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  • ISSN: 2333-7087
    Special Issue Released on Cerebrovascular Disease
    Elisabeth Breese Marsh, MD
    Associate Director
    Neurology Residency Program
    Assistant Professor of Neurology
    The Johns Hopkins University
    Acute Stroke Treatment
    Ryan J. Felling1,3#*, Roland Faigle1#, Cheng-Ying Ho2, Rafael H. Llinas1 and Victor C. Urrutia1
    Abstract: Recombinant tissue plasminogen activator (t-PA) is the only FDA approved therapy for acute ischemic stroke. Cerebral microbleeds (CMBs) or cerebral amyloid angiopathy (CAA) are currently not contraindications, however, data regarding this complex issue are limited. We report 2 cases of fatal intracerebral hemorrhage (sICH) after IV t-PA, each with evidence of CAA. Patients with CAA may have increased risk for IV thrombolysis-associated sICH. We highlight the severe and catastrophic pattern of ICH, which may be a defining characteristic, and discuss the limitations of our current understanding of the risk of thrombolysis-associated ICH in patients with CAA and/or CMBs.
    Elisabeth B. Marsh* and Rafael H. Llinas
    Introduction: Intravenous tissue plasminogen activator revolutionized the treatment of acute ischemic stroke. However, there remain situations when administration is contraindicated. Optimal treatment in these patients is less clear.
    Case Series: We describe a small case series of 7 patients presenting with fluctuating symptoms concerning for a capsular warning syndrome who were loaded with 300mg of clopidogrel. Four of the 7 had complete, resolution of their symptoms. The others experienced stabilization of their deficits and stopped fluctuating before beginning to improve, but were discharged with persistent deficits. Four patients had evidence of small vessel lacunes on diffusion weighted MRI while the others had no diffusion bright lesions.
    Conclusion: Our experience suggests that acutely loading with clopidogrel is safe and effective in the treatment of stuttering lacunes.
    Carolyn A. Cronin1* and Lisa D. Hermann2
    Background: Rapidly improving or mild symptoms is the most common reason that acute stroke patients arriving within the approved time window are not treated with intravenous tissue-type plasminogen activator (IV tPA). We reviewed outcomes at discharge for patients excluded from IV tPA because of rapidly improving or mild symptoms, with the aim of being better able to identify patients who may benefit from thrombolysis.
    Methods: All patients between April 2006 and June 2010 from our center who did not receive IV tPA with “rapidly improving or mild symptoms” as the reason for exclusion were identified. Poor outcome was defined as hospital discharge to location other than home or inability to ambulate independently at discharge.
    Results: There were 66 patients excluded from tPA treatment because of rapidly improving or mild symptoms. Eleven patients (16.7%) had poor outcomes. In 6 patients (9%), poor outcome was due to neurologic deficit. All 6 patients with neurologic deficits had right hemisphere strokes, and one also had cerebellar infarcts.
    Conclusions: Patients presenting with rapidly improving or mild symptoms do not universally have good outcomes. This may be particularly true in the case of right hemispheric ischemia where deficits are not fully reflected by NIHSS score. If a patient with a low NIHSS score is otherwise a candidate for tPA, a more detailed exam is warranted to better identify potentially disabling deficits that might benefit from thrombolysis.
    Chinar Dara1, Jee Bang1, Rebecca F. Gottesman1,2 and Argye E. Hillis1,3,4*
    Background: Neurologists generally consider hemispatial neglect to be the primary cognitive deficit following right hemisphere lesions. However, the right hemisphere has a critical role in many cognitive, communication and social functions; for example, in processing emotional prosody (tone of voice). We tested the hypothesis that impaired recognition of emotional prosody is a more accurate indicator of right hemisphere dysfunction than is neglect.
    Methods: We tested 28 right hemisphere stroke (RHS) patients and 24 hospitalized age and education matched controls with MRI, prosody testing and a hemispatial neglect battery. Emotion categorization tasks assessed recognition of emotions from prosodic cues. Receiver operating characteristic (ROC) analyses were used to compare tests in their ability to distinguish stroke patients from controls.
    Results: ROC analyses revealed that the Prosody Score was more effective than the Neglect Battery Score in distinguishing stroke patients from controls, as measured by area under the curve (AUC) ; Prosody Score = 0.84; Neglect Battery Score =0.57. The Prosody Score correctly classified 78.9%, while Neglect Score correctly classified 55.8% of participants as patients versus controls. The Prosody Score was similar to the total NIH Stroke Scale in identifying RHS patients (AUC=0.86, correctly classifying 80.1% of patients versus controls), but the tests only partially overlapped in the patients identified.
    Conclusions: Severe prosody impairment may be a better indicator of right hemisphere dysfunction than neglect. Larger studies are needed to determine if including a bedside test of Prosody with the NIH Stroke Scale would most efficiently and reliably identify right hemisphere ischemia.
    Diagnosis/Management Considerations
    Carolyn A. Cronin1*, Manuel Fortes2 and Teng C. Lee3
    Abstract: We report the case of a young man with recurrent strokes over a four year period, all occurring after leaning forward. He had suffered damage to the right subclavian and right carotid arteries in a car accident 20 years prior. Review of history and imaging concluded that all of his infarcts had been in the distribution of the right carotid artery. CT angiogram revealed that a segment at the origin of the right common carotid artery was adjacent to the sternum and kinked at the point of contact. Proposed mechanism of infarcts is position dependent intermittent vessel damage causing thrombosis and distal embolization. The patient underwent surgical repair, with no further events. This case highlights the importance of evaluating structures adjacent to vessels in patients with cryptogenic strokes.
