1,721,065 research outputs found
Worse recovery from acute attacks and faster disability accumulation highlights the unmet need for improved treatment in patients with late-onset neuromyelitis optica spectrum disorders (COPTER-LO study)
No full textObjective This study analyzed clinical characteristics, attack recovery and long-term disability accumulation in late-onset (LO ≥ 50 years at onset) versus early-onset (EO < 50 years) NMOSD. Methods This multicenter cohort study included demographic and clinical data from 446 NMOSD patients collected from 35 German Neuromyelitis Optica Study Group (NEMOS) centers. Time to disability milestones was estimated through Kaplan-Meier analysis and Cox proportional hazard regression models adjusted for sex, year of onset, immunotherapy exposure and antibody status. Generalized estimating equations (GEE) were used to compare attack outcomes. Results Of the 446 NMOSD patients analyzed (83.4% female, 85.4% AQP4-IgG-positive, median age at disease onset = 43 years), 153 had a late-onset (34.3%). AQP4-IgG+ prevalence was higher in LO- than in EO-NMOSD (94.1% vs. 80.9%, p <0.001). Optic neuritis at onset was more frequent in EO-NMOSD (27.4% vs. 42.6%, p <0.002), whereas myelitis was more common in LO-NMOSD (58.4% vs. 37.9%, p <0.001). Both groups had similar annualized attack rates (AAR, 0.51 vs. 0.54, p =0.352), but attack recovery was poorer (complete remission in 15.6% vs. 27.4%, p <0.001) and relapse-associated worsening (RAW) was higher in LO-NMOSD (RAW: 3 vs. 0.5, p <0.001). Long-term immunotherapy use was comparable. LO-NMOSD exhibited faster progression to disability endpoints (EDSS 4: HR = 2.64, 95% CI=1.81–3.84). Interpretation LO-NMOSD patients presented more often with myelitis, experienced worse attack outcomes and faster disability accumulation, despite comparable AAR, acute attack treatment and long-term treatment regimens. Accordingly, therapeutic strategies for attack and prophylactic treatment in LO-NMOSD have to be improved
Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial
No full texta prospective longitudinal MRI and clinical study
No full textDas histopathologische Korrelat der Multiplen Sklerose sind zeitlich und
örtlich disseminiert auftretende Entzündungsherde vornehmlich in der weißen
Substanz des Zentralnervensystems, die sich in T1- und T2-gewichteten
Aufnahmen der konventionellen Kernspintomographie als hypo- beziehungsweise
hyperintense Läsionen darstellen. Bei akut entzündlichen Herden lässt sich
eine Kontrastmittelanreicherung nachweisen. Darüber hinaus bieten innovative
MRT-Methoden wie die Diffusions- und Perfusionsbildgebung die Möglichkeit, in
vivo Einblicke in die entzündlichen Krankheitsprozesse und die
Läsionsentstehung auch auf gewebestruktureller Ebene zu gewinnen. Ziel der
vorliegenden Arbeit war es, bei Patienten mit hochaktivem, schubförmig-
remittierenden Krankheitsverlauf mittels konventioneller Kernspin-tomographie
die Entwicklung der Läsionen im Verlauf zu untersuchen. Gibt es einen
Zusammenhang zwischen cerebraler „Läsionslast“ und klinisch-neurologischem
Zustand? Welche Auswirkung hat der Nachweis einer Kontrastmittelanreicherung
im cerebralen MRT auf klinischen Parameter wie den Expanded Disability Status
Scale (EDSS) und Multiple Sclerosis Functional Composite (MSFC)? Zusätzlich
wurden pathophysiologische Aspekte der Entstehung einer einzelnen Läsion
untersucht. Gibt es Veränderungen der Perfusion im Prozess der
Läsionsentstehung? In welchem zeitlichen Zusammenhang stehen diese mit einer
Blut-Hirn-Schrankenstörung und einer Änderung der Diffusion. Unterscheiden
sich verschiedene Läsionstypen bezüglich Diffusion und Perfusion? Prospektiv
wurden 20 Patienten mit hoher klinischer und kernspintomographischer
Krankheitsaktivität im Durchschnitt über 11 Monate untersucht. Auch in dieser
hochaktiven Patientengruppe war ein „klinisch-radiologisches Paradox“ zu
beobachten, d.h. eine Korrelation zwischen klinischen und
kernspintomographischen Parametern ließ sich nicht belegen. Mit abnehmender
Anzahl kontrastmittelanreichernder, akut entzündlicher Läsionen in der
Bildgebung zeigte sich eine Erhöhung der MSFC-Testleistung ohne signifikante
Veränderung des EDSS. Diese Zunahme des MSFC-Wertes ist zurückzuführen auf
eine Verbesserung des Paced Auditory Serial Addition Test (PASAT), einem
