Long-term bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study.

BACKGROUND: Severe grief is highly distressing and prevalent up to 1 year post-death among people bereaved during the first wave of COVID-19, but no study has assessed changes in grief severity beyond this timeframe. AIM: Understand the trajectory of grief during the pandemic by reassessing grief symptoms in our original cohort 12-18 months post-death. DESIGN: Prospective matched cohort study. SETTINGS/PARTICIPANTS: Family members of decedents who died in an acute care hospital between November 1, 2019 and August 31, 2020 in Ottawa, Canada. Family members of patients who died of COVID (COVID +ve) were matched 2:1 with those who died of non-COVID illness (COVID -ve) during pandemic wave 1 or immediately prior to its onset (pre-COVID). Grief was assessed using the Inventory of Complicated Grief (ICG). RESULTS: Follow-up assessment was completed by 92% (111/121) of family members in the initial cohort. Mean ICG score on the 12-18-month assessment was 19.9 (SD = 11.8), and severe grief (ICG > 25) was present in 28.8% of participants. One-third (33.3%) had either a persistently high (>25) or worsening ICG score (⩾4-point increase between assessments). Using a modified Poisson regression analysis, persistently high or worsening ICG scores were associated with endotracheal intubation in the deceased, but not cause of death (COVID +ve, COVID -ve, pre-COVID) or physical presence of the family member in the final 48 h of life. CONCLUSIONS: Severe grief is a substantial source of psychological morbidity in the wake of the COVID-19 pandemic, persisting more than a year post-death. Our findings highlight an acute need for effective and scalable means of addressing severe grief.

Comorbidities, symptoms and end-of-life medication use in hospitalised decedents before and during the COVID-19 pandemic: a retrospective regional cohort study in Ottawa, Canada.

OBJECTIVE: To compare comorbidities, symptoms and end-of-life (EoL) palliative medication (antisecretories, opioids, antipsychotics and sedatives) use among decedents before and during the COVID-19 pandemic. DESIGN: In a retrospective cohort study, decedent records in three acute care hospitals were abstracted, generating a prepandemic (November 2019-February 2020) group (pre-COVID) and two intrapandemic (March-August 2020, wave 1) groups, one without (COVID-ve) and one with COVID-19 infection (COVID+ve). Control group decedents were matched 2:1 on age, sex and care service (medicine/intensive care unit (ICU)) with COVID+ve decedents. SETTING: Three regional acute care teaching hospitals in Ottawa, Canada PARTICIPANTS: Decedents (N=425): COVID+ve (n=85), COVID-ve (n=170) and pre-COVID (n=170). MAIN OUTCOME MEASURES: Data were abstracted regarding demographics, admission comorbidities and symptoms, and EoL medication use; opioid doses were standardised to parenteral morphine equivalent daily dose (MEDD), and the predictors of upper quartile MEDD in the last 24 hours of life were examined in multivariable logistic regression with adjusted ORs (aORs) and 95% CIs. RESULTS: The prevalence of dementia (41% vs 28% and 26%, p=0.03), breathlessness (63.5% vs 42% and 47%, p<0.01), cough (40% vs 27% and 19%, p<0.01) and fever (54% vs 9% and 13.5%) was higher in COVID+ve versus pre-COVID and COVID-ve groups, respectively. The median (IQR) of MEDD over the last 72 hours of life was 16.7 (9-36.5) vs 13.5 (5.7-21.8) and 10.5 (5.3-23.8) for COVID+ve versus pre-COVID and COVID-ve groups, respectively, (p=0.007). Male sex, COVID+ve grouping, ICU death and high-flow nasal cannula use predicted upper quartile MEDD dose, aORs (95% CIs): 1.84 (1.05 to 3.22), 2.62 (1.29 to 5.3), 5.14 (2.47 to 10.7) and 1.93 (1.05 to 3.52), respectively. COVID+ve group decedents used highest lorazepam and propofol doses. CONCLUSIONS: COVID-19 decedents, particularly those in ICU, required higher EoL opioid and sedating medication doses than matched prepandemic or intrapandemic controls. These findings should inform and guide clinical practice.

