A meta-analysis of Chikungunya virus in neurological disorders.

Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly neurological disorders, has occurred. The current evidence regarding the pooled prevalence of Chikungunya virus (CHIKV)-associated neurological cases (CANCs) suspected of having an arboviral aetiology is not well-understood. Therefore, this meta-analysis included 19 studies (n = 7319 patients) and aimed to determine the pooled rate of exposure to CANC. The pooled positivity rate of CANC was 12 % (95 % CI: 6-19), and Brazil was overrepresented (11/19). These estimations varied between 3 and 14 % based on the diagnostic method (real-time PCR vs. ELISA-IgM) and biological samples (cerebrospinal fluid or blood specimens) used for detection of CHIKV. Regarding the frequency of CHIKV in neurological clinical subgroups, the rates were higher among patients with myelitis (27 %), acute disseminated encephalomyelitis (27 %), Guillain-Barré syndrome (15 %), encephalitis (12 %), and meningoencephalitis (7 %). Our analysis highlights the significant burden of CANC. However, the data must be interpreted with caution due to the heterogeneity of the results, which may be related to the location of the studies covering endemic periods and/or outbreaks of CHIKV. Current surveillance resources should also focus on better characterizing the epidemiology of CHIKV infection in neurological disorders. Additionally, future studies should investigate the interactions between CHIKV and neurological diseases with the aim of gaining deeper insight into the mechanisms underlying the cause-and-effect relationship between these two phenomena.

Urodinámica de la rao en el Síndrome de Guillain-Barré post-infección por coronavirus SARS-COV-2. Revisión bibliográfica / Rao urodynamics in Guillain-Barré Syndrome post-infection by SARS-COV-2 coronavirus. Bibliographic review

INTRODUCCIÓN Y OBJETIVO: La infección por coronavirus SARS-CoV-2 se ha asociadoa la aparición de síntomas genitourinarios de novo,además de síntomas neurológicos secundarios al dañodel sistema nervioso periférico. Una de las patologíasneurológicas descritas asociadas a la infección ha sidoel síndrome de Guillain-Barré (SGB). Realizamos unarevisión de la literatura sobre la infección por SARSCoV-2 y su relación con los síntomas del tracto urinario inferior (STUI), como la retención urinaria (RAO).Se analizaron también las alteraciones vesicales derivadas de la afectación neurológica por SARS-CoV-2,como el SGB. Se presenta un caso propio.MATERIAL Y MÉTODOS: Se realizó una búsquedade la literatura utilizando una combinación de palabras clave (términos MeSH): “COVID”, “COVID-19”,“SARS-CoV-2”, “Urinary retention” y “Guillain-BarreSyndrome and Urodynamics”. Se realizaron búsquedas de artículos publicados hasta marzo de 2021. Todos los artículos identificados a partir de la búsquedabibliográfica fueron analizados, utilizando los criteriosPICOS (participantes, intervención, comparaciones,resultados, tipo de estudio) para evaluar la elegibilidadde los artículos. Se incluyeron tanto estudios prospectivos, retrospectivos, casos clínicos y revisiones sistemáticas publicadas.RESULTADOS: Se discuten los hallazgos en la literatura de las asociaciones entre COVID-19 y RAO, STUIy Síndrome de Guillain-Barré, así como sus posiblesmecanismos patogénicos. También se aporta un resumen de trabajos relevantes sobre hallazgos urodinámicos en pacientes con SGB. Los resultados seresumen en tablas anexas. Se aporta un caso de RAOasociado a COVID-19 y Síndrome de Guillain-Barrécon sus hallazgos urodinámicos.CONCLUSIÓN: A pesar de la asociación entre síntomas urinarios y SARS-CoV-2 no está bien descrita, parece que hay indicios de una posible asociación, al menos temporal entre la presentación de infección porcoronavirus SARS-Cov-2 y el desarrollo de un SGB

