RESUMO
INTRODUCTION: Allgrove syndrome is a genetic disorder characterized by a multisystem involvement manifesting mainly in childhood with esophageal achalasia, adrenal insufficiency, and alacrima. Associated neurological manifestations are frequent in patients with late-onset forms and include peripheral, central, and autonomic dysfunction. The definitive diagnosis remains genetic, but neurological symptoms/signs could be a relevant clue for the diagnosis. DISCUSSION: This syndrome is rare, but it is not impossible for it to occur in adults, so all neurologists must be alert. Moreover, in this regard, neurological symptoms can sometimes be very similar to those of motor neuron disease patients, so that, although rare, Allgrove syndrome may also enter into the differential diagnosis with the bulbar variant of amyotrophic lateral sclerosis. Nevertheless, attention to extra-neurological symptoms must remain high as these play an equally important role in reaching the diagnosis. CASE REPORT: Here we present the case of a patient with some peculiarities that are onset at an advanced age, genetic confirmation of the diagnosis, and prominent neurological involvement, which also opens the differential diagnosis to amyotrophic lateral sclerosis.
Assuntos
Insuficiência Adrenal , Esclerose Lateral Amiotrófica , Acalasia Esofágica , Doenças do Aparelho Lacrimal , Humanos , Adulto , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/genética , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/genética , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/genética , Doenças do Aparelho Lacrimal/diagnósticoRESUMO
INTRODUCTION: Contrast-induced encephalopathy is a rare and usually reversible entity due to the administration of iodinated contrast. Clinical manifestations include cortical blindness, encephalopathy, seizures and focal neurological deficits. METHODS: We report the case of a 56-year-old woman who developed global aphasia and right hemiplegia after a cerebral angiography performed for a subarachnoid haemorrhage. A prompt brain MRI resulted negative, while CT scan revealed left cerebral oedema with the cerebral sulci effacement. Complete recovery was observed in 10 days. DISCUSSION: Diagnosis of contrast-induced encephalopathy requires a temporal correlation between neurological dysfunction and administration of iodinated contrast. Usually, the symptomatology is transient with a full recovery within 48-72 h. The most common symptom is cortical blindness, while other symptoms have been rarely reported. Only 20 cases previously reported global aphasia and/or hemiplegia or mimed anterior circulation strokes. Prompt brain neuroimaging is essential in order to exclude an alternative diagnosis that requires a distinct therapeutic approach.
Assuntos
Meios de Contraste , Acidente Vascular Cerebral , Angiografia Cerebral , Meios de Contraste/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
We present the case of an immunocompetent 55-year-old woman, treated with corticosteroids, developing a cerebral fungal infection with autoptic ascertainment of aspergillosis and mucormycosis. This is the first report of cerebral co-infection by mucorales and aspergillus in an immunocompetent host. A possible explanation is that corticosteroids, even if taken for a short time, led to a transient lowering of immune function and contributed to negative outcome.
Assuntos
Anti-Inflamatórios/efeitos adversos , Encefalopatias/induzido quimicamente , Mucormicose/induzido quimicamente , Neuroaspergilose/induzido quimicamente , Prednisona/efeitos adversos , Corticosteroides/efeitos adversos , Coinfecção/induzido quimicamente , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Herpes simplex encephalitis relapses have been rarely reported, with only few cases occurring after neurosurgical interventions. A young man presented a late herpes simplex encephalitis relapse after left antero-mesial temporal resection for his refractory temporal lobe epilepsy. Eight days after surgery, he developed fever and aphasia. CSF PCR revealed more than 12,000 copies/ml of HSV-1 DNA. Intravenous acyclovir was immediately started with a complete recovery. Postoperative herpes simplex encephalitis can occur as primary infection or as relapse of previous infection. Surgical manipulation of brain parenchyma in the site of a previous infection can act as a trigger for viral reactivation. Early onset of antiviral therapy is fundamental and it is a strong predictor of clinical outcome. Despite no studies on prophylactic treatment with acyclovir in patients with previous herpes simplex encephalitis candidate to neurosurgery are available, we suggest that prophylactic treatment should be recommended.
