Background:
Neuroretinal atrophy is associated with whole-brain atrophy and disease activity in multiple sclerosis (MS). Recent findings support that subclinical visual pathway involvement might also ...occur in neuromyelitis optica spectrum disorders (NMOSDs).
Objective:
The objective of this study is to assess retinal thinning in MS and NMOSD and its association with disease activity.
Methods:
In total, 27 NMOSD and 54 propensity-score-matched MS patients underwent optical coherence tomography, visual acuity, and visual-evoked potentials at 2.4 years apart, in addition to routine clinical and magnetic resonance imaging (MRI) assessment. We excluded eyes with acute optic neuritis.
Results:
In NMOSD, we detected peripapillary retinal nerve fiber layer (pRNFL) thinning in patients with disease activity during follow-up (−0.494 µm/year), but not in stable patients (−0.012 µm/year). Macular ganglion cell-inner plexiform layer (GCIPL) thinning occurred instead in all patients (−0.279 µm/year). Relapsing–remitting multiple sclerosis (RRMS) meeting NEDA-3 criteria had no pRNFL or GCIPL thinning during follow-up. Active-disease RRMS and progressive MS, both active and stable, displayed pRNFL (−0.724, −0.586, −0.556 µm/year, respectively) and GCIPL loss.
Conclusion:
In MS, neuroretinal atrophy was associated with disease activity but occurred in progressive MS even when achieving NEDA-3 criteria. In NMOSD, pRNFL thinning was associated with non-ocular relapses due to a spreading of inflammatory activity. GCIPL thinning was found in all patients, supporting a primary retinal pathology targeting AQP4-rich structures.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking ...disease-modifying drugs.
Methods:
A modified Delphi consensus process (October 2017–June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.
Results:
Recommendations include the need for an ‘infectious diseases card’ of each patient’s infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.
Conclusion:
Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Early detection of neuromyelitis optica spectrum disorders (NMOSD), especially after optic neuritis, a presenting manifestation commonly observed also in multiple sclerosis (MS), is crucial for ...timely treatment and prognosis. Integrated visual pathway assessment with optical coherence tomography (OCT) and visual evoked potentials (VEP) may help in this task, showing in vivo different pathophysiological backgrounds. We evaluated combined VEP and OCT in a cross-sectional, single-centre study assessing 50 consecutive NMOSD patients, 57 MS patients and 52 healthy controls. After optic neuritis, VEP were more frequently absent in NMOSD compared to MS; most NMOSD eyes with recordable VEP showed prolonged latency, but extreme latency delays were less common than in MS. OCT showed predominantly axonal involvement in NMOSD, with 88% eyes (95% CI: 69-97%) displaying retinal nerve fibre layer thickness <60 µm even after first optic neuritis episode. Accuracy of OCT was further enhanced by combination with VEP into a new Z-score derived OCT-VEP index, measuring prevalence of axonal damage or demyelination. Our results suggest that integrated optic nerve assessment may elucidate differences in optic neuritis pathophysiology; conduction slowing with relatively preserved nerve fibre layer suggests MS, while severe neuroaxonal loss after optic neuritis, often hindering VEP response, characterizes NMOSD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Approximately 3–10% of patients with multiple sclerosis (MS) have onset during childhood. Pediatric MS is characterized by a relapsing-remitting course and a high relapse rate. In 2010, fingolimod ...(Gilenya®) was approved in the USA for the treatment of relapsing-remitting MS in adults. In 2018, both the United States Food and Drug Administration and the European Medicines Agency expanded the approved indications of fingolimod to include its use in children with relapsing MS, and the drug was approved in Italy for this indication in September 2020. We describe two cases of children with relapsing-remitting MS who were treated with fingolimod at IRCCS Ospedale San Raffaele Multiple Sclerosis Center (Milan, Italy) for more than 2 years. Our real-world data confirm that fingolimod is an effective therapeutic strategy for children with relapsing MS, and its use could be considered in pediatric patients with active disease.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
