April 29th 2019  | originally published at Agência FAPESP

Maria Fernanda Ziegler | Agência FAPESP – Researchers in Australia are developing implantable electronic devices for patients with epilepsy. The goal is to predict seizures, identify the pattern of seizure frequency, and even release medications to prevent further episodes. The devices are not yet marketable, but some of them are already being tested in humans.

Epilepsy affects about 1% of the world’s population, and yet it is still shrouded in stigma and mystery. In it, for some genetic or environmental reason, a group of brain cells becomes extremely active, to the point of making the electrical signals completely disorganized. This mismatch often culminates in loss of memory and convulsions.

“Epilepsy is not a rare disease and has many effects on people’s lives. Therefore, the patient needs to know that it is an electrical problem in the brain that can be predicted, monitored and treated. This takes away all the mystery of the disease which, to the unhappiness of patients, is shrouded in ignorance and superstition”, said Australian scientist Mark Cook, a professor at the University of Melbourne and director of the Department of Neurology at St. Vincent’s Hospital in Australia.

The researcher participated, in April, in the 6th BRAINN Congress, at the State University of Campinas (Unicamp). The event was conducted by the Research Institute on Neuroscience and Neurotechnology (BRAINN) – a Research, Innovation and Dissemination Center (CEPID) funded by FAPESP.

In his speech, Cook presented the new devices that, according to him, could give greater quality of life to people with epilepsy in the future. He also talked about the latest results of his research on patterns of seizures in patients with the disease.

“Each patient has a specific pattern [of seizures] – we have already proven that. Imagine, then, being able to predict when you will have one of those episodes? People could protect themselves by staying home and being accompanied, rather than engaging in some risk activity on that particular day”, Cook told Agência FAPESP.

The new devices are aimed primarily at anticipating the onset of a seizure and are being developed by the Bionics Institute through a partnership between the University of Melbourne and St. Vincent’s Hospital. The institute has donations and funds, such as the one received on the television program The Shark Tank Miami (USA) – in which Cook competed and won in a special edition on epilepsy in 2015.

Prediction

“There are two ways to detect a seizure. In one of them, it is possible to read the brain signal and detect the electrical signature that occurs before it happens. Another way is to monitor the seizures for a certain period and identify a pattern. As soon as this pattern is established, the prediction becomes very accurate”, he said.

In the first case – detecting brain electrical signals -, implantable devices that can deliver drugs are being developed. One of them was implanted two years ago in a patient in Australia, who has so far responded well to the treatment.

Researchers are also developing an equipment with implantable electrodes to apply electroshock treatment – which is another way of treating epilepsy, besides medications and surgery – but there is still no human test prediction.

To monitor seizures in order to identify patterns, devices have been developed to be inserted under the scalp or behind the ear (such as cochlear implants for the deaf).

“We realized that, if we could count the seizures reliably, it would be possible to identify each patient’s monthly, weekly, or daily patterns. This would make it safer for patients to perform everyday activities and avoid embarrassment”, said the researcher.

Based on comprehensive databases (from the SeizureTracker and NeuroVista applications), Cook and his team identified striking periodicities between one seizure and another. According to the study, more than 80% of patients had one-day intervals between seizures. Cycles of one week or three weeks or more have also been observed.

“Understanding these patterns can have significant implications for managing people’s lives and predicting crises. Typically, patients are encouraged to write journals or use cell phone applications to track the seizures. However, this has proven to be very imprecise, as seizures can cause memory loss and unconsciousness. Many times, the patient does not realize that there was a small lapse”, Cook explained.

Much more accurate than the journals, implantable devices can be used for a long time, making it possible to cross information with external conditions that may be related to seizures, such as temperature, air humidity or even stress, food and medication. Clinical testing for this device should begin in the second half of 2019. According to Cook, all devices were designed for the study of epilepsy cases, but could also be used for other conditions, such as controlling the blood sugar of diabetics, for example.

April 10th 2019  | originally published at Unicamp

Professor Li Li Min is the master of ceremonies of the event. Image: Unicamp.

“This event was designed to give researchers, especially graduate students and post-doctoral students, the opportunity to present their work and at the same time bring foreign guests, who come with different perspectives, novelties and possibilities for collaboration,” said Fernando Cendes, professor at FCM and Principal Researcher for BRAINN.

Fernando Cendes, professor of FCM and researcher responsible for BRAINN. Image: Unicamp.

