FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate or aggressive disease course is very limited. There is, therefore, a need for integrated predictive tools to inform individualised treatment decision making. PARTICIPANTS: Established with the aim of addressing this need for individualised predictive tools, FutureMS is a nationally representative, prospective observational cohort study of 440 adults with a new diagnosis of relapsing-remitting MS living in Scotland at the time of diagnosis between May 2016 and March 2019. FINDINGS TO DATE: The study aims to explore the pathobiology and determinants of disease heterogeneity in MS and combines detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow-up at year 1 is complete. Here, we describe the cohort design and present a profile of the participants at baseline and 1 year of follow-up. FUTURE PLANS: A third follow-up wave for the cohort has recently begun at 5 years after first visit and a further wave of follow-up is funded for year 10. Longer-term follow-up is anticipated thereafter.

Síndrome post-COVID-19: epidemiología, criterios diagnósticos y mecanismos patogénicos implicados / Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved

Introducción: Numerosos pacientes con COVID-19 leve o grave no tienen una recuperación completa y presentan una gran variedad de síntomas crónicos durante semanas o meses tras la infección, con frecuencia de carácter neurológico, cognitivo o psiquiátrico. Se revisan las evidencias epidemiológicas, los criterios diagnósticos y la patogenia del síndrome post-COVID-19. Desarrollo: El síndrome post-COVID-19 se define por la persistencia de signos y síntomas clínicos que surgen durante o después de padecer la COVID-19, permanecen más de 12 semanas y no se explican por un diagnóstico alternativo. Los síntomas pueden fluctuar o causar brotes. Es una entidad heterogénea que incluye el síndrome de fatiga crónica posvírica, la secuela de múltiples órganos y los efectos de la hospitalización grave/síndrome poscuidados intensivos. Se ha descrito en pacientes con COVID-19 leve o grave y con independencia de la gravedad de los síntomas en la fase aguda. Un 10-65% de los supervivientes que padeció COVID-19 leve/moderada presenta síntomas de síndrome post-COVID-19 durante 12 semanas o más. A los seis meses, los sujetos relatan un promedio de 14 síntomas persistentes. Los síntomas más frecuentes son fatiga, disnea, alteración de la atención, de la concentración, de la memoria y del sueño, ansiedad y depresión. Se desconocen los mecanismos biológicos que subyacen, aunque una respuesta autoinmunitaria e inflamatoria anómala o excesiva puede tener un papel importante. Conclusiones: Las manifestaciones clínicas son diversas, fluctuantes y variables, aunque predominan la fatiga y las quejas neurocognitivas. No existe un consenso definido sobre el síndrome post-COVID-19 y sus criterios diagnósticos no se han sometido a una evaluación psicométrica adecuada.(AU)

Introduction: Many patients with mild or severe COVID-19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection, often of a neurological, cognitive or psychiatric nature. The epidemiological evidence, diagnostic criteria and pathogenesis of post-COVID-19 syndrome are reviewed. Development: Post-COVID-19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID-19, persist for more than 12 weeks and cannot be explained by an alternative diagnosis. The symptoms can fluctuate or cause relapses. It is a heterogeneous condition that includes post-viral chronic fatigue syndrome, sequelae in multiple organs and the effects of severe hospitalisation/post-intensive care syndrome. It has been reported in patients with mild or severe COVID-19 and irrespective of the severity of the symptoms in the acute phase. Between 10% and 65% of survivors who had mild/moderate COVID-19 present symptoms of post-COVID-19 syndrome for 12 weeks or more. At six months, subjects report an average of 14 persistent symptoms. The most common symptoms are fatigue, dyspnoea, anxiety, depression, and impaired attention, concentration, memory and sleep. The underlying biological mechanisms are unknown, although an abnormal or excessive autoimmune and inflammatory response may play an important role. Conclusions: Clinical manifestations are diverse, fluctuating and variable, although fatigue and neurocognitive complaints predominate. There is no defined consensus on post-COVID-19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation.(AU)

[Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved]. / Síndrome post-COVID-19: epidemiología, criterios diagnósticos y mecanismos patogénicos implicados.

