Pre-Hospital Delay in Acute Ischemic Stroke Care: Current Findings and Future Perspectives in a Tertiary Stroke Center from Romania-A Cross-Sectional Study.

Background and objectives: The time interval between stroke onset and hospital arrival is a major barrier for reperfusion therapies in acute ischemic stroke and usually accounts for most of the onset-to-treatment delay. The present study aimed to analyze the pre-hospital delays for patients with acute ischemic stroke admitted to a tertiary stroke center in Romania and to identify the factors associated with a late hospital arrival. Material and methods: The study population consisted of 770 patients hospitalized with the diagnosis of acute ischemic stroke in the University Emergency Hospital Bucharest during a 6-month period, between 1 January and 30 June 2018. Data regarding pre-hospital delays were prospectively collected and analyzed together with the demographic and clinical characteristics of the patients. Results: In total, 31.6% of patients arrived at the hospital within 4.5 h from stroke onset and 4.4% in time intervals between 4.5 and 6 h from the onset, and 28.7% of the patients reached the hospital more than 24 h after onset of symptoms. Transport to hospital by own means was the only factor positively associated with arrival to hospital > 4.5 h from stroke onset and more than doubled the odds of late arrival. Factors negatively associated with hospital arrival > 4.5 h after stroke onset were prior diagnosis of atrial fibrillation, initial National Institute of Health Stroke Scale (NIHSS) score ≥ 16 points, presence of hemianopsia, facial palsy and sensory disturbance. Factors increasing the odds of hospital arrival after 24 h from stroke onset were living alone and living in rural areas. Conclusions: Almost one in three ischemic stroke patients presenting to our center reaches hospital more than 24 h after onset of symptoms. These findings highlight the need for urgent measures to improve not only stroke awareness but also pre-hospital protocols in order to provide timely and appropriate care for our stroke patients.

Neutrophil-to-Lymphocyte Ratio as an Independent Predictor of In-Hospital Mortality in Patients with Acute Intracerebral Hemorrhage.

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), a very low cost, widely available marker of systemic inflammation, has been proposed as a potential predictor of short-term outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH admitted to the Neurology Department during a two-year period were screened for inclusion. Based on eligibility criteria, 201 patients were included in the present analysis. Clinical, imaging, and laboratory characteristics were collected in a prespecified manner. Logistic regression models and receiver operating characteristics (ROC) curves were used to assess the performance of NLR assessed at admission (admission NLR) and 72 h later (three-day NLR) in predicting in-hospital death. Results: The median age of the study population was 70 years (IQR: 61-79), median admission NIHSS was 16 (IQR: 6-24), and median hematoma volume was 13.7 mL (IQR: 4.6-35.2 mL). Ninety patients (44.8%) died during hospitalization, and for 35 patients (17.4%) death occurred during the first three days. Several common predictors were significantly associated with in-hospital mortality in univariate analysis, including NLR assessed at admission (OR: 1.11; 95% CI: 1.04-1.18; p = 0.002). However, in multivariate analysis admission, NLR was not an independent predictor of in-hospital mortality (OR: 1.04; 95% CI: 0.9-1.1; p = 0.3). The subgroup analysis of 112 patients who survived the first 72 h of hospitalization showed that three-day NLR (OR: 1.2; 95% CI: 1.09-1.4; p < 0.001) and age (OR: 1.05; 95% CI: 1.02-1.08; p = 0.02) were the only independent predictors of in-hospital mortality. ROC curve analysis yielded an optimal cut-off value of three-day NLR for the prediction of in-hospital mortality of ≥6.3 (AUC = 0.819; 95% CI: 0.735-0.885; p < 0.0001) and Kaplan-Meier analysis proved that ICH patients with three-day NLR ≥6.3 had significantly higher odds of in-hospital death (HR: 7.37; 95% CI: 3.62-15; log-rank test; p < 0.0001). Conclusion: NLR assessed 72 h after admission is an independent predictor of in-hospital mortality in ICH patients and could be widely used in clinical practice to identify the patients at high risk of in-hospital death. Further studies to confirm this finding are needed.

