In the natural progression of amyotrophic lateral sclerosis (ALS), a state of malnutrition often develops, associated with reduced oral intake, caused by difficulties with swallowing, adequate salivation, and/or anorexia. The placement of a feeding tube should be considered at the point where patients demonstrate swallowing difficulty and/or alteration in nutritional status. The goal of this prospective work was to compare, in 50 patients having definite or probable ALS, the complications after endoscopic (PEG), or radiologically-guided gastrostomy (RIG) and to evaluate their effects on survival. RIG was proposed as first-line therapy when patients had a slow vital capacity (SVC) less than 50% of the theoretical value, or in a case where PEG was refused by the patient. Thirty patients underwent PEG procedure, and 20 had RIG. Among the decisional criteria for placing a gastrostomy tube, risk of aspiration demonstrated by using videofluoroscopy was more frequently observed in the RIG group (65%) than in the PEG group (19.2%) (p=0.002). The two patient populations at time of gastrostomy placement were comparable with respect to age, gender ratio, disease duration before gastrostomy, the form and the gravity of neurological involvement as well as for nutritional criteria. The only significant difference observed between the two groups was the level of the SVC, much lower for patients undergoing RIG: 51.6+/-25.0% versus 67.4+/-26.7% than for the PEG group (p=0.03). The frequency of all complications observed at the moment of placement of gastrostomy tube and during the first month of follow-up was not significantly different between the two groups. Kaplan-Meier survival curves from the date of gastrostomy placement were not different in univariate analysis (p=0.85). In multivariate analysis, survival was not different between one group and the other (p=0.28). The major interest of the RIG technique rests on its greater feasibility and on the possibility of utilizing it in ALS patients who have significant ventilatory compromise.

Background: Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population. Results: Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina's NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease. Conclusions: The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.

ObjectivesThis study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population.MethodsDemographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996–2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion.ResultsThe mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients).Conclusions and relevanceThis study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.

Objective: To determine the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the Republic of Uruguay.Methods: The study was performed in Uruguay (3,241,003 inhabitants) during a 2-year period (2002–2003). To ensure complete case ascertainment, multiple sources of information were used, including all the neurologists, other medical specialties, general physicians, neurophysiology laboratories, hospital medical records and death certificates. ALS diagnosis was based on El Escorial criteria. Although all patients with motor neuron disease were enrolled in the follow-up, only probable and definite cases are included in the study. Results: Between January 1st, 2002, and December 31st, 2003, 89 new patients were diagnosed with probable or definite ALS. The mean annual incidence rate was 1.37 per 100,000 persons. The incidence was higher for men (1.95) than for women (0.84) with a male to female ratio of 2:1. For both, the incidence increased throughout the years showing a peak in the 65–74 age group among men and the 55–64 age group among women. Mean age at onset of ALS disease was 58.7 years. The estimated mean annual incidence for ALS calculated by the capture recapture method was 1.42 (95% CI, 1.13–1.72). On December 31st, 2002, the crude prevalence was 1.9 per 100,000 inhabitants. Conclusions: ALS incidence is within a narrow range across countries despite the genetic, environmental and socioeconomic differences when similar prospective design, diagnosis criteria and data analyses are applied.