified, continuous intervals (eg, 30 seconds on, 5 minutes off). In addition, the patient may trigger additional stimulation on demand by holding a magnet over the implanted device. Magnet-activated stimulation may abort, diminish, or terminate a seizure.

A retrospective analysis of seizure data collected from the E03 trial demonstrated an increased likelihood of improved seizure control (aborted and decreased) after magnet activation (P = .0479). In the E04 trial, 31% of patients were able to diminish seizures and 22% of patients terminated seizures, but 47% reported no effect with the magnet.[1] The magnet may offer psychological benefits to patients by providing some sense of control over seizures when they occur.[1]

Personal Experience

Years ago, I enrolled 5 of my patients with intractable epilepsy in the open-label E04 VNS safety trial. None of the patients became seizure-free, although as a group they experienced a modest benefit in seizure reduction. One college student did not like the stimulator and insisted that it be removed, even though he had not allowed adequate time for us to assess its therapeutic effects. The other 4 patients continued to use the VNS.

Source: Medscape.com

Add-on Eslicarbazepine Reduces Partial-Onset Seizures.

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Once-daily adjunctive therapy with eslicarbazepine significantly reduced the frequency of partial-onset seizures in adult patients compared with adding a placebo, and the effect was sustained out to 1 year. In an analysis of pooled data from 3 phase-3 pivotal trials, doses of 800 mg and 1200 mg were well tolerated.

Eslicarbazepine is an oral drug that stabilizes the inactive state of voltage-gated sodium channels and blocks T-type voltage-gated calcium channels.

Patrício Soares-da-Silva, MD, PhD, head of research and development at BIAL in S. Mamede do Coronado, Portugal, the developer of the drug, presented trial results here at the XXI World Congress of Neurology (WCN).

The 3 trials had slight variations in protocols, but in general involved an 8-week observation or single-blind drug period, 2 weeks of drug titration depending on dose, a 12-week double-blind maintenance period, 4 weeks of tapering of the drug or not, and an open-label extension period. Two trials (BIA-2093-301 and 302) tested the drug at 400 mg, 800 mg, or 1200 mg daily or placebo for the maintenance period, with about 100 patients in each group. Trial BIA-2093-303 dropped the 400-mg dose (about 84 patients per group).

The pooled groups were well matched for mean age (about 37 years), sex (half were men), seizure types, duration of epilepsy (22 years), and the number of concomitant antiepileptic drugs (AEDs) they were taking. About 70% of patients in each group were receiving 2 other AEDs besides the trial drug.

Dr. Soares-da-Silva said that eslicarbazepine significantly reduced the seizure frequency in each 4-week period of the 12-week double-blind maintenance phase from 8.17 ± 0.034 with placebo (n = 279) to 6.24 ± 0.034 with 800 mg (n = 262) and to 5.95 ± 0.035 with 1200 mg (n = 253) (both P < .001 vs placebo), the primary endpoint of the trials.

The responder rate, defined as a 50% or greater reduction in seizure frequency over the 12-week period, rose from 21.5% with placebo to 36.3% with 800 mg of eslicarbazepine and 43.5% with 1200 mg.

Positive Results Continue to 1 Year

Of 857 patients completing the double-blind period, 833 entered the open-label extension phase, and 612 (73.5%) completed the full year, with a median daily dose of 800 mg. The maximum allowed dose was 1200 mg.

The drug maintained its efficacy during the open-label extension period and showed a slight rise in both the responder rate and the proportion of patients free of seizures.

Table. Eslicarbazepine Efficacy During 1-year Extension Period*

Time Period

Responder Rate (%)

Proportion of Seizure-Free Patients (%)

Weeks 5 to 16

46.1

6.3

Weeks 17 to 28

47.0

9.4

Weeks 29 to 40

48.2

10.1

Weeks 41 to 52

50.1

13.6

*Median eslicarbazepine dose was 800 mg.

 

Treatment with adjunctive eslicarbazepine was associated with improvements in mood and quality of life, as assessed by QOLIE-31 and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Whether patients had mild, moderate, or severe symptoms, all those who improved had improved significantly at the final assessment compared with baseline (all P < .001).

On the basis of the results of the pivotal trials, Dr. Soares-da-Silva said the European Medicines Agency approved eslicarbazepine for use in Europe as adjunctive therapy for adults with partial-onset seizures. It has not been approved in the United States, but he noted it is now undergoing trials in the United States as monotherapy.

