Incidence and Types of Cardiac Arrhythmias in the Peri-Ictal Period in Patients Having a Generalized Convulsive Seizure.

BACKGROUND AND OBJECTIVES: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases. METHODS: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during inpatient video-EEG monitoring for epilepsy evaluation. Exclusion criteria were status epilepticus and an obscured video recording. We analyzed semiologic and cardiorespiratory features through video-EEG (VEEG), electrocardiogram, thoracoabdominal bands, and pulse oximetry. We investigated the presence of bradycardia, asystole, supraventricular tachyarrhythmias (SVTs), premature atrial beats, premature ventricular beats, nonsustained ventricular tachycardia (NSVT), atrial fibrillation (Afib), ventricular fibrillation (VF), atrioventricular block (AVB), exaggerated sinus arrhythmia (ESA), and exaggerated sinus arrhythmia with bradycardia (ESAWB). A board-certified cardiac electrophysiologist diagnosed and classified the arrhythmia types. Bradycardia, asystole, SVT, NSVT, Afib, VF, AVB, and ESAWB were classified as arrhythmias of interest because these were of SUDEP pathophysiology value. The main outcome was the occurrence of seizure-induced arrhythmias of interest during inpatient VEEG monitoring. Moreover, yearly follow-up was conducted to identify SUDEP cases. Binary logistic generalized estimating equations were used to determine clinical-demographic and peri-ictal variables that were predictive of the presence of seizure-induced arrhythmias of interest. The z-score test for 2 population proportions was used to test whether the proportion of seizures and patients with postconvulsive ESAWB or bradycardia differed between SUDEP cases and survivors. RESULTS: This study includes data from 249 patients (mean age 37.2 ± 23.5 years, 55% female) who had 455 seizures. The most common arrhythmia was ESA, with an incidence of 137 of 382 seizures (35.9%) (106/224 patients [47.3%]). There were 50 of 352 seizure-induced arrhythmias of interest (14.2%) in 41 of 204 patients (20.1%). ESAWB was the commonest in 22 of 394 seizures (5.6%) (18/225 patients [8%]), followed by SVT in 18 of 397 seizures (4.5%) (17/228 patients [7.5%]). During follow-up (48.36 ± 31.34 months), 8 SUDEPs occurred. Seizure-induced bradycardia (3.8% vs 12.5%, z = -16.66, p < 0.01) and ESAWB (6.6% vs 25%; z = -3.03, p < 0.01) were over-represented in patients who later died of SUDEP. There was no association between arrhythmias of interest and seizure severity biomarkers (p > 0.05). DISCUSSION: Markers of seizure severity are not related to seizure-induced arrhythmias of interest, suggesting that other factors such as occult cardiac abnormalities may be relevant for their occurrence. Seizure-induced ESAWB and bradycardia were more frequent in SUDEP cases, although this observation was based on a very limited number of SUDEP patients. Further case-control studies are needed to evaluate the yield of arrhythmias of interest along with respiratory changes as potential SUDEP biomarkers.

Reliable detection of generalized convulsive seizures using an off-the-shelf digital watch: A multisite phase 2 study.

OBJECTIVE: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy. METHODS: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of (1) leave-one-patient-out cross-validation (LOPO CV) on GCS patients, (2) false alarm rate (FAR) testing on nonseizure patients, and (3) "fixed-and-frozen" prospective testing on a prospective patient cohort. Balanced accuracy, precision, sensitivity, and FAR were used to quantify the performance of the algorithm. Seizure onsets and offsets were determined by using video-electroencephalographic (EEG) monitoring. Feature importance was calculated as the mean decrease in Gini impurity during the LOPO CV testing. RESULTS: LOPO CV results showed balanced accuracy of .93 (95% confidence interval [CI] = .8-.98), precision of .68 (95% CI = .46-.85), sensitivity of .87 (95% CI = .62-.96), and FAR of .21/24 h (interquartile range [IQR] = 0-.90). Testing the algorithm on patients without seizure resulted in an FAR of .28/24 h (IQR = 0-.61). During the "fixed-and-frozen" prospective testing, two patients had three GCS, which were detected by the algorithm, while generating an FAR of .25/24 h (IQR = 0-.89). Feature importance showed that heart rate-based features outperformed accelerometer/gyroscope-based features. SIGNIFICANCE: Commercially available wearable digital watches that reliably detect GCS, with minimum false alarm rates, may overcome usage adoption and other limitations of custom-built devices. Contingent on the outcomes of a prospective phase 3 study, such devices have the potential to provide non-EEG-based seizure surveillance and forecasting in the clinical setting.

