Deep-Brain Stimulation Restores Awareness After Six Years

NEW YORK, Aug. 2 -- After deep-brain stimulation, a man in a minimally conscious state for six years has regained awareness, speech, and controlled movement, surgeons here reported. The 38-year-old man had been left unable to eat by mouth or communicate verbally after a mugging in which his skull was crushed, causing massive blunt trauma and bilateral subdural hematomas, reported Nicholas D.
Animation: Deep Brain Stimulation
Listen: Press Briefing Schiff, M.D., of Weill-Cornell Medical College, and colleagues, in the Aug. 2 issue of Nature.
The work challenges the existing practice of early treatment discontinuation for this patient population and also changes the approach to assessment and evaluation of the minimally-conscious state patient," said Dr. Schiff.
Joseph T. Giacino, Ph.D., of the New Jersey Neursocience Institute, in Edison, a co-author, said that "prior to the use of deep-brain stimulation, the patient's communication ability was inconsistent, including only slight eye or finger movements. Now, he regularly uses words and gestures and responds to questions quickly."
Dr. Giacino continued, "In addition, he now chews and swallows his food and no longer requires a feeding tube. Before, he could not use his limbs for functional movement, but he can now perform some complex movements, including those required for drinking from a cup or brushing hair. Years of severe immobility and tendon contracture, however, do greatly limit him from carrying out these tasks."
The man's mother, who asked that the family not be identified, said that he now laughs, cries, watches movies with apparent awareness, and can express both pain and love.
Although he had been left unable to communicate reliably, the man was not in a persistent vegetative state, and there was evidence from imaging studies to suggest that he had enough intact brain structures to allow for recovery, the authors said.
"Functional MRI showed preservation of a large-scale, bi-hemispheric cerebral language network, indicating that a substrate for further recovery might exist," they wrote. "Additional studies using positron emission tomography showed that the patient's resting global cerebral metabolism was markedly reduced. These observations supported our hypothesis that the patient's inconsistent behavioral responsiveness and communication reflected a global reduction in neuronal activity resulting from widespread de-afferentation and compression injuries to the thalamus and midbrain."
Deep-brain stimulation, which involves surgical implantation of electrodes and low-voltage stimulation of key brain regions, has helped reduce motor symptoms of Parkinson's disease, relieving pain from severe, intractable cluster headaches, and decreasing symptoms of severe drug-resistant depression.
The authors hypothesized that deep-brain stimulation to the central thalamus might mimic the normal role of mesial frontal cortical and brainstem circuits, which regulate cognition and help to maintain metabolic activity in the brain during wakefulness by adjusting firing rates in central thalamic neurons.
Two days after the electrodes were implanted in a 10-hour procedure, the surgeons tested the voltage potentials of the leads, and saw that patient had signs of increased arousal and sustained eye opening, and he would turn his head in both directions in response to voices.
Two months after the surgery, the investigators started titrating the patterns of electrical stimulation to search for the best response, and then tested the stimulation in a double-blind crossover phase in which the device would be switched on or off for a month at a time. This was done to help the researchers identify whether any observed improvements were due to deep-brain stimulation, the rehabilitation program the patient was undergoing, or to gradual recovery.
They found on logistic regression analysis improvements during the periods when the device was switched on that could not be accounted for by gradual improvement alone. In addition, they saw that improvements in intelligible speech and limb control occurred when the brain was being electrically stimulated during titration.
"This work reflects the exciting emerging idea that some neurological disorders can be treated by focusing on neural circuit changes rather than drug treatments and gene therapy," said Joseph J. Pancrazio, Ph.D., of the National Institute of Neurological Disorders and Stroke, which funded he study. "However, we still need to understand how deep-brain stimulation works for these disorders and to define which patients can benefit from this treatment."
In an accompanying editorial, Michael N. Shadlen, M.D., Ph.D., and Roozbeh Kiani, of the University of Washington in Seattle, said that although this was only a single case report, it offers hope to the families of patients with impaired consciousness.
"Philosophers and scientists may argue about the definition of consciousness, but neurologists have little trouble identifying its absence," they wrote. "Now, physicians are beginning to understand how it can be restored in some patients with severe brain damage."
The study was supported by the NINDS, Charles A. Dana Foundation, Cleveland Clinic Foundation Brain Neuromodulation Center, Ohio Department of Development Biomedical Research and Technology Transfer Partnership Program and Third Frontier Program, Jane and Lee Seidman Neuromodulation Research Fund, Cleveland Clinic Innovations, IntElect Medical and the National Institute on Disability and Rehabilitation Research. Authors conflicts of interest, if any, were not listed.Primary source: NatureSource reference: Schiff ND et al. "Behavioral improvements with thalamic stimulation after severe traumatic brain injury." Nature 2007. 448:600-604.