RESUMO
INTRODUCTION: Guillain-Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance. MATERIALS AND METHODS: We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7 days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7 days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer's disease (AD; n = 24). RESULTS: Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another. CONCLUSIONS: The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.
Assuntos
COVID-19 , Síndrome de Guillain-Barré , Humanos , COVID-19/complicações , SARS-CoV-2 , Síndrome de Guillain-Barré/complicações , Citocinas , Interleucina-6/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa , Estudos Retrospectivos , Interleucina-8RESUMO
BACKGROUND: Congenital fibrinogen disorders are caused by variants occurring within the fibrinogen gene cluster. We describe ten subjects with disease-causative variants, adding information on such disorders. MATERIALS AND METHODS: Ten subjects were referred to our Centre because of likely hypo/dysfibrinogenaemia. We evaluated the function and quantity of fibrinogen, using Clauss and immunoreactive assays, and performed genetic investigations by direct sequencing of alpha, beta and gamma chain-encoding genes. Mutations were analysed using SIFT and Polyphen-2 algorithms. RESULTS: We identified one afibrinogenaemic patient (alpha p.Arg178* homozygote) with bleeding/thrombotic events, three heterozygous patients with hypo/dysfibrinogenaemia (gamma p.Thr47ILeu combined with beta IVS7+1G>T; beta p.Cys95Ser; beta p.Arg196Cys) referred for bleeding or thrombotic episodes and six heterozygous subjects with hypofibrinogenaemia (alpha p.Glu41Lys; gamma p.Gly191Val; beta p.Gly288Ser; gamma p.His333Arg; gamma p.Asp342Glu and p.343-344 duplication; gamma p.Asp356Val), of whom four were symptomatic. Five novel missense changes and one novel duplication variant were found, all in hypofibrinogenaemic subjects: p.Glu41Lys (SIFT score 0, Polyphen-2 score 0.986) was identified in a woman with bleeding after major orthopaedic surgery; p.Gly191Val (SIFT score 0.02, Polyphen-2 score 1) in an asymptomatic woman; p.His333Arg (SIFT score 0, Polyphen-2 score 1) in a woman with a post-partum haemorrhage; and p.Asp342Glu (SIFT score 0.23, Polyphen-2 score 0.931); and an Asn-343 and Asp-344 duplication in a child who developed a haematoma following a fall. DISCUSSION: All but one of the novel mutations were in symptomatic subjects and are predicted to be deleterious. Our findings shed more light on genotype-phenotype relationships in congenital fibrinogen disorders.
Assuntos
Afibrinogenemia/genética , Estudos de Associação Genética , Hemorragia/genética , Heterozigoto , Mutação , Trombose/genética , Adulto , Afibrinogenemia/sangue , Feminino , Hemorragia/sangue , Humanos , Masculino , Trombose/sangueAssuntos
Traumatismos Craniocerebrais , Gerenciamento Clínico , Deficiência do Fator XIII , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/etiologia , Traumatismos Craniocerebrais/terapia , Deficiência do Fator XIII/complicações , Deficiência do Fator XIII/diagnóstico , Deficiência do Fator XIII/terapia , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/tratamento farmacológico , Tolerância Imunológica , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Feminino , HumanosRESUMO
BACKGROUND AND PURPOSE: Right-to-left shunt (RLS) due to patent foramen ovale is a well-established risk factor for cryptogenic stroke and is highly prevalent in cases of migraine, cluster headache, and obstructive apnea. It can be diagnosed by gaseous-contrast transcranial Doppler, yet in a small percentage of cases it cannot be done owing to an insufficient temporal window. The aim of the study was to compare transtemporal with transoccipital approaches for gaseous-contrast transcranial Doppler for RLS diagnosis. METHODS: We evaluated 183 subjects with a standard protocol for RLS diagnosis by simultaneously monitoring the right middle cerebral and vertebrobasilar circulations. RESULTS: Vertebrobasilar recording reached high specificity (100%) and good sensitivity (83.72%) for the diagnosis of RLS after the Valsalva maneuver. For only medium and large shunts, both sensitivity and specificity reached 100%. Time to bubble appearance after injection was higher in the vertebrobasilar circulation (4.36+/-1.7 vs 6.77+/-2.5 seconds; P<0.001). There was a positive correlation between the number of bubbles in the right middle cerebral and vertebrobasilar circulation (kappa=0.97). CONCLUSIONS: Transcranial Doppler with vertebrobasilar monitoring is highly sensitive and specific in detecting RLS, particularly when medium or large. It can be proposed for subjects with an insufficient temporal bone window.
