Initial Diagnosis Of Multiple Sclerosis Research Articles

Sensitivity and specificity of visual evoked potentials for early diagnosis of demyelinating diseases

IntroductionInternational criteria are used for the diagnosis of multiple sclerosis (MS) and Isolated Clinical Syndrome (ACS), and Neuromyelitis Optica (NMO). PEVs are not included in any of them. We intend to analyse the sensitivity and specificity of visual evoked potentials in the initial diagnosis of MS, ACS, and NMO. Patients and methodsDescriptive, observational, retrospective study of patients treated for a first episode of RR-EM, NMO, or ACS. VEPs are performed during the study of the first episode, with and without ocular symptoms, between October 2012 and March 2019. Results142 patients with suspected demyelinating disease, 100 with disease. Of them, 61 women (61%), mean age: 38.82 years ± SD 4.6. Of the total, 83 with RREM, 6 NMO, 11 ACS. Of the 6 patients with NMO, 1 (16.66%) had altered VEPs; of 11 with ACS, 2 (18.18%) with altered VEP; Of the 83 patients with RR-MS, 45 patients (54.21%) had altered VEP. The sensitivity and specificity of visual evoked potentials in MS was 92.86% and 84.74%, respectively. In NMO, the sensitivity was 16.66%, and the specificity was 93.34%. In ACS, the sensitivity was 18.18%, and the specificity was 96.94%. ConclusionThe sensitivity of VEP in our series is slightly higher than other series published in optic neuritis in RR-MS, being very low in patients with NMO and ACS. However, the very high specificity of the test in these variants can help its diagnosis. These data should be corroborated in larger series.

Can a diagnosis of multiple sclerosis be made without ruling out neuromyelitis optica spectrum disorder ?

BackgroundThe symptoms of multiple sclerosis (MS) can overlap with neuromyelitis optica spectrum disorder (NMOSD). Although testing is available for aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies, screening for NMOSD is recommended but not mandatory to establish a diagnosis of MS. Methods and resultsWe queried 319,994 individuals who filed claims for MS and NMOSD in a Truven Health Analytics (THA) database and had at least one year of uninterrupted health insurance coverage. Of this cohort, 2001 (0.62%) were diagnosed as having NMOSD after an initial diagnosis of MS, based on ICD 9/10 codes. Since THA only offers claims-based data, we initiated an individual patient-based data search at our medical center to screen for potential misdiagnoses. We identified 4/54 (7.4%) NMOSD cases that were initially diagnosed as having MS. ConclusionsThe results from our small study have significant implications––symptoms, clinical presentation or classic radiological findings perhaps cannot reliably separate MS from NMOSD. If our study findings can be replicated, guidelines to diagnose MS ought to recommend that NMOSD be excluded first despite typical clinical and radiological findings pointing to MS.

Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS)

BackgroundCognitive impairment (CI) affects approximately one-third of the patients with early multiple sclerosis (MS) and clinically isolated syndrome (CIS). Little is known about factors predicting CI and progression after initial diagnosis.MethodsNeuropsychological screening data from baseline and 1-year follow-up of a prospective multicenter cohort study (NationMS) involving 1123 patients with newly diagnosed MS or CIS were analyzed. Employing linear multilevel models, we investigated whether demographic, clinical and conventional MRI markers at baseline were predictive for CI and longitudinal cognitive changes.ResultsAt baseline, 22% of patients had CI (impairment in ≥2 cognitive domains) with highest frequencies and severity in processing speed and executive functions. Demographics (fewer years of academic education, higher age, male sex), clinical (EDSS, depressive symptoms) but no conventional MRI characteristics were linked to baseline CI. At follow-up, only 14% of patients showed CI suggesting effects of retesting. Neither baseline characteristics nor initiation of treatment between baseline and follow-up was able to predict cognitive changes within the follow-up period of 1 year.ConclusionsIdentification of risk factors for short-term cognitive change in newly diagnosed MS or CIS is insufficient using only demographic, clinical and conventional MRI data. Change-sensitive, re-test reliable cognitive tests and more sophisticated predictors need to be employed in future clinical trials and cohort studies of early-stage MS to improve prediction.

