Developing tools to evaluate quality of care management for patients living with multiple sclerosis: An original French initiative.

INTRODUCTION: Assessing the quality of care management for patients with a chronic disease such as multiple sclerosis (MS) is a major challenge for healthcare systems around the world. It needs to be carried out using tools that are recognized by professionals and patients alike, and should concern practices, systems, and scientific data. No such tools are currently available in Europe. The purpose of the present study was to develop indicators to contribute to assess the quality of care management for patients with MS in France. METHODS: An expert panel comprising 25 professionals from well known teams across France selected the indicators on the basis of consensus. In accordance with the Rand/UCLA Appropriateness Method, each expert had to agree with the recommendations, and there had to be agreement among the experts. RESULTS: The expert panel selected 48 indicators representing seven domains of care management for patients with MS: physical and rehabilitation medicine, disease progression, access to care, magnetic resonance imaging (MRI) management, relapse management, management of disease-modifying treatments, and management of the symptoms of disability progression. Some of these quality indicators (notably pertaining to MRI management) had not previously been identified in the literature. CONCLUSION: These indicators may allow professionals to comprehensively assess and compare their practices and cooperation, thereby contributing to improve the quality of care management for patients with MS in France.

Evaluation of the quality of the care pathway for patients with multiple sclerosis in France: Results of an original study of a cohort of 700 patients.

INTRODUCTION: Evaluating the quality of the care pathway for patients with chronic diseases, such as multiple sclerosis (MS), is an important issue. Process indicators are a recognized method for evaluating professional practices. However, these tools have been little developed in the field of MS, and few data are available. The aim of this study was to describe, retrospectively, with validated indicators, the quality of the care pathway in a population-based cohort of 700 patients with the first manifestations of the disease occurring between January 1, 2000 and December 31, 2001 and during the first 10 years of disease. METHOD: This assessment was based on 48 indicators specific to MS. The information required for the calculation of each indicator was collected from the source files of the 700 patients of the cohort. RESULTS: Data for the 10 years of follow-up were collected for 80% of the patients. In total, 36 indicators were calculated. These results reveal that there is room for improvement, particularly in terms of the initial assessment, access to ophthalmological evaluation, employment, obtaining an evaluation of the need for rehabilitation and access to such care. CONCLUSION: The results of this survey provide access to unprecedented new data in France, that professionals and patients can appropriate to improve the targeting of actions, to improve the quality of care further for patients with MS in France. We propose to continue this process by submitting, for discussion, a targeted list of updated indicators relating to changes in guidelines, and in issues concerning the quality of patient management.

Cost-utility of oral methylprednisolone in the treatment of multiple sclerosis relapses: Results from the COPOUSEP trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study.

BACKGROUND AND PURPOSE: Fifteen percent of patients with myasthenia gravis (MG) are refractory to conventional treatment. Case reports and a few studies show probable benefit of rituximab in these cases. Our objective was to assess the efficacy and the safety of rituximab in patients with MG, in a multicentric real-life study. METHOD: Inclusion criteria were: age > 18 years; MG with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSk) antibodies or significant decrement after repetitive nerve stimulation; Myasthenia Gravis Foundation of America (MGFA) class >II; refractory or steroid-dependent MG; and treatment with rituximab. Efficacy was assessed at 6 months using the MGFA-post-intervention status (PIS) score, the myasthenic muscle score (MMS) and the number of patients receiving steroids <10 mg/day. Data on adverse events were collected. RESULTS: Twenty-nine patients were included: 20 with anti-AChR MG, five with anti-MuSK MG and four with seronegative MG. MGFA-PIS score was improved or better (improved, minimal manifestations or remission) in 86.2% of patients after 6 months of treatment (P < 0.0001). The mean MMS increased from 68.8 to 83.1 (P < 0.0001). A decrease in steroid dosage (<10 mg/day) was effective in 57.9% of treated patients. In all, 42.8% of patients experienced adverse events: infections (21.4% of patients); infusion reaction (7%); bradycardia (3.7%); and cytopenia (7%). CONCLUSION: The present study demonstrates the efficacy and safety of rituximab in patients with MG. Additional studies remain necessary to determine the role of rituximab in the pharmacopeia of MG treatment and to establish precise recommendations for the infusion protocol.

