RESUMO
Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. This review propounds the relationship between the deregulation of T helper cells and hypoxia, mainly Th17 and HIF-1α molecular pathways, events that are involved in the occurrence of the neuroinflammation. The clinical expression of neuroinflammation is included in prevalent pathologies such as multiple sclerosis, Guillain-Barré syndrome, and Alzheimer's disease, among others. In addition, therapeutic targets are analyzed in relation to the pathways that induced neuroinflammation.
Assuntos
Síndrome de Guillain-Barré , Doenças Neuroinflamatórias , Humanos , Síndrome de Guillain-Barré/patologia , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células Th17RESUMO
BACKGROUND: This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barré syndrome (GBS) in Barranquilla, Colombia. METHODS: Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS. RESULTS: Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of ≥ 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group. CONCLUSIONS: Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.
Assuntos
Depressão/epidemiologia , Síndrome de Guillain-Barré/etiologia , Qualidade de Vida , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Depressão/diagnóstico , Surtos de Doenças , Feminino , Seguimentos , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estados Unidos/epidemiologia , Adulto Jovem , Infecção por Zika virus/virologiaRESUMO
BACKGROUND: Guillain-Barre Syndrome (GBS) is considered a complex disorder with significant environmental effect and genetic susceptibility. Genetic polymorphisms in CD1E, CD1A, IL-17, and/or ICAM1 had been proposed as susceptibility genetic variants for GBS mainly in Caucasian population. This study explores the association between selected polymorphisms in these genes and GBS susceptibility in confirmed GBS cases reported in mestizo population from northern Peru during the most recent GBS outbreak of May 2018. METHODS: A total of nine nonrelated cases and 11 controls were sequenced for the polymorphic regions of CD1A, CD1E, IL-17, and ICAM1. RESULTS: We found a significant protective association between heterozygous GA genotype in ICAM1 (241Gly/Arg) and GBS (p < .047). IL-17 was monomorphic in both controls and patients. No significant differences were found in the frequency of SNPs in CD1A and CD1E between the group with GBS patients and healthy controls. CONCLUSION: ICAM1 polymorphisms might be considered as potential genetic markers of GBS susceptibility. Further studies with larger sample size will be required to validate these findings.
Assuntos
Antígenos CD1/genética , Síndrome de Guillain-Barré/patologia , Molécula 1 de Adesão Intercelular/genética , Interleucina-17/genética , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Síndrome de Guillain-Barré/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Polimorfismo de Nucleotídeo Único , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: Countries with ongoing outbreaks of Zika virus have observed a notable rise in reported cases of Guillain-Barré syndrome (GBS), with mounting evidence of a causal link between Zika virus infection and the neurological syndrome. However, the risk of GBS following a Zika virus infection is not well characterized. In this work, we used data from 11 locations with publicly available data to estimate the risk of GBS following an infection with Zika virus, as well as the location-specific incidence of infection and the number of suspect GBS cases reported per infection. METHODS: We built a mathematical inference framework utilizing data from 11 locations that had reported suspect Zika and GBS cases, two with completed outbreaks prior to 2015 (French Polynesia and Yap) and nine others in the Americas covering partial outbreaks and where transmission was ongoing as of early 2017. RESULTS: We estimated that 2.0 (95% credible interval 0.5-4.5) reported GBS cases may occur per 10,000 Zika virus infections. The frequency of reported suspect Zika cases varied substantially and was highly uncertain, with a mean of 0.11 (95% credible interval 0.01-0.24) suspect cases reported per infection. CONCLUSIONS: These estimates can help efforts to prepare for the GBS cases that may occur during Zika epidemics and highlight the need to better understand the relationship between infection and the reported incidence of clinical disease.
Assuntos
Síndrome de Guillain-Barré/etiologia , Infecção por Zika virus/complicações , Zika virus/patogenicidade , Surtos de Doenças , Feminino , Síndrome de Guillain-Barré/patologia , Humanos , Incidência , Masculino , Infecção por Zika virus/patologiaRESUMO
Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.
