[Genetic testing in neurological diseases: a practical guide]. / Pruebas genéticas en enfermedades neurológicas: guía práctica.

During the last decades, genomic medicine has made it possible to bring the knowledge of molecular genetics to the field of medical consultation. There are several studies that contribute to the diagnosis, the definition of prognoses, as well as the possibility of providing genetic counseling based on accurate scientific data. Advances in genomic sequencing have promoted the reclassification of entities according to an etiological criterion. Such is the case of epileptic encephalopathies, ataxias, dystonias, among many other neurological conditions. Its implementation requires strategies aimed at achieving the best diagnostic yield. This requires a greater understanding of the molecular bases of each of these practices, as well as their scope. They allow reducing the time until a certain diagnosis is made and the possibility, in some cases, of improving the quality of life of those affected with the use of tailored treatments. The objective of this article was to describe current laboratory studies, their scope and emphasize the algorithms for the study of genetic diseases in general, focusing the attention on those specific to neuropediatrics, in order to promote good practices, avoiding confusion, errors, and unnecessary expenditures of money and shortening the so-called "diagnostic odyssey".

Durante las últimas décadas la medicina genómica ha llevado al ámbito de la consulta médica los conocimientos de la genética molecular. Existe un número de estudios que contribuyen en el diagnóstico, la definición de pronósticos y posibilitan un asesoramiento genético basado en datos científicos certeros. En algunas enfermedades, los avances en la secuenciación genómica, ha promovido la reclasificación de entidades según un criterio etiológico, como las encefalopatías epilépticas, las ataxias, las distonías, entre muchas condiciones médicas. Su implementación requiere, por parte de los médicos, de estrategias tendientes a alcanzar el mejor rédito diagnóstico. Es necesario para ello, una mayor comprensión de las bases moleculares de estas prácticas, así como sus alcances. Permiten reducir los tiempos hasta la concreción de un diagnóstico de certeza y la posibilidad, en algunos casos, de mejorar la calidad de vida de los afectados con la utilización de tratamientos a la medida. El objetivo de este artículo fue describir las técnicas de laboratorio actuales, sus alcances y enfatizar los algoritmos de estudio de las enfermedades genéticas, haciendo hincapié en aquellas propias de la neuropediatría, a fin de propiciar las buenas prácticas, evitando confusiones, errores, erogaciones innecesarias de dinero y acortando la llamada "odisea diagnóstica".

Challenges in the Diagnosis of SARS-CoV-2 Infection in the Nervous System.

Neurological involvement has been widely reported in SARS-CoV-2 infection. However, viral identification in the cerebrospinal fluid (CSF) is rarely found. The aim of this study is to evaluate the accuracy of virological and immunological biomarkers in CSF for the diagnosis of neuroCOVID-19. We analyzed 69 CSF samples from patients with neurological manifestations: 14 with suspected/confirmed COVID-19, with 5 additional serial CSF samples (group A), and as a control, 50 non-COVID-19 cases (group B-26 with other neuroinflammatory diseases; group C-24 with non-inflammatory diseases). Real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) was used to determine SARS-CoV-2, and specific IgG, IgM, neopterin, and protein 10 induced by gamma interferon (CXCL-10) were evaluated in the CSF samples. No samples were amplified for SARS-CoV-2 by real-time RT-PCR. The sensitivity levels of anti-SARS-CoV-2 IgG and IgM were 50% and 14.28%, respectively, with 100% specificity for both tests. CXCL-10 showed high sensitivity (95.83%) and specificity (95.83%) for detection of neuroinflammation. Serial CSF analysis showed an association between the neuroinflammatory biomarkers and outcome (death and hospital discharge) in two cases (meningoencephalitis and rhombencephalitis). The detection of SARS-CoV-2 RNA and specific immunoglobulins in the CSF can be used for neuroCOVID-19 confirmation. Additionally, CXCL-10 in the CSF may contribute to the diagnosis and monitoring of neuroCOVID-19.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas.

Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

[Subtle and subclinical neurological findings in patients with SARS-CoV-2]. / Hallazgos sutiles y subclínicos neurológicos en pacientes con SARS-CoV-2.