Mycophenolate mofetil in multiple sclerosis: a multicentre retrospective study on 344 patients.

OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive agent, sometimes used as a disease-modifying therapy for multiple sclerosis (MS). Several studies have reported the relative safety of this treatment but, to date, its efficacy has rarely been described. We performed a retrospective study to assess the safety and efficacy of MMF in patients with MS. METHODOLOGY: Three French MS centres included all of their patients treated by MMF. The main outcome criterion was annualised relapse rate (ARR) in the 1 year period after onset of MMF compared with the 1 year control period. Treatment with another immunosuppressive drug, such as mitoxantrone or cyclophosphamide, in the 2 years preceding initiation of MMF was included in a subgroup analysis. MMF safety and progression of the Expanded Disability Status Scale (EDSS) score were also assessed. RESULTS: 344 patients were included; 149 patients were previously treated with another immunosuppressant (IS group). Mean MMF treatment duration was 25.3±1.1 months. During the 1 year control period, ARR was 1.11±0.08, and for the 1 year treatment period, ARR was reduced significantly to 0.35±0.05 (p<0.0001, Wilcoxon paired test). Adverse events (occurring in 11% of patients) were mainly digestive disorders, benign infections, asthenia and transitory lymphopenia. Concerning the progression of disability, in the subgroup of patients without previous immunosuppressant treatment, EDSS remained stable between initiation and 1 year after the beginning of MMF. INTERPRETATION: Our results suggest that MMF can improve or stabilise MS patients and can be used as an alternative therapy.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

SMILE: a predictive model for Scoring the severity of relapses in MultIple scLErosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), relapse severity and residual disability are difficult to predict. Nevertheless, this information is crucial both for guiding relapse treatment strategies and for informing patients. OBJECTIVE: We, therefore, developed and validated a clinical-based model for predicting the risk of residual disability at 6 months post-relapse in MS. METHODS: We used the data of 186 patients with RRMS collected during the COPOUSEP multicentre trial. The outcome was an increase of ≥ 1 EDSS point 6 months post-relapse treatment. We used logistic regression with LASSO penalization to construct the model, and bootstrap cross-validation to internally validate it. The model was externally validated with an independent retrospective French single-centre cohort of 175 patients. RESULTS: The predictive factors contained in the model were age > 40 years, shorter disease duration, EDSS increase ≥ 1.5 points at time of relapse, EDSS = 0 before relapse, proprioceptive ataxia, and absence of subjective sensory disorders. Discriminative accuracy was acceptable in both the internal (AUC 0.82, 95% CI [0.73, 0.91]) and external (AUC 0.71, 95% CI [0.62, 0.80]) validations. CONCLUSION: The predictive model we developed should prove useful for adapting therapeutic strategy of relapse and follow-up to individual patients.

Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

[Presentation of cerebral toxocariasis with mental confusion in an adult: case report and review of the literature]. / Toxocarose cérébrale révélée par une confusion mentale chez un adulte à Nantes: cas clinique et revue de la littérature.

Toxocariasis is usually responsible for visceral larva migrans syndroms. Nervous system involvement is a rare complication. In this report, we describe one case of meningoencephalitis due to Toxocara canis in a 73-year-old man presenting with mental confusion. The diagnosis of cerebral toxocariasis was confirmed by immunodiagnosis in both serum and cerebro-spinal fluid. Cerebral toxocariasis may be suspected in patients presenting with some neurological patterns including: confusion, meningitis, meningo-encephalitis, meningo-myelitis, when the etiological assessment remains negative and the environmental context is favourable. Finding evidence of specific antibodies in both cerebro spinal fluid and serum is mandatory for the diagnosis. The main clinical features concerning cerebral toxocariasis, diagnostic tools, and therapeutic measures are discussed.

