Background

Alemtuzumab has proven to be an effective treatment for patients with highly active multiple sclerosis (MS). However, its use has been limited by adverse events (AEs) as secondary autoimmunity, being the most frequent those involving the thyroid gland, observed in around 40% of patients.

Objectives

To explore whether patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity.

Methods

A multicentre prospective longitudinal study was performed, including fifty‐four Relapsing-Remitting MS (RRMS) patients diagnosed in five Spanish hospitals. Patient blood samples were collected before initiating treatment with alemtuzumab. Autoimmune AEs were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia and/or autoimmune nephropathy. Differences were assessed using Man-Whitney U tests. Cut-off values were established using ROC curves to predict autoimmune AEs. Odds ratios were calculated by Fisher tests.

Results

Fifty‐four RRMS patients, 36 (66.7%) women, with a median (range) age of 28 (13–67) years and median (range) follow-up of 6 (0-20) years. Fourteen patients (25.9%) experienced autoimmune AEs, and all of them were dysthyroidism. No immune thrombocytopenia or nephropathies were observed. No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune AEs and those who did not. Patients who experienced autoimmune AEs before treatment onset had a higher percentage of blood CD19+ B cells (p=0.001), with a higher relative percentage of naïve B cells and plasmablasts. When explored total cell numbers, only plasmablast levels remained significant (p=0.02). A lower risk of autoimmune AEs after alemtuzumab was observed among patients with less than 7.6% of blood CD19+ B cells [odds ratio (OR) 16, confidence interval (CI) 3.86–58.95, p<0.0001] or less than 0.13% of plasmablast cells [OR 9.33, CI 2.17–42.65, p=0.002].

Conclusions

A low percentages of blood CD19+ B cells or plasmablasts before Alemtuzumab treatment predicted a lower risk of autoimmune AEs.

Background

The emergence of a new coronavirus (COVID-19) and the subsequent pandemic present a unique challenge to neurologists managing patients with multiple sclerosis (MS). Preliminary reports do not support an increased risk of severe outcome associated with disease modifying therapies (DMTs) but real-world evidence is lacking.

Objectives

To describe our experience in 14 patients with MS who have been affected by SARS-CoV-2 (with a clinical, RT-PCR, or serological diagnosis) and who were being treated with cladribine in Spain.

Methods

We conducted a consecutive clinical series study including cases occurred in Spain since January 31, 2020 when the first COVID-19 patient was detected in Spain until the end of June 2020.

Results

Patients were mostly female (64%), with an average age of 40.1 (± 12.0) years and a disease duration of 9.7 (± 8.9) years. Median EDSS was 1 (IQR 0–2.5), and the average time on treatment with cladribine was 7.7 (±5.77) months. Two patients had grade 1 lymphopenia, five patients had grade 2 lymphopenia, one patient had grade 3 lymphopenia and six patients were in normal range. Only 1 patient required hospitalization. None required ICU care, or intubation. 93% of the patients improved without any specific treatment. 2 patients (14%) were asymptomatic, 11 (79%) were mild and 1 (7%) was moderate. All recovered without sequelae. 7 of the patients (50%) had a serology test done that showed presence of anti-viral antibodies of IgG and IgM type in all cases.

In our series the patients had a favorable evolution, and all recovered. Factors that could have influenced those results could be the age of the patients, the lack of other risk factors and the mechanism of action of cladribine. It is known that the limited activity of cladribine on cells of the innate immune system and its relatively minor impact on CD8 T cells and plasma cells may have implications for maintained protection from bacterial and viral infections. Importantly, cladribine CD4+ T cell and B cells depletion is partial and transient. The short-term dosing regimen of oral cladribine, potentially reduces depleting effects on the innate immune system.

Conclusions

From this limited number of patients our observations suggest that cladribine treatment does not appear to worsen COVID-19 disease prognosis. MS is a debilitating disease and discontinuing effective treatments might have adverse consequences, benefit/risk assessment is crucial in the current context. Our patients treated with cladribine had an adequate resolution of COVID-19 and mounted an immune response, however more studies are necessary to confirm and extend our preliminary findings.

Background

Infections are an important cause of hospitalization in patients with MS. Data on outcomes of COVID-19 in patients with MS are limited

Objectives

To quantify the risks of infection, hospitalization, admission to intensive care and death due to SARS-CoV-2 infection among patients with MS relative to the general population, and to identify factors associated with risk of hospitalization

Methods

A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit (ICU) admission and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison.

Results

Two-hundred nineteen patients with MS were included in the registry, 51 of whom were hospitalized. The infection incidence rate (IR) was lower in patients with MS than the general population (adjusted IR ratio 0.78; 95% confidence interval: 0.70–0.80), but hospitalization rates were higher (adjusted relative risk 6.52 [6.13–7.04]). Disease severity was generally low, with only one ICU admission and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying therapy (DMT) and hospitalization risk.

Conclusions

Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue DMT should be based on a careful risk-benefit assessment.

Background

The SARS-CoV-2 infection has spread worlwide becoming a pandemic never before seen. Immunosuppressive (IS) treatments used in Multiple Sclerosis (MS) patients could activate the infection in asymptomatic carriers or reactivate COVID-19 in apparently recovered cases. Our similar experience in some MS patients during the pandemic lead us to design a safety protocol at our MS Unit. It was based on epidemiological data and testing for PCR in nasopharyngeal swabs and serology before administration of monoclonal antibodies, doses of pulsed disease modifying therapies (DMTs), new starts of oral DMTs and methylprednisolone pulses.

Objectives

To describe our experience in the establishment of a SARS-CoV-2 safety protocol in MS patients. We analyze its utility to prevent COVID-19 complications

Methods

Observational, prospective and clinical practice study in the establishment of a multidisciplinary safety protocol (MS Unit – Neurology/Microbiology/Preventive Medicine). Sequential protocol over time adapted to the different pandemic phases and levels of available resources.

Results

152 PCR and 140 serology tests were performed in 90 patients over 3 months. They were performed preceding the treatment with Natalizumab (96 tests), Ocrelizumab (36 tests), Rituximab (3 tests), Methylprednisolone (7 tests), Cladribine (4 tests) and Dimethyl Fumarate (3 tests). 7 asymptomatic carriers were diagnosed (7,8%), 5 of them with positive IgM+IgG serology (5,6%). 5 patients with positive IgM+IgG serology post-infection were confirmed. No COVID-19 reactivation was detected after the establishment of the protocol.

Conclusions

The combined analysis of PCR and serology increased the sensitivity of the SARS-CoV-2 infection diagnosis during the pandemic peak of cases phase. However, this does not happen at pandemic phases with less daily cases, when testing PCR alone detected the same number of cases than testing combined PCR and serology. The safety protocol reaches its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers.

Background

There are different disease-modifying therapies (DMTs) for treating patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Oral Cladribine was commercialized in 2018.

Objectives

To analyze the first year of treatment with Cladribine in RRMS patients: tolerability, security and initial approach to its effectiveness.

Methods

Retrospective, longitudinal and unicenter study in RRMS patients treated with Cladribine. We analyzed its security measuring overall lymphocyte count by Friedman Test and time to appearance of lymphopenia by Kaplan-Meier. We studied its effectiveness by comparing the following variables with the Wilcoxon Test: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and one year after starting Cladribine (statistically significant p<0’05).

Results

53 patients were studied. 88,7% were women with a mean age of 44,8 years old (DS10,25). 56,6% of the patients had a RRMS evolution of less than 10 years, 32,1% between 10 and 20 years, and 9,4% between 20 and 30 years. 64,1% had been previously treated with one or two DMTs. Patients were exposed to Cladribine for 8 months as a median (percentiles P15=2 months, P85=15 months): 36,4% patients for 6 months, 34,1% between 6-12 months and 29,5% for more than 12 months. The overall lymphocyte count reduction regarding the basal level after starting the drug was statistically significant (p<0’05). The lymphocyte count reduction rate was 52,89% during the first year of treatment and 58,99% during the second one. Tolerability was good in 93,02% of the patients. We observed significant reduction of the relapses rate after one year of treatment.

Conclusions

Cladribine seems to be a secure treatment. The most common adverse effect was lymphopenia (81,8%) but it was severe only in 9,09% of the patients and not associated with severe infections. Its tolerability was very good. Effectiveness results are positive, but, to date, they are preliminary.

Background

The new coronavirus SARS-CoV-2 infection has spread worlwide becoming a pandemic never before seen. Multiple Sclerosis (MS) patients in a state of immunosuppression (IS) may be exposed to a greater risk of COVID-19 complications, although there is increasing evidence postulating a possible protective role of selective IS.

Objectives

To describe the real-world experience in MS patients with SARS-CoV-2 infection at a MS Unit of a hospital in Madrid, Spain. We describe clinical evolution and MS treatment actions

Methods

Observational, prospective and usual clinical practice study in MS patients affected by SARS-CoV-2 infection with clinical diagnosis (at least three of the following: fever, anosmia, cough, diarrhea, myalgia) and/or microbiological diagnosis (PCR in nasopharyngeal swabs and/or serology).

Results

41 SARS-CoV-2 infection cases were registered. 21 were women with a mean age of 39,4 years old (DS10,3). 38 were relapsing-remitting MS patients and 3 had a progressive MS. The mean MS time course was nine years (DS1,4). 39 patients were treated with disease-modifying therapies (DMTs): 46,3% with oral agents, 39% with monoclonal antibodies and 10% with injectable agents. 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2,5 (DS0,7). 11 patients had clinical activity the previous year. 18 cases were confirmed by PCR and/or serology and 23 were clinically diagnosed. 17% of the patients were admitted to hospital (6 were diagnosed with pneumonia) and none required admission to the intensive care unit. There were no deaths.Three patients had other comorbidities. Admitted patients were older and had higher EDSS score without statistical significance. MS got worse in 7 patients. DMTs were stopped or delayed in 10 patients due to the SARS-CoV-2 infection.