Quality of acute stroke care in Romania: Achievements and gaps between 2017 and 2022.

Romania has one of the highest incidences of stroke and one of the highest mortality rates in Europe. The mortality rate due to treatable causes is also very high and is associated with the lowest public spending on healthcare in the European Union. Nonetheless, significant achievements in acute stroke care have been made in Romania in the last 5 years, most notably the increase of the national thrombolysis rate from 0.8% to 5.4%. Numerous educational workshops and constant communication with the stroke centers led to a solid and active stroke network. Due to the joint efforts of this stroke network and the ESO-EAST project, the quality of stroke care has significantly improved. However, Romania still faces many problems: a major lack of specialists in interventional neuroradiology and consequently a low number of stroke patients treated by thrombectomy and carotid revascularization procedures, a low number of neuro-rehabilitation centers and a country-wide lack of neurologists.

Stroke mimics treated with thrombolysis: further evidence on safety and distinctive clinical features.

BACKGROUND: Patients who present with symptoms mimicking ischaemic stroke (IS), but have a different diagnosis, are known as stroke mimics (SM). The necessity for rapid administration of intravenous thrombolysis in patients with acute IS may lead to treatment of patients with conditions mimicking stroke. A variable proportion of patients with SM (1.4-14%) are currently treated with intravenous tissue plasminogen activator therapy (IV-tPA). The outcome of these patients is generally favourable and complications are rather infrequent. We aimed to determine the frequency, clinical features and prognosis of SM patients treated with IV-tPA in an experienced stroke centre. METHODS: A prospective registry was assembled with patients treated with IV-tPA at our stroke unit from January 2004 to December 2011. We recorded age, gender, baseline National Institutes of Health Stroke Scale (NIHSS) score, treatment delay, vascular risk factors, clinical syndrome and aetiology. We retrospectively analysed the clinical characteristics of SM, safety (symptomatic intracranial haemorrhage and mortality) and outcome measures (modified Rankin Scale at 3 months, mRS) and compared them with IS patients. RESULTS: 621 patients were treated with IV-tPA during the study period, 606 (97.5%) were IS and 15 (2.4%) were SM. The aetiology of SM was somatoform disorders (5), headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome (3), herpetic encephalitis (2), glial tumours (2), and migraine with aura, focal seizure and cortical vein thrombosis in single cases. SM were younger (72 ± 14 vs. 53.7 ± 16 years, p < 0.05), had a lower baseline deficit [NIHSS 13 (9-18) vs. 8 (5-10), p < 0.05], fewer vascular risk factors, and left hemisphere symptoms were predominant (80 vs. 52.4%, p < 0.05). Global aphasia without hemiparesis (GAWH) was the presenting symptom in 8 (54%) SM and 44 (7%) IS (p < 0.05). Multimodal computed tomography was performed in 3 SM patients and showed perfusion deficits in 2 of them. No intracranial haemorrhage or disability (functional outcome at 3 months, mRS >2) was recorded in any SM patient. CONCLUSIONS: The use of intravenous thrombolysis appears to be safe in our SM patients, and prognosis is universally favourable. Somatoform disorder and HaNDL syndrome were prominent causes, and GAWH the most common presentation. The safety of thrombolysis in SM suggests that delaying or withholding treatment may be inappropriate: the benefit of thrombolysis in case of IS may outweigh the risks of treating an SM. Further studies may assess the future role of multimodal computed tomography in the differential diagnosis between IS and SM.

Serum and CSF Biomarkers Predict Active Early Cognitive Decline Rather Than Established Cognitive Impairment at the Moment of RRMS Diagnosis.

