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1.
Mol Neurobiol ; 57(12): 4921-4928, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32813238

RESUMEN

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.


Asunto(s)
Betacoronavirus , Isquemia Encefálica/etiología , Infecciones por Coronavirus/fisiopatología , Pandemias , Neumonía Viral/fisiopatología , Sistema Renina-Angiotensina/fisiología , Accidente Cerebrovascular/etiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , Barrera Hematoencefálica , Isquemia Encefálica/epidemiología , Isquemia Encefálica/inmunología , Isquemia Encefálica/fisiopatología , Quimiotaxis de Leucocito , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/fisiopatología , Citocinas/fisiología , Encefalitis Viral/complicaciones , Encefalitis Viral/fisiopatología , Hemodinámica , Humanos , Inflamación , Modelos Inmunológicos , Modelos Neurológicos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/fisiopatología , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/etiología , Peptidil-Dipeptidasa A/fisiología , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Receptores Virales/fisiología , Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/fisiopatología
2.
Rev Med Virol ; 30(5): e2118, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32687681

RESUMEN

Human Coronaviruses (HCoVs) have long been known as respiratory viruses. However, there are reports of neurological findings in HCoV infections, particularly in patients infected with the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) amid Coronavirus disease 2019 (COVID-19) pandemic. Therefore, it is essential to interpret the interaction of HCoVs and the nervous system and apply this understanding to the COVID-19 pandemic. This review of the literature analyses how HCoVs, in general, and SARS-CoV-2, in particular, affect the nervous system, highlights the various underlying mechanisms, addresses the associated neurological and psychiatric manifestations, and identifies the neurological risk factors involved. This review of literature shows the magnitude of neurological conditions associated with HCoV infections, including SARS-CoV-2. This review emphasises, that, during HCoV outbreaks, such as COVID-19, a focus on early detection of neurotropism, alertness for the resulting neurological complications, and the recognition of neurological risk factors are crucial to reduce the workload on hospitals, particularly intensive-care units and neurological departments.


Asunto(s)
Encefalopatías/epidemiología , Infecciones por Coronavirus/epidemiología , Encefalitis Viral/epidemiología , Pandemias , Neumonía Viral/epidemiología , Síndrome Respiratorio Agudo Grave/epidemiología , Betacoronavirus/patogenicidad , Encefalopatías/fisiopatología , Encefalopatías/virología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Encefalitis Viral/fisiopatología , Encefalitis Viral/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Sistema Nervioso/fisiopatología , Sistema Nervioso/virología , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Virus del SRAS/patogenicidad , Síndrome Respiratorio Agudo Grave/mortalidad , Síndrome Respiratorio Agudo Grave/fisiopatología , Síndrome Respiratorio Agudo Grave/virología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
3.
J Stroke Cerebrovasc Dis ; 29(8): 104941, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32689643

RESUMEN

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.


Asunto(s)
Betacoronavirus/patogenicidad , Encéfalo/fisiopatología , Infecciones por Coronavirus/fisiopatología , Encefalitis Viral/fisiopatología , Neumonía Viral/fisiopatología , Accidente Cerebrovascular/fisiopatología , Betacoronavirus/metabolismo , Coagulación Sanguínea , Encéfalo/metabolismo , Encéfalo/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Encefalitis Viral/epidemiología , Encefalitis Viral/metabolismo , Encefalitis Viral/virología , Interacciones Microbiota-Huesped , Humanos , Mediadores de Inflamación/metabolismo , Estrés Oxidativo , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Neumonía Viral/virología , Sistema Renina-Angiotensina , Transducción de Señal , Glicoproteína de la Espiga del Coronavirus/metabolismo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/virología , Vasodilatación , Virulencia
5.
Brain Behav Immun ; 87: 18-22, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32240762

RESUMEN

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.


