Related factors with orolingual angioedema after intravenous alteplase in acute ischemic stroke: results from a single-center cohort and meta-analysis.

INTRODUCTION: Orolingual angioedema (OA) after intravenous thrombolysis (IVT) with alteplase in acute stroke can be a life-threatening complication. Our aim was to describe its incidence, clinical features, and related factors. PATIENTS AND METHODS: We analyzed a single-center cohort of stroke patients treated with IVT in an 8-year period. We compared patients with (OA+) and without OA (OA-). A meta-analysis of previous studies was performed to identify factors related with OA. RESULTS: OA occurred in 7 out of 512 patients (1.37%; 95% CI 0.86-1.88%). Previous hypertension, diabetes, and treatment with ACE inhibitors were more frequent in OA+ compared to OA- patients (100% vs 58%, p = 0.045; 71.4% vs 21.8%, p = 0.008; and 71.4% vs. 16.6%, p = 0.002). Three out of 4 cases with unilateral OA had a contralateral insular infarct. The meta-analysis included 13 studies: 5720 stroke patients treated with IVT and 209 cases of OA. Factors related with OA were ACE inhibitor treatment (RR 5.33 [95% CI 3.07-9.26]) female sex (RR 1.94 [95% CI 1.24-3.03]), hypertension (RR 2.64 [95% CI 1.79-3.90]), diabetes (RR 1.60 [95% CI 1.16-2.21]), and dyslipidemia (RR 1.46 [95% CI 1.00-2.12]). The effect of insular infarct was inconclusive: positive when considering complete infarcts (RR 1.97 [95% CI 1.18-3.29]) and absent when partial infarcts were also included. CONCLUSIONS: OA occurred in 1.37% of the IVT-treated stroke patients. Previous treatment with ACE inhibitors, hypertension, diabetes, dyslipidemia, and female sex were associated with OA. The effect of insular infarct needs to be clarified in further studies.

Acute Stroke Care during the COVID-19 Pandemic: Reduction in the Number of Admissions of Elderly Patients and Increase in Prehospital Delays.

INTRODUCTION: We analyzed whether the coronavirus disease 2019 (COVID-19) crisis affected acute stroke care in our center during the first 2 months of lockdown in Spain. METHODS: This is a single-center, retrospective study. We collected demographic, clinical, and radiological data; time course; and treatment of patients meeting the stroke unit admission criteria from March 14 to May 14, 2020 (COVID-19 period group). Data were compared with the same period in 2019 (pre-COVID-19 period group). RESULTS: 195 patients were analyzed; 83 in the COVID-19 period group, resulting in a 26% decline of acute strokes and transient ischemic attacks (TIAs) admitted to our center compared with the previous year (p = 0.038). Ten patients (12%) tested positive for PCR SARS-CoV-2. The proportion of patients aged 65 years and over was lower in the COVID-19 period group (53 vs. 68.8%, p = 0.025). During the pandemic period, analyzed patients were more frequently smokers (27.7 vs. 10.7%, p = 0.002) and had less frequently history of prior stroke (13.3 vs. 25%, p = 0.043) or atrial fibrillation (9.6 vs. 25%, p = 0.006). ASPECTS score was lower (9 [7-10] vs. 10 [8-10], p = 0.032), NIHSS score was slightly higher (5 [2-14] vs. 4 [2-8], p = 0.122), onset-to-door time was higher (304 [93-760] vs. 197 [91.25-645] min, p = 0.104), and a lower proportion arrived within 4.5 h from onset of symptoms (43.4 vs. 58%, p = 0.043) during the CO-VID-19 period. There were no differences between proportion of patients receiving recanalization treatment (intravenous thrombolysis and/or mechanical thrombectomy) and in-hospital delays. CONCLUSION: We observed a reduction in the number of acute strokes and TIAs admitted during the COVID-19 period. This drop affected especially elderly patients, and despite a delay in their arrival to the emergency department, the proportion of patients treated with recanalization therapies was preserved.

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

OBJECTIVE: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence. METHODS: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration. RESULTS: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ2: 12.1 [p = 0.357] and χ2: 21.7 [p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively. CONCLUSIONS: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.

Cerebral amyloid angiopathy-related transient focal neurological episodes: A transient ischemic attack mimic with an increased risk of intracranial hemorrhage.

BACKGROUND: Transient focal neurological episodes (TFNEs) are a recently recognized clinical presentation of cerebral amyloid angiopathy (CAA). Our aim was to describe the clinical and radiological features of a series of patients with AS. METHODS: We included 11 patients presenting with recurrent transient focal neurological symptoms and radiological features related to CAA. RESULTS: Mean age was 76,6 and 5 patients were women. All patients reported transient, stereotyped, and recurrent episodes (6 patients had >10 episodes). Gradual spread of the symptoms was recorded in 9 patients. Initially, 3 patients were misdiagnosed as having recurrent transient ischemic attack (TIA), 6 as having seizures, and 2 as having both. Two patients were prescribed antiplatelet therapy. A cerebral MRI with T2* gradient-recalled echo sequence revealed cortical superficial siderosis (cSS) in 5 patients, cortical microbleeds in 1 patient, and both features in 5 cases. After a median follow-up of 36 months, intracranial hemorrhage (ICH) was recorded in 4 patients. All 4 had cSS in the previous cerebral MRI, and 1 was on antiplatelet therapy. CONCLUSION: CAA-related TFNEs are an underdiagnosed entity, often mimicking TIA, seizures, or migraine aura. This misdiagnosis can lead to the prescription of antiplatelet or anticoagulant therapy, which increases the risk of ICH. Our results suggest that cSS might be a radiological marker that is closely related to an increased risk of bleeding. A T2* gradient-recalled echo MRI should be performed in elderly patients with transient focal neurological symptoms suggestive of CAA.

