EEG Identifies Seizures in Hospital Patients

Electroencephalogram (EEG), which measures and records electrical activity in the brain, is a quick and efficient way of determining whether seizures are the cause of altered mental status (AMS) and spells, according to a study by scientists at the UC San Francisco.

The research, which focused on patients who had been given an EEG after being admitted to the hospital for symptoms such as AMS and spells, appears on March 27 in Mayo Clinic Proceedings.

“We have demonstrated a surprisingly high frequency of seizures – more than 7 percent – in a general inpatient population,” said senior investigator John Betjemann, MD, a UCSF assistant professor of neurology. “This tells us that EEG is an underutilized diagnostic tool, and that seizures may be an underappreciated cause of spells and AMS.”

The results are important, he said, because EEG can identify treatable causes of AMS or spells, and because “it can prompt the physician to look for an underlying reason for seizures in persons who did previously have them.”

Seizures are treatable with a number of FDA-approved anticonvulsants, he said, “so patients who are quickly diagnosed can be treated more rapidly and effectively. This may translate to shorter lengths of stay and improved patient outcomes.”

In one of the first studies of its kind, Betjemann and his team analyzed the medical records of 1,048 adults who were admitted to a regular inpatient unit of a tertiary care hospital and who underwent an EEG. They found that 7.4 percent of the patients had a seizure of some kind while being monitored.

“As I tell my patients, seizures come in all different flavors, from a dramatic convulsion to a subtle twitching of the face or hand or finger,” said Betjemann. “There might be no outward manifestation at all, other than that the person seems a little spacey. It’s easily missed by family members and physicians alike, but can be picked up by EEG.”

Another 13.4 percent of patients had epileptiform discharges, which are abnormal patterns that indicate patients are at an increased risk of seizures.

Almost 65 percent of patients had their first seizure within one hour of EEG recording, and 89 percent within six hours.

“This is good news for smaller hospitals that don’t have 24 hour EEG coverage, but that do have a technician on duty during the day,” Betjemann said.

He speculated that lack of 24-hour coverage is a major reason that EEG is not used as an inpatient diagnostic tool as often as it might be. “This paper shows that, fortunately, it’s not necessary. Almost two thirds of patients with seizures can be identified in the first hour, and almost 90 percent in the course of a shift.”

EEGs are easy to obtain, painless and noninvasive, said Betjemann. “The technician applies some paste and electrodes and hooks up the machine. All the patient has to do is rest in bed.”

Betjemann said that the next logical research step would be a prospective study. “We have to start at the beginning, see if patients are altered when they are admitted, and do an EEG in a formal standardized setting. Then we’d want to see how often EEG is changing the management of patients – either starting or stopping medications,” he said. “A patient may be having spells, and an EEG might tell you this is not a seizure, and that it’s important not to treat it with anti-epileptic medications.”

(Image: Rex Features)

Cooling may prevent trauma-induced epilepsy

In the weeks, months and years after a severe head injury, patients often experience epileptic seizures that are difficult to control. A new study in rats suggests that gently cooling the brain after injury may prevent these seizures.

“Traumatic head injury is the leading cause of acquired epilepsy in young adults, and in many cases the seizures can’t be controlled with medication,” says senior author Matthew Smyth, MD, associate professor of neurological surgery and of pediatrics at Washington University School of Medicine in St. Louis. “If we can confirm cooling’s effectiveness in human trials, this approach may give us a safe and relatively simple way to prevent epilepsy in these patients.”

The researchers reported their findings in Annals of Neurology.

Cooling the brain to protect it from injury is not a new concept. Cooling slows down the metabolic activity of nerve cells, and scientists think this may make it easier for brain cells to survive the stresses of an injury. 

Doctors currently cool infants whose brains may have had inadequate access to blood or oxygen during birth. They also cool some heart attack patients to reduce peripheral brain damage when the heart stops beating.

Smyth has been exploring the possibility of using cooling to prevent seizures or reduce their severity.

“Warmer brain cells seem to be more electrically active, and that may increase the likelihood of abnormal electrical discharges that can coalesce to form a seizure,” Smyth says. “Cooling should have the opposite effect.”

Smyth and colleagues at the University of Washington and the University of Minnesota test potential therapies in a rat model of brain injury. These rats develop chronic seizures weeks after the injury.

Researchers devised a headset that cools the rat brain. They were originally testing its ability to stop seizures when they noticed that cooling seemed to be not only stopping but also preventing seizures.