Choosing wisely? Multiple Sclerosis and Laboratory Screening for Autoimmune Differential Diagnoses

Abstract Background A variety of diseases can mimic the presentation of multiple sclerosis (MS). Diagnosing MS requires the exclusion of conditions considered in the differential diagnosis of MS. The guidelines of the German Society of Neurology (DGN) recommend analyzing 13 mandatory and 9 optional laboratory parameters. The mandatory recommendations include antinuclear antibodies (ANA) as well as antibodies against double-stranded DNA (anti-dsDNA Abs)). Methods In a cohort of MS outpatients, those patient records were analyzed in which test results for all or at least some of the recommended laboratory parameters were available. In addition to these laboratory parameters, MRI data, family history, clinical presentation, evoked potentials, and CSF findings were analyzed. Furthermore, a questionnaire was used to prospectively collect information about rheumatological symptoms relevant to the differential diagnosis of MS. Results In 197 of the included 554 patients, at least some of the recommended differential diagnostic laboratory parameters were available. In 59.4% of these patients, ANA titers ≥ 1:80 were detected. Neither ANA nor ANCA nor anti-dsDNA abs were able to distinguish between MS and non-MS. In 124 MS patients, 54.8% had positive ANA titers ≥1:80. MS patients with these titers suffered more frequently from autoimmune diseases and were more likely to have a family history of MS. Of the remaining 73 patients without MS, 67.1% were ANA positive. In this patient population, the ANA-positive patients were more frequently diagnosed with psychiatric diseases. In the prospectively surveyed MS patients with an ANA titer >1:160, no rheumatologic disease was diagnosed during the average follow-up period of 1.9 years. Conclusion In line with the "Choosing Wisely" recommendations of the American College of Rheumatology, mandatory laboratory screening appears to offer no benefit to the initial diagnosis of multiple sclerosis, unless a specific differential diagnosis is to be excluded.

Case Report: A case of neurogenic bladder in the setting of Behçet's disease after an initial diagnosis of multiple sclerosis

Behçet’s disease (BD) is an autoimmune vasculitis with an unclear etiology presenting with a classic triad of symptoms including oral and genital ulcers as well as iridocyclitis. A subset of BD patients exhibit neurological symptoms including psychiatric disturbances, balance problems, and voiding dysfunction, and the symptoms of BD can mimic other neurological diseases, including multiple sclerosis (MS). Differentiating between potential diagnoses is challenging due to the lack of specific tests for these disorders and the overlap between clinical symptoms and radiological findings. We describe the case of a 52 year old woman initially diagnosed with and treated for MS. From the urologic standpoint, she was treated for neurogenic detrusor overactivity with detrusor-sphincter-dyssynergia utilizing ileocecal augmentation cystoplasty with a continent stoma for intermittent catheterization. The patient was later diagnosed with BD in light of additional clinical findings.

Editorial

As we close out another busy year in caring for patients with multiple sclerosis (MS), the current issue of IJMSC offers another set of articles covering a broad range of topics relevant to MS clinicians and researchers.One important article deals with the initial diagnosis of MS, which is a critical step in defining subsequent treatment approaches, whether these are pharmacologic, rehabilitative, or a mixture of the two. Dr. Lalan and colleagues of the University of Mississippi Medical Center in Jackson contribute to our understanding of how to differentiate neuromyelitis optica (NMO) from MS using magnetic resonance imaging. Given that NMO is treated differently than more standard forms of MS, and that NMO patients may even worsen if given standard disease-modifying agents used in MS, this differentiation between the two entities is critical. The authors offer guidelines that are helpful to all MS clinicians, but especially to those who may not have seen this rarer form of demyelinating disease on a regular basis.Once the diagnosis of MS is established, the next step for an MS clinician is generally to consider whether a disease-modifying agent is appropriate and, if so, which one. An important subsequent step is to make sure that the patient is compliant with this agent. Dr. Dhib-Jalbut of the UMDNJ–Robert Wood Johnson Medical School in New Brunswick, New Jersey, and colleagues describe the effect of a focused training and education program using specialized nurses on compliance with interferon beta-1b in patients with early-onset MS. The program seemed to be effective in increasing patients' adherence to disease-modifying therapy.We have two contributions on specific areas of symptom management in this issue, one being a discussion of the use of a comprehensive pain management program in MS, and the other being a listing of poster presentations at a recent symposium on gait and balance in MS. While some clinicians continue to believe that MS does not cause pain, MS patients clearly experience pain from the disease as well as from multiple other causes, and most MS clinicians feel ill-equipped to effectively help patients with their pain. Dr. Sullivan and colleagues at the Cleveland Clinic in Cleveland, Ohio, describe the experience of MS patients who have chronic pain and have been enrolled in a comprehensive chronic pain rehabilitation program at the Cleveland Clinic. The authors demonstrate that MS patients can have significant improvements in pain, depression, and functioning, with results similar to those experienced by non-MS patients. Dr. Zackowski of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues have organized a symposium on gait and balance in MS for a couple of years now, and we have the pleasure of including a list of the poster abstract titles from the most recent conference in the print issue, with the full abstracts published in our online edition at IJMSC.org. We are glad to help achieve a wider audience for their excellent work on this important topic.We are particularly pleased to have a contribution from a colleague in Jordan, Dr. Hamed of the University of Jordan in Amman, which discusses the real-life experience of MS patients and how environmental factors hinder their attempts to integrate into the wider community. Dr. Hamed also discusses the potential role for occupational therapists as well as others in planning intervention programs for patients with MS. Although the study involved Jordanian MS patients, the findings are equally applicable to other countries.Closing out this issue are two helpful contributions regarding caregivers of people with MS. Ms. Gupta of Kantar Health in Princeton, New Jersey, along with colleagues at EMD Serono and Pfizer, compares the reported burden of caregiving for MS patients and Alzheimer's disease patients, finding that MS caregivers have a much heavier load in some areas. This interesting study has important implications for policymaking as well as raising our awareness of caregiving issues. Ms. Preissner and colleagues of the University of Illinois at Chicago discuss the difficulty of doing research involving MS caregivers and how to get around these issues in order to advance such research and then develop educational programs to assist the caregivers, who are so crucial to the lives of our MS patients.We also want to remind you that the deadline for submitting abstracts for the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis, to be held in the spring of 2013, is December 31, 2012. Enjoy the rest of 2012, and we at IJMSC wish you all a very happy New Year!