Age- and sex-specific analysis of patients with embolic stroke of undetermined source.

OBJECTIVE: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS). METHODS: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death. RESULTS: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively). CONCLUSIONS: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.

Efficacy of New Measures Saving Time in Acute Stroke Management: A Quantified Analysis.

BACKGROUND: Time to treatment remains the most important factor in acute ischemic stroke prognosis. We quantified the effect of new interventions reducing in-hospital delays in acute stroke management and assessed its repercussion on door-to-imaging (DTI), imaging-to-needle (ITN), and door-to-needle (DTN) times. METHODS: Prospective registry of consecutive stroke patients who were candidates for reperfusion therapy attended in a tertiary care hospital from February 1 to December 31, 2014. A series of measures aimed at reducing in-hospital delays were implemented. We compared DTI, ITN, and DTN times between patients who underwent the interventions and those who did not. RESULTS: 231 patients. DTI time was lower when personal history was reviewed and tests were ordered before patient arrival (2.5 minutes saved, P = .016) and when electrocardiogram was not made (5.4 minutes saved, P < .001). Not performing a computed tomography angiography and not waiting for coagulation results from laboratory before intravenous thrombolysis (25.5%) reduced ITN time significantly (14 and 12 minutes saved, respectively, P < .001). These interventions remained as independent predictors of a shorter ITN and DTN time. Completing all steps resulted in the lowest DTI and ITN times (13 and 19 minutes, respectively). CONCLUSIONS: Every measure is an important part of a chain focused on saving time in acute stroke: the lowest DTI and ITN times were obtained when all steps were completed. Measures shortening ITN time produced a greater impact on DTN time reduction; therefore, ITN interventions should be considered a critical part of new protocols and guidelines.

Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS2) and CHA2DS2-VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS. METHODS: We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS2 and CHA2DS2-VASc scores. RESULTS: One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS2 score 0, patients with CHADS2 score 1 and CHADS2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86-10.40, respectively). Compared with low-risk CHA2DS2-VASc score, patients with high-risk CHA2DS2-VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4). CONCLUSIONS: The risk of recurrent ischemic stroke/TIA and death in ESUS is reliably stratified by CHADS2 and CHA2DS2-VASc scores. Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc group have much higher risk of ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold, respectively.

Vascular imaging before intravenous thrombolysis: consequences of in-hospital delay in applying two diagnostic procedures.

BACKGROUND: Vascular imaging is increasingly used for diagnosis of arterial occlusions in acute ischemic stroke (AIS) patients. Our aim was to determine whether computed tomography angiography (CTA) and Doppler/duplex ultrasound (DUS) before intravenous thrombolysis (IVT) is associated with a delay in time-to-treatment. METHODS: Observational analysis of a prospective cohort of AIS patients treated with IVT from January 2009 to December 2012. Patients were classified into three groups: the noncontrast computed tomography (NCCT) group (patients studied only with NCCT before IVT), CTA group (patients who underwent CTA in addition to NCCT), and the DUS group (patients studied with NCCT+DUS). RESULTS: We treated 244 patients: 116 patients (47.5%) were studied with NCCT, 79 (32.4%) with CTA, and 49 (20.1%) with DUS. Door-to-needle time was significantly higher in the CTA group (median 60 [48-77] minutes) than in the NCCT group (51.5 [40-65]) and DUS group (48 [42-61]) (P = .008). No differences were observed for onset-to-door time and onset-to-needle time. In the multivariate linear regression analysis, onset-to-door time, prehospital stroke code activation, and performance of CTA influenced door-to-needle time. CONCLUSIONS: Performing CTA before IVT seems to increase door-to-needle time. Vascular imaging based on DUS should be considered only if this does not lead to in-hospital delay.

Phenotypic variability in a four generation family with a p.Thr666Met CACNA1A gene mutation.

BACKGROUND: Familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6 are distinct neurological disorders associated with mutations in the CACNA1A gene. Phenotypic variability and clinical overlap are recognized. PATIENTS: We describe a 2-year-old child with transiently decreased consciousness and clinical and radiological signs of early-onset cerebellar atrophy. The family history was significant, and 11 affected members across four generations indicated an unusually wide clinical spectrum including migraine, hemiplegia, coma, and progressive cerebellar ataxia. RESULTS: The p.Thr666Met mutation of the CACNA1A gene was identified in the index patient and in five of his affected relatives who were analyzed. Our patient is the youngest one of this entity diagnosed to date. CONCLUSIONS: Taking into account such a wide clinical expression of these gene mutations, it could be more accurate to speak about "channel-related diseases" to characterize the clinical expression according to the genetic analysis and to the phenotypes associated with each CACNA1A gene mutation.