[Increased risk of relapse in multiple sclerosis patients after ovarian stimulation for in vitro fertilization]. / Augmentation du risque de poussée de sclérose en plaques après stimulation ovarienne pour fécondation in vitro.

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

[Idiopathic acute transverse myelitis: application of new diagnosis criteria to 17 patients]. / Myélite aiguë transverse idiopathique: application des nouveaux critères diagnostiques à une cohorte de 17 patients.

INTRODUCTION: Idiopathic Acute Transverse Myelitis (ATM) is an inflammatory and immune-mediated disorder, distinct from infectious ATM, ATM of systemic lupus erythematosus or Sjögren's syndrome, and medullary manifestation of multiple sclerosis. Prognosis is not well-known. OBJECTIVE: To evaluate clinical, paraclinical and pronognosis data in patients selected with new diagnosis criteria, classically described in idiopathic ATM. METHODS: Seventeen patients with diagnosis criteria were retrospectively (1996-2005) studied. A telephone investigation was conducted in 2005 to obtained data on the clinical course. RESULTS: Seven men and 10 women, ranging in age from 15 to 75 years (mean: 39.8 years) met these new criteria. Our study showed that epidemiological and clinical findings as well as laboratory results were in agreement with those presented in the literature. Conversely, prognosis was better since 76p.cent of the patients could walk without assistance. The clinical presentation of some of our patients and/or their progression towards other multifocal inflammatory disorders, suggests there might be links between ATM, neuromyelitis optica (NMO) and Acute Dissemined Encephalomyelitis (ADEM). CONCLUSION: Patients with idiopathic ATM, selected with new criteria, have a rather good prognosis. ATM seems to be part of a continuum of neuroimmunologic disorders including NMO or ADEM although reasons explaining distinct focal disorders remain unclear.

[Neuropsychological and scintigraphic aspects of frontotemporal dementia preceding amyotrophic lateral sclerosis]. / Aspects neuropsychologiques et scintigraphiques des démences fronto-temporales précédant l'atteinte du motoneurone.

Between 1993 and 2001, we observed fifteen patients (ten men and five women, mean age 63 years) with frontotemporal dementia (FTD) which preceded signs of amyotrophic lateral sclerosis (ALS) which developed 21 months later. Mean disease duration in the fourteen deceased patients was 38 months. FTD associated with ALS is characterized by rapid course, predominance of disinhibited forms (orbito-basal), presence of aphasia with neologisms, and semantic memory disorders. Performed in all patients, single-photon emission computed tomography demonstrated a bifrontal pattern of low uptake, sometimes associated with low uptake in the anterior temporal region. In one patient, neuropathology revealed neuron atrophy and loss in the frontotemporal region, the anterior horns, and the hypoglossal nucleus. Ubiquitin-positive inclusions were visible in the dentate gyrus of the hippocampus and in the anterior horns. The dementia/ALS association is classically described is uncommon. It belongs to the FTD group since the Lund and Manchester consensus. Approximately 15 p.100 of patient with FTD can be expected to develop ALS. About 250 cases have been reported in the literature, half of them in the Pacific area where the incidence of ALS is high (55/100,000 inhabitants versus 1/100,000 in the rest of the world). Intermediary forms of FTD, semantic dementia, and progressive non-fluent aphasia are discussed since several cases of non-fluent progressive aphasia associated with ALS are reported in the literature. The links between these two degenerative diseases are discussed.

[Dural arteriovenous fistula. A rare cause of treatable dementia]. / Fistules durales à drainage veineux cortical. Une cause rare de démence curable.

