Towards a pathogenetic definition of multiple sclerosis in terms of integrative transformation of generic pathologic processes

2003 ◽  
Vol 61 (2) ◽  
pp. 177-181 ◽  
Author(s):  
L.M Agius
Keyword(s):  
Multiple Sclerosis ◽  
Integrative Transformation ◽  
Definition Of ◽  
Pathologic Processes

scholarly journals Cognitive Issues in Pediatric Multiple Sclerosis

2021 ◽  
Vol 11 (4) ◽  
pp. 442
Author(s):  
Emilio Portaccio ◽  
Ermelinda De Meo ◽  
Angelo Bellinvia ◽  
Maria Pia Amato
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Pediatric Patients ◽  
Leisure Activities ◽  
Disease Onset ◽  
Cognitive Profiles ◽  
Brain Growth ◽  
Network Activation ◽  
Definition Of

Multiple sclerosis (MS) is one of the leading causes of disability in young adults. The onset of MS during developmental age makes pediatric patients particularly susceptible to cognitive impairment, resulting from both disease-related damage and failure of age-expected brain growth. Despite different test batteries and definitions, cognitive impairment has been consistently reported in approximately one-third of pediatric patients with MS. However, the lack of a uniform definition of cognitive impairment and the adoption of different test batteries have led to divergent results in terms of cognitive domains more frequently affected across the cohorts explored. This heterogeneity has hampered large international collaborative studies. Moreover, research aimed at the identification of risk factors (e.g., demographic, clinical, and radiological features) or protective factors (e.g., cognitive reserve, leisure activities) for cognitive decline is still scanty. Mood disorders, such as depression and anxiety, can be detected in these patients alongside cognitive decline or in isolation, and can negatively affect quality of life scores as well as academic performances. By using MRI, cognitive impairment was attributed to damage to specific brain compartments as well as to abnormal network activation patterns. However, multimodal MRI studies are still needed in order to assess the contribution of each MRI metric to cognitive impairment. Importantly, longitudinal studies have recently demonstrated failure of age-expected brain growth and of white matter (WM) and gray matter (GM) maturation plays a relevant role in determining cognitive dysfunction, in addition to MS-related direct damage. Whether these growth retardations might result in specific cognitive profiles according to the age at disease onset has not been studied, yet. A better characterization of cognitive profiles in pediatric MS patients, as well as the definition of neuroanatomical substrates of cognitive impairment and their longitudinal evolution are needed to develop efficient therapeutic strategies against cognitive impairment in this patient population.

The McDonald Criteria for Multiple Sclerosis: time for clarification

2010 ◽  
Vol 16 (5) ◽  
pp. 566-575 ◽  
Author(s):  
Christopher H Hawkes ◽  
Gavin Giovannoni
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Evidence ◽  
Progressive Multiple Sclerosis ◽  
Cervical Cord ◽  
Primary Progressive Multiple Sclerosis ◽  
Drug Trials ◽  
Mcdonald Criteria ◽  
Skill Groups ◽  
Definition Of ◽  
Consistent Response

The McDonald Criteria for Multiple Sclerosis in general have replaced the Poser criteria. Despite this, many consider that there are still areas of ambiguity. In this study, neurologists completed a questionnaire about familiarity with, usefulness and applicability of the McDonald Criteria for Multiple Sclerosis. Understanding of ‘attack’; objective clinical evidence; ‘two or more lesions’ and their ability to interpret case scenarios was evaluated. Responses were analysed overall and by skill group. Ninety-seven consultants and 30 trainees responded, of whom 37 operated a multiple sclerosis clinic (‘experts’). Some (62%) thought the McDonald Criteria for Multiple Sclerosis were useful, and 31% found them confusing or difficult to apply; 38% thought the criteria should be applied universally, others (14—28%) favoured their use for drug trials/research, and 17% rarely used them. Thirty-six (29.1%) thought the McDonald Criteria for Multiple Sclerosis specified two categories: ‘MS and not MS’, but others considered ‘possible’ or ‘probable’ multiple sclerosis were permitted. Experts understood better ‘an attack’ and ‘objective clinical evidence’. All skill groups comprehended poorly what constituted an episode of demyelination, and whether Lhermitte’s phenomenon was acceptable as evidence for cervical cord demyelination. A consistent response was given by 44—50% to ‘two or more lesions’, although this is not well defined. Criteria for primary progressive multiple sclerosis were understood well. We conclude that the McDonald Criteria for Multiple Sclerosis have improved diagnosis but areas of misinterpretation remain, particularly the definition of ‘an attack’, ‘objective clinical evidence’ and ‘two or more lesions’. There was uncertainty about how many multiple sclerosis categories were permitted and whether the terms ‘possible’ and ‘probable’ were allowable. Further clarification might allow the criteria to be applied more consistently.

