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Współwystępowanie migreny i depresji stanowi ważny problem kliniczny. Badania populacyjne wskazują, że pacjenci chorujący na migrenę są bardziej niż populacja ogólna narażeni na rozwój depresji. Odwrotna zależność również jest obserwowana w dużych badaniach populacyjnych. Rozpowszechnienie depresji wzrasta, a w konsekwencji wzrastają także koszty jej leczenia i konsekwencje społeczne. W odniesieniu do migreny, jest to druga w kolejności choroba neurologiczna z największym obciążeniem zdrowotnym. Obie jednostki chorobowe istnieją od wielu lat, jednakże dopiero w ostatnim czasie dokonał się postęp w zakresie rozumienia jej patomechanizmu. Etiopatogeneza zarówno migreny jak i depresji nie jest do końca poznana, prawdopodobnie jest wieloczynnikowa i złożona. W literaturze uwzględniane są zaburzenia neuroprzekaźnictwa, układ immunologiczny i predyspozycja genetyczna. Autorzy prezentują teorie etiopatogenetyczne obu chorób, ich rozpowszechnienie. Dzięki postępom w poszukiwaniu przyczyn opisywanych jednostek chorobowych odkrywane i badane są nowe punkty uchwytu dla terapii. Autorzy publikacji analizują także dane dotyczące współchorobowości tych schorzeń, omawiają prawdopodobne czynniki leżące u jej podłoża. Migrena często współwystępuje z różnymi chorobami przewlekłymi. Autorzy opisują predyktory kliniczne wystąpienia depresji u osób chorujących na migrenę, podkreślając znaczenie przesiewowego badania w kierunku depresji osób chorujących na migrenę.

Zaburzenia depresyjne są obecnie diagnozowane na podstawie kryteriów diagnostycznych ICD 10 (International Classification of Diseases) i DSM V (Diagnostic and Statistical Manual of Mental Disorders), obejmują osiowe objawy depresji i objawy dodatkowe, które muszę współwystępować przez co najmniej dwa tygodnie. Migrena diagnozowana jest na podstawie Międzynarodowej Klasyfikacji Bólów Głowy. Dzieli się zasadniczo na migrenę z aurą i bez aury, a ze względu na częstość napadów na migrenę epizodyczną i przewlekłą. Strategią terapeutyczną w leczeniu depresji jest stosowanie farmakoterapii w połączeniu z psychoterapią, natomiast w leczeniu migreny strategia zależy od częstości napadów bólu głowy (migrena epizodyczna vs migrena przewlekła) i od chorób współistniejących. W zakresie farmakoterapii zaburzeń depresyjnych leczenie pierwszej linii to leki z grupy z selektywnych inhibitorów wychwytu zwrotnego serotoniny (SSRI). Poszzczególni przedstawiciele tej grupy leków różnią się cechami charakterystycznymi co jest istotne przy indywidualnych decyzjach terapeutycznych. Pozostałe grupy obejmują inne leki. Nowością jest wprowadzenie do leczenia migreny przeciwciał monoklonalnych skierowanych przeciwko białku CGRP lub receptorowi dla tego białka istnieje wiele doniesień wskazujących na szczególną przydatność przeciwciał monoklonalnych modyfikujących działanie białka CGRP – w leczeniu migreny u chorych z depresją.

The multiple sclerosis patient’s journey in Poland was described based on the data collected by the Therapeutic Programme Monitoring System (System Monitorowania Programów Terapeutycznych, SMPT) between 2014 and 2018 and a National Health Fund (Narodowy Fundusz Zdrowia, NFZ) report entitled “NFZ on Health. Multiple Sclerosis.” It was found that about 90% of patients had their first multiple sclerosis diagnosis code (ICD-10: G35) assigned by a neurologist, usually during hospital stay in the department of neurology. Further patient management was usually continued in a neurology clinic. The waiting time for further outpatient and inpatient specialist (neurology) care after the first G35 diagnosis is more than 100 days. Before G35 diagnosis, patients most often presented with their first symptoms to neurological and ophthalmic clinics and were probably referred from these clinics for a magnetic resonance imaging. The analysis of the data from the Therapeutic Programme Monitoring System showed that the median time from the onset of the first symptoms to the diagnosis of multiple sclerosis was 7.4 months, and the median time from the diagnosis to initiation of first-line disease modifying treatment was 14.82 months. The length of time from the diagnosis to disease modifying therapy had a significant impact on the degree of disability. Patients treated with highly active second-line therapies accounted for 8.5% of all patients treated in drug programmes, and the increase in the number of patients on second-line regimens and expenditure on this programme were disproportionately lower compared to the first-line programme. A programme to improve the diagnosis and the quality of care for patients with multiple sclerosis should be developed in Poland to achieve better treatment outcomes. It is crucial to reduce the waiting time for diagnosis and the time interval between diagnosis and the onset of disease modifying treatment.

Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. Results: 1729 patients (median interquartile range age 63 [50–75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3–9.6), male sex (OR, 1.4; 95% CI, 1.1–2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1–2.1), and HF (OR, 2.3; 95% CI, 1.5–3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3–0.6), β-blockers (OR, 0.6; 95% CI, 0.4–0.9), statins (OR, 0.5; 95% CI, 0.3–0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4–0.9) was associated with lower risk of death. Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

Aim of the study. The 4C Mortality Score was created to predict mortality in hospitalised patients with COVID-19 and has to date been evaluated only in respiratory system disorders. The aim of this study was to investigate its application in patients with COVID-19-associated acute ischaemic stroke (AIS). Clinical rationale for study. COVID-19 is a risk factor for AIS. COVID-19-associated AIS results in higher mortality and worse functional outcome. Predictors of functional outcome in COVID-19-associated AIS are required. Materials and methods. This was a retrospective observational study of patients with AIS hospitalised in seven neurological wards in Malopolska Voivodship (Poland) between August and December 2020. We gathered data concerning the patients’ age, sex, presence of cardiovascular risk factors, type of treatment received, and the presence of stroke-associated infections (including pneumonia, urinary tract infection and infection of unknown source). We calculated 4C Mortality Score at stroke onset, and investigated whether there was a correlation with neurological deficit measured using the National Health Institute Stroke Scale (NIHSS) and functional outcome assessed using the modified Rankin Scale (mRS) at discharge. Results. The study included 52 patients with COVID-19-associated AIS. The 4C Mortality Score at stroke onset correlated with mRS (rs = 0.565, p < 0.01) at discharge. There was also a statistically significant difference in the mean 4C Mortality Score between patients who died and patients who survived the stroke (13.08 ± 2.71 vs. 9.85 ± 3.47, p = 0.04). Conclusions and clinical implications. 4C Mortality Score predicts functional outcome at discharge in COVID-19-associated AIS patients.

