Abstract Background The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. Objective To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. Methods Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. Results The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). Conclusion A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia. COVID19 COVID 19 COVID-1 postdisease post disease life individuals multicomorbidities 202 1 older laboratoryconfirmed laboratory confirmed COVID19, 19, Federal Paulo, , Paulo) cases 3 COMPASS31 COMPASS (COMPASS-31 used not 5 1512 15 12 15.1 years male 71%, 71 71% (71%) ageusiahypogeusia ageusia hypogeusia 50%, 50 50% (50%) 49%, 49 (49%) anosmiahyposmia anosmia hyposmia 44%, 44% (44%) 31%, 31% (31%) 24%, 24 24% (24%) 20%, 20 20% (20%) 18%, 18% (18%) 16%. 16 16% . (16%) Furthermore 91 premorbidity 4 hypertension weakness breath COMPASS-3 14.85 1485 14 85 (14.8 1206 06 12.0 vs 89 8 9 8. 8.7. 87 8.7 7 8.7) 636 63 6 63.6 2.9fold 29fold fold 2.9 2 without. without without) 80 out twothirds two thirds common COVID1 COVID- COMPASS3 (COMPASS-3 151 15. (71% (50% (49% (44% (31% (24% (20% (18% (16% COMPASS- 14.8 148 (14. 120 0 12. 63. 9fold 29 2. (COMPASS- (71 (50 (49 (44 (31 (24 (20 (18 (16 14. (14 (COMPASS (7 (5 (4 (3 (2 (1 (

Resumo Antecedentes As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. Objetivo Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. Métodos Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. Resultados A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91 % dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). Conclusão Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia. COVID19 COVID 19 COVID-1 doença comorbidades 2020 1 confirmada Universidade Paulo, , Paulo) complexidade COMPASS31 COMPASS 31 (COMPASS-31 usado não 5 1512 15 12 15.1 homens 71%, 71 71% (71%) ageusiahipogeusia ageusia hipogeusia 50%, 50 50% (50%) 49%, 49 (49%) anosmiahiposmia anosmia hiposmia 44%, 44% (44%) 31%, 31% (31%) 24%, 24 24% (24%) 20%, 20 20% (20%) 18% (18% 16%. 16 16% . (16%) disso 9 prémorbidade. prémorbidade pré morbidade. morbidade pré-morbidade 4 fraqueza ar COMPASS-3 14,85 1485 14 85 (14,8 1206 06 12,0 vs 89 8 8, 8,7. 87 8,7 7 8,7) 636 63 6 63,6 risco 29 2 2. sem. sem sem) 80 destacaram comuns COVID1 COVID- 202 COMPASS3 3 (COMPASS-3 151 15. (71% (50% (49% (44% (31% (24% (20% (18 (16% COMPASS- 14,8 148 (14, 120 0 12, 63, (COMPASS- (71 (50 (49 (44 (31 (24 (20 (1 (16 14, (14 (COMPASS (7 (5 (4 (3 (2 (

Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients. Parkinsons Parkinson s (PD dysfunctions unclear β1Adrenergic βAdrenergic β1 Adrenergic β βAR AR (β1AR A1Adenosine AAdenosine A1 Adenosine A R (A1R isoproterenol, isoproterenol (isoproterenol , ISO) atenolol, atenolol (atenolol 1,3dipropyl8cyclopentyl 13dipropyl8cyclopentyl dipropylcyclopentyl 1,3 dipropyl 8 cyclopentyl 1 3 xanthine blockade IschemiaReperfusion Ischemia Reperfusion (CIR studied confirmed analysis 6hydroxydopamine hydroxydopamine 6OHDA, 6OHDA OHDA OHDA, (6-OHDA μg striatum artery CIRInduced Induced VA (VA) AVB, (AVB) LET, (LET) ECG (ECG before 83%, 83 (83% 92 92% 100 100% respectively 58%, 58 (58% 67 respectively. . 33 (33% 42 42% 25 (25% 25% respectively, cardioprotection 3dipropyl8cyclopentyl 13 1, (VA (AVB (LET 83% (83 9 58% 5 (58 (33 4 2 (25 (8 (5 (3 (2 (

