Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy.

INTRODUCTION: COVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. METHODS: The Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. RESULTS: 812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DISCUSSION: Our study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).

OBJECTIVE: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. METHODS: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). RESULTS: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. CONCLUSIONS: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.

SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

OBJECTIVE: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. METHODS: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. RESULTS: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. CONCLUSIONS: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Postinfectious Neurologic Complications in COVID-19: A Complex Case Report.

A 40-y-old woman with severe acute respiratory syndrome coronavirus 2 infection developed neurologic manifestations (confusion, agitation, seizures, dyskinesias, and parkinsonism) a few weeks after the onset of severe acute respiratory syndrome. MRI and cerebrospinal fluid analyses were unremarkable, but 18F-FDG PET/CT showed limbic and extralimbic hypermetabolism. A full recovery, alongside 18F-FDG normalization in previously hypermetabolic areas, was observed after intravenous immunoglobulin administration.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.

Incidence of early poststroke seizures during reperfusion therapies in patients with acute ischemic stroke: An observational prospective study: (TESI study: "Trombolisi/Trombectomia e crisi Epilettiche precoci nello Stroke Ischemico").

INTRODUCTION: The aim of this study was to prospectively investigate the occurrence of early poststroke seizures (within 7 days of stroke) in patients undergoing reperfusion therapies (intravenous rtPA [recombinant tissue plasminogen activator] and/or endovascular thrombectomy) in comparison to those not undergoing these procedures. METHODS: Patients aged ≥18 years with acute ischemic stroke admitted in five Italian centers were prospectively recruited. Clinical data, details on stroke type and etiology, stroke treatment, and radiological data were collected. The frequency of early poststroke seizures was assessed, and predictive factors for their occurrence were evaluated. RESULTS: Five hundred and sixteen patients (262 in the reperfusion therapies group) were included. Stroke severity on admission and at discharge was higher among patients undergoing reperfusion therapies. Ten patients (3.8%) undergoing reperfusion therapies and 6 (2.3%) of those not receiving these treatments experienced early poststroke seizures (p = 0.45). There were no differences in any of the baseline characteristics between patients experiencing and those not experiencing early seizures. CONCLUSION: The incidence of early poststroke seizures was overall rare, and no significant differences emerged between patients receiving and those not receiving reperfusion therapies. This article is part of the Special Issue "Seizures and Stroke".

The role of clinical and neuroimaging features in the diagnosis of CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.

Reducing time delays in the management of ischemic stroke patients in Northern Italy.

BACKGROUND AND PURPOSE: Thrombolysis represents the best therapy for ischemic stroke but the main limitation of its administration is time. The avoidable delay is a concept reflecting the effectiveness of management pathway. For this reason, we projected a study concerning the detection of main delays with following introduction of corrective factors. In this paper we describe the results after these corrections. MATERIALS AND METHODS: Consecutive patients admitted for ischemic stroke during a 3-months period to 35 hospitals of a macro-area of Northern Italy were enrolled. Each time of management was registered, identifying three main intervals: pre-hospital, in-hospital and total times. Previous corrective interventions were: 1.increasing of population awareness to use the Emergency Medical Service (EMS); 2.pre-notification of Emergency Department; 3.use of high urgency codes; 4.use of standardised operational algorithm. Statistical analysis was conducted using time-to-event analysis and Cox proportional hazard regression. RESULTS: 1084 patients were enrolled. EMS was alerted for 56.3% of subjects, mainly in females and severe strokes (p<0.001). Thrombolytic treatment was performed in 4.7% of patients. Median pre-hospital and in-hospital times were 113 and 105min, while total time was 240. High urgency codes at transport contributed to reduce pre-hospital and in-hospital time (p<0.05). EMS use and high urgency codes promoted thrombolysis. Treatment within 4.5hours from symptom onset was performed in 14% of patients more than the first phase of study. CONCLUSIONS: The implementation of an organizational system based on EMS and concomitant high urgency codes use was effective to reduce avoidable delay and to increase thrombolysis.