Assuntos
Circulação Cerebrovascular , Comunicação Interatrial/diagnóstico por imagem , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/métodos , Insuficiência Vertebrobasilar/diagnóstico por imagem , Adulto , Artéria Basilar/fisiopatologia , Comunicação Interatrial/fisiopatologia , Humanos , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/fisiopatologia , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Osso Occipital/anatomia & histologia , Osso Occipital/diagnóstico por imagem , Valor Preditivo dos Testes , Osso Temporal/anatomia & histologia , Osso Temporal/diagnóstico por imagem , Artéria Vertebral/fisiopatologia , Insuficiência Vertebrobasilar/etiologia , Insuficiência Vertebrobasilar/fisiopatologiaAssuntos
Anticoagulantes/uso terapêutico , Embolia/tratamento farmacológico , Heparina/uso terapêutico , Embolia Intracraniana/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Embolia/diagnóstico por imagem , Embolia/etiologia , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Embolia Intracraniana/diagnóstico por imagem , Policitemia/complicações , Policitemia/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Ultrassonografia Doppler TranscranianaRESUMO
BACKGROUND: The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children. OBJECTIVE: To determine the prevalence and possible risk factors for AU in children with CU. METHODS: Ninety-three consecutive children (52 male; median age, 7.8 years) with CU were evaluated for AU by means of autologous serum skin test (ASST) in all and serum-induced basophil histamine release (HR-urticaria test) in 52. All other known causes of CU were excluded as appropriate. RESULTS: A cause for CU was identified in 44 children (47%), whereas 49 (53%) remained idiopathic. ASST and HR-urticaria test had positive results in 22 of 49 (45%) and in 16 of 31 (52%) children with idiopathic CU compared with 1 of 44 (2%) and 5 of 21 (24%) with CU of a known cause, respectively ( P <.00001; P=.09). Sensitivity, specificity, and positive and negative predictive values of the ASST for diagnosing AU are 78%, 85%, 74%, and 88%. The prevalence of AU in childhood is 31% (15/52; 95% CI, 24%-51%). None of the variables studied were predictive for development of AU. CONCLUSION: Our results demonstrate for the first time that children have the same ability as adults to produce functionally active autoantibodies directed against IgE or IgE receptor and that AU occurs in children in as many as 30% of cases. The addition of screening for AU dramatically decreases the rate of the idiopathic form from 52% to 20%.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Imunoglobulina E/imunologia , Receptores de IgE/imunologia , Urticária/imunologia , Adolescente , Autoanticorpos/biossíntese , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Prevalência , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease. Mutations of the Cu/Zn superoxide dismutase gene (SOD1) are responsible for 20% of autosomal dominant familial ALS (FALS). RESULTS: We examined the clinical features of the first Italian FALS with the Leu144Phe SOD1 mutation. Seven affected members were identified in a six-generation pedigree. A slowly progressive course (20.4+/-14.6 years) was observed in five patients. One patient died of cardiac failure two years after the onset of the disease. The propositus is still alive. Neurological manifestations began in the legs in all patients, while bulbar signs were absent or appeared late in the course of the disease. DISCUSSION: There is evidence of a correlation between this mutation and a slowly progressive phenotype of ALS. Moreover this rare mutation might derive from a common ancestor.