Characteristics and predictors of sexual dysfunction in men with multiple sclerosis.

PURPOSE: To validate and culturally adapt the Sexual Health Inventory for Men (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT), to compare the frequency and severity of erectile dysfunction (ED) and premature ejaculation (PE) in male individuals with MS (mwMS) in comparison with healthy controls (HC) and to investigate predictors of the severity of ED and PE in mwMS. METHODS: 216 consecutive mwMS and 37 HC completed IIEF-5 and PEDT. Additionally, 114 mwMS completed the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-2), Composite Autonomic System Score-31 (COMPASS-31), and the 5-level EQ-5D questionnaire. RESULTS: The test-retest reliability was satisfactory for both questionnaires, with acceptable reliability for both questionnaires. mwMS scored less on IIEF-5 compared to HC (23, IQR 18.25-25 vs 24, IQR 20.25-25, p = 0.028). ED was present in 39.4 % of mwMS and 27.8 % of HC (p = 0.198). Definite PE was present in 12.1 %, and possible PE in 7.8 % of mwMS; and 5.6 % and 11.1 % of HC respectively (p = 0.496). An increase in EDSS was a positive predictor (Exp(B) 1.455, 95 %CI 1.135-1.886, p = 0.003) and the presence of cremasteric reflex was a negative predictor (Exp(B) 0.381, 95 %CI 0.183-0.790, p = 0.010) for the presence of ED. For the PE, disease duration was the only positive predictor in a univariable logistic regression (Exp(B) 1.084, 95 %CI 1.019-1.153, p = 0.070). CONCLUSION: SD is frequent in mwMS with EDSS being a positive and the presence of cremasteric reflex a negative predictor of ED and disease duration a positive predictor of PE symptoms.

Impact of the autonomic dysfunction on the quality of life in people with NMOSD and MS: An international cross-sectional study.

BACKGROUND: A substantial autonomic nervous system (ANS) dysfunction has been described in multiple sclerosis (MS) and recently, also in neuromyelitis optica spectrum disorder (NMOSD). The prevalence of ANS symptoms contributes to the chronic symptom burden in both diseases. The aim of our study was to assess ANS dysfunction in people with (pw) NMOSD and MS, using the Composite Autonomic Symptom Score-31 (COMPASS-31), and additionally, to evaluate if ANS dysfunction have impact on the quality of life of these patients. METHODS: We conducted cross-sectional study at three national referral neurological clinics in Serbia, Croatia, and Montenegro. A total of 180 consecutive subjects, 80 pwNMOSD and 100 pwMS, followed-up at these clinics, were enrolled in the study. Subjects included in the study completed: the validated versions of the COMPASS-31 and the Multiple Sclerosis Quality of Life-54 (MSQoL-54), and the Beck Depression Inventory (BDI). RESULTS: This study demonstrated that the total COMPASS-31 score > 0.0, implicating the presence of ANS dysfunction, was detected in almost all NMOSD and MS study participants tested (80/80, and 97/100, respectively). Our findings showed that autonomic symptom burden was statistically significantly correlated with decreased quality of life, in both NMOSD and MS cohorts. The independent predictors of the better quality of life in pwNMOSD were lower autonomic burden, particularly the absence of the orthostatic intolerance (p = 0.005), along with lower EDSS and BDI score (p ≤ 0.001). Similarly, in pwMS, independent predictors were EDSS, BDI, orthostatic intolerance, and the total COMPASS-31 (p ≤ 0.001). CONCLUSION: Our study demonstrated that a significant proportion of persons with both NMOSD and MS have considerable dysautonomic symptom burden which is correlated with the decreased quality of life. Further investigations are warranted in order to optimize treatment interventions in MS and NMOSD.

Higher MRI lesion load in multiple sclerosis is related to the N-glycosylation changes of cerebrospinal fluid immunoglobulin G.

