Deep Brain Stimulation shows promise for patients with chronic, treatment resistant Anorexia Nervosa

In a world first, a team of researchers at the Krembil Neuroscience Centre and the University Health Network have shown that Deep Brain Stimulation (DBS) in patients with chronic, severe and treatment-resistant Anorexia Nervosa (anorexia) helps some patients achieve and maintain improvements in body weight, mood, and anxiety.

The results of this trial, entitled Deep Brain Stimulation of the Subcallosal Cingulate Area for Treatment-Refractory Anorexia Nervosa: A Phase I Pilot Trial, are published in the medical journal The Lancet. The study is a collaboration between lead author Dr. Nir Lipsman a neurosurgery resident at the University of Toronto and PhD student at the Krembil Neuroscience Centre; Dr. Andres Lozano, a neurosurgeon, at the Krembil Neuroscience Centre of Toronto Western Hospital and a professor and chairman of neurosurgery at the University of Toronto, whose research lab was instrumental in conducting the DBS research; and Dr. Blake Woodside, medical director of Canada’s largest eating disorders program at Toronto General Hospital and a professor of psychiatry at the University of Toronto.

The phase one safety trial investigated the procedure in six patients who would likely continue with a chronic illness and/or die a premature death because of the severity of their condition. The study’s participants had an average age of 38, and a mean duration of illness of 18 years. In addition to the anorexia, all patients, except one, also suffered from psychiatric conditions such as major depressive disorder and obsessive-compulsive disorder. At the time of the study, all patients currently, or had previously, suffered multiple medical complications related to their anorexia – altogether, the six patients had a history of close to 50 hospitalizations during their illnesses.

Study participants were treated with Deep Brain Stimulation (DBS), a neurosurgical procedure that moderates the activity of dysfunctional brain circuits. Neuroimaging has shown that there are both structural and functional differences between anorexia patients and healthy controls in brain circuits which regulate mood, anxiety, reward and body-perception.

Patients were awake when they underwent the procedure which implanted electrodes into a specific part of the brain involved with emotion, and found to be highly important in disorders such as depression. During the procedure, each electrode contact was stimulated to look for patient response of changes in mood, anxiety or adverse effects. Once implanted, the electrodes were connected to an implanted pulse generator below the right clavicle, much like a heart pacemaker.

Testing of patients was repeated at one, three, and six-month intervals after activation of the pulse generator device. After a nine-month period following surgery, the team observed that three of the six patients had achieved weight gain which was defined as a body-mass index (BMI) significantly greater than ever experienced by the patients. For these patients, this was the longest period of sustained weight gain since the onset of their illness. Furthermore, four of the six patients also experienced simultaneous changes in mood, anxiety, control over emotional responses, urges to binge and purge and other symptoms related to anorexia, such as obsessions and compulsions. As a result of these changes, two of these patients completed an inpatient eating disorders program for the first time in the course of their illness.

“We are truly ushering in a new of era of understanding of the brain and the role it can play in certain neurological disorders,” says Dr. Lozano. “By pinpointing and correcting the precise circuits in the brain associated with the symptoms of some of these conditions, we are finding additional options to treat these illnesses.”

While the treatment is still considered experimental, it is believed to work by stimulating a specific area of the brain to reverse abnormalities linked to mood, anxiety, emotional control, obsessions and compulsions all of which are common in anorexia. In some cases after surgery, patients are then able to complete previously unsuccessful treatments for the disease. The research may not only provide an additional therapy option for these patients in the future, but also furthers practitioners’ understanding of anorexia and the factors that cause it to be persistent.

“There is an urgent need for additional therapies to help those suffering from severe anorexia,” says Dr. Woodside. “Eating disorders have the highest death rate of any mental illness and more and more women are dying from anorexia. Any treatment that could potentially change the natural course of this illness is not just offering hope but saving the lives for those that suffer from the extreme form of this condition.”

