Background and purpose
The frequency of pain and cramps is uncertain in anti‐myelin associated glycoprotein antibody (anti‐MAG) neuropathy. Whether these symptoms may affect function/quality of life ...is unknown.
Methods
A cross‐sectional study of the prevalence, correlates and impact of pain, pain subtypes and cramps, their severity, frequency and anatomical distribution was performed for 55 clinically stable patients with anti‐MAG neuropathy.
Results
Pain of any type was reported by 80% of subjects. The most common subtype was paraesthesiae and dysaesthesiae (70%). Cramps were reported by >60% of patients, with lower limb cramps in all and upper limb cramps in about 20%. Cramps affected daily activities in >30% of these subjects, sleep in 60%, ability to exercise in >30%. Total pain score correlated with several Short Form 36 health‐related quality of life (SF‐36 HR‐QoL) measures (P < 0.05), with Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) (P = 0.006) and 10‐m timed walk (P = 0.019). An independent association was ascertained with I‐RODS (P = 0.002). Different pain subtypes showed multiple associations with SF‐36 HR‐QoL measures and/or functional scales. Upper limb cramps had multiple SF‐36 HR‐QoL functional correlates, with an independent association with the Overall Neuropathy Limitation Score (ONLS) (P = 0.004). Cramp severity correlated with ONLS (P = 0.04) and I‐RODS (P = 0.028) and inversely with level of physiotherapy input (P = 0.009). Cramp frequency was associated with tremor score (P = 0.004) and multiple SF‐36 HR‐QoL subsections.
Conclusions
Neuropathic pain and cramps may affect function and quality of life in anti‐MAG neuropathy. Optimizing treatments of these symptoms, including by adequate levels of physiotherapy, may be beneficial in affected patients and requires further research.
Les patients atteints de maladie neuromusculaire sont plus à risque d’être hospitalisés en Réanimation, notamment ceux porteurs d’une insuffisance respiratoire chronique, d’une atteinte cardiaque, ...d’une mobilité restreinte ou de troubles de la déglutition.
L’objectif est de comparer les hospitalisations des patients atteints de maladie neuromusculaire en réanimation avec une population de référence, à travers l’âge, la durée moyenne de séjour, le score IGS 2, le décès, le retour direct au domicile.
Cette étude de cohorte rétrospective, unicentrique dans le service de réanimation du centre hospitalier du Mans fut réalisée entre décembre 2011 et mars 2016. Quatre-vingt-deux hospitalisations des patients atteints de maladies neuromusculaires sont inclues et comparées à l’intégralité des hospitalisations dans ce service sur cette période.
Les hospitalisations concernaient des patients atteints essentiellement de myotonie de Steinert, de dystrophie musculaire de Duchenne et Becker et de myasthénie généralisée. Ceux-ci étaient plus jeunes que ceux du groupe témoin (50,48 ans vs 59,80 ans), leur durée moyenne de séjour était deux fois plus longue (9,28jours vs 5,70jours), le score IGS 2 était moins élevé (24,41 vs 34,23) et le retour se faisait plus souvent au domicile (36,59 % vs 5,01 %).
Le score IGS 2 ne semble pas adapté pour ces pathologies. En fin d’hospitalisation, ces patients rejoignent plus fréquemment leur domicile grâce à l’aménagement de celui-ci.
Les résultats confirment la fragilité des patients atteints de maladie neuromusculaire au cours d’une hospitalisation en Réanimation.
Abstract Objective To analyse contraceptive methods and the extent of screening for breast and cervical cancer in women with neuromuscular disease, compare these results with data and guidelines for ...the general population and determine the environmental and attitudinal barriers encountered. Patients and methods A retrospective, descriptive study in a population of female neuromuscular disease patients (aged 20 to 74) monitored at a clinical reference centre. Results Complete datasets were available for 49 patients. Seventy percent used contraception (hormonal contraception in most cases). Sixty-eight percent had undergone screening for cervical cancer at some time in the previous 3 years and 100% of the patients over 50 had undergone a mammography. Architectural accessibility and practical problems were the most common barriers to care and were more frequently encountered by wheelchair-bound, ventilated patients. Conclusions In general, the patients had good access to contraceptive care and cervical and breast cancer screening. However, specific measures may be useful for the most severely disabled patients.
