Background:
Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts ...may limit the use of OCT to MS research.
Objective:
An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials.
Methods:
A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place.
Results:
The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed.
Conclusion:
Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.
Natalizumab, a therapy for multiple sclerosis (MS), has been associated with progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the CNS associated with the JC virus. ...We assessed clinical outcomes and identified variables associated with survival in 35 patients with natalizumab-associated PML.
Physicians provided Karnofsky scores and narrative descriptions of clinical status. Data were supplemented by the natalizumab global safety database.
At the time of analysis, 25 patients (71%) had survived. Survivors were younger (median 40 vs 54 years) and had lower pre-PML Expanded Disability Status Scale scores (median 3.5 vs 5.5) and a shorter time from symptom onset to diagnosis (mean 44 vs 63 days) compared with individuals with fatal cases. Of patients with nonfatal cases, 86% had unilobar or multilobar disease on brain MRI at diagnosis, whereas 70% of those with fatal cases had widespread disease. Gender, MS duration, natalizumab exposure, prior immunosuppressant use, and CSF JC viral load at diagnosis were comparable. Most patients were treated with rapid removal of natalizumab from the circulation. The majority of patients developed immune reconstitution inflammatory syndrome and were treated with corticosteroids. Among survivors with at least 6 months follow-up, disability levels were evenly distributed among mild, moderate, and severe, based on physician-reported Karnofsky scores.
Natalizumab-associated PML has improved survival compared with PML in other populations. Disability in survivors ranged from mild to severe. A shorter time from symptom onset to diagnosis and localized disease on MRI at diagnosis were associated with improved survival. These data suggest that earlier diagnosis through enhanced clinical vigilance and aggressive management may improve outcomes.
Background and purpose
Up‐to‐date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, ...disease‐modifying therapies and recommendations for monitoring disease activity into their clinical practice.
Methods
A steering committee of MS neurologists used a modified Delphi process to develop case‐ and practice‐based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case‐based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing−remitting MS (RRMS) and RRMS with breakthrough disease.
Results
Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first‐line injectables and oral treatments for mild RRMS, and moved to second‐line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented.
Conclusions
Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.
Objectives
Although many neurologists are reluctant to use natalizumab in MS (multiple sclerosis) given the increased risk for PML (progressive multifocal leukoencephalopathy), trust was regained ...with the introduction of JCV antibody titres as a potent disease‐modifying therapy. Literature shows that in patients with a negative JCV serology, the risk of PML is virtually non‐existent. Unfortunately, seroconversion causes concern amongst many neurologists. Furthermore, when patients seroconvert, it is still unclear what the risk is of passing the important threshold of 1.5.
Materials & Methods
JCV serology data of 161 patients were analysed, upon treatment with natalizumab at the University Hospital in Lille, France, between May 2012 and November 2014.
Results
Of the 81 patients who tested negative for JCV antibody at baseline, 23 (28.3%) seroconverted but only seven (8.6%) passed the threshold of 1.5. Of the 80 patients testing positive for JCV antibody at baseline, eight had an initial JCV antibody titre of 0.9 or lower of which only one of eight (12.5%) patients passed the threshold of 1.5 in the following 3 years. Eight of 15 (53.3%) patients passed this threshold if the initial serology was higher than 0.9.
Conclusions
JCV‐negative patients and JCV‐positive patients with antibody levels below or equal to 0.9 both have a low risk of surpassing the 1.5 threshold.
To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD.
The pathophysiologic significance of AD lesions, namely amyloid plaques ...and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment.
The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite AD. Paired helical filaments (PHF)-tau and Abeta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively.
NFD with PHF-tau was systematically present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (S1), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior, temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6, the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired.
The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.
Background
Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities multiple sclerosis (the most common), Balo’s concentric ...sclerosis, Schilder’s disease and acute disseminated encephalomyelitis with overlapping clinical presentation. The aim of our study was to better characterize these patients.
Methods
Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded.
Results
Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD).
Conclusion
This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.
Despite an extensive diagnostic workup, some cases of acute transverse myelitis (ATM) remain of unknown etiology and have been referred to as "idiopathic" by the Transverse Myelitis Consortium group. ...In a retrospective study of 288 patients with ATM, 45 cases (15.6%) met the criteria for idiopathic ATM. The patients formed a relatively homogeneous group in terms of clinical and MRI data, but the prognosis was highly variable.
We investigated the brain magnetic susceptibility changes induced by natalizumab-associated progressive multifocal leukoencephalopathy. We retrospectively included 12 patients with ...natalizumab-progressive multifocal leukoencephalopathy, 5 with progressive multifocal leukoencephalopathy from other causes, and 55 patients with MS without progressive multifocal leukoencephalopathy for comparison. MR imaging examinations included T2* or SWI sequences in patients with progressive multifocal leukoencephalopathy (86 examinations) and SWI in all patients with MS without progressive multifocal leukoencephalopathy. Signal abnormalities on T2* and SWI were defined as low signal intensity within the cortex and/or U-fibers and the basal ganglia. We observed T2* or SWI signal abnormalities at the chronic stage in all patients with progressive multifocal leukoencephalopathy, whereas no area of low SWI signal intensity was detected in patients without progressive multifocal leukoencephalopathy. Among the 8 patients with asymptomatic natalizumab-progressive multifocal leukoencephalopathy, susceptibility changes were observed in 6 (75%). The basal ganglia adjacent to progressive multifocal leukoencephalopathy lesions systematically appeared hypointense by using T2* and/or SWI. Brain magnetic susceptibility changes may be explained by the increased iron deposition and constitute a useful tool for the diagnosis of progressive multifocal leukoencephalopathy.
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