Monotherapy Trials

Topline results of 2 phase 3 monotherapy trials of eslicarbazepine were just reported by Sunovion Pharmaceuticals. In both trials the drug met the primary endpoints.

Treatment was well tolerated and demonstrated seizure control rates superior to those among historical controls in adult patients with partial-onset seizures with or without secondary generalization who were not well controlled with current antiepileptic drugs, a statement from Sunovion released September 17 notes.

The agent is under review by the US Food and Drug Administration (FDA) as a once-daily adjunctive therapy for partial-onset seizures in patients aged 18 years or older with epilepsy.

“Pending the outcome of FDA review of the current New Drug Application (NDA) resubmission for eslicarbazepine acetate as an adjunctive treatment, Sunovion plans to submit these data as part of a supplemental NDA in support of a monotherapy indication,” Fred Grossman, DO, senior vice president, clinical development and medical affairs at Sunovion, said in the company’s statement.

The phase 3 studies, dubbed 093-045 and 093-046, were double-blind, historical-controlled, randomized trials with identical designs. Study 093-045 included 193 patients from 67 study centers in North America, and study 093-046 included 172 patients from 41 centers in 5 countries.

The primary endpoint of both studies was the proportion of patients meeting predefined exit criteria, “signifying worsening seizure control,” the statement notes, 16 weeks after titration compared with historical controls.

In both studies, adults with partial-onset seizures that were not well controlled, defined as 4 or more partial-onset seizures in the 8 weeks before screening and no 4-week seizure-free period, with 1 to 2 AEDs, were gradually converted to monotherapy treatment with eslicarbazepine. They were then randomly assigned in a 1:2 ratio to receive 1200 or 1600 mg of eslicarbazepine daily.

Detailed results from the 2 monotherapy studies will be presented at upcoming scientific meetings, the company notes.

Difference Debated?

Asked to comment about what eslicarbazepine may add to the AED armamentarium as adjunctive therapy, session chair Reeta Kälviäinen, MD, from the Kuopio Epilepsy Center, and professor of clinical epileptology at the University of Eastern Finland in Kupio, told Medscape Medical News that it is something of a debate at the moment whether eslicarbazepine differs significantly from oxcarbazepine.

“It’s a metabolite of oxcarbazepine, and we think at the moment that it might have a little bit less adverse effects than oxcarbazepine, less hyponatremia and less idiosynchrous reactions,” she said. “And we hope that therefore it would be better tolerated, perhaps as carbamazepine, as effective as oxcarbazepine, and then you can dose it once daily, which is a benefit.”

She said that she was “a little bit disappointed” that the study did not show which AEDs eslicarbazepine might be best used with but that current studies and clinical practice may reveal the better combinations. But for now, “definitely you shouldn’t add it on top of other sodium channel blockers. That’s not the way to use it,” because of additive adverse effects.

Similarly, if a patient has problems while receiving carbamazepine or oxcarbazepine, switching to eslicarbazepine would be a bad idea. “It’s nearly the same drug, so that’s a dangerous situation. So that’s a contraindication,” Dr. Kälviäinen noted. She said clinicians are now “a little bit mixed up” in choosing among these similar drugs, and clearer studies on the differences among them are needed.

Otto Muzik, PhD, a professor of radiology and pediatrics at Wayne State Medical School in Detroit, Michigan, questioned the value of adding another drug in this same class.

“It’s still not approved in the States, and it appears to me that the FDA does not believe that there is added value,” he mentioned to Medscape Medical News. “So that means that…it’s probably going to do better than a placebo, but if you now say, ‘Give me the best combined therapy of drugs,’ and now we throw in this new drug, is it more efficacious or not, and the jury seems to be still out on that.”

Method of recording brain activity could lead to mind-reading devices.

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A brain region activated when people are asked to perform mathematical calculations in an experimental setting is similarly activated when they use numbers — or even imprecise quantitative terms, such as “more than”— in everyday conversation, according to a study by Stanford University School of Medicine scientists.

Using a novel method, the researchers collected the first solid evidence that the pattern of brain activity seen in someone performing a mathematical exercise under experimentally controlled conditions is very similar to that observed when the person engages in quantitative thought in the course of daily life. 

