Cost of managing an episode of relapse in multiple sclerosis in the United States

BACKGROUND: The purpose of this study was to determine the direct medical US cost of managing multiple sclerosis relapses. METHODS: Direct data analysis and cost modeling were employed to derive typical resource use profiles and costs in 2002 US dollars, from the perspective of a third-party payer responsible for comprehensive health-care. The location and scope of health care services provided over a 90-day period were used to define three levels of relapse management. Hospitalization and resulting subsequent care was defined as high intensity management. A medium level of intervention was defined as either use of the emergency room, an observational unit, or administration of acute treatments, such as intravenous methylprednisolone in an outpatient or home setting. The lowest intensity of care comprised physician office visits and symptom-related medications. Data were obtained from many sources including all payer inpatient, ambulatory and emergency room databases from several states, fee schedules, government reports, and literature. All charges were adjusted using cost-to-charge ratios. RESULTS: Average cost per person for high management level was $12,870, based on analysis of 4,634 hospital cases (mean age 48 years, 73$1,847 and mild episode $243. CONCLUSIONS: Management strategies leading to a reduction in the frequency and severity of a relapse, less reliance on inpatient care, or increased access to steroid infusions in the home, would have a substantial impact on the economic consequences of managing relapses

Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up

OBJECTIVES: To re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and neuromyelitis optica (NMO). METHODS: We re-screened 103/114 patients with available serum on live cell-based assays (CBA) for aquaporin-4 (AQP4)-M23-IgG and myelin-oligodendrocyte glycoprotein (MOG)-α1-IgG. Further testing included oligoclonal bands, serum levels of glial fibrillar acidic and neurofilament proteins and S100B. We show the impact of updated serology on these patients. RESULTS: Reanalysis of our original cohort revealed that AQP4-IgG seropositivity increased from 56% to 75% for NMO, 5% to 22% for CRION, 6% to 7% for RION, 0% to 7% for MSON and 5% to 6% for SION. MOG-IgG1 was identified in 25% of RION, 25% of CRION, 10% of SION, 0% of MSON and 0% of NMO. As a result, patients have been reclassified incorporating their autoantibody status. Presenting visual acuity was significantly worse in patients who were AQP4-IgG seropositive (p=0.034), but there was no relationship between antibody seropositivity and either ON relapse rate or visual acuity outcome. CONCLUSIONS: The number of patients with seronegative CRION and RION has decreased due to improved detection of autoantibodies over the past decade. It remains essential that the clinical phenotype guides both antibody testing and clinical management. Careful monitoring of the disease course is key when considering whether to treat with prophylactic immune suppression

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

New onset neuromyelitis optica in a young Nigerian woman with possible antiphospholipid syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Devic's neuromyelitis optica is an inflammatory demyelinating disease that targets the optic nerves and spinal cord. It has a worldwide distribution and distinctive features that distinguish it from multiple sclerosis. There has been no previous report of neuromyelitis optica from our practice environment, and we are not aware of any case associated with antiphospholipid syndrome in an African person.</p> <p>Case presentation</p> <p>We report the case of a 28-year-old Nigerian woman who presented with neck pain, paroxysmal tonic spasms, a positive Lhermitte's sign and spastic quadriplegia. She later developed bilateral optic neuritis and had clinical and biochemical features of antiphospholipid syndrome. Her initial magnetic resonance imaging showed a central linear hyperintense focus in the intramedullary portion of C2 to C4. Repeat magnetic resonance imaging after treatment revealed resolution of the signal intensity noticed earlier.</p> <p>Conclusion</p> <p>Neuromyelitis optica should be considered in the differential diagnoses of acute myelopathy in Africans. We also highlight the unusual association with antiphospholipid syndrome. Physicians should screen such patients for autoimmune disorders.</p

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis

BACKGROUND: The Apo-1/Fas (CD95) molecule is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor (TNF) receptor family. Both Fas and Fas ligand (FasL) are expressed in activated mature T cells, and prolonged cell activation induces susceptibility to Fas-mediated apoptosis. The Apo-1/Fas gene is located in a chromosomal region that shows linkage in multiple sclerosis (MS) genome screens, and studies indicate that there is aberrant expression of the Apo-1/Fas molecule in MS. METHODS: Mva I polymorphism on the Apo-1/Fas promoter gene was detected by PCR-RFLP from the DNA of 114 Japanese patients with conventional MS and 121 healthy controls. We investigated the association of the Mva I polymorphism in Japanese MS patients using a case-control association study design. RESULTS: We found no evidence that the polymorphism contributes to susceptibility to MS. Furthermore, there was no association between Apo-1/Fas gene polymorphisms and clinical course (relapsing-remitting course or secondary-progressive course). No significant association was observed between Apo-1/Fas gene polymorphisms and the age at disease onset. CONCLUSIONS: Overall, our findings suggest that Apo-1/Fas promoter gene polymorphisms are not conclusively related to susceptibility to MS or the clinical characteristics of Japanese patients with MS

Differential diagnosis of suspected multiple sclerosis: a consensus approach

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision

Perceived needs and satisfaction with care in people with multiple sclerosis: A two-year prospective study

<p>Abstract</p> <p>Background</p> <p>Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration.</p> <p>Methods</p> <p>The sample consisted of 219 outpatients at a MS specialist clinic. Data on perceived needs and satisfaction with care were collected every six months using a questionnaire which included various dimensions of care. The data was analysed for the whole sample and on an individual level, as well as in subgroups with regard to sex and disease severity.</p> <p>Results</p> <p>There were no statistically significant variations in the proportion of PwMS with perceived needs concerning different health-related services during the study period. However, individual variations were found with regard to both perceived needs and satisfaction with care. Few PwMS perceived a continuous need for a specific service. However, the majority perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at least sometimes. Severe MS was associated with a greater perceived need for almost all the services studied and women experienced a need for psychosocial support/counselling to a greater extent than men. In relation to the different categories of health care staff, PwMS were most satisfied with nurses with regard to all dimensions of care. They were least satisfied with the availability of psychosocial support/counselling; and information about social insurance/vocational rehabilitation.</p> <p>Conclusion</p> <p>Despite the large proportion of individuals with mild disease severity in our sample, a considerable number of needs were identified of which many, on an individual level, varied over time. Key services demanded by PwMS were identified. Also the level of satisfaction with care varied and areas with a potential for improvement were identified such as the availability of rehabilitation services including an increase in the supply of psychosocial support and counselling.</p