Scientists redesigned the study to focus on prevention. Under the new protocols, they put headsets on some of the rats that cooled their brains by less than 4 degrees Fahrenheit. Another group of rats wore headsets that did nothing. Scientists who were unaware of which rats they were observing monitored them for seizures during treatment and after the headsets were removed.

Rats that wore the inactive headset had progressively longer and more severe seizures weeks after the injury, but rats whose brains had been cooled only experienced a few very brief seizures as long as four months after injury.

Brain injury also tends to reduce cell activity at the site of the trauma, but the cooling headsets restored the normal activity levels of these cells.

The study is the first to reduce injury-related seizures without drugs, according to Smyth, who is director of the Pediatric Epilepsy Surgery program at St. Louis Children’s Hospital.

“Our results show that the brain changes that cause this type of epilepsy happen in the days and weeks after injury, not at the moment of injury or when the symptoms of epilepsy begin,” says Smyth. “If clinical trials confirm that cooling has similar effects in humans, it could change the way we treat patients with head injuries, and for the first time reduce the chance of developing epilepsy after brain injury.”

Smyth and his colleagues have been testing cooling devices in humans in the operating room, and are planning a multi-institutional trial of an implanted focal brain cooling device to evaluate the efficacy of cooling on established seizures.

How Neuroscience Will Fight Five Age-Old Afflictions

SEIZURES

A device delivers targeted drugs to calm overactive neurons

For years, large clinical trials have treated people with epilepsy using so-called deep-brain stimulation: surgically implanted electrodes that can detect a seizure and stop it with an electrical jolt. The technology leads to a 69 percent reduction in seizures after five years, according to the latest results.

Tracy Cui, a biomedical engineer at the University of Pittsburgh, hopes to improve upon that statistic. Her group has designed an electrode that would deliver both an electrical pulse and antiseizure medication. “We know where we want to apply the drug,” Cui says, “so you would not need a lot of it.”

To build the device, Cui’s team immersed a metal electrode in a solution containing two key ingredients: a molecule called a monomer and the drug CNQX. Zapping the solution with electricity causes the monomers to link together and form a long chain called a polymer. Because the polymer is positively charged, it attracts the negatively charged CNQX, leaving the engineers with their target product: an electrode coated in a film that’s infused with the drug.

The researchers then placed the electrodes in a petri dish with rat neurons. Another zap of electricity disrupted the electrostatic attraction in the film, causing the polymer to release its pharmacological payload—and nearby cells to quiet their erratic firing patterns. Cui says her team has successfully repeated the experiment in living rats. Next, she’d like to test the electrodes in epileptic rats and then begin the long process of regulatory approval for human use.

The body’s blood-brain barrier protects the organ from everything but the smallest molecules, rendering most drugs ineffective. As a result, this drug-​delivery mechanism could treat other brain disorders, Cui says. The electrodes can be loaded with any kind of small drug—like dopamine or painkillers—making it useful for treating Parkinson’s disease, chronic pain, or even drug addiction.

DEMENTIA

Electrode arrays stimulate mental processing

Dementia is one of the most well-known and frustrating brain afflictions. It damages many of the fundamental cognitive functions that make us human: working memory, decision-making, language, and logical reasoning. Alzheimer’s, Huntington’s, and Parkinson’s diseases all lead to dementia, and it’s also sometimes associated with multiple sclerosis, AIDS, and the normal process of aging.

Theodore Berger, a biomedical engineer at the University of Southern California, hopes to help people stave off the symptoms of dementia with a device implanted in the brain’s prefrontal cortex, a region crucial for sophisticated cognition. He and colleagues at Wake Forest Baptist Medical Center tested the device in a study involving five monkeys and a memory game.

First the team implanted an electrode array so that it could record from layers 2/3 and 5 of the prefrontal cortex and stimulate layer 5. The neural signals that jet back and forth between these areas relate to attention and decision-making. The team then trained the monkeys to play a computer game in which they saw a cartoon picture—such as a truck, lion, or paint palette—and had to select the same image from a panel of pictures 90 seconds later.

The scientists initially analyzed the electrical signals sent between the two cortical layers when the monkeys made a correct match. In later experiments, the team caused the array to emit the same signal just before the monkey made its decision. The animals’ accuracy improved by about 10 percent. That effect may be even more profound in an impaired brain. When the monkeys played the same game after receiving a hit of cocaine, their performance dropped by about 20 percent. But electrical stimulation restored their accuracy to normal levels.

