The Cerebrovascular Center at Johns Hopkins | Research: Cerebrovascular disorders

Research Areas

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Acute Stroke Diagnosis and Treatment

Neural Basis for Lexical Processes in Hyperacute Stroke

Neural Basis of Unilateral Spatial Neglect

Revising the National Institutes of Health Stroke Scale

Stroke in Young Adults

Visual Field Function after Chronic Stroke

Acute Stroke Diagnosis and Treatment

Under the direction of Robert Wityk, M.D.

Our research here focuses on the complex issue of blood pressure management in patients with acute ischemic stroke due to blocked blood vessels. While we know that long-term treatment of chronic hypertension is good in terms of preventing stroke, we also know from experience that lowering blood pressure rapidly in someone having an acute stroke can make them worse. In the first few hours to one day after the start of a stroke, the brain is trying to maintain blood flow. One mechanism that the body uses to accomplish this is to spontaneously raise blood pressure.

We have been looking at using this natural response to stroke as a means of improving blood flow to the brain in other patients. Certain intravenous medications are commonly used by anesthesiologists and neuro-intensivists to gradually elevate blood pressure for a variety of reasons. We are investigating if elevating the blood pressure of certain stroke patients to a moderate degree and for a short period of time might help them regain some function. These treatments are carried out with intensive neurological monitoring in the Neuro Critical Care Unit at The Johns Hopkins Hospital or the 8-bed unit at the Johns Hopkins Bayview Medical Center with the assistance of an experienced staff of neurology / critical care physicians and nurses.

Our preliminary results using sophisticated MRI studies suggest that patients who have regions of the brain that are not receiving enough blood, but are not irreversibly damaged, can show rapid improvement in terms of movement, language or visual abilities when blood pressure is carefully elevated. These results have led to a multicenter pilot clinical trial at Hopkins as well as other institutions in Baltimore and Boston.

Neural Basis for Lexical Processes in Hyperacute Stroke
RO1, DC 5375
Under the direction of Argye Hillis, M.D.

The goal of this project is to identify areas of the brain that are critical for specific cognitive processes underlying language by identifying areas of the brain where neural dysfunction causes impairment of specific language processes and where restoration of neural function leads to improvement of those language processes. These brain-language relationships are identified utilizing MR perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI), along with testing of language processing at the same time, in subjects less than 24 hours post onset of stroke. The major hypothesis is that PWI and DWI with concurrent language testing can revealareas of neural dysfunction, with or without structural damage, associated with disruption of each cognitive process underlying language tasks like naming, reading or spelling a word. The imaging and language tests together are expected to show that there are distinct areas of cortex that are essential for retrieving spoken word forms versus written word forms, and that the regions are specific to a particular grammatical word class (e.g., nouns versus verbs). It is also predicted that still other regions are crucial for representing the meanings of various types of words, or for more peripheral components of speech or written output for all types of words. It is also hypothesized that repeat DWI, PWI and language tests at three days post-onset, often after intervention to restore blood flow, will reveal the effect of reperfusion of particular areas of brain on language functions in acute stroke. Identifying these brain-language associations is critical for clinical management of aphasia caused by stroke because it will allow specific predictions about what language functions are likely to recover if blood flow can be restored to a given area.This knowledge will allow us to select the most appropriate interventions for stroke patients and weigh the risks and potential benefits of intervention.

Neural Basis of Unilateral Spatial Neglect
RO1, NS 047691
Under the direction of Argye Hillis, M.D.

Hemispatial neglect, a failure to attend or respond to stimuli on the side contralateral to a brain lesion, is a remarkably common and disabling consequence of stroke on the right side of the brain. This extraordinary syndrome may be manifest by neglecting to shave the left side of the face, eat from the left side of the plate, or read the left side of the page or initial letters of words.There has been considerable controversy regarding the sites of brain damage most likely to cause hemispatial neglect, in part because different areas of damage or tissue dysfunction cause different forms of neglect. The goal of this project is to identify the nature and the neural basis of different types of hemispatial neglect with a novel approach utilizing magnetic resonance perfusion weighted imaging (PWl) and diffusion weighted imaging (DWl), along with testing of hemispatial neglect at the same time, in patients less than 24 hours post onset of stroke, and at three days after onset. PWI shows regions of dysfunctional brain tissue caused by low blood flow, while DWl reveals densely ischemic or infarcted tissue, in acute stroke. The major hypothesis is that PWl and DWl with concurrent hemispatial neglect testing can reveal areas of neural dysfunction, with or without structural damage, associated with hemispatial neglect in different reference frames or in different tasks, before substantial reorganization. It is further hypothesized that restoration of tissue function in a given region (by restoring regional blood flow) will result in resolution of specific types of hemispatial neglect. Results are expected to reveal distinct areas of cortex crucial for spatial attention in different reference frames, and to reveal mechanisms of acute recovery of hemispatial neglect.