A leading international expert in the field of DBS research, Dr. Lozano has been exploring the potential of DBS to treat a variety of conditions. Most recently, his team began the first ever DBS trial of patients with early Alzheimer’s disease, and showed that stimulation may help improve memory. This trial has now entered its second phase and expanded to medical centres in the United States.

Parkinson’s Disease Brain Rhythms Detected

A team of scientists and clinicians at UC San Francisco has discovered how to detect abnormal brain rhythms associated with Parkinson’s by implanting electrodes within the brains of people with the disease.

The work may lead to developing the next generation of brain stimulation devices to alleviate symptoms for people with the disease.

Described this week in the journal Proceedings of the National Academy of Sciences (PNAS), the work sheds light on how Parkinson’s disease affects the brain, and is the first time anyone has been able to measure a quantitative signal from the disease within the cerebral cortex – the outermost layers of the brain that helps govern memory, physical movement and consciousness.

“Normally the individual cells of the brain are functioning independently much of the time, working together only for specific tasks,” said neurosurgeon Philip Starr, MD, PhD, a professor of neurological surgery at UCSF and senior author of the paper. But in Parkinson’s disease, he said, many brain cells display “excessive synchronization,” firing together inappropriately most of the time.

“They are locked into playing the same note as everyone else without exploring their own music,” Starr explained. This excessive synchronization leads to movement problems and other symptoms characteristic of the disease.

The new work also shows how deep brain stimulation (DBS), which electrifies regions deeper in the brain, below the cortex, can affect the cortex, itself. This discovery may change how DBS is used to treat Parkinson’s and other neurologically based movement disorders, and it may help refine the technique for other types of treatment.

How electrodes in the brain block obsessive behaviour

Deep brain stimulation helps some people with obsessive-compulsive disorder (OCD), but no one was quite sure why it is effective. A new study offers an explanation: the stimulation has surprisingly pervasive effects, fixing abnormal signalling between different parts of the brain.

A small number of people with difficult-to-treat OCD have had electrodes permanently implanted deep within their brain. Stimulating these electrodes reduces their symptoms.

To work out why stimulation has this effect, Damiaan Denys and Martijn Figee at the Academic Medical Center in Amsterdam, the Netherlands, and colleagues recorded neural activity in people with electrodes implanted into a part of the brain called the nucleus accumbens. This region is vital for conveying motivational and emotional information to the frontal cortex to guide decisions on what actions to take next. In some people with OCD, feedback loops between the two get jammed, leading them to do the same task repeatedly to reduce anxiety.

The researchers took fMRI scans as participants rested. In 13 people with OCD and implanted electrodes, there was continuous and excessive exchange of signals between the nucleus accumbens and the frontal cortex that was not seen in 11 control subjects. When the electrodes were activated, though, the neural activity of both brain regions in the people with OCD became virtually identical to that in the controls.

The researchers also used EEGs to monitor electrical activity in the brain as the 13 people with OCD viewed images linked with their obsessions, such as cleaning toilets. This time, the team observed excessive activity in the frontal cortex – and again, this activity disappeared when the electrodes were activated.

"The most striking thing is that stimulation doesn’t just affect the nucleus accumbens, but the whole network linked up with the cortex," says Figee.

The study suggests that the electrodes do more than normalise brain activity at the site where they are implanted, as had been assumed. Rather, they appear to repair entire brain circuits that had been faulty. “It resets and normalises these circuits,” says Figee.

Thomas Schlaepfer at the University of Bonn, Germany, points out that such work may allow researchers to use deep brain stimulation to learn about the causes of OCD as they treat it. “It will serve as a research platform informing us about the underlying neurobiology of such disorders,” he says.

(Image courtesy: Michael S. Okun)

Fighting disease deep inside the brain

Some 90,000 patients per year are treated for Parkinson’s disease, a number that is expected to rise by 25 percent annually. Deep Brain Stimulation (DBS), which consists of electrically stimulating the central or peripheral nervous system, is currently standard practice for treating Parkinson’s, but it can involve long, expensive surgeries with dramatic side effects. Miniature, ultra-flexible electrodes developed in Switzerland, however, could be the answer to more successful treatment for this and a host of other health issues.

