Prolonged-release (PR) fampridine is the only approved medication to improve walking in multiple sclerosis (MS), having been shown to produce a clinically meaningful improvement in walking ability in ...the subset of MS patients with Expanded Disability Status Scale 4–7. Recent responder subgroup analyses in the phase III ENHANCE study show a large effect size in terms of an increase of 20.58 points on the patient-reported 12-item MS Walking Scale in the 43% of patients classified as responders to PR-fampridine, corresponding to a standardized response mean of 1.68. Use of PR-fampridine in clinical practice varies across Europe, depending partly on whether it is reimbursed. A group of European MS experts met in June 2017 to discuss their experience with using PR-fampridine, including their views on the patient population for treatment, assessment of treatment response, re-testing and re-treatment, and stopping criteria. This article summarizes the experts’ opinions on how PR-fampridine can be used in real-world clinical practice to optimize the benefits to people with MS with impaired walking ability.
Ischemic stroke by septic embolism occurs primarily in the context of infective endocarditis or in patients with a right-to-left shunt and formation of a secondary cerebral abscess is a rare event. ...Erosion of pulmonary veins by a pulmonary abscess can lead to transcardiac septic embolism but to our knowledge no case of septic embolic ischemic stroke from a pulmonary abscess with secondary transformation into a brain abscess has been reported to date.
We report the case of a patient with a pulmonary abscess causing a septic embolic cerebral infarction which then transformed into a cerebral abscess. After antibiotic therapy and drainage of the abscess the patient could be rehabilitated and presented an impressive improvement of symptoms.
Septic embolism should be considered as cause of ischemic stroke in patients with pulmonary abscess and can be followed by formation of a secondary cerebral abscess. Early antibiotic treatment and repeated cranial CT-scans for detection of a secondary abscess should be performed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Das Buch, geschrieben von Mitgliedern der Arbeitsgemeinschaft "Klinische Geweberegeneration" der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie, vermittelt praxisnahes und aktuelles Wissen ...rund um Gelenkknorpelschäden. Schwerpunkte sind Diagnostik und moderne Therapieverfahren wie Knorpelzelltransplantation oder osteochondraler Transfer, die durch Grundlagen zur Biologie und Anatomie des Knorpels sowie Fragen der Dokumentation und Abrechnung abgerundet werden. Das Buch richtet sich an operativ tätige Orthopäden und Unfallchirurgen, aber auch Allgemeinchirurgen, Sportmediziner und Arthroskopeure.
In multiple sclerosis as the most common inflammatory demyelinating disease in Western countries, major therapeutic success has been achieved with regard to strategies targeting immunological master ...switches. These approaches effectively reduce inflammatory disease activity but fail to address ongoing neurodegeneration or disturbed regeneration. However, intense research efforts investigating molecular mechanisms of disease have identified 'druggable' targets for prevention of inflammatory neurodegeneration and disturbed regeneration. This review covers recent developments in clinical trials using optic neuritis as a model for screening such neuroprotective and neuroregenerative therapeutic approaches.
Optic neuritis has been used in a series of recent pilot studies investigating the effects of erythropoietin, simvastatin, autologous mesenchymal stem cells, phenytoin, as well as blockade of LINGO-1 (opicinumab). Of note, these studies applied novel outcome measures related to function and structure of the visual pathway, including optical coherence tomography, full-field visual-evoked potentials, multifocal visual-evoked potential, high as well as low-contrast visual acuity. Comparison of these different approaches reveals novel insights into short-term evolution of neurobiological effects during optic neuritis and the window of opportunity for therapeutic interventions.
Translation of neuroprotective and neuroregenerative approaches to clinical reality represents a huge challenge. Optic neuritis as a prototypic autoimmune demyelinating disease offers an option for testing new therapies targeting key deleterious processes in multiple sclerosis.
Abstract only
Aims/Purpose:
To characterize disease‐induced changes in the first six months after acute optic neuritis and to aid the design of future neuroprotection trials.
Methods:
...Treatment‐independent analysis of the TONE trial cohort (NCT01962571), including 103 patients with acute optic neuritis and baseline high contrast visual acuity <0.5 dec. We analysed study visits at baseline and weeks 1, 4, 16 and 26 with mixed effects linear piece‐wise models to describe the dynamics of low contrast letter acuity, contrast sensitivity, visual fields, visually evoked potentials and macular and peripapillary retinal layer thicknesses. Sample size estimates are based on a two‐sided t‐test with α=0.05, power 80%, and treatment effects equal to 50% of the mean diseased induced change.
Results:
After baseline visual loss, there was improvement of visual function with thinning of inner and swelling of outer retinal layers. Clinical trials could reduce their required size by more than half when using macular ganglion cell and inner plexiform layer thinning (33 patients/group) over peripapillary retinal nerve fibre layer thinning (79/group) as the primary outcome. Similarly, trials of functional neuroprotection could reduce their size by more than 40% when employing the inter‐eye delta of 2.5% low‐contrast letter acuity (109/group) over the affected eye's value alone (189/group) as their outcome. The respective associations to vision‐related quality of life (NEI‐VFQ overall score) were similar (Pearson's |
r
| = 0.08 vs. 0.15 and 0.38 vs. 0.39). Because inner retinal layer thicknesses remained stable after four months but functional improvements continued up to month six, trials should follow up accordingly.
Conclusions:
The negative results of the TONE trial make its participants one of the best‐characterized and largest cohorts of acute optic neuritis. Our data show that future trials may benefit from substantial efficiency gains.
Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable ...models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question whether ChP volumes could act as an interspecies marker of neuroinflammation that closely interrelates with functional impairment. Therefore, we explore ChP characteristics in neuroinflammation in patients with multiple sclerosis and in two experimental mouse models, cuprizone diet-related demyelination and experimental autoimmune encephalomyelitis. We demonstrate that ChP enlargement-reconstructed from MRI-is highly associated with acute disease activity, both in the studied mouse models and in humans. A close dependency of ChP integrity and molecular signatures of neuroinflammation is shown in the performed transcriptomic analyses. Moreover, pharmacological modulation of the blood-CSF barrier with natalizumab prevents an increase of the ChP volume. ChP enlargement is strongly linked to emerging functional impairment as depicted in the mouse models and in multiple sclerosis patients. Our findings identify ChP characteristics as robust and translatable hallmarks of acute and ongoing neuroinflammatory activity in mice and humans that could serve as a promising interspecies marker for translational and reverse-translational approaches.
Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical ...coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT.
In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots.
Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis 1667 MSON eyes and 4109 MSNON eyes and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference −20·10 μm, 95% CI −22·76 to −17·44; p<0·0001) and in MSNON eyes (–7·41 μm, −8·98 to −5·83; p<0·0001). The macula showed RNFL thinning of −6·18 μm (–8·07 to −4·28; p<0·0001) in MSON eyes and −2·15 μm (–3·15 to −1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was −16·42 μm (–19·23 to −13·60; p<0·0001) for MSON eyes and −6·31 μm (–7·75 to −4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01).
The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research.
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