BACKGROUND: Intrathecal clonal expansion of antibody-producing plasma cells in multiple sclerosis (MS) perpetuates central nervous system injury and is associated with active demyelination. Immunoglobulin G (IgG) effector functions are modulated by linked N-glycan structures. The aim of the study was to detect potential differences in N-glycosylation of IgG in serum and cerebrospinal fluid (CSF) and total sera proteins between people with MS and those in whom the diagnosis of MS was excluded. Furthermore, we investigated the association with standard laboratory biomarkers of intrathecal inflammation as well as clinical and neuroradiological disease activity. METHODS: This cross-sectional study included patients with suspected demyelinating disease. MS diagnosis was based on the 2017 McDonald criteria and controls were patients with excluded MS diagnosis. N-glycans were compared with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) markers of disease activity and biomarkers of intrathecal inflammation (cell count, CSF-IgG concentration, percentage of intrathecal IgG, oligoclonal bands (OCB), virus-specific antibody index (MRZH reaction)). RESULTS: Differences between groups were observed only in the CSF-IgG N-glycome. In MS, the presence of bisecting N-acetylglucosamine (Padj=2.63E-05) and monogalactosylation (Padj=1.49E-06) were more abundant and associated with positive OCBs. N-glycans monogalactosylated at the α6 arm FA2[6]G1 (r = 0.56) and FA2[6]BG1 (r = 0.45) correlated with percentage of intrathecal IgG, but not total CSF-IgG. This trait was also more abundant in MRZH positive people with MS who had higher MRI lesion load (P = 0.018) but unrelated to active lesions or EDSS. CONCLUSIONS: More abundant monogalactosylation of intrathecally synthesized IgG is the most prominent trait in MS and is associated with higher MRI lesion load.

Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers.

BACKGROUND: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). OBJECTIVES: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). METHODS: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. RESULTS: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. CONCLUSION: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.

COVID-19 vaccination uptake in people with multiple sclerosis compared to the general population.

OBJECTIVE: To determine the COVID-19 vaccine uptake among people with multiple sclerosis (pwMS) compared to the general population in Croatia. METHODS: Data from all pwMS entered in the MS Base register until March 24th, 2022 were extracted including age, sex, MS phenotype, disease-modifying therapy (DMT), and date of COVID-19 vaccination. Data on the general population of Croatia were obtained from the vaccination register of the Croatian Institute of Public Health. RESULTS: 64.4% pwMS were fully COVID-19 vaccinated which was comparable to 66.3% of the general population. More pwMS were fully vaccinated in the age group 20-24 (74.1% vs 51.7%), and fewer pwMS were fully vaccinated in the age group 65-69 (33.3% vs 80.4%) compared to the general population of the same age group, respectively. PwMS who received at least one dose of any COVID-19 vaccine were older (40.5 vs 37.6 years, p = 0.01), had higher EDSS (2.0 vs 1.0, p = 0.025), and had longer disease duration (6.39 vs 5.35 years, p = 0.02), were more likely to have progressive disease course (p = 0.049) and were on high efficacy DMTs (p = 0.045) compared to unvaccinated pwMS. Longer disease duration positively predicted vaccine uptake. CONCLUSION: Croatia has suboptimal COVID-19 vaccination uptake without a significant difference between the general population and pwMS.

Treatment of relapsing multiple sclerosis - recommendations of the Croatian Neurological Society.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

Short- and long-term effects of siponimod on autonomic nervous system in secondary progressive multiple sclerosis.

OBJECTIVES: The aim of this study was to investigate the short- and long-term effects of siponimod on autonomic nervous system (ANS) function, in people with secondary progressive multiple sclerosis (pwSPMS) METHODS: The following ANS tests were performed in 26 pwSPMS: a 10 min supine resting position, Valsalva maneuver, deep breathing test and a 10 min tilt-up table test. Heart rate variability (HRV) was performed for the 10 min in supine resting position (M0) and for a 3 h period after siponimod treatment initiation (M0s1-6). All ANS tests were repeated after at least 6 months of treatment with siponimod (M6). RESULTS: In all 6 intervals after siponimod ingestion (M0s1-6), standard deviation of NN intervals (SDNN) was higher compared to M0. After 6 months of continuous treatment with siponimod, SDNN was significantly lower compared to M0. At M6, Valsalva ratio and respiratory sinus arrhythmia were lower compared to M0 values (1.510±0.338 vs 1.864±0.456, p=0.003 and 7.969±2.865 vs 13.091±4.687, p<0.001, respectively). Cardiovagal index was significantly higher at M6 compared to M0 (1 (range 0-2) vs 0 (range 0-1), p=0.008, respectively). Active Magnetic Resonance Imaging (MRI) one year prior to starting siponimod was a positive predictor of M6 SDNN and Adrenergic Index (AI) at M0 was a negative predictor of M6 SDNN. CONCLUSION: This study has shown an inverse relationship in short- versus long-term effects of siponimod on ANS function. A shift towards parasympathetic predominance was observed during the first three hours after ingestion, while after 6 or more months of continuous treatment with siponimod, a shift towards sympathetic predominance was observed.

