OBJECTIVE:To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS), we present the MS Surveillance Registry (MSSR) within the US Department of Veterans Affairs (VA).BACKGROUND:Disease specific databases can be helpful in the management of neurologic conditions but few are fully integrated into the electronic health record and linked to health system data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge.METHODS:Building the MSSR was initiated by an iterative process with an IT team and MS health care providers. A common registry platform shared by other VA disease specific registries (eg, traumatic brain injury and cancer) was used to develop the IT infrastructure. MS cases were entered online into the MS Assessment Tool at selected MS Centers of Excellence (MSCoE) clinics in the US. Other large VA databases linked to MSSR are reviewed. Patient demographic and clinical characteristics were compared and contrasted with the broader VA population and other US registry populations.RESULTS:We have enrolled 1,743 patients with MS in the MSSR through fiscal year 2019 from selected MS regional programs in the VA MSCoE network. The mean age of patients was 56.0 years, with a 2.7 male:female ratio. Among those with definite MS, the mean European Database for MS Disability Score was 4.7 and 75% had ever used an MS disease modifying therapy. A summary electronic dashboard was developed for health care providers to easily access demographic and clinical data for individuals and groups of patients. Data on comorbid conditions, pharmacy and prosthetics utilization, outpatient clinic visits, and inpatient admission were documented for each patient.CONCLUSIONS:The MSSR is a unique electronic database that has enhanced clinical management of MS and serves as a national source for clinical outcomes.

It is understandable that neurologists might "curse the darkness" that engulfs the economics of multiple sclerosis (MS) care. The price of MS disease-modifying therapies (DMTs) is shocking. In 2013, the average wholesale price of all MS DMTs in the United States clustered around $65,000 a year and prices continue to increase by more than 10% per year.1 In response to skyrocketing DMT prices, insurance companies and specialty pharmacies create rules regulating coverage of MS treatments with little input from neurologists.2 Neurologists must navigate Kafkaesque health insurance bureaucracies to obtain coverage for treatments we deem appropriate for our patients. By contrast, reimbursements for neurologists illustrate that we may be undervalued. In 2013, Medicare spent $820 million for a single MS DMT, glatiramer acetate, which nearly equaled the $939 million paid to all neurologists for their evaluation and management services.3 Neurologists, the experts in the care of MS, have no influence over the rising cost of DMTs or the decisions made by the health insurance industry regarding coverage of therapies. Frustrated neurologists complain at meetings and via e-mail groups about medication cost and lack of influence, generating much heat but little light.

Objective: To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS) we present the MS Surveillance Registry (MSSR) within the US VHA Health Care System. Background: Disease specific databases can be helpful in the management of neurological conditions but few are fully integrated into the electronic medical record and linked to health systems data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge. Methods: Building the MSSR was initiated by an iterative process with an IT team and MS specialists. A common "converged registry" platform shared by other VA disease specific registries (e.g. traumatic brain injury, cancer) was used to develop the IT infrastructure. MS cases were entered into an MS Assessment Tool through a web-based note at each regional MS clinic within the mid-Atlantic and Pacific Northwest regional network. Other large VHA databases linked to MSSR are reviewed. Patient demographic and clinical characteristics were compared and contrasted with the broader VHA population and other US registry populations. Results: Of some 25,000 patients with MS actively using the VA health care system between 2013-2015, we enrolled 930 in MSSR from two geographic regions. The mean age of patients was 56.0 years, with M:F ratio of 2.7. Among those with definite MS, the mean European Database for MS score was 5.1 and 47[percnt] were currently using a DMT. A summary electronic dashboard was developed for health care providers to easily access demographic and clinical data for individuals and groups of patients. Data on co-morbid conditions, pharmacy and prosthetics utilization, outpatient clinic and inpatient admission were documented for each patient. Conclusions: The MSSR is a unique electronic database that has enhanced clinical management of MS and serves as a national source for clinical outcomes.