Introduction. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.

Background Post-stroke depressive symptoms (DS) can be chronic or transient, occurring shortly or long after stroke and lasting only few months. It remains unclear if the prognosis differs between patients with DS in the acute phase of stroke and those who develop DS several months later. We aimed to determine whether outcomes vary among patients with different trajectories of post-stroke depressive symptoms. Methods Of 698 enrolled patients with ischemic stroke, we included 335 participants (median age: 68, 48% female) who were assessed for DS both 8 days and 3 months post-stroke. We divided patients into 4 groups: without greater DS (Group 1), only earlier DS (Group 2), only later DS (Group 3), and persistent DS (Group 4). Logistic regression was used to determine the association between DS and 3- and 12-month functional outcome. Results Group 2 was predominantly female and had the highest rate of previous stroke or transient ischemic attack. Group 3 was more likely to suffer from delirium and more severe stroke. Group 4 had the highest frequency of vascular risk factors, pre-morbid psychiatric symptoms, and cognitive decline. In multivariate analysis, Group 3, but not Groups 2 and 4, had an increased risk of poor 3- and 12-month functional outcome (adjusted OR 2.59, 95% CI 1.64–4.07, P P Conclusions Different trajectories of post-stroke DS are related to different outcomes. Patients who only have later DS also have the worst prognosis.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients

Introduction The impact of an infection that requires antibiotic treatment (IRAT) after an acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT) remains unclear. Aim Here, we studied the prevalence and the profile of IRAT in patients with AIS treated with MT, aiming to identify predictive factors and prognostic implications at 90 days after stroke. Material and methods We analyzed parameters available within 24 h after AIS including demographics, risk factors, National Institutes of Health Stroke Scale (NIHSS) upon admission and 24 h later, hemorrhagic transformation (HT) on computed tomography, and several clinical and biochemical markers. The outcome measures were the modified Rankin Scale (mRS) 0-2 and 90 days post-stroke mortality. Results We included 291 patients; in 184 (63.2%) patients MT was preceded by intravenous thrombolysis (IVT), and 83 (28.5%) patients developed IRAT. Multivariate analysis showed that male sex and hemorrhagic transformation on CT taken 24 h after stroke increased the risk of IRAT. We found that younger age, male sex, lower delta NIHSS, shorter time from stroke onset to groin puncture, better recanalization and a lack of hemorrhagic transformation on CT taken 24 h after stroke favorably affected outcome at day 90. Multivariate analysis showed that older age, higher delta NIHSS, unknown stroke etiology and lack of treatment with IVT were independent predictors of death up to day 90. Infection that required antibiotic treatment did not enter in the models for the studied outcome measures. Conclusions In AIS patients treated with MT, IRAT is not an independent factor that affects favorable outcome or mortality 90 days after stroke.

Background: Olfactory dysfunction evaluated with time-consuming tests was more common in patients with multiple sclerosis (MS) than in controls and correlated with neurological deficit. The aim of the present study was to compare olfactory function between patients with relapsing-remitting MS (RRMS) and controls with short and simple screening tool—the Sniffin’ Sticks Identification Test (SSIT)—and search for its association with clinical and radiological features of the disease. Methods: The study included 30 controls and 30 patients with RRMS treated with disease-modifying therapies—injectables (interferon β or glatiramer acetate, N = 18) and oral drugs (dimethyl fumarate or fingolimod, N = 12). Hyposmia was defined as a score of 6 points or fewer in the SSIT olfactory test. The data concerning number of previous relapses, disability in Expanded Disability Status Scale (EDSS), and recent brain magnetic resonance imaging (MRI) scan were collected. Moreover, thalamic volume and third ventricle width were recorded in every patient. Additionally, cognition and fatigue in patients were evaluated 24 months after olfactory assessment with the Symbol Digit Modalities Test (SDMT) and Fatigue Scale for Motor and Cognitive Functions (FSMC), respectively. Results: Patients with RRMS had a higher risk of hyposmia than controls (66.7% vs 36.7%, OR = 1.82, 95% CI, 1.10-3.67, P = .02). Neither inflammatory (number of previous relapses or new brain MRI lesions) nor neurodegenerative (EDSS, SDMT, and FSMC scores; thalamic volume; third ventricle width) MS features did not correlate with SSIT score ( P > .05). In patients treated with oral drugs, olfactory dysfunction correlated with FSMC cognitive subscale ( r = −0.90, P = .006). Conclusions: Olfactory dysfunction is nearly twice as common in RRMS as in controls and correlates with fatigue level in patients treated with dimethyl fumarate or fingolimod.

We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.

