ARTICLE IN BRIEF
Investigators reported that short duration transcranial direct cortical stimulation transiently improved consciousness in patients in a minimally conscious state.
Transcranial direct current stimulation (tDCS), a non-invasive medium for cortical stimulation using weak polarizing currents, may temporarily improve signs of consciousness in brain-damaged patients who are in a minimally conscious state (MCS), according to a randomized-controlled trial from Belgium published in the Feb. 26 online edition of Neurology.
After a short session of tDCS was delivered over the left prefrontal cortex, MCS patients showed improvement as measured by a standardized scale, but the electrical stimulation did not, for the most part, help persons in a vegetative/unresponsive wakefulness syndrome (VS/UWS) who only show reflex movements. The electrical stimulation was compared with a sham treatment.
The improvement in signs of consciousness that was measured right after treatment was not evident when the patients were reassessed 12 months later. The study's senior author, Steven Laureys, MD, PhD — director of the Coma Science Group and clinical professor of neurology at University Hospital of Liege in Belgium — told Neurology Today that caution was needed to avoid presenting the study results as “spectacular changes.”
“It is a real yet moderate effect and should not give false hopes to families,” Dr. Laureys said in an e-mail.
An editorial accompanying the study in the same edition of Neurology noted “the article is of considerable interest as it suggests another potential treatment avenue for DOC (disorders of consciousness), as well as suggesting a promising site of intervention.” The editorial stressed that more research was needed to determine whether these short-term effects can be amplified and made more durable, which would be required for real clinical effectiveness.
The Belgium study included 55 brain-damaged patients, 30 with MCS and 25 with VS/UWS, who were hospitalized in the neurology department of the University Hospital of Liege or at a rehabilitation center. The study group, ranging in age from 15 to 85, had heterogeneous causes of brain damage. Some of the patients had suffered a traumatic brain injury; in other cases, the damage was due to a non-traumatic event such as a subarachnoid hemorrhage or anoxia. The time since brain damage ranged from seven days to 26 years.
The study was a double-blind sham-controlled design in which anodal and sham tDCS were delivered by randomized order over the left dorsolateral prefrontal cortex for 20 minutes.
Patients were assessed using the Coma Recovery Scale Revised (CRS-R) — a scale that goes from 0 to 23, with the higher score meaning higher awareness or demonstration of cognitively mediated behaviors — directly before and after anodal and sham stimulation. They also were assessed 12 months later with the Glasgow Outcome Scale-Extended to determine the long-term effect of tDCS.
“Responders” were defined as those patients who after receiving tDCS presented a sign of consciousness — intentional or functional communication, command following, visual pursuit, recognition, manipulation, localization or functional use of objects, or orientation to pain — that was not present before the treatment or before or after a sham treatment.
The article reported that 13 of the 30 MCS patients (43 percent) showed some improvement after tDCS. Five of the 13 MCS responders were at least five months post-injury. In the VS/UWS group, two patients (8 percent) showed a response. Both of them were less than three months post-injury. The associated 95% confidence interval was 0.67–0.97. [For more data, see “Treatment Effects.”]
“No correlation between tDCS response and patient outcome was observed at 12 months follow-up,” the team reported.
“From a medical perspective the changes were moderate and transient, but in some cases the patients recovered a functional communication, which represents emergence from the minimally conscious state,” said Dr. Laureys and the study's first author, physiotherapist Aurore Thibaut, a PhD candidate, in an e-mail. “For others, it was a response to command, which is the first step to restore a code of communication.
“Our study illustrates the residual capacity for neural plasticity and temporary recovery of (minimal) signs of consciousness in some patients in MCS, but does not permit us to make any claims regarding possible long-term tDCS effects in this setting,” the study authors noted.
They noted that the fact that some MCS patients responded fairly long after their initial injury was consistent with “previous evidence for late recovery and neural plasticity in MCS.” They speculated that the transient improvements in consciousness as measured by change in CRS-R “are related to improvement in attention and working memory.”
The researchers said that tDCS may offer advantages over another investigative modality, repetitive transcranial magnetic stimulation, “as it is easier to apply, causes less discomfort, and has a lower associated risk of inducing seizures — the latter being especially important in the setting of severe brain injury.”
The editorial, written by John Whyte, MD, PhD, director of the Moss Rehabilitation Research Institute in Elkins Park, PA, noted that the medical community is beginning to change its thinking on the prognosis of patients with disorders of consciousness.
“Until recently, the medical community has viewed them with great pessimism with respect to both prognosis and effective treatments,” Dr. Whyte wrote. “Within the rehabilitation community, optimizing medical stability and physical health to facilitating natural recovery is viewed as important, but attempts to accelerate recovery have generally involved off-label treatments in the absence of proven treatments. In the United States, the climate of pessimism has been self-perpetuating; health insurers often restrict access to rehabilitation for patients with DOC [disorders of consciousness], who are then transferred directly from acute care centers to long term care facilities or family homes, largely disconnected from the academic research enterprise.”
But Dr. Whyte noted that there are reasons to be more optimistic. “We now know that meaningful clinical recovery from DOC can continue for 2–5 years post-injury, at least for those with traumatic etiologies, and that a sizable minority of those with a traumatic DOC in the early months after injury can eventually reach independent levels of functioning.”
Joseph T. Giacino, PhD, an associate professor of physical medicine and rehabilitation at Harvard Medical School and director of the Disorders of Consciousness Program at Spaulding Rehabilitation Hospital in Charlestown, MA, told Neurology Today that the results from the Belgian study are “of interest because there does appear to be an effect in the MCS group.”
“They wanted to see if there was a behavior that had not previously been seen. That's a pretty high bar,” he said.
But at the same time, Dr. Giacino said, the observed changes following tDCS need to be viewed with some skepticism because the responses of persons with MCS can vary from one time to another. “I'd have to be convinced that these patients were not just normally fluctuating,” he said. Having just one “before” measurement to compare with the post tDCS score probably is not sufficient, he said.
Dr. Giacino said because the study group of brain-injured patients varied by type of brain injury sustained and length of time from onset, it was difficult to say at what point in time tDCS might work best as an intervention. Also, “with repeat stimulation over weeks or months, could you permanently change the brain to bring about potentially favorable neuroplastic changes?”
Dr. Giacino said it is becoming increasingly clear that the brain has sometimes a surprising capacity to recover from injury.
“It now appears that one in five patients who have prolonged disturbance of consciousness will regain some level of independent functioning,” he said. “The word needs to get out that this population (of patients) is dynamic. They do change.”
The following reflects the change in the total Coma Recovery Scale-Revised Scores
LINK UP FOR MORE INFORMATION:
•. Thibaut A, Bruno M-A, Ledoux D, et al. tDCS in patients with disorders of consciousness: Sham--controlled randomized double blind study. Neurology 2014; E-pub 2014 Feb. 26.
•. Whyte J. Disorders of consciousness: The changing landscape of treatment. Neurology 2014: E-pub 2014 Feb. 26.
•. Henry TR, Ezzeddine MA. Clinical and ethical challenges: Approach to the patient with transient alteration of consciousness. Neurol Clin Pract 2013; 2(3):179–186.© 2014 American Academy of Neurology
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