Assuntos
Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/virologia , Procedimentos Neurocirúrgicos/efeitos adversos , Adulto , Humanos , Masculino , Recidiva , Lobo Temporal/cirurgiaRESUMO
The above article was published online with inverted given and family names. The correct presentation has been corrected above.
RESUMO
PURPOSE: The disease course of multiple sclerosis (MS) is unpredictable, and reliable prognostic biomarkers are needed. Positron emission tomography (PET) with ß-amyloid tracers is a promising tool for evaluating white matter (WM) damage and repair. Our aim was to investigate amyloid uptake in damaged (DWM) and normal-appearing WM (NAWM) of MS patients, and to evaluate possible correlations between cerebrospinal fluid (CSF) ß-amyloid1-42 (Aß) levels, amyloid tracer uptake, and brain volumes. METHODS: Twelve MS patients were recruited and divided according to their disease activity into active and non-active groups. All participants underwent neurological examination, neuropsychological testing, lumbar puncture, brain magnetic resonance (MRI) imaging, and 18F-florbetapir PET. Aß levels were determined in CSF samples from all patients. MRI and PET images were co-registered, and mean standardized uptake values (SUV) were calculated for each patient in the NAWM and in the DWM. To calculate brain volumes, brain segmentation was performed using statistical parametric mapping software. Nonparametric statistical analyses for between-group comparisons and regression analyses were conducted. RESULTS: We found a lower SUV in DWM compared to NAWM (p < 0.001) in all patients. Decreased NAWM-SUV was observed in the active compared to non-active group (p < 0.05). Considering only active patients, NAWM volume correlated with NAWM-SUV (p = 0.01). Interestingly, CSF Aß concentration was a predictor of both NAWM-SUV (r = 0.79; p = 0.01) and NAWM volume (r = 0.81, p = 0.01). CONCLUSIONS: The correlation between CSF Aß levels and NAWM-SUV suggests that the predictive role of ß-amyloid may be linked to early myelin damage and may reflect disease activity and clinical progression.
Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Tomografia por Emissão de Pósitrons , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Tomografia por Emissão de Pósitrons/normas , Valores de Referência , Substância Branca/metabolismo , Adulto JovemRESUMO
BACKGROUND: The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized. OBJECTIVES: To evaluate retinal pathology using optical coherence tomography (OCT) and to investigate possible associations between retinal layers' thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS. METHODS: A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM). RESULTS: Compared to controls, patients' macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced ( p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning ( p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex ( p < 0.005). CONCLUSION: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.
Assuntos
Progressão da Doença , Lobo Occipital/patologia , Lobo Parietal/patologia , Células Ganglionares da Retina/patologia , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed. OBJECTIVES: To investigate the prognostic role of cerebrospinal fluid (CSF) amyloid beta1-42 (Aß) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages. METHODS: Sixty patients were recruited and followed up for 3-5 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine Aß levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads. RESULTS: Lower CSF Aß levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS; r = -0.65, p < 0.001). The multiple regression analysis confirmed CSF Aß concentration as a predictor of patients' EDSS increase (r = -0.59, p < 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690-0.933, p = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed (p > 0.05). CONCLUSION: Low CSF Aß levels may represent a predictive biomarker of disease progression in MS.
Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Progressão da Doença , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Fragmentos de Peptídeos/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Adulto , Biomarcadores/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive. OBJECTIVE: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures. METHOD: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits. RESULTS: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected). CONCLUSION: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.
Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Somatoformes/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/patologiaRESUMO
OBJECTIVE: To assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls. METHODS: Eighty-five participants were recruited: 65 with newly diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. ß-amyloid1-42 (Aß) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Aß levels (Aß(+)), while 23 had normal CSF Aß levels (Aß(-)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. RESULTS: We found an increased WM-LL in Aß(+) compared with both, healthy controls (p=0.003) and Aß(-) patients (p=0.02). Interestingly, CSF Aß concentration was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Aß(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001). CONCLUSIONS: WM damage is crucial in AD pathogenesis. The correlation between CSF Aß levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Neurodegeneration plays a major role in determining disability in multiple sclerosis (MS) patients. Hence, there is increasing need to identify reliable biomarkers, which could serve as prognostic measure of disease progression. OBJECTIVES: To assess whether cerebrospinal fluid (CSF) tau and ß-amyloid (Aß) levels were altered in newly diagnosed MS patients and correlated with disability. Moreover, we investigated whether these CSF biomarkers associate with macroscopic brain tissue damage measures. METHODS: CSF Aß and tau levels were determined by enzyme-linked immunosorbent assay in CSF samples from 48 newly diagnosed MS patients, followed-up clinically for 3 years by recording their Expanded Disability Status Scale score at 6-month intervals, and 45 controls. All patients underwent magnetic resonance imaging at baseline and at the end of follow-up to quantify their lesion load (LL). RESULTS: CSF Aß levels were significantly reduced in patients compared to controls ( p < 0.001). Lower CSF Aß levels at baseline were a disability predictor at 3-year follow-up ( p = 0.009). CSF tau levels correlated with T2- and T1-LL ( p < 0.001). CONCLUSION: CSF Aß reduction is a promising biomarker of neurodegeneration and may predict patients' clinical outcome. Therefore, CSF Aß should be considered as a potential biomarker of prognostic value.
Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Idoso , Doença de Alzheimer/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Prognóstico , Proteínas tau/líquido cefalorraquidianoRESUMO
CXCL14 is a chemokine with an atypical, yet highly conserved, primary structure characterized by a short N terminus and high sequence identity between human and mouse. Although it induces chemotaxis of monocytic cells at high concentrations, its physiological role in leukocyte trafficking remains elusive. In contrast, several studies have demonstrated that CXCL14 is a broad-spectrum antimicrobial peptide that is expressed abundantly and constitutively in epithelial tissues. In this study, we further explored the antimicrobial properties of CXCL14 against respiratory pathogens in vitro and in vivo. We found that CXCL14 potently killed Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus pneumoniae in a dose-dependent manner in part through membrane depolarization and rupture. By performing structure-activity studies, we found that the activity against Gram-negative bacteria was largely associated with the N-terminal peptide CXCL141-13. Interestingly, the central part of the molecule representing the ß-sheet also maintained â¼62% killing activity and was sufficient to induce chemotaxis of THP-1 cells. The C-terminal α-helix of CXCL14 had neither antimicrobial nor chemotactic effect. To investigate a physiological function for CXCL14 in innate immunity in vivo, we infected CXCL14-deficient mice with lung pathogens and we found that CXCL14 contributed to enhanced clearance of Streptococcus pneumoniae, but not Pseudomonas aeruginosa. Our comprehensive studies reflect the complex bactericidal mechanisms of CXCL14, and we propose that different structural features are relevant for the killing of Gram-negative and Gram-positive bacteria. Taken together, our studies show that evolutionary-conserved features of CXCL14 are important for constitutive antimicrobial defenses against pneumonia.
Assuntos
Anti-Infecciosos/farmacologia , Quimiocinas CXC/farmacologia , Infecções Pneumocócicas/imunologia , Infecções Respiratórias/imunologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologia , Monofosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Anti-Infecciosos/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Quimiocinas CXC/química , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Quimiotaxia/efeitos dos fármacos , DNA Bacteriano , Modelos Animais de Doenças , Interleucina-8/farmacologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Testes de Sensibilidade Microbiana , Modelos Moleculares , Mieloblastina/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Permeabilidade/efeitos dos fármacos , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/genética , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteólise , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/genética , Streptococcus pneumoniae/ultraestruturaRESUMO
Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1ß and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.