Today, Professor Philippe Renaud of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland reports on soft arrays of miniature electrodes developed in his Microsystems Laboratory that open new possibilities for more accurate and local DBS. At the 2013 Annual Meeting of the American Association for the Advancement of Science (AAAS) in Boston, in a symposium called “Engineering the Nervous System: Solutions to Restore Sight, Hearing, and Mobility,” he announces the start of clinical trials and early, yet promising results in patients, and describes new developments in ultra-flexible electronics that can conform to the contours of the brainstem—in the brain itself—for treating other disorders.

At AAAS, Renaud outlines the technology behind these novel electronic interfaces with the nervous system, the associated challenges, and their immense potential to enhance DBS and treat disease, even how ultra flexible electronics could lead to the auditory implants of the future and the restoration of hearing. “Although Deep Brain Stimulation has been used for the past two decades, we see little progress in its clinical outcomes,” Renaud says. “Microelectrodes have the potential to open new therapeutic routes, with more efficiency and fewer side effects through a much better and finer control of electrical activation zones.” The preliminary clinical trials related to this research are being done in conjunction with EPFL spin-off company Aleva Neurotherapeutics, the first company in the world to introduce microelectrodes in Deep Brain Stimulation leading to more precise directional stimulation.

Parkinson’s patients advised to seek Deep Brain Stimulation treatment in early stages

People with Parkinson’s disease who receive Deep Brain Stimulation (DBS) therapy in the early stages of the condition will benefit from a significant increase in quality of life, a revolutionary study from The New England Journal of Medicine has found.

World-leading neurologist and lead clinician Professor Peter Silburn from the Asia-Pacific Centre for Neuromodulation (APCN), a joint initiative of The University of Queensland (UQ) and St Andrew’s Hospital, said the results published today in the medical journal would transform the way we treat people with Parkinson’s disease.

“Before the release of this study, a typical patient with Parkinson’s disease would need to wait around 10 years or until their motor complications could no longer be treated successfully with medicine alone, before DBS surgery was considered an option,” Professor Silburn said.

“This study has confirmed the best medical practice for a person with Parkinson’s disease is to perform DBS surgery around 4 to 7 years into the condition, as opposed to waiting until the medications stop working.”

In Some Dystonia Cases, Deep Brain Therapy Benefits May Linger After Device Turned Off

Two patients freed from severe to disabling effects of dystonia through deep brain stimulation therapy continued to have symptom relief for months after their devices accidentally were fully or partly turned off, according to a report published online Feb. 11 in the journal Movement Disorders.

“Current thought is that symptoms will worsen within hours or days of device shut-off, but these two young men continued to have clinical benefit despite interruption of DBS therapy for several months. To our knowledge, these two cases represent the longest duration of retained benefit in primary generalized dystonia. Moreover, when these patients’ symptoms did return, severity was far milder than it was before DBS,” said senior author Michele Tagliati, MD, director of the Movement Disorders Program at Cedars-Sinai’s Department of Neurology.

Dystonia causes muscles to contract, with the affected body part twisting involuntarily and symptoms ranging from mild to crippling. If drugs – which often have undesirable side effects, especially at higher doses – fail to give relief, neurosurgeons and neurologists may work together to supplement medications with deep brain stimulation, aimed at modulating abnormal nerve signals. Electrical leads are implanted in the brain – one on each side – and an electrical pulse generator is placed near the collarbone. The device is then programmed with a remote, hand-held controller. Tagliati is an expert in device programming, which fine-tunes stimulation for individual patients.

Few studies have looked at the consequences of interrupted DBS therapy, although one found “fairly rapid worsening of dystonia in 14 patients after interruption of stimulation for 48 hours, with symptom severity at times becoming worse than the pre-operative baseline.” In another study of 10 patients with generalized dystonia, however, symptoms did not return in four patients when stimulation was discontinued for 48 hours.

Findings from the 10-patient study correlate well with these two cases, Tagliati said.

