Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients

Retrospective observational study on the use of acetyl-L-carnitine in ALS

: ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case-control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46-3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10-0.71). For ALSFRS-R, a mean slope of - 1.0 was observed in treated subjects compared to - 1.4 in those not treated (p = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage

Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy

: Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype-phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70-75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype-genotype correlations in the ALS population of ERR

Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy

Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

Objective: In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy. Methods: A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31.12.2015. Results: During the 6 years of the study, there were 681 incident cases with a median tracheostomy-free survival of 40 months (95% CI 36â\u80\u9344) from onset and of 26 months (95% CI 24â\u80\u9330) from diagnosis; 573 patients (84.14%) were treated with riluzole, 207 (30.39%) patients underwent gastrostomy, 246 (36.12%) non invasive ventilation, and 103 (15.15%) invasive ventilation. Patients who took treatment for â\u89¥Â 75% of disease duration from diagnosis had a median survival of 29 months compared to 18 months in patients with < 75% treatment duration. In multivariable analysis, factors independently influencing survival were age at onset (HR 1.04, 95% CI 1.02â\u80\u931.05, p < 0.001), dementia (HR 1.56, 95% CI 1.05â\u80\u932.32, p = 0.027), degree of diagnostic certainty (HR 0.88, 95% CI 0.78â\u80\u930.98, p = 0.021), gastrostomy (HR 1.46, 95% CI 1.14â\u80\u931.88, p = 0.003), NIV (HR 1.43, 95% CI 1.12â\u80\u931.82, p = 0.004), and weight loss at diagnosis (HR 1.05, 95% CI 1.03â\u80\u931.07, p < 0.001), diagnostic delay (HR 0.98, 95% CI 0.97â\u80\u930.99, p = 0.004), and % treatment duration (HR 0.98, 95% CI 0.98â\u80\u930.99, p < 0.001). Conclusions: Independently from other prognostic factors, patients who received riluzole for a longer period of time survived longer, but further population based studies are needed to verify if long-tem use of riluzole prolongs survival

Risk of Guillain-Barr\ue9 syndrome after 2010-2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barr\ue9 Syndrome (GBS) although the evidence for this link is controversial. A case-control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged 6518 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case-control analysis and a self-controlled case series analysis (SCCS). Case-control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations