Posts Tagged Sclerosis

[WEB SITE] Largest-ever study to examine anatomical alterations in the brains of epilepsy patients

Largest-ever study to examine anatomical alterations in the brains of epilepsy patients 

An international research consortium used neuroimaging techniques to analyze the brains of more than 3,800 volunteers in different countries. The largest study of its kind ever conducted set out to investigate anatomical similarities and differences in the brains of individuals with different types of epilepsy and to seek markers that could help with prognosis and treatment.

Epilepsy’s seizure frequency and severity, as well as the patient’s response to drug therapy, vary with the part of the brain affected and other poorly understood factors. Data from the scientific literature suggests that roughly one-third of patients do not respond well to anti-epileptic drugs. Research has shown that these individuals are more likely to develop cognitive and behavioral impairments over the years.

The new study was conducted by a specific working group within an international consortium called ENIGMA, short for Enhancing NeuroImaging Genetics through Meta-Analysis, established to investigate several neurological and psychiatric diseases. Twenty-four cross-sectional samples from 14 countries were included in the epilepsy study.

Altogether, the study included data for 2,149 people with epilepsy and 1,727 healthy control subjects (with no neurological or psychiatric disorders). The Brazilian Research Institute for Neuroscience and Neurotechnology (BRAINN), which participated in the multicenter study, was the center with the largest sample, comprising 291 patients and 398 controls. Hosted in Brazil, at the State University of Campinas (UNICAMP), BRAINN is a Research, Innovation and Dissemination Center (RIDC http://cepid.fapesp.br/en/home/) supported by the Sao Paulo Research Foundation – FAPESP.

“Each center was responsible for collecting and analyzing data on its own patients. All the material was then sent to the University of Southern California’s Imaging Genetics Center in the US, which consolidated the results and performed a meta-analysis,” said Fernando Cendes, a professor at UNICAMP and coordinator of BRAINN.

A differential study

All volunteers were subjected to MRI scans. According to Cendes, a specific protocol was used to acquire three-dimensional images. “This permitted image post-processing with the aid of computer software, which segmented the images into thousands of anatomical points for individual assessment and comparison,” he said.

According to the researcher, advances in neuroimaging techniques have enabled the detection of structural alterations in the brains of people with epilepsy that hadn’t been noticed previously.

Cendes also highlighted that this is the first epilepsy study built on a really large number of patients, which allowed researchers to obtain more robust data. “There were many discrepancies in earlier studies, which comprised a few dozen or hundred volunteers.”

The patients included in the study were divided into four subgroups: mesial temporal lobe epilepsy (MTLE) with left hippocampal sclerosis, MTLE with right hippocampal sclerosis, idiopathic (genetic) generalized epilepsy, and a fourth group comprising various less common subtypes of the disease.

The analysis covered both patients who had had epilepsy for years and patients who had been diagnosed recently. According to Cendes, the analysis – whose results were published in the international journal Brain – aimed at the identification of atrophied brain regions in which the cortical thickness was smaller than in the control group.

First analysis

The researchers first analyzed data from the four patient subgroups as a whole and compared them with the controls to determine whether there were anatomical alterations common to all forms of epilepsy. “We found that all four subgroups displayed atrophy in areas of the sensitive-motor cortex and also in some parts of the frontal lobe,” Cendes said.

“Ordinary MRI scans don’t show anatomical alterations in cases of genetic generalized epilepsy,” Cendes said. “One of the goals of this study was to confirm whether areas of atrophy also occur in these patients. We found that they do.”

This finding, he added, shows that in the case of MTLE, there are alterations in regions other than those in which seizures are produced (the hippocampus, parahippocampus, and amygdala). Brain impairment is, therefore, more extensive than previously thought.

Cendes also noted that a larger proportion of the brain was compromised in patients who had had the disease for longer. “This reinforces the hypothesis that more brain regions atrophy and more cognitive impairment occurs as the disease progresses.”

The next step was a separate analysis of each patient subgroup in search of alterations that characterize each form of the disease. The findings confirmed, for example, that MTLE with left hippocampal sclerosis is associated with alterations in different neuronal circuits from those associated with MTLE with right hippocampal sclerosis.

“Temporal lobe epilepsy occurs in a specific brain region and is therefore termed a focal form of the disease. It’s also the most common treatment-refractory subtype of epilepsy in adults,” Cendes said. “We know it has different and more severe effects when it involves the left hemisphere than the right. They’re different diseases.”

“These two forms of the disease are not mere mirror-images of each other,” he said. “When the left hemisphere is involved, the seizures are more intense and diffuse. It used to be thought that this happened because the left hemisphere is dominant for language, but this doesn’t appear to be the only reason. Somehow, it’s more vulnerable than the right hemisphere.”