Conclusions

All the MS patients studied had a good outcome of the SARS-CoV-2 infection. Only 17% of them required admission to hospital and 14,6% of the cases were asymptomatic. 95% of the patients were treated with DMTs. From our experience, the SARS-CoV-2 infection does not seem to entail a more aggressive form of the disease in this group of patients. Selective IS may favor the good evolution. Larger clinical registers are needed to establish solid conclusions.

Background

Background: There is an association between motor and cognitive impairment in patients with multiple sclerosis (MS) over their disease course and strong evidence that physical therapy can prevent disability progression in these patients. Virtual reality (VR) has emerged as a promising treatment approach in rehabilitation for patients with MS due to its potential to increase patient motivation and rehabilitation adherence. However, there is a lack of studies about its safety, feasibility and effectiveness in MS patients.

Objectives

Objectives: The objective of this study protocol is to evaluate the feasibility, adherence, safety and effectiveness of a virtual reality rehabilitation (VRR) program in MS patients compared to a conventional rehabilitation (CR) program.

Methods

Methods: A randomized, prospective, open-label, controlled feasibility study will be conducted in a sample of 48 individuals diagnosed with MS. Participants will be allocated 2:1 to the VRR group (32) or CR group (16). Both groups will perform 8 in-hospital physical therapy sessions of 2 hours each, twice a week over 4 weeks. The VRR group will perform half of these sessions with a VRR tool. In addition, both groups will continue rehabilitation at home for 5 months. The VRR program was designed by a multidisciplinary group of healthcare professionals (neurologists, physiatrists, physiotherapists, neuropsychologists) according to a validated CR program. Feasibility will be assessed by the User Satisfaction Evaluation Questionnaire (USEQ). Secondary outcomes include adherence, disability, spasms and spasticity, balance, fatigue, activities of daily living, depression, anxiety, work status, cognition, demographic and clinical characteristics (in the VRR and CR groups), and safety (in the VRR group). Outcome measures will be assessed at baseline and at 1 and 6 months from the start of rehabilitation.

Results

Results: Due to the present comunication is a description of an ongoing study protocol there are stil not results to present.

Conclusions

Conclusions: A better understanding of long-term patient satisfaction with a VRR program specifically designed for MS patients would allow us to optimize the rehabilitation program and to collect valuable information for its implementation in the clinical practice. Additionally, the study will provide information on long-term adherence, changes in motor symptoms, cognitive function and patient-reported outcomes after the rehabilitation program. Altogether, the results from this study will help to gather valuable knowledge on the use of rehabilitation with a new VR tool in MS patients.

Background

Ocrelizumab is a monoclonal antibody approved for relapsing-remitting primary progressive multiple sclerosis (MS) acting against B lymphocytes that expresses CD20. The CD 20 antigen is a cell surface antigen found on pre-B lymphocytes, mature B lymphocytes, memory B lymphocytes, and a T cell subtype (CD3+ CD20+) that also expresses CD20. Clinical trials have shown that the use of this drug can produce a reduction in immunoglobulin levels which might be related to infections; however, there is little data about the influence of this immunomodulatory treatment on CD3+ T lymphocytes.

Objectives

To analyze differences in CD3+ T lymphocyte counts in patients under treatment with Ocrelizumab and their relationship with the development of infections.

Methods

We performed an observational retrospective case-control study nested in a cohort of MS patients under treatment with Ocrelizumab. Cases were patients who developed infections and controls were patients who did not develop any type of infection during treatment.

Results

We included 33 patients, mean age 39 years old (SD:9.6), mean MS duration 9 years (SD:5.8), 66.7% women, 38.7% developed infections during treatment. Mean CD3+ T lymphocytes count was 1157.6 (SD:498) at baseline, 1373 (SD:621.9) CD3+ T lymphocytes at 3 months, 1221 (SD:439) CD3+ T lymphocytes at 6 months and 1405 (SD:836) at 12 months. We did not find statistical differences between groups, although there was a tendency towards a higher mean CD3+ T lymphocyte count at three months (1781.2;SD:399.9) in patients who did not develop infections as compared to the mean CD3+ T lymphocytes count at three months (1047.1; SD: 595.1) in patients who developed infections (p=0.064).

Conclusions

Our preliminary data did reveal statistical differences in the total CD3+ T lymphocyte count between patients under Ocrelizumab treatment, although there was a tendency towards a higher count at 3 months in patients who did not develop infections. Weather the putative effect of Ocrelizumab on T cell subtype (CD3+ CD20+) might be related to the development of infections needs further research.

Background

Ocrelizumab is the first drug approved as disease modifying treatment for primary progressive (PP) multiple sclerosis (MS). As a humanized monoclonal antibody targeting CD20 cells, it is widely known that ocrelizumab treatment results in B cells depletion, but less is known about the effects of this drug in other blood leukocyte subsets of PPMS patients.

Objectives

To explore the changes induced by ocrelizumab in blood immune cells of PPMS patients to further understand their effects in the abnormal inflammatory response.

Methods

Multi-centre prospective longitudinal study including fifty‐three PPMS patients who initiated ocrelizumab treatment. Effector, memory, and regulatory cells were analyzed by flow cytometry at baseline and after 6 months of treatment. To assess differences between baseline and after 6 months, Wilcoxon matched paired tests were used and p values were corrected using Bonferroni test.