INTRODUCTION AND OBJECTIVE: The SARS-CoV-2 coronavirus infection has beenassociated with the development of the novo genitourinary symptoms and neurological symptomssecondary to peripheral nervous system damage.One of the neurological pathologies described associated with the infection has been Guillain-Barrésyndrome (GBS). We conducted a review of the literature on SARS-CoV-2 infection and its relationshipwith lower urinary tract symptoms (LUTS), such asurinary retention (AUR). Bladder alterations derived from neurological involvement by SARS-CoV-2,such as GBS, were also analyzed. An own case ispresented.MATERIAL AND METHODS: A literature searchwas performed using a combination of keywords(MeSH terms): “COVID”, “COVID-19”, “SARS-CoV-2”,“Urinary retention” and “Guillain-Barre Syndromeand Urodynamics”. We searched for articles published up to March 2021. All articles identified fromthe bibliographic search were analyzed, using thePICOS criteria (participants, intervention, comparisons, results, type of study) to assess the eligibility of the articles. Both prospective and retrospective studies, clinical cases and published systematicreviews were included.RESULTS: Findings in the academic literatureabout the associations between COVID-19 and RAO,LUTS and Guillain-Barré Syndrome are discussed,as well as their possible pathogenic mechanisms,A summary of relevant studies on urodynamic findings in GBS patients is also provided. The resultsare summarized in attached tables. A case of AURassociated with COVID-19 and Guillain-Barré Syndrome is provided, with its urodynamic findings.CONCLUSION: Although the association betweenurinary symptoms and SARS-CoV-2 is not well described, there seems to be evidence of a possibleassociation, at least temporary, between the presentation of SARS-Cov-2 infection and the development of GBS with secondary LUT neurophysiologyalterations.

Casos clínicos de los síndromes de Guillain-Barré y Miller-Fisher relacionados con la COVID-19 / Clinical cases of Guillain-Barré and Miller-Fisher syndromes linked to COVID-19

Introducción: la enfermedad por coronavirus del 2019 (COVID-19), causada por el nuevo coronavirus SARSCoV-2, se ha asociado con el desarrollo de enfermedades neurológicas como el síndrome de Guillain-Barré (SGB) y sus variantes. En el presente trabajo se reportan dos casos de síndromes desmielizantes asociados con la COVID-19. Casos clínicos: hombre de 53 años con SGB y mujer de 29 años con la variante del síndrome de Miller-Fisher (SMF), respectivamente. Ambos presentaron los signos y síntomas neurológicos clásicos de polineuropatía desmielinizante que caracterizan a estos síndromes. De las pruebas bioquímicas paraclínicas, el aumento de proteínas en líquido cefalorraquídeo fue distintiva. La positividad de la RT-qPCR para el SARS-CoV-2 indicó la asociación de los SGB y SMF con la COVID-19. Ambos pacientes se trataron con inmunoglobulina intravenosa y mostraron mejoría. La electromiografía realizada en semanas posteriores aún mostrabaafectación desmielinizante crónica. Conclusión: los casos de los SGB y SMF, junto con otros casos similares reportados en todo el mundo, proporcionan más evidencia para el SARS-CoV-2 como nueva posible etiología de estas raras enfermedades neurológicas.

Background: coronavirus disease 2019 (COVID-19), caused by the new coronavirus SARS CoV-2, has been associated with the development of neurological diseases such as Guillain-Barré syndrome (GBS) and its variants. In the present work, two cases of demyelinating syndromes associated with COVID-19 are reported. Clinical cases: 53-year-old male with GBS and and 29-yearold female with Miller-Fisher syndrome (MFS) variant, respectively. Both patients presented the classic neurological signs and symptoms of demyelinating polyneuropathy that characterizes the syndromes. From the paraclinical biochemical tests, the increase of proteins in cerebrospinal fluid was distinctive. The positivity of the RT-qPCR for SARSCoV-2 suggested the association of GBS and MFS with COVID-19. Both patients were treated with intravenous immunoglobulin showing improvement. Electromyography performed weeks ahead still showed chronic demyelinating involvement. Conclusion: The cases of GBS and MFS, along with other similar cases reported around the world, provide further evidence for SARS-CoV-2 as a new possible etiology of these rare neurological diseases.