OBJECTIVE:To characterize patients misdiagnosed with multiple sclerosis (MS).METHODS:Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS.RESULTS:Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms.CONCLUSIONS:Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS) and hypothesize common causes for misdiagnosis. Background: Misdiagnosis of MS is a persistent if not growing problem despite, and perhaps because of, improved radiographic diagnostic techniques. Few studies have characterized the contemporary spectrum of MS misdiagnosis. Methods: Over 13 months, neurologists at four academic MS Centers submitted data concerning individual patients whom they had evaluated and determined to have been misdiagnosed with MS. Results: Of 110 misdiagnosed patients, 51 (46[percnt]) had "definite" and 59 (54[percnt]) "probable" misdiagnoses according to study definitions. The most frequent primary diagnoses were migraine alone or in combination with other diagnoses 24 (21[percnt]), fibromyalgia 16 (15[percnt]), nonspecific or non-localizing neurological symptoms with abnormal MRI 13 (12[percnt]), and conversion or psychogenic disorder 12 (11[percnt]). 27 additional diagnoses were reported. 32 (29[percnt]) of patients carried a misdiagnosis between 3-9 years and 29 (26[percnt]) for 10-20 years. 77 (70[percnt]) had taken disease modifying therapy, including natalizumab 14 (13[percnt]), mitoxantrone 2 (2[percnt]), cyclophosphamide 1 (1[percnt]). Four (4[percnt]) had participated in a research study of an MS therapy. In 79 (72[percnt]) of patients, participating neurologists indicated that there was evidence an earlier missed opportunity to make a correct diagnosis and 34 (31[percnt]) suffered unnecessary morbidity as a direct result of a misdiagnosis. Inappropriate attribution of symptoms to demyelinating disease contributed to misdiagnosis in 72 (65[percnt]) patients, and reliance upon historical symptoms without corroborating objective evidence of a lesion in 53 (48[percnt]). Over-reliance on MRI abnormalities to satisfy dissemination in space in a patient with nonspecific neurological symptoms contributed to misdiagnosis in 66 (60[percnt]). Conclusions: Misdiagnosis of MS is a common problem that may lead to treatment-related as well as psychosocial morbidity. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important causes of misdiagnosis.

The US Food and Drug Administration has registered 13 multiple sclerosis (MS) disease-modifying therapies (DMTs). The medications are not interchangeable as they vary in route of administration, efficacy, and safety profile. Selecting the appropriate MS DMT for individual patients requires shared decision-making between patients and neurologists. To reduce costs, insurance companies acting through pharmacy benefit companies restrict access to MS DMTs through tiered coverage and other regulations. We discuss how policies established by insurance companies that limit access to MS DMTs interfere with the process of shared decision-making and harm patients. We present potential actions that neurologists can take to change how insurance companies manage MS DMTs.

Objective: To examine the pricing trajectories in the United States of disease-modifying therapies (DMT) for multiple sclerosis (MS) over the last 20 years and assess the influences on rising prices. Methods: We estimated the trend in annual drug costs for 9 DMTs using published drug pricing data from 1993 to 2013. We compared changes in DMT costs to general and prescription drug inflation during the same period. We also compared the cost trajectories for first-generation MS DMTs interferon (IFN)–β-1b, IFN-β-1a IM, and glatiramer acetate with contemporaneously approved biologic tumor necrosis factor (TNF) inhibitors. Results: First-generation DMTs, originally costing $8,000 to $11,000, now cost about $60,000 per year. Costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%–60% higher than existing DMTs. Significant increases in the cost trajectory of the first-generation DMTs occurred following the Food and Drug Administration approvals of IFN-β-1a SC (2002) and natalizumab (reintroduced 2006) and remained high following introduction of fingolimod (2010). Similar changes did not occur with TNF inhibitor biologics during these time intervals. DMT costs in the United States currently are 2 to 3 times higher than in other comparable countries. Conclusions: MS DMT costs have accelerated at rates well beyond inflation and substantially above rates observed for drugs in a similar biologic class. There is an urgent need for clinicians, payers, and manufacturers in the United States to confront the soaring costs of DMTs.