scholarly journals Perceptions of Health Status in Multiple Sclerosis Patients and Their Doctors

2013 ◽  
Vol 40 (2) ◽  
pp. 210-218 ◽  
Author(s):  
Marcelo Kremenchutzky ◽  
Len Walt
Keyword(s):  
Multiple Sclerosis ◽  
Health Status ◽  
Bodily Pain ◽  
Kappa Statistic ◽  
Patient Perceptions ◽  
Mean Values ◽  
Health Domains ◽  
Important Health ◽  
Definition Of ◽  
Multiple Sclerosis Patients

Objective:To compare neurologist and patient perceptions of multiple sclerosis (MS)-related health status.Methods:MS patients (n=99) were recruited from six sites in Canada. Following a consultation with their neurologist, patients estimated their relapse frequency, rated their general health and quality of life (QoL), reviewed descriptions of eight health domains and selected the three most important, and completed a utility assessment using the standard gamble (SG). Concurrently, neurologists independently used the same instruments to rate their patients' health status. Assessments were compared on the basis of paired mean values of both groups and the degree of exact agreement quantified by intraclass coefficient (ICC) and kappa analyses, which yield values of 1.0 with 100% agreement.Results:There were significant differences (p<0.001) between patient and neurologist ratings for relapses in the last year (0.86 vs. 0.4, respectively), QoL (61.2 vs. 69.7 (maximum score = 100) and utility (0.864 vs. 0.971); ICC analysis revealed moderate to poor levels of agreement (0.56 for QoL to 0.03 for SG). There was little concordance in identification of important health domain and the only significant associations were in bodily pain and social functioning (kappa statistic = 0.24, p = 0.026 for both). Neurologists identified physical functioning domains as important, while patients placed more emphasis on mental health domains.Conclusions:Discrepancies between neurologist and patient perceptions of MS were observed. The study identifies a need to educate neurologists on the recognition of MS health domains that are important in the definition of patient QoL.

scholarly journals Diagnosing and quantifying a common deficit in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2299-e2308 ◽  
Author(s):  
J.A. Nij Bijvank ◽  
L.J. van Rijn ◽  
L.J. Balk ◽  
H.S. Tan ◽  
B.M.J. Uitdehaag ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Diagnostic Accuracy ◽  
Peak Velocity ◽  
Area Under The Curve ◽  
Interquartile Range ◽  
Characteristic Analysis ◽  
Related Quality ◽  
Definition Of