Revising the National Institutes of Health Stroke Scale (NIHSS)
Development of a modified NIHSS using cognitive testing and diffusion and perfusion-weighted MR imaging
Under the direction of Rebecca Gottesman, M.D. with Dr. Argye Hillis, M.D.

The purpose of this study is to modify the existing National Institutes of Health Stroke Scale (NIHSS) using simple cognitive tests. The current NIHSS is more heavily weighted towards motor deficits as well as towards dominant- hemispheric deficits. A stroke in the nondominant hemisphere will have a lower NIHSS score than an equivalent-sized stroke in the dominant hemisphere. Because of this, the NIHSS does not represent functional outcome well after stroke, although it is often used as an endpoint in clinical trials and in assessments of functional prognosis and recovery. This is partly due to the fact that the NIHSS represents already infarcted tissue, seen using diffusion-weighted imaging (DWI). However, perfusion-weighted imaging (PWI) is more representative of cognitive dysfunction. We think PWI is a more direct representation of true functional outcome. Cognitive tests appear to correlate more strongly with PWI than does the NIHSS. For this reason, we plan to use a subset of these cognitive tests (those that most accurately represent volume of hypoperfusion, or PWI) in combination with the NIHSS to create a more relevant scale in the assessment of patient outcome.

Stroke in Young Adults

Under the direction of Robert Wityk, M.D.

Stroke in young adults (under the age of 45 to 50 years old) is often completely unexpected by the patient and frequently unexplained by the physician. In this patient population, strokes tend to be due to unusual disorders and in fully a third of patients, no clear cause is found despite extensive testing. As a tertiary referral center, we make use of extensive resources and expertise in allied fields of neuroradiology, neurosurgery, cardiology, hematology, rheumatology (Vasculitis Center) and rehabilitation medicine to bring the most advanced diagnostic and treatment options to patients with this uncommon problem.

Over the years, Johns Hopkins has developed clinical research registries to try and learn more about possible causes for some of these conditions, and to offer the best multidisciplinary treatment options. Examples include the following:

Arterial dissection of cerebral vessels is perhaps the most common cause of stroke in otherwise healthy persons. There are many misperceptions about the outcome and long-term risk of dissection.

Fibromuscular dysplasia may be associated with dissection, but generally is a rather benign condition when it involves the cerebral arteries.

Moyamoya disease -- in collaboration with pediatric neurology and neurosurgery, we also see a number of patients with this strange condition in which the arteries in the brain gradually narrow down and occlude. Considerable controversy surrounds the appropriate treatment of this condition. I have treated some patients with minimal intervention, and we have had success in selected patients with bypass surgery or even intracranial angioplasty. Our investigations using perfusion MRI techniques to follow this condition may give us tools to predict how patients will do long-term.

Patent Foramen Ovale (PFO) -- the appropriate management of the common cardiac condition in a young stroke patient is poorly understood, and we strongly support the use of clinical trials to gather scientific evidence for medical or interventional treatments.

Visual Field Function after Chronic Stroke
Reorganization of the neural substrates of visual perception after posterior cerebral artery stroke
Under the direction of Rebecca Gottesman, M.D. with Argye Hillis. M.D.

The purpose of this study is to explore the extent of reorganization of visual field function after chronic stroke. A common method of localizing brain areas critical for specific functions is to identify chronic stroke patients with a specific functional deficit and compare structural neuroimaging scans with patients who lack this specific deficit. The location that is involved in the former, but not latter, of these patients is then felt to account for the function in question (a lesion overlap/ subtraction technique). However, this technique does not always match other neuroanatomic knowledge because it does not account for reorganization after stroke, which may cause a chronic stroke patient to have involvement of a particular brain region without a deficit in the function controlled by that region. We anticipate that the flaws with this technique in chronic stroke patients will be apparent in a study of patients with visual field deficits after posterior cerebral artery (PCA) strokes. Although it is recognized that the striate cortex is responsible for visual field function, we hypothesize that the lesion overlap/ subtraction technique will fail to recognize the striate cortex as the location of importance in patients with visual field deficits, and that instead it will suggest that the problem is due to stroke in more distal PCA areas (those involved in larger strokes, as these patients are less likely to have adequate reorganization). We are performing visual field testing on patients who had strokes in the PCA territory at least six months prior to enrollment and will use the lesion overlap/ subtraction technique to test our hypotheses. We also will pursue functional MRI testing in a subset of these patients to assess the brain regions to which visual fields reorganize during recovery.