Background

Background: In multiple sclerosis (MS), randomized controlled trials (RCT) have provided relevant information about the efficacy and safety in ideal scenarios. While RCT are powerful tools for developing scientific evidence based on their high internal validity, there is always uncertainty about the generalizability, especially since the populations enrolled in such studies may differ in significant ways from those seen in clinical practice.

Objectives

Objective: to describe the frequency and clinical profile of MS patients under disease modifying treatment in Argentina that would have not fulfilled inclusion criteria in RCT.

Methods

Methods: MS patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177) were analyzed. RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. From May 2018 to March 2020, the centers and principal investigators were contacted and incorporated into the Registry. All patients with definite MS and receiving DMT at 31 December 2019 were screened, those with EDSS >6, phenotypes secondary progressive (SP) and primary progressive (PP)(with other DMT than ocrelizumab) and age <18 and >55 years old were included in the analysis.

Results

Results: A total of 1782 patients with MS receiving DMT were screened, of whom 465 (26%)would not have been included in a pivotal trial. From the 465,218 had and EDSS >6, 67 had phenotype SP and 19 PP; 292 were patients with <18 and >55 years of age (2 under 18 years old). Most prescribed DMT among patients with EDSS >6 was fingolimod (31%), among age >55 was beta interferon (35%), phenotype SP fingolimod (30%) and PP fingolimod and glatiramer acetate (each 26%).

Conclusions

Conclusion: in our registry, we found a significant number of MS patients who would have not been included in pivotal trials, receiving DMT. Real life evidence is highly relevant to assess effectiveness as well as safety of DMT in this subset of patients.

Background

Similarly, to what occurs with MS prevalence, it has been previously described that oligoclonal bands (OCB) prevalence follows a latitudinal gradient being more frequent farther away from the equator. Argentina has the particularity of being longitudinally extensive (21°46’S to 66°13’S). Previous epidemiological studies from Argentina have not found an MS prevalence latitudinal gradient.

Objectives

The aim of the present study is to describe the prevalence of OCB in CSF in patients with MS, CIS and RIS included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177) and to investigate if the prevalence follows a latitudinal gradient.

Methods

RelevarEM is a longitudinal, observational MS and NMOSD registry in Argentina. For each province, an average latitude was calculated using extreme N and S latitudes obtained from Google Maps. Regarding OCB, pattern II or III where considered as positive. The frequency of OCB was calculated for each diagnostic category (MS, CIS, RIS) and for each province. Statistical analysis was carried out using SPSS v22. Multivariate logistical regression analysis was performed considering OCB as a dichotomic dependent variable and latitude as an ordinal independent variable, adjusted by clinically relevant variables. Also, the percentage of patients OCB positive for each province was calculated and linear correlation was tested.

Results

We included 2866 patients from different locations in Argentina (92.4% MS, 5.8% CIS and 1.8% RIS). The mean age at diagnosis (SD) was 32.7 (11.2), 35.2 (10.7) and 40.7 (11.2) for MS, CIS and RIS patients, respectively. Lumbar puncture was performed in 54.6%, 63.9%, and 43.4% of MS, CIS and RIS patients, respectively. OCB where positive in 75.4%, 55.7% and 60.9% of MS, CIS and RIS patients, respectively. No association was found between OCB positivity and latitude, adjusted by gender, age at diagnosis and diagnostic category. No linear correlation was found between the percentage of OCB positive patients and latitude.

Conclusions

Similarly, to what has been described regarding MS prevalence, OCB positivity does not seem to follow a latitudinal gradient in Argentina. Also, OCB positivity in our study is lower that described in previous reports from other world regions.

Background

Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system of multifactorial origin. Studies about the prevalence of cancer in MS population are scarce and results are conflicting. Previous studies described a higher prevalence as well as an increased risk of cancer in MS patients while there are others that found no differences regarding general population.

Objectives

The aim of our study was to estimate the prevalence of cancer in a large sample of multiple sclerosis patients in Argentina.

Methods

the eligible study population and cohort selection included all patients with definite MS included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177) at 31 December 2019. History of current or past cancer diagnosis, was collected. Prevalence rates and 95% CI were calculated.

Results

We analyzed 2647 MS patients. 14 malignancies were identified. Overall prevalence of cancer was 0.53% (CI95% 0.02-0.08%). 78.6% were female, 85.8% relapsing remitting MS, median (IQR) disease duration: 10.5 (6-13) years; median (IQR) age at diagnosis: 42.5 (37-49); median (IQR) age at study date: 52.5, median (IQR); current EDSS: 2 (1.5-4.5); 42% patients were untreated and 58% under DMT (beta interferon 1a: 14.3%, 1b: 7.1%, glatiramer acetate: 7.1% and fingolimod: 28.6%). Most frequent malignancy was breast cancer (28.6%).

