William J Hicks

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.

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.

Recruiting Patients With Stroke Into Cell Therapy Trials A Review

IMPORTANCE Clinical trials are under way to test the safety and efficacy of different types of cell therapies in patients with ischemic stroke. The informed consent process for recruitment of patients with stroke in cell therapy trials is complex and requires extensive discussions on multiple aspects. OBSERVATIONS Various issues in approaching patients with stroke and their families and discussing participation in cell therapy studies are described, including participation in clinical trials, clarifying the perception of stem cell therapy and the risks of bone marrow harvest, and discussing risks vs benefits, cell-based therapies for chronic stroke, and consent for minority and immigrant populations. CONCLUSIONS AND RELEVANCE Informed consent for cell therapy studies in patients with stroke requires lengthy discussions about several issues unique to clinical trials in stroke patients. Careful thought is needed to create an informative consent process.

E-095 Early Hyperglycemia Predicts Poor Outcome Despite Successful Stroke Thrombectomy

Objective Our goal was to identify medical co-morbidities which negatively prognosticate outcome in stroke patients who have successful endovascular reperfusion after imaging-based selection. Methods With approval, we retrospectively reviewed stroke interventions in the intracranial carotid and M1 middle cerebral artery at our institution over a two year period. All patients are screened for small infarcts based on a non-contrast head CT and perfusion imaging for treatment eligibility. For analysis, we included those patients with successful reperfusion only. We collected stroke risk factors, time to treatment, stroke scale, and additional medical co-morbidities: cardiomyopathy, chronic lung disease, chronic kidney disease, body mass index >30, early hyperglycemia (any 24 hour post-procedure blood sugar >150 gm/dl), history of malignancy, and dementia. These co-variates were placed into a univariate analysis to identify predictors for a poor outcome, defined as a modified Rankin Scale >2 at 90 days. Covariates with a p value of <0.2 were included in a multiple logistic regression model to identify independent predictors. Results We analyzed 120 patients with mean age 70 (SD 13) years, median NIHSS 16, and mean time to reperfusion 408 (SD 345) minutes. Poor outcome was seen in 44 patients (37%) with mortality in 21 patients (17.5%). After controlling for age and stroke score, early hyperglycemia was the only co-variate independently associated with poor outcome (OR 2.72, 95% CI 1.04–7.06, p = 0.04) and mortality (OR 3.18, 95% CI 1.28–7.86, p = 0.013). Conclusions In selected stroke patients with successful endovascular reperfusion, early hyperglycemia may be independently associated with poor outcome and mortality over other medical co-morbidities. Further prospective study confirming this effect may further develop treatment strategies to prevent this injury. Disclosures K. Dezse: None. S. Bajgur: None. A. Harrison: None. J. Mejilla: None. W. Hicks: None. T. Davis: None. P. Pema: None. R. Budzik: None. N. Vora: 2; C; Medtronic Neurovascular, Microvention Neurovascular. 3; C; Medtronic Neurovascular.