Catastrophic Demyelinating Encephalomyelitis After Intrathecal and Intravenous Stem Cell Transplantation in a Patient With Multiple Sclerosis

Stem cell transplantation is an investigational therapy for multiple sclerosis. The authors describe a case of catastrophic demyelinating encephalomyelitis following stem cell transplantation in a 17-year-old girl. Nine months after an initial diagnosis of multiple sclerosis, she underwent stem cell transplantation in Costa Rica. Subsequently, she deteriorated and was transported back to the United States with headache and vomiting progressing to quadriparesis, locked-in syndrome, and superimposed encephalopathy. Magnetic resonance imaging and brain biopsy were consistent with fulminant demyelinating encephalomyelitis with enhancing parenchyma and leptomeninges. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and high protein. The protracted illness required tracheostomy and gastrostomy. After methyleprednisone, intravenous immunoglobulin, and cyclophosphamide, she improved during 2.5 months to an ambulatory, functionally independent state. Subsequently, typical less severe multiple sclerosis relapses occurred. This case demonstrates that stem cell transplantation may provoke life-threatening encephalomyelitis in patients with multiple sclerosis. This highlights the need to restrict transplantation to trials with appropriate safety controls.

Interferon Beta Treatment in Neuromyelitis Optica

To describe a patient with neuromyelitis optica (NMO) whose aquaporin 4 (AQP4) antibody levels increased following treatment with interferon beta. Prospective clinical and laboratory case report. Institutional referral center for multiple sclerosis (MS). Patient One patient with an initial diagnosis of MS that was later revised to NMO. A course of interferon beta-1a followed by conventional immunosuppression. Blood samples were collected from the onset of treatment, and clinical and laboratory assessment was performed. Serum levels of AQP4 antibody and number and characteristics of neurological relapses. After 3 relapses during a 10-month period despite interferon beta-1a treatment, the diagnosis of AQP4 antibody-positive NMO was made and treatment was switched to prednisolone and methotrexate. The AQP4 antibody titers rose dramatically during treatment with interferon beta, and then fell when conventional immunosuppressive therapy was substituted; the patient has remained relapse-free for the subsequent years. Although previous articles have suggested that interferon beta may increase relapses in NMO, this is the first to illustrate an increase in AQP4 antibodies associated with such treatment.

Group Coaching for Individuals with Multiple Sclerosis

The physical, emotional, and mental changes associated with multiple sclerosis (MS) can disrupt patients' lives on many levels and interfere with their pursuit of life goals. Health-care practitioners usually work with people with MS in traditional medical settings—for example, upon initial diagnosis of MS or after an exacerbation of symptoms. Because of the nature of such settings and the current state of health care, it is challenging to provide the ongoing support and guidance that patients need to work toward life goals that were in place before the onset of their illness. Coaching is a talk-based process that uses tools and techniques designed to help individuals make progress toward their life goals. Coaching in a group format is an emerging method for guiding people with similar situations or needs toward their goals. The pilot group coaching project described here provides initial evidence that group coaching may be a valuable service-delivery model for expanding possibilities for individuals with MS living in the community.

CIS case studies

The onset of multiple sclerosis presents in 85% of cases as a subacute clinical event, the so-called clinically isolated syndrome. This event involves either focal or multifocal brain regions, most frequently the optic nerve, brainstem or spinal cord. The initial diagnosis of multiple sclerosis necessitates the demonstration of dissemination of pathology in time and space, as well as the exclusion of other alternative diagnoses, and can be challenging. Confirming a diagnosis of multiple sclerosis is a sensitive time for both patient and physician. The patient is faced with a difficult diagnosis and the physician must consider making difficult treatment decisions regarding therapy and follow-up care. This article presents a number of case studies that illustrate the diversity of presentation of clinically isolated syndrome and the challenges associated with confirming a diagnosis of multiple sclerosis.