The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT ...in a cohort of patients with severe Pompe disease.
We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared.
Twelve patients (7 males) were identified. Median age at symptom onset was 24years IQR=15.5; 36.0. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h IQR=21.88; 24.00 (min 20; max 24). ERT was initiated at a median age of 52.5years IQR=35.75; 66.50. Median treatment duration was 55months IQR=39.5; 81.0. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m.
Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities.
•The efficacy of ERT in patients at an advanced stage of Pompe disease, confined in a wheelchair and ventilator dependent, has not been proven in a randomized trial.•We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT.•During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90minutes and two increased their assisted walking distance, by 80 and 20meters.•Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk.
Pompe disease (PD) is caused by a deficiency of lysosomal acid α-glucosidase resulting from mutations in the
GAA
gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder ...(classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the
GAA
mutations, to establish the disease epidemiology, and to identify potential genotype-phenotype correlations in French late-onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty-six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty-three different mutations were identified in the
GAA
gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in-frame deletions, and one large deletion. The common c.-32-13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.-32-13T>G mutation had an older mean age at onset than patients non-exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late-onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late-onset PD patients through a nationwide study covering more than 40 years.
Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, ...long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy of ERT, clinical data and blood samples from LOPD patients undergoing ERT for >4 years (n = 28) or untreated (n = 10) were collected and analyzed. In treated LOPD patients, anti-rhGAA antibodies peaked within the first 1000 days of ERT, while long-term exposure to rhGAA resulted in clearance of antibodies with residual production of non-neutralizing IgG. Analysis of T cell responses to rhGAA showed detectable T cell reactivity only after in vitro restimulation. Upregulation of several cytokines and chemokines was detectable in both treated and untreated LOPD subjects, while IL2 secretion was detectable only in subjects who received ERT. These results indicate that long-term ERT in LOPD patients results in a decrease in antibody titers and residual production of non-inhibitory IgGs. Immune responses to GAA following long-term ERT do not seem to affect efficacy of ERT and are consistent with an immunomodulatory effect possibly mediated by regulatory T cells.
Despite a wide clinical spectrum, the adult form of Pompe disease is the most common one, and represents more than 90% of diagnosed patients in France. Since the marketing of enzyme replacement ...therapy (alglucosidase alfa, Myozyme), all reports to date in adults demonstrated an improvement of the walking distance, and a trend toward stabilization of respiratory function, but the majority of these studies were less than 5 years of duration. We report here the findings from 158 treated patients included in the French Pompe Registry, who underwent regular clinical assessments based on commonly used standardized tests (6‐minute walking test, MFM scale, sitting vital capacity, MIP and MEP). For longitudinal analyses, the linear mixed effects models were used to assess trends in primary endpoints over time under ERT. A two‐phase model better described the changes in distance traveled in the 6‐minute walk test and MFM. 6MWT showed an initial significant increase (1.4% ± 0.5/year) followed by a progressive decline (−2.3%/year), with a cut‐off point at 2.2 years. A similar pattern was observed in total MFM score (6.6% ± 2.3/year followed by a − 1.1%/year decline after 0.5 years). A single‐phase decline with a slope of −0.9 ± 0.1%/year (P < .001) was observed for FVC, and MEP remained stable over the all duration of follow‐up. This study provides further evidence that ERT improves walking abilities and likely stabilizes respiratory function in adult patients with Pompe disease, with a ceiling effect for the 6MWT in the first 3 years of treatment.
Background: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent ...studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs.
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