“We’re now able to eavesdrop on the brain in real life,” said Josef Parvizi, MD, PhD, associate professor of neurology and neurological sciences and director of Stanford’s Human Intracranial Cognitive Electrophysiology Program. Parvizi is the senior author of the study, published Oct. 15 in Nature Communications. The study’s lead authors are postdoctoral scholar Mohammad Dastjerdi, MD, PhD, and graduate student Muge Ozker.

The finding could lead to “mind-reading” applications that, for example, would allow a patient who is rendered mute by a stroke to communicate via passive thinking. Conceivably, it could also lead to more dystopian outcomes: chip implants that spy on or even control people’s thoughts.

“This is exciting, and a little scary,” said Henry Greely, JD, the Deane F. and Kate Edelman Johnson Professor of Law and steering committee chair of the Stanford Center for Biomedical Ethics, who played no role in the study but is familiar with its contents and described himself as “very impressed” by the findings. “It demonstrates, first, that we can see when someone’s dealing with numbers and, second, that we may conceivably someday be able to manipulate the brain to affect how someone deals with numbers.”

The researchers monitored electrical activity in a region of the brain called the intraparietal sulcus, known to be important in attention and eye and hand motion. Previous studies have hinted that some nerve-cell clusters in this area are also involved in numerosity, the mathematical equivalent of literacy. 

However, the techniques that previous studies have used, such as functional magnetic resonance imaging, are limited in their ability to study brain activity in real-life settings and to pinpoint the precise timing of nerve cells’ firing patterns. These studies have focused on testing just one specific function in one specific brain region, and have tried to eliminate or otherwise account for every possible confounding factor. In addition, the experimental subjects would have to lie more or less motionless inside a dark, tubular chamber whose silence would be punctuated by constant, loud, mechanical, banging noises while images flashed on a computer screen.

“This is not real life,” said Parvizi. “You’re not in your room, having a cup of tea and experiencing life’s events spontaneously.” A profoundly important question, he said, is: “How does a population of nerve cells that has been shown experimentally to be important in a particular function work in real life?” 

His team’s method, called intracranial recording, provided exquisite anatomical and temporal precision and allowed the scientists to monitor brain activity when people were immersed in real-life situations. Parvizi and his associates tapped into the brains of three volunteers who were being evaluated for possible surgical treatment of their recurring, drug-resistant epileptic seizures.

The procedure involves temporarily removing a portion of a patient’s skull and positioning packets of electrodes against the exposed brain surface. For up to a week, patients remain hooked up to the monitoring apparatus while the electrodes pick up electrical activity within the brain. This monitoring continues uninterrupted for patients’ entire hospital stay, capturing their inevitable repeated seizures and enabling neurologists to determine the exact spot in each patient’s brain where the seizures are originating.

During this whole time, patients remain tethered to the monitoring apparatus and mostly confined to their beds. But otherwise, except for the typical intrusions of a hospital setting, they are comfortable, free of pain and free to eat, drink, think, talk to friends and family in person or on the phone, or watch videos.

The electrodes implanted in patients’ heads are like wiretaps, each eavesdropping on a population of several hundred thousand nerve cells and reporting back to a computer.

In the study, participants’ actions were also monitored by video cameras throughout their stay. This allowed the researchers later to correlate patients’ voluntary activities in a real-life setting with nerve-cell behavior in the monitored brain region. 

As part of the study, volunteers answered true/false questions that popped up on a laptop screen, one after another. Some questions required calculation — for instance, is it true or false that 2+4=5? — while others demanded what scientists call episodic memory — true or false: I had coffee at breakfast this morning. In other instances, patients were simply asked to stare at the crosshairs at the center of an otherwise blank screen to capture the brain’s so-called “resting state.”

Consistent with other studies, Parvizi’s team found that electrical activity in a particular group of nerve cells in the intraparietal sulcus spiked when, and only when, volunteers were performing calculations.

Afterward, Parvizi and his colleagues analyzed each volunteer’s daily electrode record, identified many spikes in intraparietal-sulcus activity that occurred outside experimental settings, and turned to the recorded video footage to see exactly what the volunteer had been doing when such spikes occurred.

They found that when a patient mentioned a number — or even a quantitative reference, such as “some more,” “many” or “bigger than the other one” — there was a spike of electrical activity in the same nerve-cell population of the intraparietal sulcus that was activated when the patient was doing calculations under experimental conditions. 