Sudomotor dysfunction in people with neuromyelitis optica spectrum disorders.

BACKGROUND AND PURPOSE: The aim was to determine the extent of sudomotor dysfunction in people with neuromyelitis optica spectrum disorder (pwNMOSD) and to compare findings with a historical cohort of people with relapsing-remitting multiple sclerosis (pwRRMS). METHODS: Forty-eight pwNMOSD were enrolled from four clinical centers. All participants completed the Composite Autonomic Symptom Score 31 to screen for symptoms of sudomotor dysfunction. Sudomotor function was assessed using the quantitative sudomotor axon reflex test. The results were compared with a historical cohort of 35 pwRRMS matched for age, sex and disease duration. RESULTS: Symptoms of sudomotor dysfunction, defined by a score in the Composite Autonomic Symptom Score 31 secretomotor domain >0, were present in 26 (54%) of pwNMOSD. The quantitative sudomotor axon reflex test confirmed a sudomotor dysfunction in 25 (52.1%) of pwNMOSD; in 14 of them (29.2%) sudomotor dysfunction was moderate or severe. No difference was observed between pwNMOSD and pwRRMS in any of the studied parameters. However, symptomatic sudomotor dysfunction was more frequent in pwNMOSD (n = 8, 22.9%) compared to pwRRMS (n = 1, 3%; p = 0.028). In a multivariable logistic regression analysis, statistically significant predictors for symptomatic sudomotor failure were age and diagnosis of neuromyelitis optica spectrum disorder. CONCLUSIONS: Sudomotor dysfunction is common in pwNMOSD and more often symptomatic compared to pwRRMS.

Hypogammaglobulinemia, infections and COVID-19 in people with multiple sclerosis treated with ocrelizumab.

OBJECTIVE: To determine the influence of immunoglobulins (Ig) level on the rate of infections in people with multiple sclerosis (pwMS) treated with ocrelizumab. METHODS: We enrolled 109 consecutive pwMS treated with ocrelizumab with a mean follow-up of 2.69±0.56 (1.36-4.27) years. We have retrospectively searched our electronic database and the following information was collected: age, sex, MS characteristics, number of ocrelizumab cycles, infections, duration of the infection, hospitalization due to infection, treatment of the infection, and COVID-19 characteristics. Ig levels were measured within 14 days before each ocrelizumab infusion. RESULTS: Number of pwMS with values of IgM and IgG below lower level of normal at baseline was 3 (2.8%) and 2 (2.8%), respectively; and before 6th cycle of ocrelizumab 5 (13.5%) and 5 (13.5%), respectively. Levels of IgM were steadily decreasing over time, while levels of IgG started to show statistically significant drop only after 5th cycle of ocrelizumab. 58.7% pwMS experienced infection during treatment, with a median number of infections per pwMS being 1, range 0-4. Female sex increased the risk of any infection (HR 2.561, 95%CI 1.382-4.774, p=0.003). Higher age and smaller drop in IgM before 3rd ocrelizumab cycle increased the risk for infection requiring hospitalization (HR 1.086, 95%CI 1.018-1.159, p=0.013 and HR 9.216, 95%CI 1.124-75.558, p=0.039, respectively). Longer disease duration increased the risk for COVID-19 (HR 1.075, 95%CI 1.002-1.154, p=0.045). CONCLUSION: The present findings broaden limited real-world data on infection and COVID-19 risk in pwMS treated with ocrelizumab.

Humoral and cellular immunity in convalescent and vaccinated COVID-19 people with multiple sclerosis: Effects of disease modifying therapies.

