DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy / 대한뇌졸중학회지

Background@#and Purpose The benefit regarding co-treatment with intravenous (IV) thrombolysis before mechanical thrombectomy in acute ischemic stroke with large vessel occlusion remains unclear. To test the hypothesis that clinical outcome of ischemic stroke patients with intracranial internal carotid artery, middle cerebral artery or basilar artery occlusion treated with direct endovascular thrombectomy within 4.5 hours will be non-inferior compared with that of standard bridging IV thrombolysis followed by endovascular thrombectomy. @*Methods@#To randomize 780 patients 1:1 to direct thrombectomy or bridging IV thrombolysis with thrombectomy. An international-multicenter prospective randomized open label blinded endpoint trial (PROBE) (ClincalTrials.gov identifier: NCT03494920). @*Results@#Primary endpoint is functional independence defined as modified Rankin Scale (mRS) 0–2 or return to baseline at 90 days. Secondary end points include ordinal mRS analysis, good angiographic reperfusion (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b–3), safety endpoints include symptomatic intracerebral hemorrhage and death. @*Conclusions@#DIRECT-SAFE will provide unique information regarding the impact of direct thrombectomy in patients with large vessel occlusion, including patients with basilar artery occlusion, with comparison across different ethnic groups.

Aeromedical retrieval diagnostic trends during a period of Coronavirus 2019 lockdown

BackgroundWe aimed to compare the pre, lockdown, and post-lockdown aeromedical retrieval (AR) diagnostic reasons and patient demographics during a period of Coronavirus 2019 (COVID-19) social isolation. MethodsAn observational study with retrospective data collection, consisting of Australians who received an AR between the 26 January to the 23 June 2020. The main outcome measures were patient diagnostic category proportions and trends prior (28 January to 15 March), during (16 March to 4 May), and following (5 May to 23 June 2020) social isolation restrictions. ResultsThere were 16981 ARs consisting of 1959 (11.5) primary evacuations (PE) and 12724 (88.5) inter-hospital transfer (IHT), with a population median age of 52 years old (interquartile range [IQR] 29.0-69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were a total of 6 confirmed and 209 suspected cases of COVID-19, with the majority of cases (n = 114; 53.0%) in the social isolation period. As compared to pre-restriction, the odds of retrieval for the restriction and post-restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post-restriction periods (OR 1.12 95% CI 1.02-1.24 and OR 1.18 95% CI 1.08-1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31 95% CI 1.04-1.64), and increases for congenital conditions in the restriction period (OR 2.56 95% CI 1.39-4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72 95% CI 0.53-0.98). There were lower odds during the post-restriction period for a retrievals of the respiratory system (OR 0.78 95% CI 0.67-0.93), and disease of the skin (OR 0.78 95% CI 0.6-1.0). Distribution between the 2019 and 2020 time periods differed (p< 0.05), with the lockdown period resulting in a significant reduction in activity. ConclusionThe lockdown period resulted in increased AR rates of circulatory and congenital conditions. However, this period also resulted in a reduction of overall activity, possibly due to a reduction in other infectious disease rates, such as influenza, due to social distancing.

Effects of modified-release fampridine on upper limb impairment in patients with Multiple Sclerosis.

BACKGROUND: Modified-release 4-aminopyridine (fampridine-MR) is used in the symptomatic treatment of walking disability in patients with multiple sclerosis (MS).  Its potential for use in other MS symptoms remains unproven and its mode of action in this context is uncertain. Interest is growing in the use of upper limb outcome measures in clinical trials in patients with Multiple Sclerosis, particularly in advanced or progressive disease.  This study tests the following hypotheses: (1) Fampridine-MR improves upper limb function in patients with MS and upper limb impairment.  (2) Treatment with fampridine-MR is associated with measurable alterations in objective electrophysiological parameters (evoked potentials and transcranial magnetic stimulation (TMS)) which may predict response to drug treatment. METHODS: Study population: patients with MS of any disease subtype, duration and severity who have symptomatic impairment of one or both upper limbs.  A healthy control group was included for validation of clinical and electrophysiological measures.  Study design: randomised double blind placebo-controlled trial.  Treatment details: participants allocated to either fampridine-MR 10 mg bd or placebo of identical appearance for 8 weeks.  Primary outcome: performance on 9-hole peg test (9HPT) after 4 weeks.  Secondary outcomes: persistence of effect on 9HPT; grip strength; visual acuity and contrast sensitivity; modified fatigue impact scale score; sensory discrimination capacity; visual, somatosensory and motor evoked potentials; resting motor threshold; paired-pulse TMS; peripheral nerve conduction studies. RESULTS: 40 patients with MS (60% female, median age 52, median disease duration 13.5 years, median EDSS 6.0) were enrolled.  Treatment with fampridine-MR was not associated with any change in upper limb function as measured by the clinical primary or secondary outcomes.  Treatment with fampridine-MR was also not associated with any difference in electrophysiological measures of upper limb function.  This held true after adjustment for hand dominance, disease duration and severity.  Four patients withdrew from the trial because of lack of efficacy or side-effects; all were in the placebo arm.  Three patients were admitted to hospital during the study period; one with MS exacerbation (placebo group), one with syncope (drug group) and one with UTI (drug group); otherwise there were no serious adverse events. CONCLUSION: Treatment with fampridine-MR was well-tolerated but did not produce clinical benefit in terms of upper limb function, vision or fatigue, nor was there any measurable effect on objective electrophysiological parameters.

Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. METHODS: We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). RESULTS: Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) (p=0.001), by 73.9% in diastolic BP (DBP) (p0.05). CONCLUSIONS: In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.

Ischaemic stroke in young adults: A comparative study between Malaysia and Australia

Background and Objectives: There is a paucity of comparative studies on young strokes between populations of different ethnicities and geographical regions. The purpose of this study was to compare the patterns, risk factors and etiologies of ischaemic stroke in younger patients between stroke registries in Malaysia and Australia. Methods: From January 2007 to March 2008, all consecutive ischaemic stroke patients from the age of 18 to 49 were studied. Results: There were 67 patients for Malaysia and 61 for Australia, with 4 deaths in the Malaysian series (case-fatality of 6%), and no deaths for Australia. The mean age was 41.5±8.8 yrs for Malaysia and 40.1±8.8 years for Australia. The ethnic origin was Malays, Chinese and Indian for Malaysia, and Caucasians (85%) for Australia. The sex ratio was M : F = 1.4 : 1 for Malaysia and 1.54 :1 for Australia. The differences in risk factors for Malaysia versus Australia were: Diabetes (OR 7.25; 95% CI 2.78-19.45), hypertension (OR 6.42; 95% CI 2.75-15.22) and chronic renal disease (OR 5.2; 95% CI 1.02-35.87). Conversely, smoking was a signifi cant risk factor for Australia (OR 2.75; 95% CI 1.2-6.37). The Malaysian patients have signifi cantly higher proportions of large vessel atherosclerosis and small vessel occlusion by TOAST classifi cation, accounting for 60% of patients, while the Australian series had greater proportions of cardioembolism and patients in the determined aetiologies category, specifi cally vascular dissection. Conclusion: There were signifi cantly more large vessel atherosclerosis and small vessel occlusion among young Malaysians with ischaemic stroke as compared to Australia.