Assuntos
Doenças Transmissíveis/patologia , Síndrome de Guillain-Barré/patologia , Mielite Transversa/patologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/microbiologia , Síndrome de Guillain-Barré/virologia , Humanos , Imunidade , Mielite Transversa/imunologia , Mielite Transversa/microbiologia , Mielite Transversa/virologiaRESUMO
Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.
Assuntos
Autopsia , Coinfecção/virologia , Síndrome de Guillain-Barré/complicações , Infecção por Zika virus/complicações , Idoso , Coinfecção/patologia , Síndrome de Guillain-Barré/patologia , Síndrome de Guillain-Barré/virologia , Humanos , Masculino , Porto Rico , Infecção por Zika virus/patologia , Infecção por Zika virus/virologiaAssuntos
Encefalomielite Aguda Disseminada/diagnóstico por imagem , Síndrome de Guillain-Barré/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Pré-Escolar , Encefalomielite Aguda Disseminada/complicações , Encefalomielite Aguda Disseminada/patologia , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/patologia , Humanos , Imageamento por Ressonância Magnética , MasculinoAssuntos
Dengue/complicações , Síndrome de Guillain-Barré/etiologia , Meningoencefalite/etiologia , Adulto , Dengue/líquido cefalorraquidiano , Dengue/patologia , Feminino , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/patologia , Humanos , Inflamação , Imageamento por Ressonância Magnética , Masculino , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/patologia , Pessoa de Meia-Idade , Neuroimagem , Estudos RetrospectivosRESUMO
An experimental model of Guillain-Barré Syndrome has been established in recent years. Rabbits develop disease upon immunization with a single dose of an emulsion containing bovine brain gangliosides, KLH and complete Freund's adjuvant. Within a period of four to ten weeks after immunization, they began to produce anti-ganglioside IgG-antibodies first, and to show clinical signs of neuropathy afterwards. In addition to gangliosides, KLH is a requirement for antibody production and disease triggering. Although KLH is commonly used as an immunological carrier protein, an anti-KLH-specific immune response was necessary for induction of both events. KLH is a glycoprotein carrying most of the immunogenicity in its glycan moiety. Between 20% to 80% of anti-ganglioside IgG-antibodies present in sick rabbit sera cross-reacted with KLH, indicating that both immune responses are related. The terminal Gal-ß(1,3)-GalNAc glycan (present in gangliosides and KLH) is proposed as "key" antigenic determinant involved in inducing the anti-ganglioside immune response. These results are discussed in the context of the "binding site drift" hypothesis.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Formação de Anticorpos/efeitos dos fármacos , Síndrome de Guillain-Barré , Hemocianinas/efeitos adversos , Imunização/efeitos adversos , Modelos Imunológicos , Adjuvantes Imunológicos/farmacologia , Animais , Modelos Animais de Doenças , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/patologia , Hemocianinas/farmacologia , Humanos , CoelhosRESUMO
El Virus ZIKA se extendió por muchos países y se vinculó a Sindrome de Guillain Barre en una alta proporción de pacientes. Objetivos: determinar el comportamiento clínicoepidemiológico de Síndrome de Guillain Barré (SGB) e infección por ZIKV en el Hospital Ruíz y Páez, Ciudad Bolívar, Estado Bolívar, Venezuela, en 2015-2016. Métodos: estudio descriptivo, prospectivo, diseño longitudinal. La muestra correspondió a 30 pacientes ingresados con diagnóstico de SGB e infección por ZIKV. Resultados: Los síntomas principales fueron: debilidad muscular progresiva (66.67%), parestesias (40.00%) y parálisis (26.67%). El 40.00% refirió infección previa por ZIKV; Se realizaron pruebas serológicas al 100% de los pacientes y en 93.33% se encontró hiperproteinorraquia; De acuerdo a los criterios de Brighton se estableció que todos los pacientes en estudio eran casos de SGB (nivel de certeza tipo 2) Al menos 63.33% eran nivel de certeza tipo 1, al tener los reportes electrofisiológicos. Todos, cumplían con los criterios de Asbury & Cornblath (1990) para diagnóstico de SGB. Evolución: recibió plasmaféresis el 46,66% de la muestra y 83.33% egresó por mejoría. Conclusión: Los resultados expuestos establecen clara vinculación ZIKV-SGB(AU)