Background: There are severe neurological conditions in patients with COVID-19, such as: cerebrovascular disease, Guillain-Barré syndrome, encephalitis, acute hemorrhagic necrotizing encephalopathy and myelitis. Objective: We describe that the patient with SARS-CoV 2 with respiratory symptoms has subtle or subclinical neurological manifestations. Material and methods: Observational, cross-sectional, analytical study, which included patients aged 18-65 years with respiratory symptoms and a confirmed diagnosis of COVID-19. Intubated patients with chronic neurodegenerative diseases or pre-existing neurological compromise were excluded. Semiology of the headache and neurological examination were performed; Serum levels of glucose, protein, electrolytes, lactate, C-reactive protein, lactic dehydrogenase, and D-dimer were measured. Cerebrospinal fluid (CSF) analysis and electroencephalogram (EEG) were also performed in patients who accepted the risks. Results: A high prevalence of subtle neurological manifestations was found in patients with COVID-19 with only a respiratory clinical picture. Headache, anosmia, dysgeusia, and hypopalesthesia predominated in the early stages, with frequent abnormal findings in the CSF (>70%) and less frequently in the EEG (<20%). Conclusions: Headache, anosmia, dysgeusia and hypoesthesia were frequent at the beginning of the infection, together with abnormal findings in CSF and EEG, without other neurological symptoms or neurological disease.

Introducción: existen condiciones neurológicas severas en pacientes con COVID-19, como: enfermedad cerebrovascular, síndrome de Guillain-Barré, encefalitis, encefalopatía necrotizante hemorrágica aguda y mielitis. Objetivo: describimos que el paciente con SARS-CoV-2 con síntomas respiratorios tiene manifestaciones neurológicas sutiles o subclínicas. Material y métodos: estudio observacional, transversal, analítico, que incluyó pacientes de 18-65 años con síntomas respiratorios y diagnóstico de COVID-19 confirmado. Se excluyeron pacientes intubados, con enfermedades neurodegenerativas crónicas o compromiso neurológico preexistente. Se realizó semiología de la cefalea y exploración neurológica; Se midieron los niveles séricos de glucosa, proteínas, electrolitos, lactato, proteína C reactiva, deshidrogenasa láctica y dímero D. También se realizaron análisis de líquido cefalorraquídeo (LCR) y un electroencefalograma (EEG) en los pacientes que aceptaron los riesgos. Resultados: se encontró alta prevalencia de manifestaciones neurológicas sutiles en pacientes con COVID-19 con solo cuadro clínico respiratorio. Cefalea, anosmia, disgeusia e hipopalestesia predominaron en las primeras etapas, con hallazgos anormales frecuentes en el LCR (>70%) y con menos frecuencia en el EEG (<20%). Conclusiones: la cefalea, anosmia, disgeusia e hipoestesia fueron frecuentes al inicio de la infección, junto con hallazgos anormales en LCR y EEG, sin otros síntomas neurológicos ni enfermedad neurológica.

Profile of neurological disorders in a tertiary center of education in orthopedics.

BACKGROUND: Neurological conditions can cause secondary orthopedic disorders and can result from orthopedic surgical procedures. In addition, misdiagnosis and overtreatment involve both specialties. Epidemiological studies of neurological patients in tertiary units are often performed in emergency departments of general hospitals or rehabilitation centers. OBJECTIVE: Describe the clinical and epidemiologic profile of neurological disorders in a Brazilian federal tertiary center and education hospital in orthopedics in Rio de Janeiro. METHODS: We performed a retrospective study of the medical records of patients attended by neurology specialists of the internal medicine's department of the National Institute of Traumatology and Orthopedics from February 2014 to March 2020. RESULTS: We reviewed neurological referrals in the medical records of 1,349 patients in the period. The mean age of patients was 49.67 years (standard deviation [SD] ± 18.99). There was a predominance of females, corresponding to 751 (55.7%) patients. Regarding ethnicity, 684 (50.7%) participants were white, 550 (40.8%) non-white, and 115 (8.5%) non-classified. Peripheral neuropathies (34.1%), osteoarticular diseases (10%), epilepsy (8.3%), developmental disorders (7.9%), and neuromuscular diseases (7.3%) were the 5 groups with the largest numbers of cases. CONCLUSION: The sample consisted mostly of females and white individuals, and approximately one third of the cases were of peripheral neuropathies. Epidemiological studies in neurology from tertiary centers of another medical specialty can improve the professional development of both specialties. This interdisciplinary approach can also optimize resources, help avoid misdiagnosis, and reduce disability.