“It appears that several factors – age, duration of disease, length of time the patient has received DBS treatment and stimulation parameters – determine which patients may retain symptom relief after prolonged DBS interruption. Our two patients were young, 20 years old. They both began DBS therapy a relatively short time after disease onset; one at four years and the other at seven years. One had received continuous stimulation for five years and the other for 18 months before stimulation was interrupted,” Tagliati said.

“We can’t say for certain why these factors make the difference,” he added, “But we theorize that a younger brain with shorter exposure to the negative effects of dystonia may be more responsive to therapy and have greater ‘plasticity’ to adapt back to normal. Both of our patients received DBS therapy at a lower energy than most patients experience, suggesting the possibility that low-frequency stimulation over an extended time may help retrain the brain’s low-frequency electrical activity.”

Both instances of device shut-off were accidental and were discovered during doctor visits after mild symptoms returned. The patient who had undergone five years of DBS therapy had only one stimulator turned off for about three months; the one stimulating the left side of his brain remained active. In the other patient, the left device had been off for about seven months and the right one for two months, Tagliati said.

Tagliati was senior author of a 2011 Journal of Neurology article on a study showing that for patients suffering from dystonia, deep brain therapy tends to get better, quicker results when started earlier rather than later.

“We knew from earlier work that younger patients with shorter disease duration had better clinical outcomes in the short term. In our 2011 article, we reported that they fare best in the long term, as well. That study uniquely showed that age and disease duration play complementary roles in predicting long-term clinical outcomes. The good news for older patients is that while they may not see the rapid gains of younger patients, their symptoms may gradually improve over several years,” Tagliati said.

Deep brain stimulation improves autistic boy’s symptoms

Electrodes implanted deep in the brain of a boy with severe autism have enabled him to live a more normal life. The treatment reduced his destructive behavior and allowed the formerly nonverbal boy to speak a few words, scientists report online January 21 in Frontiers in Human Neuroscience.

The results are the first to use brain stimulation to alleviate symptoms of autism. Scientists caution that interpreting the results broadly is impossible without larger, systematic studies, but even so neurosurgeon Ali Rezai of the Ohio State University Wexner Medical Center in Columbus calls the boys’ gains “intriguing and promising.”

The boy in the study, who was 13 at the time of his experimental surgery, suffered from severe autism symptoms: He couldn’t talk or make eye contact, woke up screaming repeatedly during the night, and habitually injured himself so badly that his parents restrained him almost constantly to protect him. Multiple rounds of psychiatric drugs failed to stave off his worsening symptoms.

In an effort to help him, doctors led by Volker Sturm of the University Hospital of Cologne in Germany implanted electrodes into the boy’s brain. Through trial and error, the doctors realized that stimulating a part of the amygdala, a brain structure important for emotions and memory, improved the boy’s symptoms. Stimulating other brain areas had no effect or worsened his symptoms.

After eight weeks of continuous electrical stimulation, the boy shifted on a clinical scale that measures irritability from “severely ill” to “moderately ill.” The boy also improved on a scale that measures autism symptoms. He began to make eye contact and was better able to control his behavior.

Alzheimer’s researchers trying brain zaps

It has the makings of a science fiction movie: zap someone’s brain with mild jolts of electricity to try to stave off the creeping memory loss of Alzheimer’s disease.

And it’s not easy. Holes are drilled into the patient’s skull so tiny wires can be implanted into just the right spot.

A dramatic shift is beginning in the frustrating struggle to find something to slow the damage of this epidemic: The first U.S. experiments with “brain pacemakers” for Alzheimer’s are getting under way. Scientists are looking beyond drugs to implants in the hunt for much-needed new treatments.

The research is in its infancy. Only a few dozen people with early-stage Alzheimer’s will be implanted in a handful of hospitals. No one knows if it might work, and if it does, how long the effects might last.

Kathy Sanford was among the first to sign up. The Ohio woman’s early-stage Alzheimer’s was gradually getting worse. She still lived independently, posting reminders to herself, but no longer could work. Medications weren’t helping.

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