Evaluation of the use of high-efficacy treatments (HETs) in patients with relapsing-remitting multiple sclerosis in Argentina.

BACKGROUND: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years. METHODS: A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included. RESULTS: Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0-1 year) and in treatment-experienced patients it was 5 years (IQR: 3-9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2. CONCLUSION: The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS.

Clinical outcomes and prognostic factors in patients with optic neuritis related to NMOSD and MOGAD in distinct ethnic groups from Latin America.

BACKGROUND: Optic neuritis (ON) can be an initial manifestation of neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin 4-antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD). Additionally, both diseases may have overlapping paraclinical and radiological features. These diseases may have different outcomes and prognoses. We aimed to compare clinical outcomes and prognostic features of patients with NMOSD and MOGAD presenting ON as first attack, from different ethnic groups in Latin America. METHODS: We conducted a retrospective observational multicenter study in patients from Argentina (n = 61), Chile (n = 18), Ecuador (n = 27), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 49) with MOGAD or NMOSD related ON. Predictors of disability outcomes at last follow-up, namely visual disability (Visual Functional System Score ≥4), motor disability (permanent inability to walk further than 100 m unaided) and wheelchair dependence based on EDSS score were evaluated. RESULTS: After a mean disease duration of 42.7 (±40.2) months in NMOSD and 19.7 (±23.6) in MOGAD, 55% and 22% (p>0.001) experienced permanent severe visual disability (visual acuity from 20/100 to 20/200), 22% and 6% (p = 0.01) permanent motor disability and 11% and 0% (p = 0.04) had become wheelchair dependent, respectively. Older age at disease onset was a predictor of severe visual disability (OR=1,03 CI95%1.01-1.05, p = 0.03); older age at disease onset (OR=1,04 CI95%1.01-1.07, p = 0.01), higher number of relapses (OR=1,32 CI95%1.02-1.71, p = 0.03) and rituximab treatment (OR=0,36 CI95%0.14-0.90, p = 0.02) were predictors of permanent motor disability, whereas ON associated with myelitis at disease onset was a predictor of wheelchair dependency (OR=4,16, CI95%1.23-14.08, p = 0,02) in NMOSD patients. No differences were found when evaluating distinct ethnic groups (Mixed vs. Caucasian vs. Afro-descendant) CONCLUSIONS: NMOSD was associated with poorer clinical outcomes than MOGAD. Ethnicity was not associated with prognostic factors. Distinct predictors of permanent visual and motor disability and wheelchair dependency in NMOSD patients were found.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Incidence of COVID-19 after vaccination in people with multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

The objective of the study was to evaluate the incidence of COVID-19 after complete vaccination in people with multiple sclerosis (PwMS) included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). METHODS: cohort study conducted between May 2021 and December 2021. The primary outcome was the appearance of infection during the follow-up time (at least three months after complete vaccination (second dose)). Data was collected through the contact between the treating physician and the patient. Specific information was requested (date, symptoms, need for hospitalization, ventilatory assistance, treatment, and evolution). The contact was made every 30 days during the period of 3 months after the full dose vaccination. A positive COVID-19 case was defined according to the definition established by the Ministry of Health in Argentina. Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density. RESULTS: A total of 576 PwMS were included, mean age 45.2 ± 13 years, 432 (75%) RRMS, 403 (70%) were female. The mean and median time of follow-up after the second dose was 91 ± 17 and 94 ± 21 days respectively. Most frequent first and second dose received was Astra-Zeneca vaccine, followed by Sputnik V vaccine. During follow-up a total of twenty COVID-19 cases were observed for a total exposure time of 39,557 days. The overall cumulative incidence for the observed period was 3.4% (SE 0.4%) with an overall incidence density of 5 × 10.000 patients/day (95%CI 0.7-12). We observed more cases in woman than men with an incidence density of 6 × 10.000 patients/day (95%CI 0.9-9) vs. 3 × 10.000 patients/day (95%CI 0.2-6) respectively, but not significantly different (IRR 1.7 95% CI 0.56-7.37 p = 0.15). CONCLUSION: we found an incidence density of breakthrough COVID-19 infection of 5 × 10.000 patients/day (95%CI 0.7-12) after vaccination in Argentina.

Bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study.

BACKGROUND: The COVID-19 pandemic has caused millions of deaths worldwide, leading to symptoms of grief among the bereaved. Neither the burden of severe grief nor its predictors are fully known within the context of the pandemic. AIM: To determine the prevalence and predictors of severe grief in family members who were bereaved early in the COVID-19 pandemic. DESIGN: Prospective, matched cohort study. SETTING/PARTICIPANTS: Family members of people who died in an acute hospital in Ottawa, Canada between November 1, 2019 and August 31, 2020. We matched relatives of patients who died of COVID (COVID +ve) with those who died of non-COVID illness either during wave 1 of the pandemic (COVID -ve) or immediately prior to its onset (pre-COVID). We abstracted decedents' medical records, contacted family members >6 months post loss, and assessed grief symptoms using the Inventory of Complicated Grief-revised. RESULTS: We abstracted data for 425 decedents (85 COVID +ve, 170 COVID -ve, and 170 pre-COVID), and 110 of 165 contacted family members (67%) consented to participate. Pre-COVID family members were physically present more in the last 48 h of life; the COVID +ve cohort were more present virtually. Overall, 35 family members (28.9%) had severe grief symptoms, and the prevalence was similar among the cohorts (p = 0.91). Grief severity was not correlated with demographic factors, physical presence in the final 48 h of life, intubation, or relationship with the deceased. CONCLUSION: Severe grief is common among family members bereaved during the COVID-19 pandemic, regardless of the cause or circumstances of death, and even if their loss took place before the onset of the pandemic. This suggests that aspects of the pandemic itself contribute to severe grief, and factors that normally mitigate grief may not be as effective.

Evaluation of adherence to treatment in patients with multiple sclerosis from Latin America.

INTRODUCTION AND AIM: Several factors have been associated with poor adherence to disease-modifying drugs (DMD). The aim of this study is to evaluate the adherence to DMD in people with multiple sclerosis (PwMS) in Argentina and Ecuador. METHODS: A cross-sectional study was performed. The study was carried out between June 2020 and October 2020, and 303 PwMS treated with DMD were included. Patients undergoing immune reconstitution treatments were excluded. Two definitions of DMD adherence were previously determined. Adherence to MS treatments was assessed using the multiple sclerosis treatment adherence questionnaire (MS-TAQ). The logistic regression model was used to evaluate factors related to adherence, and p < 0.05 was considered significant. RESULT: The mean age at study entry for patients was 40.7 ± 11.2 years, 207 (68.3%) were female, and the mean EDSS score was 2.2 ± 1.9. The overall adherence in our sample was 78.1% (79.7% in Argentina and 76% Ecuador, p = 0.23). Patients using infusion therapies significantly more often belonged to the adherent group (p = 0.042). Sharing decision-making (OR = 3.4, 95% CI: 1.7-6.9, p = 0.01), lower EDSS (OR = 0.8, 95% IC: 0.6-0.9, p = 0.004), and lower treatment duration (OR = 0.8, 95% IC: 0.6-0.9, p = 0.001) were independent predictors of adherence in our multivariate model. CONCLUSION: We found a prevalence of non-adherence similar to that previously reported. Furthermore, new factors associated with lower adherence were identified.

Comparative end-of-life communication and support in hospitalised decedents before and during the COVID-19 pandemic: a retrospective regional cohort study in Ottawa, Canada.

