Posts Tagged Thalamus

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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[WEB SITE] 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.

 

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[WEB SITE] UCLA researchers use noninvasive ultrasound technique to jump-start the brain of coma patient

A 25-year-old man recovering from a coma has made remarkable progress following a treatment at UCLA to jump-start his brain using ultrasound. The technique uses sonic stimulation to excite the neurons in the thalamus, an egg-shaped structure that serves as the brain’s central hub for processing information.

“It’s almost as if we were jump-starting the neurons back into function,” said Martin Monti, the study’s lead author and a UCLA associate professor of psychology and neurosurgery. “Until now, the only way to achieve this was a risky surgical procedure known as deep brain stimulation, in which electrodes are implanted directly inside the thalamus,” he said. “Our approach directly targets the thalamus but is noninvasive.”

Monti said the researchers expected the positive result, but he cautioned that the procedure requires further study on additional patients before they determine whether it could be used consistently to help other people recovering from comas.

“It is possible that we were just very lucky and happened to have stimulated the patient just as he was spontaneously recovering,” Monti said.

A report on the treatment is published in the journal Brain Stimulation. This is the first time the approach has been used to treat severe brain injury.

The technique, called low-intensity focused ultrasound pulsation, was pioneered by Alexander Bystritsky, a UCLA professor of psychiatry and biobehavioral sciences in the Semel Institute for Neuroscience and Human Behavior and a co-author of the study. Bystritsky is also a founder of Brainsonix, a Sherman Oaks, California-based company that provided the device the researchers used in the study.

That device, about the size of a coffee cup saucer, creates a small sphere of acoustic energy that can be aimed at different regions of the brain to excite brain tissue. For the new study, researchers placed it by the side of the man’s head and activated it 10 times for 30 seconds each, in a 10-minute period.

Monti said the device is safe because it emits only a small amount of energy — less than a conventional Doppler ultrasound.

Before the procedure began, the man showed only minimal signs of being conscious and of understanding speech — for example, he could perform small, limited movements when asked. By the day after the treatment, his responses had improved measurably. Three days later, the patient had regained full consciousness and full language comprehension, and he could reliably communicate by nodding his head “yes” or shaking his head “no.” He even made a fist-bump gesture to say goodbye to one of his doctors.

“The changes were remarkable,” Monti said.

The technique targets the thalamus because, in people whose mental function is deeply impaired after a coma, thalamus performance is typically diminished. And medications that are commonly prescribed to people who are coming out of a coma target the thalamus only indirectly.

Under the direction of Paul Vespa, a UCLA professor of neurology and neurosurgery at the David Geffen School of Medicine at UCLA, the researchers plan to test the procedure on several more people beginning this fall at the Ronald Reagan UCLA Medical Center. Those tests will be conducted in partnership with the UCLA Brain Injury Research Center and funded in part by the Dana Foundation and the Tiny Blue Dot Foundation.

If the technology helps other people recovering from coma, Monti said, it could eventually be used to build a portable device — perhaps incorporated into a helmet — as a low-cost way to help “wake up” patients, perhaps even those who are in a vegetative or minimally conscious state. Currently, there is almost no effective treatment for such patients, he said.

Source: University of California – Los Angeles

Source: UCLA researchers use noninvasive ultrasound technique to jump-start the brain of coma patient

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