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Introduction : Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods : A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 ( C9orf72 ) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results : For the ALS group, the statistical model explained 38.8% of variance in ECAS total ( p  < 0.001), 59.4% of executive functions ( p  < 0.001), and 55% of behavioral symptoms ( p  < 0.001). For controls, it accounted for 52.8% of variance in ECAS total ( p  < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups ( p  < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls ( p  = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients ( p  = 0.009). Conclusion : This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.

Background: C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort., Methods: Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared. ALS al Rating Scale-Revised (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) were used to evaluate functional and cognitive performance, respectively. Survival analysis was performed using Kaplan Meier log-rank test and Cox proportional hazards model., Results: We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, p = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, p = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, p = 0.003) and more frequent MND family history (65.5 vs 11.4 %, p < 0.001). Gender, ethnicity, onset site, diagnostic delay, disease progression rate until diagnosis (ΔF), ALSFRS-R and time until non-invasive ventilation did not differ between groups. Cognitive/behavioural symptoms and ECAS did not differ between groups, except a worse visuospatial score in C9RE+ group (p = 0.035). Death rate was 1.8 and 1.6 times higher in C9RE+ patients with MND and ALS, respectively. Significant survival prognostic factors in C9RE+ group were diagnosis delay (HR = 0.96, 95 %CI 0.92-0.99, p = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26-2.96, p = 0.002)., Conclusion: Our study corroborates most previous cohorts' findings, but harbours some singularities regarding onset site, phenotype, and cognitive profile, that contribute to a better understanding of C9RE epidemiology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Digital health interventions including telehealth, mobile health, artificial intelligence, big data, robotics, extended reality, computational and high-fidelity bench simulations are an integral part of the path toward precision medicine. Current applications encompass risk factor modification, chronic disease management, clinical decision support, diagnostics interpretation, preprocedural planning, evidence generation, education, and training. Despite the acknowledged potential, their development and implementation have faced several challenges and constraints, meaning few digital health tools have reached daily clinical practice. As a result, the Portuguese Society of Cardiology Study Group on Digital Health set out to outline the main digital health applications, address some of the roadblocks hampering large-scale deployment, and discuss future directions in support of cardiovascular health at large., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: The lack of standardised definitions for heart failure outcome measures limits the ability to reliably assess effectiveness of heart failure therapies. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) aimed to produce a catalogue of internationally endorsed data definitions for heart failure outcome measures., Methods: Following the EuroHeart methods for the development of cardiovascular data standards, a working group was formed of representatives from the European Society of Cardiology Heart Failure Association and other leading heart failure experts. A systematic review of observational and randomised clinical trials identified current outcome measures, which was supplemented by clinical practice guidelines and existing registries for contemporary definitions. A modified Delphi process was employed to gain consensus for variable inclusion and whether collection should be mandatory (Level 1) or optional (Level 2) within EuroHeart. In addition, a set of complementary outcome measures were identified by the Working Group as of scientific and clinical importance for longitudinal monitoring for people with heart failure., Results: Five Level 1 and two Level 2 outcome measures were selected and defined, alongside five complementary monitoring outcomes for patients with heart failure., Conclusion: We present a structured, hierarchical catalogue of internationally endorsed heart failure outcome measures. This will facilitate quality improvement, high quality observational research, registry-based trials, and post market surveillance of medical devices., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background : The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. Objectives : This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS. Methods : 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed. Results : ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients. Discussion : Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.

Identified as a potential reference pathogen by the WHO Guidelines for Drinking-Water Quality, Rotavirus (RV) is among the main enteric viruses that cause waterborne diseases. The aim of this study was to identify and correlate the presence of RV in collective and individual water sources of rural communities in the state of Goiás, within the seasons in which the collections were made (rainy and dry seasons). For this, 86 water samples in the dry period and 160 samples in the rainy period were collected. Concentration of water samples, extraction of viral genetic material and molecular tests were performed. When analyzing the presence of RV in the samples, taking into consideration the period studied, RV was found to be more prevalent in the dry season (54.7%) than in the rainy season (20%), showing a strong statistical association with the dry season ( p -value < 0.001). The presence of pathogenic microorganisms in water is a public risk issue, enabling the emergence of outbreaks, endemics and epidemics. In the present research, there was an association between the presence of Rotavirus and the dry period of the year when compared to the rainy period.