Asunto(s)
Infecciones por Coronavirus/fisiopatología , Enfermedades del Sistema Nervioso/fisiopatología , Neumonía Viral/fisiopatología , Betacoronavirus , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/fisiopatología , Coronavirus Humano 229E , Infecciones por Coronavirus/complicaciones , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Disgeusia/etiología , Disgeusia/fisiopatología , Encefalitis/etiología , Encefalitis/fisiopatología , Encefalitis Viral/etiología , Encefalitis Viral/fisiopatología , Síndrome de Guillain-Barré/etiología , Síndrome de Guillain-Barré/fisiopatología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Enfermedades del Sistema Nervioso/etiología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/virología , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Pandemias , Neumonía Viral/complicaciones , Polineuropatías/etiología , Polineuropatías/fisiopatología , Virus del SRAS , Convulsiones/etiología , Convulsiones/fisiopatología , Síndrome Respiratorio Agudo Grave/complicaciones , Síndrome Respiratorio Agudo Grave/fisiopatología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatología
6.
Clin Neurol Neurosurg ; 185: 105492, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31470359

RESUMEN

Neurological complications of Epstein Barr virus (EBV) infection are infrequent and may include occasionally encephalitis, usually with a benign evolution. We here report on an aggressive case of EBV encephalitis in a 14-year-old boy with extensive basal ganglia involvement, and to a lesser degree of brain cortex who presented atypically with akinetic mutism and non-convulsive status epilepticus, requiring intensive care but showed a favorable outcome. EBV encephalitis is uncommon and its best management is unclear. Its pathophysiology is not well understood but could include autoimmunity. Onconeuronal and synaptic antibodies were negative in serum and cerebrospinal fluid, including the dopamine D2 receptor. To the best of our knowledge, this is the first report to evaluate antibodies to D2 receptors in EBV encephalitis. Corticosteroid therapy is usually recommended but the use of acyclovir is controversial. Intensive care is required in severe cases to assure a favorable outcome.


Asunto(s)
Mutismo Acinético/fisiopatología , Enfermedades de los Ganglios Basales/fisiopatología , Encefalitis Viral/fisiopatología , Infecciones por Virus de Epstein-Barr/fisiopatología , Estado Epiléptico/fisiopatología , Adolescente , Mutismo Acinético/diagnóstico por imagen , Mutismo Acinético/inmunología , Mutismo Acinético/terapia , Anticonvulsivantes/uso terapéutico , Autoanticuerpos/inmunología , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/inmunología , Enfermedades de los Ganglios Basales/terapia , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/inmunología , Edema Encefálico/fisiopatología , Edema Encefálico/terapia , Cromonar , Electroencefalografía , Encefalitis Viral/diagnóstico , Encefalitis Viral/inmunología , Encefalitis Viral/terapia , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/terapia , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Receptores de Dopamina D2/inmunología , Recuperación de la Función , Estado Epiléptico/inmunología , Estado Epiléptico/terapia
7.
Pediatr Neurol ; 96: 70-73, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30935719

RESUMEN

BACKGROUND: Enterovirus-A71 causes outbreaks of brainstem encephalitis, ranging from self-limited disease to acute flaccid paralysis. The aim of this study was to assess the role of cerebrospinal fluid (CSF) neopterin as a biomarker of disease severity in children with enterovirus-related brainstem encephalitis. METHODS: A descriptive, prospective cohort study was conducted from April 2016 to March 2017 in a tertiary hospital. Pediatric patients with a diagnosis of brainstem encephalitis with or without myelitis due to enterovirus infection were enrolled. The final study group comprised a convenience sample including all patients with sufficient CSF volume for neopterin determination. The major variables considered in estimating the severity were the diagnosis of encephalomyelitis, the presence of lesions and extensive lesions on brain and spinal magnetic resonance imaging (MRI), hospital stay length greater than seven days, and sequelae at day 30. RESULTS: Of 60 patients, CSF neopterin could be measured in 36. Median age was 26 months (interquartile range: 19 to 32). Thirty-three were diagnosed with brainstem encephalitis and three with encephalomyelitis. Enterovirus-A71 was the only identified genotype (25 of 25). CSF neopterin levels were elevated (>61 nmol/L) in 33 of 36 (92%), with a median of 347 nmol/L (interquartile range: 204 to 525). CSF neopterin was useful to distinguish patients with lesions on MRI (area under the receiver operating characteristic curve = 0.76; P = 0.02) and extensive lesions (area under the receiver operating characteristic curve = 0.76; P = 0.04). CONCLUSIONS: This study suggests an association between CSF neopterin levels and the presence of inflammatory lesions on MRI.


