Background: Idiopathic intracranial hypertension (IIH) is an increasingly prevalent disease bearing the risk of visual impairment and affecting quality of life. Clinical presentation and outcome are heterogeneous. Large, well-characterized cohorts are scarce.Here, we describe the Vienna-Idiopathic-Intracranial-Hypertension (VIIH) database aiming to characterize the clinical spectrum, diagnostic findings, therapeutic management, and outcome of IIH.Methods: We identified patients with IIH according to the modified Dandy criteria who were treated at our center between 2014 and 2021. Methodology and structure of the VIIH database are described in detail including demographics, clinical parameters, magnetic resonance imaging, optical coherence tomography, transorbital sonography, treatment, and outcome.Results: Of 113 patients, 89% were female (mean age 32.3 years). Median body mass index (BMI) was 31.8, with 85% overweight (BMI>25). Papilledema was found in 95% with 5% classified as IIH without papilledema. Headache was present in 84% and showed migrainous features in 43%. Median opening pressure in lumbar puncture was 31cmH2O.Pharmacotherapy (predominantly acetazolamide) was established in 99%, 56% required at least one therapeutic lumbar puncture and 13% surgical intervention. After a median follow-up of 3.7 years, 43% had not achieved significant weight loss, papilledema was present in 59% and headache in 76% (58% improved). Comparing initial presentation to follow-up, perimetry was abnormal in 67% vs. 50% (8% worsened, 24% improved) and transorbital sonography in 87% vs. 65% with a median optic nerve sheath diameter of 5.4mm vs. 4.9mm. Median peripapillary retinal nerve fiber layer thickness had decreased from 199µm to 99µm and ganglion cell layer volume from 1.13mm3 to 1.05mm3.Conclusions: The VIIH database constitutes a large representative cohort, characterizing IIH-related symptoms, diagnostic findings, treatment, and outcome parameters and emphasizing substantial long-term sequelae of IIH. Future analyses will aim to refine phenotyping and identify factors predicting outcome.
Objective To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH). Background Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance. Methods We investigated patients with IIH from the Vienna‐IIH‐database and differentiated migraine (IIH‐MIG) from non‐migraine headache (IIH‐nonMIG) and without headache (IIH‐noHA). Using multivariable models, we analyzed the impact of IIH‐MIG on headache and visual outcomes 12 months after diagnosis. Results Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m2, median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH‐MIG, 37% to IIH‐nonMIG (11% tension‐type, 26% unclassifiable), and 17% to IIH‐noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH‐MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH‐nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH‐nonMIG and 63% in IIH‐noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow‐up. In contrast, visual worsening was significantly less common in IIH‐MIG (9% vs. 28% in IIH‐nonMIG and 31% in IIH‐noHA, p = 0.045). In multivariable models, IIH‐MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40–0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12–0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04–0.82, p < 0.001). Conclusions In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome.
Background and purpose: SARS-CoV2 vaccination is recommended for patients with multiple sclerosis (pwMS), but response may be limited by disease-modifying-treatments (DMTs). The aim of this study was to compare the rates of humoral immune response and safety of SARS-CoV-2 vaccines in pwMS and healthy controls (HCs). Methods:In this multicenter prospective study on 456 pwMS and 116 HCs, SARS-CoV-2-IgG response was measured 3 months after the first vaccine dose. The primary endpoint was defined as proportion of patients developing antibodies (seroconversion). Secondary endpoints included antibody level, safety and efficacy.Results: Compared to 97.4% in HCs, seroconversion occurred in 96.7% (88/91) untreated pwMS, 97.1% of patients (135/139) on immunomodulatory DMTs and 61.1% (138/226; p < 0.001) on immunosuppressive DMTs. Seroconversion was lowest in patients on antiCD20 monoclonal antibodies (CD20 mAbs; 52.6%) followed by sphingosine-1phosphate-receptor-modulators (S1PMs; 63.6%). In the S1PM subgroup, seroconversion increased with lymphocyte count (odds ratio [OR] 1.31 per 0.1 G/L; p = 0.035). In pwMS on CD20 mAbs, B-cell depletion decreased seroconversion (OR 0.52; p = 0.038), whereas time since last DMT did not. Safety of SARS-CoV-2 vaccines in pwMS was excellent. Conclusions:Humoral response to SARS-CoV2 vaccines in pwMS is generally excellent.While reduced by immunosuppressive DMTs, most importantly by B-cell-depleting CD20 mAbs and S1PMs, seroconversion is still expected in the majority of patients. SARS-CoV2 vaccination should be offered to every MS patient.
Monoclonal antibodies have become a mainstay in the treatment of patients with relapsing multiple sclerosis (RMS) and provide some benefit to patients with primary progressive MS. They are highly precise by specifically targeting molecules displayed on cells involved in distinct immune mechanisms of MS pathophysiology. They not only differ in the target antigen they recognize but also by the mode of action that generates their therapeutic effect. Natalizumab, an $$\alpha$$ α 4$$\beta$$ β 1 integrin antagonist, works via binding to cell surface receptors, blocking the interaction with their ligands and, in that way, preventing the migration of leukocytes across the blood–brain barrier. On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. However, potential adverse effects may be serious and can necessitate treatment discontinuation. Most importantly, those are the risk for (opportunistic) infections, but also secondary autoimmune diseases or malignancies. Monoclonal antibodies also carry the risk of infusion/injection-related reactions, primarily in early phases of treatment. By careful patient selection and monitoring during therapy, the occurrence of these potentially serious adverse effects can be minimized. Monoclonal antibodies are characterized by a relatively long pharmacologic half-life and pharmacodynamic effects, which provides advantages such as permitting infrequent dosing, but also creates disadvantages regarding vaccination and family planning. This review presents an overview of currently available monoclonal antibodies for the treatment of RMS, including their mechanism of action, efficacy and safety profile. Furthermore, we provide practical recommendations for risk management, vaccination, and family planning.
Background and purpose COVID‐19 continues to challenge neurologists in counseling persons with multiple sclerosis (pwMS) regarding disease‐modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID‐19 outcome in pwMS. Methods We included pwMS with polymerase chain reaction‐confirmed COVID‐19 diagnosis from a nationwide population‐based registry. COVID‐19 outcome was classified as either mild or severe. Impact of DMT, specifically anti‐CD20 monoclonal antibodies (anti‐CD20), and vaccination on COVID‐19 outcome was determined by multivariate models adjusted for a priori risk (determined by a cumulative risk score comprising age, disability, and comorbidities). Results Of 317 pwMS with COVID‐19 (mean age = 41.8 years [SD = 12.4], 72.9% female, median Expanded Disability Status Scale = 1.5 [range = 0–8.5], 77% on DMT [16% on anti‐CD20]), 92.7% had a mild course and 7.3% a severe course, with 2.2% dying from COVID‐19. Ninety‐seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS‐CoV‐2 infection (range = 1–9), severe COVID‐19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS ( p = 0.018). A priori risk robustly predicted COVID‐19 severity ( R 2 = 0.605, p < 0.001). Adjusting for a priori risk, anti‐CD20 treatment was associated with increased COVID‐19 severity (odds ratio [OR] = 3.3, R 2 = 0.113, p = 0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID‐19 (OR = 0.21, R 2 = 0.144, p < 0.001). Conclusions In a population‐based MS cohort, COVID‐19 course is primarily predicted by a priori risk (depending on age, disability, and comorbidities) explaining about 60% of variance. Anti‐CD20 treatment is associated with a moderately increased risk, whereas reassuringly vaccination provides protection from severe COVID‐19.
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