Dementia involves far more complicated circuitry than these two layers of the brain. But once scientists better understand exactly how dementia works, it may be possible to combine several implants to each target a specific region.

BLINDNESS

Gene therapy converts cells into photoreceptors, restoring eyesight

Millions of people lose their eyesight when disease damages the photoreceptor cells in their retinas. These cells, called rods and cones, play a pivotal role in vision: They convert incoming light into electrical impulses that the brain interprets as an image.

In recent years, a handful of companies have developed electrode-array implants that bypass the damaged cells. A microprocessor translates information from a video camera into electric pulses that stimulate the retina; as a result, blind subjects in clinical trials have been able to distinguish objects and even read very large type. But the implanted arrays have one big drawback: They stimulate only a small number of retinal cells—about 60 out of 100,000—which ultimately limits a person’s visual resolution.

A gene therapy being developed by Michigan-based RetroSense could replace thousands of damaged retinal cells. The company’s technology targets the layer of the retina containing ganglion cells. Normally, ganglion cells transmit the electric signal from the rods and cones to the brain. But RetroSense inserts a gene that makes the ganglion cells sensitive to light; they take over the job of the photoreceptors. So far, scientists have successfully tested the technology on rodents and monkeys. In rat studies, the gene therapy allowed the animals to see well enough to detect the edge of a platform as they neared it.

The company plans to launch the first clinical trial of the technology next year, with nine subjects blinded by a disease called retinitis pigmentosa. Unlike the surgeries to implant electrode arrays, the procedure to inject gene therapy will take just minutes and requires only local anesthesia. “The visual signal that comes from the ganglion cells may not be encoded in exactly the fashion that they’re used to,” says Peter Francis, chief medical officer of RetroSense. “But what is likely to happen is that their brain is going to adapt.”

PARALYSIS

A brain-machine interface controls limbs while sensing what they touch

Last year, clinical trials involving brain implants gave great hope to people with severe spinal cord injuries. Two paralyzed subjects imagined picking up a cup of coffee. Electrode arrays decoded those neural instructions in real time and sent them to a robotic arm, which brought the coffee to their lips.

But to move limbs with any real precision, the brain also requires tactile feedback. Miguel Nicolelis, a biomedical engineer at Duke University, has now demonstrated that brain-machine interfaces can simultaneously control motion and relay a sense of touch—at least in virtual reality.

For the experiment, Nicolelis’s team inserted electrodes in two brain areas in monkeys: the motor cortex, which controls movement, and the nearby somatosensory cortex, which interprets touch signals from the outside world. Then the monkeys played a computer game in which they controlled a virtual arm—first by using a joystick and eventually by simply imagining the movement. The arm could touch three identical-looking gray circles. But each circle had a different virtual “texture” that sent a distinct electrical pattern to the monkeys’ somatosensory cortex. The monkeys learned to select the texture that produced a treat, proving that the implant was both sending and receiving neural messages.

This year, a study in Brazil will test the ability of 10 to 20 patients with spinal cord injuries to control an exoskeleton using the implant. Nicolelis, an ardent fan of Brazilian soccer, has set a strict timetable for his team: A nonprofit consortium he created, the Walk Again Project, plans to outfit a paraplegic man with a robotic exoskeleton and take him to the 2014 World Cup in São Paulo, where he will deliver the opening kick.

DEAFNESS

Stem cells repair a damaged auditory nerve, improving hearing

Over the past 25 years, more than 30,000 people with hearing loss have received an electronic implant that replaces the cochlea, the snail-shaped organ in the inner ear whose cells transform sound waves into electrical signals. The device acts as a microphone, picking up sounds from the environment and transmitting them to the auditory nerve, which carries them on to the brain.

But a cochlear implant won’t help the 10 percent of people whose profound hearing loss is caused by damage to the auditory nerve. Fortunately for this group, a team of British scientists has found a way to restore that nerve using stem cells.

The researchers exposed human embryonic stem cells to growth factors, substances that cause them to differentiate into the precursors of auditory neurons. Then they injected some 50,000 of these cells into the cochleas of gerbils whose auditory nerves had been damaged. (Gerbils are often used as models of deafness because their range of hearing is similar to that of people.) Three months after the transplant, about one third of the original number of auditory neurons had been restored; some appeared to form projections that connected to the brain stem. The animals’ hearing improved, on average, by 46 percent.

It will be years before the technique is tested in humans. Once it is, researchers say, it has the potential to help not only those with nerve damage but also people with more widespread impairment whose auditory nerve must be repaired in order to receive a cochlear implant.