Relation between COVID-19 and Guillain-Barre syndrome in adults. Systematic review / Relación entre COVID-10 y sindrome Guillain-Barre en adultos. Revisión sistemática

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Síndrome de Guillain-Barré asociado a infección por COVID-19: revisión de casos publicados / Guillain-Barré syndrome associated to COVID-19 infection: a review of published case reports

INTRODUCCIÓN: La pandemia por la enfermedad por coronavirus 2019 (COVID-19) es un importante problema para la salud mundial. Hay un incremento en las complicaciones neurológicas reconocidas por la COVID-19, incluyendo el síndrome de Guillain-Barré (SGB) y sus variantes. DESARROLLO: Se realizó una revisión de los casos publicados en los últimos meses de SGB asociado a infección por COVID-19. Incluimos a 48 pacientes (31 hombres; edad media: 56,4 años). Los síntomas de COVID-19 más comunes fueron tos (60,4%) y fiebre (56,3%). El tiempo promedio entre los síntomas de COVID-19 y el SGB fue de 12,1 días, pero nueve pacientes (18,8%) desarrollaron SGB en menos de siete días. Once pacientes (22,9%) presentaron afectación de los nervios craneales en ausencia de debilidad muscular, 36 presentaron la variante clásica sensitivomotora (75%) y uno tuvo una variante motora pura (2,1%). El patrón electrofisiológico se consideró desmielinizante en el 82,4% de las variantes generalizadas. La presencia de hiposmia/disgeusia estuvo asociada con una latencia menor a los siete días hasta el inicio de los síntomas del SGB (30 frente a 15,6%) y a la afectación de los nervios craneales en ausencia de debilidad (30,8 frente a 17,1%). La mayoría de los pacientes (87,5%) fueron tratados con inmunoglobulina endovenosa. La evolución neurológica fue favorable en el 64,6%, el 29,2% tuvo insuficiencia respiratoria y hubo un 4,2% de muertes. CONCLUSIONES: El SGB en pacientes con infección por SARS-CoV-2 es similar clínica y electrofisiológicamente a las formas clásicas. Se requieren más estudios para comprender si la frecuencia del SGB realmente aumentó debido a la pandemia por COVID-19 y explorar los mecanismos patógenos involucrados

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic is a major worldwide health disorder. There is an increasing number of neurological complications recognized with COVID-19 including patients with GBS and its variants. DEVELOPMENT: A review of the clinical cases of GBS associated to COVID-19 infection published in the last months has been developed. We included 48 patients (31 men, mean age 56.4 years). The most common COVID-19 symptoms were cough (60.4%) and fever (56.3%). Mean time from COVID-19 symptoms to neurologic manifestations was 12.1 days, but in nine patients (18.8%) developed GBS within seven days. Eleven patients (22.9%) presented cranial nerve involvement in the absence of muscle weakness; 36 presented the classic sensory motor variant (75%) and one had a pure motor variant (2.1%). The electrodiagnostic pattern was considered demyelinating in 82.4% of the generalized variants. The presence of hyposmia/dysgeusia was associated with a latency shorter than seven days to GBS onset of symptoms (30% vs 15.6%), and cranial nerve involvement in the absence of weakness (30.8% vs 17.1%). Most patients (87.5%) were treated with intravenous immunoglobulin. Neurological outcome was favorable in 64.6%; 29.2% had respiratory failure and 4.2% died shortly after being admitted. CONCLUSIONS: GBS in patients with SARS-CoV-2 infection resembles clinically and electrophysiology the classical forms. Further studies are necessary to understand whether GBS frequency is actually increased due to SARS-CoV-2 infection and explore pathogenic mechanisms

Síndrome de Guillain-Barré en el embarazo / Guillain-Barré syndrome in pregnancy

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Guillain-Barre syndrome related to COVID-19: muscle and nerve biopsy findings