(1) Background: Cognitive impairment (CI) begins early in the evolution of multiple sclerosis (MS) but may only become obvious in the later stages of the disease. Little data is available regarding predictive biomarkers for early, active cognitive decline in relapse remitting MS (RRMS) patients. (2) Methods: 50 RRMS patients in the first 6 months following diagnosis were included. The minimum follow-up was one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-up. Cognitive performance was assessed at baseline and 12-month follow-up; (3) Results: Statistically significant differences were found for patients undergoing active cognitive decline for sNfL z-scores at baseline and 3 months, CSF NfL baseline values, CSF Aß42 and the Bremso score as well. The logistic regression model based on these 5 variables was statistically significant, χ2(4) = 22.335, p < 0.0001, R2 = 0.671, with a sensitivity of 57.1%, specificity of 97.4%, a positive predictive value of 80% and a negative predictive value of 92.6%. (4) Conclusions: Our study shows that serum biomarkers (adjusted sNfL z-scores at baseline and 3 months) and CSF biomarkers (CSF NfL baseline values, CSF Aß42), combined with a clinical score (BREMSO), can accurately predict an early cognitive decline for RRMS patients at the moment of diagnosis.

Low Fluctuation of Symptoms May Delay Diagnosis of Myasthenia Gravis: A Case Series.

INTRODUCTION: Myasthenia gravis is an autoimmune disorder affecting neuromuscular transmission, and its hallmark is fluctuating muscular weakness affecting the ocular, bulbar, respiratory, or limb muscles. Our objective is to highlight the difficulties encountered in diagnosing this disorder in patients lacking this characteristic phenomenon. METHODS: Three cases of patients presenting with progressive weakness of bulbar and ocular muscles, in whom a lack of fluctuation delayed the diagnosis of myasthenia gravis, are described. RESULTS: Amyotrophic lateral sclerosis was considered in two of the patients, while cavernous sinus thrombosis was initially diagnosed in the third. Electrodiagnostic, pharmacologic, and serologic testing ultimately established the diagnosis of myasthenia gravis. CONCLUSION: While the typical clinical pattern of myasthenia gravis is well known and easily recognizable, there are cases when the diagnosis, and thus the treatment, is delayed because of low or absent fluctuation of symptoms. The acknowledgment of this probably underestimated presentation is important for expeditious management.

Cranial cerebrospinal fluid leak and intracranial hypotension syndrome - a case report.

Spontaneous intracranial hypotension is a rare clinical entity caused in most cases by a cerebrospinal fluid leak occurring at the level of the spinal cord. Cranial dural leaks have been previously reported as a cause of orthostatic headaches but, as opposed to spinal dural leaks, were not associated with other findings characteristic of spontaneous intracranial hypotension. We present the case of a male admitted for severe orthostatic headache. The patient had a history of intermittent postural headaches, dizziness, and symptoms consistent with post-nasal drip, which appeared several years after head trauma. Brain imaging showed signs consistent with intracranial hypotension: bilateral hygromas, subarachnoid hemorrhage, superficial siderosis, diffuse contrast enhancement of the pachymeninges, and superior sagittal sinus engorgement. No spinal leak could be identified by magnetic resonance imaging, and the patient had a rapid remission of symptoms with conservative management. Further work-up identified an old temporal bone fracture which created a route of egress between the posterior fossa and the mastoid cells. Otorhinolaryngology examination showed pulsatile bloody discharge and liquorrhea at the level of the left pharyngeal opening of the Eustachian tube. The orthostatic character of the headache, as well as the brain imaging findings, were consistent with intracranial hypotension syndrome caused by a cranial dural leak. Clinical signs and imaging findings consistent with the diagnosis of apparently "spontaneous" intracranial hypotension should prompt the search for a cranial dural leak if a spinal leak is not identified.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Stress cardiomyopathy misinterpreted as ST-segment elevation myocardial infarction in a patient with aneurysmal subarachnoid hemorrhage: a case report.

