•Oral methylprednisolone is cost-effective when administered in the hospital.•When administered at home, it is more effective and less costly.•Its use is associated with millions in cost savings.•It ...should be widely prescribed to treat multiple sclerosis relapses.
Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy.
A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years.
In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was €15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system.
Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.
Objective
As exercise intolerance and exercise‐induced myalgia are commonly encountered in metabolic myopathies, functional screening tests are commonly used during the diagnostic work‐up. Our ...objective was to evaluate the accuracy of isometric handgrip test (IHT) and progressive cycle ergometer test (PCET) to identify McArdle disease and myoadenylate deaminase (MAD) deficiency and to propose diagnostic algorithms using exercise‐induced lactate and ammonia variations.
Methods
A prospective sample of 46 patients underwent an IHT and a PCET as part of their exercise‐induced myalgia and intolerance evaluation. The two diagnostics tests were compared against the results of muscle biopsy and/or the presence of mutations in PYGM. A total of 6 patients had McArdle disease, 5 a complete MAD deficiency (MAD absent), 12 a partial MAD deficiency, and 23 patients had normal muscle biopsy and acylcarnitine profile (disease control).
Results
The two functional tests could diagnose all McArdle patients with statistical significance, combining a low lactate variation (IHT: <1 mmol/L, AUC = 0.963, P < .0001; PCET: <1 mmol/L, AUC = 0.990, P < .0001) and a large ammonia variation (IHT: >100 μmol/L, AUC = 0.944, P = .0005; PCET: >20 μmol/L, AUC = 1). PCET was superior to IHT for MAD absent diagnosis, combining very low ammonia variation (<10 μmol/L, AUC = 0.910, P < .0001) and moderate lactate variation (>1 mmol/L).
Conclusions
PCET‐based decision tree was more accurate than IHT, with respective generalized squared correlations of 0.796 vs 0.668. IHT and PCET are both interesting diagnostic tools to identify McArdle disease, whereas cycle ergometer exercise is more efficient to diagnose complete MAD deficiency.
Congenital myasthenic syndromes (CMSs) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. Mutations of
DOK7
have recently been described in ...recessive forms of CMS. Dok-7 is a cytoplasmic post-synaptic protein co-activator of the muscle-specific receptor-tyrosine kinase (MuSK) involved in neuromuscular synaptogenesis and maintenance. We report clinical, morphological and molecular data on 15 patients with mutations in
DOK7
. Eleven different mutations (5 novel) were identified and all patients but one were found to carry at least the common c.1124_1127dupTGCC mutation. Patients with
DOK7
mutations have a particular limb-girdle pattern, without tubular aggregates but a frequent lipidosis on the muscle biopsy. Changes in pre- and post-synaptic compartments of the neuromuscular junction were also observed in muscle biopsies: terminal axons showed defective branching which resulted in a unique terminal axon contacting en passant postsynaptic cups. Clinical features, muscle biopsy findings or response to therapy were confusing in several patients. Characterization of this distinct phenotype is essential to provide clues for targeted genetic screening and to predict the therapeutic response to anticholinesterase treatments or ephedrine as has been suggested.
Pompe disease is a rare autosomal recessive muscle lysosomal glycogenosis, characterised by limb-girdle muscle weakness and frequent respiratory involvement. The French Pompe registry was created in ...2004 with the initial aim of studying the natural history of French patients with adult Pompe disease. Since the marketing in 2006 of enzyme replacement therapy (alglucosidase alfa, Myozyme®), the French Pompe registry has also been used to prospectively gather the biological and clinical follow-up data of all adult patients currently treated in France. This report describes the main clinical and molecular features, at the time of inclusion in the French registry, of 126 patients followed up in 21 hospital-based neuromuscular or metabolic centres. Sixty-five men and 61 women have been included in the registry. Median age at inclusion was 49 years, and the median age at onset of progressive limb weakness was 35 years. Fifty-five percent of the patients were walking without assistance, 24% were using a stick or a walking frame, and 21% were using a wheelchair. Forty-six percent of the patients needed ventilatory assistance, which was non-invasive in 35% of the cases. When performed, muscle biopsies showed specific features of Pompe disease in less than two-thirds of the cases, confirming the importance of acid alpha-glucosidase enzymatic assessment to establish the diagnosis. Molecular analysis detected the common c.-32-13T>G mutation, in at least one allele, in 90% of patients. The French Pompe registry is so far the largest country-based prospective study of patients with Pompe disease, and further analysis will be performed to study the impact of enzyme replacement therapy on the progression of the disease.