Subtest der kognitive Leistungsfähigkeit misst. An einer zweiten unabhängigen
Gruppe mit 28 Patienten konnte bestätigt werden, dass das PASAT-Testergebnis
bei gleichzeitigem Nachweis von kontrastmittelpositiven Herden im cerebralen
MRT signifikant schlechter war als ohne Kontrastmittelnachweis. Da die
weiteren Subtests des MSFC (Nine-Hole Peg Test und 25-foot Timed Walk Test)
keinen Unterschied zeigten, wurde somit der Nachweis erbracht, dass die durch
Kontrastmittelanreicherung im cerebralen MRT angezeigte Krankheitsaktivität
insbesondere zu einer Beeinträchtigung der kognitiven Leistung bei körperlich
stabilen Patienten führt. Bei der Entwicklung einer einzelnen entzündlichen
Läsion in der Perfusions- und Diffusionsbildgebung, konnte gezeigt werden,
dass die Perfusion als erster Parameter ansteigt. Dieser Anstieg ist vor
Zunahme des Apparent Diffusion Coefficient und vor Störung der Blut-Hirn-
Schranke zu beobachten. In ringförmig kontrastmittelanreichernden Läsionen
weist das nicht anreichernde Zentrum der Läsion eine im Vergleich zum
anreichernden Anteil reduzierte Perfusion auf, was zu einer vermehrten
Gewebedestruktionen beitragen könnte. Bei MS-Herden, die sich zu
T1-hypointensen Läsionen entwickeln, sinkt der kapilläre Blutfluss und das
Blutvolumen unter Ausgangsniveau, dies ist ein möglicher Hinweis auf
Ausbildung einer minderperfundierten Glianarbe. Abschließend kann festgestellt
werden, dass die konventionelle MRT-Bildgebung für bestimmte Aspekte der
Multiplen Sklerose nur eine begrenzte Aussagekraft hat. Sie stellt einen
Surrogatparameter dar, von dem nur sehr eingeschränkt auf den klinischen
Zustand und Verlauf des Patienten geschlossen werden kann.The histopathological equivalent of multiple sclerosis (MS) are inflammatory
plaques disseminated in space and time and located predominantly in the white
matter of the central nervous system. In T1 and T2 weighted scans of
conventional magnetic resonance tomography they appear as hypo- respectively
hyperintense lesions. Innovative MRI methods like diffusion- and perfusion
imaging bear the opportunity to gain in vivo insights in inflammatory
processes and lesion development on the level of tissue structure. The aim of
this work was to analyse longitudinally the development of lesion load in
patients with a highly active relapsing-remitting course of disease. Is there
a correlation between lesion load and neurological condition? Which effect
does the proof of contrast agent enhancement in the cerebral MRI have on
clinical parameters? In addition pathophysiological aspects of the formation
of a single lesion were investigated. Are there changes of perfusion in the
process of lesion formation? How is the chronological sequence in respect to
blood-brain-barrier disruption and changes in diffusion? Are various types of
lesions different regarding diffusion and perfusion? Twenty patients with high
clinical and MRI disease activity were investigated on average over a period
of 11 months. Also, in this highly active group of patients the “clinic-
radiological paradox” was observed. That means, a correlation between clinical
and MRI parameter could not be proven. With decreasing number of contrast
enhancing inflammatory lesions in the MRI the result of the Multiple Sclerosis
Functional Composite (MSFC) increased while the Expanded Disability Status
Scale remained stable. The improvement of the MSFC performance is caused by an
increase of the Paced Auditory Serial Addition Test (PASAT), a subtest
measuring cognitive capability. With a second independent group of 28 patients
we affirmed that comparing time points with and without proof of contrast
enhancing lesions the PASAT is significantly worse when Gd-enhancement is
detectable. As the further subtests of the MSFC (Nine-Hole Peg Test und
25-foot Timed Walk Test) remained unchanged, we showed, that cognitive
performance is affected by the appearance of contrast agent enhancement as a
surrogate marker of inflammatory activity in otherwise physically stable MS
patients. Focusing on the development of a single inflammatory lesion in
perfusion and diffusion imaging we proofed that perfusion parameters increase
at the very first. This can be observed even before the rising of the Apparent
Diffusion Coefficient and before disruption of the blood-brain-barrier.
