Amyotrophic lateral sclerosis: a new missense mutation in the SOD1 gene

Copper-zinc superoxide dismutase-1 (SOD1) is the second most common mutated gene in amyotrophic lateral sclerosis (ALS). To date more than 150 missense mutations of SOD1 have been reported. The objective of this study was to describe a novel SOD1 mutation and its phenotypic expression. We describe a 74-year-old Caucasian man who began to complain of progressive weakness and atrophy of the right hand and over 10 months developed a severe tetraparesis, with atrophies of upper and lower limbs and neck muscles, dysphagia, and dyspnea that led to percutaneous endoscopic gastrostomy and tracheotomy. A diagnosis of ALS was made. Genetic analysis identified a heterozygous mutation in exon 4 of SOD1 that results in the amino acid substitution from arginine to cysteine at position 115 (p.R115C). We identified a novel pathogenic SOD1 mutation in a patient with a very rapid disease progression and aggressive phenotype providing additional information on the wide range of SOD1 mutations in apparently sporadic ALS and confirming the possibility of a strong genotype-phenotype correlation for distinct SOD1 mutations.     

"Ultrasound comet-tail images": a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water

BACKGROUND: Echographic examination of the lung surface may reveal multiple "comet-tail images" originating from water-thickened interlobular septa. These images could be useful for noninvasive assessment of interstitial pulmonary edema. STUDY OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of lung comet-tail images compared with chest radiography, wedge pressure, and extravascular lung water (EVLW) quantified by the indicator dilution method (PiCCO System, version 4.1; Pulsion Medical Systems; Munich, Germany). METHODS AND PATIENTS: We enrolled 20 patients (mean age, 62.6 +/- 11.5 years [+/- SD]). Patients were studied before, immediately after, and 24 h following cardiac surgery with chest ultrasound, chest radiography, pulmonary artery catheterization, and the PiCCO system. Performing echo scanning (right and left hemithorax, from second to fourth intercostal space, from parasternal to midaxillary line), an individual patient comet score was obtained by summing the number of comets in each scanned space. RESULTS: A total of 60 comparisons were obtained. Significant positive linear correlations were found between comet score and EVLW determined by the PiCCO System (r = 0.42, p = 0.001), between comet score and wedge pressure (r = 0.48, p = 0.01), and between comet score and radiologic lung water score (r = 0.60, p = 0.0001). CONCLUSIONS: The presence and the number of comet-tail images provide reliable information on interstitial pulmonary edema. Therefore, ultrasonography represent an attractive, easy-to-use, bedside diagnostic tool for assessing cardiac function and pulmonary congestion.     

Simultaneous occurrence of peripheral T-cell lymphoma unspecified and B-cell small lymphocytic lymphoma. Report of 2 cases

We report on 2 composite lymphomas occurring in elderly patients, morphologically characterized by the combination of peripheral T-cell lymphoma (PTCL) unspecified and B-cell small lymphocytic lymphoma. Immunohistochemistry provided objective confirmation of the coexistence of the 2 malignancies, as did molecular biology by revealing clonal T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements. One of the patients had no history of indolent lymphoma either at the personal and family level, whereas the other showed a strong familial predisposition, his mother and sister having suffered from B-cell chronic lymphocytic leukemia. Epstein-Barr virus was detected in the PTCL component of 1 case, but was negative in the other. To the best of our knowledge, the simultaneous occurrence of PTCL unspecified and B-cell small lymphocytic lymphoma is an exceptional event; the possible pathogenetic correlations between the 2 neoplasms are discussed.     

Mitral valve surgery after a failed MitraClip procedure

OBJECTIVESAmong patients undergoing transcatheter mitral valve repair with the MitraClip device, a relevant proportion (2–6%) requires open mitral valve surgery within 1 year after unsuccessful clip implantation. The goal of this review is to pool data from different reports to provide a comprehensive overview of mitral valve surgery outcomes after the MitraClip procedure and estimate in-hospital and follow-up mortality. Open in a separate windowMETHODSAll published clinical studies reporting on surgical intervention for a failed MitraClip procedure were evaluated for inclusion in this meta-analysis. The primary study outcome was in-hospital mortality. Secondary outcomes were in-hospital adverse events and follow-up mortality. Pooled estimate rates and 95% confidence intervals (CIs) of study outcomes were calculated using a DerSimionian–Laird binary random-effects model. To assess heterogeneity across studies, we used the Cochrane Q statistic to compute I² values.RESULTSOverall, 20 reports were included, comprising 172 patients. Mean age was 70.5 years (95% CI 67.2–73.7 years). The underlying mitral valve disease was functional mitral regurgitation in 50% and degenerative mitral regurgitation in 49% of cases. The indication for surgery was persistent or recurrent mitral regurgitation (grade >2) in 93% of patients, whereas 6% of patients presented with mitral stenosis. At the time of the operation, 80% of patients presented in New York Heart Association functional class III–IV. Despite favourable intraoperative results, in-hospital mortality was 15%. The rate of periprocedural cerebrovascular accidents was 6%. At a mean follow-up of 12 months, all-cause death was 26.5%. Mitral valve replacement was most commonly required because the possibility of valve repair was jeopardized, likely due to severe valve injury after clip implantation.CONCLUSIONSSurgical intervention after failed transcatheter mitral valve intervention is burdened by high in-hospital and 1-year mortality, which reflects reflecting the high-risk baseline profile of the patients. Mitral valve replacement is usually required due to leaflet injury.     

