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

Several retrospective studies have demonstrated the clinical benefits of immunosuppressive therapies (IST) such as azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) for reducing relapse rates in neuromyelitis optica spectrum disorders (NMOSD) patients. However, there is considerable uncertainty regarding the relative benefits and harms associated with each of these IST in real world clinical practice and current data describing the strategies are limited

Objectives

The objective of this study was to describe the incidence of relapses in patients with NMOSD under IST included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

Methods

We conducted a retrospective cohort study from RelevarEM. RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. From May 2018 to June 2020, the centers and principal investigators were contacted, and patients were incorporated into the Registry. NMOSD patients were defined based on the 2015 International Consensus Diagnostic Criteria for NMOSD. Relapses during the study period, demographics and radiological (e.g. new/enlarging and/or enhancing-contrast MRI lesions) data were collected. Only patients under IST were included in the analysis. Patients contributed person-years of follow-up for the study period. Incidence rates and 95% CI were calculated. Thus, global and associated with each IST incidence density rate of relapses was estimated.

Results

We included a total of 132 (77% women) NMOSD patients with a median age at diagnosis of 36 years (27-47) and a disease duration of 6 years (4-10). Aquaporin-4 antibody was positive in 54.8%. At the time of entering the registry, 39.4% were treated with RTX, 33.3% with AZA, 3.6% MMF. The global incidence density rate of relapse was 0.032/person-year (CI95% 0,021-0,048), for RTX 0.051 (CI95% 0,024-0,1) and for AZA 0,031 (CI95% 0,016-0,06). There were no relapses in the group of MMF during this period of time.

Conclusions

This study showed a low incidence density rate of relapses in NMOSD patients under IST during this study period. Further studies will help expand our initial findings, hopefully leading to improve treatment options for NMOSD patients.

Background

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been described in aquaporin-4-antibodies(AQP4-Ab)-negative neuromyelitis optica spectrum disorders (NMOSD) patients.

Objectives

We aimed to investigate the percentage of AQP4-Ab-negative NMOSD patients who are positive for MOG-Ab included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177).

Methods

RelevarEM is a longitudinal, strictly observational multiple sclerosis (MS) and NMOSD registry in Argentina. Epidemiological, serological test and neuroimaging (MRI) data from NMOSD were described.

Results

A total of 165 patients (79 AQP4-Ab positive, 67 AQP4-Ab negative and 19 unknown) were included. Of these, 155 patients fulfilled the 2015 NMOSD diagnostic criteria. Of 67 AQP4-Ab-negative patients, 36 were tested for MOG-Ab and 10 of them (31.8%) tested positive. Presence of relapses during the previous 6 months (40% vs. 12.9%), shorter disease duration (3.9 vs. 7.5 years), lower disability (2.3 vs. 3.4) and treatment duration (1.5 vs. 3.4 years) and both optic neuritis (90% vs. 44.5%) and optic nerve lesion on MRI (80% vs. 25.1%) were significantly associated with MOG-Ab-positive compared with NMOSD respectively

Conclusions

This is the first study of the longitudinal Argentinean registry of MS and NMOSD describing and comparing diseases that contributes to provide reliable real-world data in the country. We observed that 31.8% (10/36) of the AQP4-ab-negative patients tested for MOG-Ab were positive for this antibody, in line with results from other world regions.

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

Sleep abnormalities are very common among patients with multiple sclerosis (MS) affecting approximately 60% of them but still remain under-recognized and inadequately addressed. Some common types of sleep disorders include insomnia, sleep-related movement disorders, sleep-related breathing disorders, and circadian rhythm disorders affecting MS populations.

In 25-35% of MS patients sleep interruptions are present, with sleep fragmentation, both in the macro and microstructure, and this condition may explain, in part, the presentation of fatigue.

Objectives

Correlate sleep-related disorders with the presence of fatigue and its severity in patients with relapsing-remitting MS (RRMS).

Methods

24 patients with RRMS were evaluated between March 1, 2018 and February 28, 2020.

Each patient underwent: Modified Fatigue Impact Scale, Insomnia Severity Index, STOP-BANG, Pittsburgh Sleep Quality Index and nocturnal polysomnography with oxygen saturation.

The data was analyzed using the Minitab® 15.1.20.0 package.

Results

24 patients were included; 75% female (3:1); mean age 36.3 years, (± 9); with mean 1.96 (± 0.8) years since diagnosis. 58% presented some alteration in sleep patterns, predominating awakenings and micro-awakenings fragmentation.

Regarding the presence of fatigue in patients with sleep disorders, it was observed that the ones with altered structure (micro-awakenings / awakenings or intervened wakefulness) have presented a considerably higher score on the fatigue scale. Patients with adequate structure presented a mean of 18.3 (± 15), while those who presented a fragmented structure due to awakenings and micro-awakenings presented a mean of 34.58 (± 23.74).

In relation to the sleep quality, a higher score was detected in patients considered as poor sleepers (mean 32.21 ± 21.95), compared to patients with adequate rest (mean 16.2 ± 13.77). The same occurs concerning insomnia, where a higher score on fatigue scale is detected in patients with moderate severity clinical insomnia (mean 49.5 ± 9.32) in relation to those without clinically significant insomnia (mean 20.42 ± 23.12).

Conclusions

The results suggest that sleep alterations are involved in fatigue clinical expression in RRMS patients, supporting the importance of exploring their presence in initial evaluation. In this way, we could improve not only sleep structure and quality, but also fatigue in our patients, improving their quality of life and quality years.

Background

Patients with multiple sclerosis (MS) often have unrecognized sleep abnormalities, more frequently than the general population. Mainly respiratory disorders, insomnia, REM sleep disorders, narcolepsy and restless legs syndrome are reported. Sleep-related disorders can affect the quality of life (QOL) in patients diagnosed with MS.

Objectives

Analyze sleep-related disorders in patients with relapsing-remitting multiple sclerosis (RRMS) and their possible impact on QOL.

Methods

24 patients with RRMS were evaluated between March 1, 2018 and February 28, 2020.

Each patient underwent: Multiple Sclerosis Quality of Life 54 (MSQOL-54), Insomnia Severity Index, STOP-BANG, Pittsburgh Sleep Quality Index and nocturnal polysomnography with oxygen saturation.

The data was analyzed using the Minitab® 15.1.20.0 package.

Results

24 patients were included; 75% female; mean age 36.3 years, (± 9); with a mean of 1.96 (± 0.8) years after diagnosis.

58% presented some alteration in sleep patterns, predominating awakenings and micro-awakenings fragmentation.

Analyzing patients QOL according to sleep disorders, those who presented some structure alteration obtained a lower QOL scale score (mean 77.2 [± 12.76] in patients with normal structure and mean 66.75 [± 15.34] in those with awakenings and micro-awakenings structure fragmented).

Patients with clinical insomnia had a lower QOL scale score, highlighting an inverse relationship between the QOL and the severity of the insomnia. Patients without clinically significant insomnia presented a QOL scale mean 76.93 (± 14.08), while in patients with clinical insomnia of moderate severity the mean was 57.75 (± 16.38).

Regarding the quality of sleep, categorizing this variable into normal and poor sleepers, 79% were in the second group. Analyzing the QOL according to this variable, those who presented an adequate quality of sleep, showed better QOL.

Conclusions

Sleep-related disorders are a common problem among people with MS. These disorders can be serious enough to interfere with physical, social, emotional and mental functioning for those who suffer from them, generating a significant impact on people's QOL.

Our results demonstrate the sleep abnormalities in RRMS patients, supporting the need and importance of exploring their presence in initial evaluation.

The development of preventive strategies and interventions that reduce sleep alterations could improve QOL in patient with RRMS.

Background

There are scarce data from Argentina or Latin America that evaluate family planning (FP) in women with multiple sclerosis (WwMS).

Objectives

The purpose of this study was to assess family planning experience and knowledge among Argentinian women with multiple sclerosis

Methods

604 WwMS from 10 MS Argentinian centers were invited to answer an online survey. Demographics, disease characteristics, disease modifying treatment (DMDs), knowledge and influences on FP, parenthood desire, occurrence of unplanned pregnancies were collected.

Results

A total of 433 (71.68%) WwMS completed the survey, mean age 32.4 ±11.0 years, mean EDSS 1.88 ±1.99, disease evolution ≤ 3 years 29.9%, motherhood before MS diagnosis 42.1%. A total of 82 WwMS became pregnant after MS diagnosis and regarding last pregnancy, 63.41% were planned and 36.58% unplanned. 53% of unplanned did not received information on FP. 55.8% stopped DMDs after pregnancy confirmation. In WwMS of reproductive age, 230 ≤ 40 years were identified. 49,6% considered FP an important factor in choice of treatment. Out of 230, 88.69% experienced concerns regarding maternity and MS, 32.2% changed maternity longing after MS diagnosis and 48.69% have future motherhood desire. Age 32.37 ±5.56, MS evolution ≤5 years, EDSS<3, no pregnancy before MS diagnosis and neurologist discussed FP planning, were significantly associated with future desire for motherhood (p<0.05).

Conclusions

The research highlights that pregnancy remains an important concern among WwMS. More than half of unplanned pregnancies did not receive FP. FP should be discussed not only out of a desire for motherhood, but also as part of the treatment decision process.

Background

Sleep abnormalities are very common among patients with multiple sclerosis (MS) affecting approximately 60% of them but still remain under-recognized and inadequately addressed. Some common types of sleep disorders include insomnia, sleep-related movement disorders, sleep-related breathing disorders, and circadian rhythm disorders affecting MS populations.

In 25-35% of MS patients sleep interruptions are present, with sleep fragmentation, both in the macro and microstructure, and this condition may explain, in part, the presentation of fatigue.

Objectives

Correlate sleep-related disorders with the presence of fatigue and its severity in patients with relapsing-remitting MS (RRMS).

Methods

24 patients with RRMS were evaluated between March 1, 2018 and February 28, 2020.

Each patient underwent: Modified Fatigue Impact Scale, Insomnia Severity Index, STOP-BANG, Pittsburgh Sleep Quality Index and nocturnal polysomnography with oxygen saturation.

The data was analyzed using the Minitab® 15.1.20.0 package.

Results

24 patients were included; 75% female (3:1); mean age 36.3 years, (± 9); with mean 1.96 (± 0.8) years since diagnosis. 58% presented some alteration in sleep patterns, predominating awakenings and micro-awakenings fragmentation.

Regarding the presence of fatigue in patients with sleep disorders, it was observed that the ones with altered structure (micro-awakenings / awakenings or intervened wakefulness) have presented a considerably higher score on the fatigue scale. Patients with adequate structure presented a mean of 18.3 (± 15), while those who presented a fragmented structure due to awakenings and micro-awakenings presented a mean of 34.58 (± 23.74).

In relation to the sleep quality, a higher score was detected in patients considered as poor sleepers (mean 32.21 ± 21.95), compared to patients with adequate rest (mean 16.2 ± 13.77). The same occurs concerning insomnia, where a higher score on fatigue scale is detected in patients with moderate severity clinical insomnia (mean 49.5 ± 9.32) in relation to those without clinically significant insomnia (mean 20.42 ± 23.12).

Conclusions

The results suggest that sleep alterations are involved in fatigue clinical expression in RRMS patients, supporting the importance of exploring their presence in initial evaluation. In this way, we could improve not only sleep structure and quality, but also fatigue in our patients, improving their quality of life and quality years.

Background

Patients with multiple sclerosis (MS) often have unrecognized sleep abnormalities, more frequently than the general population. Mainly respiratory disorders, insomnia, REM sleep disorders, narcolepsy and restless legs syndrome are reported. Sleep-related disorders can affect the quality of life (QOL) in patients diagnosed with MS.

Objectives

Analyze sleep-related disorders in patients with relapsing-remitting multiple sclerosis (RRMS) and their possible impact on QOL.

Methods

24 patients with RRMS were evaluated between March 1, 2018 and February 28, 2020.

Each patient underwent: Multiple Sclerosis Quality of Life 54 (MSQOL-54), Insomnia Severity Index, STOP-BANG, Pittsburgh Sleep Quality Index and nocturnal polysomnography with oxygen saturation.

The data was analyzed using the Minitab® 15.1.20.0 package.

Results

24 patients were included; 75% female; mean age 36.3 years, (± 9); with a mean of 1.96 (± 0.8) years after diagnosis.

58% presented some alteration in sleep patterns, predominating awakenings and micro-awakenings fragmentation.

Analyzing patients QOL according to sleep disorders, those who presented some structure alteration obtained a lower QOL scale score (mean 77.2 [± 12.76] in patients with normal structure and mean 66.75 [± 15.34] in those with awakenings and micro-awakenings structure fragmented).

Patients with clinical insomnia had a lower QOL scale score, highlighting an inverse relationship between the QOL and the severity of the insomnia. Patients without clinically significant insomnia presented a QOL scale mean 76.93 (± 14.08), while in patients with clinical insomnia of moderate severity the mean was 57.75 (± 16.38).

Regarding the quality of sleep, categorizing this variable into normal and poor sleepers, 79% were in the second group. Analyzing the QOL according to this variable, those who presented an adequate quality of sleep, showed better QOL.

Conclusions

Sleep-related disorders are a common problem among people with MS. These disorders can be serious enough to interfere with physical, social, emotional and mental functioning for those who suffer from them, generating a significant impact on people's QOL.

Our results demonstrate the sleep abnormalities in RRMS patients, supporting the need and importance of exploring their presence in initial evaluation.

The development of preventive strategies and interventions that reduce sleep alterations could improve QOL in patient with RRMS.