ObjectiveWe present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS).MethodsA validated standardized infrared oculography protocol (DEMoNS [Demonstrate Eye Movement Networks with Saccades]) was used for quantifying prosaccades in patients with MS and healthy controls (HCs). The versional dysconjugacy index (VDI) was calculated, which describes the ratio between the abducting and adducting eye. The VDI was determined for peak velocity, peak acceleration, peak velocity divided by amplitude, and area under the curve (AUC) of the saccadic trajectory. We calculated the diagnostic accuracy for the several VDI parameters by a receiver operating characteristic analysis comparing HCs and patients with MS. The National Eye Institute Visual Function Questionnaire–25 was used to investigate vision-related quality of life of MS patients with INO.ResultsTwo hundred ten patients with MS and 58 HCs were included. The highest diagnostic accuracy was achieved by the VDI AUC of 15° horizontal prosaccades. Based on a combined VDI AUC and peak velocity divided by amplitude detection, the prevalence of an INO in MS calculated to 34%. In the INO group, 35.2% of the patients with MS reported any complaints of double vision, compared to 18.4% in the non-INO group (p = 0.010). MS patients with an INO had a lower overall vision-related quality of life (median 89.9, interquartile range 12.8) compared to patients without an INO (median 91.8, interquartile range 9.3, p = 0.011).ConclusionsThis study provides an accurate quantitative and clinically relevant definition of an INO in MS. This infrared oculography-based INO standard will require prospective validation. The high prevalence of INO in MS provides an anatomically well described and accurately quantifiable model for treatment trials in MS.

scholarly journals Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis

2019 ◽  
Vol 12 ◽  
pp. 175628641983780 ◽  
Author(s):  
Luca Prosperini ◽  
Revere P. Kinkel ◽  
Augusto A. Miravalle ◽  
Pietro Iaffaldano ◽  
Simone Fantaccini
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Disease Activity ◽  
Meta Analysis ◽  
Random Effect ◽  
Patient Characteristics ◽  
Increased Risk ◽  
Disease Reactivation ◽  
Definition Of ◽  
High Level

Background: Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ interruption may result in recrudescence of disease activity. Objective: The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data. Methods: PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse. Results: The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation ( p ⩽ 0.05). Conclusions: Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.

Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters

2002 ◽  
Vol 8 (6) ◽  
pp. 523-526 ◽  
Author(s):  
P Flachenecker ◽  
T Kümpfel ◽  
B Kallmann ◽  
M Gottschalk ◽  
O Grauer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Physical Disability ◽  
Rating Scales ◽  
Disease Duration ◽  
Correlation Coefficients ◽  
Clinical Activity ◽  
Impact Scale ◽  
Fatigue Severity ◽  
Underlying Mechanisms ◽  
Definition Of

Objectives: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). To delineate more clearly the frequency and type of fatigue, we first compared four widely used fatigue scales in consecutive MS patients. Secondly, to further clarify the nature of fatigue, we investigated its relation to physical disability, course of the disease, immunotherapy, and depression. Patients and Methods: Between February and September 2000, 151 consecutive MS patients entering our outpatient clinic (94 relapsing-remitting, 50 secondary progressive, and 7 primary progressive patients; mean age 29.0-7.3 years, mean disease duration 9.9-6.7 years, median EDSS 3.5) filled in a standardized questionnaire including four fatigue scales - Fatigue Severity Scale (FSS), MS-specific FSS (MFSS), Modified Fatigue Impact Scale (MFIS), and Visual Analogue Scale (VAS). Patients were included in the ‘MS-related fatigue group’ (MS-F) when they stated in the questionnaire that fatigue: 1) is one of their three most disabling symptoms; 2) occurs daily or on most of the days; and 3) limits their activities at home or at work. Patients fulfilling none of these criteria were classified as ‘MS-related nonfatigue group’ (MS-NF). Depression was measured by Beck’s Depression Inventory (BDI). Results: Although all scales showed significant differences between MS-F and MS-NF, correlation between these scales was, at best, moderate (correlation coefficients ranging from 0.06 to 0.56). The most discriminative scales were FSS and MFIS, showing no overlap of the 10th and 90th percentiles for the MS-F and MS-NF groups, with cut-off values of 4.6 and 38, respectively. Depression (BDI≥18) was present in 24 of 148 patients who filled in the BDI (16%). FSS was significantly correlated with physical disability (r =0.33, p <0.0001) and BDI (r =0.41, p<0.0001), but not with age, disease duration, clinical activity, and treatment with interferon-b. In multivariate analysis, however, only BDI independently predicted fatigue. Conclusions: The association of fatigue and depression suggests that there might be either common underlying mechanisms or interdependence by a cause-and-effect relationship that requires further investigation. The weak correlation within various fatigue scales is best explained by the fact that fatigue is a multidimensional symptom and, therefore, the available tests measure and weight different aspects of fatigue. Our findings underline the necessity for a more exact definition of fatigue and the development of more valid tools if these are to be used to evaluate treatments.