INTRODUCTION: Many patients with mild or severe COVID-19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection, often of a neurological, cognitive or psychiatric nature. The epidemiological evidence, diagnostic criteria and pathogenesis of post-COVID-19 syndrome are reviewed. DEVELOPMENT: Post-COVID-19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID-19, persist for more than 12 weeks and cannot be explained by an alternative diagnosis. The symptoms can fluctuate or cause relapses. It is a heterogeneous condition that includes post-viral chronic fatigue syndrome, sequelae in multiple organs and the effects of severe hospitalisation/post-intensive care syndrome. It has been reported in patients with mild or severe COVID-19 and irrespective of the severity of the symptoms in the acute phase. Between 10% and 65% of survivors who had mild/moderate COVID-19 present symptoms of post-COVID-19 syndrome for 12 weeks or more. At six months, subjects report an average of 14 persistent symptoms. The most common symptoms are fatigue, dyspnoea, anxiety, depression, and impaired attention, concentration, memory and sleep. The underlying biological mechanisms are unknown, although an abnormal or excessive autoimmune and inflammatory response may play an important role. CONCLUSIONS: Clinical manifestations are diverse, fluctuating and variable, although fatigue and neurocognitive complaints predominate. There is no defined consensus on post-COVID-19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation.

TITLE: Síndrome post-COVID-19: epidemiología, criterios diagnósticos y mecanismos patogénicos implicados.Introducción. Numerosos pacientes con COVID-19 leve o grave no tienen una recuperación completa y presentan una gran variedad de síntomas crónicos durante semanas o meses tras la infección, con frecuencia de carácter neurológico, cognitivo o psiquiátrico. Se revisan las evidencias epidemiológicas, los criterios diagnósticos y la patogenia del síndrome post-COVID-19. Desarrollo. El síndrome post-COVID-19 se define por la persistencia de signos y síntomas clínicos que surgen durante o después de padecer la COVID-19, permanecen más de 12 semanas y no se explican por un diagnóstico alternativo. Los síntomas pueden fluctuar o causar brotes. Es una entidad heterogénea que incluye el síndrome de fatiga crónica posvírica, la secuela de múltiples órganos y los efectos de la hospitalización grave/síndrome poscuidados intensivos. Se ha descrito en pacientes con COVID-19 leve o grave y con independencia de la gravedad de los síntomas en la fase aguda. Un 10-65% de los supervivientes que padeció COVID-19 leve/moderada presenta síntomas de síndrome post-COVID-19 durante 12 semanas o más. A los seis meses, los sujetos relatan un promedio de 14 síntomas persistentes. Los síntomas más frecuentes son fatiga, disnea, alteración de la atención, de la concentración, de la memoria y del sueño, ansiedad y depresión. Se desconocen los mecanismos biológicos que subyacen, aunque una respuesta autoinmunitaria e inflamatoria anómala o excesiva puede tener un papel importante. Conclusiones. Las manifestaciones clínicas son diversas, fluctuantes y variables, aunque predominan la fatiga y las quejas neurocognitivas. No existe un consenso definido sobre el síndrome post-COVID-19 y sus criterios diagnósticos no se han sometido a una evaluación psicométrica adecuada.

Epidemiology, pathophysiology, and classification of the neurological symptoms of post-COVID-19 syndrome.

Introduction: Post-COVID-19 syndrome is a series of chronic signs and symptoms that may appear after SARS-CoV-2 infection, including fatigue, dyspnoea, chest pain, palpitations, anxiety, depression, and joint and muscle pain. The purpose of this study was to review the controversies on post-COVID-19 syndrome, the frequency of neurological symptoms, and the potential pathophysiological mechanisms. Methods: We present a narrative review of studies published in PubMed since the beginning of the pandemic (January 2020-July 2021). Results: Patients with history of COVID-19 have been found to present persistent neurological symptoms, including cognitive complaints, memory and concentration problems, headache, anosmia, ageusia, vertigo, and insomnia. Post-COVID-19 syndrome is a heterogeneous disease that lacks a universally accepted definition, which may explain the great variability in the estimated prevalence (2.3%-85%) and symptom duration. The criteria differentiating post-COVID-19 syndrome from chronic fatigue syndrome or critical illness syndrome are ambiguous. Risk factors include older age, female sex, certain comorbidities, and greater number of symptoms in the acute phase. The pathophysiology of the syndrome is largely unknown, although it is probably multifactorial, including immunological mechanisms, neural network dysfunction, neurotransmitter alterations, persistent viral damage, and functional impairment. Conclusions: Post-COVID-19 syndrome may present after mild or even asymptomatic SARS-CoV-2 infection, causing limitations in activities of daily living and in quality of life. Further research will clarify the origin and most appropriate management of these neurological alterations.

