Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. Methods: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. Results: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. Conclusions: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

The strengths of the registry are discussed. The registry has proven to be an invaluable tool to NM disease research and has increased Canada's visibility as a competitive location for the conduct of clinical trials for NM therapies.

Background: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. Objective: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. Methods: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. Results: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. Conclusions: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

The previous TREAT-NMD Duchenne muscular dystrophy (DMD) dataset was designed mainly to support clinical trial feasibility and recruitment. Therapeutic developments, anticipation of post-marketing surveillance and interest in better understanding the disease natural history, meant the dataset needed to be updated to meet these new requirements. To reach consensus on a new version of data items that can be shared amongst the stakeholder community, and used by all registries collecting data from DMD patients, a working group (WG) including clinical experts, patient representatives and registry curators met in 2019 to workshop an updated dataset. Using an established TREAT-NMD project methodology, a consensus was achieved for new data items including for hospitalisations and comorbidities, nutrition, therapies and others. The feasibility of implementing the new dataset into existing registries was evaluated in a pilot exercise with 14 registries. The results of the pilot exercise were then shared with the WG and discussed in a further dataset development workshop to finalise the new DMD dataset. The updated dataset includes items. Based on the pilot exercise feedback, 49% of the new data items were already collected. 74% of new items were rated as very easy to moderately difficult to collect. 39 items rated as challenging were taken to the WG for re-evaluation. Version 1.1 of the new DMD dataset for clinically reported registries was published in February 2021. A separate focus group is reviewing a proposed dataset for patient reported registries. Collaborating with its global alliance of registries, leading clinicians and other partners, TREAT-NMD is ideally positioned to advance the expansion of the DMD dataset, to enable registries to be a reliable source of data in the collection of real-world evidence and to capture valuable information for regulatory purposes and post marketing activities.

Neuromuscular Disorders 31 (2021) S47-S162 interventions that patients have accessed and 4) Review use of mobility aids and home adaptations. 150 responses have been collected across the whole UK. They are mainly adult patients (74%) with a median age of 34 years of age. 41% of them are women. 17% are non-sitters, 48% sitters and 23% walkers. SMA type is mainly represented by type 3 (48%) followed by type 2 (34%). The model of care reported showed that physiotherapists (66,1%-community and specialized), neurologists in a specialized centre (65.3%), GP (54.8%) and occupational therapists in community setting (56.5%) are the most commonly visited health care professionals. On the other hand, psychological or emotional support is only accessed by 13.7% of the population. Nurses, pulmonologists and respiratory physiotherapists are normally seen in a specialised service setting and only by a smaller proportion (31 to 16 %) of the population. Despite being reported by a high percentage of responders, access to physiotherapy is mainly for paediatric patients (97%), dropping to only 44% of the adult population spread across community and specialised services. The present results, despite not being representative of the overall SMA population in the UK, show an initial impression of the real-world access to care for people with SMA. Further collection of responses will allow a more thorough analysis of the different services across the country.

Amyotrophic lateral sclerosis (ALS) is a fatal disease primarily affecting motor neurons. In Europe and North America, about 5 % of ALS patients report a positive family history (familial ALS, fALS). The remaining is classified as sporadic ALS (sALS). A genetic basis for ALS has been demonstrated for both fALS and sALS and variants in > 40 genes have been associated with ALS. Following linkage analysis in families with Mendelian dominantly inherited fALS, mutations in the gene encoding the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 ( SOD1 ) were discovered in 1993. Since then, more than 200 mutations in SOD1 have been described. We here report a novel SOD1 homozygous mutation with an early onset, rapidly progressive phenotype in a family with two affected members from southern Egypt. The parents are cousins with three children. At age 10 years old, the youngest son initially developed a foot drop of one limb followed by a rapidly progressive disease affecting the other limbs and bulbar innervated muscles. He died from respiratory failure at the age of 12 years. At age 25 years, the eldest sister developed ALS with a similar phenotype. She is still alive at age 28 years. Both patients were diagnosed to have ALS according to the revised El Escorial criteria. SOD1 DNA analysis was performed using bi-directional Sanger sequencing of the 5 exons and adjacent 30-50 bp intronic sequences. Mutations in a number of other ALS-causing genes were excluded. Genetic screening revealed a novel exon 3 homozygous p.Ser69Pro SOD1 mutation in the affected female patient; while her parents and unaffected younger brother are heterozygous for the mutation (no sample is available from the deceased son). So, we report a novel homozygous p.Ser69Pro SOD1 mutation associated with early onset of asymmetrical weakness of lower limbs with a rapidly ascending paresis. It is likely that her deceased brother had the same genotype. The early onset and rapidity of evolution of disease suggest a strong dose-effect of the mutant SOD1 protein. Exon 3 mutations in SOD1 are frequently associated with reduced disease penetrance but we cannot exclude the possibility that the p.Ser69Pro SOD1 also predisposes heterozygous individuals for ALS later in life.

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