Patients with neuromuscular diseases (NMD) have undergone considerable technological progress in terms of diagnosis and treatment over the past few years. Specifically, next-generation sequencing (NGS) has significantly expanded genetic diagnosis. Despite this, some patients remain undiagnosed and therefore without access to specific treatments. Analyses of epidemiology and diagnostic approaches in reference centers are required to determine effective strategies to improve diagnostic rates. We studied the proportion of each NMD and associated investigations in the patient population of the Neuromuscular Reference Center (NMRC) of Liege, Belgium, in 2023. The investigation tools used included laboratory testing, muscle biopsy, muscle imaging, single-gene sequencing, targeted NGS panels, and whole-exome sequencing (WES). Of the 1084 patients who were regularly followed up, more than one-third had neuropathies (36.6

Assessing the efficacy of investigational drugs in ambulant patients with Duchenne muscular dystrophy (DMD) is challenging due to a lack of objective, reliable, and sensitive outcome measures, especially in patients <4 years old (yo). Using the ActiMyo/Syde wearable device to accurately measure ambulation in the daily life, we recently secured primary endpoint qualification of SV95C (95th centile of stride velocity, the 5% most rapid strides) by the European Medicines Agency, in ambulant DMD from the age of 4. The multicentre ActiLiège-Next study aims to determine the feasibility, robustness & sensitivity of SV95C in children 1-14yo and to gather 3-year longitudinal data from ambulant DMD patients and healthy controls. ActiMyo/Syde sensors are worn on the ankle by patients daily for the first 3 months and then for 1 month daily every 3 months, and by controls for 1 month daily every 6 to 12 months. 116 DMD patients aged 1 to 14 yo (median±SD: 7.0±3.0yo) and 43 controls (8.8±3.7yo) were enrolled, of which 26 patients and 10 controls were younger than 4yo. SV95C reliability at baseline was excellent, with an ICC of 0.97 (patients ≥4yo) and 0.92 (patients <4yo). SV95C was statistically different between DMD and controls, including in patients <4yo. The Spearman correlation with North Star Ambulatory Assessment, 6-Minute Walk Test, 4-stair climbing test and time to rise from floor was 0.72, 0.60, -0.73 and -0.70 respectively (n=76-84; p<0.001). In patients ≥4yo, median SV95C relative change from baseline at 6 and 12 months was 0.3% (n=56) and -8.4% (n=48) respectively, with a marked decline in patients ≥8yo. All available longitudinal data will be shared (6-month and 18-month data for <4yo and 4-14yo patients, respectively). If these promising results and good metric properties are confirmed, SV95C could be the first functional assessment that can be used in all ambulant DMD including those below the age of 4 and enable development and approval of new treatments. 88 ambulant DMD patients aged 4 to 14 years old (median ± SD: 7.9 ± 2.4yo) and 33 age-matched healthy controls (9.8 ± 2.6yo) were enrolled. SV95C reliability at baseline was excellent, with an age-independent intraclass correlation greater than 0.97. The Spearman correlation with North Star Ambulatory Assessment, 6-Minute Walk Test, 4-stair climbing test and time to rise from floor was 0.70, 0.55, -0.74 and -0.70 respectively (n=75-79; p<0.001). Median SV95C relative change from baseline at 6 and 12 months was 0.3% (n=56) and -8.4% (n=48) respectively, with a marked decline in patients ≥8 years old (-3.6% and -11.9% respectively, n=27 and 23). These data confirm the excellent reliability, external validity and responsiveness of SV95C in ambulant DMD patients above 4 years of age. The available 18-month follow-up data will be presented.

Several newborn screening (NBS) programs for Spinal Muscular Atrophy (SMA) have demonstrated feasibility-reliability and short-term efficacy of PCR-based universal SMA NBS, but longer-term data are needed to precise the benefit of this intervention. In addition, the comparison with external control groups can reinforce the level of evidence and support robust health economic assessment. The aim of this study is to compare the medical, quality of life and economic data for SMA patients diagnosed by NBS and those identified by symptoms, in the same country, during the same time period. We collected data on all SMA patients born in Flanders and the Wallonia-Brussels Federation (FWB) between January 1, 2019 (the date on which the entire FWB began screening for SMA) and 30 November 2022 (the date on which Flanders began screening). We compared the median age of diagnosis and initiation of treatment, the treatment, scores on motor development scales, and the age of acquisition of sitting and walking. We also collected quality of life data for parents, utility data for children, and costs associated with the disease. A total of 30 patients were included in the analysis: 16 patients in FWB (7 with 2 SMN2 copies, 4 with 3 copies and 5 with 4 copies) and 13 in Flanders. One patient with a point mutation was not identified by NBS in FWB. Patients in FWB were initially treated by nusinersen (n = 5) risdiplam (n = 3) and onasemnogene abeparvovec (n = 7) at 36 days of life on average (29, 37, and 44 days respectively for patients with 2, 3 and 4 SMN2 copies of SMN2). Two patients shifted from nusinersen to risdiplam, one from nusinersen to onasemnogene abeparvovec and one from risdiplam to onasemnogene abeparvovec. One patient with 4 SMN2 copies was still untreated at 26 months. Median follow up was 32 months (9-54 months). All patients over 18 months with 3 and 4 SMN2 copies acquired ambulation (median age: 17 months, 13-24 months). Of the 7 patients with 2 SMN2 copies, 2 are not yet 18 months old, 4 are walking, and one aged 24 months is not yet walking. One child with 2 SMN2 copies have non-invasive nocturnal ventilation. None of the children needed nutritional support at the time of the last follow-up. Data in Flanders, where NBS was not implemented in the studied time, are currently collected, and will be presented during the congress. Our data shows that middle term outcome of patients identified by NBS is very good so far. Estimation of health care cost saving will be presented.