INTRODUCTION: Malignant cerebral edema develops in a small subset of patients with hemispheric strokes, precipitating deterioration and death if decompressive hemicraniectomy (DHC) is not performed in a timely manner. Predicting which stroke patients will develop malignant edema is imprecise based on clinical data alone. Head computed tomography (CT) imaging is often performed at baseline and 24-hours. We determined the incremental value of incorporating imaging-derived features from serial CTs to enhance prediction of malignant edema. METHODS: We identified hemispheric stroke patients at three sites with NIHSS ≥ 7 who had baseline as well as 24-hour clinical and CT-imaging data. We extracted quantitative imaging features from baseline and follow-up CTs, including CSF volume, intracranial reserve (CSF/cranial volume), as well as midline shift (MLS) and infarct-related hypodensity volume. Potentially lethal malignant edema was defined as requiring DHC or dying with MLS over 5-mm. We built machine-learning models using logistic regression first with baseline data and then adding 24-hour data including reduction in CSF volume (ΔCSF). Model performance was evaluated with cross-validation using metrics of recall (sensitivity), precision (predictive value), as well as area under receiver-operating-characteristic and precision-recall curves (AUROC, AUPRC). RESULTS: Twenty of 361 patients (6%) died or underwent DHC. Baseline clinical variables alone had recall of 60% with low precision (7%), AUROC 0.59, AUPRC 0.15. Adding baseline intracranial reserve improved recall to 80% and AUROC to 0.82 but precision remained only 16% (AUPRC 0.28). Incorporating ΔCSF improved AUPRC to 0.53 (AUROC 0.91) while all imaging features further improved prediction (recall 90%, precision 38%, AUROC 0.96, AUPRC 0.66). CONCLUSION: Incorporating quantitative CT-based imaging features from baseline and 24-hour CT enhances identification of patients with malignant edema needing DHC. Further refinements and external validation of such imaging-based machine learning models are required.

ObjectiveTo examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS).MethodsFor the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes.ResultsPatients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18–14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001).ConclusionIn this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.

OBJECTIVE:To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). PATIENTS AND METHODS:This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. RESULTS:Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (β -0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. CONCLUSION:Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Aim of the study. To report pregnancy, delivery and perinatal outcomes in women with epilepsy seen in university clinics in Poland. Clinical rationale for the study. Women with epilepsy are reported to be at increased risk of adverse pregnancy and foetal outcomes. Materials and methods. The following data was collected in 171 pregnant women seen in two university epilepsy clinics: epilepsy characteristics and treatment, seizure frequency, pregnancy outcomes, perinatal outcomes, and feeding method. Results. The mean age of patients at the time of delivery was 28.8 years, and most women were nulliparous. Almost 80% of patients were on monotherapy and the majority were prescribed antiepileptic drugs with low teratogenic potential. 53.8% of patients were seizure-free during pregnancy. Half of the cohort delivered by caesarean section and the majority delivered in term. Nearly all newborns scored > 7 Apgar points. Major congenital malformation was diagnosed in only one foetus. Any adverse pregnancy/neonatal outcome was found in 13% of patients. Two thirds of women reported breastfeeding at any time. Conclusions and clinical implications. Almost 90% of women continued antiepileptic therapy during pregnancy. 46% of patients had epileptic seizures during pregnancy. Any adverse pregnancy/neonatal outcome was found in 13% of women with epilepsy. The majority of patients delivered healthy babies. Further studies are needed to find risk factors for adverse pregnancy/neonatal outcomes in women with epilepsy in Poland.

Background and Purpose— Cerebral edema (CED) develops in the hours to days after stroke; the resulting increase in brain volume may lead to midline shift (MLS) and neurological deterioration. The time course and implications of edema formation are not well characterized across the spectrum of stroke. We analyzed displacement of cerebrospinal fluid (ΔCSF) as a dynamic quantitative imaging biomarker of edema formation. Methods— We selected subjects enrolled in a stroke cohort study who presented within 6 hours of onset and had baseline and ≥1 follow-up brain computed tomography scans available. We applied a neural network-based algorithm to quantify hemispheric CSF volume at each imaging time point and modeled CSF trajectory over time (using a piecewise linear mixed-effects model). We evaluated ΔCSF within the first 24 hours as an early biomarker of CED (defined as developing MLS on computed tomography beyond 24 hours) and poor outcome (modified Rankin Scale score, 3–6). Results— We had serial imaging in 738 subjects with stroke, of whom 91 (13%) developed CED with MLS. Age did not differ (69 versus 70 years), but baseline National Institutes of Health Stroke Scale was higher (16 versus 7) and baseline CSF volume lower (132 versus 161 mL, both P P Conclusions— CSF volumetrics provides quantitative evaluation of early edema formation. ΔCSF from baseline to 24-hour computed tomography is a promising early biomarker for the development of MLS and worse neurological outcome.

Malignant cerebral edema is a devastating complication of stroke, resulting in deterioration and death if hemicraniectomy is not performed prior to herniation. Current approaches for predicting this relatively rare complication often require advanced imaging and still suffer from suboptimal performance. We performed a pilot study to evaluate whether neural networks incorporating data extracted from routine computed tomography (CT) imaging could enhance prediction of edema in a large diverse stroke cohort. An automated imaging pipeline retrospectively extracted volumetric data, including cerebrospinal fluid (CSF) volumes and the hemispheric CSF volume ratio, from baseline and 24 h CT scans performed in participants of an international stroke cohort study. Fully connected and long short-term memory (LSTM) neural networks were trained using serial clinical and imaging data to predict those who would require hemicraniectomy or die with midline shift. The performance of these models was tested, in comparison with regression models and the Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score, using cross-validation to construct precision-recall curves. Twenty of 598 patients developed malignant edema (12 required surgery, 8 died). The regression model provided 95% recall but only 32% precision (area under the precision-recall curve [AUPRC] 0.74), similar to the EDEMA score (precision 28%, AUPRC 0.66). The fully connected network did not perform better (precision 33%, AUPRC 0.71), but the LSTM model provided 100% recall and 87% precision (AUPRC 0.97) in the overall cohort and the subgroup with a National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 (p = 0.0001 vs. regression and fully connected models). Features providing the most predictive importance were the hemispheric CSF ratio and NIHSS score measured at 24 h. An LSTM neural network incorporating volumetric data extracted from routine CT scans identified all cases of malignant cerebral edema by 24 h after stroke, with significantly fewer false positives than a fully connected neural network, regression model, and the validated EDEMA score. This preliminary work requires prospective validation but provides proof of principle that a deep learning framework could assist in selecting patients for surgery prior to deterioration.

