Secondary progressive multiple sclerosis: A national consensus paper on diagnostic criteria.

BACKGROUND: In clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care. METHODS: Eight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document. RESULTS: Based on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was≤5.0) or of +0.5 point (if the previous EDSS was≥5.5), with a pyramidal or cerebellar functional system score≥2 and without setting a minimum EDSS score; or, in case of a stable EDSS score≥4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS. CONCLUSIONS: The experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

[Prognostics factors of renal failure in multiple sclerosis]. / Facteurs pronostiques d'urétéro-hydronéphrose (UHN) chez les patients atteints de sclérose en plaques (SEP).

INTRODUCTION: Urinary symptoms occur in 50 to 80% of patients with Multiple Sclerosis (MS). This study was conducted to determine prevalence of renal failure during MS follow-up and to investigate the correlation of these complications with disease characteristics and urodynamic findings. METHODS: One hundred and twenty-one consecutive patients have been followed for (MS) (61 men and 60 women) between 1995 and 2009 in our institution. The demographic findings of patients were documented. The history was obtained and a detailed neurological and urological physical examination was performed for all patients. Urological symptoms (urgency, frequency, urge incontinence, dysuria), urinary scores (UPS and International Consultation on Incontinence Questionnaire [ICIQ]) and renal failure were recorded. All patients underwent ultrasound imaging of the bladder during their follow-up and on the last evaluation. Expanded Disability Status Scale (EDSS) was evaluated during neurologic follow-up. For each patient mean onset age of disease, mean onset age of micturation disorders, mean illness duration and mean urological follow-up duration were recorded. Urodynamic investigation was performed for all patients. Urodynamic assessment was carried out according to the International Continence Society (ICS) standards (detrusor overactivity, detrusor/sphincteric dyssynergia and low bladder compliance). RESULTS: Mean illness duration was 13.8 years (1-50). According to the history and clinical findings, 21 patients had primary-progressive (PPMS), 59 relapsing-remitting (RRMS) and 41 secondary-progressive multiple sclerosis (SPMS). Four patients have shown renal failure during their follow-up (3.3% - three men and one woman). Renal failure was associated with disease characteristic (SPMS - EDSS score >6.5), mean illness duration (30 years [12-48]) and low bladder compliance (17 [7-23]) (P=0.03; P=0.02; P=0.049). CONCLUSION: Relationship between renal failure, disease characteristics and urodynamic findings was suggested in our study. More accurate follow-up might be used for SPMS (EDSS >6.5), longer mean illness duration (>30 years), and low bladder compliance (<30).

Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease.

BACKGROUND: Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer's disease susceptibility. Lipid lowering agents (LLAs) may have implications for the prevention of Alzheimer's disease. OBJECTIVE: To investigate whether LLAs are associated with a slower cognitive decline in Alzheimer's disease. METHODS: An observational study in 342 Alzheimer patients followed in a memory clinic for 34.8 months (mean age 73.5 years, mini-mental state examination score (MMSE) 21.3 at entry); 129 were dyslipaemic treated with LLAs (47% with statins), 105 were untreated dyslipaemic, and 108 were normolipaemic. The rate of cognitive decline was calculated as the difference between the first and last MMSE score, divided by the time between the measurements, expressed by year. Patients were divided into slow and fast decliners according to their annual rate of decline (lower or higher than the median annual rate of decline in the total population). RESULTS: Patients treated with LLAs had a slower decline on the MMSE (1.5 point/year, p = 0.0102) than patients with untreated dyslipaemia (2.4 points/year), or normolipaemic patients (2.6 points/year). Patients with a slower decline were more likely to be treated with LLAs. Logistic regression analysis, with low annual cognitive decline as the dependent variable, showed that the independent variable LLA (treated with or not) was positively associated with the probability of lower cognitive decline (odds ratio = 0.45, p = 0.002). CONCLUSIONS: LLAs may slow cognitive decline in Alzheimer's disease and have a neuroprotective effect. This should be confirmed by placebo controlled randomised trials in patients with Alzheimer's disease and no dyslipaemia.

[Infectious myelopathies: clinical, serological, and prognostic patterns]. / Myélopathies infectieuses: profils cliniques, paracliniques et évolutifs.

INTRODUCTION: Serological confirmation of an infectious acute myelitis injury is difficult to confirm as it is sometimes due to a post-infectious etiology. OBJECTIVES: The aim of this study was to define the clinical, biological and prognostic patterns of infectious myelitis. PATIENTS AND METHODS: This retrospective study included 153 subjects hospitalized in the department of neurology between 1993 and 2002 for treatment of a noncompressive acute myelopathy. Biological confirmation of recent infection was obtained in 12 patients (8 p. 100). RESULTS: An infectious syndrome, beginning prior to the neurological symptoms, was found in 67 percent of patients. The clinical symptoms were severe with loss of sensoromotor and sphincter functions and ascending spinal cord dysfunction (acute transverse myelopathy). Spinal cord MRI showed extended centromedullar high intensity signals with rapid and complete regression. CSF analysis cell count was above 30/mm3 with hyperproteinorachia, in 75 percent and 58 percent of patients respectively. CSF electrophoresis did not detect oligoclonal bands. Clinical outcome was good in all patients except one, however sphincter disorders recovered slowly. DISCUSSION: Our study illustrates a stereotypical clinical, biological and prognostic pattern for infectious acute myelitis. These findings contribute significantly to therapeutic decision making and establishing prognosis at the initial phase of acute myelopathy.

[Acute upper limb ischemia in a young adult without cardiac disease. Value of transesophageal echocardiography]. / Ischémie aiguë des membres supérieurs chez une adulte jeune sans cardiopathie. Intérêt de l'échographie transoesophagienne.

The authors report the case of a 34-year old woman with no previous cardiovascular disease who was admitted to hospital for acute ischaemia of the right arm due to embolism, preceded by two episodes of pain and tingling of the left arm related to subacute ischaemia. After right embolectomy, with no possibility of controlateral disobliteration an effective anticoagulation, no cardiac source of embolism could be found; However, transoesophageal echography showed a large mobile thrombus in the aortic arch implanted just before the origin of the left subclavian artery. The only explanation for embolism to the right arm was a retro-oesophageal subclavian artery which was confirmed by scanner. Doppler and arteriography. These investigations, however, did not allow visualisation of the aortic thrombus. In view of the risk of recurrent embolism, a thrombectomy was performed without cardiopulmonary bypass, associated with correction of the vascular abnormality with no complications. This case shows that oesophageal echography is a useful investigation in the work up of acute arterial obstruction in young patients with no cardiac disease.