Sabrina Paganoni

Background: Assistive technology offers an important means of compensating for lost upper extremity function in adults with progressive neuromuscular diseases (NMD), enabling participation in daily activities, supporting independence, and promoting quality of life. However, the range of available technologies and the evidence supporting their use have not been comprehensively summarized. Aim: The aim of this scoping review was to identify and characterize upper extremity assistive technologies tested in adults with NMD and to summarize the current evidence regarding their functional applications and clinical outcomes. Materials and Methods: Electronic searches for published and unpublished literature were conducted using MEDLINE, Embase.com, Web of Science, Cochrane Central, and IEEE Xplore. The search strategy incorporated controlled vocabulary and free‐text synonyms for the concepts of upper extremity, rehabilitation, selected progressive neurodegenerative diseases, and assistive equipment. Following title/abstract and full‐text screening, studies evaluating assistive devices tested on adults with NMD during functional task performance were included. Results: After screening 2289 articles, 27 studies met the inclusion criteria. The studies collectively demonstrate the potential benefits and diverse range of assistive devices available to support upper extremity function. These devices ranged from low‐tech solutions, such as static mobile arm supports and fabricated splints, to high‐tech devices, including dynamic mobile arm supports, robotic systems, exoskeletons, and brain–computer interface systems. However, most studies were feasibility or case studies that primarily demonstrated proof of concept, with limited evidence regarding long‐term effectiveness, functional outcomes, or quality of life. Discussion: The findings illustrate the rapidly evolving landscape of upper extremity assistive devices for adults with NMD and their potential to improve functional performance, while highlighting the need for prospective studies that assess meaningful improvements in function, participation, and quality of life. Conclusions: As advances in disease‐modifying therapies extend survival and preserve function for individuals with NMD, interdisciplinary collaboration among engineers, clinicians, therapists, individuals with NMD, caregivers, and regulators will be essential to develop, evaluate, and implement assistive technologies that meet users' evolving needs.

Introduction/Aims: Respiratory weakness, typically monitored as vital capacity (VC), is a central feature of amyotrophic lateral sclerosis (ALS). VC is increasingly measured remotely in participants' homes, although in‐clinic assessment remains the standard. We tested concordance between at‐home and in‐clinic VC to determine trial eligibility, track progression, and predict survival in a large ALS trial. Methods: At‐home and in‐clinic VC were assessed at baseline and approximately every 8 weeks for a year in the first four regimens of the HEALEY ALS Platform Trial. At‐home assessments were coached via live videoconference and centrally reviewed. VC measurements, expressed as percent of predicted normal (% PN ), were compared cross‐sectionally, longitudinally, and for predicting survival time. Data from 233 participants with 3–8 paired at‐home and in‐clinic VC assessments completed < 14 days apart were analyzed. Results: At‐home and in‐clinic VC were well correlated (Lin's r _c = 0.82) with no systematic bias. At‐home VC ≥ 60% PN predicted in‐clinic VC ≥ 60% PN with a positive predictive value of 91% and a negative predictive value of 65%. VC slopes were moderately correlated ( r _c = 0.68). At‐home VC progressed 28% faster than in‐clinic VC with proportionately less variance (at‐home [ SE ] = −1.882 [0.153] % PN /month, in‐clinic = −1.476 [0.131] % PN /month). Slopes of at‐home and in‐clinic VC explained 15% and 17% of variation in future survival time, respectively. Discussion: At‐home and in‐clinic VC were well correlated cross‐sectionally. At‐home VC performed well tracking longitudinal change and predicting survival. The reduced participant burden of assessment and concordance with in‐clinic measurement support use of at‐home monitoring of VC.

Introduction/Aims: Tofersen is a gene‐targeted therapy for individuals with superoxide dismutase 1 ( SOD1 ) (+) amyotrophic lateral sclerosis (ALS). Prior to U.S. Food and Drug Administration (FDA) approval, tofersen was made available through expanded access protocol. This study describes the clinical and operational experience of administering tofersen through expanded access protocols at a single academic medical center in the U.S. Methods: Individuals with symptomatic SOD1 (+) ALS (≥ 18 years), who were ineligible for traditional ALS clinical trials, received tofersen via bedside lumbar punctures at Massachusetts General Hospital. Treatment was provided through single‐patient and intermediate‐sized expanded access protocols prior to FDA approval. Demographic and clinical characteristics, referral‐to‐treatment timelines, safety outcomes, and operational costs were collected. Results: Eleven individuals with SOD1 (+) ALS received monthly intrathecal tofersen over a two‐year period (July 2021 to July 2023). Most participants were female, and 81.8% had leg‐onset ALS. The mean (SD) referral‐to‐first dose duration was 36 (22.4) days. A total of 120 doses were administered over a two‐year period. Tofersen was safe and well tolerated, with no treatment‐related serious adverse events. Operational costs totaled $336,620, supported by philanthropy and insurance. The company provided the drug for free. Discussion: This experience demonstrates the feasibility of implementing a resource‐intensive expanded access protocol within an academic medical center using a mixed funding model to facilitate early access to emerging ALS therapies.