ObjectiveTo determine the contribution of common genetic variants to risk of early onset ischemic stroke (IS).MethodsWe performed a meta-analysis of genome-wide association studies of early onset IS, ages 18-59, using individual level data or summary statistics in 16,927 cases and 576,353 non-stroke controls from 48 different studies across North America, Europe, and Asia. We further compared effect sizes at our most genome-wide significant loci between early and late onset IS and compared polygenic risk scores for venous thromboembolism between early versus later onset IS.ResultsWe observed an association between early onset IS and ABO, a known stroke locus. The effect size of the peak ABO SNP, rs8176685, was significantly larger in early compared to late onset IS (OR 1.17 (95% C.I.: 1.11-1.22) vs 1.05 (0.99-1.12); p for interaction = 0.008). Analysis of genetically determined ABO blood groups revealed that early onset IS cases were more likely to have blood group A and less likely to have blood group O compared to both non-stroke controls and to late onset IS cases. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with early, compared to late, onset IS (p=0.008).ConclusionThe ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with early onset IS, compared with late onset IS, supporting a stronger role of prothrombotic factors in early onset IS.

(1) Background: To report and analyze the presence of residual symptoms after SARS-CoV-2 infection among Polish patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). (2) Methods: The study included 426 individuals with MS treated with DMTs and confirmed SARS-CoV-2 infection from 12 Polish MS centers. The data were collected through to 31 May 2021. The information included demographics, specific MS characteristics, course of SARS-CoV-2 infection, and residual (general and neurological) symptoms lasting more than four and 12 weeks after the initial infection. The results were obtained using maximum likelihood estimates for odds ratio and logistic regression. (3) Results: A total of 44.84% patients with MS reported symptoms lasting between four and 12 weeks after the initial infection, 24.41% people had symptoms that resolved up to 12 weeks, and 20.42% patients had symptoms that lasted over 12 weeks. The most common symptoms were: fatigue, disturbance of concentration, attention, and memory, cognitive complaints, and headache. None of the DMTs were predisposed to the development of residual symptoms after the initial infection. A total of 11.97% of patients had relapse three months prior or after SARS-CoV-2 infection. (4) Conclusion: Almost half of individuals with MS treated with different DMTs had residual symptoms after SARS-CoV-2 infection. None of the DMTs raised the probability of developing post-acute COVID symptoms.

BACKGROUND AND PURPOSE Delirium is a serious complication after stroke. It remains unclear whether different motor subtypes of delirium are associated with diverse risk factors and outcomes. The aim was to investigate if delirium subtypes differ in predisposing factors, clinical characteristics and outcomes. METHODS In all, 698 patients with ischaemic stroke or transient ischaemic attack (median age 73 years; 53.7% female) were prospectively included. Core features of delirium during the first 7 days after admission were examined. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for delirium were used. Pre-stroke characteristics were compared between different delirium subtypes and logistic regression and Cox proportional hazard models were used to explore the association between delirium, functional outcome and death. RESULTS Hyperactive, hypoactive and mixed delirium were diagnosed in 28, 75 and 66 patients, respectively. Patients with hyperactive delirium had less severe neurological deficit on admission and more often had transient ischaemic attack compared with patients with hypoactive and mixed delirium. Compared with patients with hypoactive delirium, those with hyperactive delirium more often suffered from irritability/lability prior to stroke. Hyperactive and hypoactive delirium did not differ in age, sex, comorbidities, pre-stroke dependency, cognitive decline and severity of delirium. Hyperactive, hypoactive and mixed delirium were associated with an increased risk of poor 3- and 12-month functional outcome compared with patients without delirium. Moreover, patients with hypoactive and mixed delirium had an elevated risk of death. CONCLUSIONS Hyperactive delirium is associated with less severe stroke and higher scores of pre-existing irritability/lability. All three motor subtypes of delirium are associated with poor outcome, although hyperactive delirium seems to have a less unfavourable prognosis.

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer’s disease. Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology. Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients. Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.

While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological brain age. We here first examine whether radiomics analysis of the texture of brain T2-FLAIR MRI images can be used to predict brain age in stroke patients. We then assess the clinical determinants of accelerated brain aging and, finally, its impact on post-stroke functional outcomes. Leveraging a multisite cohort of 4,163 ischemic stroke patients, we show that older-appearing patients have more hypertension, diabetes mellitus, prior strokes, and smoking history and are more likely to develop worse post-stroke outcomes than their younger-appearing counterparts. Our results strengthen the importance of preventive medicine for maintaining brain health in stroke patients as they age and suggest a novel methodology to capture previously undescribed prognostic information available on commonly acquired MRI sequences during routine stroke care.

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health. NIH-NINDS (MRI-GENIE: R01NS086905 - PI NR; K23NS064052, R01NS082285 - NR; SiGN: U01 NS069208 - JR, SK; R01NS059775, R01NS063925, R01NS082285, P50NS051343, R01NS086905, U01 NS069208 - OW); NIH NIBIB (NAC P41EB015902 PG, U01NS030678 Kissela, Kleindorfer; EB015325 OW); ISGS (R01NS423733 P.I. JM, Swedish Heart and Lung Foundation, Lund University, Region Skåne, the Freemasons Lodge of Instruction Eos Lund, Skåne University Hospital, the Foundation of Färs &Frosta (One of Sparbanken Skånes ownership Foundations), and the Swedish Stroke Association - AL, Swedish Research Council and the Swedish Heart and Lung Foundation, the Swedish State under the ALF agreement CJ, Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (Funding for Research in Health PI051737, PI10/02064, PI12/01238 and PI15/00451 JJ-C), Fondos FEDER/EDRF Red de Investigación Cardiovascular (RD12/0042/0020 JJ-C), Fundació la Marató TV3 (76/C/2011 - JJ-C) and Recercaixa13 (JJ086116 JJ-C), Wistron Corporation (PG); The European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 753896 - MS; RL is a senior clinical investigator of FWO Flanders; MB was supported by the ISITE-ULNE Fundation, the Société Française de Neuroradiologie, the Société Française de Radiologie, the Thérèse and René Planiol Fundation; ME was supported by the American Academy of Neurology and MGH Executive Council on Research; TT was supported by the Helsinki University Central Hospital, Sigrid Juselius Foundation, Sahlgrenska University Hospital, and University of Gothenburg. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article of the decision to submit it for publication.