Assuntos
Imunidade Inata , Pulmão/imunologia , Células Mieloides/imunologia , Pneumonia Pneumocócica/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Fumar/imunologia , Streptococcus pneumoniae/imunologia , Animais , Carga Bacteriana , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Interações Hospedeiro-Patógeno , Mediadores da Inflamação/imunologia , Interleucina-1beta/imunologia , Cinética , Labirintite/imunologia , Labirintite/microbiologia , Pulmão/microbiologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/microbiologia , Células Mieloides/microbiologia , Neutrófilos/imunologia , Neutrófilos/microbiologia , Pneumonia Pneumocócica/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , Receptores Tipo I de Interleucina-1/genética , Receptores Tipo I de Interleucina-1/metabolismo , Serpinas/genética , Serpinas/metabolismo , Fumar/efeitos adversos , Streptococcus pneumoniae/patogenicidadeRESUMO
Serpinb1 is an inhibitor of neutrophil granule serine proteases cathepsin G, proteinase-3 and elastase. One of its core physiological functions is to protect neutrophils from granule protease-mediated cell death. Mice lacking Serpinb1a (Sb1a-/-), its mouse ortholog, have reduced bone marrow neutrophil numbers due to cell death mediated by cathepsin G and the mice show increased susceptibility to lung infections. Here, we show that conditional deletion of Serpinb1a using the Lyz2-cre and Cebpa-cre knock-in mice effectively leads to recombination-mediated deletion in neutrophils but protein-null neutrophils were only obtained using the latter recombinase-expressing strain. Absence of Serpinb1a protein in neutrophils caused neutropenia and increased granule permeabilization-induced cell death. We then generated transgenic mice expressing human Serpinb1 in neutrophils under the human MRP8 (S100A8) promoter. Serpinb1a expression levels in founder lines correlated positively with increased neutrophil survival when crossed with Sb1a-/- mice, which had their defective neutrophil phenotype rescued in the higher expressing transgenic line. Using new conditional and transgenic mouse models, our study demonstrates the presence of a relatively low Serpinb1a protein threshold in neutrophils that is required for sustained survival. These models will also be helpful in delineating recently described functions of Serpinb1 in metabolism and cancer.
Assuntos
Deleção de Genes , Células Mieloides/metabolismo , Neutrófilos/citologia , Serpinas/deficiência , Serpinas/genética , Alelos , Animais , Sobrevivência Celular , Técnicas de Introdução de Genes , Humanos , Camundongos Transgênicos , Recombinação GenéticaAssuntos
Isquemia Encefálica/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Endocardite Bacteriana/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Infecções Estreptocócicas/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico por imagem , Adulto , Isquemia Encefálica/etiologia , Neoplasias do Colo/complicações , Diagnóstico Diferencial , Endocardite Bacteriana/etiologia , Humanos , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/microbiologia , Masculino , Infecções Estreptocócicas/complicações , Streptococcus gallolyticus/isolamento & purificação , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part of the central nervous system. This presentation has been associated with heterozygous mutations in CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10. We aimed to investigate the genetic defect underlying multiple cerebral and vertebral cavernous malformations in a multigenerational Italian family. CASE PRESENTATION: The proband is a 49-year-old man who underwent cerebral MRI in his thirties for persistent haeadache and tingling in his left arm and leg and was diagnosed with multiple supratentorial cavernous angiomas. A right frontal angioma with radiological evidence of a recent bleeding was surgically removed when he was 39 years old and he was thereafter asymptomatic. Magnetic resonance imaging revealed multiple cerebral cavernous malformations in seven members of his familily. Four subjects were asymptomatic. Other family mambers displayed heterogeneous clinical features including seizures and recurrent brain haemorrhages. Sequence analysis in the proband disclosed a novel heterozygous nucleotide substitution (c.263-10A > G) in intron 5 of CCM1. This variant is predicted to create an abnormal acceptor splice site and segregated in affected relatives available for molecular screening. The analysis of CCM1 transcript in proband's lymphocytes confirmed the partial retention of intron 3 resulting in a premature termination codon. CONCLUSIONS: Our findings demonstrate that c.263-10A > G mutation is associated with cerebral cavernous malformations. A better knowledge of the disease-associated phenotype may lead to an early diagnosis and to an appropriate clinical surveillance in affected patients.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Feminino , Humanos , Proteína KRIT1 , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Fragmento de RestriçãoRESUMO