The roles of blink reflex and sympathetic skin response in multiple sclerosis diagnosis.

The neurological history and examination are important in multiple sclerosis (MS) diagnosis, but early and accurate diagnosis of MS often requires judicious use of paraclinical information. Electrophysiologic techniques have an important role in demonstrating lesions that are clincally silent but magnetic resonance imaging (MRI) is accepted as the most sensitive paraclincal test for detecting asymptomatic dissemination in space for MS patients. In order to test the sensitivity of electrophysiologic techniques in diagnosing asymptomatic MS lesions, we performed blink reflex (BR) and sympathetic skin response (SSR) studies on 13 female (mean age 39 -/+ 9 years) and 8 male (mean age 35 -/+ 14 years) patients with a diagnosis of definite MS who do not have any clinical symptoms nor signs referable to brainstem or autonomic system dysfunction. Forty three percent of patients on SSR testing and 40% of patients on BR testing demonstrated abnormal results. In countries with unfavorable economic conditions, diagnosis, especially the follow-up evaluation of MS patients, poses a major dilemma. The role of diagnostic techniques in MS diagnosis when MRI is available is an economic problem. Diagnostic evaluation adds to the cost of health expenses. We usually choose to perform MRI only at the initial diagnosis of MS and perform follow-up evaluations during remissions and exacerbations with the aid of electrophysiologic techniques. We stress the importance of electrophysiologic screenings in MS patients because they provide data that cannot be obtained through clinical evaluations only with a little cost.

The use of interferon beta at the time of initial diagnosis of multiple sclerosis

Dr Hodgkinson points out the increasing evidence that damage to axons as well as to myelin can occur early in the clinical course of multiple sclerosis (MS) and accumulates over time. This indicates the need for a safe effective treatment for MS from its onset. The main question here is whether interferon beta meets this need. Dr Macdonell makes it clear that when considering this therapy one has to take into account the nature of the disease at the time of clinical presentation. Currently it is unclear whether interferon beta is beneficial in secondary progressive MS, and so its initiation at this stage of MS is probably best avoided. Certainly interferon beta should be avoided in primary progressive MS at present, as there is no evidence that it has a beneficial clinical effect and indeed there is one report that it actually worsens the clinical picture by increasing spasticity.

Should all patients with an initial diagnosis of multiple sclerosis be treated with Beta Interferon?

Should all patients with an initial diagnosis of multiple sclerosis be treated with Beta Interferon?

Should all patients with an initial diagnosis of multiple sclerosis be treated with Beta Interferon? The case against

Should all patients with an initial diagnosis of multiple sclerosis be treated with Beta Interferon? The case against

Delay in diagnosis of X-linked adrenoleukodystrophy

In 16 consecutive patients with clinically suspected and biochemically proven X-linked adrenoleukodystrophy (X-ALD), total delay (interval between onset of symptoms and diagnosis) and specialist delay (interval between referral to a specialist and diagnosis) were determined. All patients previously were unaware of the existence of X-ALD in their families. From the time of onset of symptoms attributable to this disease until diagnosis, mean total delay was 9.9 (range 1–33) years and mean specialist delay was 8.4 (range 0–33) years. Three patients who presented with adrenocortical insufficiency had mean total and specialist delays of 17.3 (range 9–33) years. Five patients with an initial diagnosis of multiple sclerosis had mean total and specialist delays of 12.8 (range 5–25) and 11.2 (range 1–23) years, respectively. In 12 patients with adrenomyeloneuropathy-the second most frequent phenotype of X-ALD — mean total delay was 11.0 (range 2–33) years and mean specialist delay 9.1 (range 0–33) years. Since 1981 X-ALD can be reliably diagnosed on the basis of elevated levels of very long chain fatty acids in plasma and/or cultured fibroblasts. The delays therefore must have been due to the unfamiliarity with the clinical manifestations and diagnostic possibilities of this disease. Once X-ALD is diagnosed, dietary treatment and/or bone marrow transplantation may be considered. Genetic counseling should be performed, and screening of other family members is essential for the early identification of affected relatives.

Quantitative MRI studies for assessment of multiple sclerosis.

Although magnetic resonance imaging (MRI) is a valuable aid in the initial diagnosis of multiple sclerosis (MS), quantitatively MRI has been disappointing in staging and evaluating therapy protocols by means of serial examinations. In this study, image processing algorithms were developed for the global analysis of MR images of the cerebrum. Limited three-dimensional segmentation was achieved through histogram analysis by these algorithms, which are essentially operator independent. The effects of coil response and tip angles, patient positioning, and interslice gap thicknesses were examined for 10 MS patients with repeated examinations for a total of 72 images. Effects of technique and instrumentation errors were approximately 6%, and agreement between two independent operators for measuring the total MR pixel sum from periventricular effusions and intense MS plaques was better than 97% with a standard deviation of 2.9%.