Ictal Central Apnea Is Predictive of Mesial Temporal Seizure Onset: An Intracranial Investigation.

OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.

Stimulation-induced respiratory enhancement in corticothalamic regions.

OBJECTIVE: We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing. METHODS: Twenty-nine patients with medically intractable epilepsy were prospectively recruited in an epilepsy monitoring unit while undergoing stereoelectroencephalographic evaluation. Direct electrical stimulation in cortical and thalamic regions was carried out using low (<1 Hz) and high (≥10 Hz) frequencies, and low (<5 mA) and high (≥5 mA) current intensities, with pulse width of .1 ms. Electrocardiography, arterial oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ), oronasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. Airflow signal was used to estimate breathing rate, tidal volume, and minute ventilation (MV) changes during stimulation, compared to baseline. RESULTS: Electrical stimulation increased MV in the amygdala, anterior cingulate, anterior insula, temporal pole, and thalamus, with an average increase in MV of 20.8% ± 28.9% (range = 0.2%-165.6%) in 19 patients. MV changes were associated with SpO2 and ETCO2 changes (p < .001). Effects on respiration were parameter and site dependent. Within amygdala, low-frequency stimulation of the medial region produced 78.49% greater MV change (p < .001) compared to high-frequency stimulation. Longer stimulation produced greater MV changes (an increase of 4.47% in MV for every additional 10 s, p = .04). SIGNIFICANCE: Stimulation of amygdala, anterior cingulate gyrus, anterior insula, temporal pole, and thalamus, using certain stimulation paradigms, enhances respiration. Among tested paradigms, low-frequency, low-intensity, long-duration stimulation of the medial amygdala is the most effective breathing enhancement stimulation strategy. Such approaches may pave the way for the future development of neuromodulatory techniques that aid rescue from seizure-related apnea, potentially as a targeted sudden unexpected death in epilepsy prevention method.

Protocols for multimodal polygraphy for cardiorespiratory monitoring in the epilepsy monitoring unit. Part I: Clinical acquisition.

Multimodal polygraphy including cardiorespiratory monitoring in the Epilepsy Monitoring is becoming increasingly important. In addition to simultaneous recording of video and EEG, the combination of these techniques not only improves seizure detection, it enhances patient safety and provides information on autonomic clinical symptoms, which may be contributory to localization of seizure foci. However, there are currently no consensus guidelines, nor adequate information on devices available for multimodal polygraphy for cardiorespiratory monitoring in the Epilepsy Monitoring Unit. Our purpose here is to provide protocols and information on devices for such monitoring. Suggested parameters include respiratory inductance plethysmography (thoraco-abdominal belts for respiratory rate), pulse oximetry and four-lead electrocardiography. Detailed knowledge of devices, their operability and acquisition optimization enables accurate interpretation of signal and differentiation of abnormalities from artifacts. Multimodal polygraphy brings new opportunities for identification of peri-ictal cardiorespiratory abnormalities, and may identify high SUDEP risk individuals.

Protocols for multimodal polygraphy for cardiorespiratory monitoring in the epilepsy monitoring unit. Part II - Research acquisition.