Time to hospital admission and start of treatment in patients with ischemic stroke in northern Italy and predictors of delay.

BACKGROUND AND PURPOSE: Early treatment (i.e. thrombolysis) is crucial for a successful care of ischemic stroke. In the management of stroke, two phases are crucial: the pre-hospital and the in-hospital interval. This work investigated factors influencing pre- and in-hospital delay in a large geographic area of Northern Italy. METHODS: Enrolled were patients presenting with ischemic stroke in four administrative districts of Northern Italy (Como, Lecco, Sondrio and Varese) over a 4-month period. Pre-hospital time and in-hospital time with single management steps were recorded prospectively. Age, gender, recruiting hospital, EMS transport and triage codes, clinical severity and thrombolytic treatment were also recorded. Univariate and multivariate analysis of factors predicting pre- and in-hospital delay were performed. RESULTS: Median pre-hospital time and in-hospital time were, respectively, 120 min (interquartile range, IQR 62-271) and 150 min (IQR 80-214). Pre-hospital time was halved in patients hospitalized via EMS (p<0.001) and clinically more severe (p<0.001). At multivariate analysis, transport code was associated with delay at any time (p<0.05). CONCLUSIONS: EMS use and transport code predicted treatment delay in patients with ischemic stroke. A more intensive use of EMS and high urgency codes could help increase the number of stroke patients treated appropriately.

R583Q CACNA1A variant in SHM1 and ataxia: case report and literature update.

Familial hemiplegic migraine (FHM) type 1 is a rare monogenic dominant autosomal disease due to CACNA1A gene mutations. Besides the classical phenotype, mutations on CACNA1A gene are associated with a broader spectrum of clinical features including cerebellar ataxia, making FHM1 a complex channelopathy. We report the case of a patient carrying the p.Arg583Gln mutation affected by hemiplegic migraine and late onset ataxia and we performed a literature review about the clinical features of p.Arg583Gln. Although p.Arg583Gln mutations are associated with a heterogeneous phenotype, carriers present cerebellar signs which consisted generally in ataxia and dysmetria, with intention tremor appearing mostly in advanced age, often progressive and permanent. The heterogeneous spectrum of CACNA1A gene mutations probably causes sporadic hemiplegic migraine (SHM) to be misdiagnosed. Given the therapeutic opportunities, SHM/FHM1 should be considered in differential diagnosis of patients with cerebellar ataxia and migraine with aura.

Stroke management in northern Lombardy: organization of an emergency-urgency network and development of a connection between prehospital and in-hospital settings.

Stroke is the leading cause of disability in adulthood, and the principal aim of care in cerebrovascular disease is the reduction of this negative outcome and mortality. Several studies demonstrated the efficacy of thrombolytic therapy in ischemic stroke, but up to 80% of cases could not be treated because the diagnostic workup exceeds the time limit. In this article, we described the design of a study conducted in the northern Lombardy, within the district of Sondrio, Lecco, Como, and Varese. The awaited results of this study are reduction of avoidable delay, organization of an operative stroke emergency network, and identification of highly specialized structures. The study schedules education and data registration with implementation and training of acute stroke management algorithms. The use of standardized protocols during prehospital and in-hospital phase can optimize acute stroke pathways. The results of this study could contribute to the assessment of an effective and homogeneous health system to manage acute stroke.

A case of posterior reversible encephalopathy during polyarteritis nodosa vasculitis.

Posterior reversible encephalopathy is a distinctive syndrome associated with different diseases and drugs. Disease evolution is frequently favorable with an adequate treatment. Damage typically involves parietal-occipital lobes even if a more anterior diffusion has been described. Here, we report the case of a woman affected by Polyarteritis Nodosa, who suddenly complicated with decreased consciousness and seizures, during an acute hypertensive state. MRI imaging showed increased T2 and FLAIR signal in posterior regions. Her neurological evolution was positive, according to arterial pressure correction, although the systemic vasculitis was still ongoing, hence affecting final prognosis.