BACKGROUND: the involvement of the peripheral nervous system (PNS) in COVID-19 is rare and, to date, morphological aspects from muscle and nerve biopsies have not been reported. Here, we describe a case of Guillain-Barré Syndrome (GBS) related to COVID-19 and demonstrate findings from peripheral nerve and skeletal muscle biopsies. A 79-year-old man presented with progressive weakness in both legs over one-week, evolving to both arms and urinary retention within 6 days. Four days earlier, he had a cough, febrile sensation and mild respiratory discomfort. On admission, his was afebrile, and without respiratory distress. A neurological examination disclosed asymmetric proximal weakness, diminished reflexes and no sensitive abnormalities. Three days later, the patient presented with bilateral facial weakness and proximal muscle strength worsened. Deep tendon reflexes and plantar responses were absent. Both superficial and profound sensitivity were decreased. From this point, oxygen saturation worsened, and the patient was placed on mechanical ventilation. CSF testing revealed one cell and protein 185 mg/dl. A chest CT showed the presence of ground-glass opacities and RT-PCR for SARS-CoV-2 was positive. The muscle biopsy revealed moderate neuromyopathic findings with positive expression for MHC-class I, C5b9, CD8 and CD68. The nerve biopsy showed inflammatory infiltrates predominantly with endoneurial compound formed by CD45 and CD68. The patient was treated with Oseltamivir for 9 days followed by IVIG for 5 days and died three days later of septic shock. DISCUSSION: this is the first documented case of GBS associated with COVID-19 with a muscle and nerve anatomopathological study. A systematic review about neurological complications caused by COVID-19 described 11 patients with GBS. The morphological features reported in our patient showed signs of involvement of the immune system, suggesting that direct viral invasion could have played a role in the pathogenesis of peripheral nerve injury. Hereafter, further research will be necessary to understand the triggers for these cells migrating into the peripheral nerve.

INTRODUÇÃO: O envolvimento do sistema nervoso periférico (SNP) na COVID-19 é raro e, até o momento, os aspectos morfológicos de biópsias de músculo e nervo não foram relatados. Descrevemos um caso de Síndrome de Guillain-Barré (SGB) na vigência de COVID-19 destacando os achados na biopsia de músculo e nervo. Um homem de 79 anos apresentou fraqueza progressiva em ambas as pernas ao longo de uma semana, evoluindo para ambos os braços e retenção urinária em 6 dias. Quatro dias antes, apresentou tosse, sensação febril e leve desconforto respiratório. Na admissão, apresentava-se afebril e sem alteração respiratória. O exame neurológico mostrou fraqueza proximal assimétrica, reflexos diminuídos e sensibilidade preservada. Três dias após, o paciente evoluiu com fraqueza facial bilateral e piora da força muscular proximal. Reflexos tendinosos profundos e cutâneo plantar ausentes bilateralmente. A sensibilidade superficial e profunda estavam diminuídas. Evoluiu com piora na saturação de oxigênio sendo colocado sob ventilação mecânica. O exame de liquor revelou uma célula e aumento de proteína (185 mg / dl). A TC de tórax revelou a presença de opacidades em vidro fosco e o RT-PCR para SARS-CoV-2 foi positivo. A biópsia muscular mostrou achados neuromiopáticos moderados com imunoexpressão positiva para MHC classe I, C5b9, CD8 e CD68. A biópsia de nervo revelou infiltrado inflamatório inflamatórios predominantemente endoneural composto por CD45 e CD68. O paciente foi tratado com Oseltamivir por 9 dias seguido de IVIG por 5 dias indo a óbito após três dias por choque séptico. DISCUSSÃO: Este é o primeiro caso documentado de SGB associada a COVID-19 com estudo anatomopatológico de músculo e nervo. Uma revisão sistemática de complicações neurológicas associadas à COVID-19 descreveu 11 pacientes com SGB. As características morfológicas em nosso paciente mostrando sinais de envolvimento do sistema imunológico sugere que a invasão viral direta pode ter colaborado no processo patogênico da lesão neuromuscular. A partir daí, mais pesquisas serão necessárias para entender os gatilhos para essas células migrarem para o nervo periférico.