Background: Patient-reported outcomes are important for clinical research and care, yet administering and scoring the questionnaires requires considerable effort and time. The Patient Reported Outcomes Measurement Information System (PROMIS) could considerably reduce administrative obstacles and lessen survey burden for participants. Objective: Assess the feasibility and validity of PROMIS, compared to commonly-used legacy measures for multiple sclerosis (MS). Methods: In this cross-sectional survey, 133 participants with confirmed MS completed legacy surveys and PROMIS Computerized Adaptive Tests (CATs) for depression, anxiety, pain, fatigue and physical function. We conducted a multi-trait, multi-method analysis and verified results with confirmatory factor analysis. Results: The correlations between PROMIS and the corresponding legacy measures were large (0.67 to 0.87). The multi-trait, multi-method criteria were generally well met, providing good evidence of the validity of PROMIS measures. PROMIS surveys asked fewer questions and required substantially less time to complete than the legacy scales. Conclusions: Our results provide evidence of the construct validity of PROMIS for use with MS patients. Several aspects of the PROMIS CATs made them an important resource, including: (a) less time was required to complete them; (b) missing data was reduced; and (c) the automatic scoring referenced the general population. Our findings support the use of PROMIS in MS research and may have broader implications for clinical care, as well.

The Journal of Alternative and Complementary MedicineVol. 20, No. 5 Oral Abstract Session 08: Research MethodologyImproving the Patient-Reported Outcome Experience for Participants and PI's: Feasibility and Validity of PROMISAngela Senders, Douglas Hanes, Dennis Bourdette, Ruth Whitham, and Lynne ShintoAngela SendersSearch for more papers by this author, Douglas HanesSearch for more papers by this author, Dennis BourdetteSearch for more papers by this author, Ruth WhithamSearch for more papers by this author, and Lynne ShintoSearch for more papers by this authorPublished Online:7 May 2014https://doi.org/10.1089/acm.2014.5030.abstractAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Improving the Patient-Reported Outcome Experience for Participants and PI's: Feasibility and Validity of PROMIS." The Journal of Alternative and Complementary Medicine, 20(5), p. A13FiguresReferencesRelatedDetailsCited byComputerized Adaptive Testing in Pediatric Brain Tumor ClinicsJournal of Pain and Symptom Management, Vol. 54, No. 3 Volume 20Issue 5May 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Angela Senders, Douglas Hanes, Dennis Bourdette, Ruth Whitham, and Lynne Shinto.Improving the Patient-Reported Outcome Experience for Participants and PI's: Feasibility and Validity of PROMIS.The Journal of Alternative and Complementary Medicine.May 2014.A13-A13.http://doi.org/10.1089/acm.2014.5030.abstractPublished in Volume: 20 Issue 5: May 7, 2014PDF download

Background: In short-term trials, dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS). The tolerability and effects of dalfampridine-ER in clinical practice have not been reported. Objectives: The objective of this paper is to determine the clinical tolerability and effects of dalfampridine on walking and community participation. Methods: All patients at the Portland VA Medical Center prescribed dalfampridine-ER over one year completed the Timed 25-Foot Walk (T25FW), Multiple Sclerosis Walking Scale-12 (MSWS-12), Two-Minute Timed Walk (2MTW), and Community Integration Questionnaire (CIQ) at baseline and follow-up clinic visits. Ongoing use and measures over one year were analyzed. Results: A total of 39 patients (mean age 56.5 years, mean disease duration 19.5 years, 82% male, 38% relapsing–remitting MS, 62% progressive MS) were prescribed dalfampridine-ER. Twenty-four (62%) continued to take dalfampridine-ER. At initial follow-up, all measures improved significantly from baseline (T25FW: –2.7 s, p = 0.004; 2MTW: 41 feet (ft), p = 0.002; MSWS12: –11, p < 0.001; CIQ: 1.2, p = 0.003). At one year, walking endurance and self-perceived walking were still significantly improved (2MTW: 33 ft, p = 0.03; MSWS-12: 5.9, p = 0.007). Conclusions: Dalfampridine-ER was associated with short-term improvements in walking speed and community participation, and sustained improvements in walking endurance and self-perceived impact of MS on walking for one year. Our study supports the utility of this medication in late MS.

