Modern endovascular treatments of occlusive pediatric acute ischemic strokes: case series and review of the literature.

PURPOSE: Literature on the endovascular treatment of occlusive acute ischemic stroke (AIS) in the pediatric population remains nebulous. Clinical trials evaluating the role of systemic and intra-arterial thrombolysis, and mechanical thrombectomy have been strictly isolated to the adult population and largely unknown in their safety and efficacy in the pediatric group. METHODS: The authors present a review of the literature and their own two cases of occlusive acute ischemic stroke in children younger than the age of 10 years who were treated with modern endovascular devices, specifically with stent retrievers, and discuss their clinical and technical considerations as well as their limitations. RESULTS: In both pediatric patients, a combination of stent retriever and Penumbra aspiration were used to achieve Thrombolysis In Cerebral Infarction (TICI) 2a or greater with reduction of overall stroke burden. A reduction of National Institutes of Health Stroke Scale (NIHSS) of 8 or greater was achieved at discharge. At 3-month follow-up, the patients had a NIHSS of 6 and 2, respectively. One patient continued to improve from NIHSS of 6 to 3 at 6 months. CONCLUSION: In carefully, selected pediatric patients, modern endovascular techniques may be used to treat occlusive pediatric AIS. However, larger clinical trials are needed to evaluate the overall safety and effectiveness.

Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results.

BACKGROUND: The Study of Etravirine Neuropsychiatric Symptoms versus Efavirenz (SENSE) trial compared etravirine with efavirenz in treatment-naive patients. The primary endpoint was neuropsychiatric adverse events up to week 12; HIV RNA suppression at week 48 was a secondary endpoint. METHODS: Patients with HIV RNA more than 5000  copies/ml were randomized to etravirine 400  mg once daily (n = 79) or efavirenz (n = 78), plus two nucleoside analogues. HIV RNA less than 50  copies/ml at week 48 was analysed using the time to loss of virological response (TLOVR) algorithm. Drug resistance at treatment failure and safety endpoints were also evaluated. RESULTS: At baseline, the median CD4 cell count was 302  cells/µl and HIV RNA was 4.8 log10  copies/ml. In the intent to treat TLOVR analysis at week 48, 60 of 79 (76%) patients on etravirine versus 58 of 78 (74%) on efavirenz had HIV RNA less than 50  copies/ml. In the on-treatment analysis, 60 of 65 (92%) taking etravirine had HIV RNA les than 50 copies/ml versus 58 of 65 (89%) for efavirenz: etravirine showed noninferior efficacy versus efavirenz in both analyses (P < 0.05). Four patients had virological failure in the etravirine arm: none developed resistance to nucleoside analogues or nonnucleosides. Seven patients had virological failure in the efavirenz arm: three developed treatment-emergent resistance to nucleoside analogues and/or nonnucleosides. At the week 48 visit, the percentage with ongoing neuropsychiatric adverse events was 6.3% for etravirine and 21.5% for efavirenz (P = 0.011). CONCLUSION: First-line treatment with etravirine 400 mg once daily and two nucleoside reverse transcriptase inhibitors (NRTIs) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTIs. None of the patients with virological failure in the etravirine arm developed resistance to nonnucleosides.

A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population.

BACKGROUND: Although efavirenz is a universally recommended treatment for naive HIV-infected individuals, neuropsychiatric adverse events are common. METHODS: The Study of Efavirenz NeuropSychiatric Events versus Etravirine (SENSE) trial is a double-blind, placebo-controlled study in which 157 treatment-naive individuals with HIV-RNA higher than 5000 copies/ml were randomized to etravirine 400 mg once daily (n = 79) or to efavirenz 600 mg once daily (n = 78), with two investigator-selected nucleoside reverse transcriptase inhibitors (NRTIs). The primary end point was the percentage of patients with grade 1-4 drug-related treatment-emergent neuropsychiatric adverse events up to week 12. RESULTS: The study population were 81% men and 85% whites, with a median age of 36 years, baseline CD4 cell counts of 302 cells/µl and HIV-RNA of 4.8 log10 copies/ml. In the intent-to-treat analysis, 13 of 79 individuals (16.5%) in the etravirine arm and 36 of 78 individuals (46.2%) in the efavirenz arm showed at least one grade 1-4 drug-related treatment-emergent neuropsychiatric adverse event (P < 0.001). The number with at least one grade 2-4 drug-related treatment-emergent neuropsychiatric adverse event was four of 79 individuals (5.1%) in the etravirine arm and 13 of 78 individuals (16.7%) in the efavirenz arm (P = 0.019). The change in HIV-RNA to week 12 was -2.9 log10 in both treatment arms. The median rise in CD4 cell counts was 146 cells/µl in the etravirine arm and 121 cells/µl in the efavirenz arm. CONCLUSIONS: After 12 weeks, first-line treatment with etravirine 400 mg once daily with two NRTIs was associated with significantly fewer neuropsychiatric adverse events when compared with efavirenz with two NRTIs. The virological and immunological efficacy profile was similar between the two arms.