Cats and humans suffer from similar forms of epilepsy

Epilepsy arises when the brain is temporarily swamped by uncoordinated signals from nerve cells. Research at the Vetmeduni Vienna has now uncovered a cause of a particular type of epilepsy in cats. Surprisingly, an incorrectly channelled immune response seems to be responsible for the condition, which closely resembles a form of epilepsy in humans. The work is published in the current issue of the Journal of Veterinary Internal Medicine.

There is something sinister about epilepsy: the disease affects the very core of our being, our brain. Epileptic attacks can lead to seizures throughout the body or in parts of it. Clouding of consciousness or memory lapses are also possible. The causes are still only partially understood but in some cases brain tumours, infections, inflammations of the brain or metabolic diseases have been implicated.

Epilepsy is not confined to humans and many animals also suffer from it. Together with partners in Oxford and Budapest, Akos Pakozdy and his colleagues at the University of Veterinary Medicine, Vienna have managed to identify the cause of a certain form of epilepsy in cats, in which the body’s own immune system attacks particular proteins in the cell membranes of nerve cells. The symptoms include twitching facial muscles, a fixed stare, chewing motions and heavy dribbling. Based on their clinical experience, the researchers believe that this form of epilepsy is fairly widespread in cats. Interestingly, a highly similar type of epilepsy occurs in humans: an inflammation in the brain, known as limbic encephalitis, leads to epileptic seizures that generally manifest themselves in the arm and the facial muscles on only one side of the body.

Pakozdy and his colleagues have found antibodies in the blood of epileptic cats that react to proteins in the cell membranes of nerve cells. The proteins form the building blocks of ion channels that are involved in the production of nerve signals. The same ion channels are affected in the corresponding human form of epilepsy. They control the membrane’s permeability to potassium ions based on the electric potential across the membrane, thereby helping generate the rapid nerve signals of the so-called action potential.

Immunotherapy for cats?
If the immune system attacks components of these ion channels, the production of nerve signals is disrupted. There is an increased release of neurotransmitters, which leads directly to the symptoms of epilepsy. Previous work – in another group – on human patients has shown that normal anti-epilepsy medication has hardly any effect on this form of epilepsy. However, immunotherapy has proven to be relatively effective. Pakozdy’s work now shows that “limbic encephalitis in cats has the same cause as it does in humans, where the origins have been known for years. It is important that cats with epilepsy are diagnosed early, so that the correct form of therapy can be started. We believe this will dramatically increase the chances of a successful treatment. It seems as though epileptic cats might benefit from treatment with immune preparations.”

(Image: Thinkstock)

Promising new finding for therapies to treat persistent seizures in epileptic patients

In a promising finding for epileptic patients suffering from persistent seizures known as status epilepticus, researchers reported today that new medication could help halt these devastating seizures. To do so, it would have to work directly to antagonize NMDA receptors, the predominant molecular device for controlling synaptic activity and memory function in the brain.

"Despite the development of new medications to prevent seizures, status epilepticus remains a life-threatening condition that can cause extensive brain damage in the patients that survive these persistent seizures," said David E. Naylor, MD, PhD, a lead researcher at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) and corresponding author of the new study. "Our research holds promise for the development of new therapies to treat this devastating condition because we have found a potential new target for medical intervention that should bolster the current standard therapies to treat the acute seizures. It may also prevent the long-term adverse effects of persistent seizure activity on the brain."

The research, reported online in the Neurology of Disease journal, used animal models to assess cellular activity in the brain during persistent seizures. It found that the seizure activity seemed to force the NMDA receptors from the interior to the surface of nerve cells causing their activity to increase by approximately 38%.

"The increased presence of the NMDA receptors on the cell surface during these seizures may explain the successful use of NMDA antagonists – medication that inhibits the activity of the NMDA receptors in the brain – in the latter stages of a seizure, long after other medications have stopped working," said Dr. Naylor. "We concluded that medications that suppress the activity of the NMDA receptors, in conjunction with other medications, may be successful in stopping persistent seizures. Further research is, of course, needed."

Simple Innovation to Electrodes Makes a Big Difference

The electroencephalogram (EEG) for human uses has been around since 1924. Small metal discs placed along the scalp measure electrical activity in the human brain, important in diagnosing or evaluating epilepsy, sleep disorders and other conditions.

But these electrodes have changed little since their introduction, and are far from perfect. Among other things, they pick up extraneous noise and movement in addition to brain wave activity, often making the readings difficult to interpret.