Regarding ring enhancing lesions, a decreased perfusion was measured in the
non-enhancing centre compared to the enhancing part of the lesion. This may
contribute to an augmented destruction of tissue in this area. In MS lesions
which develop to a T1 hypointensity, capillar bloodflow and volume decline
below base level, conceivably a hint to the formation of a less perfused glial
scar. Summarizing we have to state, that conventional MRI imaging is a
surrogate parameter that allows only very restricted conclusions on the
clinical state and course of a MS patient. Innovative MRI methods offer the
opportunity to answer in vivo questions of tissue structure in the
pathogenesis of MS
CHANCE NMO Study
No full textBackground and Objectives To evaluate costs and health-related quality of life (HRQoL) of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Methods In this multicenter cross-sectional study, data on consumption of medical and nonmedical resources and work ability were assessed via patient questionnaires. Costs were analyzed in Euros for 2018 from the societal perspective. HRQoL was captured by the EuroQoL Group 5 Dimension 5 Level Scale (EQ-5D-5L) questionnaire. Clinical data were retrieved from the Neuromyelitis Optica Study Group (NEMOS) database. Results Two hundred twelve patients (80% women, median age 50 [19–83] years, median disease duration 7 [0–43] years, median Expanded Disability Status Scale [EDSS] score 3.5 [0–8.5], 66% aquaporin-4 immunoglobulin G [IgG] positive, 22% MOG IgG positive, 12% double seronegative) were analyzed. The mean total annual per capita cost of illness accounted for €59,574 (95% CI 51,225–68,293 or US dollars [USD] 70,297, 95% CI 60,445–80,586), and the mean index value of the EQ-5D-5L was 0.693 (95% CI 0.65–0.73). The most important cost drivers were informal care costs (28% of total costs), indirect costs (23%), and drugs (16%), especially immunotherapeutics. Costs showed a positive correlation with disease severity (ρ = 0.56, 95% CI 0.45–0.65); in the EDSS score 6.5 to 8.5 subgroup, the mean annual costs were €129,687 (95% CI 101,946–160,336 or USD 153,031, 95% CI 120,296–189,196). The HRQoL revealed a negative correlation to disease severity (ρ = −0.69, 95% CI −0.76 to −0.61); in the EDSS score 6.5 to 8.5 subgroup, the EQ-5D-5L mean index value was 0.195 (95% CI 0.13–0.28). Neither antibody status nor disease duration influenced the total annual costs or HRQoL. Discussion These German data from the era without approved preventive immunotherapies show enormous effects of the diseases on costs and quality of life. An early and cost-effective therapy should be provided to prevent long-term disability and to preserve quality of life
Time to disability milestones and annualized relapse rates in NMOSD and MOGAD
No full textObjective To investigate accumulation of disability in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein‐antibody‐associated disease (MOGAD) in a changing treatment landscape. We aimed to identify risk factors for the development of disability milestones in relation to disease duration, number of attacks, and age. Methods We analyzed data from individuals with NMOSD and MOGAD from the German Neuromyelitis Optica Study Group registry. Applying survival analyses, we estimated risk factors and computed time to disability milestones as defined by the EDSS. Results We included 483 patients: 298 AQP4‐IgG + NMOSD, 52 AQP4‐IgG ‐ /MOG‐IgG ‐ NMOSD patients, and 133 patients with MOGAD. Despite comparable annualized attack rates, disability milestones occurred earlier and after less attacks in NMOSD patients than MOGAD patients (median time to EDSS 3: AQP4‐IgG+ NMOSD 7.7 (95%CI 6.6 – 9.6) years, AQP4‐IgG ‐ /MOG‐IgG ‐ NMOSD 8.7 ) years, MOGAD 14.1 (95%CI 10.4 – 27.6) years; EDSS 4: 11.9 (95%CI 9.7 – 14.7), 11.6 (95% lower CI 7.6) and 20.4 (95% lower CI 14.1) years; EDSS 6: 20.1 (95%CI 16.5 – 32.1), 20.7 (95% lower CI 11.6), and 37.3 (95% lower CI 29.4) years; and EDSS 7: 34.2 (95% lower CI 31.1) for AQP4‐IgG + NMOSD). Higher age at onset increased the risk for all disability milestones, while risk of disability decreased over time. Interpretation AQP4‐IgG + NMOSD, AQP4‐IgG ‐ /MOG‐IgG ‐ NMOSD and MOGAD patients show distinctive relapse‐associated disability progression, with MOGAD having a less severe disease course. Investigator‐initiated research has led to increasing awareness and improved treatment strategies appearing to ameliorate disease outcomes for NMOSD and MOGAD. This article is protected by copyright. All rights reserved
Differential associations of intrathecally produced immunoglubulin (Ig)G and IgM with radiological findings in early multiple sclerosis
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study
Full text linkObjective: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. Materials and methods: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. Results: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). Conclusion: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system
- …