In the GGE group, the researchers observed atrophy in the thalamus, a central deep-lying brain region above the hypothalamus, and in the motor cortex. “These are subtle alterations but were observed in patients with epilepsy and not in the controls,” Cendes said.

Genetic generalized epilepsies (GGEs) may involve all brain regions but can usually be controlled by drugs and are less damaging to patients.

Future developments

From the vantage point of the coordinator for the FAPESP-funded center, the findings published in the article will benefit research in the area and will also have future implications for the diagnosis of the disease. In parallel with their anatomical analysis, the group is also evaluating genetic alterations that may explain certain hereditary patterns in brain atrophy. The results of this genetic analysis will be published soon.

“If we know there are more or less specific signatures of the different epileptic subtypes, instead of looking for alterations everywhere in the brain, we can focus on suspect regions, reducing cost, saving time and bolstering the statistical power of the analysis. Next, we’ll be able to correlate these alterations with cognitive and behavioral dysfunction,” Cendes said.

 

via Largest-ever study to examine anatomical alterations in the brains of epilepsy patients

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[WEB SITE] Learning stress-reducing techniques may benefit people with epilepsy

Learning techniques to help manage stress may help people with epilepsy reduce how often they have seizures, according to a study published in the February 14, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Despite all the advances we have made with new drugs for epilepsy, at least one-third of people continue to have seizures, so new options are greatly needed,” said study author Sheryl R. Haut, MD, of Montefiore Medical Center and the Albert Einstein College of Medicine in the Bronx, NY, and member of the American Academy of Neurology. “Since stress is the most common seizure trigger reported by patients, research into reducing stress could be valuable.”

The study involved people with seizures that did not respond well to medication. While all of the 66 participants were taking drugs for seizures, all continued to have at least four seizures during about two months before the study started.

During the three-month treatment period all of the participants met with a psychologist for training on a behavioral technique that they were then asked to practice twice a day, following an audio recording. If they had a day where they had signs that they were likely to have a seizure soon, they were asked to practice the technique another time that day. The participants filled out daily electronic diaries on any seizures, their stress level, and other factors such as sleep and mood.

Half of the participants learned the progressive muscle relaxation technique, a stress reduction method where each muscle set is tensed and relaxed, along with breathing techniques. The other participants were the control group-;they took part in a technique called focused attention. They did similar movements as the other group, but without the muscle relaxation, plus other tasks focusing on attention, such as writing down their activities from the day before. The study was conducted in a blinded fashion so that participants and evaluators were not aware of treatment group assignment.

Before the study, the researchers had hypothesized that the people doing the muscle relaxing exercises would show more benefits from the study than the people doing the focused attention exercises, but instead they found that both groups showed a benefit-;and the amount of benefit was the same.

The group doing the muscle relaxing exercises had 29 percent fewer seizures during the study than they did before it started, while the focused attention group had 25 percent fewer seizures, which is not a significant difference, Haut said. She added that study participants were highly motivated as was shown by the nearly 85 percent diary completion rate over a five-month period.

“It’s possible that the control group received some of the benefits of treatment in the same way as the ‘active’ group, since they both met with a psychologist and every day monitored their mood, stress levels and other factors, so they may have been better able to recognize symptoms and respond to stress,” said Haut. “Either way, the study showed that using stress-reducing techniques can be beneficial for people with difficult-to-treat epilepsy, which is good news.”

Haut said more research is needed with larger numbers of people and testing other stress reducing techniques like mindfulness based cognitive therapy to determine how these techniques could help improve quality of life for people with epilepsy.

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[BLOG POST] Stroke, MS patients walk significantly better with neural stimulation

Robert Bush has multiple sclerosis (MS), which sapped his ability to walk five years ago. Joseph McGlynn suffered a stroke that seriously impaired his left side, also five years ago.

Using technology designed by Case Western Reserve University and the Advanced Platform Technology and Functional Electrical Stimulation centers at the Louis Stokes Cleveland Veterans Affairs Medical Center, the two men got their feet back under them.

Two studies, published in the American Journal of Physical Medicine and Rehabilitation, show that functional electrical stimulation (FES) significantly helped McGlynn and Bush to effectively walk at the medical center.

“I went in there and I could barely take two steps,” said Bush, 42, who researchers believe is the world’s first MS patient to “test-drive” an implanted FES system. The proof-of-feasibility test lasted 90 days. “At the end,” said Bush, of Columbus, Ohio, “I was walking down the hallway. To me, it was monumental.” A video of him walking with and without the system can be found at: https://youtu.be/17JYaKkdRYs.