OBJECTIVE: To compare end-of-life in-person family presence, patient-family communication and healthcare team-family communication encounters in hospitalised decedents before and during the COVID-19 pandemic. DESIGN: In a regional multicentre retrospective cohort study, electronic health record data were abstracted for a prepandemic group (pre-COVID) and two intrapandemic (March-August 2020, wave 1) groups, one COVID-19 free (COVID-ve) and one with COVID-19 infection (COVID+ve). Pre-COVID and COVID-ve groups were matched 2:1 (age, sex and care service) with the COVID+ve group. SETTING: One quaternary and two tertiary adult, acute care hospitals in Ottawa, Canada. PARTICIPANTS: Decedents (n=425): COVID+ve (n=85), COVID-ve (n=170) and pre-COVID (n=170). MAIN OUTCOME MEASURES: End-of-life (last 48 hours) in-person family presence and virtual (video) patient-family communication, and end-of-life (last 5 days) virtual team-family communication encounter occurrences were examined using logistic regression with ORs and 95% CIs. End-of-life (last 5 days) rates of in-person and telephone team-family communication encounters were examined using mixed-effects negative binomial models with incidence rate ratios (IRRs) and 95% CIs. RESULTS: End-of-life in-person family presence decreased progressively across pre-COVID (90.6%), COVID-ve (79.4%) and COVID+ve (47.1%) groups: adjusted ORs=0.38 (0.2-0.73) and 0.09 (0.04-0.17) for COVID-ve and COVID+ve groups, respectively. COVID-ve and COVID+ve groups had reduced in-person but increased telephone team-family communication encounters: IRRs=0.76 (0.64-0.9) and 0.61 (0.47-0.79) for in-person, and IRRs=2.6 (2.1-3.3) and 4.8 (3.7-6.1) for telephone communications, respectively. Virtual team-family communication encounters occurred in 17/85 (20%) and 10/170 (5.9%) of the COVID+ve and COVID-ve groups, respectively: adjusted OR=3.68 (1.51-8.95). CONCLUSIONS: In hospitalised COVID-19 pandemic wave 1 decedents, in-person family presence and in-person team-family communication encounters decreased at end of life, particularly in the COVID+ve group; virtual modalities were adopted for communication, and telephone use increased in team-family communication encounters. The implications of these communication changes for the patient, family and healthcare team warrant further study.

¿ Can COVID-19 exacerbate multiple sclerosis symptoms? A case series analysis.

INTRODUCTION: Peripheral inflammation can exacerbate pre-existing lesions in the Central Nervous System (CNS) in the context of neurodegenerative diseases, including Multiple Sclerosis (MS). OBJECTIVE: To analyze the clinical effect of COVID-19 infection, as a generator of peripheral inflammation, in a MS patients group. METHODS: A retrospective analysis of 400 medical records of MS patients from a referral center was carried out. MS patients who presented COVID-19 were surveyed about symptoms exacerbation: type, duration and onset of exacerbation, previous vaccination against COVID-19 and MS severity. Clinical and demographic information from the medical records were included. Descriptive and inferential analysis were performed using the GraphPad Prism V6. RESULTS: 41 patients were included, 61% (n = 25) reported neurological worsening, 9.7% (n = 4) as relapses, and 7.3% (n = 3) required corticosteroids. We found significant differences in the EDSS between patients who exacerbated their MS symptoms and those who did not (p = 0.03). When performing a multivariate regression analysis, we found that EDSS was independently associated with the presence of exacerbations of MS in the context of SARS-CoV2 infection (OR = 2.44, p = 0.022). CONCLUSIONS: This preliminary study suggests that COVID-19 infection could trigger exacerbations of MS symptoms. New studies are needed to elucidate the relationship between COVID-19 and MS.

Clinical and demographic characteristics of male MS patients included in the national registry-RelevarEM. Does sex or phenotype make the difference in the association with poor prognosis?

BACKGROUND: In multiple sclerosis demographics there is a well-known female prevalence and male patients have been less specifically evaluated in clinical studies, though some clinical differences have been reported between sexes. OBJECTIVE: The objective of this study was to assess clinical and demographic differences between male and female patients included in the national Argentine MS Registry-RelevarEM. MATERIAL AND METHODS: This study was observational, retrospective, and was based on the data of 3099 MS patients included as of 04 April 2021. The statistical analysis plan included bivariate analyses with the crude data and also after adjustment for the MS phenotype, further categorized as progressive-onset MS or relapsing-onset MS. In the adjusted analysis, the Mantel-Haenszel odds ratio was compared to the crude odds ratio, to account for the phenotype as a confounder. RESULTS: The data from 1,074 (34.7%) men and 2,025 (65.3%) women with MS diagnosis were analysed. Males presented primary progressive disease two times more often than women (11% and 5%, respectively). In the crude analyses by sex, the presence of exclusively infratentorial lesions in the magnetic resonance imaging studies was more frequent in males than in females, but after adjustment by MS onset phenotype, such difference was only present in males with relapsing-onset MS (p = 0.00006). Similarly, worse Expanded Disability Status Scale scores were confirmed only in men with relapsing-onset disease after phenotype adjustment (p = 0.02). CONCLUSION: We did not find any statistically significant clinical or demographic difference between sexes when the progressive MS phenotype was specifically considered. However, the differences we found between the clinical phenotypes are in line with the literature and highlight the importance of stratifying the analyses by sex and phenotype when designing MS studies.