Introduction/Aims: Reliable biomarkers for amyotrophic lateral sclerosis (ALS) remain limited. Although previous studies have shown altered cerebrospinal fluid (CSF) tau measures in ALS, the clinical relevance of plasma tau species as biomarkers remains unclear. Here, we sought to determine whether total tau, tau phosphorylated at T181 (pTau‐T181), and their ratio are altered in ALS and whether these measures correlate with disease progression. Methods: Plasma samples were obtained from two independent cohorts from the Northeast ALS Consortium (NEALS) Biofluid Repository (cohort 1: n = 76 ALS and n = 52 healthy controls [HC]; cohort 2: n = 98 ALS and n = 90 HC). Cohort 1 (mean age ALS 61.8 years; 63% male) included longitudinal samples; cohort 2 (mean age ALS 45.8 years; 51% male) was cross‐sectional. Tau measures were quantified using Quanterix Simoa (cohort 1) and Meso Scale Discovery (MSD) (cohort 2) platforms. Results: In cohort 1, total tau was lower in ALS versus HC (0.88 vs. 1.49 pg/mL), whereas pTau‐T181 (30.29 vs. 12.97 pg/mL) and pTau‐T181:tau ratio (52.07 vs. 13.18 pg/mL) were higher. In cohort 2, total tau (40.07 vs. 25.85 pg/mL), pTau‐T181 (6.77 vs. 2.18 pg/mL), and their ratio (0.37 vs. 0.098 pg/mL) were elevated in ALS. Plasma measures in cohort 1 did not correlate with decline on the revised ALS Functional Rating Scale (ALSFRS‐R). Brain‐derived tau (BD‐tau) was elevated in ALS (10.07 vs. 5.65 pg/mL) in a subset of samples from cohort 1. Discussion: Collectively, plasma pTau‐T181 levels are consistently elevated in ALS, supporting future studies to define its potential utility as an ALS biomarker.

Given the lack of consensus on serious illness conversations (SIC) in amyotrophic lateral sclerosis (ALS) by using telehealth, we aim to provide practical strategies in this setting. Over the past 5 years, there has been substantial growth in telehealth, especially after the global COVID-19 pandemic. In ALS, telehealth has become an increasingly used tool for providing clinical care, especially as the disease progresses, when travel becomes challenging and geographic constraints arise. As ALS advances, clinicians often have SIC with individuals living with ALS and their caregivers using telehealth. In the literature, few recommendations are available to improve telehealth communication in the neuropalliative setting. We present 3 case scenarios showcasing telehealth strategies for SICs, with specific considerations for individuals living with ALS. We provide a strategy, CARE in ALS, to support telehealth communication in individuals with speech impairments. We hope to provide practical guidance for health care clinicians in this specific setting.

This study explores the experiences and perceptions of people living with amyotrophic lateral sclerosis (pALS), their caregivers, and healthcare providers regarding participation in clinical trials. The study tested the hypothesis, based on existing literature, that geographic distance from multidisciplinary ALS clinics is the primary barrier to awareness and participation in clinical trials. A road trip was conducted to engage individuals, particularly those residing more than 90 miles from specialized clinics. Qualitative and semi-quantitative methods were used to collect data from in-person interviews conducted with pALS, their caregivers, and healthcare providers in urban (high population density), suburban (residential areas on the outskirts of urban centers), and rural (sparsely populated) settings across the East Coast of the US. Thematic analysis was employed to interpret the data. Based on the interviews, a trusted, supportive, and knowledgeable medical team knowledgeable about ALS research emerged as a critical factor influencing patient participation decisions. Geographic distance alone did not meaningfully impact research interest or awareness. Healthcare providers faced challenges, including time constraints and limited access to updated information about studies, which hindered their ability to promote participation. Healthcare providers cited informal partnerships with advocacy organizations and research centers as crucial for facilitating research participation. Tailored communication strategies that leverage established relationships between pALS and their trusted healthcare providers may enhance research participation. As decentralized research models evolve, improving trial education and access and fostering knowledge and trust could significantly boost enrollment in ALS clinical research.

Background: Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1‐year prospective follow‐up study on PLS and efforts to distinguish it from ALS. Methods: Seventy‐six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1‐year follow‐up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification. Results: Seventy participants completed 1‐year follow‐up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS. Conclusions: In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow‐up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1‐year follow‐up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.