Conclusions

The prevalence of cancer in MS population identified in Argentina was 0.53% (CI 95% 0.02-0.08), being females more affected than males and breast cancer the most frequent one.

Background

Data on the rates of infections among patients with multiple sclerosis (MS) are sparse and even more from Latin American countries.

Objectives

The objective of this study was to quantify the incidence of severe infections (SI) in patients with MS included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

Methods

RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. From May 2018 to March 2020, the centers and principal investigators were contacted and incorporated into the Registry. SI were defined as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the study period. Incidence rates and 95% CI were calculated.

Results

A total of 2158 patients with MS were included, mean age 42 (IIQ 34-52), 65,5% (1576) were female, 82,3% were RRMS. During the period (May 2018-March 2020), 28 SI were reported (IR 1.16, 95%CI 0.77-1.68). In patients with SI, the mean age was 54 (min 43- max 63, p<0.01) years, 11 (39%) were secondary progressive MS (p<0.01), the mean EDSS was 6.5 (range 5-8)(p<0.01), mean disease duration 12 years (p<0.01). 42% of patients were free of MS treatment while 17% were on injectables, 25% on orals and 10% on monoclonal antibodies (p=0.24). The most common sites of severe infection were the lower respiratory tract (39%)

Conclusions

IR of severe infection during the study period was 1.16 (95%CI 0.77-1.68). Most frequent SI were in SPMS and older patients while no relation was observed regarding MS treatment.

Background

Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (ab)-associated disease or MOG-IgG-associated encephalomyelitis (MOG-EM) was previously considered a benign entity but mounting evidence shows there are patients who experience severe and frequent relapses and ultimately acquire significant neurological disability.

There are some evidence about (MOG-EM) in hematopoietic receptors, with good prognosis, but these information is limited in solid organ receptors.

Objectives

To describe a case of MOG EM with aggressive course treated with steroids, azathioprine and rituximab in a solid organ receptor

Methods

We report a case of MOG EM with aggressive course treated with steroids, azathioprine and rituximab in a kidney organ recipient.

Results

He was diagnosed with a haemolytic uremic syndrome during his childhood, so he progressed to end stage kidney failure. At age of 20 he received a kidney transplant from his mother and a second new transplant at age 29 was indicated due to solid organ rejection. In the following months, a malign mammary nodule appeared so he was under tamoxifen for the next year. At 38 yo, he presented to the emergency department referred a 15-days-history of bilateral optic neuritis(ON) without other focal signs at the neurological exam and under treatment with deltisone, cyclosporine and micofenolate for immunosuppression, enalapril, and lovastatine. Acute renal failure was detected due to kidney confirmed through biopsy. Brain MRI and Lumbar puncture were made, CSF, Anti aqp4 and Anti Mog were unremarkable and treated with methylprednisolone and plasmapheresis. The diagnosis was atypical ON by inmunosupression drugs in the context of decreased glomerular filtrate. His visual acuity improved in the consecutives months. Against he received methylprednisolone and plasmapheresis. Throated out others causes, Azathioprine was started.

A new relapse was presented in few days, showing a long extensive transverse myelitis (LETM) at dorsal levels appeared, without supratentorial lesions; CSF with increased proteins levels, against infectious causes was dismissed, MOG-Ab were positive in CSF and plasma. Steroids, plasmapheresis and rituximab were started. Two months after encephalopathy signs appeared. A new MRI showed acute supratentorial lesion and LETM at cervical levels. A pulmonary sepsis appeared like a complication an instable haemodynamic, so we had a wide range of treatment. The patient died few days after.

Conclusions

MOG EM is a heterogenous sometimes severe disease. We report an aggressive and fulminant form in a previous immunosuppressive patient. We discuss the presence of Anti MOG disease as comorbidity in association to other immunological conditions. The aim of this report is increased the experience in this condition

Background

In addition to sensory, motor, and cognitive symptoms, multiple sclerosis (MS) involves diverse socio-emotional disorders. However, no work has experimentally studied the processing of social emotions (those that are triggered in interpersonal contexts) in this population.

Objectives

We aim to report preliminary results on the processing of two social emotions, envy and Schadenfreude (pleasure in the misfortune of others), in MS patients relative to healthy controls.