ANTECEDENTES: Condições neurológicas tanto podem causar distúrbios ortopédicos secundários como podem ser consequências de procedimentos cirúrgicos ortopédicos. Além disso, erros de diagnóstico e sobre tratamento também envolvem ambas as especialidades. Estudos epidemiológicos de atendimento neurológico em unidades terciárias de saúde são geralmente realizados em serviços de emergência ou em centros de reabilitação. OBJETIVO: Descrever o perfil clínico e epidemiológico de diagnósticos em neurologia em um centro terciário de saúde no Brasil e hospital de educação em ortopedia no Rio de Janeiro. MéTODOS: Realizamos um estudo retrospectivo com revisão de prontuários dos pacientes atendidos pela neurologia do setor de clínica médica do Instituto Nacional de Traumatologia e Ortopedia no período de fevereiro de 2014 a março de 2020. RESULTADOS: Revisamos os prontuários de 1.349 pacientes atendidos pela neurologia no período. A média de idade dos pacientes foi de 49,67 anos (desvio padrão [DP] ± 18,99). Houve predomínio do sexo feminino correspondendo a 751 (55,7%) dos atendimentos. Quanto à etnia, a amostra foi composta de 684 (50,7%) de brancos, 550 (40,8%) de não brancos e 115 (8,5%) de não classificados. Neuropatias periféricas (34,1%), doenças osteoarticulares (10%), epilepsias (8,3%), transtornos do desenvolvimento (7,9%) e doenças neuromusculares (7,3%) corresponderam aos 5 grupos com os maiores números de casos. CONCLUSãO: A amostra se constituiu predominante de indivíduos do sexo feminino, brancos, e cerca de um terço dos casos corresponderam às neuropatias periféricas. Estudos de perfil de atendimento neurológico em hospitais terciários de outra especialidade médica podem aperfeiçoar a capacitação de ambos os profissionais. Esta abordagem interdisciplinar também pode otimizar recursos, contribuir para evitar erros diagnósticos e reduzir incapacidades.

Measurement properties of outcome measures used in neurological telerehabilitation: A systematic review using COSMIN checklist.

OBJECTIVE: To summarize the measurement properties (reliability, validity, and responsiveness) and the clinical utility of measurement tools used in telerehabilitation in individuals with neurological conditions. DESIGN: Systematic review. SUBJECTS: Individuals with neurological conditions. INTERVENTION: Not applicable. MAIN MEASURES: The methodological quality of the studies using the COSMIN Risk of Bias Checklist, the quality of the measurement properties using the criteria for good measurement properties, and the clinical utility of the measurements using the Tyson & Connell scale. RESULTS: From the 22,188 identified studies, 47 were included. Forty-three measurement tools were identified. The main modes of administration were telephone and videoconference. Studies involved mostly individuals with stroke, multiple sclerosis, and Alzheimer's disease. Criterion validity and reliability were the most investigated measurement properties. None of the tools had their responsiveness investigated. Twenty-two measurement tools have at least one measurement property evaluated as "sufficient" in a study with appropriate methodological quality ("very good" or "adequate"). Nineteen measurement tools showed adequate clinical utility. Eight measurement tools, investigated in individuals with stroke, spinal cord injury or Alzheimer's disease, all administered by telephone, were recommended. CONCLUSION: The present results can be used to assist in choosing appropriate measurement tools, both in research and clinical practice, during telerehabilitation in individuals with neurological conditions. Measurement error, content validity, structural validity, and responsiveness need to be further investigated. In addition, the measurement properties of tools used in telerehabilitation in other neurological conditions, such as Huntington's disease, should also be investigated. REGISTRATION NUMBER: CRD42021257662.

Havana syndrome: a scoping review of the existing literature.

Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called "Havana syndrome" (HS). MEDLINE, Scopus, and Ovid databases from 2016 until 24 September 2021 were systematically searched for the related published manuscripts. The following search strategy was implemented: "Havana syndrome" OR "Neurological Symptoms and US Diplomats". The primary search yielded 120 publications. Only five original studies and 18 non-original articles were considered to be relevant. While these studies provided a constellation of signs and symptoms for HS, none provided a good level of evidence. In conclusion, Havana syndrome is a nonspecific neurological illness with an unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms. This syndrome should be considered and investigated as a health concern, and not as a political issue.

