Objectives: This retrospective single-center study aimed to investigate the risk factors, outcomes and complication rates in patients older vs. younger than 80 years treated with intravenous alteplase.Methods: Data of 1,253 thrombolysed patients were analyzed between January 1, 2004 and August 31, 2016. Vascular risk factors, stroke severity based on the NIHSS score, functional outcome using modified Rankin Scale (mRS), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between two subgroups (<80 and ≥80 years).Results: 1,125 patients were included, 199 (17.6%) among them were aged over 80 years, majority (63.3%) were female (p < 0.00001). Mean age was 68.2 ± 12.4 years, i.e., 64.7 ± 10.8 years and 84.3 ± 3.4 years in the younger and the older groups, respectively (p < 0.001). Atrial fibrillation and pre-stroke anticoagulation among patients over 80 years was more likely (p < 0.0005 and p = 0.02, respectively). NIHSS scores on admission and at 24 h were higher in elderly patients (p < 0.0001). ASPECT score at 24 h was less favorable in elderly patients (p = 0.007) and was associated with worse outcome. At 3 months, 59.8% of the patients from the older group had an unfavorable outcome (p < 0.0001), however 34.7% had independent outcome. The one-year- survival was significantly worse in the older group (p < 0.0001). The incidence of SICH was lower among older patients. In a logistic regression model, atrial fibrillation, heart failure, diabetes mellitus and smoking were proven as a significant independent risk factors for worse outcome.Conclusion: Although, the outcomes were less favorable in patients over 80 years of age, our results support the feasibility of using intravenous thrombolysis among patients over 80 years of age.

Rationale: Stroke is one of the leading causes of death in all developed countries. In Hungary, more than 10,000 patients die annually due to cerebrovascular diseases according to the WHO Mortality Database. Of these patients, 10–15 % suffer non-traumatic intracerebral hemorrhage (ICH). ICH results in a higher rate of mortality as compared to ischemic stroke and outcomes are difficult to predict. In the IRONHEART study, we aim to test various hemostasis parameters and clinical neurophysiological examinations in evaluating outcome in ICH.Methods: In this prospective, observational study, we plan to enroll consecutive patients with non-traumatic spontaneous ICH admitted to a single Stroke Center (Department of Neurology, University of Debrecen, Hungary). The protocol of the IRONHEART study includes the investigation of detailed clinical, laboratory investigations, and various neurophysiological examinations. Stroke severity is quantified based on the National Institutes of Health Stroke Scale (NIHSS) on admission and day 7, 14, and 90 after the onset of stroke. Cranial CT is performed on admission, day 14, and 90 to estimate the ICH volume. Modified Rankin Scale (mRS) is used for evaluating the long-term outcome (90 days post-event). Blood is drawn immediately on admission for specific hemostasis tests. Digital and quantitative EEG techniques and motor evoked potential (MEP) are performed to evaluate the prognosis of cerebral hemorrhage on admission (within 24–48 h), immediately before discharge (~10–14 days later), and 3 months after the event.Outcomes: The following outcomes are investigated: primary outcomes: mortality by day 14 and day 90, secondary long-term outcome at 90 days post-event where mRS 0–2 is defined as favorable long-term outcome.Discussion: If associations between outcomes and the investigated parameters (hemostasis and neurophysiological examinations) are confirmed, results might aid prognosis assessment in this subtype of stroke with particularly high mortality. Improving clinical grading systems on ICH severity and outcomes by including the investigated parameters could help to better guide the management of these patients in the future.