McGlynn, 69, of North Royalton, Ohio, could walk with a cane, but not easily. With the technology switched on, he covered far more ground and his pace was twice as fast during his 30-week study.

“It’s helped with balance and confidence,” said McGlynn, who used to tread a lot of stairs maintaining equipment at a steel plant. “I’m confident now that I can walk without stumbling and falling.” A video of him walking with and without aid of the system can be found here: https://youtu.be/3CYq-FSFQLM.

Nathan Makowski, an investigator at the Cleveland FES Center, created by Case Western Reserve and the Cleveland VA, said that FES technology has been used primarily for therapy in stroke patients in the past. “This, though, is a more long-term assistive system,” he said.

Addressing needs

The researchers hope these studies will lay the foundation for implanted systems that restore some independence to people with MS or who have suffered a stroke.

Their numbers are substantial. The National Multiple Sclerosis Society estimates that more than 2.3 million people have the disease worldwide. Surveys have found that 93 percent suffer gait impairment within 10 years of diagnosis and 13 percent report they are unable to walk twice a week. Other research has found that 6 million to 7 million people live with stroke nationally and nearly 30 percent require assistance to walk.

“In both cases, there is a disconnect between the brain and muscles,” said Stephen Selkirk, MD, a neurologist at the VA’s Spinal Cord Injury Division and assistant professor of neurology at Case Western Reserve School of Medicine. “This system replaces the lost connection.”

The system includes implanted electrodes that tie into nerves that control muscles collectively, called hip and knee flexors and ankle dorsoflexors. In healthy people, the muscles work in seamless coordination each step they take.

When Bush or McGlynn walks, he pushes a button on an external controller, which sends signals to a pulse generator, which then sends electrical pulses to the electrodes. The pulses stimulate the nerves, which in turn stimulate the muscles in both of Bush’s legs and McGlynn’s left leg.

“Both guys were taking steps the first time we turned the systems on,” said Ron Triolo, a professor of orthopaedics and biomedical engineering at Case Western Reserve and executive director of the Advanced Platform Technology (APT) Center. “When Robert Bush took a step, it wasn’t’ pretty, but we saw the potential.”

In each patient, “the pulses are sent in a pattern that is close to how normal muscles work,” said Rudi Kobetic, a principal investigator at the Stokes Cleveland VA and APT Center. “We try to time the pattern to stimulation so that it’s integrated with their ability. Similar to regular physical therapy, we can see results.”

Significant improvement

Both men gained strength and endurance through repeated use of the systems and fine-tuning by the researchers.

Bush went from the two steps to consistently walking more than 30 yards during the trial. In that time, he used a walker to help maintain his balance.

“When they turned it on the first time, I was surprised how well it worked,” said Bush, who had to give up his construction career due to the disease. “I lifted my knee like I was high-stepping. Once we got it fine-tuned and I got walking, I thought it was amazing. I still think it’s amazing.”

McGlynn’s gait became noticeably more symmetrical and energetic, the researchers said. His gait without the system was about 19 yards per minute; with the system, 47 yards per minute. Training with the system improved McGlynn’s speed when it was turned off to 23 yards per minute, indicating therapeutic benefit.

“Distance is a challenge,” he said. Initially, he could walk 83 yards but improved to 1,550 yards–nearly a mile–at the faster gait. “I work up a good sweat and that makes me feel good,” he said.

Due to his improvements, the research team is developing a system that McGlynn can use at home and outside.

“I’ll be able to walk for exercise and hopefully be able to walk into church and into a restaurant,” McGlynn said.

When Bush’s trial ended, surgeons removed his implanted electrodes. The researchers are seeking funding to fit him with a permanent FES system in a clinical trial.

In the meantime, Bush is now back to using a wheelchair but working to maintain his strength and flexibility, repeatedly standing and sitting while holding onto a rail or standing for long periods of time. “I’m keeping things ready for when they get the green light,” he said.

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Other researchers who contributed to the two studies are the APT Center’s Lisa Lombardo, physical therapist; Kevin Foglyano, biomedical engineer; and Gilles Pinault, MD, a surgeon and co-director of the center.

Source: Stroke, MS patients walk significantly better with neural stimulation | EurekAlert! Science News

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[WEB SITE] Cannabidiol shows promise to reduce seizures for people with difficult-to-treat epilepsy

Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology’s 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a “high.”

Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.

When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.

Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.

“Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control,” said study author Anup Patel, MD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.

For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.

Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.

Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.

Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.

Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.

There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.

Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.

“Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures,” said Patel. “This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients.”

There is currently a plan to submit a New Drug Application to the FDA later this year.

Source: Cannabidiol shows promise to reduce seizures for people with difficult-to-treat epilepsy

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