Training of neurologists for the 21st century: cultural and professional skills.

Training of neurologists for the near future is a challenge due to the likely advances in neuroscientific methods, which will change much of our knowledge on diagnosis and treatment of neurological diseases. OBJECTIVE: to comment on what may be more likely to be a constant in the very near future and to recommend how to prepare the neurologist for the 21st century. METHODS: through a critical review of recent articles on the teaching of Neurology, to present a personal view on the subject. RESULTS: Diagnostic methods and therapeutic resources in Neurology will be greatly improved, but the central core of teaching young neurologists will continue to be the clinical/anatomical correlation. The neurologist must be prepared to be the primary physician in the care of patients with neurological disorders, although the roles of consultant and clinical neuroscientist must also be considered. In addition to technical knowledge, the neurologist must be prepared to discuss not only distressing issues related to the specialty, such as the risks of genetic diseases for family members of their patients, the inexorable progression of some diseases and the need for palliative care, but also problems not directly related to Neurology that cause anxiety and depression in the patient or that are the main reason for the initial consultation. CONCLUSION: neurology will be an even more important area of medicine and the neurologist must be well prepared to be the primary doctor to diagnose, treat and follow the patient with neurological disorders. In addition to technical knowledge, training in doctor-patient relations should be highlighted.

NeuroCOVID-19: a critical review.

BACKGROUND: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon. OBJECTIVE: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge. METHODS: Narrative review. RESULTS: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists. CONCLUSION: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword - putting patient's suffering in the spotlight, but with a tradeoff in methodological consistency.

Serum glial fibrillary acidic protein is a body fluid biomarker: A valuable prognostic for neurological disease - A systematic review.

Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological disorders, astrocyte disintegration leads to the release of glial fibrillary acidic protein (GFAP) from tissue into the bloodstream. Elevated serum levels of GFAP can serve as blood biomarkers, and a useful prognostic tool to facilitate the early diagnosis of several neurological diseases ranging from stroke to neurodegenerative disorders. This systematic review synthesizes studies published between January 2012 and September 2021 that used GFAP as a potential blood biomarker to detect neurological disorders. The following electronic databases were accessed: MEDLINE, Scopus, and Web of Science. In all the databases, the following search strategy was used: ¨GFAP¨ OR ¨glial fibrillary acidic protein¨ AND ¨neurological¨ OR ¨neurodegenerative¨ AND ¨plasma¨ OR ¨serum¨. The initial search identified 1152 articles. After the exclusion criteria were applied, 48 publications that reported GFAP levels in neurological disorders were identified. A total of16 different neurological disorders that have plasmatic GFAP levels as a possible biomarker for the disease were described in the articles, being: multiple sclerosis, frontotemporal lobar degeneration, Alzheimer's disease, Parkinson disease, COVID-19, epileptic seizures, Wilson Disease, diabetic ketoacidosis, schizophrenia, autism spectrum disorders, major depressive disorder, glioblastoma, spinal cord injury, asthma, neuromyelitis optica spectrum disorder and Friedreich's ataxia. Our review shows an association between GFAP levels and the disease being studied, suggesting that elevated GFAP levels are a potentially valuable diagnostic biomarker in the evaluation of different neurological diseases.

Prevalence and clinical features of neurological disorders in dogs attended at Federal Rural University of Rio de Janeiro (2017-2018) / Caracterização clínica dos distúrbios neurológicos observados em cães atendidos na Universidade Federal Rural do Rio de Janeiro (2017-2018)

Neurological disorders are frequent in small animal veterinary clinics and studies giving regional justification for such disorders are essential so that veterinarians can be better prepared. The objective of this retrospective study was to describe the clinical and epidemiological aspects of dogs with neurological disorders treated at the Veterinary Hospital of Federal Rural University of Rio de Janeiro, between August 2017 and April 2018. The study describes the location of the lesions and their etiology according to the acronym VITAMIN-D, as well as the distribution of cases according to sex, breed and age. One hundred and twenty-two (122) dogs were included, of which 58% (n=71) were males and 42% (n=51) females. The age distribution ranged from two months to 18 years old; 16% were less than two years old, 50% between two and seven years old and 34% were more than seven years old. The most affected breeds were Mixed Breed dogs (43%), Poodles (9%) and Dachshunds (7%). The diagnoses were confirmed in 54 animals (44%) and in 68 (56%) remained presumptive. The most common location was the spinal cord (61%), where the T3-L3 region was the most affected (35%), followed by multifocal (20%) and forebrain (10%). The most frequent categories were degenerative (24%), inflammatory/infectious (23%) and traumatic (20%) diseases. Intervertebral disc disease was the most observed, corresponding to 21.3% of all cases. The results showed that the neurological diseases in this Veterinary Hospital were more prevalent in young male adults with spinal cord diseases of degenerative nature.(AU)