Introducción: El término "síndrome post-COVID" se emplea para describir una serie de signos y síntomas crónicos que pueden surgir tras la infección por el virus SARS-CoV-2, como fatiga, disnea, dolor torácico, palpitaciones, ansiedad, depresión, dolores articulares y musculares entre otros. El objetivo es revisar las controversias asociadas al síndrome post-COVID-19, la frecuencia de los síntomas neurológicos y su posible fisiopatología. Métodos: Revisión narrativa crítica de los estudios publicados desde el inicio de la pandemia en pubmed (enero 2020 a julio 2021). Resultados: Síntomas neurológicos persistentes (quejas cognitivas, problemas de memoria y concentración; cefalea, anosmia, ageusia, vértigo, insomnio, etc) se han descrito en personas que padecieron COVID-19. El síndrome post-COVID-19 no es una entidad homogénea y no tiene una definición universalmente aceptada, lo que explica la variación en las estimaciones sobre prevalencia (2,3%­85%) y duración de los síntomas. Los criterios que lo distinguen del síndrome de fatiga crónica o el síndrome del paciente crítico son ambiguos. Los factores de riesgo incluyen edad, sexo (mujer), comorbidades, y número de síntomas en la fase aguda. La fisiopatología es en gran medida desconocida, pero probablemente multifactorial, incluyendo mecanismos inmunológicos, disfunción de redes neuronales y alteración de neurotransmisores, daño viral persistente, y cuadros de origen funcional, entre otros. Conclusiones: Los síntomas post-COVID-19 pueden surgir tras padecer una infección leve o incluso asintomática, y causa limitaciones en las actividades de la vida diaria y calidad de vida. El progreso en la investigación nos ayudará a aclarar el origen y manejo de estas complejas alteraciones neurológicas.

Neurological complications of coronavirus and COVID-19. / Complicaciones neurológicas por coronavirus y COVID-19.

INTRODUCTION: Clinical and experimental studies have shown that the coronavirus family has a certain tropism for the central nervous system. Seven types of coronavirus can infect humans. DEVELOPMENT: Coronaviruses are not always confined to the respiratory tract, and under certain conditions they can invade the central nervous system and cause neurological pathologies. The potential for neuroinvasion is well documented in most human coronaviruses (OC-43, 229E, MERS and SARS) and in some animal coronaviruses (porcine haemagglutinating encephalomyelitis coronavirus). Neurological symptoms have been reported in patients affected by COVID-19, such as headache, dizziness, myalgia and anosmia, as well as cases of encephalopathy, encephalitis, necrotising haemorrhagic encephalopathy, stroke, epileptic seizures, rhabdomyolysis and Guillain-Barre syndrome, associated with SARS-CoV-2 infection. CONCLUSIONS: Future epidemiological studies and case records should elucidate the real incidence of these neurological complications, their pathogenic mechanisms and their therapeutic options.

TITLE: Complicaciones neurológicas por coronavirus y COVID-19.Introducción. Estudios clínicos y experimentales han demostrado que la familia de los coronavirus tiene un cierto tropismo por el sistema nervioso central. Siete tipos de coronavirus pueden contagiar al ser humano. Desarrollo. Los coronavirus no siempre permanecen confinados en el tracto respiratorio, y en determinadas condiciones pueden invadir el sistema nervioso central y causar patologías neurológicas. La capacidad potencial de neuroinvasión está bien documentada en la mayor parte de los coronavirus humanos (OC-43, 229E, MERS y SARS) y en algunos coronavirus animales (coronavirus de la encefalomielitis hemaglutinante porcina). Se han descrito síntomas neurológicos en pacientes afectos por COVID-19, como cefalea, mareo, mialgias y anosmia, así como casos de encefalopatía, encefalitis, encefalopatía necrotizante hemorrágica, ictus, crisis epilépticas, rabdomiólisis y síndrome de Guillain-Barré, asociados a la infección por el SARS-CoV-2. Conclusiones. Futuros estudios epidemiológicos y registros de casos deben elucidar la incidencia real de estas complicaciones neurológicas, sus mecanismos patogénicos y sus opciones terapéuticas.

