Cœur et sarcoglycanopathies Fayssoil, A.; Nardi, O.; Orlikowski, D. ...
Revue neurologique,
November 2012, Letnik:
168, Številka:
11
Journal Article, Conference Proceeding
Recenzirano
Les sarcoglycanopathies sont des maladies neuromusculaires de transmission autosomique récessive, en rapport avec des mutations affectant les sarcoglycanes. La sémiologie clinique est surtout marquée ...par une myopathie des ceintures. Cet article est une mise au point des atteintes cardiaques décrites dans ce groupe de pathologies.
Sarcoglycanopathies (SG) are autosomic recessive muscular dystrophies, secondary to mutations of the sarcoglycan complex. Clinical pictures include muscle weakness affecting mainly the proximal limb girdle musculature. We review heart involvement in this group of disease.
Résumé Le projet TeleResp (2007–2011), réalisé dans le cadre de l’appel ANR-TecSan 2007, a été conduit par la société RBI en partenariat avec l’hôpital Raymond-Poincaré de Garches et le CHU de ...Grenoble. L’objectif principal de ce projet est de développer un outil de mesure et d’acquisition sans fil des signaux respiratoires (mesurés par pléthysmographie par inductance), d’oxymétrie, de position du sujet, de pression buccale et de mouvements des membres. Les champs d’application prévus dans le cadre de ce projet sont l’utilisation à domicile du matériel, d’une part, pour le monitorage de la respiration chez des patients atteints de pathologies neuromusculaires nécessitant une ventilation mécanique et, d’autre part, pour le diagnostic du syndrome d’apnée du sommeil. L’originalité de ce projet réside dans la réalisation d’un matériel utilisable à domicile, dans le milieu habituel du patient en évitant des contraintes de port d’appareils de mesure. Ce nouveau système est évalué, puis validé par les deux centres d’études cliniques. L’ambition de ce projet est de proposer des logiciels d’aide au diagnostic dont la conception a nécessité des travaux de recherches sur la justesse des signaux transmis, la fusion des données issues des capteurs et l’identification des données pertinentes. Répondant à une forte demande du marché, l’enjeu majeur du projet TeleResp est le déploiement industriel, la commercialisation d’un dispositif médical non invasif, autonome et novateur dans la surveillance et le diagnostic de troubles respiratoires, plus particulièrement au cours du sommeil, qui constituent un réel problème de santé publique.
Background. Little is known about the epidemiology and the prognostic factors of Guillain—Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). Methods. We prospectively ...followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. Results. Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P = .052). The main factors associated with long-term neurological sequelae (21%) were older age (P <.001) and assisted ventilation during hospitalization (P = .005). The number of CMV-GBS cases decreased between 1996 and 2006 (P = .019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). Conclusions. This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.
Background and purpose
To describe a large series of patients with α, β, and γ sarcoglycanopathies (LGMD‐R3, R4, and R5) and study phenotypic correlations and disease progression.
Methods
A ...multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time‐to‐event analysis was performed.
Results
One hundred patients (54 γ‐SG; 41 α‐SG; 5 β‐SG) from 80 families were included. The γ‐SG patients had earlier disease onset than α‐SG patients (5.5 vs. 8 years; p = 0.022) and β‐SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow‐up of 22.9 years, 65.3% of patients were wheelchair‐bound (66.7% α‐SG, 67.3% γ‐SG, 40% β‐SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ‐SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α‐SG patients showed genetic heterogeneity, whereas >90% of γ‐SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified.
Conclusions
This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.
This large multicentric Parisian series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset and absence of sarcoglycan expression on muscle biopsy are predictors of severity of disease and loss of ambulation, and should be taken into account in future clinical trials.
