Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke.

OBJECTIVE: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS). METHODS: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. RESULTS: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). INTERPRETATION: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218.

Optimizing prediction scores for poor outcome after intra-arterial therapy in anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. METHODS: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University. RESULTS: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. CONCLUSIONS: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Hyperkyphotic posture and risk of injurious falls in older persons: the Rancho Bernardo Study.

OBJECTIVE: Falls among older adults can have serious physical and emotional consequences, ultimately leading to a loss of independence. Improved identification of those at risk for falls could lead to effective interventions. Because hyperkyphotic posture is associated with impaired physical functioning, we hypothesized that kyphosis may also be associated with falls. METHODS: Participants were 1883 older adults from the Rancho Bernardo Study. Between 1988 and 1991, kyphosis was measured using a system of 1.7-cm blocks placed under the participants' heads if they were unable to lie flat without neck hyperextension. Data on falls including injurious falls, demographics, health, and habits were obtained from a self-administered questionnaire completed at the same visit. RESULTS: Hyperkyphosis was defined as requiring the use of > or = 1 blocks (n = 595, 31.6%). In this cohort, men were more likely to be hyperkyphotic than were women (p <.0001). Of those who fell, 36.3% were hyperkyphotic, versus 30.2% among those who did not fall (p =.015). Those who fell were older, more likely to be women, had lower body mass index, did not exercise, did not drink alcohol, and had poor self-reported physical and emotional health. In age- and sex-adjusted models, those with hyperkyphosis were at 1.38-fold increased odds of experiencing an injurious fall (95% confidence interval [CI], 1.05-1.91; p =.02) that increased to 1.48 using a cutoff of > or = 2 blocks versus < or = 1 blocks (95% CI, 1.10-2.00; p =.01). Although women were more likely to fall, after adjustment for possible confounders, men with moderate hyperkyphosis were at greatest fall risk. CONCLUSIONS: Moderate hyperkyphotic posture may signify an easily identifiable independent risk factor for injurious falls in older men, with the association being less pronounced in older women.