Our study aimed to explore the association between serum C-reactive protein (CRP) and post-stroke depressive symptoms. We prospectively recruited 572 patients with ischemic stroke or transient ischemic attack in whom serum CRP level was measured within 48 h after stroke onset. Depressive symptoms were assessed at day 8 and 3 months after stroke in 405 and 306 patients, respectively. Patients with greater depressive symptoms at day 8 and patients with greater depressive symptoms 3 months after stroke had higher CRP level (median: 7.9 vs 4.3 mg/L, P 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30–3.28, P 4.3 mg/L was associated with depressive symptoms 3 months after stroke (OR: 1.79, 95%CI: 1.06–3.02, P = 0.03). In the multivariate analysis, higher CRP level was related to depressive symptoms at day 8 (OR: 2.23, 95%CI: 1.28–3.90, P

Background Inflammation is associated with poor outcome after stroke. A relationship between ex vivo cytokine synthesis and stroke outcome remains unclear. We explored an association between ex vivo cytokine release, circulating interleukin (IL)-6 as a marker of systemic inflammation, and stroke prognosis. We assessed the utility of ex vivo synthesized cytokines for predicting stroke outcome. Methods We collected blood from 248 ischemic stroke patients and stimulated it ex vivo with lipopolysaccharide. We measured concentration of synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12) and plasma IL-6. We assessed functional outcome 3 months after stroke using the modified Rankin Scale. To assess the prognostic ability of cytokines, we applied multivariate logistic regression, cluster analysis, and construction of multimarker score. Results Decreased release of IP-10, TNFα, IL-1β, and IL-12; increased release of IL-10 and IL-8; and higher plasma IL-6 level were associated with poor outcome. Cluster analysis identified three groups of patients with distinct cytokine profiles. The group with the worst outcome demonstrated high synthesis of IL-10, IL-8, IL-1β, and IL-6 and low synthesis of IL-12, IP-10, and TNFα accompanied by high circulating IL-6 level. The group with the best prognosis showed high synthesis of TNFα, IP-10, IL-12, IL-1β, and IL-6; low synthesis of IL-10 and IL-8; and low plasma IL-6. Patients with intermediate outcome had low synthesis of all cytokines accompanied by low circulating IL-6. We constructed a multimarker score composed of ex vivo released IL-12, IL-10, TNFα, and plasma IL-6. Addition of this score to clinical variables led to significant increase in c-statistic (0.81 vs 0.73, p = 0.02) and net reclassification improvement. Conclusion The decreased ex vivo release of pro-inflammatory cytokines and increased release of IL-10 and IL-8 are related to poor outcome after stroke. Cytokine-based multimarker score adds prognostic value to clinical model for predicting stroke outcome.

Aim of the study Genetic (idiopathic) generalized epilepsies (GGEs) account for nearly one-third of all epilepsies. The frequency of status epilepticus (SE) in patients with GGEs has been poorly studied. Therefore, this study aimed to evaluate the frequency of different forms of SE in a cohort of patients with GGEs. Materials and methods Among 153 patients with GGEs treated at the university epilepsy clinic in the period between 1998 and 2018, those with SE were retrospectively identified. Results Absence SE was diagnosed in 8 patients (13 episodes), while myoclonic SE was found in 2 patients (2 episodes). No cases of tonic-clonic SE were detected in the study cohort. Most SE episodes were found to be provoked by ill-advised antiepileptic drugs or changes in drug regimen. In all the subjects, SE was stopped by intravenous administration of diazepam and/or valproate. Long-term outcome of epilepsy was good, with most patients (70%) being seizure-free. Conclusion Status epilepticus is not a rare phenomenon in patients with genetic generalized epilepsies, with absence SE being the most common type. Most cases of SE are provoked by ill-advised AEDs or changes in drug regimen. Status epilepticus in GGEs can be easily treated with benozdiazepines and/or valproate. Status epilepticus in GGEs can be easily treated with benozdiazepines and/or valproate.

Introduction Reperfusion therapy for acute ischaemic stroke used within a time window of 6 h following symptom onset, although currently the treatment of choice, is characterised by certain limitations and carries certain risks. Aim To assess the potential for predicting the risks and limitations of reperfusion therapy by means of advanced neuroimaging. Material and methods For this purpose, the baseline CT scans of patients with ischaemic stroke treated by means of mechanical thrombectomy were assessed retrospectively using the Combined Multimodal Computed Tomography Score (CMCTS), modified to account for the perfusion examination of a limited area. These data were then combined with radiological and clinical outcomes, in particular haemorrhagic stroke transformation and scoring on a modified Rankin scale (mRS). Results Based on material from 85 patients, the scoring system we employed enabled us to distinguish a group that did not benefit from treatment with specificity and a positive predictive value of 100%, and a negative predictive value of 64%. Neither the relationship between the score and early haemorrhagic complications, nor the effectiveness or severity of the course of the thrombectomy procedure itself was confirmed. Conclusions There is no justification for the use of reperfusion procedures in acute ischaemic stroke in the anterior circulation in patients with initially unfavourable multimodal computed tomography scores.

ContextHigh loads in the elbow during baseball pitching can lead to serious injuries, including injuries to the ulnar collateral ligament. These injuries have substantial implications for individual pitchers and their teams, especially at the professional level of competition. With a trend toward increased ball velocity in professional baseball, controversy still exists regarding the strength of the relationship between ball velocity and elbow-varus torque.ObjectiveTo examine the relationship between fastball velocity and elbow-varus torque in professional pitchers using between- and within-subjects statistical analyses.DesignCross-sectional study.SettingMotion-analysis laboratory.Patients or Other ParticipantsUsing the previously collected biomechanical data of 452 professional baseball pitchers, we performed a retrospective analysis of the 64 pitchers (52 right-hand dominant, 12 left-hand dominant; age = 21.8 ± 2.0 years, height = 1.90 ± 0.05 m, mass = 94.6 ± 7.8 kg) with fastball velocity distributions that enabled between- and within-subjects statistical analyses.Main Outcome Measure(s)We measured ball velocity using a radar gun and 3-dimensional motion data using a 12-camera automated motion-capture system sampling at 240 Hz. We calculated elbow-varus torque using inverse-dynamics techniques and then analyzed the relationship between ball velocity and elbow torque using both a simple linear regression model and a mixed linear model with random intercepts.ResultsThe between-subjects analyses displayed a weak positive association between ball velocity and elbow-varus torque (R2 = 0.076, P = .03). The within-subjects analyses showed a considerably stronger positive association (R2 = 0.957, P < .001).ConclusionsWhen comparing 2 professional baseball pitchers, higher velocity may not necessarily indicate higher elbow-varus torque due to the confounding effects of pitcher-specific differences (eg, detailed anthropometrics and pitching mechanics). However, within an individual pitcher, higher ball velocity was strongly associated with higher elbow-varus torque.

ObjectiveNeuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.MethodsWe analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).ResultsRadiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health.

Producción Científica, Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases., Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - ( Projects PI 11/0176 and PI18/01338), Instituto de Salud Carlos III - (Project CM18/00198), Agencia de Gestión de Ayudas Universitarias y de Investigación (AGAUR) y Fondo Social Europeo - (Grant 2020FI_B1 00157), Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (Project CD20/00043), Instituto de Salud Carlos III - (Projects FI19/00309, CP12/03298, CPII17/00027, CPII19/00020)

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke., Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Background Repetitive pitching places tremendous forces on the shoulder and elbow which can lead to upper extremity (UE) or lower extremity (LE) overuse injuries. # Purpose The purpose of this study was to evaluate pre-season physical measurements in collegiate baseball players and track in-season baseball throwing volume to determine which factors may predict throwing overuse injuries. # Study Design Retrospective Cohort study. # Methods Baseline preseason mobility, strength, endurance, and perception of function were measured in 17 collegiate baseball pitchers. Participants were then followed during the course of the season to collect rate of individual exposure, estimated pitch volume, and rating of perceived exertion in order to determine if changes in workload contributed to risk of injury using an Acute-to-Chronic Workload ratio (ACWR). # Results Participants developing an injury had greater shoulder internal rotator strength (p=0.04) and grip strength in a neutral position (p=0.03). A significant relationship was identified between ACWR and UE injuries (p

As swelling occurs, CSF is preferentially displaced from the ischemic hemisphere. The ratio of CSF volume in the stroke-affected hemisphere to that in the contralateral hemisphere may quantify the progression of cerebral edema. We automatically segmented CSF from 1,875 routine CTs performed within 96 hours of stroke onset in 924 participants of a stroke cohort study. In 737 subjects with follow-up imaging beyond 24-hours, edema severity was classified as affecting less than one-third of the hemisphere (CED-1), large hemispheric infarction (LHI, over one-third the hemisphere), without midline shift (CED-2) or with midline shift (CED-3). Malignant edema was LHI resulting in deterioration, requiring osmotic therapy, surgery, or resulting in death. Hemispheric CSF ratio was lower on baseline CT in those with LHI (0.91 vs. 0.97, p

Introduction: The aim of this study was to analyse the general features and usefulness of the time elapsed between the start of contrast agent infusion and its appearance in the aortic arch in acute ischaemic stroke patients subjected to baseline computed tomographic angiography. This is, to the best of our knowledge, the first study of this parameter in a clinical context. We will refer to it hereafter as ‘needle-to-aorta delay’ (NAD). Material and methods: The following were recorded: the time it took iodinated contrast media to reach the aorta, the site of occlusion, and automatic perfusion assessments of infarct and salvageable tissue volumes. Demographic data such as age and sex, comorbidities, and clinical factors including heart rate, blood pressure, time elapsed from symptom onset, initial stroke severity, and course of disease, were also assessed. Results: We analysed 252 cases of stroke. NAD correlated with tissue at risk volume, and was greater for patients with hypertension and atrial fibrillation. The observed time was significantly shorter with less favourable core-to-penumbra ratios. No link was found between NAD and either the rate of infarct progression or the long-term clinical result. Conclusions: Although no clinical benefit was proven as a result of measuring the time it took contrast media to reach the aorta, our study implies that not only is the brain subject to circulation, but it may also affect its functioning.

Background: Previous studies on inflammatory biomarkers in acute ischemic stroke (AIS) produced divergent results. We evaluated whether C-reactive protein (CRP) and white blood cell count (WBC) measured fasting 12–24 h after intravenous thrombolysis (IVT) were associated with outcome in AIS patients without concomitant infection. Methods: The study included 352 AIS patients treated with IVT. Excluded were patients with community-acquired or nosocomial infection. Outcome was measured on discharge and 90 days after stroke onset with the modified Rankin scale (mRS) and defined as poor outcome (mRS 3–6) or death (mRS = 6). Results: Final analysis included 158 patients (median age 72 years (interquartile range 63-82), 53.2% (n = 84) women). Poor outcome on discharge and at day 90 was 3.8-fold and 5.8-fold higher for patients with CRP ≥ 8.65 mg/L (fifth quintile of CRP), respectively, compared with first quintile (&lt, 1.71 mg/L). These results remained significant after adjustment for potential confounders (odds ratio (OR) on discharge = 10.68, 95% CI: 2.54–44.83, OR at day 90 after stroke = 7.21, 95% CI: 1.44–36.00). In-hospital death was 6.3-fold higher for patients with fifth quintile of CRP as compared with first quintile and remained independent from other variables (OR = 4.79, 95% CI: 1.29–17.88). Independent predictors of 90-day mortality were WBC &lt, 6.4 × 109 /L (OR = 5.00, 95% CI: 1.49–16.78), baseline National Institute of Health Stroke Scale (NIHSS) score (OR = 1.13 per point, 95% CI: 1.01–1.25) and bleeding brain complications (OR = 5.53, 95% CI: 1.59–19.25) but not CRP ≥ 8.65 mg/L. Conclusions: Non-infective CRP levels are an independent risk factor for poor short- and long-term outcomes and in-hospital mortality in AIS patients treated with IVT. Decreased WBC but not CRP is a predictor for 90-day mortality.