[Neurological complications associated with dengue virus infection]. / Complicaciones neurologicas asociadas a la infeccion por el virus del dengue.

INTRODUCTION: Dengue is an arboviral infection caused by the dengue virus. The neurological complications associated with this infection are reviewed. DEVELOPMENT: The neurotropic nature of dengue virus has been confirmed in epidemiological studies, case series and histopathological studies. The range of neurological complications is 5.6-14.6%, and they are more frequent in serotypes 1 and 3. Encephalopathy is the most common neurological syndrome (0.5-6%) and its prevalence is higher in children and adolescents. The detection of the viral antigen in brain tissue and the presence of pleocytosis or RNA in cerebrospinal fluid are evidence of the neurotropic nature of dengue virus, which manifests itself in the form of encephalitis. Neurological syndromes during convalescence (disseminated acute cerebellitis, opsoclonus-myoclonus syndrome, mononeuritis, poly-radiculoneuritis and plexitis) appear to be immunomediated. Myelitis can occur during acute dengue virus infection and through an immunomediated mechanism in the convalescence phase. Myalgias, myositis, rhabdomyolysis and hypokalemic paralysis are examples of muscular dysfunction associated with the dengue virus. The incidence of stroke is 0.26%, and may be ischaemic or haemorrhagic. Ophthalmological complications include maculopathy, retinal haemorrhage, optic neuropathy and vitritis. CONCLUSIONS: The spectrum of neurological complications from dengue virus is broad. There are no reliable data on its real incidence because most of the studies published to date are isolated series or cases.

TITLE: Complicaciones neurologicas asociadas a la infeccion por el virus del dengue.Introduccion. El dengue es una infeccion arboviral causada por el virus del dengue. Se revisan las complicaciones neurologicas asociadas a dicha infeccion. Desarrollo. El caracter neurotropo del virus del dengue se ha confirmado en estudios epidemiologicos, series de casos y estudios histopatologicos. El rango de complicaciones neurologicas es del 5,6-14,6%, y son mas frecuentes en los serotipos 1 y 3. La encefalopatia es el sindrome neurologico mas comun (0,5-6%); su prevalencia es mayor en los niños y los adolescentes. La deteccion del antigeno viral en el tejido cerebral y la presencia de pleocitosis o ARN en el liquido cefalorraquideo son evidencia del caracter neurotropo del virus del dengue, que se manifiesta en forma de encefalitis. Los sindromes neurologicos durante la fase de convalecencia (encefalomielitis aguda diseminada, cerebelitis, opsoclonia-mioclonia, mononeuritis, polirradiculoneuritis y plexitis) parecen ser inmunomediados. La mielitis puede suceder durante la infeccion aguda por el virus del dengue y por un mecanismo inmunomediado en la fase de convalecencia. Mialgias, miositis, rabdomiolisis y paralisis hipopotasemica son ejemplos de disfuncion muscular asociada al virus del dengue. La incidencia de ictus es del 0,26%, y puede ser isquemico o hemorragico. Las complicaciones oftalmologicas incluyen maculopatia, hemorragia retiniana, neuropatia optica y vitritis. Conclusiones. El espectro de complicaciones neurologicas por el virus del dengue es amplio. No existen datos fiables sobre su incidencia real porque la mayor parte de los estudios publicados son series o casos aislados.

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.

INTRODUCTION: The American continent is very rich in psychoactive plants and fungi, and many pre-Columbian Mesoamerican cultures used them for magical, therapeutic and religious purposes. OBJECTIVES: The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. RESULTS: Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp contains bufotoxins with hallucinogenic properties, and was used since the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. CONCLUSIONS: The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica.

High-altitude headache and acute mountain sickness.