Results

Ocrelizumab decreased numbers of naïve and memory B cells (p<0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha (p<0.0001 in all cases). A reduction of CD20+ T cell numbers (p=0.02) and percentages (p<0.0001) was also observed. We also detected a clear remodelation of the T cell compartment characterized by relative increases of the naïve/effector ratio in CD4+ (p=0.002) and CD8+ (p=0.002) T cells, and relative decreases of CD4+ (p=0.03) and CD8+ (p=0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p=0.002), with no changes in those producing inflammatory cytokines. All these changes resulted in a reduction of serum neurofilament light chain (sNfL) levels (p=0.009).

Conclusions

Effector B cell depletion by ocrelizumab treatment induces changes in the T cell response of PPMS patients towards a low inflammatory profile. This resulted in a decrease of sNfL levels.

Background

Cladribine in a desoxiadenosine analogue approved for Multiple Sclerosis (MS) treatment. It produces rapid B and T cells depletion, associating lymphopenia in some cases the first months after treatment. Neutropenia is extremely rare.

Objectives

We present one patient with MS that develops severe neutropenia after the second dose of the first cycle of cladribine.

Methods

We reviewed patient's clinical history, complementary tests and outcome, as well as available bibliography about this topic.

Results

53 year-old female with past medical history of psoriasis. She suffered from an optic neuritis in 2008. Brain MRI done then showed typical MS lesions. Because of clinical and radiological stability, she did not receive any disease modifying therapy until 2018. Then, she was started on dimethyl fumarate that was discontinued a few months later due to lymphopenia and joints pain. Once the lymphocyte count was normal, she was started on cladribine in December 2019. One week after the second dose of the first cycle, she presented with asthenia. Gabapentine had also been added due to neuropathic pain. Blood test revealed severe leucopenia (0.51 x 10⁹/l), grade IV lymphopenia (0.19 x 10⁹/l) and grade IV neutropenia (0.20 x 10⁹/l). Rest of the bool count and smear were normal. Bone marrow aspirate showed slight hypocellularity with good representation of the three series, suggestive of post-chemotherapy aplasia recovery, indicative of cladribine induced neutropenia. Granulocyte colony stimulating factor was administered during 2 days, with progressive recovery until normal neutrophil count was achieved within 10 days. Grade II lymphopenia persists (0.74 x 10⁹/l) after 3 months. The patient has remained afebrile and without any incidence. Evaluation of the second cycle of cladribine according to clinical, radiological and blood test evolution is still pending.

Conclusions

Neutropenia is a very rare adverse effect of cladribine in MS treatment, but it may be life-threatening. Thus, clinical and blood test monitoring is essential. In the case presented, we postulated that gabapentine may have an additive effect in cladribine hematologic toxicity.

Background

Tocilizumab is a monoclonal antibody against IL-6 that has been used to treat Neuromyelitis Optica spectrum disorders (NMOSD), generally intravenous. The evidence about its subcutaneous formulation to treat these diseases is scarce, but its efficacy seems to be similar. During SARS-CoV-2 pandemic, decreasing hospital attendance became a priority. According to this, subcutaneous formulations may represent a good therapeutic option in this context.

Objectives

We present 3 cases of NMSOD who initiated subcutaneous tocilizumab during SARS-CoV-2 pandemic, with very good tolerability in all the cases.

Methods

Retrospective and observational study. We reviewed clinical charts, patients’ outcomes and available bibliography.

Results

Patient 1: 74 year-old male, diagnosed with Neuromyelitis Optica (NMO) in 2010. He was started on rituximab in 2012. In 2018, he suffered from two optic neuritis (despite the absence of CD19+ and CD27+ cells in peripheral blood). Because of that, in 2019, rituximab was switched to intravenous tocilizumab, with good response and tolerability. In April 2020, due to SARS-CoV-2 pandemic, it was switched to subcutaneous tocilizumab in order to avoid hospital attendance, with very good tolerability.

Patient 2: 40 year-old female, diagnosed with NMOSD vs CRION (chronic relapsing inflammatory optic neuropathy). Positive anti-NMO antibodies and negative anti-MOG antibodies were found. She was started on rituximab in 2015. In December 2019, she suffered from an optic neuritis despite having no CD19+ cells in peripheral blood. Hence, rituximab was switched to intravenous tocilizumab without any incidence. In March 2020, she was started on subcutaneous tocilizumab once a week because of the pandemic, with very good tolerability.

Patient 3: 28 year-old female, diagnosed with seropositive NMO in 2012, treated with rituximab since 2014, free of relapses since them. In May 2020, we decided to switch to tocilizumab (subcutaneous to decrease hospital visits due to SARS-CoV-2 pandemic) because of hypogammaglobulinemia and repeated respiratory tract infections.

Conclusions

Tocilizumab may be an option to treat NMOSD patients. Subcutaneous form decreases hospital visits and, according to our experience, is very well tolerated. Therefore, we postulate it can be a good alternative in the current situation.

