Minimally Conscious Patient Makes Strides Following Deep Brain Stimulation

A 38-year-old man in a minimally conscious state for more than six years has regained the ability to speak and orally ingest food after thalamic deep brain stimulation, according to a study in the August 2 Nature. The case study demonstrates the need for the improved diagnosis of disorders of consciousness through regular reassessment of patients’ brain activity, say those involved with his improvement.

“We’re seeing a recuperative capability of the brain that we assumed wasn’t there,” Joseph J. Fins, MD, a coauthor of the study, told Neurology Reviews. “But there is a capability there, and what we’ve done is try to harness it and accelerate it here, amplifying the circuits and accelerating the process.” Dr. Fins is Chief of the Division of Medical Ethics at Weill Medical College of Cornell University in New York City, where he is also a Professor of Medicine, of Public Health, and of Medicine in Psychiatry; in addition, he is Director of Medical Ethics at New York Presbyterian-Weill Cornell Medical Center, also in New York City.

Dr. Fins and his coinvestigators emphasized that the success was achieved in just one patient, the culmination of 10 years of research by a team of neurologists, neurosurgeons, neuropsychologists, rehabilitation specialists, and ethicists. The group was headed by Nicholas D. Schiff, MD, Director of Weill Medical College’s Laboratory of Cognitive Neuromodulation.

MISSED OPPORTUNITIES FOR IMPROVEMENT

The patient had sustained a closed head injury following an assault, resulting in bilateral subdural hematomas “with significant mass effect that resulted in subfalcine and central herniation” and initially left him in a deep coma, said the authors. Twelve weeks later, he was transferred to an inpatient brain injury rehabilitation program, “where physical, occupational, speech, and related therapies were performed for the next 21 months,” reported the researchers. The patient’s level of arousal improved, and he was inconsistently able to follow commands, which indicated to clinicians that he had advanced to the minimally conscious state; then, at 24 months post injury, he was transferred to a long-term care facility, where he failed to recover consistent command-following or communication ability. For recruitment to the current study, six-and-a-half years after the initial injury, the patient was readmitted to a rehabilitation program and reassessed for continued therapy.

Coauthor Ali Rezai, MD, Professor of Neurosurgery and Director of the Center for Neurological Restoration at the Cleveland Clinic, told Neurology Reviews, “Patients with severe traumatic brain injury should undergo a more comprehensive follow-up evaluation after they are discharged from acute care settings.” He proposed use of routine assessment tools, such as the coma recovery scale and brain imaging. These, in addition to quantification of a patient’s consciousness, communication and behavior, and motor and sensory characteristics with assessments performed on multiple occasions, “will help to further the diagnosis and classification of severe traumatic brain injury and will facilitate [therapeutic] development,” said Dr. Rezai.

Dr. Fins concurs: “There needs to be more vigilance in the diagnostic assessment of these patients, and [clinicians must] appreciate [that a patient’s status] can change over time,” he said. “One examination does not suffice, because behaviors are not always going to be elicited on a single exam.” The current protocol, he noted, has led to a high rate of misdiagnosis, with many minimally conscious patients being identified as vegetative. A small study by Childs et al found a 37% misdiagnosis rate for patients diagnosed as being in a coma or persistent vegetative state; the rate was greater with traumatic injury. Andrews et al reported a 43% misdiagnosis rate, with some patients presumed to have been vegetative for longer than one year.

DIAGNOSTIC REFINEMENT AND THERAPEUTIC ENGAGEMENT

It may be difficult for a patient’s physician to challenge a vegetative diagnosis with inconsistently reproducible instances of consciousness—a hallmark of the minimally conscious state—noted Dr. Fins; but the distinction is crucial. Minimally conscious patients have intact, but dormant, neural networks. With the onset of continuous bilateral stimulation, the patient represented in the Nature article showed “several qualitative changes in behavior during deep brain stimulation titration that correlated with abrupt changes in [JFK Coma Recovery Scale–Revised] subscale scores,” said the authors. There were longer periods of eye opening and increased responsiveness to command, they reported, and the patient displayed the first instances of functional object use and intelligible verbalization two days later.

In addition, the patient takes three meals a day by mouth, and although he can perform self-feeding movements, muscle deterioration and contractures prevent him from feeding himself—still a significant improvement from his dependence on IV feedings before the study. “His mind has progressed ahead of his deteriorated body,” said Dr. Fins. The patient can also repeat the first 16 words of the Pledge of Allegiance and is getting back a sense of personal identity by responding to an old nickname. “So he is regaining a sense of self.”

“The behavioral improvements described in this report are notable, given their late emergence and potential functional significance,” said the study authors. “However, the generalizability of the results is unknown, and expectations raised by this report should be tempered.”

Dr. Fins noted that he and his coinvestigators have obtained Investigational Device Exemptions for 11 more minimally conscious patients. “Hopefully, we’ll develop a little bit of variance,” he said, which may lead to a diagnostic refinement of which subset of minimally conscious patients will and will not respond to deep brain stimulation. He and Dr. Rezai both noted that other potential therapeutic options for patients in a minimally conscious state, such as pharmacologic therapies like Ambien® (zolpidem tartrate) and Paxil® (paroxetine), or a combination of a pharmacologic agent and deep brain stimulation, remain to be investigated as well.            

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