multiple sclerosis (MS)

#Diagnosis of #multiple sclerosis: 2016 MAGNIMS criteria just as good as the 2010 #McDonald criteria

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  • The Lancet Neurology

Background

In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria.

Methods

Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16–60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis.

Findings

Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50.0 months [IQR 27.0–78.4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0.91 [95% CI 0.85–0.94] and 2016 MAGNIMS 0.93 [0.88–0.96]), similar specificity (0.33 [0.25–0.42] and 0.32 [0.24–0.41]), and similar area under the curve values (AUC; 0.62 [0.57–0.67] and 0.63 [0.58–0.67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0.92 [0.87–0.96], specificity 0.31 [0.23–0.40], AUC 0.62 [0.57–0.66]) or cortical lesions (sensitivity 0.92 [0.87–0.95], specificity 0.32 [0.24–0.41], AUC 0.62 [0.57–0.67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0.85 [0.78–0.90], slightly higher specificity (0.40 [0.32–0.50], and similar AUC (0.63 [0.57–0.68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0.92 [0.87–0.96]), and slightly lower specificity (0.26 [0.18–0.34]) and AUC (0.59 [0.55–0.64]). AUC values were also similar for DIT (2010 McDonald 0.61 [0.55–0.67] and 2016 MAGNIMS 0.61 [0.55–0.66]) and DIS plus DIT (0.62 [0.56–0.67] and 0.64 [0.58–0.69]).

Interpretation

The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria.

Funding

UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation.

Anúncios

#Multiple sclerosis is associated with #atrophy of retinal ganglion cells and axons

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Background

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.

Methods

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.

Findings

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).

Interpretation

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.

Funding

None.

Petzold A, Balcer LJ, Calabresi PA, et al. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2017 Oct;16(10):797-812.doi: 10.1016/S1474-4422(17)30278-8.

Mothers who breastfeed show reduced risk of MS

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No association was seen with number of pregnancies, use of hormonal contraceptives, or age at first birth.

Mothers who breastfeed for at least 15 months over one or more pregnancies may be less likely to develop multiple sclerosis (MS), according to new research.

In a study published in Neurology , 397 women with MS or its precursor, clinically isolated syndrome, were compared to 433 controls matched for race and age. The women were given in-person questionnaires about pregnancies, breastfeeding, hormonal contraceptive use and other factors.

Women who had breastfed for a cumulative amount of 15 months or more with one or more children, were 53 per cent less likely to develop MS or clinically isolated syndrome than women who had a total of 0-4 months of breastfeeding. Women who were age 15 or older at the time of their first menstrual cycle were 44 per cent less likely to develop MS than women who were 11 years old or younger at the time of their first menstruation.

The number of years a woman ovulated was not associated with MS risk. No association was seen with number of pregnancies, use of hormonal contraceptives or age at first birth.

High coffee consumption may reduce likelihood of MS

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Individuals who drank more than six cups a day had a 30 per cent lower risk of developing MS.

Once again, a study provides evidence for the beneficial effects of coffee. According to the study published in “The Journal of Neurology, Neurosurgery & Psychiatry”, high coffee consumption is linked to a lower risk of developing multiple sclerosis (MS).

Scientists from the Karolinska Institute in Stockholm (Sweden) based their findings on two representative studies from Sweden and the USA. In total, 2.780 MS patients were compared with some 3,970 healthy controls. All participants were interviewed about their daily coffee consumption across different time periods, ranging from adolescence to when they reached 40 years, or older.

Both studies showed that individuals with lower daily coffee consumption were at a higher risk of MS, even after data adjustment for potential influencing factors. In the Swedish study, people who drank more than six cups of coffee every day (more than 900 millilitres) had a 28 to 30 per cent lower risk of MS compared to those who never drank coffee. In the US study, the likelihood of developing MS was 26 to 31 per cent lower if people drank more than 948 millilitres of coffee daily over a period of several years.

Of course, no firm conclusions about cause and effect can be drawn from an observational study, emphasised the researchers. Nevertheless, the results provide further evidence of caffeine’s neuroprotective effect, which may even be able to prevent diseases such as Alzheimer’s and Parkinson’s. In any case, the role of coffee and its components in the development of these diseases clearly needs to be further researched.

Some herpes viruses can infect neurons

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Some gammaherpesviruses may underlie some symptoms of neurological diseases, providing potential new treatment options.

A certain group of herpes viruses can – contrary to previous assumptions – infect human neurons. This is the outcome of a study based on laboratory trials, published in “mBio”. Accordingly, the subgroup of gammaherpesviruses may be the underlying cause for some symptoms of neurological diseases.

Scientists from the University of Pennsylvania, Philadelphia, conducted the experiments because the cerebrospinal fluid of patients with neurological diseases, such as Alzheimer’s, multiple sclerosis (MS) and cerebellar ataxia, teemed with Epstein-Barr virus (EBV). In lab experiments, clinicians then tested if EBV and the Kaposi’s sarcoma-associated herpes virus (KSHV), which belongs to the family of gammeherpesviruses, can infect fetal and neuroblastoma cells.

In both cell types, contact with the viruses (marked with a fluorescent protein) led to the appearance of fluorescent signals in the infected cells and the appearance of key viral proteins. Furthermore, the liquid in which the viruses were grown, contained functional virus particles capable of infecting other cells. Treatment with the drug acyclovir, which inhibits EBV and related viruses, reduced the production of virus particles.

Although causality has not yet been confirmed, the virus seems to be associated with the neuropathology, said the researchers. It may therefore be responsible for some of the symptoms, and antiviral medications could present a suitable therapeutic strategy, say the study authors.