Background

It´s stated that as we get older, cognitive processes change. Healthy control (HC) and people with multiple sclerosis (MS) share a decrement in speed of processing with age. Nevertheless, demyelinating and neurodegenerative characteristics of MS may implicate neuropsychological differences when analyzing aging.

Objectives

To study the differences in cognitive processes between MS patients and HC when considering two age groups: yound adults and older ones.

Methods

We had two groups: MS from 45 to 55 years old (MS1) and from 56 to 70 (MS2) and a HC group (HC1 and HC2) paired in age and years of education (YoE). We applied a neuropsychological comprehensive battery including Symbol Digit Modality Test (SDMT), PASAT 3”, Spanish California Verbal Learning Test (TAVEC), Spatial Recall Test (SPART), Brief Visual Memory Test (BVMT-R), Five Digit Test (5DT), WAIS-Digits and Corsi and verbal fluency (letter, category and exclusion). Mild (MCI) and moderated (ModCI) cognitive impairment was based on Z scores for the following cognitive domains: speed of processing (SP), attention, working memory, verbal and visual memory and executive functions.

Results

We assessed 137 MS patients, 62,7% women with a mean age of 52.7, secondary education (M=14.3) with a mean Expanded Disability Status Scale (EDSS) of 3.3 (Mode=6), relapsing-remitting MS (82,5%) after a mean of 14,3 years having MS. We also evaluated 34 matching HC. MS patients were MCI (43.1%) followed by no impairment (33.6%) and they were equivalent in age, YoE or EDSS. When comparing groups, HC1 scored higher than HC2 in SDMT (p<0.001), SPART-recall (p=0.21) and they retrieved more words in TAVEC when cued were offered short-term (p=0.024), long-term (p=0.034) and free long-term recall (p=0.043). When MS group was analyzed, MS1 performed better than MS2 in SDMT (P=0.004), total learning in TAVEC (p=0.026 list A and p=0.004 list B), hits and dyads in PASAT (p=0.004 and P=0.01), digits-forward (p=0.035) and exclusion fluency (p=0.014). When comparing the same age group, MS1 scored lower in SMDT, SPART learning and recall compared to HC1. In older group, MS2 showed less hits and dyads in PASAT with higher interference errors and less fluency in exclusion trial compared to HC2.

Conclusions

Cognitive ageing for MS patients is different: as HC, they get slower when processing information but they also perform worse in verbal and visual learning tasks together with executive functioning, whereas for HC the cognitive deficit is more memory-specific related. When younger, MS were equal to HC but slower. When older, MS displayed dysexecutive aspects instead of mainly amnesic ones. The added cognitive features of the older MS group support the idea of an added subcortical damage, responsible of a frontal-like neuropsychological profile.

Background

Background: Cognitive complaints have been previously related to depressive symptoms in multiple sclerosis (MS), whereas self-reported executive performance has been postulated as generally reliable. Nevertheless, little is known about dysexecutive complaints (DC) and its relationship with depression and anxiety.

Objectives

Objective: (i) Study self-reported dysexecutive symptoms in attention, motivation, executive control, social behavior and emotional regulation in MS compared to control group (HC). (ii) Analyse the relation between cognitive complaints and emotional symptoms.

Methods

Methods: We collect 30 MS patients from the clinic (63% women; mean age, 43.93 y.o.; 10 years of evolution of the disease; EDSS mean 2.4; 16.6 years of schooling) and 30 healthy controls (HC) (58% women; mean age, 39.6. y.o.; 15.03 years of schooling). Participants are requested to complete the Inventory of Prefrontal Symptoms (IPS), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Statistical analysis was performed.

Results

Results: Significant differences were found in the IPS sub-scales: attention (p<0.00), Motivation (p<0.00) and social behavior (p<0.00) between MS and HC; no differences were found in executive control and emotional regulation. Significant differences were also found in BDI and Trait Anxiety (TA) between both groups, but not in state anxiety (SA). Significant correlations (p<0.05) were found between emotional symptoms and IPS Subscales. A linear regression was performed finding that BDI and trait anxiety explained 87.3% of variance for IPS total score; in addition, TA explained 38.7% of the variance of motivation, 38.5% of executive control, 26.5% of social behavior and 42.3% of emotional regulation for MS group, while SA explained 26% of the attention complaints.

Conclusions

Conclusion: MS report more subjective complaints of attention, motivation and social behavior than HC and more TA and depression symptoms. Whereas SA significantly predicts a high percentage of attention symptoms, TA predicts social inadequacy, emotional regulation problems, lack of motivation for action and difficulties in executive control. These results consider the extent to which DC are related to emotional problems, objective cognitive deficits or personality factors and whether anxious personality in MS is as an emotional consequence of the disease or whether this pattern is related to structural changes that affect the tools to deal with stressful situations.

Background

Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune, neurodegenerative disease. Around 19% of treated patients with relapsing-remitting MS progress to Secondary Progressive MS (SPMS) 15 years after disease onset, representing the most severe stage of the disease. MS symptoms lead to a general disability, impacting the quality of life of patients and also being related with an important economic burden on the National Health System, the patients, their caregivers and the whole society.