Summary Aims of the study A brain-computer interface aims at restoring communication and control in severely disabled people by identification and classification of EEG features such as event-related ...potentials (ERPs). The aim of this study is to compare different modalities of EEG recording for extraction of ERPs. The first comparison evaluates the performance of six disc electrodes with that of the EMOTIV headset, while the second evaluates three different electrode types (disc, needle, and large squared electrode). Material and methods Ten healthy volunteers gave informed consent and were randomized to try the traditional EEG system (six disc electrodes with gel and skin preparation) or the EMOTIV Headset first. Together with the six disc electrodes, a needle and a square electrode of larger surface were simultaneously recording near lead Cz. Each modality was evaluated over three sessions of auditory P300 separated by one hour. Results No statically significant effect was found for the electrode type, nor was the interaction between electrode type and session number. There was no statistically significant difference of performance between the EMOTIV and the six traditional EEG disc electrodes, although there was a trend showing worse performance of the EMOTIV headset. However, the modality-session interaction was highly significant ( P < 0.001) showing that, while the performance of the six disc electrodes stay constant over sessions, the performance of the EMOTIV headset drops dramatically between 2 and 3 h of use. Finally, the evaluation of comfort by participants revealed an increasing discomfort with the EMOTIV headset starting with the second hour of use. Conclusion Our study does not recommend the use of one modality over another based on performance but suggests the choice should be made on more practical considerations such as the expected length of use, the availability of skilled labor for system setup and above all, the patient comfort.
Introduction
Late‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to ...be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.
Methods
Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity FVC) and motor functions (Six‐Minute Walk Test 6MWT) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.
Results
Twenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.
Discussion
At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.
Conclusion
Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. ...Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies.
We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018–2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was<or≥the mean (15.6%). Adverse events were recorded.
We identified 18 patients who received 4 to 8 Nusinersen injections. No significant improvements occurred over time in any of the MFM scores or lung function test results, which did not differ between groups. The COPM performance score improved significantly from day 0 to day 303 in the high-MFM group and the COPM satisfaction score in the overall population from D0 to D183. Half the patients achieved the minimal clinically important difference for both COPM scores.
The overall stability of conventional motor assessment in this population with advanced disabilities is encouraging to use more sensitive tools based on self-perception and autonomy in daily life activities, such as COPM. Our finding of a significant COPM performance score improvement from days 0 to 303 only in the patients with initial MFM-32 scores above the mean in the population suggests that the severity of the baseline disabilities may affect treatment efficacy.
IV, retrospective observational cohort study.
Background and purpose
Data on interruption of enzyme replacement therapy (ERT) are scarce in late onset Pompe disease. Due to the COVID‐19 crisis, eight neuromuscular reference centers in France ...were obligated to stop the treatment for 31 patients.
Methods
We collected the motor and respiratory data from our French registry, before COVID‐19 and at treatment restart.
Results
In 2.2 months (mean), patients showed a significant deterioration of 37 m (mean) in the 6‐min walk test and a loss of 210 ml (mean) of forced vital capacity, without ad integrum restoration after 3 months of ERT restart.
Conclusions
This national study based on data from the French Pompe Registry shows that the interruption of ERT, even as short as a few months, worsens Pompe patients' motor and respiratory function.
Even brief suspension of approximately 2 months of enzyme therapy in patients with late onset Pompe disease results in significant motor and respiratory degradation. In this case, ad integrum recovery is not guaranteed 3 months after the treatment restart.
Strokes related to intracranial aneurysm or arteriopathy have been reported in a few patients with late-onset Pompe disease. These reports suggested that cerebral vessel involvement could be an ...underrecognized complication of this disease.
We report cerebral artery involvement in three French patients with late-onset Pompe disease.
The first patient died at age 35 years from complications of a giant fusiform aneurysm of the basilar artery, and her 34-year-old sister showed evidence of dolichoectatic basilar artery on magnetic resonance angiography. A dilative arteriopathy complicated with carotid artery dissection was diagnosed in the third patient, aged 50 years. Two patients are currently being treated with enzyme replacement therapy (alglucosidase alfa), and regular angiographic follow-up showed the absence of progression of vascular abnormalities in one of them.
These observations, combined with previously reported cases, confirm that Pompe disease should be recognized as a predisposing condition to dilative arteriopathy and cerebral aneurysm formation, although the real incidence of these vascular complications remains unknown.
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