At the opening table, Unicamp´s Rector Marcelo Knobel highlighted the multidisciplinarity characteristic of the Center, which brings together research in the areas of genetics, neurobiology, pharmacology, neuroimaging, computer science, robotics, physics and engineering, as a fundamental aspect for the expansion of knowledge and rapid advances that have been achieved by the group. Also present were the pro-rector of research, Munir Skaf; the FCM director, Luiz Carlos Zeferino; and the coordinator of education and diffusion of knowledge at BRAINN and professor at FCM, Li Li Min.

Fernando Cendes also highlighted the growth of participants outside BRAINN in this edition of the Congress, which will feature presentations by researchers from various Brazilian centers. “This creates a very healthy and interesting atmosphere in which students can exchange ideas, start new collaborations and eventually find new opportunities to continue their work,” he said.

The Institute, which celebrates its fifth anniversary, goes on to its second phase as a CEPID, and its funding has been approved for the next six years, according to Gabriela Castellano, a professor at the Institute of Physics Gleb Wataghin (IFGW) and organizer of the event.

Gabriela Castellano, lecturer at the Institute of Physics Gleb Wataghin (IFGW) and organizer of the event. Image: Unicamp.

Precision Medicine

As part of the preliminary program of the Congress, Unicamp hosted, on Saturday (30), the VII Workshop of the Brazilian Initiative of Precision Medicine (BIPMed). According to Iscia Lopes Cendes, director of BIPMed, the initiative, which began in 2015, aims to facilitate the implementation of genomic medicine and precision medicine in Brazil.

According to the director, the main advance announced at the workshop was a new resolution by Brazil´s Ministry of Health, which incorporates, for the first time, a genomic test – called “Exoma” – as part of the exams covered by the Unified Health System (SUS). “This ordinance happened because a cost-effectiveness study was presented showing that it is worthwhile to include this test in the investigation of patients with intellectual disability. This study was done by a PhD student, Joana Prota, who went to Brasilia, wrote the entire technical recommendation based on the results and finally convinced [the government] that it would be important to incorporate this test”, reported Iscia Cendes.

Iscia Lopes Cendes, director of BIPMed. Image: Unicamp.

According to her, intellectual disability is not a rare thing in children and is often associated with epilepsy. The examination will provide diagnostic confirmation and clarification for the health professionals involved in the care of these children. “[This] is the demonstration that investment in research can return, sometimes even rapidly, to the general public in terms of defining new public policies,” said the director of BIPMed.

Robotics

Using technology to improve people’s quality of life is the goal of the Neural and Cognitive Engineering Group, which is part of Spain’s Higher Council for Scientific Research (CSIC), coordinated by Eduardo Rocon, responsible for the first talk of the Congress. “In the group, we are all Engineers, physical or computer engineers, but all our projects deal with hospitals. It is the clinicians who better understand the problems involved in the pathologies we want to work on”, he said.

According to Rocon, technology has much to contribute to healthcare, coming up with solutions to lessen the limitations caused by some diseases. “Chemical medicine has helped extend people’s lifespan. Many live today 80, 90 years. But in these last years of our lives, we have a number of limitations, due to some syndromes that do not kill but prevent an independent life. The technology, with advances in artificial intelligence algorithms and processors, that allow you to do much more complex things in much smaller devices, can increasingly bring up solutions to help improve our lives”, Rocon said.

Eduardo Rocon coordinates the Group of Neural and Cognitive Engineering, that integrates the Superior Council of Scientific Investigations Spain. Image: Unicamp.

One of the study topics developed by the group sought to understand tremors of the upper limbs, present in patients with Parkinson’s and other brain-related pathologies. In the first phase of the study, the group sought to distinguish between tremor and voluntary movements. Thus, an exoskeleton was produced, which applied forces on the upper limb to cancel the tremor. “It was a robot that had a series of motors and was able to control the flexion-extension of the wrist, the prone-supination of the forearm and the flexion extension of the elbow”, he explained.

Although successful, the exoskeleton did not meet the daily needs of patients, who did not intend to “carry a robot in their arms to go to a restaurant, for example”, the researcher reported.

But according to Rocon, the knowledge generated allowed the continuity of the research and the development of a kind of glove, which used the patient´s own human muscles to cancel the tremor. “It was the same concept: to measure, separate the tremor in real time and stimulate the muscles to cancel this tremor”, he explained.

In the next phase of the research, the group sought a solution that could be implanted within the body and succeeded in canceling the tremor by stimulating related areas of the brain. “We went from a solution that was not acceptable to users to much more acceptable and marketable solutions that people can use on a daily basis”, Rocon said.

The research has now been transferred to a US company, which has the resources needed to develop the product. According to Rocon, the outlook is that in 5 or 10 years the product will hit the market. “Currently, they are doing clinical validation in the United States. The idea is that a fully implantable solution, one that goes under the skin, comes to the market”, he said.