Indrani Acosta

Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia

Background: Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. Methods: Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. Results: Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0–1). Conclusions: Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct.

Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC).

Rationale Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. Aims The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. Study Design This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. Outcomes The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

Pharmacological Deep Vein Thrombosis Prophylaxis Does Not Lead to Hematoma Expansion in Intracerebral Hemorrhage With Intraventricular Extension

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are at high risk for development of deep venous thrombosis. Current guidelines state that low-dose subcutaneous low molecular weight heparin or unfractionated heparin may be considered at 3 to 4 days from onset. However, insufficient data exist on hematoma volume in patients with ICH before and after pharmacological deep venous thrombosis prophylaxis, leaving physicians with uncertainty regarding the safety of this practice. Methods— We identified patients from our stroke registry (June 2003 to December 2007) who presented with ICH only or ICH+intraventricular hemorrhage and received either low molecular weight heparin subcutaneously or unfractionated heparin within 7 days of admission and had a repeat CT scan performed within 4 days of starting deep venous thrombosis prophylaxis. We calculated the change in hematoma volume from the admission and posttreatment CTs. Hematoma volume was calculated using the ABC/2 method and intraventricular hemorrhage volumes were calculated using a published method of hand drawn regions of interest. Results— We identified 73 patients with a mean age of 63 years and median National Institutes of Health Stroke Scale score 11.5. The mean baseline total hematoma volume was 25.8 mL±23.2 mL. There was an absolute change in hematoma volume from pre- and posttreatment CT of −4.3 mL±11.0 mL. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological deep venous thrombosis prophylaxis within 2 or 4 days after ICH found no increase in hematoma size. Conclusions— Pharmacological deep venous thrombosis prophylaxis given subcutaneously in patients with ICH and/or intraventricular hemorrhage in the subacute period is generally not associated with hematoma growth.

Neurofluctuation in patients with subcortical ischemic stroke

Objective: The purpose of this study was to assess the incidence of deterioration, fluctuation, and associated risk of poor outcome in patients with subcortical stroke (SCS). Methods: We conducted a prospective observational study, enrolling patients admitted with SCS based on their clinical examination and imaging studies. An NIH Stroke Scale evaluation was performed daily and whenever deterioration in examination was detected. Neurologic deterioration was defined as a motor score increase of at least 1 on the NIH Stroke Scale. Modified Rankin Scale scores at discharge were used to assess outcome. Results: Among 90 enrolled patients, 37 (41%) deteriorated, 75% of them in the first 24 hours after enrollment. Administration of tissue plasminogen activator was significantly associated with deterioration (hazard ratio 2.25; 95% confidence interval [CI]: 1.13–4.49) even after controlling for the association of deterioration with the early poststroke period. Deterioration conferred an increased risk of poor outcome (modified Rankin Scale scores 3–6) at discharge (relative risk: 1.80; 95% CI: 1.71–1.93). Reversion back to predeterioration deficits occurred in 38% of patients, and was associated with reduced risk of poor outcome at discharge (relative risk: 0.12; 95% CI: 0.02–0.83). Treatment with tissue plasminogen activator conferred better chances of spontaneous recovery to predeterioration deficits after initial deterioration (hazard ratio: 4.36; 95% CI: 1.36–14.01). Conclusion: More than 40% of patients with SCS deteriorate neurologically. Deterioration tends to occur early after stroke, spontaneously reverses in approximately one-third of cases, and poses an increased risk of poor outcome. Therapies are needed to prevent, arrest, or reverse deterioration in patients with SCS.

Predicting the need for hospital admission of TIA patients

BACKGROUND It is unknown which patient will benefit most from hospital admission after transient ischemic attack (TIA). Our aim was to define predictors of a positive hospital outcome. METHODS We used two cohorts of TIA patients: the University of Texas at Houston Stroke Center (UTH); and Tel-Aviv Sourasky Medical Center in Israel (TASMC) for external validation. We retrospectively reviewed medical records and imaging data. We defined positive yield (PY) of the hospital admission as identification of stroke etiologies that profoundly changes clinical management. RESULTS The UTH cohort included 178 patients. 24.7% had PY. In the multivariate analysis, the following were associated with PY: coronary disease (CAD); age; and acute infarct on DWI. We then derived a composite score termed the PY score to predict PY. One point is scored for: age>60, CAD, and acute infarct on DWI. The proportion of PY by PY score was as follows: 0-6%; 1-22%; 2-47%; 3-67% (p<0.001). In the validation cohort PY score was highly predictive of PY and performed in a very similar manner. CONCLUSIONS Our data suggest, the PY score may enable physicians to make better admission decisions and result in better, safer and more economical care for TIA patients.