INTRODUCTION: Headache is the most common complication associated with exposure to high altitude, and can appear as an isolated high-altitude headache (HAH) or in conjunction with acute mountain sickness (AMS). The purpose of this article is to review several aspects related to diagnosis and treatment of HAH. DEVELOPMENT: HAH occurs in 80% of all individuals at altitudes higher than 3000 meters. The second edition of ICHD-II includes HAH in the chapter entitled "Headaches attributed to disorder of homeostasis". Hypoxia elicits a neurohumoral and haemodynamic response that may provoke increased capillary pressure and oedema. Hypoxia-induced cerebral vasodilation is a probable cause of HAH. The main symptom of AMS is headache, frequently accompanied by sleep disorders, fatigue, dizziness and instability, nausea and anorexia. Some degree of individual susceptibility and considerable inter-individual variability seem to be present in AMS. High-altitude cerebral oedema is the most severe form of AMS, and may occur above 2500 meters. Brain MRI studies have found variable degrees of oedema in subcortical white matter and the splenium of the corpus callosum. HAH can be treated with paracetamol or ibuprofen. Pharmacological treatment of AMS is intended to increase ventilatory drive with drugs such as acetazolamide, and reduce inflammation and cytokine release by means of steroids. CONCLUSIONS: Symptom escalation seems to be present along the continuum containing HAH, AMS, and high-altitude cerebral oedema.

Curares y timbós, venenos del Amazonas / Curares and timbós, poisons used in the Amazon

Introducción. Los indígenas que habitaban los ríos Orinoco y Amazonas emplearon durante siglos diversos venenos de origen vegetal. Se revisan los aspectos históricos y etnográficos del uso de curares y timbós en la región amazónica. Desarrollo. El curare se prepara hirviendo las raíces, corteza y tallos de diversas plantas de las familias Loganiaceae (Strychnos) y Menispermaceae (Chondrodendron, Curarea y Abuta). Los curares de la Amazonía oriental proceden de diferentes especies de Strychnos que contienen alcaloides cuaternarios, que actúan como bloqueadores de la unión neuromuscular. Se emplean para cazar animales salvajes y la muerte se produce por parálisis de los músculos esqueléticos. Los primeros músculos que se paralizan son los oculares, cuello y nuca, y después los miembros; el diafragma es el músculo que más tarda en paralizarse. Las primeras crónicas que relataron su uso proceden de Fernández de Oviedo, Cristoval de Acuña, Antonio de Ulloa y José Gumilla. La Condamine, Humboldt, Waterton y Schomburgk, entre otros, llevaron a cabo diversos estudios etnobotánicos sobre el curare. Los venenos ictiotóxicos de origen vegetal, llamados timbós o barbascos, se caracterizan por una gran solubilidad, rápida difusión y elevada actividad. Al menos 70 especies vegetales se emplean para intoxicar los peces en los afluentes del Amazonas y facilitar su pesca. Sapindáceas, papilionáceas, euforbiáceas y teofrastáceas contienen sustancias ictiotóxicas, como rotenona o saponinas. Conclusión. Los relatos etnohistóricos y etnográficos muestran un gran conocimiento de las propiedades tóxicas de los curares y timbós por parte de las culturas amazónicas (AU)

Introduction. The natives that dwell along the banks of the Orinoco and Amazon rivers have used different poisons from plants for centuries. The study reviews the historical and ethnographic aspects of the use of curares and timbós in the Amazonian region. Development. Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrodendron, Curarea and Abuta). The curares of the eastern Amazon are extracted from different species of Strychnos that contain quaternary alkaloids, which act by blocking the neuromuscular junction. They are used to hunt wild animals and death comes about due to paralysis of the skeletal muscles. The first muscles to be paralysed are those of the eyes, nose and neck, and then those in the limbs; the diaphragm is the muscle that takes the longest to become paralysed. The earliest chronicles reporting their use were written by Fernández de Oviedo, Cristoval de Acuña, Antonio de Ulloa and José Gumilla. La Condamine, Humbolt, Waterton and Schomburgk, among others, carried out a number of different ethnobotanical studies on curare. The ichthyotoxic poisons from plants, which are known as timbós or barbascos, are characterised by their high level of solubility, their fast diffusion and their high rate of activity. At least 70 plant species are used to poison the fish in the tributaries of the Amazon with the aim of make fishing easier. Sapindaceae, Papilionaceae, Euphorbiaceae and Theophrastaceae contain ichthyotoxic substances, such as rotenone or saponins. Conclusions. Ethnohistorical and ethnographic accounts show that the Amazonian cultures have a deep understanding of the toxic properties of curares and timbós (AU)