OBJECTIVES: To determine anti-SARS-Cov2 antibodies and T-cell immunity in convalescent people with multiple sclerosis (pwMS) and/or pwMS vaccinated against Covid-19, depending on the disease modifying therapy, and in comparison to healthy controls (HC). METHODS: 75 participants were enrolled: Group 1-29 (38.7%) COVID-19 convalescent participants; Group 2-34 (45.3%) COVID-19 vaccinated; Group 3-12 (16.0%) COVID-19 convalescent participants who were later vaccinated against COVID-19. Cellular immunity was evaluated by determination of number of CD4+ and CD8+ cells secreting TNFα, IFNγ, and IL2 after stimulation with SARS-CoV-2 peptides. RESULTS: pwMS treated with ocrelizumab were less likely to develop humoral immunity after COVID-19 recovery or vaccination. No difference was observed in the cellular immunity in all studied parameters between pwMS treated with ocrelizumab compared to HC or pwMS who were treatment naïve or on first line therapies. These findings were consistent in convalescent, vaccinated, and convalescent+vaccinated participants. COVID-19 vaccinated convalescent pwMS on ocrelizumab compared to COVID-19 convalescent HC who were vaccinated did not show statistically difference in the rate of seroconversion nor titers of SARS-CoV-2 antibodies. CONCLUSION: Presence of cellular immunity in pwMS on B-cell depleting therapies is reassuring, as at least partial protection from more severe COVID-19 outcomes can be expected.

Product review on MAbs (alemtuzumab and ocrelizumab) for the treatment of multiple sclerosis.

Traditionally, the management of active relapsing remitting MS was based on the, so-called, maintenance therapy, which is characterized by continuous treatment with particular disease modifying therapy (DMT), and a return of disease activity when the drug is discontinued. Another approach is characterized by a short treatment course of a DMT, which is hypothesized to act as an immune reconstitution therapy (IRT), with the potential to protect against relapses for years after a short course of treatment. Introduction of monoclonal antibodies in the treatment of MS has revolutionized MS treatment in the last decade. However, given the increasingly complex landscape of DMTs approved for MS, people with MS and neurologists are constantly faced with the question which DMT is the most appropriate for the given patient, a question we still do not have an answer to. In this product review, we will discuss the first DMT that acts as IRT, an anti-CD52 monoclonal antibody alemtuzumab and an anti CD20 monoclonal antibody, ocrelizumab that has the potential to act as an IRT, but is administered continuously. Special emphasis will be given on safety in the context of COVID-19 pandemics and vaccination strategies.

Humoral immune response in convalescent COVID-19 people with multiple sclerosis treated with high-efficacy disease-modifying therapies: A multicenter, case-control study.

AIM: To determine the influence of high-efficacy disease modifying therapy (DMT) on the development of IgG SARS-CoV-2 antibody response in COVID-19 convalescent people with multiple sclerosis (pwMS). METHODS: Seventy-four pwMS taking high-efficacy DMTs (specifically natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine and ublituximab) and diagnosed with COVID-19 and 44 healthy persons (HC) were enrolled. SARS-CoV2 antibodies were tested with Elecsys® Anti-SARSCoV-2 S assay. RESULTS: pwMS taking high-efficacy DMTs had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to healthy controls (33 negative pwMS [44.6%] compared to one negative HC [2.3%], p < 0.001). pwMS taking B-cell depleting therapy (ocrelizumab and ublituximab) had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to pwMS on all other DMTs (29 negative pwMS on B-cell therapy [64.4%] compared to four negative pwMS on all other DMTs [13.8%], p < 0.001). Out of other DMTs, two (33.3%) pwMS taking fingolimod and two (16.7%) pwMS taking cladribine failed to develop IgG SARS-COV-2 antibodies. B-cell depleting therapy independently predicted negative titer of IgG SARS-CoV-2 antibody (Exp[B] =0.014, 95%CI 0.002-0.110, p < 0.001). CONCLUSIONS: A significant proportion of convalescent COVID-19 pwMS on high-efficacy DMTs will not develop IgG SARS-CoV-2 antibodies. B-cell depleting therapies independently predict negative and low titer of IgG SARS-CoV-2 antibody.

Effectiveness and safety of alemtuzumab in the treatment of active relapsing-remitting multiple sclerosis: a multicenter, observational study.