Asunto(s)
Tronco Encefálico , Encefalitis Viral/líquido cefalorraquídeo , Encefalomielitis/líquido cefalorraquídeo , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/líquido cefalorraquídeo , Neopterin/líquido cefalorraquídeo , Tronco Encefálico/patología , Tronco Encefálico/fisiopatología , Tronco Encefálico/virología , Preescolar , Encefalitis Viral/patología , Encefalitis Viral/fisiopatología , Encefalitis Viral/virología , Encefalomielitis/patología , Encefalomielitis/fisiopatología , Encefalomielitis/virología , Infecciones por Enterovirus/patología , Infecciones por Enterovirus/fisiopatología , Infecciones por Enterovirus/virología , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos
8.
Neurology ; 92(21): e2406-e2420, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-31028126

RESUMEN

OBJECTIVE: To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection. METHODS: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak. RESULTS: Eighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13-17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12-75.22; p = 0.039). CONCLUSIONS: NeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.


Asunto(s)
Enfermedades de los Nervios Craneales/terapia , Encefalitis Viral/terapia , Encefalomielitis/terapia , Síndrome de Guillain-Barré/fisiopatología , Infección por el Virus Zika/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedades de los Nervios Craneales/metabolismo , Enfermedades de los Nervios Craneales/fisiopatología , Encefalitis Viral/metabolismo , Encefalitis Viral/fisiopatología , Encefalomielitis/metabolismo , Encefalomielitis/fisiopatología , Femenino , Hospitalización , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , ARN Viral/sangre , ARN Viral/líquido cefalorraquídeo , ARN Viral/orina , Respiración Artificial , Resultado del Tratamiento , Indias Occidentales , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/fisiopatología
9.
Brain Res ; 1707: 227-232, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30468725

RESUMEN

Cognitive and memory impairment are related to cholinergic dysfunction and are important complications of viral encephalitis, In view of paucity of studies on cholinergic dysfunction in encephalitis, this study has been undertaken. We report acetyl choline esterase (AChE) and muscurinic 2 (M2) receptor levels in herpes simplex encephalitis (HSE) and Japanese encephalitis (JE) patients, and correlate these with cognitive functions and MRI findings. Patients with JE and HSE were evaluated for consciousness, neurological and MRI findings, plasma AChE and M2 receptor levels on admission and after one year. Twenty-nine patients with JE and 23 with HSE were included. Admission AChE levels in JE (48.32 ±â€¯5.36 nmol/min/ml) and HSE (41.92 ±â€¯5.12 nmol/min/ml) were significantly lower compared with controls (70.50 ±â€¯8.30 nmol/min/ml). M2 receptor levels were also low in JE (4.52 ±â€¯0.56 ng/ml) and HSE (4.35 ±â€¯0.57 ng/ml) compared with controls (7.95 ±â€¯0.41 ng/ml). In JE, AChE activity (r = 0.43, p = 0.02) and M2 receptor levels (r = 0.43, p = 0.02) correlated with caudate involvement, and AChE activity (r = 0.76, p = 0.03) with Mini Mental State Examination ( MMSE) score. In HSE, M2 receptor levels (r = 0.53, p = 0.03) correlated with MMSE. The levels of AChE and M2 receptors increased at one year compared to the baseline, which was greater in JE than in HSE. Both AChE and M2 receptors were reduced in JE and HSE and correlated with cognition at one year. Recovery of these biomarkers was more in JE than HSE.