Introduction and Objectives: Digital health (DH) is a broad concept, bringing together technology and healthcare, that is playing an increasingly important role in the daily routine of healthcare professionals (HCPs) and promises to contribute to the prevention and treatment of cardiovascular disease. There are no solid data on the position of Portuguese HCPs toward the implementation of DH in cardiovascular medicine. This national cross-sectional study aims to provide a snapshot of DH implementation in Portuguese cardiovascular HCP routines and to identify both expectations and barriers to its adoption., Methods: An 18-question survey was created specifically for this study and distributed to 1174 individuals on the Portuguese Society of Cardiology mailing list., Results: We collected 117 valid responses (response rate 10%). Almost all participants had smartphones and laptops, and two-thirds had tablets. Electronic medical information systems were the most used DH tool (84% of respondents) and were considered the most important for improving cardiovascular care. Implantable technologies (sensors and devices), telemedicine and social media were used by more than two out of three respondents and considered «very important» or «extremely important» by most of them. Most participants showed positive expectations regarding the impact of DH in cardiovascular medicine: 78% agreed that DH could improve health outcomes, 64% that it promotes health literacy and 63% that it could decrease healthcare costs. The top-rated barriers were patients' inability to use smartphones, limited access to electronic devices, and lack of legal regulation of DH., Conclusion: Most Portuguese cardiovascular HCPs had at least three electronic devices (mainly smartphones, laptops and tablets) and showed positive expectations regarding DH's current and future impact on cardiovascular medicine. Patient DH literacy, technology adoption, and DH regulation were identified as the most important barriers to increasing the adoption of DH tools in cardiovascular medicine., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Atherosclerotic plaque fluorine-18 sodium fluoride ( 18 F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18 F-NaF uptake., Methods: Subjects with high CV risk but without CV events underwent 18 F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18 F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18 F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18 F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation., Results: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL -1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18 F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003)., Conclusion: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18 F-NaF uptake was significantly reduced after six months of high-intensity statin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction/aims: The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP)., Methods: We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients., Results: We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP., Discussion: In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction and Objectives: Three-dimensional (3D) model simulation provides the opportunity to manipulate real devices and learn intervention skills in a realistic, controlled, and safe environment. To ensure that simulators provide a realistic surrogate to real procedures they must undergo scientific validation. We aimed to evaluate the 3D-printed simulator SimulHeart® for face and content validity to demonstrate its value as a training tool in interventional cardiology (IC)., Methods: Health professionals were recruited from sixteen Portuguese IC units. All participants received a 30-minute theoretical introduction, 10-minute demonstration of each task and then performed the intervention on a 3D-printed simulator (SimulHeart®). Finally, a post-training questionnaire focusing on the appearance of the simulation, simulation content, and satisfaction/self-efficacy was administered., Results: We included 56 participants: 16 "experts" (general and interventional cardiologists), 26 "novices" (cardiology residents), and 14 nurses and allied professionals. On a five-point Likert scale, the overall mean score of face validity was 4.38±0.35 and the overall mean score of content validity was 4.69±0.32. There was no statistically significant difference in the scores provided by "experts" and "novices". Participants reported a high level of satisfaction/self-efficacy with 60.7% considering it strongly improved their skills. The majority (82.1%) "agreed" or "strongly agreed" that after the simulation they felt confident to perform the procedure on a patient., Conclusion: The 3D-printed simulator (SimulHeart®) showed excellent face and content validity. 3D simulation may play an important role in future IC training programs. Further research is required to correlate simulator performance with clinical performance in real patients., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23-75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex ( p < 0.001), spinal onset ( p = 0.018), and FVC ≥ 80% ( p = 0.038). CK was 23.4% higher in spinal-onset ALS patients ( p < 0.001). High CK levels were not linked with an increased risk of death ( p = 0.334) in Cox multivariate regression analysis. CK ≥ P90 (HR = 1.001, p = 0.038), shorter disease duration (HR = 0.937, p < 0.001), lower pCMAP (HR = 0.082, p < 0.001), and higher ΔFS (HR = 1.968, p < 0.001) were risk factors for respiratory failure. The association between high CK levels and poorer respiratory outcomes could derive from cellular metabolic stress or a specific phenotype associated with faster respiratory decline. Our study suggests that CK measurement at diagnosis should be more extensively investigated as a possible marker of poor respiratory outcome in future studies, including a larger population of patients., Competing Interests: The authors declare no conflicts of interest.

