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Abstract Background In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration. Methods To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis. Results This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood–brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation. Conclusions We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain. Graphical Abstract

Narcolepsy is a primary disorder of the central nervous system resulting from genetic, environmental, and immunological interactions defined as excessive daytime sleepiness plus cataplexy, hallucinations, sleep paralysis, and sleep fragmentation. The pathophysiology is not entirely known, but the interaction among genetic predisposition, environmental exposition, and immune component with consequent hypocretin-1 deficiency is the model to explain narcolepsy type I. The mechanism of narcolepsy type II is less understood. There is a delay of over ten years for the diagnosis of narcolepsy around the world. Patients with narcolepsy have many comorbidities with a negative impact on quality of life. The treatment of narcolepsy must contain an educational approach for the family, coworkers, and patients. Scheduled naps and sleep hygiene are essential to minimize the dose of medications. Much progress has been seen in the pharmacological treatment of narcolepsy with new stimulants, different presentations of oxybate, and recent studies with orexin agonists. Narcolepsy is a rare disease that needs to be more understood and highlighted to avoid delayed diagnosis and severe disabilities in patients.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered a microbiome. The number of bacteria almost equal that of human cells, however, the genome of these bacteria may be almost 100 times larger than the human genome. Every aspect of the physiology and health can be influenced by the microbiome living in various parts of our body. Any imbalance in the microbiome composition or function is seen as dysbiosis. Different types of dysbiosis are seen and the corresponding symptoms depend on the site of microbial imbalance. The contribution of the intestinal and extra-intestinal microbiota to influence systemic activities is through interplay between different axes. Whole body dysbiosis is a complex process involving gut microbiome and non-gut related microbiome. It is still at the stage of infancy and has not yet been fully understood. Dysbiosis can be influenced by genetic factors, lifestyle habits, diet including ultra-processed foods and food additives, as well as medications. Dysbiosis has been associated with many systemic diseases and cannot be diagnosed through standard blood tests or investigations. Microbiota derived metabolites can be analyzed and can be useful in the management of dysbiosis. Whole body dysbiosis can be addressed by altering lifestyle factors, proper diet and microbial modulation. The effect of these interventions in humans depends on the beneficial microbiome alteration mostly based on animal studies with evolving evidence from human studies. There is tremendous potential for the human microbiome in the diagnosis, treatment, and prognosis of diseases, as well as, for the monitoring of health and disease in humans. Whole body system-based approach to the diagnosis of dysbiosis is better than a pure taxonomic approach. Whole body dysbiosis could be a new therapeutic target in the management of various health conditions.

Background Epilepsy is a common neurological disease that affects people all over the world, but it is rarely described in indigenous peoples.

The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

Abstract Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Background Blepharospasm is a focal dystonia that affects the orbicularis oculi muscles. The interest in nonmotor symptoms is due to their impact on quality of life.

Abstract Background Brain iron accumulation neurodegeneration (NBIA) comprises a group of rare diseases characterized by deposits of this metal in brain structures. It presents a great variability of progression, which can be fast enough to lead the patient to death in the first years of life, or slow enough to be confused with non-progressive diseases. Case presentation Female, 19-year-old patient, cesarean delivery at 38 weeks of gestation. History of multiple sclerosis in a second-degree paternal aunt. Normal neuropsychomotor growth and development up to 11 months, when changes in gait began. After that, it got worse, with decreased muscle strength and falls, but it progressed so slowly that she was diagnosed with cerebral palsy, a non-progressive condition. At the age of 16, she underwent molecular analysis by exome sequencing, being diagnosed with the NBIA Phospholipase A2 (PLAN) variant. Currently doing physical therapy, hydrotherapy, occupational therapy and sertraline. Conclusions The report draws attention to the variability of the disease and the possibility of confusion with other diagnoses, which may delay proper management.

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.

Sleep has important clinical implications for neurorehabilitation after stroke. We aimed to systematically explore sleep (including naps) as an essential factor in the neurorehabilitation of patients after stroke. After titles and abstracts were screened, 49 full texts were reviewed, and 7 were included in this review. Data were extracted and assessed for quality and risk of bias. We looked at any neurorehabilitation setting, and compared sleep with no sleep and explored these factors in stroke patients versus healthy individuals. Rehabilitation is critical for many activities that may need to be learned or re-learned following stroke and for returning to everyday life. In this context, sleep is essential in neurorehabilitation and physical therapy practice as it supports neuroplasticity, memory, and learning. The available data suggest that sleep should be considered in the treatment plan for successfully targeted physiotherapy to optimize cognitive and motor learning. Physical therapists should advise about sleep hygiene and therapies to improve sleep, both quality and quantity.

This clinical guideline supported by the Brazilian Sleep Association comprises a brief history of the development of Brazilian sleep physiotherapy, outlines the role of the physiotherapist as part of a sleep health team, and describes the clinical guidelines in respect of the management of some sleep disorders by the physiotherapist (including sleep breathing disorders, i.e., obstructive sleep apnea, central sleep apnea, upper airway resistance syndrome, hypoventilation syndromes and overlap syndrome, and pediatric sleep breathing disorders; sleep bruxism; circadian rhythms disturbances; insomnia; and Willis-Ekbom disease/periodic limb movement disorder. This clinical practice guideline reflects the state of the art at the time of publication and will be reviewed and updated as new information becomes available.

