Clockwise from bottom: Anna M. Barrett, MD, associate professor, Physical Medicine and Rehabilitation, UMDNJ-New Jersey Medical School (NJMS) and director, Stroke Rehabilitation Research, Kessler Medical Rehabilitation Research and Education Corporation (KMRREC); Karen Kelly and Shpresa Ahmeti, Stroke Rehabilitation Research Assistants at KMRREC; Siby Varughese, MA, RN, Stroke Rehabilitation Research Coordinator, KMRREC

Innovative research helps stroke patients by Anna M. Barrett

It is estimated that about half of the 5.4 million people in the U.S. who have experienced a stroke have some type of cognitive or mental processing problem, speech or language disorder, visual-spatial disorder, memory loss or other problems. Since ancient times, attempts have been made to treat many of these issues. However, until recently it was believed that unless recovery occurred in the first three to six months following stroke, recovery was not possible. Research has proven differently.

Stroke is a major health issue in the U.S. causing not only paralysis but, for millions of Americans, cognitive or mental processing problems. These include communication, visual-spatial, and memory disorders, among other impairments. Much work is needed to improve rehabilitation to restore people with thinking and cognitive problems, including acquired speech and language disorders (aphasia), and issues with computing distances and space (spatial neglect), to their former lives.

In the Stroke Rehabilitation Research Laboratory at KMRREC, my staff and I explore new means of helping people improve post-stroke cognition. The Stroke Laboratory’s studies attempt to apply principles derived from experimental psychology, psychobiology and cognitive neuroscience to unlock the brain’s lost visual-spatial and communication potential.

Spatial neglect is a failure to respond, report, attend or orient to stimuli presented to the side of space opposite a brain lesion associated with functional disability. It occurs more commonly in patients with right hemisphere brain damage than in those with left hemisphere damage. For example, after a stroke on the right side of the brain, individuals may not detect objects on their left, or may asymmetrically represent or act on their environment. This imbalanced behavior cannot be fully explained by sensory abnormality—an abnormal drawing from memory, for example (see Figure 1), may be produced without the artist’s actually “looking at” what is drawn, except via mental imagery. Rather, spatial neglect may be a problem with coordinating perception, representation and action. While the severity of spatial neglect usually lessens over time, it is still a major predictor of long-term disability, and thus may play a role in regaining independence in the chronic phase of post-stroke recovery.

	Figure 1: This drawing was produced by a client with spatial neglect after damage to the right side of the brain. Although he is drawing from memory, we can see that part of his "visual concept" is missing. Because each side of the brain controls the opposite side of the body, people with spatial neglect after right sided stroke usually have trouble with items and events on the left.
	Figure 2: The left hemisphere of the brain contains critical processors for speech and language. When the left side of the brain is damaged, speech and language disorder (aphasia) can result. In this image, the large white arrow points to an area of damaged tissue (which is white, while normal brain is dark) in the brain's left hemisphere. White regions centrally in the picture represent fluid (small black arrow), which normally circulates throughout the brain and distributes needed dissolved substances for cell function.

Unfortunately, chronic spatial deficits might be difficult to detect reliably. In a study funded by the National Institutes of Health-National Institute of Neurological Disorders and Stroke, the Stroke Laboratory is working to standardize systematic detection of mild deficits, using a video testing method sensitive to small errors. For example, a client might try to mark the center of a line while viewing his hand and a stimulus on a video screen. A video mixer can be used to right-left reverse the image, so that leftward movement appears on the screen to be moving to the right, and vice versa. As people with visual-spatial problems monitor their own bodies in this mirror-reversed manner, we can calculate whether errors may be primarily attributed to deficient perceptual awareness (seeing or knowing where) or intentional action such as aiming. These two error types may originate from problems in different systems, mediated by different brain regions.

Safe and adaptive movement in complex environments is the basis for functional independence and daily life competence. Spatial function is clinically assessed only in near space, although we are often required to distribute attention over large spatial areas beyond arms’ reach (sports, navigating in a mall or an airport, driving). My collaborators and I are among a few laboratories in the world examining the neuropsychological mechanisms of far bias and distractibility in brain-injured post-stroke patients. When problems are identified in far space, however, it is not clear which treatments would be most appropriate. In the current set of experiments, the group will investigate whether people with far space deficits improve while wearing an eye patch, a treatment that I (as well as others) have reported may benefit near space symptoms.

The long-term goal of this work is to translate spatial science to new and more effective treatments of post-stroke spatial attentional disorders. The laboratory recently proposed a follow-up group of studies in this direction, attempting to assess effects of several other available treatments. The aim is to determine if specific therapies targeted to deficits may be more effective. Although there are no known benefits to the video assessment performed as part of the NIH-funded spatial neglect studies, behavioral stimulation and visual-motor practice theoretically might improve performance. The mirror-reversal apparatus is also similar to prism and virtual-reality treatments being used at other centers for spatial neglect. Our laboratory is working to examine whether using the video apparatus may benefit performance, and if so, to adapt the video apparatus to wide use in clinical settings where prism prescriptions or virtual reality equipment may not be practical.

A second study being performed in the Stroke Laboratory, funded by UCB Pharma, Inc., focuses on the pharmacological treatment of stroke-related aphasia. Effective approaches for patients with aphasia may often be limited to management (e.g. family counseling) and vicariation (e.g., computer devices). More than one million people with acquired speech, language and communication disorders in the U.S. need remediative therapies to improve their symptoms and return them to their previous activities.

Piracetam is one of the few medications reported to improve aphasia in previous studies, but it is not available in the U.S. I proposed to UCB Pharma, Inc. a pilot study investigating whether levetiracetam (Keppra), currently approved for treatment of epilepsy, may improve aphasia symptoms. Levetiracetam, related to piracetam, has been associated with memory improvement in a scopolamine-induced amnesia rodent model. In an open-label, multiple-baseline prospective pilot study, the stroke laboratory will administer levetiracetam to 50 patients with chronic aphasia and serially examine their speech and language function to determine if any improvement in spontaneous speech, verbal fluency, naming, repetition, discourse and memory occurs.

Quality care is integral to the cognitive recovery process. Rehabilitation therapy is an important part of this care. Scientific treatment approaches are extremely valuable in planning care and in counseling individuals and their families about adaptation to the disabling conditions associated with stroke. I am working collaboratively with other scientists at KMRREC, as well as at NJMS, Montclair State University, Seton Hall University, Penn State University and other institutions to remain in the forefront of progress towards helping people maximize recovery after stroke.

This article was written with the assistance of Monifa Springer, MPH, and Siby Varughese, BSN, RN, MA.

Anna M. Barrett, MD, is an associate professor of physical medicine and rehabilitation at UMDNJ-New Jersey Medical School and director of stroke rehabilitation research, neurology and neurosciences at KMRREC. Dr. Barrett has clinical research interests in behavioral neurology, cognitive neuroscience, and neurorehabilitation. She received the 2004 Ohio State University Harold Brenner Pepinsky early career award, and two career development awards from the National Institutes of Health. Dr. Barrett completed her undergraduate work simultaneously at Harvard University and Radcliffe College, her medical school training at New York University School of Medicine, neurology residency training at Columbia-Presbyterian/The Neurological Institute in New York, and a fellowship in Behavioral Neurology/Neuropsychology at the University of Florida College of Medicine.