X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disorder caused by mutations in the myotubularin (MTM1) gene, affecting 1:50000 male births. The clinical severity varies, however the need for ventilatory support is often inevitable. At present, no approved therapies are available for XLMTM. Patient management is mainly supportive. A first MTM1 gene replacement therapy tested in a clinical trial showed notable improvements on ventilator dependence and motor function but raised serious safety concerns. Forty patients have been enrolled in our European prospective natural history study of patients with XL-MTM designed to characterize the disease course by using standardized evaluations adjusted for age, ambulatory and respiratory status. At 3-year follow-up, data were available for 26 patients (65%) with a mean age of 14.3 (min 3.4, max 53.8) years. Drop-outs were due to loss to follow-up (n=1), death (n=1) and early withdrawal from the study (n=3). Nineteen percent (5/26) of patients were under the age of 6 years old. Among non-ambulant patients at baseline (n=19), only 1 acquired the ability to walk during the study. Respiratory function, strength and motor function did not statistically change. Muscle strength measured by MyoPinch and MyoGrip showed a mean decline of -1,04 kg (n=20) and -0.33kg (n=20) respectively. MFM D1 showed the most important decline of -2.98% at 36 months. Nine patients presented with a mean increase of grip strength of 1.5kg (SD 4.18) (n=13). Ten patients showed a mean increase of the pinch strength of 0.16kg (SD 0.71) (n=14). Correlation data will be presented. This first multicentric longitudinal natural history in all types of patients with XL-MTM demonstrates clearly that patients experience a decline over years that can be reliably measured. We have identified several strength-, functional and respiratory outcomes that can be used to build robust clinical trials in this population.

The objective of the study was to assess the cost-effectiveness of real-world spinal muscular atrophy newborn screening followed by treatment. We modeled the lifetime cost-effectiveness of the spinal muscular atrophy newborn screening followed by treatment (screening) compared to treatment without screening (no screening) from the Belgian healthcare perspective. Real-world data, including quality of life, costs, and motor development data, were collected on 12 patients identified by screening and 43 patients identified by their symptoms. "Screening" was associated with slightly higher healthcare costs ( C 6,858,061 vs. C 6,738,120) but more quality-adjusted life years (QALY) (40.95 vs. 20.34) compared to "no screening", leading to an incremental cost-effectiveness ratio of C 5,820 per QALY gained. "Screening" was dominant from a societal perspective (negative incremental costs: C-14,457; incremental QALY = 20.61), when incorporating the burden on caregivers (negative incremental costs = C-74,353; incremental QALY = 27.51), and when the treatment was chosen by the parents (negative incremental costs = C-2,596,748; incremental QALY = 20.61). Spinal muscular atrophy newborn screening coupled with early treatment is thus cost-effective compared with late treatment following clinical diagnosis and is dominant when societal perspective, caregiver burden, and treatment based on parental preference were considered.(c) 2023 Elsevier B.V. All rights reserved.

Cystic echinococcosis is a zoonosis caused by the larval form of the tapeworm Echinococcus granulosus . It has a worldwide distribution and represents a particularly significant economic and health burden in endemic areas. The most affected organs are the liver and the lungs. Cerebral involvement is relatively rare. This is a case study of a clinical presentation of cerebral cystic echinococcosis in a 5-year-old female patient of Moroccan origin who had developed recurrent seizures. Currently, diagnosis is based on radiological imaging in the context of anamnestic suspicion. Beyond the conclusions that can be drawn from the various case reports, there are no guidelines on management methods or randomized controlled trials that have compared management methods, and their absence can be deleterious for children. We present this clinical case report to add to the existing ones and to assist clinicians in their therapeutic decision-making while they await guidelines.