Objectives

There are limited published data on the economic impact of SPMS. The main objective of the study was to estimate the economic impact of SPMS in Spain.

Methods

DISCOVER (CBAF312AES01) is an observational, non-interventional, cross-sectional, retrospective and multicenter study, including 297 SPMS patients ≥18 years treated and monitored according to routine clinical practice in Spain in 34 public hospitals. All data was collected in one single visit. Primary endpoint: total annual cost per patient, including direct healthcare and non-healthcare costs and indirect costs. Interim results from 99 patients are presented.

Results

62.6% females; mean (SD) age 53.1 (9.3) years; 40.4% with higher education; 86.9% living with a relative. Mean (SD) time since first MS diagnosis was 17.5 (8.9) years and since progression to SPMS 5.2 (4.3) years. At diagnosis, mean (SD) EDSS was 2.0 (1.1), being 5.0 (1.1) at the time of progression and 5.9 (0.8) at the study visit, 47.5% patients reaching EDSS>6. 12.8% of patients presented relapses between 12-24 months before the study. According to EQ-5D-5L, mean (SD) utility (<1) was 0.48 (0.27) for patients with Gd+ lesions and/or relapses 2 years before. According to EQ-5D-5L, mean (SD) utility (<1) for patients with cognitive impairment was 0.45 (0.29) vs 0.51 (0.21) for those without it. Mean (SD) utility for Spanish general population was 0.897 (0.21). EDSS score showed a significative effect (P=0.0074) on the economic burden of the disease, with total costs increasing from 14,546€ (EDSS 4-4.5) to 21,918€ (EDSS 5-5.5) and 26,832€ (EDSS=6). Costs related to patients with EDSS=6 from the societal, patient and healthcare system were 6,441€, 8,450€ and 11,941€, respectively.

Conclusions

Interim results of the DISCOVER study revealed a significant economic impact of MS progression, highlighting the importance of implementing therapeutic strategies specific to the SPMS patient within the early stages of progression.

Background

Patients with neuromyelitis optica spectrum disorders (NMOSD) experience a spectrum of symptoms negatively impacting on daily living and quality of life. The systematic assessment of patient perspectives has the capacity to provide crucial clinical information that could otherwise be lost when relying on clinical evaluation alone. However, the patient experience living with NMOSD is limited, in particular implementing standardized patient-reported outcomes (PROs).

Objectives

The primary objective of this study protocol is to assess the health-related quality of life and well-being of NMOSD patients.

Methods

A multicenter, non-interventional, cross-sectional study will be conducted with patients diagnosed with NMOSD (2015 Wingerchuk criteria) (PERSPECTIVES-NMO Study). Primary outcomes measures will be the 29-item Multiple Sclerosis Impact Scale and the Satisfaction with Life Scale. Demographic characteristics, clinical and imaging outcomes will be collected, including the number and type of attacks, antibody status, Expanded Disability Status Scale score, Nine-Hole Peg Test, Timed 25-Foot Walk, and Magnetic Resonance Imaging findings. Cognition will be evaluated using the Rao Brief Repeatable Neuropsychological Battery. Additional outcomes from the patient´s perspective (PROs) will be collected, including symptoms severity (SymptoMScreen questionnaire), fatigue (Fatigue Impact Scale for Daily Use), pain (MOS Pain Effects Scale), mood (Beck Depression Inventory-Fast Screen), perception of stigma (8-item Stigma Scale for Chronic Illness), and work-related difficulties (23-item Multiple Sclerosis Work Difficulties Questionnaire).

Results

Patient recruitment began in December 2019 with a planned total sample of 70 patients. The study is currently ongoing.

Conclusions

The study results are expected to provide meaningful insights into the clinical burden of disease. A better understanding of patient experiences may foster the development of patient-centered specific plans and more targeted rehabilitation in clinical practice.

Background

Pediatric Multiple Sclerosis (MS) is defined as MS with an onset before age 18. It is an infrequent disease that entails between 3% and 5% of all MS diagnoses. It can accrue significant disability at a younger age than adult MS, therefore it is a more aggressive disease. Disease-modifying therapies (DMTs) in children and adolescents are used based on clinical experience. Fingolimod is the first DMT approved in data sheet as a treatment for pediatric MS after the clinical trial PARADIGMS.

Objectives

We present our experience with 7 patients with pediatric MS. We describe tolerability, security and effectiveness in our patirents.

Methods

Observational, retrospective and usual clinical practice study in pediatric MS patients treated with Fingolimod.

We analyzed security and effectiveness: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and after starting Fingolimod

Results

We present 7 patients with pediatric MS (5 girls and 2 boys). The mean age of onset of the disease was 15,1 years old (DS1,5). The mean annualized relapse rate in the year before Fingolimod was 1,6 (DS0). The mean number of enhancing lesions in basal Magnetic Resonance Imaging (MRI) was 3,7 (DS6,4) and the mean number of lesions in T2 sequences was 20 (DS2,8). Six patients had spinal cord lesions. The median age at onset of Fingolimod was 16 years old. Three patients were naive and the rest of them had been previously treated with injectable agents. Patients were exposed to Fingolimod for 22,3 months as an average (DS25). They did not present new relapses nor radiological activity on MRI after starting Fingolimod. No adverse effects were reported during the treatment.