ZIKA virus has extended to many countries and was the cause of Guillain-Barre Syndrome in a high proportion of the patients. Objectives: to determinate the clinical and epidemiological behavior of this combination in the Hospital Ruíz y Páez, Ciudad Bolívar, Venezuela. Methods: this was a descriptive, prospective, longitudinal study. The sample was of 30 patients admitted with Guillain-Barre´s Syndrome (GBS) and ZIKA Virus infection. Results: the major symptoms were: progressive muscular weakness 66.67%, paresthesias 40.00% and paralysis 26.67%. 40.00% had presented previous ZIKV. In 93.33% high contents in CSF were found. Serologic studies were realized in all patients: positive ZIKV IgM was present in 73.33% and IgG in 26.67% positiva para ZIKV. Due to their clinical conditions, 36.67% wwere admitted to the ICU. Following Brighton´s criteria and Asbury & Cornblath, all had the diagnosis of GBS. Evolutión: plasmapheresis was used in 46,66% and 83.33% improved and left the hospital. Conclusion: In this study there was a clear evidence of ZIKV infection in patients con GBS(AU)
Assuntos
Humanos , Masculino , Feminino , Doenças Transmissíveis , Síndrome de Guillain-Barré/patologia , Zika virus , Venezuela , Epidemiologia , Medicina InternaRESUMO
We report a 23-year-old woman with rapid onset of proximal and distal limb weakness and areflexia, associated with tumor-like spinal nerve root enlargement and markedly elevated cerebrospinal fluid protein. Our patient developed the inability to walk within days, without preceding illness. Within two weeks, she had near-complete bilateral wrist and foot drop. Her cranial nerves and respiratory function remained intact. She received intravenous immunoglobulin early on for suspected Guillain-barre syndrome but remained wheelchair-bound until 6 Plasma exchange sessions were completed. After that, she continued to improve with intravenous immunoglobulin dosed every 3-4 weeks. Prominent demyelinating features were found on NCS, with cerebrospinal fluid protein of 415 mg/dL. Comprehensive infectious work-up was negative. Magnetic resonance imaging of lumbosacral and cervical spine showed tumor-like masses mistaken for neurofibromatosis (axial diameter, 7.5-10 mm). Repeated magnetic resonance imaging 6 months later showed persistent nerve root enlargement, despite the patient's improved functional status.
Assuntos
Síndrome de Guillain-Barré/patologia , Imunoglobulinas Intravenosas/uso terapêutico , Debilidade Muscular/patologia , Troca Plasmática , Raízes Nervosas Espinhais/patologia , Feminino , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/terapia , Humanos , Imageamento por Ressonância Magnética , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Elevated cerebrospinal fluid (CSF) total protein (TP) concentration (mainly due to a dysfunctional blood-CSF barrier (B-CSFB)) with normal cell count is a hallmark for the diagnosis of Guillain-Barriota syndrome (GBS). AIMS: This work presents the evaluation of B-CSFB dysfunction with respect to the course, severity, and clinical features of GBS. MATERIALS AND METHODS: A sample of CSF was collected on admission from 68 patients of both genders (15 children and 53 adults) diagnosed with GBS. A follow-up CSF sample was obtained approximately 15 days after admission. TP concentration was determined in the CSF and 7.5% polycrylamide gel electrophoresis was employed for serum and CSF protein fractioning. A low percentage of prealbumin fraction was considered a test of impaired B-CSFB. RESULTS: Elevated TP concentration and lower prealbumin were observed in almost 70% of the patients on admission, but this percentage was lower (52.4%) during the first week from onset of symptoms. Both variables were directly associated with the time of evolution of the disease and also with a greater clinical severity. Follow-up CSF studies showed higher CSF TP and lower prealbumin percentages, while deceased patients did not display this response pattern in the follow-up CSF. CONCLUSIONS: B-CSFB dysfunction was present in only half of the patients with GBS during the first week from onset and it was directly associated with progression and clinical severity; nevertheless, a low B-CSFB dysfunction response during follow-up was associated with a lethal outcome, suggesting it could also serve a 'protective' effect during regeneration.
