Endovascular therapy for ischemic stroke with perfusion-imaging selection.

BACKGROUND: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS: We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS: The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).

Effectiveness and Safety of Antibiotics for Preventing Pneumonia and Improving Outcome after Acute Stroke: Systematic Review and Meta-analysis.

BACKGROUND: Pneumonia is a common complication after stroke which increases morbidity and mortality. This systematic review was conducted to evaluate the efficacy and safety of antibiotics for the prevention of pneumonia after acute stroke. METHODS: Medline, EMBASE, and Cochrane databases were searched for randomized controlled trials comparing preventive antibiotics to placebo or no antibiotics after acute stroke. The primary outcome was poststroke pneumonia. Secondary outcomes were all infections, urinary tract infections, death, dependency, length of hospital stay, and adverse events. Treatment effects were summarized using random effects metaanalysis. RESULTS: Six trials (4111 patients) were eligible for inclusion. The median National Institute of Health Stroke Scale score in included trials ranged from 5 to 16.5. The proportion of dysphagia ranged from 26% to 100%. Preventive antibiotics were commenced within 48hours after acute stroke. Compared to control, preventive antibiotics reduced the risk of poststroke pneumonia (RR .75, 95%CI ·.57-.99), and all infections (RR .58, 95%CI .48-.69). There was no significant difference in the risks of dependency (RR 0.99, 95%CI 0·80-1·11), or mortality (RR .96, 95%CI .78-1.19) between the preventive antibiotics and control groups. Preventive antibiotics did not increase the risk of elevated liver enzymes (RR 1.20, 95% CI .97-1.49). Preventive antibiotics had uncertain effects on the risks of other adverse events. CONCLUSION: Preventive antibiotics reduced the risk of post-stroke pneumonia. However, there is insufficient evidence to currently recommend routine use of preventive antibiotics after acute stroke.

Frequency of post-stroke pneumonia: Systematic review and meta-analysis of observational studies.

BACKGROUND: Post-stroke pneumonia and other infectious complications are serious conditions whose frequency varies widely across studies. AIMS: We conducted a systematic review to estimate the frequency of post-stroke pneumonia and other types of major infection. SUMMARY OF REVIEW: MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched for prospective studies with consecutive recruitment of stroke patients. The primary outcome was post-stroke pneumonia. Secondary outcomes were any infection and urinary tract infection. Quality assessment was done using Newcastle Ottawa scale. Heterogeneity of estimates across study populations was calculated using Cochran's Q (heterogeneity χ2) and I2 statistics. A total of 47 studies (139,432 patients) with 48 sample populations were eligible for inclusion. Mean age of patients was 68.3 years and their mean National Institute of Health Stroke Scale score was 8.2. The pooled frequency of post-stroke pneumonia was 12.3% (95% confidence interval [CI] 11%-13.6%; I2 = 98%). The pooled frequency from 2011 to 2017 was 13.5% (95% CI 11.8%-15.3%; I2 = 98%) and comparable with earlier periods (P interaction = 0.31). The pooled frequency in studies in stroke units was 8% (95% CI 7.1%-9%; I2 = 78%) and significantly lower than other locations (P interaction = 0.001). The pooled frequency of post-stroke infection was 21% (95% CI 13%-29.3%; I2 = 99%) and of post-stroke urinary tract infection was 7.9% (95% CI 6.7%-9.3%; I2 = 96%). CONCLUSION: Approximately 1 in 10 stroke patients experience pneumonia during the acute period of hospital care. The frequency of post-stroke pneumonia has remained stable in recent decades but is lower in patients receiving stroke unit care compared to management in other ward settings.

Rare presentation of a treatable disorder: glutaric aciduria type 1.

A 32-year-old female patient presented with migraine and a bipolar disorder with frontal lobe dysfunction and bilateral pyramidal tract signs on examination. MRI brain revealed confluent bilateral symmetric white matter signal abnormality on T2 and FLAIR images with mild cerebral atrophy. Classic widening of Sylvian fissures and CSF space anterior to temporal lobes was seen. In view of the clinical and radiologic findings suggestive of a leukodystrophy, she was investigated for the same. Her investigations revealed an high level of urinary glutaric acid 857 mmol/mol creatinine (normal <4mmol/mol creatinine) and 3-hydroxyglutaric acid 44 mmol/mol creatinine (normal <1 mmol/mol creatinine) and plasma glutaryl carnitine 1.2 micromol/L; (normal <0.34 micromol/L). This was diagnostic of glutaric aciduria type 1. She was started on L-carnitine with which she showed clinical improvement. Testing for urinary organic acids is important when looking for treatable metabolic disorders (such as glutaric aciduria type I) in patients with leukodystrophy.

Vertebrobasilar dissections: case series comparing patients with and without dissecting aneurysms.

Vertebrobasilar dissections are being increasingly diagnosed due to better awareness and increased availability of modern imaging techniques of the intracranial and extracranial arteries. The clinical presentation and outcome in patients with vertebrobasilar dissections may be complicated by dissecting aneurysms. The aim of this retrospective study was to compare the clinical profile of patients with vertebrobasilar dissections with and without dissecting aneurysms, and to determine predisposing factors to the development of aneurysms. Thirty patients (19 [63%] male; median age 44.5 years) were identified. The patients were divided into two groups, an aneurysmal dissection group with seven patients and a non-aneurysmal dissection group with 23 patients. Eight (27%) patients presented with dissection after trivial trauma, three (10%) following high-speed vehicular trauma, two (7%) were associated with infection, but most (57%) were apparently spontaneous. Migraine with aura (p=0.008) and female sex (p=0.03) were observed more frequently in the aneurysmal dissection group. Though vascular risk factors other than hypertension and atrial fibrillation were seen in a greater percentage of patients in the non-aneurysmal dissection group, this was not statistically significant. Patients were treated with antiplatelet agents (n=8) or warfarin (n=13) or underwent an endovascular intervention (n=6). Post-discharge data were available in 19 patients, of whom 14 (74%) were independent at a median follow-up of 4 months. Female sex and migraine with aura may predispose to the formation of acute dissecting aneurysms and this requires further research. Larger, prospective studies are required to ascertain epidemiologic and etiologic factors predisposing patients to the development of both intracranial and extracranial dissecting aneurysms in the vertebrobasilar circulation.

A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA).

BACKGROUND AND HYPOTHESIS: Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4·5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with 'dual target' vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging 'mismatch' within 4·5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone. STUDY DESIGN: EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0·9 mg/kg intravenous tissue plasminogen activator within 4·5 h of stroke onset who have good prestroke functional status (modified Rankin Scale <2, no upper age limit) will undergo multimodal computed tomography or magnetic resonance imaging. Patients who also meet dual target imaging criteria: vessel occlusion (internal carotid or middle cerebral artery) and mismatch (perfusion lesion : ischemic core mismatch ratio >1·2, absolute mismatch >10 ml, ischemic core volume <70 ml) will be randomized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator, or tissue plasminogen activator alone. STUDY OUTCOMES: The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.