RESUMO
Pentraxin-3 (PTX3) is a component of humoral innate immunity with essential functions both in promotion and resolution of inflammation. We aimed to study the PTX3 in the plasma and in the muscle of patients with idiopathic inflammatory myopathies (IIM) and whether PTX3 may correlate with disease activity. Plasma PTX3 levels were assessed in 20 patients with IIMs, 10 dermatomyositis (DM), and 10 polymyositis (PM), compared to 10 patients with rheumatoid arthritis (RA) and 10 healthy donors (HDs) aged, sex, and body mass index matched. Disease activity in IIMs was assessed by Myositis Disease Activity Assessment Visual Analog Scale (MYOACT), while disease activity score on 28 joints (DAS28) was used for RA patients. Muscle histopathology and immunohistochemical (IHC) analyses were also performed. Mean plasma PTX3 levels were significantly higher in IIM patients than HDs (518 ± 260 pg/ml vs. 275 ± 114 pg/ml, P = 0.009). Linear regression analysis adjusted for age, sex, and disease duration showed a direct correlation between PTX3 and CPK levels (ß: 0.590), MYOACT (ß: 0.759), and physician global assessment of disease activity (ß: 0.832) in IIMs. No association between PTX3 levels and DAS28 was found in RA. Global PTX3 pixel fraction was higher in IIM than HDs muscle, but a lower PTX3 expression was found in perifascicular areas of DM and in myofibers with sarcolemmal staining for membrane attack complement. PTX3 plasma levels were increased in IIMs and correlated with disease activity suggesting a possible role as biomarker of disease activity. PTX3 showed a different distribution in DM or PM muscle.
Assuntos
Artrite Reumatoide , Miosite , Polimiosite , Humanos , Idoso , Proteína C-Reativa/metabolismo , BiomarcadoresRESUMO
BACKGROUND: Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. OBJECTIVE: The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. METHODS: Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected). RESULTS: Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index. CONCLUSIONS: Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS.
Assuntos
Atenção/fisiologia , Transtornos Cognitivos/etiologia , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/fisiopatologia , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/diagnóstico , Doenças Desmielinizantes/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologiaRESUMO
BACKGROUND AND PURPOSE: To evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS). METHODS: Cerebrospinal fluid NFL levels of 37 cases of sporadic ALS were measured and the time of symptom spreading from spinal or bulbar localization to both (TTG) was evaluated in all patients. RESULTS: Kaplan-Meier analysis showed a short TTG in patients with high NFL levels (log-rank test chi-squared = 19.4, P < 0.0001). In a multivariate regression model patients with NFL levels above the median had an eight-fold higher risk of generalization (adjusted hazard ratio 7.9, 95% confidence interval 2.9-21.4, P < 0.0001) compared with those with NFL levels below the median. CONCLUSIONS: This study shows that in sporadic ALS NFL, a marker of neurodegeneration, is correlated with TTG, a clinical intermediate parameter of survivorship.
Assuntos
Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Progressão da Doença , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de TempoRESUMO
Background: This case presents a detailed forensic examination of a unique femicide case followed by the perpetrator's suicide. Case report: On a Sunday afternoon, a 52 year old man killed his 43 year old partner in their home with eleven stab wounds. A few minutes later, he committed suicide by suspending himself to a tree in their home garden by means of a rope. This unique case is interesting because of the combination of methods used for both homicide and suicide, as well as the relationship dynamics between the victim and perpetrator. The perpetrator committed homicide by stabbing and then hanged himself. Conclusion: The case adds valuable knowledge to Forensic Medicine, advocating for increased awareness and preventive measures against domestic and gender-based violence. This report provides an in-depth analysis of a homicide-suicide incident, focusing on a unique case of homicide-suicide. It serves to highlight the global crisis of femicide. The case is situated within the context of gender- based violence, illustrating how such acts are deeply rooted in societal norms. It highlights patterns of intimate partner violence, where emotional factors play a significant role. Forensic analysis uncovered the overkill nature of the homicide, indicating excessive injuries beyond what was necessary for death, reflecting the psychological turmoil of the perpetrator. It emphasizes the importance of identifying signs of potential violence in domestic settings and implementing interventions for mental health support and the prevention of genderbased violence.
Assuntos
Homicídio , Suicídio Consumado , Ferimentos Perfurantes , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Asfixia/etiologia , Lesões do PescoçoRESUMO
BACKGROUND: To date there are no biomarkers with proven reliability as a measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS. METHODS: Thirty-seven consecutive patients with ALS, 25 with chronic inflammatory demyelinating polyneuropathy and 21 with other neurodegenerative diseases were evaluated. CSF NFL levels were assayed by two-site solid-phase sandwich ELISA. In patients with ALS, neurological status was assessed by the revised ALS Functional Rating Scale (ALSFRS-r) and the Medical Research Council scale, and the progression of the disease was evaluated using the 'diagnostic delay' and the 'progression rate'. RESULTS: Cerebrospinal fluid NFL levels were higher in ALS cases than in controls (P < 0.0001). Using receiver operating curve analysis, an optimal NFL cut-off of 1981 ng/l discriminated between patients with ALS and neurological controls, with a sensitivity of 78.4% and specificity of 72.5%. Multivariate logistic regression confirmed the association between CSF NFL levels and the presence of ALS (age and sex adjusted odds ratio for ALS 8.9; 95% CI 3.1-25.8; P < 0.0001). In ALS, CSF NFL negatively correlated with the diagnostic delay (P < 0.0001) and the ALSFRS-r (P = 0.014) and positively with the progression rate (P < 0.0001). CONCLUSIONS: High CSF NFL levels were found in patients with ALS, reflecting the burden of neurodegeneration. The significant relation between CSF NFL levels and disease progression suggests that NFL may be a useful marker of disease activity and progression in ALS.
Assuntos
Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes. OBJECTIVE: To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO. DESIGN: Observational, multicentre, prospective, cross sectional study. METHODS: Serum samples were collected from 48 relapsing-remitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry. RESULTS: MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p<0.001). High serum NAA values, exceeding the 95th percentile of serum NAA values in healthy controls, were found in 100% of patients with MS and in no patient with NMO. No differences in serum NAA levels were found between NMO and healthy controls. In MS, serum and CSF NAA levels correlated with disability score. CONCLUSIONS: Determination of serum and CSF NAA levels may represent a suitable tool in the diagnostic laboratory workup to differentiate MS and NMO.