BACKGROUND AND PURPOSE: Aim of this study was to evaluated anxiety, depression, and possible negative implications on work activities during the Sars-CoV-2 pandemic, in a group of Multiple Sclerosis (MS) patients at risk of flu-like syndrome (FLS) compared with FLS- free treatments. METHODS: The present study included patients treated with interferon-ß (IFNß), glatiramer, and natalizumab for at least one year. Collected data included the diagnosis of COVID-19 infection, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), together with questions about FLS, change in work habits, use of antipyretics, anxiety, and depression. RESULTS: 100 patients were included in the study. Six patients in IFNß and 5 in the natalizumab group had a confirmed COVID-19 infection. 68% in the IFNß patients reported FLS and only one reported an increase in flu-like frequency during the pandemic; 14% reported lower compliance with treatment, and 40% reported uptake of antipyretics several times. Only one IFNß patient reported having lost more working days than the previous year. The average BAI (p = 0.039) was higher in natalizumab group. Correcting these data by age, sex and EDSS to a multivariate analysis we did not find any statistically significant difference in terms of BAI and BDI-II between the three treatment groups. CONCLUSIONS: FLS were not perceived as COVID19-like symptoms but as expected by traditional pharmacological treatments indeed. These data suggest that IFNß can be used safely.
Assuntos
Antipiréticos , COVID-19 , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Interferon beta/efeitos adversos , SARS-CoV-2 , Natalizumab/uso terapêutico , Depressão/epidemiologia , Depressão/diagnóstico , Pandemias , Antipiréticos/uso terapêutico , COVID-19/epidemiologia , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Ansiedade/diagnósticoRESUMO
BACKGROUND: SARS-COV-2 infection has been associated to long-lasting neuropsychiatric sequelae, including cognitive deficits, that persist after one year. However, longitudinal monitoring has been scarcely performed. Here, in a sample of COVID-19 patients, we monitor cognitive, psychological and quality of life-related profiles up to 22 months from resolution of respiratory disease. METHODS: Out of 657 COVID-19 patients screened at Manzoni Hospital (Lecco, Italy), 22 underwent neuropsychological testing because of subjective cognitive disturbances at 6 months, 16 months, and 22 months. Tests of memory, attention, and executive functions were administered, along with questionnaires for depressive and Post-traumatic stress disorder (PTSD) symptoms, psychological well-being and quality of life. Cross-sectional descriptives, correlational, as well as longitudinal analyses considering COVID19-severity were carried out. A preliminary comparison with a sample of obstructive sleep apneas patients was also performed. RESULTS: Around 50% of COVID-19 patients presented with cognitive deficits at t0. The most affected domain was verbal memory. Pathological scores diminished over time, but a high rate of borderline scores was still observable. Longitudinal analyses highlighted improvements in verbal and non-verbal long term memory, as well as attention, and executive functioning. Depression and PTSD-related symptoms were present in 30% of patients. The latter decreased over time and were associated to attentional-executive performance. CONCLUSIONS: Cognitive dysfunctions in COVID-19 patients may extend over 1 year, yet showing a significant recovery in several cases. Cognitive alterations are accompanied by a significant psychological distress. Many patients displaying borderline scores, especially those at higher risk of dementia, deserve clinical monitoring.
Assuntos
COVID-19 , Disfunção Cognitiva , Humanos , Qualidade de Vida , Estudos Transversais , COVID-19/complicações , SARS-CoV-2 , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Testes Neuropsicológicos , CogniçãoRESUMO
BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.