    Jennifer L. Dearborn*, Victor C. Urrutia, and Steven R. Zeiler
    Abstract: The interrelationship between stroke and cancer is complex. Cancer and stroke may occur independently in a given patient, or cancer may directly or indirectly lead to stroke via: hypercoaguability, non-bacterial thrombotic endocarditis (NBTE), direct tumor compression of blood vessels, or treatment-related effects which potentiate stroke. Patients with cryptogenic stroke are relatively common, and under the right circumstances, may provide an opportunity to screen for occult malignancy. In this review, we discuss relevant data linking stroke and cancer as well as propose a testable algorithm for cancer screening in the patient with cryptogenic stroke. Future directions should focus on validating patient-care algorithms in prospective clinical trials to provide an evidence base for this important issue.
    John C. Probasco1*, Tiffany Chang1, David Victor2 and Paul Nyquist1
    Introduction: Ischemic stroke has been associated with stunned myocardium and neurogenic pulmonary edema (NPE). We studied a population of patients with large vessel brainstem ischemic stroke to see if there was an increased risk of pulmonary edema associated with strokes in this region independent of myocardial stunning.
    Hypothesis: Large vessel ischemic strokes of the brainstem are associated with neurogenic pulmonary edema and occur independently of myocardial stunning.
    Methods: This is a retrospective case control study of 1,278 patient admissions. Two hundred ten patients were identified with large vessel ischemic stroke or transient ischemic attack (mean age 65 years, 55% female, 50% black). Infarction locations included: brainstem (N=22), right middle cerebral artery involving the insula (N=38), left middle cerebral artery involving the insula (N=37), and transient ischemic attack (N=113). Multivariate logistic regression models for presence of echocardiographic wall motion abnormalities, QTc-interval prolongation, elevated serum troponin, and pulmonary edema were developed to examine the relative contribution of stroke location and markers of cardiopulmonary dysfunction to each respective outcome, controlling for patient characteristics.
    Results: Large vessel brainstem stroke was associated with pulmonary edema (adjusted OR 29.23, 95% CI 1.90-449.51) but not cardiac abnormalities. Large vessel left middle cerebral artery stroke was also associated with pulmonary edema (76.44, 6.93-843.54) as well as QTc-interval prolongation (4.55, 10.77-19.24). Large vessel right middle cerebral artery stroke was associated with pulmonary edema (10.88, 1.02-116.70) as well as elevated serum troponin (10.51, 1.71-64.82).
    Conclusion: In a retrospective case control study, large vessel brainstem stroke was associated with the development of pulmonary edema independent of cardiac abnormalities associated with myocardial stunning, suggesting a separate brainstem pathophysiologic mechanism which directly affects the lungs but not the heart.
    Aiham Albaeni1, Shaker M. Eid1*, Dhananjay Vaidya2 and Nisha Chandra-Strobos3
    Background: Despite 50 years of research, prognostication post cardiac arrest traditionally occurs at 72 hours. We tested the accuracy of a novel bedside score within 24 hours of hospital admission, in predicting neurologically intact survival.
    Methods: We studied 192 adults following non-traumatic out-of-hospital cardiac arrest. In a 50% random modeling sample, a model for survival to discharge with good neurological outcome was developed using univariate analysis and stepwise multivariate logistic regression for predictor selection. The diagnostic efficiency of this modeled score was assessed in the remaining 50% sample using receiver operating characteristic (ROC) analysis.
    Results: In this study, 20% of patients survived to discharge with good neurological outcome. The final logistic regression model in the modeling sample retained three predictors: initial rhythm Ventricular Fibrillation, Return of Spontaneous Circulation ≤ 20 minutes from collapse, and Brainstem Reflex Score ≥ 3 within 24 hours. These variables were used to develop a three-point Out of Hospital Cardiac Arrest score. The area under the (ROC) curve was 0.84 [95% CI, 0.75-0.93] in the modeling sample and 0.92 [95% CI, 0.87-0.98] in the validation sample. A score ≥ 2 predicted good neurological outcome with a sensitivity of 79%, a specificity of 92%, and a negative predictive value of 93%. A score ≥1 had a sensitivity of 100% and a negative predictive value of 100%; however, the specificity was only 55%.
    Conclusion: This study demonstrates that a score based on clinical and easily accessible variables within 24 hours can predict neurologically intact survival following cardiac arrest.
    Donna C. Tippett1,2,3*, John K. Niparko4 and Argye E. Hillis1,3,5
    Abstract: Recent advances in neuroimaging contribute to new insights regarding brain-behavior relationships and expand understanding of the functional neuroanatomy of language. Modern concepts of the functional neuroanatomy of language invoke rich and complex models of language comprehension and expression, such as dual stream networks. Increasingly, aphasia is seen as a disruption of cognitive processes underlying language. Rehabilitation of aphasia incorporates evidence based and person-centered approaches. Novel techniques, such as methods of delivering cortical brain stimulation to modulate cortical excitability, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, are just beginning to be explored. In this review, we discuss the historical context of the foundations of neuroscientific approaches to language. We sample the emergent theoretical models of the neural substrates of language and cognitive processes underlying aphasia that contribute to more refined and nuanced concepts of language. Current concepts of aphasia rehabilitation are reviewed, including the promising role of cortical stimulation as an adjunct to behavioral therapy and changes in therapeutic approaches based on principles of neuroplasticity and evidence-based/person-centered practice to optimize functional outcomes.
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