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ALS Cases (als + case)
Selected AbstractsFamilial aggregation of amyotrophic lateral sclerosis,ANNALS OF NEUROLOGY, Issue 1 2009Fang Fang MD Objective To assess the relative risk for amyotrophic lateral sclerosis (ALS) in families of ALS patients. Methods We conducted a cohort study based on the Swedish Multi-Generation Register in 1961 to 2005. Among 6,671 probands (first ALS case in the family), 1,909 full siblings, 13,947 children, and 5,405 spouses were identified (exposed group). Other persons in the Multi-Generation Register, who were siblings, children, or spouses to persons without ALS, served as the reference group. Relative risks for ALS among the exposed group, compared with the reference group, were calculated from Poisson regression models. Concurrence of ALS within twins was assessed in 86,441 twin pairs registered in the Swedish Twin Register. Results Nine cases of ALS were noted among the siblings and 37 cases among the children of the probands, giving a 17-fold risk among the siblings (95% confidence interval, 8.1,30.4) and a 9-fold risk among the children (95% confidence interval, 6.2,12.0), compared with the reference group. Siblings and children had a greater excess risk if the proband was diagnosed at a younger age, and the excess risks decreased with increasing age at diagnosis of the proband (p < 0.001). Spouses had no significantly increased risk (p = 0.27). Two cases were identified among the cotwins of ALS probands, giving a relative risk of 32 (95% confidence interval, 5.2,102.6). Interpretation The siblings and children of ALS patients have an about 10-fold risk for ALS compared with the reference group. The excess risks vary with both age and kinship, indicating a major genetic role in familial ALS. Ann Neurol 2009;66:94,99 [source] Signs and symptoms at diagnosis of amyotrophic lateral sclerosis: a population-based study in southern ItalyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2006S. Zoccolella Amyotrophic lateral sclerosis (ALS) diagnostic criteria are used to select patients for clinical trials based on different levels of diagnostic certainty, according to the spread of upper (UMN) and lower motoneuron (LMN) signs in different anatomic regions. However, the clinical presentation of ALS patients is extremely variable and this can delay the time to diagnosis and decrease the likelihood for trial entry. The aims of the study were to describe the signs and symptoms of diagnosis in a population-based incident cohort of ALS cases, using the El Escorial (EEC) and the Revised Airlie Diagnostic Criteria (AHC). The source of the study was a prospective population-based registry established in Puglia, southern Italy, in 1997. The diagnosis and the classification of the cases were based on EEC and AHC. All incident ALS cases during the period 1998,1999 were enrolled and followed up. During the surveillance period, we identified 130 ALS incident cases, and bulbar-ALS represented 20% of our cohort. The highest risk for bulbar onset was among subjects aged >75 years [RR: 20.1, 95% confidence interval (CI) 3.4,118.0] compared with subjects aged <55 years and among females compared with males (Relative risk (RR): 2.75, 95% CI: 1,7.3). The vast majority of patients (72%) referred progressive muscle weakness in the limbs as the presenting symptom. Eighty percent of cases presented contemporary bulbar or spinal involvement; UMN signs in the bulbar region were present in 24% of cases and any motoneuronal sign in thoracic region in only 15% of the cases. In this population-based series, progressive muscle weakness was the most common presenting sign; bulbar onset was associated with advanced age and female sex. UMN signs in the bulbar region and any motoneuronal sign in the thoracic region were observed in 20% of our case series. This may represent the main limitation to show the spread of signs during diagnostic assessment for inclusion in epidemiological studies and clinical trials. [source] Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathyNEUROPATHOLOGY, Issue 2 2010Tetsuaki Arai Transactivation response (TAR) DNA-binding protein of Mr 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathy. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role for the pathological process. In cultured cells, transfected C-terminal fragments of TDP-43 are more prone to form aggregates than full-length TDP-43. Transfecting the C-terminal fragment of TDP-43 harboring pathogenic mutations of TDP-43 gene identified in familial and sporadic ALS cases into cells enhanced the aggregate formation. Furthermore, we found that methylene blue and dimebon inhibit aggregation of TDP-43 in these cellular models. Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics. [source] FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosisANNALS OF NEUROLOGY, Issue 6 2010Han-Xiang Deng MD Objective Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are familial (FALS). Recent studies have shown that mutations in FUS are causal in approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic mechanism of the mutant FUS-mediated ALS and potential roles of FUS in non-FUS ALS remain to be investigated. Methods Immunostaining was performed on postmortem spinal cords from 78 ALS cases, including SALS (n = 52), ALS with dementia (ALS/dementia, n = 10), and FALS (n = 16). In addition, postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also studied. In total, 100 cases were studied. Results FUS-immunoreactive inclusions were observed in spinal anterior horn neurons in all SALS and FALS cases, except for those with SOD1 mutations. The FUS-containing inclusions were also immunoreactive with antibodies to TDP43, p62, and ubiquitin. A fraction of tested FUS antibodies recognized FUS inclusions, and specific antigen retrieval protocol appeared to be important for detection of the skein-like FUS inclusions. Interpretation Although mutations in FUS account for only a small fraction of FALS and SALS, our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying SALS, non-SOD1 FALS, ALS/dementia, and related disorders. Our data also indicate that SOD1-linked ALS may have a pathogenic pathway distinct from SALS and other types of FALS. ANN NEUROL 2010;67:739,748 [source] Smoking and risk for amyotrophic lateral sclerosis: Analysis of the EPIC cohort,ANNALS OF NEUROLOGY, Issue 4 2009Valentina Gallo MD Objective Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14,3.14), while former smokers at the time of enrolment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94,2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33,3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure. Ann Neurol 2009;65:378,385. [source] | ||||||||||