Asunto(s)
Encefalitis por Herpes Simple/fisiopatología , Encefalitis Japonesa/fisiopatología , Receptores de Superficie Celular/metabolismo , Acetilcolina , Acetilcolinesterasa , Adolescente , Adulto , Anciano , Encéfalo/fisiopatología , Niño , Colinérgicos , Encefalitis Viral/fisiopatología , Femenino , Humanos , India/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Receptor Muscarínico M2/análisis , Receptor Muscarínico M2/metabolismo , Receptores de Superficie Celular/análisis , Receptores Colinérgicos/análisis , Receptores Colinérgicos/metabolismo
10.
Annu Rev Virol ; 5(1): 255-272, 2018 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-30265628

RESUMEN

Flaviviruses are major emerging human pathogens on a global scale. Some flaviviruses can infect the central nervous system of the host and therefore are regarded as neurotropic. The most clinically relevant classical neurotropic flaviviruses include Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus. In this review, we focus on these flaviviruses and revisit the concepts of flaviviral neurotropism, neuropathogenicity, neuroinvasion, and resultant neuropathogenesis. We attempt to synthesize the current knowledge about interactions between the central nervous system and flaviviruses from the neuroanatomical and neuropathological perspectives and address some misconceptions and controversies. We hope that revisiting these neuropathological concepts will improve the understanding of flaviviral neuroinfections. This, in turn, may provide further guiding foundations for relevant studies of other emerging or geographically expanding flaviviruses with neuropathogenic potential, such as Zika virus and dengue virus, and pave the way for intelligent therapeutic strategies harnessing potentially beneficial, protective host responses to interfere with disease progression and outcome.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie)/patogenicidad , Virus de la Encefalitis Transmitidos por Garrapatas/patogenicidad , Encefalitis Viral/patología , Encefalitis Viral/virología , Interacciones Huésped-Patógeno , Virus del Nilo Occidental/patogenicidad , Animales , Encefalitis Viral/fisiopatología , Humanos , Tropismo Viral
11.
J Integr Neurosci ; 17(3-4): 493-501, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29710730

RESUMEN

OBJECTIVE: Our aim was to study the character of quantitative EEG of viral encephalitis. METHOD: Collect the EEG data of hospitalized children with viral encephalitis diagnosed by pediatricians from January 2013 to September 2016, and EEG data of normal cases at the same age were control group. Using quantitative EEG analysis technologies to obtain power spectrum value, power spectrum value, 1 power spectrum value, 12 power spectrum value, 21 power spectrum value, and 12 power spectrum value. Relative power spectrum values of 2 and were obtained by calculation. All the cases were divided into 5 groups according to the EEG character: age 3 group, age 4 group, age 5-6 group, age 7-9-year group, and age 10-14-year group. Viral encephalitis group and normal cases group were statistically compared to obtain characters of quantitative EEG with viral encephalitis. RESULTS: Power spectrum values and power spectrum values of 3-14-year-old cases with encephalitis increased. 1 power spectrum values existed in age 3 group with viral encephalitis and declined at the post-head lead, while 11 and 12 power spectrum values existed in age 4-14 group with viral encephalitis declined at the post-head lead. The value of 2 Power spectrum values of age 3-9 group was limited in diagnosing viral encephalitis. 1 and 12 power spectrum values decrease in age 10-14 group with viral encephalitis. Relative power spectrum values of 2 and increased in age 3-14 group with viral encephalitis; Relative power spectrum values of decreased in age 3-14 group with viral encephalitis, most lead of relative power spectrum decreased in age 3-14 group with viral encephalitis. CONCLUSION: The character of quantitative EEG of cases with viral encephalitis is similar to EEG, but more detailed, more precise, more intuitive and can be used for clinical diagnose of viral encephalitis.