Migraine is a common primary headache disease, which reduces quality of life. About 8% of migraineurs suffer from chronic migraine (CM), which is the most severe and troublesome type. It has been proven that onabotulinumtoxinA (ONA-BoNT/A) significantly improves CM, presumably inhibiting the release of calcitonin gene-related peptide (CGRP) and other neurotransmitters from c-fibres endings, and thus decreasing activation of nociceptive pathways and transmission of pain. The aim of this position paper was to assess the place of ONA-BoNT/A for the prophylaxis of CM in adults. The authors have compared the efficacy, safety and tolerance of the toxin to those of classical oral preventive therapies as well as to recently introduced anti-CGRP-pathway monoclonal antibodies. The results of randomised controlled studies of ONA-BoNT/A have been compared to open label (real world practice) trials.

Objectives Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. Methods We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. Results Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p = 0.003). These associations were independent of depressive symptoms. Conclusion Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

IntroductionNeuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of describing the texture of conventional images beyond what meets the naked eye, radiomic analyses hold potential for evaluating brain health. We sought to: 1) evaluate this novel approach to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and 2) uncover associations between predictive radiomic features and patients’ clinical phenotypes.MethodsOur analyses were based on a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images and corresponding deep-learning-generated total brain and WMH segmentation. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with the most stable selected features predictive of WMH burden and then related this signature to clinical variables (age, sex, hypertension (HTN), atrial fibrillation (AF), diabetes mellitus (DM), coronary artery disease (CAD), and history of smoking) using canonical correlation analysis.ResultsRadiomic features were highly predictive of WMH burden (R2=0.855±0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1-6CV7=.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and DM, CV4 by HTN, CV5 by AF and DM, CV6 by CAD, and CV7 by CAD and DM.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes. Further research could evaluate radiomics to predict the progression of WMH.Research in contextEvidence before this studyWe did a systematic review on PubMed until December 1, 2020, for original articles and reviews in which radiomics were used to characterize stroke or cerebrovascular diseases. Radiomic analyses cover a broad ensemble of high-throughput quantification methods applicable to digitalized medical images that extract high-dimensional data by describing a given region of interest by its size, shape, histogram, and relationship between voxels. We used the search terms “radiomics” or “texture analysis”, and “stroke”, “cerebrovascular disease”, “small vessel disease”, or “white matter hyperintensities”. Our research identified 24 studies, 18 studying radiomics of stroke lesions and 6 studying cerebrovascular diseases. All the latter six studies were based on MRI (T1-FLAIR, dynamic contrast-enhanced imaging, T1 & T2-FLAIR, T2-FLAIR post-contrast, T2-FLAIR, and T2-TSE images). Four studies were describing small vessel disease, and two were predicting longitudinal progression of WMH. The average sample size was small with 96 patients included (maximum: 204). One study on 141 patients identified 7 T1-FLAIR radiomic features correlated with cardiovascular risk factors (age and hyperlipidemia) using univariate correlations. All studies were monocentric and performed on a single MRI scanner.Added value of this studyTo date and to the best of our knowledge, this is the largest radiomics study performed on cerebrovascular disease or any topic, and one of the very few to include a great diversity of participating sites with diverse clinical MRI scanners. This study is the first one to establish a radiomic signature of WMH and to interpret its relationship with common cardiovascular risk factors. Our findings add to the body of evidence that damage caused by small vessel disease extend beyond the visible white matter hyperintensities, but the added value resides in the detection of that subvisible damage on routinely acquired T2-FLAIR imaging. It also suggests that cardiovascular phenotypes might manifest in distinct textural patterns detectable on conventional clinical-grade T2-FLAIR images.Implications of all the available evidenceAssessing brain structural integrity has implications for treatment selection, follow-up, prognosis, and recovery prediction in stroke patients but also other neurological disease populations. Measuring cerebral parenchymal structural integrity usually requires advanced imaging such as diffusion tensor imaging or functional MRI. Translation of those neuroimaging biomarkers remains uncommon in clinical practice mainly because of their time-consuming and costly acquisition. Our study provides a potential novel solution to assess brains’ structural integrity applicable to standard, routinely acquired T2-FLAIR imaging.Future research could, for instance, benchmark this radiomics approach against diffusion or functional MRI metrics in the prediction of cognitive or functional outcomes after stroke.

INTRODUCTION: The study assessed the prevalence and risk factors for SARS-CoV-2 infection in patients with epilepsy (PWE). Additionally, the course of COVID-19 and its impact on seizure control was investigated. MATERIAL AND METHODS: Subjects with definite (confirmed by positive RT-PCR nasopharyngeal swab or serum anti-SARS-CoV-2 antibodies) and probable COVID-19 were identified via telephone survey among PWE treated at the university epilepsy clinic. RESULTS: Of 252 screened subjects, 17 (6.7%) had definite and 14 (5.5%) probable COVID-19. The percentage of PWE with definite COVID-19 was much higher than the percentage of subjects with confirmed COVID-19 in Polish general population (3.65%). In the heterogenous population of PWE, including patients with drug-resistant epilepsy, physical/intellectual disability, and comorbidities, we were not able to identify any risk factors for contracting COVID-19. The course of infection was mild or moderate in all subjects, not requiring oxygen therapy or respiratory support. The most common symptoms were fever, fatigue, headaches, muscle aches, and loss of smell/taste and continued for approximately 7-21 days, except for loss of smell/taste which lasted usually several weeks. Seizure exacerbation was noted in only one pregnant patient with confirmed COVID-19 and it was likely related to decreased serum level of levetiracetam in the third trimester. CONCLUSION: The study provided reassuring findings related to the low risk of seizure exacerbation in PWE during the course of COVID-19. Patients with epilepsy may be at increased risk of SARS-CoV-2 infection. Epilepsy characteristics are not likely to modify the risk of COVID-19.