Degree of microstructural changes within T1-SE versus T1-GE hypointense lesions in multiple sclerosis: relevance for the definition of “black holes”

2020 ◽  
Vol 30 (7) ◽  
pp. 3843-3851
Author(s):  
Caterina Lapucci ◽  
Nicola Romano ◽  
Simona Schiavi ◽  
Laura Saitta ◽  
Antonio Uccelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
Microstructural Changes ◽  
Definition Of

scholarly journals Aggressive multiple sclerosis (2): Treatment

2020 ◽  
Vol 26 (9) ◽  
pp. 1045-1063 ◽  
Author(s):  
Georgina Arrambide ◽  
Ellen Iacobaeus ◽  
Maria Pia Amato ◽  
Tobias Derfuss ◽  
Sandra Vukusic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Current Knowledge ◽  
Companion Paper ◽  
Therapeutic Window ◽  
Future Research ◽  
Permanent Disability ◽  
European Committee ◽  
Efficacious Treatment ◽  
History Of ◽  
Definition Of

The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.

Challenges in multiple sclerosis diagnosis: Misunderstanding and misapplication of the McDonald criteria

2020 ◽  
pp. 135245852091049 ◽  
Author(s):  
Andrew J Solomon ◽  
Roman Pettigrew ◽  
Robert T Naismith ◽  
Salim Chahin ◽  
Stephen Krieger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Subcortical White Matter ◽  
Web Based ◽  
Mcdonald Criteria ◽  
Correct Definition ◽  
Objective Evidence ◽  
Core Elements ◽  
Magnetic Resonance Imaging Mri ◽  
Definition Of

Objective: To assess comprehension and application of the McDonald criteria. Background: Studies suggest that knowledge gaps for specific core elements of the McDonald criteria may contribute to multiple sclerosis (MS) misdiagnosis. Methods: Neurology residents (NR) and multiple sclerosis specialists (MSS) in North America completed a web-based survey. Results: A total of 160 participants were included: 72 NR and 88 MSS. Syndromes incorrectly identified as typical of MS included: complete transverse myelopathy (35% NR and 15% MSS), intractable vomiting/nausea/hiccoughs (20% NR and 5% MSS), and bilateral optic neuritis/unilateral optic neuritis with poor visual recovery (17% NR and 10% MSS). Periventricular magnetic resonance imaging (MRI) lesions were correctly identified by 39% NR and 52% MSS, and juxtacortical lesions were correctly identified by 28% NR and 53% MSS. The correct definition of “periventricular” was chosen by 38% NR and 61% MSS, and that of “juxtacortical” was chosen by 19% NR and 54% MSS. Regions incorrectly identified for MRI dissemination in space fulfillment included the optic nerve (31% NR and 26% MSS) and the subcortical white matter (11% NR and 18% MSS). The majority of participants assessed previous non-specific neurological symptoms without objective evidence of a central nervous system (CNS) lesion as sufficient for clinical dissemination in time. Conclusion: The McDonald criteria are often misunderstood and misapplied. Concerted educational efforts may prevent MS misdiagnosis.

scholarly journals Differential diagnosis of suspected multiple sclerosis: a consensus approach

2008 ◽  
Vol 14 (9) ◽  
pp. 1157-1174 ◽  
Author(s):  
DH Miller ◽  
BG Weinshenker ◽  
M Filippi ◽  
BL Banwell ◽  
JA Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Differential Diagnosis ◽  
Evidence Base ◽  
Demyelinating Diseases ◽  
Future Research ◽  
International Panel ◽  
The Central Nervous System ◽  
Definition Of ◽  
Demyelinating Disorders ◽  
Diagnosis Criteria

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.

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