Introduction: Nusinersen was approved for 5q spinal muscular atrophy (SMA), irrespective of age, SMA type or functional status. Nonetheless, long-term data on adults with milder phenotypes are scarce. We aimed to characterize evolution on motor and respiratory function in our cohort of adults with type 3 SMA., Methods: We conducted a longitudinal retrospective single-center study, including adults (≥18 years) with type 3 SMA under nusinersen for > 22 months. We reported on motor scores and spirometry parameters., Results: Ten patients were included, with a median follow-up of 34 months (range = 22-46). Four patients (40%) were walkers. None used non-invasive ventilation. In Revised Upper Limb Module (RULM) and Expanded Hammersmith Functional Motor Scale (HFMSE), difference of medians increased at 6, 22 and 46 months comparing to baseline (-0.5 vs. + 1.5 vs. + 2.5 in RULM; + 4.0 vs. + 7.5 vs. + 6.0 in HFMSE). Two (50%) walkers presented a clinically meaningful improvement in 6-min walk distance. We did not report any clinically meaningful decrement in motor scores. Spirometry parameters showed an increasing difference of medians in maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (-3 vs. + 13.4 vs. + 28.7 percentage points of predicted value for MIP; + 11.8 vs. + 13.1 vs. 13.3 percentage points of predicted value for MEP)., Discussion: Our cohort supports a sustained benefit of nusinersen in adults with type 3 SMA, in motor and respiratory function. Multicentric studies are still warranted., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in about 2% of all patients. Tofersen is a novel oligonucleotide antisense drug specifically developed to treat SOD1-ALS patients., Areas Covered: Our review covers and discusses tofersen pharmacological properties and its phase I/II and III clinical trials results. Other available drugs and their limitations are also addressed., Expert Opinion: VALOR study failed to meet the primary endpoint (change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to week 28, tofersen arm vs. placebo), but a significant reduction in plasma neurofilament light chain (NfL) levels was observed in tofersen arm (60% vs. 20%). PrefALS study has proposed plasma NfL has a potential biomarker for presymptomatic treatment, since it increases 6-12 months before phenoconversion. There is probably a delay between plasma NfL reduction and the clinical benefit. ATLAS study will allow more insights regarding tofersen clinical efficacy in disease progression rate, survival, and even disease onset delay in presymptomatic SOD1 carriers.

Background: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients., Material and Methods: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed., Results: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited., Conclusions: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier., Competing Interests: Declaration of competing interest Miguel Oliveira Santos and Mamede de Carvalho received support from Sanofi. The other authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction/aims: In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS., Methods: We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H' RI ) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H' Pre ) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H' Pos )., Results: Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H' RI 0.35 vs. 0.11, p = .036; H' Pre 1.0 vs. 5.0, p = .001; H' Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition., Discussion: Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS., (© 2024 Wiley Periodicals LLC.)

Stroke is a significant public health problem, with non-valvular atrial fibrillation (NVAF) being one of its main causes. This cardiovascular arrhythmia predisposes to the production of intracardiac thrombi, mostly formed in the left atrial appendage (LAA). When there are contraindications to treatment with oral anticoagulants, another therapeutic option to reduce the possibility of thrombus formation in the LAA is the implantation of an occlusion device by cardiac catheterization. The effectiveness of LAA occlusion is dependent on accurate preprocedural device sizing and proper device positioning at the LAA ostium, to ensure sufficient device anchoring and avoid peri-device leaks. Additive manufacturing, commonly known as three-dimensional printing (3DP), of LAA models is beginning to emerge in the scientific literature to address these challenges through procedural simulation. This review aims at clarifying the impact of 3DP on preprocedural planning of LAA occlusion, specifically in the training of cardiac surgeons and in the assessment of the perfect adjustment between the LAA and the biomedical implant., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Background and Purpose: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function of ALS patients is uncertain., Methods: A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO 2 mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t-test, χ 2 , or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan-Meier analysis assessed survival. p < 0.05 was considered significant., Results: We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS-R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO 2 mean (p = 0.014)., Conclusions: ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Primary lateral sclerosis (PLS) is a rare, adult-onset and slowly progressive motor neuron disorder whose clinical core is characterized by upper motor neuron (UMN) dysfunction. Its formal diagnosis is clinically based and disease duration-dependent. Differentiating PLS from other disorders involving UMN can be challenging, particularly in the early stages., Areas Covered: Our review covers and discusses different aspects of the PLS field, including the diagnostic criteria and its limitations, its differential diagnosis and their major pitfalls, and the actual role of neurophysiology, neuroimaging, genetics, and molecular biomarkers. Symptomatic treatment of the different manifestations is also addressed. The authors searched MEDLINE and Scopus. They also searched the reference lists of articles identified by our search strategy and reviewed and selected those deemed relevant. They selected papers and studies based on the quality of the report, significance of the findings, and on the author's critical appraise and expertise., Expert Opinion: It is important to investigate novel molecular biomarkers and plan multicenter clinical trials for PLS. However, this will require a large international project to recruit enough patients, particularly given the diagnostic uncertainty of the current clinical criteria. A better understanding of PLS pathophysiology is crucial for designing disease-targeted therapies.