Assuntos
Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Síndrome de Guillain-Barré , Adolescente , Adulto , Barreira Hematoencefálica/fisiopatologia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Albumina/líquido cefalorraquidiano , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
A variety of plants and seeds, some of which are used for therapeutic and nutritional purposes, can cause neurotoxic symptoms. The ingestion of the green or ripe fruit of the Karwinskia humboldtiana (buckthorn), a bush known in Mexico as coyotillo or tullidora, causes a flaccid, symmetric, progressive, and ascending palsy of the lower limbs, which, in severe cases, can cause bulbar palsy and death. The neurologic symptoms are similar to those of poliomyelitis, Guillain-Barré syndrome, and other polyradiculoneuritis syndromes, for which it is often mistaken. The clinical diagnosis of intoxicated patients can be difficult without a history of the fruit ingestion. We present a report of three siblings with buckthorn intoxication.
Assuntos
Karwinskia/intoxicação , Intoxicação por Plantas/fisiopatologia , Polineuropatias/etiologia , Polineuropatias/patologia , Adolescente , Criança , Pré-Escolar , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/patologia , Diagnóstico Diferencial , Eletromiografia , Síndrome de Guillain-Barré/patologia , Humanos , Masculino , Debilidade Muscular/etiologia , Intoxicação por Plantas/patologia , Plantas Tóxicas , Irmãos , Nervo Sural/patologiaRESUMO
AIMS: The purpose of this study was to evaluate the clinical and electrophysiological variables that are linked to prognosis in Guillain Barre syndrome (GBS) in children. PATIENTS AND METHODS: A retrospective cohort study was conducted on 99 children admitted to hospital after being diagnosed as suffering from GBS over a 3 year period. The time before reaching functional grade III on the Hughes scale was taken into account for the outcome, and the following factors were considered to be prediction variables: the electrical excitability of the motor nerves, the need for assisted ventilation, the presence of dysautonomia, age, the degree of maximum weakness on day 10 after the onset of the disease, cranial nerve involvement and origin (town or country). RESULTS: Patients with an excitable pattern, i.e. the presence of an electrical response in at least one of the three motor nerves, at the onset of the disease reached functional grade III on Hughes scale 3.55 times (CI 95% 1.5 6.0) quicker than individuals with a non excitable pattern after adjusting the variable with the strength of the quadriceps and a electromyography study that revealed signs of denervation in the anterior tibial muscle. The clinical variable associated with a favourable prognosis was the presence of any kind of muscular activity in the quadriceps (muscular strength between 1 and 5), regardless of different degrees of strength. Thus, patients with some muscular activity in the quadriceps on day 10 after the onset of the disease reached functional grade III 3.6 times (CI 95% 1.8 7.1) quicker than those who did not present any activity (muscular strength= 0). No differences were found in the time the two physiopathological types, acute axonal neuropathy and demyelinating polyneuropathy, required to reach Hughes grade III. CONCLUSION: The absence of electrical excitability in the motor nerves and the absence of muscular activity in the quadriceps on day 10 of the disease are factors that are independently related to a prolonged recovery time in children with GBS.