Motor-evoked potentials in amyotrophic lateral sclerosis: potential implications in detecting subclinical UMN involvement in lower motor neuron phenotype

Journal of Neurology - In amyotrophic lateral sclerosis (ALS), the involvement of lower motor neuron is well defined by electromyography, whereas a reliable marker of upper motor neuron (UMN)...     

Mitral valve reserve in double-orifice technique: an exercise echocardiographic study

BACKGROUND AND AIM OF THE STUDY: The edge-to-edge technique is used to restore valvular competence in mitral insufficiency. The efficacy of the method is under debate due to the potential for creating functional mitral stenosis. An exercise echocardiographic study was carried out to investigate valve function and hemodynamics in patients who had undergone double-orifice mitral valve repair. METHODS: Thirty patients (mean age 49.1 +/- 12.7 years) with previous double-orifice mitral valve repair underwent exercise echocardiography (10 W/min). An annular prosthesis was present in 28 patients (93%). The mean and maximum mitral valve gradient, planimetric valve area, stroke volume, systolic pulmonary artery pressure, heart rate and systolic blood pressure were measured at baseline and at peak stress. RESULTS: At peak stress, heart rate (77.7 +/- 12.2 versus 118.6 +/- 26.0 beats/min, p < 0.00001), systolic blood pressure (124.1 +/- 10.9 versus 146.6 +/- 22.8 mmHg, p < 0.00001) and stroke volume (78.0 +/- 10.2 versus 97.0 +/- 15.1 ml, p < 0.00001) were significantly increased, showing a physiological behavior of the mitral valve. The mean mitral valve gradient (2.8 +/- 1.3 versus 4.6 +/- 1.9 mmHg, p < 0.00001), maximum mitral valve gradient (6.4 +/- 2.8 versus 10.5 +/- 4.6 mmHg, p < 0.00002) and systolic pulmonary artery pressure (22.8 +/- 6.1 versus 28.2 +/- 9.9 mmHg, p < 0.001) were increased, but not to pathologic levels. Planimetric valve area increased significantly (3.2 +/- 0.6 versus 4.3 +/- 0.7 cm2, p < 0.00001). A significant negative linear correlation was found between the relative change in mitral valve area and planimetric valve area at rest (r = -0.51, p < 0.05). CONCLUSION: The double-orifice repair, even with concomitant ring annuloplasty, does not cause mitral valve obstruction, either at baseline or during physical exercise, and does not affect valve hemodynamic and valve reserve.     

Role of cytokines in gonarthrosis and knee prosthesis aseptic loosening

Cytokines, which have been demonstrated in synovial fluids during various joint diseases, play an important role in mediating synovial inflammation and in regulating the immune response of many inflammatory processes. We studied synovial fluid, serum, and synovial fragments obtained from 33 patients—10 affected by serious gonarthrosis re-quiring a prosthetic implant, 8 with knee prosthesis aseptic loosening, and (as controls) 15 affected by degenerative meniscopathies—to evaluate the degree of inflammation and level of interleukins (IL-2, IL-4, IL-6, IL-10) and interferon secretion. Histological analysis revealed slightly more infiltration by inflammatory cells in the synovial tissue of patients with gonarthrosis and knee prosthesis aseptic loosening than in that of the control group, with a high prevalence of macrophages. Moreover, we observed enhanced production of the studied cytokines, especially in synovial fluid as compared to serum, indicating that in the pathological conditions examined the inflammatory events are mainly localized. Because the role of these cytokines is to modulate inflammation, better knowledge of the involvement of cells and their soluble mediators in articular damage could guide immunomodulating treatment.