Background Sleep disorders such as obstructive sleep apnea and restless legs syndrome are prevalent in the general population and patients with chronic diseases such as multiple sclerosis (MS).

Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.

ABSTRACT Background: Loss of teeth has been associated with neurological and sleep disorders. It is considered to be a predictor of stroke and leads to modifications of airway patency and predisposition to obstructive sleep apnea. Objective: To investigate sleep quality, risk of obstructive sleep apnea and excessive sleepiness among post-stroke patients with tooth loss attending the Neurovascular Clinic of the Federal University of São Paulo. Methods: The prevalence rates of different types of stroke were assessed among 130 patients with different degrees of tooth loss, along with the presence of sleep disturbances, risk of obstructive sleep apnea and excessive daytime sleepiness. Results: The prevalence of ischemic stroke was 94.6%, with either no significant disability or slight disability. Our sample had poor sleep quality, and a high risk of obstructive sleep apnea, but without excessive daytime sleepiness. Half of our sample had lost between 9 and 31 teeth, and more than 25% had edentulism. The majority used full removable dental prostheses, and more than half of these individuals slept without removing the prosthesis. Conclusions: We found high prevalence of poor sleep quality and high risk of obstructive sleep apnea among post-stroke patients with tooth loss. This indicates the need for further studies on treating and preventing sleep disturbances in stroke patients with tooth loss.

Background: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration. Methods: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis. Results: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood–brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation. Conclusions: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Narcolepsy is a disease resulting from the loss of hypocretin-producing cells or other dysfunctions of the hypocretinergic system. In addition to sleep disorders, affected patients may experience increased weight gain, olfactory changes, and poorer quality of life. Methods: This study aimed to investigate the relationship between narcolepsy and weight gain, years of study, sleep parameters, and olfactory dysfunction in patients with narcolepsy type 1 and narcolepsy type 2. Anthropometric, olfactory, socioeducational, and excessive daytime sleepiness evaluations were performed in 77 patients. Results: Greater weight gain and abdominal obesity were observed in patients with type 1 narcolepsy. Patients with higher education level had lower scores of daytime sleepiness, higher scores on the olfactory function test, and lower rates of abdominal obesity. Discussion: Patients with narcolepsy type 1 showed an increased body weight and abdominal obesity when compared to narcolepsy type 2. The patients with a higher schooling level showed a reduction of the daytime sleepiness scores, lower rates of abdominal obesity, and better scores on the olfactory function test. Conclusion: Among all the patients with narcolepsy, the data indicated that aging and hypocretin deficiency are associated with abdominal obesity, while years of study is the variable that mostly influences olfaction function.

As práticas e manifestações racistas foram concebidas e normalizadas ao longo da histórica brasileira, repercutindo, inclusive, no âmbito cultural, fazendo-se presente em músicas, produções audiovisuais e também na Literatura. O presente estudo busca aprofundar a relação entre o racismo e o Direito na Literatura contemporânea, vislumbrando os espaços para a pluralidade literária e para a inclusão de autores negros na Sociedade da Informação, repercutindo o enfoque do contexto contemporâneo para a concreção da cidadania sob a perspectiva decolonial. Foi realizada uma pesquisa de cunho bibliográfico buscando o aprofundamento da temática. Nesse sentido, foi possível considerar, por fim, que, ao coexistir na literatura o racismo estrutural, faz-se necessário que novos caminhos, baseados na visão decolonialista, abram-se para que, na contemporaneidade, os negros protagonizem seus feitos reais.

ABSTRACT Background: Neurological disorders are significant causes of morbidity and mortality worldwide. However, data about general neurological inpatient admissions in Brazil is limited. Objective: To investigate the prevalence of neurological disorders according to disease group and lesion site among patients admitted to a general Neurology ward. Methods: This was an observational and descriptive study. The hospital discharge database for the Neurology ward was surveyed in accordance with the International Classification of Diseases, 10th edition (ICD-10), from September 2008 to October 2019. The final diagnosis was classified into neurological disorder groups and site. Results: Overall, 2,606 clinical neurological patient files were included, with mean length of hospitalization of 16.7 days and a total of 325 readmissions (12.5%). The overall mortality rate in the ward was 3.8% (100 patients). Among all the diagnoses, cerebrovascular disease was the most prevalent (45.8%), followed by inflammatory disorders (22.2%). The brain was the most common lesion site (66.0%), followed by peripheral nerves (10.0%) and meninges and cerebrospinal fluid (7.7%). Conclusions: The disease pattern upon admission showed that a majority of the cases consisted of cerebrovascular disorders and that the brain was the most frequently affected structure, although we observed that a wide variety of cases were admitted, encompassing all neurological disorders.

Abstract Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.