That was an unexpected finding. “We found that this region is activated not only when reading numbers or thinking about them, but also when patients were referring more obliquely to quantities,” said Parvizi.

“These nerve cells are not firing chaotically,” he said. “They’re very specialized, active only when the subject starts thinking about numbers. When the subject is reminiscing, laughing or talking, they’re not activated.” Thus, it was possible to know, simply by consulting the electronic record of participants’ brain activity, whether they were engaged in quantitative thought during nonexperimental conditions.

Any fears of impending mind control are, at a minimum, premature, said Greely. “Practically speaking, it’s not the simplest thing in the world to go around implanting electrodes in people’s brains. It will not be done tomorrow, or easily, or surreptitiously.”

Parvizi agreed. “We’re still in early days with this,” he said. “If this is a baseball game, we’re not even in the first inning. We just got a ticket to enter the stadium.”

– See more at: http://med.stanford.edu/ism/2013/october/parvizi.html#sthash.bBfPaTiH.dpuf

Epilepsy Risk for Men Reduced with Exercise.

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Story at-a-glance

  • Men who had a high level of fitness when they were young were 79 percent less likely to develop epilepsy later in life compared to those with low fitness levels
  • Compared to young men with average fitness levels, the high-fitness group was still 36 percent less likely to develop epilepsy
  • Exercise may protect the brain and create a stronger brain reserve, which may reduce epilepsy risk
  • If you have epilepsy, exercising may help to reduce the frequency of seizures.

 

The next time you work out, take a moment to think about all of the wonderful ways it is benefitting your body. And I’m not only talking about your muscles or your six-pack abs… I’m referring to you brain.

Exercise is emerging as a key player in brain health at various stages of life and has been shown to prevent cognitive decline, moderate brain damage caused by drinking and even lower your risk of brain diseases like Alzheimer’s. Now, researchers have uncovered yet another brain benefit of exercise – a reduced risk of epilepsy.

Vigorous Exercise May Reduce Epilepsy Risk by Up to 80 Percent

In a study involving more than 1.1 million men who were followed for an average of 25 years, those who had a high level of fitness when they were young were 79 percent less likely to develop epilepsy later in life compared to those with low fitness levels.1

Compared to young men with average fitness levels, the high-fitness group was still 36 percent less likely to develop epilepsy. This is the first study in humans to reveal that exercise may impact epilepsy risk. One of the study’s researchers noted:2

“Exercise may affect epilepsy risk in two ways. It may protect the brain and create stronger brain reserve, or it may simply be that people who are fit early in life tend to also be fit later in life, which in turn affects disease risk.”

Exercise May Reduce Seizure Frequency in People with Epilepsy

Epilepsy is a neurological disorder involving disturbed nerve cell activity in your brain. This results in seizures that may include a staring spell, confusion, uncontrollable jerking movements and loss of consciousness or awareness. Obviously, this presents risks of falls and injuries that may occur if you have a seizure while driving or even exercising.

For this reason, people with epilepsy have previously been discouraged from participating in physical activity, and this stigma remains today even though medical recommendations have long since changed.

Now, exercise is highly recommended for people with epilepsy, for starters because it helps to reduce stress levels, which can sometimes trigger seizures. In fact, physical activity has been shown to decrease seizure frequency,3 as well as lead to improved cardiovascular and psychological health in people with epilepsy.4

Tips for Exercising if You Have Seizures

If you have epilepsy, make sure you exercise with a buddy or a personal trainer who knows what to do if you have a seizure. A medical alert bracelet can also be worn.

Try to exercise in a safe area, such as a grassy field or on a gym mat, and wear elbow and knee pads. If you’ll be swimming, be sure you wear a life vest and never go swimming alone (a strong swimmer should be with you at all times in case you need help).

If you’ll be exercising on a bicycle, stay away from busy streets (and wear a helmet)… likewise if you’ll be hiking — stick to simpler trails, not those with steep drop-offs or cliffs. If you have epilepsy, you’ll need to take special care during activities that pose a risk of a blow to your head, such as football; if you do engage in such sports be sure to wear a helmet.

Generally speaking, however, you can exercise normally if you have epilepsy, but do use commonsense precautions – avoid getting over-tired or overheated, and avoid exercising when it’s very hot. As an aside, if you have epilepsy, be sure to get your vitamin D levels checked. When epileptic patients improved their vitamin D levels, their seizures were reduced by an average of 40 percent in one study.5

What Else Can Exercise Do for Your Brain?