Asunto(s)
Encéfalo/fisiopatología , Electroencefalografía , Encefalitis Viral/fisiopatología , Adolescente , Niño , Preescolar , Electroencefalografía/métodos , Encefalitis Viral/diagnóstico , Humanos , Procesamiento de Señales Asistido por Computador
13.
Clin Interv Aging ; 12: 1655-1659, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29062227

RESUMEN

PURPOSE: The number of cognitive deterioration patients has been steadily increasing as the population ages in China. Patients with cognitive deterioration demonstrated diverse patterns, often making the diagnosis difficult, especially in rapidly progressive cognitive deterioration (RPCD) patients. The purpose of this study was to exhibit the disease spectrum and frequency of noncerebrovascular RPCD in patients from a medical college hospital of southeastern China. MATERIALS AND METHODS: We performed a 2-year retrospective cohort study including 310 RPCD patients who had been admitted to the Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, from January 1, 2015 to December 31, 2016. RPCD patients' information on epidemiologic data and clinical aspects were collected. All the data were analyzed using SPSS. RESULTS: Of a total of 310 patients hospitalized for RPCD diagnosis, mean age of onset was 55.92±18.89 years. The most common cause of RPCD was viral encephalitis, accounting for 21.9% (68) of the cases, followed by Alzheimer's disease and autoimmune encephalitis, accounting for 14.5% (45) and 9.0% (28) of the cases, respectively. Creutzfeldt-Jakob disease accounted for 7.1% (22) of the cases. Patients in the secondary RPCD group tended to be younger than those in the primary RPCD group and experienced a more rapid progression course. CONCLUSION: Our study suggests that the most common causes of RPCD are secondary neurological diseases and most of them are potentially reversible under appropriate treatment of the underlying disease. The spectrum and frequency of RPCD in our cohort is comparable with a previous study performed in the European population.


Asunto(s)
Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/fisiopatología , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/fisiopatología , China/epidemiología , Síndrome de Creutzfeldt-Jakob/epidemiología , Síndrome de Creutzfeldt-Jakob/fisiopatología , Progresión de la Enfermedad , Encefalitis/epidemiología , Encefalitis/fisiopatología , Encefalitis Viral/epidemiología , Encefalitis Viral/fisiopatología , Femenino , Enfermedad de Hashimoto/epidemiología , Enfermedad de Hashimoto/fisiopatología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
J Neurosci ; 37(29): 6877-6893, 2017 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-28630251

RESUMEN

Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antiviral agents, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing the level of virus available for entry into the brain and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.SIGNIFICANCE STATEMENT Cytomegalovirus (CMV) can irreversibly damage the developing brain. No anti-CMV drugs are available for use during fetal development, and treatment during the neonatal period has substantial limitations. We studied the anti-CMV actions of valnoctamide (VCD), a psychiatric sedative that appears to lack teratogenicity and toxicity, in the newborn mouse brain, a developmental period that parallels that of an early second-trimester human fetus. In infected mice, subcutaneous VCD reaches the brain and suppresses viral replication within the CNS, rescuing the animals from CMV-induced brain defects and neurological problems. Treatment of uninfected control animals exerts no detectable adverse effects. VCD also blocks CMV replication in human fetal brain cells.


Asunto(s)
Amidas/administración & dosificación , Trastornos del Conocimiento/prevención & control , Trastornos del Conocimiento/fisiopatología , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/fisiopatología , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/fisiopatología , Animales , Animales Recién Nacidos , Antivirales/administración & dosificación , Trastornos del Conocimiento/patología , Infecciones por Citomegalovirus/patología , Relación Dosis-Respuesta a Droga , Encefalitis Viral/patología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Resultado del Tratamiento
15.
Clin Microbiol Infect ; 23(11): 874-881, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28344164

RESUMEN

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.