We have used a peptide derived from Acanthamoeba castellanii (ACA) to treat the relapsing phase of EAE that develops in SJL mice following immunization with the PLP 139-151 peptide. The native sequence of the ACA 81-95 peptide that shares key residues with the PLP 139-151 peptide is weakly encephalitogenic in SJL mice but is not recognized by antiserum from SJL mice immunized with PLP 139-151. A single amino acid change to the ACA 81-95 peptide sequence significantly enhanced its encephalitogenicity. When administered to SJL mice as a nonlinear peptide octamer, the modified ACA peptide prevented relapsing episodes of EAE in SJL mice previously immunized with the PLP 139-151 encephalitogenic peptide.

Background: Health care providers recommend an annual visit to a multiple sclerosis specialty care provider.Objective: To examine potential barriers to the implementation of this recommendation in the Veterans Health Administration.Design: Observational cohort study.Setting: Veterans Health Administration.Participants: Participants were drawn from the Veterans Affairs Multiple Sclerosis National Data Repository and were included if they had an outpatient visit in 2007 and were alive in 2008 (N = 14,723).Main Outcome Measurements: Specialty care visit, receipt of medical services.Results: A total of 9643 (65.5%) participants had a specialty care visit in 2007. Veterans who were service connected, had greater medical comorbidity, and who lived in urban settings were more likely to have received a specialty care visit. Veterans who were older and had to travel greater distances to a center were less likely to have a specialty care visit.Conclusions: Access to care in rural areas and areas at a greater distance from a major medical center represent notable barriers to rehabilitation and other multiple sclerosis-related care.

Background: Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.Objectives: To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren's Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren's Syndrome.Methods: Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.Results: Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren's Syndrome.Conclusions: Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.

Upon recovery from the initial episode of experimental autoimmune encephalomyelitis (EAE), virtually all SJL mice develop relapsing/remitting episodes of disease. These relapses may occur due to the reactivation of memory T cells initially stimulated as part of the disease-inducing protocol or naïve T-cell populations stimulated by distinct encephalitogens derived from the inflammatory disease process (epitope spread). We have used encephalitogen-specific non-linear peptide octamers to modify the course of relapsing EAE (rEAE) in SJL mice immunized with an oliogodendrocyte-specific protein peptide (OSP 55–71). Our studies show that the peptide-octamers, which target the T cells stimulated by the priming encephalitogen, but not other candidate encephalitogens, prevent rEAE.

The depiction of Judgment Day on the facade of the Cathedral of Notre Dame shows an angel weighing the good and evil of souls to determine whence they go. Hanging on one side are devils tilting the scale in the wrong direction. In making decisions about treating multiple sclerosis (MS) with immunotherapies, we weigh risks and benefits. For us, the devil is in the details of those risks and benefits. If we underestimate risks or overestimate benefits, the scales can tilt in the wrong direction. In 2000, the Food and Drug Administration (FDA) registered the chemotherapy drug, mitoxantrone, for the treatment of aggressive relapsing-remitting MS and secondary progressive MS (SPMS). The FDA based its decision largely on the results of a placebo-controlled trial conducted by the Mitoxantrone for Multiple Sclerosis (MIMS) Study Group. FDA approval came when the only published data from the trial were in abstracts.1,2 When the complete report of the MIMS trial was finally published in 2002,3 neurologists were already using mitoxantrone to treat SPMS. In 2003, the Therapeutics and Technology Assessment (TTA) Subcommittee of the American Academy of Neurology (AAN) reviewed the evidence on mitoxantrone for the treatment of MS.4 The TTA subcommittee noted that there were blinding problems with the MIMS trial, the study …