SUMMARY OBJECTIVE: This study aimed to evaluate the concept of health professionals affiliated with the Brazilian League of Epilepsy on whether or not to inform patients about the risk factors related to the occurrence of sudden unexpected death in epilepsy. METHODS: A descriptive research of inquiry was conducted with direct survey on the Brazilian neurologist's view, regarding medical behavior in the health area to report or not about the risk of sudden unexpected death in epilepsy. Data collection consisted of a structured questionnaire available online. RESULTS: The study population consisted of a sample of 44 Brazilian League of Epilepsy members who answered the questionnaire, of which 25 (56.8%) were men and 19 (43.2%) were women. Among the analyzed questionnaires, 79.5% reported that they were aware of the risk factors for sudden unexpected death in epilepsy and 18.2% admitted not knowing the potential risk factors for sudden unexpected death in epilepsy. Notably, 59.1% of these professionals thought that an early discussion with the patient about sudden unexpected death in epilepsy must be considered. The majority (70%) felt that the neurologist should do this, and 22% believed that the subject should be discussed with psychologists. It was noted that 84.1% of respondents did not discuss or discussed only with some of their patients about the risk factors for sudden unexpected death in epilepsy. CONCLUSIONS: There is a need for encouraging early discussion of sudden unexpected death in epilepsy with epilepsy patients if the patient asks about the risks related to epilepsy and its treatment, when treatment adherence is low, in cases of intractable epilepsy with strong indication for surgical treatment, and when polytherapy is needed.

ABSTRACT There is increasing evidence that COVID-19 can be associated with ischemic stroke (COVID-stroke). The frequency and pathogenesis of COVID-stroke, however, remains largely unknown. This narrative review aimed at summarizing and discussing current knowledge about frequency and pathogenesis of COVID-stroke in 455 patients collected from the literature. COVID-stroke occurs in all age groups and predominantly in males. The anterior circulation is more frequently affected than the posterior circulation. COVID-stroke is most frequently embolic. The severity of COVID-stroke ranges from NIHSS 3 to 32. Cardiovascular risk factors are highly prevalent in patients with COVID-stroke. COVID-stroke occurs simultaneously with the onset of pulmonary manifestations or up to 40 days later. Clinical manifestations of COVID-19 are most frequently mild or even absent. The majority of patients with COVID-stroke achieve complete or partial recovery, but in one-quarter of patients, the outcome is fatal. In conclusion, the frequency of ischemic stroke has not increased since the outbreak of the SARS-CoV-2 pandemic. COVID-stroke predominantly affects males and the anterior circulation. COVID-stroke is multifactorial but predominantly embolic and more frequently attributable to cardiovascular risk factors than to coagulopathy.

RESUMO Introdução: A presente minirrevisão tem como objetivo resumir e discutir os avanços dos aspectos clínicos, fisiopatológicos, de diagnóstico, tratamento e evolução das neuropatias dos nervos periféricos associadas à COVID-19. Métodos: Revisão da literatura. Resultados: Foram avaliados 105 artigos sobre neuropatia associada à COVID-19. Nesses estudos, 261 pacientes apresentaram boa evolução. As neuropatias dos nervos periféricos em pacientes com COVID-19 são frequentes e se devem, principalmente, aos mecanismos immunológicos ou efeitos colaterais neurotóxicos dos medicamentos utilizados para o tratamento da COVID-19, a fatores de risco pré-existentes, como diabetes e, em menor parte, à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia viral. Os medicamentos neurotóxicos, como daptomicina, linezolida, lopinavir, ritonavir, hidro-cloroquina, cisatracúrio, clindamicina e glicocorticoides devem ser administrados com cautela, e os pacientes deve ser adequadamente admitidos nos leitos da UTI para prevenir o desenvolvimento de neuropatia associada à COVID-19. Pacientes com síndrome de Guillain-Barré (GBS) se beneficiam de imunoglobulinas, plasmaférese e esteroides. Conclusões: As neuropatias dos nervos periféricos em pacientes com COVID-19 são raras e predominantemente devidas aos efeitos colaterais neurotóxicos das mecanismos immunológicos ou drogas utilizadas para o tratamento de COVID-19 e, em menor parte, devido à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia infeciosa.

ABSTRACT Background: This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies. Methods: Literature review. Results: Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids. Conclusions: Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.

ABSTRACT Purpose To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. Results It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). Conclusions These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.

Abstract Purpose To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). Methods CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. Results In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. Conclusion The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.