Nutritional problem is frequently observed in pediatric patients with spinal muscular atrophy (SMA).In this study, we aimed to investigate the nutritional status in Chinese patients with SMA.Clinical data including the body weight, length, body mass index (BMI) and the levels of serum 25-hydroxy Vitamin D (25-OHD) of SMA patients from January 2022 to March 2022 were collected and analyzed.We used the Z-score (standard deviation) to analyze the BMI.The levels of serum 25-OHD were graded as follows: 75-250nmol/L for normal, 50-75nmol/L for insufficiency, less than 50nmol/L for deficiency.A total of 41 pediatric patients with SMA (8 case of SMA type 1, 20 case of SMA type 2, and 13 case of SMA type 3) with ages ranging from 12 months old to 15 years old were included.Nearly 25% of SMA patients showed nutritional problems.Malnutrition was observed in 50% (4/8) of SMA 1 patients, 10% (2/20) of SMA 2 patients and 15.3% (2/13) of SMA 3 patients; overweight was found in 5% (1/20) of SMA 2 patients and 15.3% (2/13) of SMA 3 patients.The 25-OHD deficiency was observed in 25% (2/8) of SMA 1 patients, 30% (6/20) of SMA 2 patients, and 38.5% (5/13) of SMA 3 patients.The 25-OHD insufficiency was found in 25% (5/20) of SMA 2 patients and 23.1% (3/13) of SMA 3 patients.This study showed that malnutrition was common in SMA 1 patients, 25-OHD deficiency or insufficiency was frequent among the three types of SMA.Disease management with adjusting the diet structure and more outdoor activities would improve the nutritional problems.In this study, we demonstrated the baseline nutrition situations in a Chinese cohort of pediatric patients with SMA.

Three new treatments have recently been approved in spinal muscular atrophy (SMA). They reduce mortality in the infantile form, but also allow significant motor benefits in all SMA types. This benefit is inversely correlated with disease duration at treatment initiation. In this context, we have implemented a SMA newborn screening (NBS) program in Southern Belgium in 2018. Given the increasing importance of economic considerations for policy makers, this study aims to assess the cost-effectiveness of the SMA NBS followed with a disease-modifying treatment compared with disease-modifying treatment without SMA NBS. A previously published Markov model was adapted for this study to compare SMA NBS vs without NBS, with a lifetime horizon, from the Belgian payer perspective. Real life data including quality of life, cost and motor development data collected in 55 SMA patients (43 patients identified by their symptoms and treated at least after 2.5 months of life and 12 patients identified by NBS, treated, and followed up for a minimum of 18 months) were used to populate the model. SMA NBS was associated with lower total healthcare costs (about €2 million/patient) and more quality-adjusted life years (QALY) compared to treated SMA without NBS, leading to the dominance of SMA NBS. Treatments costs were rather similar between SMA NBS and without SMA, but disease costs substantially decreased (by about 75%) with SMA NBS. Total saved costs increased markedly when using a societal perspective and when incorporating caregivers’ perspectives (loss of works / QoL). The dominance of SMA NBS was confirmed by various deterministic analyses and by a probabilistic sensitivity analysis. In conclusion, this study reveals that SMA NBS coupled with one of the three available treatments leads to substantial better health outcomes for lower total healthcare costs compared to no screening, making NBS highly beneficial for both patients and society. Three new treatments have recently been approved in spinal muscular atrophy (SMA). They reduce mortality in the infantile form, but also allow significant motor benefits in all SMA types. This benefit is inversely correlated with disease duration at treatment initiation. In this context, we have implemented a SMA newborn screening (NBS) program in Southern Belgium in 2018. Given the increasing importance of economic considerations for policy makers, this study aims to assess the cost-effectiveness of the SMA NBS followed with a disease-modifying treatment compared with disease-modifying treatment without SMA NBS. A previously published Markov model was adapted for this study to compare SMA NBS vs without NBS, with a lifetime horizon, from the Belgian payer perspective. Real life data including quality of life, cost and motor development data collected in 55 SMA patients (43 patients identified by their symptoms and treated at least after 2.5 months of life and 12 patients identified by NBS, treated, and followed up for a minimum of 18 months) were used to populate the model. SMA NBS was associated with lower total healthcare costs (about €2 million/patient) and more quality-adjusted life years (QALY) compared to treated SMA without NBS, leading to the dominance of SMA NBS. Treatments costs were rather similar between SMA NBS and without SMA, but disease costs substantially decreased (by about 75%) with SMA NBS. Total saved costs increased markedly when using a societal perspective and when incorporating caregivers’ perspectives (loss of works / QoL). The dominance of SMA NBS was confirmed by various deterministic analyses and by a probabilistic sensitivity analysis. In conclusion, this study reveals that SMA NBS coupled with one of the three available treatments leads to substantial better health outcomes for lower total healthcare costs compared to no screening, making NBS highly beneficial for both patients and society.

Introduction Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative neuromuscular disease that presents primarily in children. Abnormalities in the SMN1 gene cause reduced levels of the survival motor neuron (SMN) protein, while a second gene, SMN2, produces low levels of functional SMN protein. Currently available drugs do not cure, so a significant unmet need remains for patients treated after symptom onset.Areas covered Drugs available in the clinic, investigational agents and key questions for researchers are discussed. A pragmatic search of the literature was performed to identify therapies in late stages of preclinical, or in early stages of clinical development. This list was compared to the CureSMA pipeline for completeness. Drugs approved for indications that have potential for impact for SMA were included. These drugs target the primary deficiency in SMN protein or other pathways involved in SMA pathophysiology that are not SMN-protein dependent.Expert opinion Children treated after the onset of symptoms continue to have significant disability. Given the heterogeneity of the population phenotype evidenced by variable response to initial therapy, age at treatment onset and the need to demonstrate added value beyond approved therapeutics, the clinical development of new drugs will be challenging.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.