Asunto(s)
Tronco Encefálico/virología , Brotes de Enfermedades/estadística & datos numéricos , Encefalitis Viral , Enterovirus Humano A/genética , Infecciones por Enterovirus , Antiinflamatorios/uso terapéutico , Preescolar , Encefalitis Viral/epidemiología , Encefalitis Viral/fisiopatología , Encefalitis Viral/terapia , Encefalitis Viral/virología , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/fisiopatología , Infecciones por Enterovirus/terapia , Infecciones por Enterovirus/virología , Femenino , Humanos , Lactante , Masculino , Epidemiología Molecular , España/epidemiología
16.
BMC Infect Dis ; 17(1): 153, 2017 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-28212620

RESUMEN

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.


Asunto(s)
Encefalitis Viral/diagnóstico , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/virología , Hemorragia/diagnóstico , Edema Pulmonar/diagnóstico , Trastornos Respiratorios/diagnóstico , Autopsia , Niño , Preescolar , China/epidemiología , Coma , Brotes de Enfermedades , Progresión de la Enfermedad , Encefalitis Viral/mortalidad , Encefalitis Viral/fisiopatología , Enterovirus Humano A/aislamiento & purificación , Infecciones por Enterovirus/mortalidad , Infecciones por Enterovirus/fisiopatología , Femenino , Hemorragia/mortalidad , Hemorragia/fisiopatología , Humanos , Lactante , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Edema Pulmonar/mortalidad , Edema Pulmonar/fisiopatología , Trastornos Respiratorios/mortalidad , Trastornos Respiratorios/fisiopatología , Frecuencia Respiratoria/fisiología
17.
Int J Neurosci ; 127(1): 44-50, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26732732

RESUMEN

No biomarker has been established as a prognostic indicator of acute encephalopathy associated with various etiological factors. In this study, we examined useful prognostic biomarkers in patients with acute encephalopathy associated with respiratory syncytial virus (RSV) infection. The subjects were 11 children with RSV-associated encephalopathy admitted to our hospital. We measured the levels of interleukin (IL)-6, brain-derived neurotrophic factor (BDNF) and nitrogen oxide (NO)x in cerebrospinal fluid collected on the day of admission. Using the pediatric cerebral performance categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. Concerning neurologic prognosis, sequelae were noted in more than 50% of the subjects. There was no association between prognosis and age/sex. Increases in the levels of all biomarkers were observed in all subjects. IL-6 and BDNF levels were correlated with PCPC score, but not with NOx. Of the biomarkers investigated, the IL-6 and BDNF levels in cerebrospinal fluid were shown to be correlated with neurologic prognosis. Because many patients with this disease had severe sequelae, assessment should be conducted by early evaluation of the biomarkers examined in this study with respect to the clinical course.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/fisiopatología , Interleucina-6/líquido cefalorraquídeo , Óxidos de Nitrógeno/líquido cefalorraquídeo , Infecciones por Virus Sincitial Respiratorio/líquido cefalorraquídeo , Índice de Severidad de la Enfermedad , Adolescente , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Masculino , Pronóstico
18.
Virus Res ; 227: 220-230, 2017 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-27794455

RESUMEN

OBJECTIVES: Human Immunodeficiency Virus (HIV) infection can induce neurocognitive complications classified as HIV-associated neurocognitive disorder (HAND). The chitinase family is associated with innate immunity cells and many infectious diseases. METHODS: We analyzed microarray datasets obtained from NCBI in order to verify the expression of chitinase family genes in hippocampus of uninfected rhesus macaques versus those with histopathologic evidence of Simian Immunodeficiency Virus Encephalitis (SIVE). Moreover, we have analysed two human microarray datasets to verify the results obtained in macaques hippocampus affected by SIVE. For these studies, we have also used the open source tools Genome-scale Integrated Analysis of gene Networks in Tissues (GIANT) to identify the chitinase genes network. RESULTS: CHIT1, CHI3L1 and CHI3L2 levels were significantly increased in SIVE hippocampus as compared to non-infected control specimens. Furthermore, we found a negative correlation between CHIA vs. Brain Viral Load (BVL). These data was confirmed partially in human brain section of HAD/HIVE subjects. Also, we showed that HIV-1 was able to modulate the expression of CHIT1, CHI3L1, CHI3L2 and CHID1 in human macrophages. CONCLUSIONS: These results suggest that chitinase gene expression is altered in SIVE and in HAD/HIVE brain sections and call for more studies examining whether this is a protective immunological reaction or a destructive tissue response to encephalitis.