Relación entre COVID-19 y síndrome de Guillain-Barré en adultos. Revisión sistemática / Relation between COVID-19 and Guillain-Barré syndrome in adults. Systematic review

INTRODUCCIÓN: Se han reportado distintos casos de pacientes con cuadro de síndrome de Guillain-Barré asociado a COVID-19, pero falta mucha información aún sobre esta asociación y sus implicancias, el objetivo de esta revisión es analizar la evidencia disponible en esta temática en la población adulta. Material y MÉTODOS: Se realizó una revisión sistemática de estudios publicados en buscadores científicos: PubMed, Cochrane, Science Direct, Medline, OMS COVID-19. RESULTADOS: Se identificaron 45 estudios, los cuales se analizaron y completaron utilizando la plataforma Covidence, incluyendo para el análisis final 24 artículos y sumando un total de 30 pacientes. CONCLUSIONES: Se demuestra una asociación fuerte entre ambas patologías, además, los estudios analizados recalcan diferencias en la presentación de la enfermedad con mayor gravedad en los cuadros de síndrome de Guillain-Barré asociados a COVID-19

INTRODUCTION: Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population. MATERIAL AND METHODS: A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database. RESULTS: We identified 45 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients. CONCLUSIONS: We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19

Síndrome de Guillain-Barré asociado a zika; análisis de la cohorte delegacional en la región Veracruz norte durante 2016-2017 / Guillain-Barré syndrome associated with Zika virus infection: Analysis of a cohort from the region of northern Veracruz in 2016-2017

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Disfunción de barrera y síndrome de Guillain-Barré como exponentes del daño endotelial en la COVID-19 / Barrier dysfunction and Guillain-Barré syndrome as exponents of endothelial damage in COVID-19

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Síndrome de Guillain Barré asociado a infección por SARS-CoV-2 / Guillain-Barré syndrome associated with SARS-CoV-2 infection

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Síndrome de Guillain-Barré fatal tras infección por virus SARS-CoV2 / Fatal Guillain-Barre syndrome after infection with SARS-CoV-2

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Síndrome de guillain-barré tras infección por COVID-19 / Guillain-barré syndrome after covid-19 infection

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SARS-CoV-2, nuevo agente causal del síndrome de Guillain-Barré / SARS-CoV-2, a new causal agent of Guillain-Barré syndrome

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Síndrome de Guillain-Barré asociado a zika, experiencia americana. Estudio bibliométrico / Guillain-Barré syndrome associated with zika virus infection in the Americas: A bibliometric study

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Síndrome de Guillain-Barré como forma de presentación de la infección por SARS-CoV-2 / Guillain-Barré syndrome as the first manifestation of SARS-CoV-2 infection

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Síndrome de Guillain-Barré tras infección por SARS-CoV-2. Comentarios tras la publicación de 16 nuevos casos / Guillain-Barré syndrome associated with SARS-CoV-2 infection. Comments after 16 published cases

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Guillain-Barré syndrome associated with arboviruses in the state of Pernambuco in 2016 / Síndrome de Guillain-Barré associada à arboviroses no estado de Pernambuco em 2016 / Síndrome de Guillain-Barré asociado a arbovirosis en el Estado de Pernambuco en 2016

Abstract Introduction: In 2016, Brazil presented an increase in the notifications related to neurological syndromes with previous register of a febrile illness compatible with arboviruses, including Guillain-Barré syndrome (GBS). Such disease is responsible for the most frequent occurrence of flaccid paralysis in the world, causing bilateral ascending muscle weakness that might affect the respiratory tract. Objective: To investigate the incidence of Guillain-Barré syndrome associated with arboviruses in Pernambuco in 2016 and to describe the confirmed/probable cases. Method: This is an observational retrospective study of GBS cases with a background of infection from dengue, chikungunya, or Zika virus notified to the Pernambuco Health State Secretariat (SES-PE). Cases notified from January 1st to December 31st, 2016 were included, which were considered as possible GBS at the time of notification. The suspect cases were investigated and classified as confirmed/probable by the positive laboratory test result, excluding the possibility of infection. Results: Forty-three suspect cases of GBS after previous arbovirus infection were notified. From these, 23 were classified as confirmed/probable for the etiological agents chikungunya and/or dengue. The mean age of the affected individuals was 37.22 ± 21.29 years and they were mostly female (56.5%). The annual incidence of GBS after arbovirus infection was 0.24 cases per 100 thousand inhabitants in the state. The neurological condition was mainly characterized by the presence of movement (91.3%) and walking (78.3%) alterations. Conclusion: The findings of this research confirm the current set of evidence and show the likelihood of GBS being a severe neurological complication of these arboviruses.