Purpose: According to guidelines, to shorten the treatment window, acute ischaemic stroke (AIS) treatment by intravenous thrombolysis (IVT) can be done based on the results of head computed tomography (CT) without contrast. The impact of large vessel occlusion (LVO) on computed tomography angiography (CTA) in stroke prognosis in patients treated IVT or IVT and mechanical thrombectomy (MT), where indicated, has not yet been studied systematically. We investigated the influence of LVO in consecutive AIS patients on haemorrhagic transformation (HT) on CT 24 h after treatment, mRS < 2 on discharge (unfavourable outcome), and in-hospital mortality. Material and methods: We analysed several parameters within 24 h after AIS: demographics, risk factors, mRS score pre-stroke, NIHSS upon admission and 24 h later, several clinical and biochemical parameters, and chronic treatment. Results: We registered 1209 patients, of whom 362 (29.9%) received IVT and 108 had MT, where indicated. Admission CTA showed LVO in 197 patients (54.4%). Multivariate regression analysis showed that the presence of LVO and lower delta NIHSS (NIHSS on admission minus NIHSS 24 hours later) were independent parameters affecting HT risk. Multivariate analysis showed that the presence LVO and also older age, female sex, lower delta NIHSS, HT, stroke-associated infection, CRP levels ≥ 10 mg/L, and higher WBC count affected unfavourable outcome on discharge. LVO did not affect in-hospital mortality. Conclusions: LVO in AIS patients treated by IVT or IVT and MT affects the risk of HT and unfavourable short-term outcome but not in-hospital mortality.

Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, it remains unclear whether it could be reflected in prodromal symptom features. This study aimed to compare a broad spectrum of prodromal signs and symptoms between males and females in the 7-year period before the definite diagnosis of MS. Data came from the central register of the national payer of services, financed under the public healthcare system in Poland. They covered a 7-year period of patient health record claims, from 2009 to 2016. The following groups of symptoms were significant with women: musculoskeletal (p &lt, 0.001), ophthalmic (p &lt, 0.001), laryngological (p &lt, 0.001), digestive system (p &lt, 0.001), urinary tract (p &lt, 0.001), mental (p &lt, 0.001), cardiovascular (p &lt, 0.001), complaints and headaches (p &lt, 0.001). There was also a weak correlation with head injuries (p = 0.03) while dermatological and reproductive system complaints did not appear to be significant (p &lt, 0.05). For males, the following groups of symptoms were significant: musculoskeletal (p &lt, 0.001), laryngological (p = 0.007), cardiovascular system symptoms (p &lt, 0.001), and headaches (p &lt, 0.001). Interestingly, reproductive system problems were overrepresented in the male population (p = 0.008). There was no significant correlation with MS risk for dermatological, digestive, urinary, and mental complaints. Similarly, head injuries were not significant. Our results shed more light on well-known differences in the epidemiological and clinical characteristics between sexes in multiple sclerosis, and show differences in prodromal complaints before MS onset.

BACKGROUND AND PURPOSE Depression and apathy are frequent neuropsychiatric disturbances after stroke and may appear together. Despite the overlap in symptoms between poststroke depression and apathy, these two syndromes might be associated with different prognoses and benefit from different treatments. We aimed to disentangle the relationship between early depressive and apathetic symptoms and outcome after stroke. METHODS Of 698 enrolled patients with ischemic stroke, we included 443 participants (median age = 69 years, 51% female) who underwent depressive and apathetic symptom assessment on Day 8 after stroke. We divided patients into four groups: without greater depressive and apathetic symptoms (Group 1), with only apathetic symptoms (Group 2), with only depressive symptoms (Group 3), and with both depressive and apathetic symptoms (Group 4). RESULTS After adjusting for age and stroke severity, Group 2 and Group 4 had an increased risk of poor 3-month outcome (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.16-3.38, p = 0.01 and OR = 1.58, 95% CI = 1.24-2.01, p

Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS baseline – NIHSS 24hours = ΔNIHSS 6-24h ), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS 6 –24h . In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS 6–24h was examined. Finally, the association of ΔNIHSS 6 –24h with 90-day favorable outcomes (modified Rankin Scale score 0–2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4–16), and median ΔNIHSS 6 –24h was 2 (interquartile range, 0–5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS 6 –24h (R 2 =0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R 2 =0.27), but much of the variance remained unexplained. ΔNIHSS 6 –24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS 3 –24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS 6–24h , captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS 6 –24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

Our aim was to compare human and computer accuracy in reading medical images of acute stroke patients. We analyzed data of patients who underwent assessment of Alberta Stroke Program Early CT Score (ASPECTS) and CT Perfusion (CTP) via Rapid Processing of Perfusion and Diffusion (RAPID) software RAPID ASPECTS, and RAPID CTP), compared to radiologist reports and manual measurements. We compared volumes calculated by RAPID CTP software with those selected by scanner-equipped software (GE). For reference, follow-up images were manually assessed in accordance with the Alberta Stroke Program Early CT Score (ASPECTS) territories retrospectively. Although exact ASPECTS score agreement between the automatic and manual methods, and between each method and follow-up, was poor, crossing of the threshold for reperfusion therapy was characterized by an 80% match. CT perfusion analyses yielded only slight agreement (kappa = 0.193) in the qualification of patients for therapy. Either automatic or manual scoring methods of non-contrast images imply similar clinical decisions in real-world circumstances. However, volume measurements performed by fully automatic and manually assisted systems are not comparable. Thresholds devised and validated for computer algorithms are not compatible with measurements performed manually using other software and should not be applied to setups other than those with which they were developed.

Delirium is a common and serious complication of stroke. Early prediction of delirium is important for preventive strategies and close monitoring of high-risk patients. Pre-existing degenerative and vascular changes in the brain could predispose to delirium. We aimed to determine if computed tomography (CT)-based indices could provide additional information about a risk of stroke-associated delirium beyond easiest-to-access clinical predictors. Using semi-quantitative scales (global cortical atrophy, age-related white matter changes, and Scheltens scale), we assessed global and regional brain atrophy and white matter changes in 88 stroke patients with delirium and 142 patients without delirium matched for age and stroke severity. Patients with delirium had greater global and local brain atrophy (the right temporal region, the left parieto-occipital region, the right frontal and occipital horn, and the right and left temporal horn) than patients without delirium. Scores of white matter changes did not differ between groups with exception of greater white matter damage in the right parieto-occipital area in patients with delirium. The discriminatory properties of studied radiological indices were modest (areas under receiver operator curves: 0.58-0.64). CT-based indices of brain atrophy and white matter changes do not provide additional information about a risk of post-stroke delirium beyond the most important clinical predictors.

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology.

Background Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. Methods A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. Results Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. Conclusion IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.