Conclusions

The mean age of our patients is similar to the pivotal clinical trial, mostly postpubertal and with a highly active disease. Fingolimod seems to be a very effective and secure treatment in our patients with pediatric MS, with a very good tolerability and adhesion.

Background

The SARS-CoV-2 infection has spread worlwide becoming a pandemic never before seen. Immunosuppressive (IS) treatments used in Multiple Sclerosis (MS) patients could activate the infection in asymptomatic carriers or reactivate COVID-19 in apparently recovered cases. Our similar experience in some MS patients during the pandemic lead us to design a safety protocol at our MS Unit. It was based on epidemiological data and testing for PCR in nasopharyngeal swabs and serology before administration of monoclonal antibodies, doses of pulsed disease modifying therapies (DMTs), new starts of oral DMTs and methylprednisolone pulses.

Objectives

To describe our experience in the establishment of a SARS-CoV-2 safety protocol in MS patients. We analyze its utility to prevent COVID-19 complications

Methods

Observational, prospective and clinical practice study in the establishment of a multidisciplinary safety protocol (MS Unit – Neurology/Microbiology/Preventive Medicine). Sequential protocol over time adapted to the different pandemic phases and levels of available resources.

Results

152 PCR and 140 serology tests were performed in 90 patients over 3 months. They were performed preceding the treatment with Natalizumab (96 tests), Ocrelizumab (36 tests), Rituximab (3 tests), Methylprednisolone (7 tests), Cladribine (4 tests) and Dimethyl Fumarate (3 tests). 7 asymptomatic carriers were diagnosed (7,8%), 5 of them with positive IgM+IgG serology (5,6%). 5 patients with positive IgM+IgG serology post-infection were confirmed. No COVID-19 reactivation was detected after the establishment of the protocol.

Conclusions

The combined analysis of PCR and serology increased the sensitivity of the SARS-CoV-2 infection diagnosis during the pandemic peak of cases phase. However, this does not happen at pandemic phases with less daily cases, when testing PCR alone detected the same number of cases than testing combined PCR and serology. The safety protocol reaches its objective of avoiding disease reactivation and clinical activation in asymptomatic carriers.

Background

There are different disease-modifying therapies (DMTs) for treating patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Oral Cladribine was commercialized in 2018.

Objectives

To analyze the first year of treatment with Cladribine in RRMS patients: tolerability, security and initial approach to its effectiveness.

Methods

Retrospective, longitudinal and unicenter study in RRMS patients treated with Cladribine. We analyzed its security measuring overall lymphocyte count by Friedman Test and time to appearance of lymphopenia by Kaplan-Meier. We studied its effectiveness by comparing the following variables with the Wilcoxon Test: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and one year after starting Cladribine (statistically significant p<0’05).

Results

53 patients were studied. 88,7% were women with a mean age of 44,8 years old (DS10,25). 56,6% of the patients had a RRMS evolution of less than 10 years, 32,1% between 10 and 20 years, and 9,4% between 20 and 30 years. 64,1% had been previously treated with one or two DMTs. Patients were exposed to Cladribine for 8 months as a median (percentiles P15=2 months, P85=15 months): 36,4% patients for 6 months, 34,1% between 6-12 months and 29,5% for more than 12 months. The overall lymphocyte count reduction regarding the basal level after starting the drug was statistically significant (p<0’05). The lymphocyte count reduction rate was 52,89% during the first year of treatment and 58,99% during the second one. Tolerability was good in 93,02% of the patients. We observed significant reduction of the relapses rate after one year of treatment.

Conclusions

Cladribine seems to be a secure treatment. The most common adverse effect was lymphopenia (81,8%) but it was severe only in 9,09% of the patients and not associated with severe infections. Its tolerability was very good. Effectiveness results are positive, but, to date, they are preliminary.

Background

The new coronavirus SARS-CoV-2 infection has spread worlwide becoming a pandemic never before seen. Multiple Sclerosis (MS) patients in a state of immunosuppression (IS) may be exposed to a greater risk of COVID-19 complications, although there is increasing evidence postulating a possible protective role of selective IS.

Objectives

To describe the real-world experience in MS patients with SARS-CoV-2 infection at a MS Unit of a hospital in Madrid, Spain. We describe clinical evolution and MS treatment actions

Methods

Observational, prospective and usual clinical practice study in MS patients affected by SARS-CoV-2 infection with clinical diagnosis (at least three of the following: fever, anosmia, cough, diarrhea, myalgia) and/or microbiological diagnosis (PCR in nasopharyngeal swabs and/or serology).