Introduction/Aims: Durable medical equipment (DME)—wheelchairs, non‐invasive ventilation, gastrostomy tubes, and communication devices—provides vital support for individuals with amyotrophic lateral sclerosis (ALS). Here, we describe DME use in COURAGE‐ALS evaluating reldesemtiv's efficacy and safety in ALS, to evaluate if DME use can be considered an endpoint of interest in ALS trials. Methods: COURAGE‐ALS, a multicentre, double‐blind, randomized, placebo‐controlled clinical trial was conducted at 83 sites in the United States, Canada, Europe, and Australia. Participants were randomized 2:1 to receive reldesemtiv or placebo for 24 weeks, followed by 24 weeks of active drug treatment. Exploratory outcomes included reasons for prescribing, extent of use, DME types, and regional differences. Results: Among 482 participants, 166 (34.4%) were using at least one DME item at baseline. Among 276 participants completing study visits through Week 24, 130 (47.1%) initiated use of a total of 188 new DME items post‐baseline through 24 weeks. Manual wheelchairs were most used at baseline (89 items) and initiated (47 items) during the trial. Both baseline DME use and initiating a new item were associated with lower ALS Functional Rating Scale‐Revised scores and worse quality of life. The trial was terminated early due to futility. Treatment assignment did not impact DME use. Regional disparities were noted. Discussion: This study shows that DME is commonly prescribed to ALS trial participants. Further understanding of geographic differences in DME access and their impact on clinical outcomes is warranted prior to including DME use as an endpoint in ALS trials. Trial Registration: ClinicalTrials.gov identifier: (NCT04944784)

Background: Accessing multidisciplinary care poses challenges for people living with amyotrophic lateral sclerosis (ALS) due to mobility issues. As ALS care rarely requires hospital‐based technology, most care is available through home visits. The Daniella Lipper ALS House Call Program (HCP) at Massachusetts General Hospital (MGH), launched in 2017 in collaboration with Compassionate Care ALS, has pioneered home‐based ALS care in Eastern Massachusetts. Methods: A retrospective chart review of ALS and primary lateral sclerosis (PLS) patients enrolled in the HCP at MGH was conducted. Data on demographics, visit details, and procedures performed during home visits were collected from electronic health records for patients seen from January 2024 to December 2024. Results: In 2024, the ALS HCP conducted 959 visits for 142 patients (average age: 68 years, range: 36–93; 47.9% female). Of these patients, 137 (96.5%) were diagnosed with ALS and 5 (3.5%) with PLS. Notably, 61 patients (43%) received care exclusively at home. Key interventions included 44 gastrostomy tube exchanges and 59 respiratory assessments, both of which significantly reduced hospital visits. The average distance traveled by the care team was 30.32 miles per visit. Conclusions: The Daniella Lipper ALS HCP at MGH brings ALS expertise into the patient’s home, minimizing travel burdens and ensuring continuity of care. The program illustrates the feasibility and impact of home‐based ALS care, suggesting potential for broader implementation across the nation. Development will focus on expanding services, such as tracheostomy changes in the homes, and on creating sustainable models for similar initiatives.

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Pridopidine, a selective sigma-1 receptor agonist, was evaluated in Regimen D of the HEALEY ALS Platform Trial. Although the primary endpoint (ALS Functional Rating Scale-Revised (ALSFRS-R) total score accounting for survival at 24 weeks) was not met, a predefined subgroup analysis suggested slowed disease progression in ALS patients with definite and early disease (Methods: The randomized, double-blind, placebo-controlled phase 2 trial assigned participants to pridopidine 45 mg bid or placebo, and placebo patients were shared across four trial regimens. The primary outcome was ALSFRS-R total score, with secondary outcomes assessing respiratory, bulbar, and speech functions. Results: Of 163 participants randomized to Regimen D, 72 met subgroup criteria (pridopidine: n = 37; shared placebo: n = 35). At week 24, pridopidine slowed ALSFRS-R total score decline (32%; Δ2.90, p = 0.03) and slowed decline of ALSFRS-R respiratory function (62%; Δ1.20, p = 0.03) and dyspnea (88%; Δ0.85, p = 0.005). ALSFRS-R-Bulbar function stabilized, with articulation and speaking rate declines reduced by 93% (Δ0.43, p = 0.0007) and 70% (Δ0.43, p = 0.002), respectively. Pridopidine was well-tolerated, with a safety profile comparable to placebo. All p values are nominal. Conclusion: Post hoc subgroup analysis suggests therapeutic benefits of pridopidine in patients that had definite/probable ALS and with early-disease progression, supporting further evaluation in a Phase 3 trial.