Dural fistulas are acquired arteriovenous shunts, accounting for 10-15p.cent of cerebrovascular malformations. Symptoms are commonly tinnitus or intracranial hemorrhage. Rarely, patients with dural fistulas can present with rapid cognitive impairment. We report two women with rapidly evolving dementia. Cerebral angiography revealed dural arteriovenous fistula, with retrograde drainage into cortical veins, related to thrombosis of both transverse sinuses. Intra-arterial and intra-venous endovascular approaches failed to cure the fistula. Venous embolization via a transcranial approach was required to occlude the fistula, leading to resolution of the symptoms. Dural arteriovenous fistulas may lead to dementia with diffuse white matter changes related to venous ischemia, and must be considered as a reversible cause of vascular dementia. A transcranial approach for venous embolization is sometimes required.

[Ptosis and mastication disorders revealing concurrent myasthenia gravis and chronic polyradiculoneuritis]. / Ptosis et troubles de la mastication révélateurs d'une association myasthénie et polyradiculonévrite chronique.

Although myasthenia gravis (MG) has frequently been associated with other autoimmune disorders, it has only rarely been reported in conjunction with diseases of the nervous system. A 74-year-old patient with hypertension suddenly presented left unilateral ptosis and mastication disorders. Clinical examination showed a concomitant loss of strength distally and reduced deep tendon reflex. Electrophysiologic data indicated a diagnosis of MG and chronic inflammatory demyelinating polyneuropathy; acetylcholine receptor antibody was elevated at 4.1 nmol/L (normal < 2 nmol/L). Improvement was rapid after initiation of pyridostigmine in association with corticosteroid (1 mg/kg/day). One month later, the cranial nerve deficit disappeared and strength was normal. It is likely that a basic abnormality of immune regulation was responsible for the emergence of diseases with different clinical presentations, but similar immunopathogenesis. Corticosteroid seemed to be the most effective treatment.

[Late cerebrovascular complications of cardiac transplantation]. / Les complications cérébro-vasculaires tardives de la transplantation cardiaque.

The occurrence of stroke after the post-operative period of cardiac transplantation is a rare event, and the role of the cardiac transplant in these patients, who often have various vascular risk factors, is unclear. We reviewed the clinical records of 303 consecutive patients with orthotopic cardiac transplantation performed from March 1985 to December 1996 and selected those who developed a stroke over the first 2 months postoperatively, in order to evaluate the frequency and the mechanisms of late cerebrovascular complications. Four patients had presented cerebral infarct and two intracranial hemorrhage. The overall risk of late cerebrovascular complications was 2.6p.100 at 5 years. Ischemic stroke was related to cardiac embolus in one patient, lacunar infarction in another, and was of undetermined etiology in two cases. In addition to vascular risk factors prior to transplantation and the development of intracardiac thrombus, immunosuppressive therapy, the surgical procedure and cardiac rejection may play a role in the occurrence of stroke in such patients.

Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients.

BACKGROUND: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. OBJECTIVE: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. METHODS: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. RESULTS: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. CONCLUSION: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.

Multiple sclerosis and access to healthcare in the Pays de la Loire region: preliminary study based on 130 self-applied double questionnaires.

OBJECTIVE: To check whether the use of an autoquestionnaire is adapted to obtain information about perceptions of multiple sclerosis (MS) patients concerning access to healthcare in the Pays de la Loire region of France. PATIENTS AND METHODS: Patients with MS were asked to complete a questionnaire concerning access to 31 healthcare professionals or social services. The questionnaires were anonymous and consisted of one page for the patient and one page for a member of his or her entourage. The questionnaires were returned in a prepaid stamped addressed envelope. The first 130 exploitable questionnaires were analysed. RESULTS: Over 50% of patients with MS found access to general practitioners, neurologists, nurses and pharmacists useful, as well as access to less MS-specific specialists, for example, dentists, ophthalmologists or gynaecologists. Physical medicine and rehabilitation practitioners were not required until later in the course of the disease. Patients and their entourage rated the importance of access to care differently for bladder and sexual problems, and for support for cognitive and psychological problems. CONCLUSION: This study validates the use of a questionnaire to obtain information about patient perceptions of access to healthcare. The study also suggests a hierarchy of care needs, insufficient patient information, and disparities in access to care related to where the patients live.