Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.

OBJECTIVES: Acute stroke management has changed dramatically over the recent years, where a timely assessment is driven by the expanding treatment options of acute ischaemic stroke. This increases the risk in treating non-stroke patients (stroke mimics) with a possibly hazardous intravenous thrombolysis treatment (IVT). SETTING: Patients of the thrombolysis registry of Södersjukhuset AB, a secondary health centre in Stockholm, were retrospectively studied to determine complications and outcome after IVT in strokes and stroke mimics. PARTICIPANTS: Consecutively, 674 recruited patients from 1 January 2008 to 1 December 2013 were analysed regarding demographics and outcome at 3 months after onset of symptoms. RESULTS: Ischaemic stroke was confirmed in 625 patients (93%), and 48 patients (7%) were stroke mimics. Patients with strokes were older than stroke mimics 72 (IQR: 64-81) vs 54 years (IQR 40-67), p<0.0001. Antihypertensive and antithrombotic treatment were more common in patients with stroke (p<0.0001 and p=0.006, respectively). National Institute of Health Stroke Scale did not differ at time of presentation. Excellent outcome defined as modified Rankin Scale score 0-1, at 3 months, was less common in stroke than in stroke mimics (50% vs 87.5%, p<0.0001). No stroke mimic had a symptomatic intracerebral haemorrhage. Age of less than 40 years may be a predictor for a patient to be a stroke mimic (OR: 8.7, 95% CI: 3.2 to 24.0, p<0.0001). CONCLUSIONS: Stroke mimics receiving IVT had a more favourable outcome compared with patients with stroke, and showed no haemorrhagic complications. Age below 40 years may be a predictor for stroke mimics.

Higher prehospital priority level of stroke improves thrombolysis frequency and time to stroke unit: the Hyper Acute STroke Alarm (HASTA) study.

BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences. METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel. RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention. CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.

Functional energetics of CD4+-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system- (CNS-) infection that typically occurs in a subset of immunocompromised individuals. An increasing incidence of PML has recently been reported in patients receiving monoclonal antibody (mAb) therapy for the treatment of autoimmune diseases, particularly those treated with natalizumab, efalizumab and rituximab. Intracellular CD4(+)-ATP-concentration (iATP) functionally reflects cellular immunocompetence and inversely correlates with risk of infections during immunosuppressive therapy. We investigated whether iATP may assist in individualized risk stratification for opportunistic infections during mAb-treatment. METHODOLOGY/PRINCIPAL FINDINGS: iATP in PHA-stimulated, immunoselected CD4(+)-cells was analyzed using an FDA-approved assay. iATP of mAb-associated PML (natalizumab (n = 8), rituximab (n = 2), efalizumab (n = 1)), or other cases of opportunistic CNS-infections (HIV-associated PML (n = 2), spontaneous PML, PML in a psoriasis patient under fumaric acids, natalizumab-associated herpes simplex encephalitis (n = 1 each)) was reduced by 59% (194.5±29 ng/ml, mean±SEM) in comparison to healthy controls (HC, 479.9±19.8 ng/ml, p<0.0001). iATP in 14 of these 16 patients was at or below 3(rd) percentile of healthy controls, similar to HIV-patients (n = 18). In contrast, CD4(+)-cell numbers were reduced in only 7 of 15 patients, for whom cell counts were available. iATP correlated with mitochondrial transmembrane potential (ΔΨ(m)) (iATP/ΔΨ(m)-correlation:tau = 0.49, p = 0.03). Whereas mean iATP of cross-sectionally analysed natalizumab-treated patients was unaltered (448.7±12 ng/ml, n = 150), iATP was moderately decreased (316.2±26.1 ng/ml, p = 0.04) in patients (n = 7) who had been treated already during the pivotal phase III trials and had received natalizumab for more than 6 years. 2/92 (2%) patients with less than 24 months natalizumab treatment revealed very low iATP at or below the 3(rd) percentile of HC, whereas 10/58 (17%) of the patients treated for more than 24 months had such low iATP-concentrations. CONCLUSION: Our results suggest that bioenergetic parameters such as iATP may assist in risk stratification under mAb-immunotherapy of autoimmune disorders.