Multimodal polygraphy including cardiorespiratory monitoring is a valuable tool for epilepsy and sudden unexpected death in epilepsy (SUDEP) research. Broader applications in research into stress, anxiety, mood and other domains exist. Polygraphy techniques used during video electroencephalogram (EEG) recordings provide information on cardiac and respiratory changes in the peri-ictal period. In addition, such monitoring in brain mapping during chronic intracranial EEG evaluations has helped the understanding of pathomechanisms that lead to seizure induced cardiorespiratory dysfunction. Our aim here is to provide protocols and information on devices that may be used in the Epilepsy Monitoring Unit, in addition to proposed standard of care data acquisition. These devices include oronasal thermistors, oronasal pressure transducers, capnography, transcutaneous CO2 sensors, and continuous noninvasive blood pressure monitoring. Standard protocols for cardiorespiratory monitoring simultaneously with video EEG recording, may be useful in the study of cardiorespiratory phenomena in persons with epilepsy.

The cognitive impact of guard shifts in physicians: a before-after study.

OBJECTIVE: We intend to evaluate the change of different cognitive functions after a guard shift in physicians. METHODS: A descriptive observational study was performed. The study population included Spanish physicians who were asked to complete before and immediately after their guard shift the following tests: Digit Span, TMT-A, TMT-B, Symbol Digit, Stroop, Free and Cued Selective Reminding, creep and formal fluency, Visual Orientation and Space Perception tests, and the Leeds Sleep Questionnaire. RESULTS: Thirty subjects were included in the study among which 43.3% were female. The mean subjective impression of the guard shift was 4.47/10 (2.57) and was correlated with the number of sleep hours during the guard shift (r = 0.72, p < 0.001). Statistically significant differences in the comparison between pre- and post-guard period results were found for the Symbol Digit test (88.27 vs. 81.47, p = 0.005), Digit Span test (7.43 vs. 7.00, p = 0.025), Free and Cued Selective Reminding Test (22.73 vs. 21.20, p = 0.002), categorical fluency (39.03 vs. 34.53, p = 0.008), and phonemic fluency (19.57 vs. 16.13, p = 0.001). CONCLUSIONS: The realization of guard shift was associated with a lower yield in several cognitive functions, especially in tasks related to executive function and attention.

Understanding the diagnoses and medical care experience of patients with new daily persistent headache: a qualitative study in Spain.

OBJECTIVE: To explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care. DESIGN: A qualitative phenomenological study was conducted. SETTING: A specialised headache unit at two university hospitals in Spain between February 2017 and December 2018. PARTICIPANTS: Patients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition). METHODS: Purposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers' field notes and patients' drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients' drawings. Also, Guillemin's proposal was used to analyse the contents of drawings. RESULTS: Nineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication-minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor-patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients. CONCLUSIONS: An in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients' knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients' beliefs.

Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke.

Background and Purpose: We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Methods: Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Results: Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1­22.3] P=0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2­1.5], P<0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7­30.90], P<0.001). Conclusions: One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

Linear Headache: A Novel Entity or a Variant of Nummular Headache? Clinical Characteristics and Treatment Response in a Series of 16 Patients.

OBJECTIVE: Linear headache has been recently described as an episodic or chronic unilateral pain distributed along a fixed linear trajectory, which combines some characteristics of epicrania fugax and nummular headache. The aim of this study was to describe the clinical characteristics and therapeutic response of a series of 16 new patients. DESIGN: This is an observational study with a series of cases. SETTING: The study period encompassed June 2014 to June 2019. Demographic, clinical, and therapeutic response data were recorded. METHODS: We included all consecutive patients who presented pain with the following characteristics: sharply contoured, fixed in size and shape, with linear shape, without movement along a trajectory, and not circumscribed to the territory of any nerve. RESULTS: Twelve patients were women, and four were men. The mean age at onset was 40.1 years. Pain was described as pressing in seven patients, burning in five, and electric or stabbing in two each. Symptomatic treatment had been used by 13 patients (81.2%), with analgesics being the most frequent treatment used. Thirteen patients received preventive treatment. The response to oral medications and anesthetic blockade was insufficient. OnabotulinumtoxinA was used in six cases, with an optimal (>75%) response observed in half. CONCLUSION: Linear headache appears to be a distinct headache syndrome from epicrania fugax or nummular headache. Preventive treatment is often required. The drug with the best response was onabotulinumtoxinA.