La maladie de Pompe est une glycogénose musculaire rare, de transmission autosomique récessive, caractérisée par une faiblesse des ceintures, fréquemment associée à une insuffisance respiratoire. Le registre français de la maladie de Pompe a été créé en 2004, avec pour objectif initial d’étudier l’histoire naturelle des patients atteints de la forme adulte de la maladie de Pompe. Depuis la commercialisation de l’enzymothérapie substitutive par alglucosidase alfa (Myozyme®) en 2006, le registre français de la maladie de Pompe a aussi permis le recueil de données cliniques et biologiques pour l’ensemble des patients adultes actuellement traités en France. Ce travail décrit les principales caractéristiques cliniques et moléculaires des 126 patients adultes, qui sont suivis dans 21 centres de référence de maladies neuromusculaires ou métaboliques. Soixante-cinq hommes et 61 femmes ont été inclus dans le registre. L’âge médian à l’inclusion était de 49ans ; l’âge médian du début de la faiblesse musculaire évolutive des ceintures était de 35ans. Soixante-cinq pour cent des patients pouvaient marcher sans aide, 24 % avaient recours à l’aide d’une canne ou d’un déambulateur, et 21 % avaient recours au fauteuil roulant. Quarante-six pour cent des patients avaient recours à une ventilation assistée, avec une ventilation non invasive dans 35 % des cas. La biopsie musculaire montrait des anomalies caractéristiques de la maladie de Pompe dans moins de deux tiers des cas, lorsqu’elle avait été pratiquée, confirmant ainsi l’importance du dosage enzymatique de l’activité alpha-glucosidase acide pour établir le diagnostic. Les analyses moléculaires ont permis de détecter la présence de la mutation commune c.-32-13T>G sur au moins un des deux allèles chez 90 % des patients. Le registre français de la maladie de Pompe a permis de constituer la plus grande cohorte de patients adultes atteints de cette maladie, et suivis de façon prospective, à l’échelle d’un pays. Des analyses complémentaires sont en cours afin d’étudier les effets de l’enzymothérapie substitutive sur l’évolution de la maladie.
Population-based stroke registries are necessary to evaluate the precise burden of stroke. The methodology used in the Brest Stroke Registry and an estimation of its completeness are described.
'Hot ...pursuit' as well as 'cold pursuit' were used, and five sources of identification were included: emergency wards, brain imaging, practitioners, death certificates and hospital-based electronic research. Ascertainment for each case was certified by a neurologist. Inclusion criteria were: (1) age >15 years; (2) a stroke defined by WHO criteria or all neurological deficits lasting at least 1 h. Completeness was estimated using capture-recapture method.
For 2008, 2009 and 2010, 851, 898, 823 patients were collected, respectively. The number of sources of identification per patient was as follows: one source: 30.8, 24.1 and 18.7%; two sources: 54.5, 42.9 and 31.0%; three sources: 13.4, 30.1 and 46%; four sources: 1.3, 3.0 and 3.8%. Capture-recapture analysis showed data completeness over 90%. Standardized cumulative first-ever stroke incidence using a world standard population was 87 in 2008, 87 in 2009 and 84 in 2010.
Case ascertainment by a neurologist, numerous sources, as well as 'hot' and 'cold' pursuit can provide a reliably large data set suitable for further epidemiological studies.
Harlequin phenomenon is characterized by a strictly unilateral erythrosis of the face with flushing and hyperhydrosis, and controlaterally a pale anhydrotic aspect. This syndrome can occur alone or ...associated to other dysautonomic phenomena such as Horner syndrome, Adie syndrome or Ross syndrome.
We report three cases: two patients presented a Harlequin sign, associated with Horner syndrome for one and Ross syndrome for the second. The etiologic investigation was normal, allowing recognizing the idiopathic nature of the disorder. For the third patient, Harlequin syndrome was observed in a neoplastic context due to breast cancer, metastatic dissemination, and bone metastases involving the right side of the T2 body.
We reviewed the literature: 108 cases have been described. This syndrome occurred alone in 48 patients and was associated with other dysautonomic syndromes such as Horner syndrome in 38 patients, Holmes Adie syndrome in six, and Ross syndrome in six; both Ross and Holmes Adie syndrome were associated five cases and associations were not reported in five patients. The pathophysiological mechanisms of this autonomic cranial neuropathy, the possible etiologies, and therapeutic management were discussed.
Harlequin phenomenon with flushing and unilateral hyperhydrosis is rare, occurring alone or in combination with other autonomic syndromes of the face. Idiopathic in two-thirds of cases, Harlequin phenomenon does not require specific treatment; sympathectomy may be discussed in the severe cases with a significant social impact.
We report a case of inflammatory cerebral amyloid angiopathy (CAA) that led to rapid cognitive decline, seizures, visual hallucinations, hyperproteinorrachia and right hemispheric leukopathy. Brain ...biopsy gave the diagnosis of CAA. Although no inflammatory infiltrate was found in the biopsy sample, corticosteroids led to a regression of the radiological lesions without significant clinical improvement. CAA is a rare disease, defined by lesions of classical cerebral amyloid angiopathy and perivascular infiltrates in contact with the affected vessels. In cases of rapidly progressive dementia associated with leukopathy, inflammatory amyloid angiopathy should be considered as cognitive disorders may improve after immunosuppressive therapy.