Walt Besio thinks he has a better way.

The National Science Foundation-funded scientist, who is associate professor of biomedical engineering at the University of Rhode Island, has invented a new and improved electrode, one that produces a performance difference that he says is akin to “taking the rabbit ears you used to have for your television set, and converting to high definition.”

His innovation is relatively simple, but apparently makes a big difference. Besio added two new metal rings around the basic disc, a change that eliminates outside noises and improves spatial resolution.

"EEG has two main problems: It’s very noisy and contaminated with artifacts, and it’s spatial resolution is bad," he explains. "We have improved the signal-to-noise ratio. It’s four times better than it was before. Because it is now a very local signal, it means we can put electrodes closer together, which improves spatial resolution, meaning you can better determine where the signal is coming from."

The additional rings work almost like an inner tube tossed on top of a rippling body of water. “The water is flat in the center of the inner tube and choppy on the outside,” he says. “The outer rings on the electrodes behave like that inner tube.”

For researchers and clinicians, having improved electrodes could open up potential new uses, as well as improve current ones-more accurate epilepsy diagnosis, for example, as well as the promise of “reading” someone’s thoughts in the future, with the goal, for example, of activating an otherwise inert body part, such as an arm or leg, and ultimately helping people with spinal cord injuries.

The aim is to have the highly sensitive electrodes first translate a person’s thoughts into electrical impulses that can be read by a computer, then, eventually move to robots, and later, limbs. Other scientists are conducting similar research, but Besio wants to show “that it works better with these types of electrodes.”

Study supports link between stress, epileptic seizures

Scientists have long thought that stress plays a role in epileptic seizures, and new evidence suggests that epilepsy patients who believe this is the case experience a different brain response when faced with a nerve-wracking situation.

Researchers from the University of Cincinnati performed functional MRI brain scans during a stressful math exercise on 16 epilepsy patients who pegged stress as a factor in their seizure control and seven patients who did not. While both groups performed similarly on the test, those who perceived stress to have an impact on their epilepsy showed greater brain activation than the others during intimidating parts of the test.

"One of the things we often hear is that a lot of epilepsy patients feel their seizures are affected by stress … but no one had really looked at their [brain response] or other elements of their physiological response," said study author Jane Allendorfer, an instructor of neurology at the University of Alabama at Birmingham. Allendorfer worked at University of Cincinnati while the study was conducted.

"We were a bit surprised to see this difference," she added, "but really excited to see it as well because this is something that hadn’t been done before."

The research was scheduled to be presented Monday at the annual meeting of the American Epilepsy Society, in San Diego. Data presented at scientific conferences often has not been peer-reviewed or published and is considered preliminary.

A brain disorder producing repeated seizures, epilepsy affects more than 2 million people in the United States, according to the U.S. Centers for Disease Control and Prevention. An estimated 50 million to 65 million people are affected by the condition worldwide.

Brain Cooling to Treat Epilepsy Moves Closer to Human Application

Neuroscientists from Japan’s Yamaguchi University today reported during the 66th annual scientific meeting of the American Epilepsy Society (AES) that chronic focal brain cooling suppresses seizures during wakefulness and achieves the effect without significantly affecting brain function. Their research, and that of others in the field, provides critical evidence that this approach to seizure control has reached a stage where testing in humans will soon be possible.

Focal brain cooling is well established as an effective method for suppressing seizures. But the technology for creating a practical device with potential clinical application has only recently become available and tested in rodents. More evidence from large animals and humans is needed prior to testing in clinical trials for drug-resistant epilepsy.

The Yamaguchi researchers implanted two feline and two non-human primates with a titanium cooling plate, or heat exchanger. The brain cooling device was placed in contact with the brain surface over cortex areas responsible for movement and sensation. Seizures were then induced in the motor cortex. Brain wave recordings to assess seizure activity and temperature recordings were performed under wakefulness.

According to Masami Fujii, M.D.,Ph.D., and Takao Inoue, Ph.D., and Michiyasu Suzuki, M.D., Ph.D., who presented the report, seizure discharges were significantly suppressed at 15˚C (59˚F).

“The results of our study suggest that focal brain cooling has a strong effect to suppress the epileptiform seizures under the awake condition,” Dr. Fujii said. “Moreover, implantation of the device for at least five months did not result in detrimental changes in brain tissue subjected to cooling compared to tissue from a similar site in the opposing hemisphere.”