To the Editor: From February 28 through March 21, 2020, in three hospitals in northern Italy, we examined five patients who had Guillain-Barré syndrome after the onset of coronavirus disease 2019 , the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During that period, an estimated 1000 to 1200 patients with Covid-19 were admitted to these hospitals. Four of the patients in this series had a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome, and one had a negative nasopharyngeal swab and negative bronchoalveolar lavage but subsequently had a positive serologic test for the virus. Detailed case reports are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.The first symptoms of Guillain-Barré syndrome were lower-limb weakness and paresthesia in four patients and facial diplegia followed by ataxia and paresthesia in one patient (Table 1). Generalized, flaccid tetraparesis or tetraplegia evolved over a period of 36 hours to 4 days in four patients; three received mechanical ventilation. The interval between the onset of symptoms of Covid-19 and the first symptoms of Guillain-Barré syndrome ranged from 5 to 10 days (Table 1 and Fig. S1 in the Supplementary Appendix). None of the patients had dysautonomic features.On analysis of the cerebrospinal fluid (CSF), two patients had a normal protein level and all the patients had a white-cell count of less than 5 per cubic millimeter. Antiganglioside antibodies were absent in the three patients who were tested. In all the patients, a real-time polymerase-chain-reaction assay of the CSF was negative for SARS-CoV-2. Results of electrophysiological studies are shown in Table S1. Compound muscle action potential amplitudes were low but could be obtained; two patients had prolonged motor distal latencies. On electromyography, fibrillation potentials were pres-* Covid-19 denotes coronavirus disease 2019, CSF cerebrospinal fluid, ICU intensive care unit, IVIG intravenous immune globulin, MRI magnetic resonance imaging, PCR polymerase chain reaction, and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2. † On CSF analysis, all the patients had a normal glucose level and IgG index and a polyclonal pattern on electrophoresis. The normal range for the protein level is 15 to 45 mg per deciliter. ‡ An enzyme-linked immunosorbent assay was used to test for antibodies to GM1, GQ1b, and GD1b.

Background: Strokes are the leading cause of epileptic seizures in adults and account for 50% of seizures in those over the age of 65 years. The use of antiepileptic drugs to prevent recurrent poststroke seizures is recommended. Methods: One hundred and twenty-eight patients with poststroke seizures were randomly allocated to treatment with either levetiracetam (LEV) or sustained-release carbamazepine (CBZ) in a multicenter randomized open-label study. After a titration study phase (2 weeks), the optimal individual dose of trial medication was determined and treatment was continued for another 52 weeks. The primary endpoint was defined as the proportion of seizure-free patients; the secondary endpoints were: evaluation of time recurrence to the first seizure, EEG tracings, cognitive functions and side effects. Results: Of 128 patients, 22 discontinued the trial prematurely; thus a total of 106 patients (52 treated with LEV and 54 treated with CBZ) were included in the analysis. The results of the study were as follows: no significant difference in number of seizure-free patients between LEV and CBZ (p = 0.08); time to the first recurrence tended to be longer among patients on LEV; there was no correlation between the therapeutic effect and the EEG findings in either treatment group; LEV caused significantly fewer (p = 0.02) side effects than CBZ; attention deficit, frontal executive functions and functional scales (Activities of Daily Living and Instrumental Activities of Daily Living indices) were significantly worse in the CBZ group. Conclusions: This trial suggests that LEV may be a valid alternative to CBZ in poststroke seizures, particularly in terms of efficacy and safety. In addition, our results show that LEV has significant advantages over CBZ on cognitive functions. This trial also indicates that LEV in monotherapy is a safe and effective therapeutic option in elderly patients who have suffered epileptic seizures following a stroke.