Background: Non-traumatic intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes and results in a higher rate of mortality as compared to ischemic strokes. In the IRONHEART study, we aimed to find out whether a modified in vitro clot lysis assay method, that includes the effect of neutrophil extracellular traps (NETs) might predict ICH outcomes.Patients and Methods: In this prospective, observational study, 89 consecutive non-traumatic ICH patients were enrolled. Exclusion criteria included aneurysm rupture, cancer, liver- or kidney failure or hemorrhagic diathesis. On admission, detailed clinical and laboratory investigations were performed. ICH volume was estimated based on CT performed on admission, day 14 and 90. A conventional in vitro clot lysis assay (CLA) and a modified CLA (mCLA) including cell-free-DNA and histones were performed from stored platelet-free plasma taken on admission. Clot formation and lysis in case of both assays were defined using the following variables calculated from the turbidimetric curves: maximum absorbance, time to maximum absorbance, clot lysis times (CLT) and area under the curve (CLA AUC). Long-term ICH outcomes were defined 90 days post-event by the modified Rankin Scale (mRS). All patients or relatives provided written informed consent.Results: Patients with more severe stroke (NIHSS>10) presented significantly shorter clot lysis times of the mCLA in the presence of DNA and histone as compared to patients with milder stroke [10%CLT: NIHSS 0–10: median 31.5 (IQR: 21.0–40.0) min vs. NIHSS>10: 24 (18–31.0) min, p = 0.032]. Shorter clot lysis times of the mCLA showed significant association with non-survival by day 14 and with unfavorable long-term outcomes [mRS 0–1: 36.0 (22.5.0–51.0) min; mRS 2–5: 23.5 (18.0–36.0) min and mRS 6: 22.5 (18.0–30.5) min, p = 0.027]. Estimated ICH volume showed significant negative correlation with mCLA parameters, including 10%CLT (r = −0.3050, p = 0.009). ROC analysis proved good diagnostic performance of mCLA for predicting poor long-term outcomes [AUC: 0.73 (0.57–0.89)]. In a Kaplan-Meier survival analysis, those patients who presented with an mCLA 10%CLT result of >38.5 min on admission showed significantly better survival as compared to those with shorter clot lysis results (p=0.010).Conclusion: Parameters of mCLA correlate with ICH bleeding volume and might be useful to predict ICH outcomes.

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease, which may lead to severe disability or even death. Although many factors may influence the outcome, neurophysiological examinations might also play a role in its course. Our aim was to examine whether the findings of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) can predict the prognosis of these patients.Methods: Between June 1 2017 and June 15 2021, 116 consecutive patients with ICH were enrolled prospectively in our observational study. Clinical examinations and non-Contrast computed tomography (NCCT) scan were done on admission for ICH; follow-up NCCT scans were taken at 14 ± 2 days and at 3 months ± 7 days after stroke onset. EEG and TMS examinations were also carried out.Results: Of the patients in the study, 65.5% were male, and the mean age of the study population was 70 years. Most patients had a history of hypertension, 50.8% of whom had been untreated. In almost 20% of the cases, excessive hypertension was measured on admission, accompanied with >10 mmol/L blood glucose level, whereas their Glasgow Coma Scale was 12 on average. Presence of blood in the ventricles or subarachnoid space and high blood and perihematomal volumes meant poor prognosis. Pathological EEG was prognostic of a worse outcome. With TMS examination at 14 days, it might be possible to estimate outcome in a univariate model and the absence, or reduction of the amplitude of the motor evoked potentials was associated with poor prognosis.Conclusion: Together with the clinical symptoms, the volume of bleeding, perihematomal edema (or their combined volume), and neurophysiological examinations like EEG and TMS play an important role in the neurological outcome of patients with ICH. This might affect the patients' rehabilitation plans in the future, since with the help of the examinations the subset of patients with potential for recovery could be identified.

