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Background and ObjectivesDetailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion.MethodsWe performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models.ResultsIn patients >80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg.DiscussionTNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients.Trial Registration InformationNCT02388061, NCT03340493.Classification of EvidenceThis study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.

Background and ObjectivesThe relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging.MethodsIn a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA; ClinicalTrials.govNCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion.ResultsRegions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%–70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%–32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%–28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median −3.3%, interquartile range −11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32–15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22–16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = −4.06, 95% CI 6.78–1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35–10.20, p = 0.011) in multivariable analysis.DiscussionCerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted.Classification of EvidenceThis study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.

ObjectiveWe aimed to investigate the effect of a code stroke system on the development of poststroke epilepsy.MethodsWe retrospectively analyzed consecutive patients treated with IV thrombolysis under or outside the code stroke system between 2003 and 2012. Patients were followed up for at least 2 years or until death. Factors with p < 0.1 in univariate comparisons were selected for multivariable logistic and Cox regression.ResultsA total of 409 patients met the eligibility criteria. Their median age at stroke onset was 75 years (interquartile range 64–83 years); 220 (53.8%) were male. The median follow-up duration was 1,074 days (interquartile range 119–1,671 days). Thirty-two patients (7.8%) had poststroke seizures during follow-up, comprising 7 (1.7%) with acute symptomatic seizures and 25 (6.1%) with late-onset seizures. Twenty-six patients (6.4%) fulfilled the definition of poststroke epilepsy. Three hundred eighteen patients (77.8%) were treated with the code stroke system while 91 (22.2%) were not. After adjustment for age and stroke etiology, use of the code stroke system was associated with decreased odds of poststroke epilepsy (odds ratio = 0.36, 95% confidence interval 0.14–0.87, p = 0.024). Cox regression showed lower adjusted hazard rates for poststroke epilepsy within 5 years for patients managed under the code stroke system (hazard ratio = 0.60, 95% confidence interval 0.47–0.79, p < 0.001).ConclusionThe code stroke system was associated with reduced odds and instantaneous risk of poststroke epilepsy. Further studies are required to identify the contribution of the individual components and mechanisms against epileptogenesis after stroke.Classification of evidenceThis study provides Class III evidence that for people with acute ischemic stroke, implementation of a code stroke system reduces the risk of poststroke epilepsy.

OBJECTIVE: To test the transferability of the Helsinki stroke thrombolysis model that achieved a median 20-minute door-to-needle time (DNT) to an Australian health care setting. METHODS: The existing "code stroke" model at the Royal Melbourne Hospital was evaluated and restructured to include key components of the Helsinki model: 1) ambulance prenotification with patient details alerting the stroke team to meet the patient on arrival; 2) patients transferred directly from triage onto the CT table on the ambulance stretcher; and 3) tissue plasminogen activator (tPA) delivered in CT immediately after imaging. We analyzed our prospective, consecutive tPA registry for effects of these protocol changes on our DNT after implementation during business hours (8 am to 5 pm Monday-Friday) from May 2012. RESULTS: There were 48 patients treated with tPA in the 8 months after the protocol change. Compared with 85 patients treated in 2011, the median (interquartile range) DNT was reduced from 61 (43-75) minutes to 46 (24-79) minutes (p = 0.040). All of the effect came from the change in the in-hours DNT, down from 43 (33-59) to 25 (19-48) minutes (p = 0.009), whereas the out-of-hours delays remain unchanged, from 67 (55-82) to 62 (44-95) minutes (p = 0.835). CONCLUSION: We demonstrated rapid transferability of an optimized tPA protocol to a different health care setting. With the cooperation of ambulance, emergency, and stroke teams, we succeeded in the absence of a dedicated neurologic emergency department or electronic patient records, which are features of the Finnish system. The next challenge is providing the same service out-of-hours.

Case reports. #### Case 1. A previously healthy 38-year-old man presented with acute urinary retention and constipation after 4 days of progressive weakness affecting all 4 limbs and patchy sensory disturbance over the trunk and upper arms. Ten days prior to the onset of symptoms, he had received H1N1 09 influenza (Panvax H1N1, CSL Biotherapies, Parkville, Australia) vaccination and had experienced a spontaneously resolving febrile reaction 24–48 hours following administration. MRI of the brain, cervical, thoracic, and lumbar spine was performed (figure,A). Several areas of central cord T2 signal hyperintensity were demonstrated, extending from C3 to C6 and from T7 to L1, and a diagnosis of longitudinally extensive transverse myelitis was made. Serologic investigations for infective and autoimmune etiologies were unremarkable. CSF demonstrated an inflammatory pattern, with 80 × 106/L lymphocytes and 0.78 g/L total protein. Figure MRI from clinical cases (A) MRI thoracic spine, demonstrating extensive longitudinal intramedullary T2 hyperintensity. (B) MRI cervical spine, demonstrating multilevel cord edema and hyperintensity of proximal thoracic segments. The patient received IV methylprednisolone (1 g/d for 3 days), with resolution in power and sphincter function over the following 10 days. #### Case 2. A previously healthy 19-year-old …