Results

41 SARS-CoV-2 infection cases were registered. 21 were women with a mean age of 39,4 years old (DS10,3). 38 were relapsing-remitting MS patients and 3 had a progressive MS. The mean MS time course was nine years (DS1,4). 39 patients were treated with disease-modifying therapies (DMTs): 46,3% with oral agents, 39% with monoclonal antibodies and 10% with injectable agents. 27 patients were previously treated with other DMTs. The median Expanded Disability Status Scale (EDSS) was 2,5 (DS0,7). 11 patients had clinical activity the previous year. 18 cases were confirmed by PCR and/or serology and 23 were clinically diagnosed. 17% of the patients were admitted to hospital (6 were diagnosed with pneumonia) and none required admission to the intensive care unit. There were no deaths.Three patients had other comorbidities. Admitted patients were older and had higher EDSS score without statistical significance. MS got worse in 7 patients. DMTs were stopped or delayed in 10 patients due to the SARS-CoV-2 infection.

Conclusions

All the MS patients studied had a good outcome of the SARS-CoV-2 infection. Only 17% of them required admission to hospital and 14,6% of the cases were asymptomatic. 95% of the patients were treated with DMTs. From our experience, the SARS-CoV-2 infection does not seem to entail a more aggressive form of the disease in this group of patients. Selective IS may favor the good evolution. Larger clinical registers are needed to establish solid conclusions.

Background

Background: There is an association between motor and cognitive impairment in patients with multiple sclerosis (MS) over their disease course and strong evidence that physical therapy can prevent disability progression in these patients. Virtual reality (VR) has emerged as a promising treatment approach in rehabilitation for patients with MS due to its potential to increase patient motivation and rehabilitation adherence. However, there is a lack of studies about its safety, feasibility and effectiveness in MS patients.

Objectives

Objectives: The objective of this study protocol is to evaluate the feasibility, adherence, safety and effectiveness of a virtual reality rehabilitation (VRR) program in MS patients compared to a conventional rehabilitation (CR) program.

Methods

Methods: A randomized, prospective, open-label, controlled feasibility study will be conducted in a sample of 48 individuals diagnosed with MS. Participants will be allocated 2:1 to the VRR group (32) or CR group (16). Both groups will perform 8 in-hospital physical therapy sessions of 2 hours each, twice a week over 4 weeks. The VRR group will perform half of these sessions with a VRR tool. In addition, both groups will continue rehabilitation at home for 5 months. The VRR program was designed by a multidisciplinary group of healthcare professionals (neurologists, physiatrists, physiotherapists, neuropsychologists) according to a validated CR program. Feasibility will be assessed by the User Satisfaction Evaluation Questionnaire (USEQ). Secondary outcomes include adherence, disability, spasms and spasticity, balance, fatigue, activities of daily living, depression, anxiety, work status, cognition, demographic and clinical characteristics (in the VRR and CR groups), and safety (in the VRR group). Outcome measures will be assessed at baseline and at 1 and 6 months from the start of rehabilitation.

Results

Results: Due to the present comunication is a description of an ongoing study protocol there are stil not results to present.

Conclusions

Conclusions: A better understanding of long-term patient satisfaction with a VRR program specifically designed for MS patients would allow us to optimize the rehabilitation program and to collect valuable information for its implementation in the clinical practice. Additionally, the study will provide information on long-term adherence, changes in motor symptoms, cognitive function and patient-reported outcomes after the rehabilitation program. Altogether, the results from this study will help to gather valuable knowledge on the use of rehabilitation with a new VR tool in MS patients.

Background

Pediatric Multiple Sclerosis (MS) is defined as MS with an onset before age 18. It is an infrequent disease that entails between 3% and 5% of all MS diagnoses. It can accrue significant disability at a younger age than adult MS, therefore it is a more aggressive disease. Disease-modifying therapies (DMTs) in children and adolescents are used based on clinical experience. Fingolimod is the first DMT approved in data sheet as a treatment for pediatric MS after the clinical trial PARADIGMS.

Objectives

We present our experience with 7 patients with pediatric MS. We describe tolerability, security and effectiveness in our patirents.

Methods

Observational, retrospective and usual clinical practice study in pediatric MS patients treated with Fingolimod.

We analyzed security and effectiveness: relapses, Expanded Disability Status Scale (EDSS) score and gadolinium enhancing lesions before and after starting Fingolimod

Results

We present 7 patients with pediatric MS (5 girls and 2 boys). The mean age of onset of the disease was 15,1 years old (DS1,5). The mean annualized relapse rate in the year before Fingolimod was 1,6 (DS0). The mean number of enhancing lesions in basal Magnetic Resonance Imaging (MRI) was 3,7 (DS6,4) and the mean number of lesions in T2 sequences was 20 (DS2,8). Six patients had spinal cord lesions. The median age at onset of Fingolimod was 16 years old. Three patients were naive and the rest of them had been previously treated with injectable agents. Patients were exposed to Fingolimod for 22,3 months as an average (DS25). They did not present new relapses nor radiological activity on MRI after starting Fingolimod. No adverse effects were reported during the treatment.

Conclusions

The mean age of our patients is similar to the pivotal clinical trial, mostly postpubertal and with a highly active disease. Fingolimod seems to be a very effective and secure treatment in our patients with pediatric MS, with a very good tolerability and adhesion.