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Cerebrospinal fluid (CSF) kappa free light chain (KFLC) index has been described as a reliable marker of intrathecal IgG synthesis to diagnose multiple sclerosis (MS). Our aims were: (1) to compare the efficiency of KFLC through different interpretation approaches in diagnosing MS. (2) to evaluate the prognostic value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). We enrolled 133 MS patients and 240 with other neurological diseases (93 inflammatory including 18 RIS-CIS, 147 non-inflammatory). Albumin, lambda free light chain (LFLC) and KFLC were measured in the CSF and serum by nephelometry. We included two groups of markers: (a) corrected for blood-CSF barrier permeability: immunoglobulin G (IgG), KFLC and LFLC indexes. (b) CSF ratios (not including albumin and serum-correction): CSF KFLC/LFLC, CSF KFLC/IgG, CSF LFLC/IgG. KFLC were significantly higher in MS patients compared to those with other diseases (both inflammatory or not). KFLC index and CSF KFLC/IgG ratio showed high sensitivity (93% and 86.5%) and moderate specificity (85% and 88%) in diagnosing MS. RIS-CIS patients who converted to MS showed greater KFLC index and CSF KFLC/IgG. Despite OB are confirmed to be the gold-standard to detect intrathecal IgG synthesis, the KFLC confirmed their accuracy in MS diagnosis. A “kappa-oriented” response characterizes MS and has a prognostic impact in the RIS-CIS population.

Background Cerebrospinal fluid (CSF) kappa-free light chains (KFLC) are becoming a diagnostic biomarker for multiple sclerosis (MS). Objectives We aimed to compare the diagnostic performance of intrathecal synthesis biomarkers to that of oligoclonal bands (OB) in diagnosing MS, radiological and clinical isolated syndromes (RIS-CIS) on a large cohort of patients collected over 10 years. Methods We collected 1124 patients (58% females) in 10 years who underwent CSF analysis for intrathecal synthesis in the diagnostic work-up, and they were classified according to their diagnosis as 417 MS, 287 with other neurological inflammatory disorders (including 76 RIS-CIS), and 420 non-inflammatory diseases (excluding lymphoproliferative and infective diagnosis). Results MS patients significantly differ from all other groups (including if considering the RIS-CIS cohort) for CSF KFLC, KFLC intrathecal fraction (IF), Kappa index, and OB. Evaluating the diagnostic performance, the Kappa index cut-off was 6.4 for diagnosing MS and 5.7 for predicting OB. A diagnostic algorithm could avoid IEF if the Kappa index is higher than 20. Conclusions The KFLC index confirmed its accuracy for MS diagnosis in this large Italian cohort, adding information also in the RIS-CIS population.

Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the central nervous system (CNS). Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke and requiring prompt initiation of treatment with antiplatelet drugs or anticoagulant therapy. In these cases, alterations of the coagulation system at various levels caused by multiple effects of antiphospholipid antibodies (aPL) have been postulated to explain the vascular damage to the CNS in APS. However, several nonvascular neurological manifestations of APS have progressively emerged over the past years. Nonthrombotic, immune-mediated mechanisms altering physiological basal ganglia function have been recently suggested to play a central role in the pathogenesis of these manifestations that include, among others, movement disorders such as chorea and behavioral and cognitive alterations. Similar clinical manifestations have been described in other autoimmune CNS diseases such as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune-mediated basal ganglia disorders is expanding, possibly sharing some pathophysiological mechanisms. In this review, we will focus on thrombotic and nonthrombotic neurological manifestations of APS with particular attention to immune-mediated actions of aPL on the vascular system and the basal ganglia.

BackgroundA few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).ObjectiveTo analyse the efficacy of rituximab in a large CIDP cohort.MethodsA retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders.ResultsNine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1–6) and lasted for a median period of 1 year (range, 1–5).ConclusionsRituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.

Background Visual hallucinations (VHs) are frequent non-motor complication of Parkinson’s disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene ( DR ) variants and psychosis in Alzheimer’s disease, addictions, schizophrenia, and bipolar disorder. However, there are only a few studies on DR variants and VHs in PD, which did not provide conclusive results. Objectives The present study aimed to determine whether genetic differences of DR are associated with visual hallucinations (VHs) in a cohort of Parkinson’s disease (PD) patients. Methods A case-control study of 84 PD subjects, 42 with and 42 without VHs,that were matched for age, gender, disease duration, and dopaminergic medication was conducted. Polymerase chain reaction for SNPs in both D1-like ( DRD1 A-48G [rs4532] and C62T [rs686], DRD5T798C [rs6283]) and D2-like DR ( DRD2 G2137A [rs1800497] and C957T [rs6277], DRD3 G25A [rs6280] and G712C [rs1800828], DRD4 C616G [rs747302] and nR VNTR 48bp) analyzed genomic DNA. Results Patients carrying allele T at DRD1 C62T had an increased risk of VHs, expressed as OR (95 % CI, p value), of 10.7 (2.9–40, p  = 0.0001). Moreover, patients with DRD1 -48 GG and 62TT genotype displayed shorter time to VHs, whereas a longer time to VHs was found in subjects carrying the DRD4 CG alleles. Conclusions PD patients with VHs display higher frequency of DR SNPs associated with increased D1-like activity and decreased D2-like activity. Our data are in line with associations reported in other neurodegenerative and psychiatric conditions. Results likely provide valuable information for personalizing pharmacological therapy in PD patients.