OBJECTIVE: So far, a limited number of real-world evidence studies about the effectiveness and safety of alemtuzumab (ALM) have been published, some of them with a relatively small number of included patients. We aimed to study the efficacy and safety of ALM in real-world clinical practice in two MS centers in Slovenia and Croatia. METHODS: This was a retrospective chart review of 71 consecutive patients with relapsing-remitting MS who were treated with ALM from 2015 till 2018. The following data were collected: gender, age at disease onset, disease duration at ALM initiation, previous disease modifying therapy, number of relapses, active MRI lesions, and EDSS in the year prior to ALM initiation and every year of follow-up. RESULTS: All patients completed the standard dosing schedule and were followed for a mean time of 3.2±1.1 years after the initiation of treatment. Complete data for the 2 years after treatment (relapses, EDSS, and MRI) were available for 48 patients, of which 14 (29.2%) achieved NEDA. Clinical NEDA was achieved in 38 out of 63 participants (60.3%). In year 1, 24 out of 57 (42.1%) patients achieved NEDA. In year 2, 26 out of 41 (63.4%) patients achieved NEDA. Lower EDSS prior to starting ALM was the only independent predictor of NEDA in a multivariable model. Adverse events occurred in 58 participants (84.1%), with no new safety signals identified. CONCLUSION: According to the data from our cohort of early active RRMS patients we conclude ALM efficacy remains high in the real-world clinical practice.

Approaches and challenges in the diagnosis and management of secondary progressive multiple sclerosis: A Central Eastern European perspective from healthcare professionals.

Secondary progressive multiple sclerosis (SPMS) is a debilitating condition characterized by gradual worsening after an initial relapsing disease course. Despite the recent advances in our understanding of the disease, the diagnosis and treatment of SPMS continue to be challenging in routine clinical practice. The aim of this review article is to present the views of leading MS experts on the challenges in the diagnosis and management of SPMS and clinicians' perspectives in Central and Eastern Europe. This article also provides recommendations of MS experts to improve the situation with diagnosis and management of SPMS. Many countries within Central and Eastern Europe have high prevalence of MS (>100 per 100,000 population). Consistent with the global trend, in the absence of reliable tests or biomarkers, SPMS at early stage remains undiagnosed. Due to diagnostic uncertainty and lack of a universally accepted disease definition, clinicians rely more on retrospective analysis of the clinical symptoms to confirm the diagnosis. With the lack of awareness and poor understanding of the timing of the onset of SPMS, clinicians may tend to direct attention to relapses than the symptoms of progression, which leads to underestimation of SPMS. Although several predictors of progression to SPMS have been identified, their predictive value is highly variable. Therefore, defining the transitioning period as a separate stage of MS is essential. According to experts' opinion, frequent follow-up of patients and periodic assessment of progression are recommended for the timely identification of patients transitioning from RRMS to SPMS. MSProDiscuss Tool is an example of a quick assessment tool for identifying patients progressing from RRMS to SPMS. MS progression is usually assessed by changes in Expanded Disability Status Scale (EDSS) scores. As EDSS scores tend to fluctuate when measured in the short term (3-6 months), a longer period (≥12 months) may be needed to confirm the progression. Assessment of cognitive function is also important for evaluating secondary progression. Compartmentalization of inflammation within the central nervous system is an important reason behind the limited success of disease-modifying therapies (DMTs) for treating SPMS. Most of the DMTs fail to cross the blood-brain barrier; only 38% of the tested DMTs achieved their primary endpoint in SPMS. In Europe, siponimod is the first oral treatment for adults with active SPMS. Particularly, in Central and Eastern Europe, patients with SPMS are still being prescribed less efficacious DMTs and interferons. The absence of alternative treatments in SPMS supports the use of new products (siponimod and others); however the decision to initiate siponimod therapy in more severe patients (EDSS score of 7 or higher) should be individualized in consultation with the payers. The focus should be on early treatment initiation to delay disease progression.

Autonomic nervous system abnormalities predict cardiovascular changes after initiation of siponimod in secondary progressive multiple sclerosis.