Methods

We evaluated 15 patients with relapsing-remitting MS and 15 control subjects matched for gender, age, educational level, executive functioning, and anxious and depressive symptoms. In an ecological paradigm (validated and reported in other populations), participants read sentences denoting fortunate experiences (designed to evoke envy) and unfortunate experiences (designed to evoke Schadenfreude) of different characters and judged how much envy and pleasure they felt, respectively. The situations belonged to three dimensions: merit (undeserved fortunate experiences for the envy condition and deserved unfortunate experiences for the Schadenfreude condition), morality (fortunate or unfortunate experiences related to moral transgressions) and legality (fortunate or unfortunate experiences related to transgressions of laws). Neutral events were also included as a control condition. We compared the emotional levels reported by each group in each experimental condition.

Results

Compared to the control group, MS patients reported experiencing lower levels of envy (t = 2.22, p = .02) and Schadenfreude (t = 1.74, p = .04) in the merit dimension. Likewise, they tended to have lower scores in total envy ratings (t = 1.61; p = .06) and in the moral dimension (t = 1.68; p = .05), although these results did not reach statistical significance.

Conclusions

To our knowledge, this is the first experimental assessment of social emotions in MS patients. Our preliminary results suggest a possible alteration in particular subdomains, particularly those involving merit. Despite their exploratory nature, these data invite further research to corroborate or refine the observed patterns. Acknowledging and characterizing the impact of socio-emotional symptoms on MS offers new vistas on the multidimensional impact of the disease, laying the foundations for new evaluation and intervention strategies.

FUNDING

This work is partially supported by grants from CONICET; CONICYT/FONDECYT Regular (1170010); FONCYT-PICT 2017-1818; FONCYT-PICT 2017-1820; FONDAP 15150012; Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH; GBHI ALZ UK-20-639295; and NIH NIA R01 AG057234.

Background

Aggressive MS (AMS) describes a form of the disease with a rapid progressive course leading to significant disability in multiple neurologic systems or even death in a relatively short time after onset. Despite there being no consensus on the exact definition of AMS, several studies performed during the last years have tried to better identify and understand the frequency and distribution as well as the progression and treatment response in order to determine more accurately which patients with AMS would most benefit from higher-efficacy, higher-risk treatments

Objectives

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (AMS) as well as to compare clinical and radiological characteristics in AMS and non-AMS patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

Methods

The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-AMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset.

Results

A total of 2158 patients with MS were included: 74 AMS and 2084 non-AMS. The prevalence of AMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p=0.003), older at MS onset (p<0.001), have primary progressive MS (PPMS) phenotype (p=0.03), multifocal presentation (p<0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p=0.004 and p=0.002, respectively).

Conclusions

3.4% of our patient population could be considered AMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesion on MRI at clinical presentation all had higher odds of having AMS.

Background

Disparities about health care access in females were previously reported. In Argentina, previous studies have shown the unequal access to health care in MS patients stratified by health coverage, but no information were obtained regarding disparities in the access by gender

Objectives

The objective of the study was to evaluate whether disparities in the access to healthcare was identified in women with multiple sclerosis (MS) in Argentina.

Methods

A cross-sectional study based on a self-administered survey was carried in 13 provinces from Argentina. We asked about demographic and clinical aspects of the disease as well as the access and barriers to MS care through self-report measures on waiting time for both neurological visits and MRI test, disease modifying treatment (DMTs) access and waiting time for delivery of DMTs. We applied multivariate analysis via both logistic and lineal regression to evaluate the impact of different factors on health care resources utilization

Results

We included 219 patients, mean age 39 (± 16) years and a female predominance 149 (68%). There were no differences between females and males in RRMS phenotype (92% vs. 89%), mean EDSS (2.5 ± 1 vs. 2.2 ± 1.3), mean age at disease onset (38±4 vs. 36 ±5 years) and working status (currently full time employed 63% vs. 68%) respectively. 97% of males vs. 89% of females received DMDs (p=0.02). No differences in neurological visits between females and males (at least 2 visits during the last year) (98% vs. 95%) neither MRI test (93% vs. 97%) was identified, respectively. Females reported longer waiting time for delivery of first DMDs (7.1 ±2 vs. 5.1 ±1.1 weeks, p=0.02) and longer waiting time for delivery of DMDs at follow-up DMDs (4.1 ±0.6 vs. 3.1 ±1 weeks, p=0.03). No differences in legal actions were identified between gender (22 % females vs. 19 % males).

Conclusions

despite no differences between demographic and clinical aspects, we identified an increased time for delivery of DMTs in female MS patients compared to males in our region.