In this paper, we consider the mechanical effect of the sulfate attack on concrete. The durability analysis of concrete structures in contact to external sulfate solutions requires the definition of a proper diffusion-reaction model, for the computation of the varying sulfate concentration and of the consequent ettringite formation, coupled to a mechanical model for the prediction of swelling and material degradation. In this work, we make use of a two-ions formulation of the reactive-diffusion problem and we propose a bi-phase chemo-elastic damage model aimed to simulate the mechanical response of concrete and apt to be used in structural analyses.

Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used in the diagnosis of PD and its differentiation from atypical parkinsonian syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian patients. In this blinded cross-sectional study (NOBIS study), two expert neuro-sonologists performed TCS in 25 PD patients and 29 age- and sex-matched controls. The study participants were completely hidden to the TCS investigators using large drapery. One month later, the SN TCS recordings were re-read by the initial investigator, and cross-read by the second reader. Diagnostic accuracy was estimated on the first reading, intra-reader reliability on re-reading, and inter-reader reliability on cross-readings. The mean SN echogenic area was larger in the patients (0.24 cm 2 ) than in the controls (0.15 cm 2 ; Mann–Whitney test, p  < 0.001). SN measures did not differ between right and left, or between ipsilateral and contralateral to the clinically more affected side. There was no correlation between SN echogenicity and PD severity or duration. High intra-reader (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of SN measurements was found. The diagnostic accuracy for the detection of PD was high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83–1.00) with an optimum cut-off value for SN echogenic area of 0.18 cm 2 with the device used here (specificity 0.83–0.90; sensitivity 0.72–0.92). This study supports the use of SN TCS in the diagnostic workup of PD if performed by trained readers.

We studied the effects of treatment with olmesartan/amlodipine and olmesartan/hydrochlorothiazide on inflammatory and metabolic parameters (including new-onset diabetes as a secondary endpoint) in non-diabetic hypertensive patients with metabolic syndrome (MetS). A total of 120 patients with MetS and stage I and II hypertension were randomized to olmesartan 20 mg/amlodipine 5 mg or olmesartan 20 mg/hydrochlorothiazide 12.5 mg. If target systolic blood pressure (<140 mm Hg) was not reached, doses were doubled after 13 weeks; doxazosin 4 mg was added after 26 weeks, and doubled after 39 weeks; follow-up ended at 78 weeks. At each visit, blood pressure (BP), fasting plasma glucose, insulin, adiponectin, tumour necrosis factor-α, C-reactive protein (CRP), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukins-1β, -6 and -8, and albuminuria were measured; BP was similarly reduced in both groups; 80% of patients reached target BP. Reductions in albuminuria were also similar (50%). Only olmesartan/amlodipine reduced the insulin resistance index (24%, P <0.01), increased plasma adiponectin (16%, P <0.05) and significantly reduced all of the inflammation markers studied, except CRP, which showed a similar reduction in each group. The risk of new-onset diabetes was significantly lower with olmesartan/amlodipine ( P =0.02). Both olmesartan-based combinations were effective, but the amlodipine combination resulted in metabolic and anti-inflammatory effects that may have advantages over the hydrochlorothiazide combination.

Perforin (PRF) has a key role in the function of cytotoxic T and natural killer cells. Rare variations of PRF1 predispose to autoimmunity. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, involving defective lymphocyte apoptosis. The aim of this study was to investigate the role of PRF1 in CIDP. The entire coding region of PRF1 was sequenced in 94 patients and 158 controls. We found three missense variations leading to amino acid substitutions and one nonsense variation resulting in a premature stop codon. All variations would decrease PRF activity. Their overall frequency was significantly higher in patients than in controls (odds ratio (OR)=4.47). The most frequent variation was p.Ala91Val (OR=3.92) previously associated with other autoimmune diseases. Clinical analysis showed that PRF1 variations were more frequent in relapsing patients and in patients displaying axonal damage. These data suggest that PRF1 variations may influence CIDP development and course.

This paper presents the study of the mechanical behavior of a microstructure designed to detect acceleration and angular velocity simultaneously. The new resonant micro-sensor proposed, fabricated by the ThELMA© surface-micromachining technique, bases detection of two components of external acceleration (one in-plane component and one out-of plane component) and two components of angular velocity (roll and yaw) on the variation of frequency of several elements set in resonance. The device, despite its small dimensions, provides a differential decoupled detection of four external quantities thanks to the presence of four slender beams resonating in bending and four torsional resonators.