Hope for progress even after a 450-foot fall, trial shows, defying pessimism that hurts research and families<\/p>\n
New research may upend the widely held view of traumatic brain injury as a permanently debilitating condition. The findings indicate that electrical stimulation can reawaken quiescent brain circuitry, leading to functional improvements that have the potential to restore work and social activities to patients\u2019 lives.<\/p>\n
The early stage trial, by investigators at Harvard-affiliated Spaulding Rehabilitation Hospital and colleagues at institutions around the country, including Weill Cornell Medicine, Stanford University, the Cleveland Clinic, and the University of Utah, was completed by five of the six enrolled patients. It yielded improvements of between 15 percent and 52 percent on a standard test of executive function, which involves attention, inhibition, reasoning, problem-solving, and other key aspects of mental processing.<\/p>\n
The study, published in December in Nature Medicine, relied on \u201cdeep brain stimulation,\u201d in which a battery-powered device is implanted under a patient\u2019s skin. Electrodes extend from the device to a part of the thalamus, which routes signals from one section of the brain to another.<\/p>\n
\u201cThere\u2019s a lot of ways to shut parts of the system down,\u201d said Joseph Giacino, Spaulding\u2019s director of rehabilitation neuropsychology and a professor of physical medicine and rehabilitation at Harvard Medical School, who helped design the study. \u201cOne is by direct damage to specific structures. Then you have the more common situation where I can damage the pathways that connect those structures and I get the same effect.<\/p>\n
\u201cIf the thalamus \u2014 this key relay station and signaling system \u2014 is damaged, it can\u2019t activate or upregulate those circuits that are relatively spared and could work and perform their role if they had the right input.\u201d<\/p>\n
The volunteers had suffered moderate to severe brain injury from either a motor vehicle accident or a fall \u2014 one from 450 feet and another from roughly 60 feet. The accidents occurred between three and 18 years earlier, long enough that the victims were considered past the immediate post-injury phase when most healing takes place. Each had recovered enough to perform the activities of daily living \u2014 personal hygiene, dressing, and feeding themselves \u2014 but had not regained pre-injury levels of work, study, and social activities.<\/p>\n
A common view of brain injury, held by both laypeople and the medical community, is that the affected cells cannot regrow, leading to permanent disability. In this case, investigators tested an alternate theory: The idea that some \u2014 perhaps many \u2014 injuries disrupt signaling between parts of the brain, and it is the loss of communication, rather than cell death, that causes much of the decline in function. If that\u2019s the case, they say, then it\u2019s possible that stimulating brain regions important in communication can restore some function.<\/p>\n
The five volunteers received deep-brain stimulation for 12 hours a day for three months. To gauge results, the researchers selected a standard test of executive function called the \u201ctrail making test part B\u201d and established 10 percent improvement as a clinically relevant threshold.<\/p>\n
By the study\u2019s end, all five patients had exceeded the 10 percent threshold, producing an average improvement of 31.75 percent. The greatest gains, more than 40 percent, were seen in the two who had suffered falls and had the deepest initial deficits. But even those with mild impairment improved by more than 20 percent. Two participants, one injured in a car accident and a second hit by a car while riding a bicycle, regained the ability to work, albeit at reduced capacity, and socialize. The functional status of the other volunteers remained stable.<\/p>\n
One mother called her daughter\u2019s improvement \u201cprofound\u201d and \u201ca miracle.\u201d None of the participants were \u201ccured,\u201d however. Rather, the implant plays a long-term role analogous to that of a cardiac pacemaker. Even though the trial\u2019s experimental phase concluded years ago, all five participants still have their devices. Some have had new batteries installed.<\/p>\n
The researchers don\u2019t understand precisely how deep-brain stimulation improves functioning, but they are skeptical that the artificial signals replace neural messages. The team\u2019s favored explanation, Giacino said, is that the stimulation serves to activate the thalamus, which in turn upregulates viable downstream parts of the brain, restoring at least some signaling capacity.<\/p>\n
\u201cI think what it\u2019s doing is putting the brain into a state of readiness, so when the demands are there to engage a particular network or subsystem, it can do that,\u201d he said.<\/p>\n
Patients in the study saw improvements to capabilities that had been considered set in stone for as long as 18 years. This doesn\u2019t mean that deep-brain stimulation is likely to be a universal answer, Giacino noted. And though the work suggests that not all loss of function is due to cell death in specific parts of the brain, some of it undoubtedly is. But overall, the results suggest that it\u2019s time to rethink the idea that brain injury is permanent, he said. A Phase 2 study, set to involve about 50 people, is now in the planning stages.<\/p>\n
\u201cThe degree of nihilistic belief that exists, both among the lay public and clinicians who see persons with severe brain injury, is remarkable and hugely problematic,\u201d Giacino said. \u201cThis belief that if you have a severe brain injury you\u2019re fated to do poorly \u2014 you\u2019ll get some period of time in which your brain will naturally try to heal itself and then you\u2019re at your final outcome \u2014 has been a problem for clinical practice, for research, for funding, and for people who have severe brain injury and their families.\u201d<\/p>\n
The progress of patients in the trial, he added, \u201chelps chip away at the nihilism that really makes our work so much more difficult.\u201d<\/p>\n
Source: Alvin Powell (Harvard Staff Writer); Illustrations by Liz Zonarich\/Harvard Staff<\/strong><\/p>\n Image: For this study, researchers electrically stimulated the thalamus, the region responsible for routing signals from one part of the brain to another.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Hope for progress even after a 450-foot fall, trial shows, defying pessimism that hurts research and families New research may upend the widely held view of traumatic brain injury as a permanently debilitating condition. The findings indicate that electrical stimulation can reawaken quiescent brain circuitry, leading to functional improvements that have the potential to restore\u2026<\/p>\n","protected":false},"author":2,"featured_media":17604,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_scj_primary_category_id":96,"_scj_featured":false,"_scj_featured_from":"","_scj_featured_until":"","_scj_featured_order":0,"_scj_visibility_class":"current","_scj_layout_family":"standard","_scj_article_style":"","_scj_display_overrides":[],"_scj_intro_image_id":17604,"_scj_intro_alt":"A win for science, and patients, against brain injury \u2018nihilism\u2019","_scj_intro_caption":"","_scj_intro_class":"","_scj_intro_float":"","_scj_full_image_id":17604,"_scj_full_alt":"A win for science, and patients, against brain injury \u2018nihilism\u2019","_scj_full_caption":"","_scj_full_class":"","_scj_full_float":"","_scj_media_type":"","_scj_media_provider":"","_scj_media_external_id":"","_scj_media_url":"","_scj_media_poster_id":0,"_scj_media_width":0,"_scj_media_height":0,"_scj_media_aspect_ratio":"","_scj_media_description":"","_scj_gallery_items":[],"_scj_related_post_ids":[],"_scj_additional_authors":[],"scj_layout_family":"standard","scj_media_provider":"","scj_media_url":"","scj_full_caption":"","footnotes":""},"categories":[96],"tags":[],"class_list":["post-17605","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-biotechnology"],"yoast_head":"\n