OBJECTIVE: The aim of this study was to identify whether autonomic nervous system (ANS) dysfunction identified prior to treatment initiation can predict siponimod related decrease in heart rate (HR) after treatment initiation. METHODS: In 26 people with secondary progressive multiple sclerosis (SPMS) the following ANS testing protocol was applied: 10-min supine resting position, Valsalva maneuver, deep breathing test, 10 min tilt-up table test, 5-min supine resting period, ingestion of siponimod, followed by 180-min supine resting period recordings. Heart rate variability (HRV) parameters were investigated as possible predictors of decrease in HR (ΔHR) after treatment initiation. RESULTS: After treatment initiation, there was a statistically significant drop in HR (71.1 ± 9.2 to 66.3 ± 8.1, p < 0.001) and elevation of systolic blood pressure (sBP) (113.2 ± 12.4 to 117.1 ± 10.8, p = 0.04). Values of the diastolic BP (dBP) followed similar trend as did sBP, however not reaching statistical significance (72.8 ± 9.6 to 74.9 ± 8.3, p = 0.13). In a multivariable regression model, disease duration and standard deviation of NN intervals (SDNN) were identified as independent predictors for ΔHR, where increase in SDNN and longer disease duration predict smaller ΔHR. CONCLUSION: ANS abnormalities may predict cardiovascular abnormalities associated with treatment initiation with siponimod. SIGNIFICANCE: Results of this study may help mitigate risks associated with siponimod treatment.

Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness.

OBJECTIVE: To evaluate clinical and laboratory effects of delaying ocrelizumab infusions during the COVID-19 pandemics in people with multiple sclerosis (pwMS). METHODS: We have retrospectively searched our electronic database and identified 33 pwMS who had a delay in treatment due to COVID-19 pandemics. The following data were extracted: age, sex, multiple sclerosis (MS) phenotype: relapsing-remitting (RRMS) or primary progressive multiple sclerosis (PPMS), disease duration, Expanded Disability Status scale (EDSS), previous disease modifying therapy (DMT), number of ocrelizumab cycles prior to the lockdown, dates of first ocrelizumab infusion, last ocrelizumab infusion prior to the lockdown and delayed ocrelizumab infusion after the lockdown. Flow cytometry results, relapses and EDSS progression prior to the delayed ocrelizumab infusion after the lockdown were extracted. RESULTS: The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse. In a multivariable linear regression analysis, time from last ocrelizumab infusion to lymphocyte sampling prior to the next infusion was the only significant predictor for CD19+ B cells count, when corrected for the number of previous ocrelizumab cycles and MS phenotype (RRMS or PPMS) (B=7.981, 95% C.I. 3.277-12.686, p=0.002). CONCLUSIONS: We have not shown clinical consequences of delaying ocrelizumab due to COVID-19 pandemics. However, the delay in dosing of ocrelizumab was an independent predictor of repopulation of B cells.

Acute pancreatitis after ocrelizumab treatment for relapsing remitting multiple sclerosis.

Ocrelizumab is an anti-CD20 monoclonal antibody used in the treatment of relapsing remitting and primary progressive multiple sclerosis. The main side effects are infusion-related with long term administration raising the risk of infections. During randomized controlled trials five cases of pancreatitis have been reported. We present a case of a patient with no risk factors for pancreatitis who after administration developed acute pancreatitis albeit with a good recovery.

Evolution of tongue somatosensory evoked potentials in people with multiple sclerosis.

INTRODUCTION: The aim of the present study was to investigate the long-term evolution of tongue somatosensory evoked potentials (tSSEP) in people with multiple sclerosis (pwMS). METHODS: Out of initial 121 participants, after two-year follow-up, the data were available for 74 and after four-year follow-up for 58 pwMS. In all pwMS complete neurological examination, brain MRI, cervical spinal cord MRI (if available) and tSSEP were performed at baseline visit (M0). Complete neurological examination and tSSEP were performed 2 and 4 years later (M24 and M48). tSSEP results were interpreted in the form of ordinal tSSEP score and quantitative tSSEP zscore calculated from the sum of z-transformed tSSEP latencies. RESULTS: Differences in tSSEP scores and tSSEP zscores in three different timepoints showed significant worsening of both scores over time. For the tSSEP score the difference was significant for M0-M24 and M0-M48 visits, but not for M24-M48 visits. For the tSSEP zscore the difference was significant for M0-M48 and M24-M48 visits, but not for M0-M24 visits. The only significant negative predictor found for the tSSEP score improvement was presence of cervical spinal cord lesions on the MRI. A moderate to high correlation was observed between both forms of tSSEP score at all three timepoints. CONCLUSION: This study demonstrates a significant deterioration of trigeminal sensory pathway in MS over time, giving further insight into trigeminal system damage in pwMS.