Along with potentially reducing your risk for epilepsy quite significantly, scientific evidence shows that physical exercise helps you build a brain that not only resists shrinkage, but also increases cognitive abilities.6 In one review of more than 100 studies, both aerobic and resistance training were found to be important for maintaining cognitive and brain health in old age.7 Moderate exercise may even reverse normal brain shrinkage by 2 percent, effectively reversing age-related hippocampus degeneration, which is associated with dementia and poor memory, by one to two years.8

Not to mention, other contributing factors to brain disease caused by the normal aging process may also include a decrease in blood flow to your brain, and the accumulation of environmental toxins in your brain. Exercise can help ameliorate both of these conditions by increasing blood flow to your brain, thereby increasing oxygen supply to your brain and encouraging a more vigorous release and removal of accumulated toxins through better blood circulation.

You’ve Got to Move It… Or You Might Lose It

If you work out religiously for three months, then suddenly stop for an extended period, your muscle tone will definitely suffer. This is one of the more obvious examples that your body is designed for regular exercise, not sporadic or infrequent activity.

Likewise, research suggests that the brain benefits of exercise also quickly fade if your exercise program stops. The silver lining is that the opposite also appears to hold true. While the benefits of exercise might fade fast, they can also be achieved relatively quickly.

Exercising – even briefly – can change your DNA in a way that readies your body for increased muscle strength and fat burning. It also boosts your natural human growth hormone (HGH) production, which is important for maintaining muscle mass as you age. If you’re approaching middle-age or beyond, you might be thinking that it’s too late for you to get in shape, but this is not the case. Remember, you are never too old to start exercising and start reaping the mental and physical benefits that physical activity has to offer.

 

If you have epilepsy and are unable to control the seizures, or have refractory epilepsy – or know someone who is affected – please view the video above, which is my interview with Dr. Thomas Seyfried about the ketogenic diet. The ketogenic diet has been used for managing seizures for quite some time, and is now recognized as an important component for the management of refractory seizures in children. A ketogenic diet calls for eliminating all but non-starchy vegetable carbohydrates, and replacing them with healthy fats and high-quality protein.

Eating this way will help you convert from carb-burning mode to fat burning, as well, so it provides many benefits beyond seizure control. According to Dr. Seyfried, the mechanism by which the ketogenic diet manages seizures is not clear, but the results speak for themselves. You can learn more about the ketogenic diet here.

Want to Boost Your Brainpower? Try This Exercise ‘Prescription’

The more active you stay, the better your brain (and overall health) is likely to be. This includes not only specifically engaging in exercise and other physically demanding activities but also making an effort to sit less. To get all the benefits exercise has to offer, you’ll want to strive for a varied and well-rounded fitness program that incorporates a variety of exercises. I recommend incorporating the following types of exercise into your program:

    • High-Intensity Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercisewith gentle recovery periods. The HIIT approach I personally prefer and recommend is the Peak Fitness method of 30 seconds of maximum effort followed by 90 seconds of recuperation.

I personally modified the number of repetitions from 8 to 6 this year, as it was sometimes just too strenuous for me to do all 8. So by listening to my body and cutting it back to 6 reps, I can now easily tolerate the workout and go full out. You can see a demonstration of Peak Fitness in the video I did.

    • Strength Training: If you want, you can increase the intensity by slowing it down. You need enough repetitions to exhaust your muscles. The weight should be heavy enough that this can be done in fewer than 12 repetitions, yet light enough to do a minimum of four repetitions. It is also important NOT to exercise the same muscle groups every day. They need at least two days of rest to recover, repair and rebuild. For more information about using super slow weight training as a form of HIIT, please see my interview with Dr. Doug McGuff.
    • Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability.

Exercise programs like Pilates, yoga and Foundation Training are great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.

    • Stretching: My favorite type of stretching is Active Isolated Stretching (AIS) developed by Aaron Mattes. With AIS, you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.
    • Non-Exercise Activity: One of the newest recommendations I have is based on information from NASA scientist Dr. Joan Vernikos, who I recently interviewed: simply set a timer when you are sitting and stand up every 10 minutes. I even modify this further by doing jump squats at times in addition to standing up. This will help counteract the dangerous consequences of excessive sitting.