Neurological symptoms in Covid-19 patients in the emergency department.

BACKGROUND: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. METHODS: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test. RESULTS: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant. CONCLUSION: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.

Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. METHODS: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20). RESULTS: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p

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.

Anosmia is associated with lower in-hospital mortality in COVID-19.

BACKGROUND: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity. METHODS: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression. RESULTS: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48)). CONCLUSIONS: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.

Clinical characterization of delayed alcohol-induced headache: A study of 1,108 participants.

OBJECTIVE: To evaluate the International Classification of Headache Disorders (ICHD) criteria and to characterize the clinical phenotype of delayed alcohol-induced headache (DAIH). METHODS: We conducted a cross-sectional study of university students who voluntarily consumed alcohol and experienced headache. Participants completed a survey that included demographic and clinical data. We analyzed the phenotype of the headache, validated ICHD phenotype criteria for DAIH, and analyzed whether participants fulfilled criteria for low-CSF-pressure headache or migraine. RESULTS: A total of 1,108 participants were included (58% female, mean age 23 years, 41% with headache history). Mean alcohol intake was 158 g; spirits were consumed by 60% of the participants; beer was consumed by 41%; and wine was consumed by 18%. The ICHD criteria for DAIH were met in 95% of the participants. Headache duration (mean, 6.7 hours) correlated with total grams of alcohol consumed (r = 0.62, p = 0.03). Pain was bilateral in 85% of patients with predominantly frontal topography (43%). Pain quality was mainly pressing (60%) or pulsatile (39%) and was aggravated by physical activity in 83% of participants. ICHD low-CSF pressure-headache criteria were fulfilled in 58% of patients, and migraine criteria were fulfilled by 36%. CONCLUSIONS: DAIH is a moderate-intensity headache, is typically bilateral, and presents with frontal predominance and a pressing quality. The phenotype of DAIH combines features of both migraine and low-CSF-pressure headaches.

Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

Frequency and Type of Red Flags in Patients With Covid-19 and Headache: A Series of 104 Hospitalized Patients.

OBJECTIVE: In this study, we aimed to evaluate the frequency of the main red flags in patients with headache who do have Covid-19. BACKGROUND: Headache is one of the most frequent neurologic symptoms of Coronavirus disease 2019 (Covid-19). Diagnosis of secondary headache disorders is still based on the presence of red flags. DESIGN AND METHODS: Cross-sectional study of hospitalized patients with confirmed Covid-19 disease. We interrogated every patient about the presence of headache and if so, a headache expert conducted a structured interview assessing the presence and type of the main red flags. We evaluated the presence of laboratory abnormalities on admission. RESULTS: We screened 576 consecutive patients, 130/576 (22.6%) described headache, and 104 were included in the study. Mean age of patients was 56.7 (standard deviation: 11.2) and 66/104 (63.4%) were female. Red flags concerning prior medical history were present in 79/104 (76.0%) cases, and those related to the headache itself were observed in 99/104 (95.2%) patients. All patients 104/104 (100%) described systemic symptoms and 86/104 (82.7%) some neurologic symptoms. Laboratory results were abnormal in 98/104 (94.2%) cases. The most frequent red flags were fever, in 93/104 (89.4%) patients, cough, in 89/104 (85.6% cases), and increased C-reactive protein in 84/100 (84.0%) cases. CONCLUSION: In patients with Covid-19 that described the headache red flags were present in most cases. There was not any universal red flag, being necessary the comprehensive evaluation of all of them.

Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study.

INTRODUCTION: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. METHODS: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. RESULTS: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. CONCLUSION: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.