Cardiac abnormalities are frequently reported in acute subarachnoid hemorrhage (SAH) patients. However, frank ST-elevation and myocardial dysfunction mimicking acute coronary syndrome is a rare occurrence. Systemic and local catecholamine release mediate myocardial injury and may explain raised troponin levels, concordant regional wall motion abnormalities and systolic dysfunction. These findings can pose a significant problem in the acute setting where "time-is-muscle" paradigm can rush clinicians towards a "rule-in" diagnosis of acute myocardial infarction. We present the case of a 60-year-old male who arrived at a regional emergency department with loss of consciousness, chest pain and headache. His ECG showed ST-elevation in precordial leads with corresponding region wall motion abnormalities and dynamically elevated troponin levels which supported a diagnosis of acute myocardial infarction. Percutaneous coronary intervention was attempted but found no hemodynamically significant lesions and the patient was managed conservatively with antithrombotic treatment. Further work-up for his headache led to the diagnosis of aneurysmal SAH and subsequent endovascular coiling. The patient was discharged with a good clinical outcome. We discuss the potential catastrophic consequences of interpreting neurologic myocardial stunning as STEMI. Use of potent antithrombotic therapies, like bridging thrombolysis, in this setting can lead to dismal consequences. Clinical history should still be carefully obtained in the acute setting in this era of sensitive biomarkers.

Clinical Characteristics and Outcomes of Patients with Intracerebral Hemorrhage - A Feasibility Study on Romanian Patients.

Intracerebral hemorrhage is a significant public health problem, as it is a disease associated with overwhelming mortality and disability. We performed a retrospective feasibility study of patients admitted with acute intracerebral hemorrhage in our department for four months. Our aims were to identify peculiarities of the risk factors, demographic and clinical characteristics of intracerebral hemorrhage patients from our population, to estimate a feasible recruitment rate for a larger prospective study of patients with intracerebral hemorrhage and to analyze and correct potential drawbacks in the methodology of a more extensive prospective study of patients with intracerebral hemorrhage hospitalized in our department. During the study period, we admitted 53 patients with intracerebral hemorrhage in our department. The mean age of the patients was 69.1 years, and 53% were men. Arterial hypertension was the most common etiologic factor leading to intracerebral hemorrhage. 50.01% of patients died during hospitalization, 31.19% were discharged with significant disability, and 18.8% had a favorable short-term outcome. Higher hematoma volumes, male sex, deep location of the hemorrhage, and age between 51 and 60 years were factors associated with an unfavorable short-term outcome.

Opsoclonus-Myoclonus Syndrome Associated With West-Nile Virus Infection: Case Report and Review of the Literature.

Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with different autoimmune, infectious and paraneoplastic aetiologies or in most cases idiopathic. We report the case of a 75-year-old woman who was admitted in our department in early fall for altered mental status, opsoclonus, multifocal myoclonus, truncal titubation and generalized tremor, preceded by a 5 day prodrome consisting of malaise, nausea, fever and vomiting. Brain computed tomography and MRI scans showed no significant abnormalities and cerebrospinal fluid changes consisted of mildly increased protein content and number of white cells. Work-up for paraneoplastic and autoimmune causes of OMS was negative but serologic tests identified positive IgM and IgG antibodies against West Nile virus (WNV). The patient was treated with Dexamethasone and Clonazepam with progressive improvement of mental status, myoclonus, opsoclonus and associated neurologic signs. Six months after the acute illness she had complete recovery. To our knowledge this is the 14th case of WNV associated OMS reported in the literature so far. We briefly describe the clinical course of the other reported cases together with the different treatment strategies that have been employed.

Etiologic classification of ischemic stroke: Where do we stand?