Going to the gym a few times a week for an hour simply isn’t going to counteract hours upon hours of chronic uninterrupted sitting, which essentially mimics a microgravity situation, i.e. you’re not exerting your body against gravity. Only frequent non-exercise movement will do that. The key point is to move and shift position often, when you’re sitting down. Meaning, you want to interrupt your sitting as often as possible.

Poststroke Seizures.

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Stroke is the most common cause of seizures in the elderly, and seizures are among the most common neurologic sequelae of stroke. About 10% of all stroke patients experience seizures, from stroke onset until several years later. This review discusses current understanding of the epidemiology, pathogenesis, classification, clinical manifestations, diagnostic studies, differential diagnosis, and management issues of seizures associated with various cerebrovascular lesions, with a focus on anticonvulsant use in the elderly.

Poststroke seizures are a common and treatable phenomenon, whereas the development of epilepsy is relatively rare. Cerebrovascular lesions associated with the development of seizures include the following: intracerebral (parenchymal) and subarachnoid hemorrhage and cerebral venous thrombosis, with or without venous infarction; lesions involving the cerbral cortex; larger neurologic deficits or disability at presentation; and revascularization procedures involving the extracranial internal carotid artery. The treatment of poststroke seizures is no different than the approach to treatment of partial-onset seizures due to other cerebral lesions, and poststroke seizures usually respond well to a single antiepileptic drug. Given their tolerability, the newer generations of anticonvulsant agents hold promise in treating older patients. Given the low incidence of poststroke epilepsy, there is no indication for seizure prophylaxis in patients with acute ischemic stroke who have not had a well-documented first event. The need for chronic anticonvulsant use should be evaluated periodically, perhaps every 6 months. Despite the absence of clinical data documenting effectiveness, most patients presenting with intracerebral or subarachnoid hemorrhage should receive short-term antiepileptic prophylaxis.45– 46

Future areas of research regarding poststroke seizures include assessing their impact on initial lesion size and on delayed patient outcomes, determining the appropriateness of chronic antiepileptic therapy after a single seizure, and establishing risk factors for the reperfusion syndrome. Poststroke epilepsy may also become an important basic model in research that aims to prevent the transformation of injured cerebral tissue into an epileptic focus.

 

Source: JAMA

 

P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study.

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Background

Studies in rodent models of epilepsy suggest that multidrug efflux transporters at the blood—brain barrier, such as P-glycoprotein, might contribute to pharmacoresistance by reducing target-site concentrations of antiepileptic drugs. We assessed P-glycoprotein activity in vivo in patients with temporal lobe epilepsy.

Methods

We selected 16 patients with pharmacoresistant temporal lobe epilepsy who had seizures despite treatment with at least two antiepileptic drugs, eight patients who had been seizure-free on antiepileptic drugs for at least a year after 3 or more years of active temporal lobe epilepsy, and 17 healthy controls. All participants had a baseline PET scan with the P-glycoprotein substrate (R)-[11C]verapamil. Pharmacoresistant patients and healthy controls then received a 30-min infusion of the P-glycoprotein-inhibitor tariquidar followed by another (R)-[11C]verapamil PET scan 60 min later. Seizure-free patients had a second scan on the same day, but without tariquidar infusion. Voxel-by-voxel, we calculated the (R)-[11C]verapamil plasma-to-brain transport rate constant, K1 (mL/min/cm3). Low baseline K1 and attenuated K1 increases after tariquidar correspond to high P-glycoprotein activity.

Findings

Between October, 2008, and November, 2011, we completed (R)-[11C]verapamil PET studies in 14 pharmacoresistant patients, eight seizure-free patients, and 13 healthy controls. Voxel-based analysis revealed that pharmacoresistant patients had lower baseline K1, corresponding to higher baseline P-glycoprotein activity, than seizure-free patients in ipsilateral amygdala (0·031 vs 0·036 mL/min/cm3; p=0·014), bilateral parahippocampus (0·032 vs 0·037; p<0·0001), fusiform gyrus (0·036 vs 0·041; p<0·0001), inferior temporal gyrus (0·035 vs 0·041; p<0·0001), and middle temporal gyrus (0·038 vs0·044; p<0·0001). Higher P-glycoprotein activity was associated with higher seizure frequency in whole-brain grey matter (p=0·016) and the hippocampus (p=0·029). In healthy controls, we noted a 56·8% increase of whole-brain K1 after 2 mg/kg tariquidar, and 57·9% for 3 mg/kg; in patients with pharmacoresistant temporal lobe epilepsy, whole-brain K1 increased by only 21·9% for 2 mg/kg and 42·6% after 3 mg/kg. This difference in tariquidar response was most pronounced in the sclerotic hippocampus (mean 24·5% increase in patients vs mean 65% increase in healthy controls, p<0·0001).