Desordens neurológicas são frequentes na clínica de pequenos animais. Estudos caracterizando a casuística regio-nal são fundamentais para melhor instrução e preparo técnico do médico veterinário. O objetivo deste trabalho retrospectivo foi descrever os aspectos clínicos e epidemiológicos de cães com distúrbios neurológicos atendidos no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro, entre agosto de 2017 e abril de 2018, caracterizando a localização da lesão e etiologia de acordo com o acrônimo VITAMINA-D, bem como a distribuição dos casos em relação ao sexo, raça e faixa etária. Foram incluídos 122 cães, com 58% (n=71) dos casos em machos e 42% (n=51) em fêmeas. A distribuição etária variou de dois meses a 18 anos, sendo 16% dos animais menores de dois anos, 50% entre dois e sete anos e 34% maiores de sete anos. As raças mais observadas foram SRD (43%), Poodle (9%) e Dachshund (7%). O diagnóstico etiológico foi confirmado em 54 animais (44%) e em 68 (56%) permaneceu como presuntivo. A localização mais comum foi na medula espinhal (61%), sendo a região entre T3-L3 a mais acometida (35%), seguida por multifocal (20%) e prosencéfalo (10%). As categorias mais frequentes foram de doenças degenerativas (24%), inflamatórias/infecciosas (23%) e traumáticas (20%). Dos cães com doenças degenerativas, a doença do disco intervertebral foi mais observada (21,3% do total dos casos). Com base nos resultados obti-dos, pode-se concluir que, na casuística regional deste Hospital, as doenças neurológicas foram mais prevalentes em machos, adultos jovens e com localização medular de origem degenerativa.(AU)

[Neurological manifestations in patients with severe COVID-19 in a tertiary care center]. / Manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención.

Background: The SARS-CoV-2 disease, called COVID-19, emerged in China has acquired pandemic dimensions. According to the WHO situational report of March 15, 2021, the global fatality rate is 2.2%; in Mexico, around 194 944 deaths have been confirmed by COVID-19. Studies in China identified that patients with severe COVID-19, when compared with those who had non-severe COVID-19, presented more severe neurological manifestations. Objective: To determine the frequency of neurological symptoms and manifestations in patients with severe COVID-19 in a tertiary care center. Material and methods: A cross-sectional, observational and analytical study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, in patients hospitalized with severe COVID-19. Results: 183 cases were analyzed, of which 130 were men (71%). The median age was 55 years (IQR: 44-65). The neurological symptoms were: headache, anosmia and dysgeusia. Neurological manifestations occurred in 27 patients (16%), the most frequent was ischemic-type cerebrovascular disease (CVD) in 12 (44%), in patients older than 76.5 years vs. 54 years (p = 0.000), with history of cardiovascular disease. Conclusions: The most frequent neurological symptoms were headache, anosmia and dysgeusia. The most frequent neurological manifestation was ischemic CVD that appeared in older patients with severe COVID-19 with a history of cardiovascular disease.

Introducción: la enfermedad por SARS-CoV-2 denominada COVID-19 originada en China adquirió dimensiones pandémicas. De acuerdo con el reporte situacional de la OMS al 15 de marzo de 2021, la tasa de letalidad global es del 2.2%; en México se han confirmado alrededor de 194 944 defunciones por COVID-19. Estudios en China identificaron que los pacientes con COVID-19 severo, al compararlos con aquellos que cursaron con COVID-19 no severo, presentaron manifestaciones neurológicas más graves. Objetivo: determinar la frecuencia de síntomas y manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención. Material y métodos: estudio transversal, observacional y analítico, llevado a cabo en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, en pacientes hospitalizados con COVID-19 severo. Resultados: se analizaron 183 casos, de los cuales 130 eran hombres (71%). La mediana de edad fue de 55 años (RIC: 44-65). Los síntomas neurológicos fueron: cefalea, anosmia y disgeusia. Las manifestaciones neurológicas se presentaron en 27 pacientes, la más frecuente fue la enfermedad vascular cerebral tipo isquémica (EVC) en 12 pacientes (44%) en pacientes con mayor edad, 76.5 frente a 54 años (p = 0.000), y con antecedente de enfermedad cardiovascular. Conclusiones: los síntomas neurológicos más frecuentes fueron cefalea, anosmia y disgeusia. La manifestación neurológica más frecuente fue la EVC isquémica que se presentó en pacientes con COVID-19 severo de mayor edad y con antecedente de enfermedad cardiovascular.