During the COVID-19 pandemic, concerns raised regarding the use of immunosuppressants in multiple sclerosis, even if current data do not support an increased risk of infection. Although fingolimod ...can be temporarily suspended during COVID-19, the benefit-risk balance of suspension can be challenging. Till now, no adverse events have been described after the resumption of fingolimod, following a previous discontinuation. We report the occurrence of atrioventricular block following fingolimod restart. Fingolimod acts on sphingosine-1-phosphate-axis, a pathway that is altered with COVID-19 and hypoxic conditions. Herein we discuss how these metabolic changes may have influenced fingolimod pharmacology leading to a cardiac event.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Neuropsychiatric manifestations are highly prevalent in systemic lupus erythematosus (SLE)-patients. We aimed to unravel the substrates of these manifestations by investigating abnormalities of ...resting state (RS) functional connectivity (FC) and their correlations with neuropsychiatric variables in SLE-patients. Thirty-two SLE-patients and 32 age- and sex-matched healthy controls (HC) underwent brain 3T RS fMRI. Neuropsychological assessment was performed for all SLE-patients. The main large-scale cognitive and psychiatric functional networks were derived and between-group comparisons and correlations with neuropsychological measures were performed. Compared to HC, SLE-patients exhibited increased RS FC in the right middle cingulate cortex and decreased RS FC in the left precuneus within default-mode network (DMN). They also showed increased RS FC in the left cerebellar crus I and left posterior cingulate cortex, and decreased RS FC in the left angular gyrus within working-memory networks (WMN). Compared to HC, SLE-patients exhibited increased RS FC in the left insular cortex and decreased RS FC in the right anterior cingulate cortex within salience network (SN), as well as decreased RS FC in the right middle frontal gyrus within executive-control network (ECN). Correlation analysis indicated a maladaptive role for left angular gyrus and cerebellar RS FC abnormalities in WMN, affecting memory and executive functions; and for precuneus and insular abnormalities in DMN and SN for psychiatric symptoms. Cingulate cortex modifications within DMN and SN correlated with better memory and global cognitive performance. Significant RS FC alterations in relevant cognitive and psychiatric networks occur in SLE-patients and participate in the pathophysiology of neuropsychiatric symptoms.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:
In multiple sclerosis (MS), up to 57% of white matter lesions are chronically active. These slowly expanding lesions (SELs) contribute to disability progression.
Objective:
The aim of ...this study is to compare fingolimod and natalizumab effects on progressive linearly enlarging lesions (i.e. SELs), a putative biomarker of smouldering inflammation.
Methods:
Relapsing-remitting MS patients starting fingolimod (n = 24) or natalizumab (n = 28) underwent 3T brain magnetic resonance imaging (MRI) at baseline, months 6, 12 and 24. SELs were identified among baseline-visible lesions showing ⩾ 12.5% of annual increase, calculated by linearly fitting the Jacobian of the nonlinear deformation field between timepoints obtained combining T1- and T2-weighted scans. SEL burden, magnetization transfer ratio (MTR) and T1 signal intensity were compared using linear models.
Results:
The prevalences of fingolimod (75%) and natalizumab patients (46%) with ⩾ 1 SEL were not significantly different (adjusted-p = 0.08). Fingolimod group had higher SEL number and volume (adjusted-p ⩽ 0.047, not false discovery rate (FDR) survived). In both groups, SELs versus non-SELs showed lower MTR and T1 signal intensity (adjusted-p ⩽ 0.01, FDR-survived). Longitudinally, non-SEL MTR increased in both treatment groups (adjusted-p ⩽ 0.005, FDR-survived). T1 signal intensity decreased in SELs with both treatments (adjusted-p ⩽ 0.049, FDR-survived in fingolimod group) and increased in natalizumab non-SELs (adjusted-p = 0.03, FDR-survived).
Conclusion:
The effects of natalizumab and fingolimod on SEL occurrence seem modest, with natalizumab being slightly more effective. Both treatments may promote reparative mechanisms in stable or chronic inactive lesions.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent ...scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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