BackgroundNon-traumatic intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes and leads to a higher rate of mortality as compared to ischemic strokes. We aimed to find out whether the thrombin generation assay (TGA) could predict outcomes in patients with ICH.Patients and methodsIn this prospective, observational study, 87 consecutive patients with ICH and 164 healthy controls were included. Computed tomography (CT), detailed clinical investigation, and laboratory investigations were performed from patients on admission. TGA was performed using stored platelet poor plasma obtained on admission. Lag time, endogen thrombin potential (ETP), peak thrombin, and time to peak parameters were calculated. Short- and long-term outcomes of ICH were defined at 14 days and 3 months post-event according to the NIHSS and the modified Rankin Scale (mRS), respectively.ResultsPeak thrombin was significantly higher in patients as compared to controls (397.2 ± 93.9 vs. 306 ± 85.3 nM, p < 0.0001). Lag time, ETP, and time to peak parameters showed a significant positive correlation with CRP in both groups. In patients with worse long-term functional outcomes, peak thrombin was significantly higher as compared to those with favorable outcomes [mRS 2–6 median: 402.5 (IQR:344.8–473.8) vs. mRS 0–1: 326.4 (294.2–416.1) nM, p = 0.0096]. Based on the statistically optimal threshold of 339.1 nM peak thrombin, the sensitivity and specificity of this parameter to determine mRS 2–6 as an outcome were 80.8 and 64.7%, respectively. In a binary logistic regression model including age, sex, BMI, smoking status, NIHSS on admission, D-dimer, and peak thrombin (>339.1 nM), only NIHSS and the peak thrombin parameters remained in the model as significant, independent predictors of poor outcome. Lag time and time to peak showed a modest, significant negative correlation with intracerebral bleeding volume on admission (r = −0.2603, p = 0.0231 and r = −0.3698, p = 0.0010, respectively). During the follow-up of patients, estimated hemorrhage volumes on day 90 showed significant positive association with the ETP and peak thrombin parameters (r = 0.3838, p = 0.0363 and r = 0.5383, p = 0.0021, respectively).ConclusionIn patients with ICH, TG was increased as compared to healthy controls, which might be explained by the presence of higher inflammatory parameters in patients. Peak thrombin measured on admission might be a useful tool to predict outcomes in patients with ICH.

Background: Stroke is a major cause of death and disability presenting with acute focal neurological symptoms of vascular origin. Several other disorders may cause symptoms similar to a stroke, referred as stroke mimics. Misdiagnosis of stroke mimics may lead to potentially harmful treatments, including thrombolysis. Intoxication is a rare, but possible cause of stroke mimic. We present three cases of ethylene glycol poisoning presenting as acute stroke mimic within the time window of thrombolytic therapy. Case presentations: The first patient (54-year-old, male) had nystagmus, dysarthria and truncal ataxia on admission. Cerebral CT and CT-angiography were negative. Vertebrobasilar stroke was suspected and intravenous thrombolysis was performed. A few hours later confusion, somnolence and hyperventilation developed. Arterial blood gas analysis showed metabolic acidosis. Toxicology screening revealed the presence of ethylene glycol in a toxic range. Due to the prompt treatment the patient was discharged 9 days later in a symptom-free state. The second patient (78-year-old, male) was admitted with central type of nystagmus, gaze palsy, dysarthria and ataxia. In the absence of exclusion criteria, thrombolysis was performed. A few hours later his condition deteriorated, he became comatose and tetraplegic with partially absent brainstem reflexes. Arterial blood gas analysis revealed severe metabolic acidosis. The ethylene glycol level was 159 mg/dL. Despite the appropriate treatment, he died. The third patient (54-year-old, male) with a history of chronic alcoholism was presented after an epileptic seizure with mixed aphasia and confusion. Stroke could not be excluded, therefore thrombolysis was performed. Arterial blood gases were normal, however toxicological screening revealed a serum etyhlene-glycol concentration of 16,54 mg/dL. Six days after admission he became symptom-free and was discharged home. Conclusions: Our cases show that ethylene glycol intoxication in its early phase may mimic acute stroke resulting in an unnecessary thrombolytic therapy. Symptoms not characteristic of a stroke, such as hyperventilation, agitation, and disturbance of consciousness, may appear later and warn of intoxication. The final diagnosis of ethylene-glycol intoxication can be established by a severe metabolic acidosis and toxicological screening. Close monitoring of symptoms might contribute to early recognition of ethylene-glycol intoxication and its effective treatment.

