Elevated Blood Alcohol Concentration Is Associated with Improved Clinical Outcomes of Intravenous Thrombolysis Treatment in Acute Ischemic Stroke Patients-A Retrospective Study.

BACKGROUND: Intravenous thrombolysis (IVT) improves acute ischemic stroke (AIS) outcomes, but with limited success. In addition, ethanol potentiates the effect of r-tPA in ischemia models. METHODS: The effect of acute alcohol consumption on IVT outcomes was investigated in a retrospective cohort study. AIS patients with detectable blood alcohol concentration (BAC) during IVT were included (alcohol group; n = 60). For each case, 3 control subjects who underwent IVT but denied alcohol consumption were matched in terms of age, sex, affected brain area, and stroke severity. Outcomes were determined using the NIHSS at 7 days and the modified Rankin scale (mRS) at 90 days. RESULTS: Patients were younger and had a less severe stroke than in a standard stroke study. Favorable long-term outcomes (mRS 0-2) occurred significantly more frequently in the alcohol group compared to controls (90% vs. 63%, p < 0.001). However, the rates of hemorrhagic transformation were similar. Multiple logistic regression models identified elevated BAC as a significant protective factor against unfavorable short-term (OR: 0.091, 95% CI: 0.036-0.227, p < 0.001) and long-term outcomes (OR: 0.187, 95% CI: 0.066-0.535, p = 0.002). In patients with BAC > 0.2%, significantly lower NIHSS was observed at 3 and 7 days after IVT vs. in those with 0.01-0.2% ethanol levels. CONCLUSION: Elevated BAC is associated with improved outcomes in IVT-treated AIS without affecting safety.

Thrombin generation as a predictor of outcomes in patients with non-traumatic intracerebral hemorrhage.

Background: Non-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 methods: In 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. Results: Peak 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). Conclusion: In 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.

Effects of acute alcohol consumption on neuronal activity and cerebral vasomotor response.

INTRODUCTION: In the majority of European countries, driving after drinking small-moderate amount of alcohol is legal. Motivated by our previous studies on cerebral hemodynamics, we aimed to study whether a small-moderate blood alcohol content (BAC), at which driving is legal in some countries (0.8 g/L), influences the neuronal activity, neurovascular coupling, and cerebral vasoreactivity. METHODS: Analyses of pattern-reversal visual evoked potential (VEP) and transcranial Doppler (TCD) examinations were performed in thirty young healthy adults before and 30 min after alcohol consumption. Cerebral vasoreactivity was evaluated by breath holding test in both middle cerebral arteries. By using a visual cortex stimulation paradigm, visually evoked flow velocity response during reading was measured in both posterior cerebral arteries (PCA). RESULTS: The BAC was 0.82 g/L and 0.94 g/L 30 and 60 min after drinking alcohol, respectively. Latency of the VEP P100 wave increased after alcohol consumption. Resting absolute flow velocity values increased, whereas pulsatility indices in the PCA decreased after alcohol ingestion, indicating vasodilation of cerebral microvessels. Breath holding index and the visually evoked maximum relative flow velocity increase in the PCA and steepness of rise of the flow velocity curve were smaller after than before alcohol consumption. CONCLUSION: BAC close to a legal value at which driving is allowed in some European countries inhibited the neuronal activity and resulted in dilation of cerebral arterioles. Cerebral vasodilation may explain the decrease of cerebral vasoreactivity and might contribute to the disturbance of visually evoked flow response after alcohol consumption.

Neurophysiological Examinations as Adjunctive Tool to Imaging Techniques in Spontaneous Intracerebral Hemorrhage: IRONHEART Study.

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.

A Modified in vitro Clot Lysis Assay Predicts Outcomes in Non-traumatic Intracerebral Hemorrhage Stroke Patients-The IRONHEART Study.

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.

Prognostic Value of Various Hemostasis Parameters and Neurophysiological Examinations in Spontaneous Intracerebral Hemorrhage: The IRONHEART Study Protocol.

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.

Effect of reading with direct or indirect light on the visually evoked flow response in the posterior cerebral artery.

PURPOSE: Reading with direct light from computer monitors or tablets may cause visual fatigue and hamper reading comprehension. Our aim was to compare the blood flow response in the supplying artery of the visual cortex when reading from tablet screen or from paper. The neurovascular coupling was tested also after 15-minute reading from either monitor or paper. METHODS: Flow velocity responses evoked by reading from paper and from monitor were measured by transcranial Doppler sonography in a random sequence in both posterior cerebral arteries (PCAs) of 20 young healthy adults. Afterward, PCA flow response evoked by reading from paper was also investigated after 15 minutes reading on the same tablet or paper, in a random order. RESULTS: Reading from monitor with its own source of light and reading from paper with indirect light caused very similar PCA flow response. Moreover, the flow velocity increase, evoked by reading form paper did not differ after 15-minute reading from monitor or from paper. CONCLUSIONS: Reading with direct or indirect light produces similar flow response in the occipital cortex.

Acute alcohol intoxication may cause delay in stroke treatment - case reports.

BACKGROUND: The signs and symptoms of acute alcohol intoxication resemble those of vertebrobasilar stroke. Due to their shared symptoms including double vision, nystagmus, dysarthria, and ataxia, the differential diagnosis of alcohol intoxication and vertebrobasilar stroke may pose a challenge. Moreover, if alcohol intoxication and stroke occur simultaneously, the signs and symptoms of stroke may be attributed to the effects of alcohol, leading to delayed stroke diagnosis and failure to perform reperfusion therapy. CASE PRESENTATIONS: Three cases of alcohol intoxication and stroke are presented. The first patient (female, 50 years old) had dysarthria, nystagmus and trunk ataxia on admission. Her blood alcohol level was 2.3‰. The symptoms improved after forced diuresis, but 5.5 h later progression was observed, and the patient developed diplopia and dysphagia in addition to her initial symptoms. Angiography showed occlusion of the basilar artery. Intraarterial thrombolysis was performed. The second patient (male, 62 years old) developed diplopia, dysarthria and trunk ataxia after consuming 4-units of alcohol, and his symptoms were attributed to alcohol intoxication. Two hours later, neurological examination revealed dysphagia and mild right-sided hemiparesis, which questioned the causal relationship between the symptoms and alcohol consumption. Cerebral CT was negative, and intravenous thrombolysis was administered. The third patient (male, 55 years old) consumed 10 units of alcohol before falling asleep. Three hours later, his relatives tried to wake him up. He was unresponsive, which was attributed to alcohol intoxication. When he woke up 8 h later, right-sided hemiparesis and aphasia were observed, and cerebral CT already revealed irreversible ischemic changes. CONCLUSIONS: Our cases show that alcohol consumption may interfere with stroke diagnosis by mimicking the signs and symptoms of vertebrobasilar stroke. Moreover, attributing the symptoms of stroke to alcohol intoxication may delay stroke diagnosis resulting in failure of reperfusion therapy. Based on our observations we conclude that stroke should be considered in the case of worsening symptoms, dysphagia, hemiparesis and disproportionately severe signs that cannot be attributed to the amount of alcohol consumed. In the case of ambiguity, ambulance should be called, and if stroke cannot be excluded, specific therapy should be administered.