Resumo Introdução: No Brasil, em 2016, houve aumento das notificações relacionadas às síndromes neurológicas com registro anterior de doença febril compatível com infecção por arboviroses, dentre elas a Síndrome de Guillain- Barré (SGB). Trata-se da ocorrência mais frequente de paralisia flácida no mundo, causa fraqueza muscular bilateral ascendente e pode atingir as vias respiratórias. Objetivo: Analisar a incidência da Síndrome de Guillain- Barré associada à arboviroses em Pernambuco no ano de 2016 e descrever os casos confirmados/prováveis. Método: Trata-se de um estudo observacional retrospectivo dos casos de SGB com histórico de infecção prévia por dengue, chikungunya ou vírus Zika, notificados à Secretaria Estadual de Saúde de Pernambuco (SES-PE). Foram incluídos casos notificados de 1º de janeiro a 31 de dezembro de 2016 considerados suspeitos de SGB no momento da notificação. Os casos suspeitos foram investigados e classificados como confirmados/prováveis através de resultado de exame laboratorial positivo, excluída a possibilidade de infecção. Resultados: Foram notificados 43 casos suspeitos de SGB após infecção prévia por arbovírus. Destes, 23 foram classificados como confirmados/prováveis para os agentes etiológicos chikungunya e/ou dengue, sendo a média de idade igual a 37,22 ± 21,29 anos e maioria do sexo feminino (56,5%). A incidência anual de SGB após infecção por arbovírus foi de 0,24 casos por 100 mil habitantes no estado. O quadro neurológico foi caracterizado prioritariamente pela presença de alterações motoras (91,3%) e na marcha (78,3%). Conclusão: Os achados da presente pesquisa acrescentam ao conjunto de evidências sobre a possibilidade de a SGB se apresentar como uma grave complicação neurológica dessas arboviroses.

Resumen Introducción: En Brasil, en 2016, hubo aumento de las notificaciones relacionadas con los síndromes neurológicos con registro anterior de enfermedad febril compatible con infección por arbovirosis, entre ellas el Síndrome de Guillain-Barré (SGB). Se trata de la aparición más frecuente de parálisis flácida en el mundo, causa debilidad muscular bilateral ascendente y puede alcanzar las vías respiratorias. Objetivo: Analizar la incidencia del Síndrome de Guillain-Barré asociada a los arbovirosis en Pernambuco en el año 2016 y describir los casos confirmados / probables. Método: Se trata de un estudio observacional retrospectivo de los casos de SGB con antecedentes de infección previa por dengue, chikungunya o virus Zika, notificados a la Secretaría Estatal de Salud de Pernambuco (SES-PE). Se incluyeron casos notificados del 1 de enero al 31 de diciembre de 2016 considerados sospechosos de SGB en el momento de la notificación. Los casos sospechosos fueron investigados y clasificados como confirmados / probables a través del resultado de un examen de laboratorio positivo, excluida la posibilidad de infección por otros agentes virales. Resultados: Se han notificado 43 casos sospechosos de SGB tras la infección previa por arbovirus. De estos, 23 fueron clasificados como confirmados / probables para los agentes etiológicos chikungunya y / o dengue, siendo la media de edad igual a 37,22 ± 21,29 años y la mayoría del sexo femenino (56,5%). La incidencia anual de SGB tras infección por arbovirus fue de 0,24 casos por 100 mil habitantes en el estado. El cuadro neurológico fue caracterizado prioritariamente por la presencia de alteraciones motoras (91,3%) y en la marcha (78,3%). Conclusión: Los hallazgos de la presente investigación añaden al conjunto de evidencias sobre la posibilidad de que la SGB se presente como una grave complicación neurológica de esas arbovirosis.