Stroke is a major cause of death and disability presenting with acute focal neurological symptoms of vascular origin. Several other disorders may cause symptoms similar to a stroke, referred to as stroke mimics. The misdiagnosis of stroke mimics may lead to potentially harmful treatments, including thrombolysis. Intoxication is a rare, but possible, cause of stroke mimic. We present three cases of ethylene glycol poisoning presenting as an acute stroke mimic within the time window of thrombolytic therapy. Two of three patients (a 54-year-old male and a 78-year-old male) had dysarthria, nystagmus, and truncal ataxia on admission. The third patient with a history of chronic alcoholism presented after an epileptic seizure with mixed aphasia and confusion. Non-contrast cerebral computed tomography and computed tomography angiography were negative in all three cases. As stroke could not be excluded in any of the patients, thrombolysis was performed. However, after some hours, two of the three patients developed agitation, somnolence, and hyperventilation. One patient's consciousness deteriorated rapidly, and he became comatose and tetraplegic. A blood gas analysis showed acidosis in two of the three patients, and toxicological screening revealed ethylene glycol intoxication in all three cases. Due to the appropriate treatment, two of the three patients became symptom-free; however, one of the three patients died. Our cases show that ethylene glycol intoxication in its early phase may mimic acute stroke, resulting in unnecessary thrombolytic therapy. Symptoms not characteristic of a stroke, such as hyperventilation, agitation, and disturbance of consciousness, may appear later and warn of intoxication. The final diagnosis of ethylene glycol intoxication can be established by severe metabolic acidosis and toxicological screening. Close monitoring of symptoms might contribute to the early recognition of ethylene glycol intoxication and its effective treatment.

IntroductionAcute ischemic stroke (AIS) is a potentially devastating disease with high disability and mortality. Recombinant tissue plasminogen activator (rt-PA) is an effective treatment with a 2–8% possible risk for symptomatic intracranial hemorrhage (sICH). Our aim was to investigate the risk factors and long-term clinical outcomes of ICH in patients after rt-PA treatment.MethodsConsecutive patients with AIS, thrombolysed at the Department of Neurology, University of Debrecen, between 1 January 2004 and 31 August 2016 were enrolled prospectively. Risk factors, stroke severity based on the National Institute of Health Stroke Scale (NIHSS), functional outcome using the modified Rankin scale, and mortality at 1 year were compared in patients with and without ICH following rt-PA treatment. We evaluated clinical characteristics and prognosis by hemorrhage type based on the Heidelberg Bleeding Classification. Descriptive statistics, the chi-square test, the Mann–Whitney U-test, ANOVA, the Kruskal–Wallis test, a survival analysis, and logistic regression were performed as appropriate.ResultsOut of 1,252 patients with thrombolysis, ICH developed in 138 patients, with 37 (2.95%) being symptomatic. Mean ages in the ICH and non-ICH groups differed significantly (p = 0.041). On admission, the 24-h NIHSS after thrombolysis was higher in patients with ICH (p < 0.0001). Large vessel occlusion was more prevalent in patients with ICH (p = 0.0095). The ICH risk was lower after intravenous thrombolysis than intra-arterial or combined thrombolysis (p < 0.0001). Both at 3 months and 1 year, the outcome was worse in patients with ICH compared to patients without ICH group (p < 0.0001). Mortality and poor outcome were more prevalent in all hemorrhage types with a tendency for massive bleeding associated with unfavorable prognosis. At 3 months with the logistic regression model, the worse outcome was detected in patients with ICH after thrombolysis, at 1 year in patients with ICH after thrombolysis and smoking.DiscussionOlder age, higher NIHSS, large vessel occlusion, and intra-arterial thrombolysis may correlate with ICH. The unfavorable outcome is more common in patients with ICH. Precise scoring of post-thrombolysis bleeding might be a useful tool in the evaluation of the patient's prognosis. Our findings may help to identify predictors and estimate the prognosis of ICH in patients with AIS treated with rt-PA.