Interpretation

Our results support the hypothesis that there is an association between P-glycoprotein overactivity in some regions of the brain and pharmacoresistance in temporal lobe epilepsy. If this relation is confirmed, and P-glycoprotein can be identified as a contributor to pharmacoresistance, overcoming P-glycoprotein overactivity could be investigated as a potential treatment strategy.

Source: Lancet

Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy..

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To explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial.

METHODS: This is a double-blind randomized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.
RESULTS: At entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of epilepsy of 21.5 years (treatment group) and 23.7 years (active control group), respectively. eTNS was well-tolerated. Side effects included anxiety (4%), headache (4%), and skin irritation (14%). The responder rate, defined as >50% reduction in seizure frequency, was 30.2% for the treatment group vs 21.1% for the active control group for the 18-week treatment period (not significant, p = 0.31, generalized estimating equation [GEE] model). The treatment group experienced a significant within-group improvement in responder rate over the 18-week treatment period (from 17.8% at 6 weeks to 40.5% at 18 weeks, p = 0.01, GEE). Subjects in the treatment group were more likely to respond than patients randomized to control (odds ratio 1.73, confidence interval 0.59-0.51). eTNS was associated with reductions in seizure frequency as measured by the response ratio (p = 0.04, analysis of variance [ANOVA]), and improvements in mood on the Beck Depression Inventory (p = 0.02, ANOVA).
CONCLUSIONS: This study provides preliminary evidence that eTNS is safe and may be effective in subjects with DRE. Side effects were primarily limited to anxiety, headache, and skin irritation. These results will serve as a basis to inform and power a larger multicenter phase III clinical trial. CLASSIFICATION OF EVIDENCE: This phase II study provides Class II evidence that trigeminal nerve stimulation may be safe and effective in reducing seizures in people with DRE.

Source: Neurology

When Should a Patient Be Referred for Epilepsy Surgery Evaluation?

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A new Web-based tool is available to help clinicians decide when to refer a patient for evaluation.

Evidence suggests that the low rate of referral for epilepsy surgery evaluation is in part caused by clinicians’ doubts about patient eligibility. To improve the rate of appropriate referrals, researchers have now developed and tested a Web-based decision-making tool.

A clinician panel that included epilepsy specialists and general neurologists surveyed the literature to identify eligibility criteria for entrance into epilepsy surgery studies, which they used to create a systematic, stepwise decision-making tool. The criteria were based on magnetic resonance imaging and electroencephalography findings, frequency of disabling seizures, presence of adverse effects related to antiepileptic drug (AED) use, and number of AEDs tried. The panel then used the tool to rate 2646 clinical scenarios as “appropriate,” “inappropriate,” or “uncertain” to refer the described patient for epilepsy surgery evaluation. The reviewers rated 62% of scenarios as inappropriate for surgery evaluation referral, 21% as appropriate, and 17% as uncertain. The reviewers disagreed in only 0.8% of cases, all of which involved either incomplete clinical investigations or nondisabling seizures. The Web-based tool is published at www.epilepsycases.com.

Comment: The panel developed this tool because of the persistent, frustrating absence of improvement in the relative number and timely referral of appropriate candidates for epilepsy surgery evaluation, despite decades of accumulating evidence and excellent guidelines supporting the efficacy and relatively low risks of epilepsy surgery. Astonishingly, time to surgical evaluation and treatment for adults remains approximately 20 years (CNS Spectr 2004; 9:136).

Regardless of any limitations in the data and methods used to develop this tool, it can aid in changing practice. Notably, the authors used only variables important in considering referral for epilepsy surgery evaluation, not the more extensive data points necessary for determining actual surgery candidacy. As the authors emphasize, the tool must be validated and, most importantly, updated as new pertinent knowledge becomes available. This should not be difficult, and the tool is easy to use. The challenge will be making target physicians aware of the tool and its importance.

Source: Journal Watch Neurology