Background and Purpose-Not many data on stroke epidemiology come from studies on islands. This is the first report on a Mediterranean archipelago population. Methods-Using recommended criteria, from July 1, 1999, to June 30, 2002, information was collected on first-ever stroke and 30-day case fatality in Aeolian island residents (13 431). Results-The overall crude incidence rate was 154 of 100 000 (95% CI, 118 to 197; 128 4,5,6 This is the first report providing comparable data on stroke in a Mediterranean archipelago population. Subjects and MethodsThe Aeolian archipelago (116.1 km 2 ) includes 7 volcanic islands off the northeast Sicilian coast. The climate is typically Mediterranean. In-migration and out-migration is very limited. At the 2001 census, the study population (13 431) was not significantly different from the Italian population (Figure). Moreover, it had not changed very much in the last 10 years (ϩ1% comparing Census 1991 with 2001). Agriculture, fishing, and tourism are the main activities.Medical care (free of charge) is supplied only by the National Health Service (NHS) through 10 general practitioners (GPs), 10 first aid stations, and a general hospital without computed tomography (CT) equipment. The nearest NHS referral centers (in Sicily) are Milazzo, with a neurological division and CT equipment, and Messina, with multiple facilities.The study was based on "standard ideal criteria," including World Health Organization (WHO) definition, first-ever-in-a-lifetime stroke, complete case ascertainment based on multiple overlapping sources, and prospective study design. 1 It was performed from July 1, 1999, to June 30, 2002, thanks to the full cooperation of all Aeolian physicians and GPs in particular, who were trained to fill in a clinical schedule to notify the team of suspected stroke cases. Whenever possible, patients were hospitalized in our neurology unit in Messina to undergo assessment. In nonhospitalized patients, diagnosis was based mainly on the reports of local doctors after all potential cases had been revised and discussed with them. To achieve complete case ascertainment, we contacted GPs monthly and verified: Aeolian first aid station and hospital registries; records of mobile emergency services; admission and discharge lists from the island general hospital, the medical and neurological hospital divisions in Milazzo and Messina and from the university departments of medical (including geriatric unit) and neurological sciences (including neurology, neurosurgery, and intensive care unit) in Messina; and death certificates of Aeolian residents.Crude incidence rates together with 95% CIs for single binominal proportions were calculated by the exact approach (2001 census CI, 12.12 to 42.20). Six men and 9 women (mean age 79.2; range 52 to 90Ϯ9.9 years of age) died within 30 days because of the qualifying stroke (nϭ12) or cardiovascular events (nϭ3). Among them, 8 had illdefined, 4 ischemic, and 3 hemorrhagic stroke.

Summary:Purpose: To estimate the prevalence and define the clinical characteristics of epileptic disorders in the 13,431 residents of the Sicilian Aeolian archipelago, on June 1, 1999.Methods: All established or suspected cases were identified by the neurologists of our working group from available medical information sources. Possible epilepsy cases were then evaluated by the epileptologists by using a standardized questionnaire. The patients were further reviewed by the whole research team to confirm the clinical diagnosis. For a more detailed syndromic definition, some patients underwent EEG or neuroradiologic investigations or both.Results: The crude point prevalence rate of active epilepsy was 3.13 (95% confidence interval, 2.2-4.2). The prevalence rate age-adjusted to the 2001 Italian population was 3.01. Females had a slightly higher prevalence rate than did males. The highest age-specific prevalence was found in patients aged 5 to 14 years (5.05) and in those aged 65 to 74 years (5.41). Partial seizures with or without secondary generalization were more common (61.7%) than were generalized seizures. Eighty-three percent of cases had symptomatic or cryptogenic localizationrelated epilepsies, and 8.5% had idiopathic (generalized or partial) epilepsies. Epilepsy was unclassified in 8.5% of cases.Conclusions: The prevalence of active epilepsy in the Aeolian islands is lower than that in other developed areas, including northern Italy, but is similar to that in Sicily. Partial seizures were the most common type, and localization-related symptomatic epilepsies were the largest syndromic category.

Background: Although several authors have studied the association between patent foramen ovale (PFO) and ischaemic stroke, the matter is still controversial; few have suggested an association between cryptogenetic stroke and PFO, while others have denied this association. The aim of this study was to evaluate PFO prevalence in the whole ischaemic stroke population, independently from age and stroke subtypes and to identify the characteristics associated with the presence of PFO. Methods: SISIFO study was a multicenter, prospective, single-wave, cross-sectional survey conducted on consecutive patients with acute ischemic stroke admitted to selected clinical centres. Data regarding vascular risk factors were registered for each patient; all patients underwent computed tomography scan and/or magnetic resonance imaging of the brain; an electrocardiogram and standard laboratory blood tests were performed. A Doppler ultrasound study of extra-cranial arteries was performed too. The cases were classified according to TOAST and OCSP criteria. Each patient underwent transcranial Doppler or transcranial color-coded duplex sonography with bubble test as diagnostic tool for right-to-left-shunt. Where right-to-left shunt was detected, PFO presence was confirmed by echocardiography. Findings: 1,130 consecutive patients were included. We found a PFO in 247 (21.9%; 95% CI, 19.5-24.3%) patients; PFO was present in 23.5% of patients with cryptogenic stroke and in 21.3% of patients with stroke of known causes; this difference was not statistically significant. At the univariate analysis, decreasing age, hypertension, diabetes mellitus, and atrial fibrillation, and stroke characteristics such as NIHSS, OCSP and TOAST were predictors of PFO presence. At the multivariate analysis, we found a significant interaction between age and OCSP syndrome. Being LACI the reference category, the prevalence of PFO in PACI and POCI decreased significantly along with age, whereas there was no change in TACI. Conclusion: If any relationship exists between stroke and PFO, this is more likely in PACI and POCI at a younger age. Our results are consistent with recent findings that underline PFO alone must not be considered a significant independent predictor for stroke; so the presence of PFO alone doesn't permit rushed causal correlations or ‘therapeutic aggressiveness'.