Despite major technological advances in ischemic stroke diagnostic techniques, our current understanding of stroke mechanisms and etiology continues to remain unclear in a significant percent of patients. As a result, several etiological ischemic stroke classifications have emerged during the last two decades but their reliability and validity is far from perfect and further world-wide research is needed in order to achieve the so much needed "standard reference language". An ideal ischemic stroke classification should both comprise all underlying pathologies that could potentially concur to an index event and emphasize the most likely etiological and pathophysiological mechanism. Currently available approaches to ischemic stroke classification are either phenotypic or causative in nature, a multitude of criteria being published by different authors. Phenotypic classifications are targeted towards describing the concurring underlying pathologies, without highlighting the most probable ischemic stroke etiology, while causative classifications focus on establishing the most likely cause, neglecting other associated diseases. A judicious use of this two different concepts might improve clinical research as well as daily clinical practice.

Vertebral Artery Dissection: a Contemporary Perspective.

Arterial dissections are among the most frequent causes of stroke in young adults. Usually they are associated with trauma, but as the modern imaging tools are evolving, more dissections are being diagnosed and more etiologies are being described. Vertebral artery dissections (VADs) have the distinct particularity that they can cause ischemic stroke (in the brainstem, cerebellum or even the spinal cord), but also subarachnoid hemorrhage, when the dissection occurs in the intracranial segment of the vertebral artery. We present a review of the literature, going over etiology, clinical aspects, diagnosis and treatment of VADs and we illustrate the theory with three different types of VAD from our clinical experience.

Transient Global Amnesia After Cerebral Angiography With Iomeprol: A Case Report.

Transient global amnesia is now considered a very rare complication of cerebral angiography. Various etiological mechanisms have been suggested to account for this complication, but no consensus has been reached yet. This case report documents one of the few reported cases of cerebral angiography-related transient global amnesia associated with magnetic resonance imaging (MRI) evidence of unilateral hippocampal ischemia, most probably as a consequence of a transient reduction in regional hippocampal blood flow. However, the possibility of a direct neurotoxic effect of the nonionic contrast media Iomeprol on the Cornu ammonis - field 1 neurons cannot be firmly ruled out.We describe the case of a 54-year-old woman admitted to our department for left upper limb weakness with acute onset 8 days before. The brain computed tomography (CT) scan performed at admission revealed subacute ischemic lesions in the right watershed superficial territories and a right thalamic lacunar infarct. Diagnostic digital subtraction cerebral angiography was performed 4 days after admission with the nonionic contrast media Iomeprol. A few minutes after completion of the procedure, the patient developed symptoms suggestive for transient global amnesia. The brain MRI performed 22 hours after the onset of symptoms demonstrated increased signal within the lateral part of the right hippocampus on the diffusion-weighted imaging (DWI) sequences, associated with a corresponding reduction in the apparent diffusion coefficient (ADC) and increased signal on the fluid-attenuated inversion recovery (FLAIR) sequences, consistent with acute hippocampal ischemia and several T2/FLAIR hyperintensities in the right watershed superficial territories and in the right thalamus, corresponding to the lesions already identified on the CT scan performed at admission. A follow-up MRI, performed 2 months later, demonstrated the disappearance of the increased signal within the right hippocampus on the DWI, T2/FLAIR, and ADC sequences.The precise mechanism of transient global amnesia related to cerebral angiography is still unclear, and further studies aimed to determine the definite pathophysiology of this syndrome and consequently to establish specific preventive measures are needed. Although the condition itself is considered to be self-limited, the long-term prognosis and the risk of recurrence in the cases where subsequent angiographic procedures are performed are not established yet.

Endocarditis and stroke.

Endocarditis is an important, although less common, cause of cerebral embolism. All forms of endocarditis share an initial common pathophysiologic pathway, best illustrated by the non-bacterial thrombotic form, but also a final potential for embolization. Stroke associated with endocarditis has signifficant mortality and morbidity rates, especially due to the frequent concomitant multiple sites of brain embolization. In this article we aim to briefly review endocarditis with a focus on stroke as a complication, while also presenting case correlates from our department.