Asunto(s)
Quitinasas/genética , Encefalitis Viral/genética , Encefalitis Viral/virología , Expresión Génica , VIH-1 , Virus de la Inmunodeficiencia de los Simios , Animales , Disfunción Cognitiva , Susceptibilidad a Enfermedades , Encefalitis Viral/metabolismo , Encefalitis Viral/fisiopatología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Hipocampo/metabolismo , Hipocampo/virología , Humanos , Macaca mulatta , Macrófagos/metabolismo , Macrófagos/virología , Masculino , Familia de Multigenes , ARN Mensajero/genética , ARN Mensajero/metabolismo , Carga Viral
19.
Acta Ophthalmol ; 95(1): 66-73, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27966268

RESUMEN

PURPOSE: To evaluate ophthalmological abnormalities in children with acute encephalitis. METHODS: Thirty-six children included in a hospital-based prospectively and consecutively collected cohort of children with acute encephalitis were investigated for ophthalmological abnormalities. The investigation included clinical ophthalmological examination, fundus photography, neuro-ophthalmological examinations as well as visual and stereo acuity. Results on laboratory examinations, clinical findings, neuroimaging and electroencephalography registrations were recorded for all children. RESULTS: The median age was 4.0 years (Interquartile Range 1.9-9.8). The aetiology was identified in 74% of cases. Three of 36 patients were found to have abnormal ophthalmological findings related to the encephalitis. Transient sixth nerve palsy was seen in a 15-year-old child and transient visual impairment was seen in a 3.5-year-old child. Bilateral miosis and ptosis, i.e. autonomic nerve system symptoms, were seen in an 11-month-old child, with herpes simplex 1 and N-methyl-d-aspartate receptor antibody encephalitis. All three children recovered and improved their ophthalmological function with time. CONCLUSION: Only 3 of 36 children were found to have ophthalmological abnormalities due to encephalitis and they all improved with time. Thus, ophthalmological consultation does not seem to fit in a screening programme for childhood encephalitis but should be considered in selected cases.


Asunto(s)
Encefalitis Viral/complicaciones , Oftalmopatías/etiología , Enfermedad Aguda , Adolescente , Niño , Preescolar , Electroencefalografía , Encefalitis Viral/diagnóstico , Encefalitis Viral/fisiopatología , Oftalmopatías/diagnóstico , Oftalmopatías/fisiopatología , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Agudeza Visual/fisiología
20.
Emerg Microbes Infect ; 5(7): e75, 2016 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-27436364

RESUMEN

Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases.


Asunto(s)
Descubrimiento de Drogas , Enterovirus Humano A/inmunología , Infecciones por Enterovirus/prevención & control , Enfermedad de Boca, Mano y Pie/prevención & control , Vacunas Virales , Animales , China , Aprobación de Drogas , Encefalitis Viral/fisiopatología , Encefalitis Viral/prevención & control , Encefalitis Viral/virología , Enterovirus/clasificación , Enterovirus/inmunología , Enterovirus Humano B/inmunología , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/inmunología , Infecciones por Enterovirus/virología , Genotipo , Humanos , Miocarditis/fisiopatología , Miocarditis/prevención & control , Miocarditis/virología , Vacunas de Productos Inactivados
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