Neurologic Manifestations of Noncongenital Zika Virus in Children.

We evaluated neurologic complications following noncongenital Zika virus infection in 11 children who presented with central nervous system signs. Zika virus RNA was detected by real-time reverse transcription-polymerase chain reaction in cerebrospinal fluid. Approximately one-quarter of patients required antiepileptic medication in follow-up, and 2 children progressed to learning difficulties or developmental delay.

Neurological Complications Acquired During Pediatric Critical Illness: Exploratory "Mixed Graphical Modeling" Analysis Using Serum Biomarker Levels.

OBJECTIVES: Neurologic complications, consisting of the acute development of a neurologic disorder, that is, not present at admission but develops during the course of illness, can be difficult to detect in the PICU due to sedation, neuromuscular blockade, and young age. We evaluated the direct relationships of serum biomarkers and clinical variables to the development of neurologic complications. Analysis was performed using mixed graphical models, a machine learning approach that allows inference of cause-effect associations from continuous and discrete data. DESIGN: Secondary analysis of a previous prospective observational study. SETTING: PICU, single quaternary-care center. PATIENTS: Individuals admitted to the PICU, younger than18 years old, with intravascular access via an indwelling catheter. INTERVENTIONS: None. MEASUREMENTS: About 101 patients were included in this analysis. Serum (days 1-7) was analyzed for glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and alpha-II spectrin breakdown product 150 utilizing enzyme-linked immunosorbent assays. Serum levels of neuron-specific enolase, myelin basic protein, and S100 calcium binding protein B used in these models were reported previously. Demographic data, use of selected clinical therapies, lengths of stay, and ancillary neurologic testing (head CT, brain MRI, and electroencephalogram) results were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm was applied to the dataset. MAIN RESULTS: About 13 of 101 patients developed a neurologic complication during their critical illness. The mixed graphical model identified peak levels of the neuronal biomarker neuron-specific enolase and ubiquitin C-terminal hydrolase-L1, and the astrocyte biomarker glial fibrillary acidic protein to be the direct causal determinants for the development of a neurologic complication; in contrast, clinical variables including age, sex, length of stay, and primary neurologic diagnosis were not direct causal determinants. CONCLUSIONS: Graphical models that include biomarkers in addition to clinical data are promising methods to evaluate direct relationships in the development of neurologic complications in critically ill children. Future work is required to validate and refine these models further, to determine if they can be used to predict which patients are at risk for/or with early neurologic complications.

Cou Cou, flying fish and a whole exome please... lessons learned from genetic testing in Barbados.

Millions of patients, with suspected complex neurogenetic disorders, living in resource limited regions around the world have no access to genetic testing despite the rapidly expanding availability and decreasing costs of genetic testing in first world nations. The barriers to increasing availability of genetic testing in resource limited nations are multifactorial but can be attributed, in large part, to a lack of awareness of the power of genetic testing to lead to a rapid, cost-effective, diagnosis that potentially will have profound clinical implications on treatment and patient outcomes. We report our experience with whole exome sequencing (WES) done for the first time in 5 patients of African descent with a suspected neurogenetic disorder living in a resource limited setting on the Eastern Caribbean island of Barbados. A diagnostic pathogenic mutation was found in 3 patients in the SCN1A, STXBP1 and SCN4A, who clinically were diagnosed with Dravet syndrome, Lennox-Gastaut syndrome, paramytonia and seizures respectively. A variant of undetermined significance was found in a patient with global developmental delays, hypotonia, with abnormal eye movements. In one patient WES was non-diagnostic. This result highlights the high yield of WES in carefully selected patients with a neurologic disease and the need for increase access to genetic testing in resource limited settings globally.