Accumulative risk of clinical event in high-risk radiologically isolated syndrome in Argentina: data from the nationwide registry RelevarEM.

INTRODUCTION: We aimed to analyze the accumulative risk of MRI and OB factors for evolution from RIS to MS in subjects included in the Argentinean MS registry (NCT03375177). METHODS: RIS subjects were identified according to RIS diagnosis criteria. Subjects were longitudinally followed with clinical and MRI at intervals of 6 months. Time from RIS identification to the first clinical event was estimated using Kaplan-Meier. Multivariable Cox regression models were created to assess the independent predictive value of demographic characteristics, as well as clinical, OB and MRI data on time to the first clinical event. The single and increased risk factor of evolution of RIS was quantified. RESULTS: A total of 88 RIS subjects, mean follow-up time 42 ± 4 months were included. 39 (44.3%) and 23 (26.1%) had a new MRI lesion or a clinical event, respectively, during the follow-up. OB (HR 5.9, 95% CI 1.29-10.1, p = 0.004), infratentorial lesions (HR 3.7, 95% CI 1.09-7.5) and spinal cord lesions (HR 5.3, 95% CI 1.4-8.2, p = 0.01) at RIS identification were independent predictors associated with a subsequent clinical event. The accumulative risk showed that when two of the three factors (OB, infratentorial or spinal cord lesions) were present the HR was 10.4, 95% CI 4.4-22, p < 0.001, and when three factors were present, it was HR 15.6, 95% CI 5.7-28, p < 0.001 for a relapse. CONCLUSION: The presence of three factors significantly increased the risk of clinical event; high-risk subjects should probably be managed by a different approach than those used for individuals without high-risk factors.

Chiasmatic lesions on conventional magnetic resonance imaging during the first event of optic neuritis in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease in a Latin American cohort.

BACKGROUND AND PURPOSE: Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS: We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS: A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group. CONCLUSIONS: Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.

[Atypical clinical manifestations as a form of presentation in multiple sclerosis]. / Manifestaciones clínicas atípicas como forma de presentación de la esclerosis múltiple.

The atypical clinical features in multiple sclerosis (MS) have been rarely reported and suggest the possibility of an alternative diagnosis. The aim was to describe the clinical and demographic characteristics of MS patients who debuted with atypical symptoms and to estimate the sensitivity, specificity and positive predictive value (PPV) for MS diagnosis. A retrospective analysis of clinical records was performed. The following data were recorded: patients with MS diagnosis according to current diagnostic criteria at the time of diagnosis, type of symptom at the onset, time to second relapse, presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and radiological red flags on MRI. A descriptive and inferential analysis was performed using the chi square test, and sensitivity, specificity and PPV were calculated. Six hundred two patients were diagnosed with MS, of which 22 (3.65%) had an atypical clinical presentation. 54.5% were women. The mean age was 29 years (SD ± 11.7). The most common atypical symptom was peripheral facial palsy (27%). The PPV for atypical onset was 6.14%; p < 0.001. Sensitivity and specificity of these symptoms to MS diagnosis were 3.65% and 19%, respectively. In our research, the presence of atypical symptoms at the onset of MS was very low. Other diseases must be excluded, taking into account their low sensitivity, specificity and PPV.

Las manifestaciones clínicas atípicas al inicio de la esclerosis múltiple (EM) son poco frecuentes y sugieren la posibilidad de un diagnóstico alternativo. El objetivo fue describir las características clínicas en la EM con síntomas atípicos al inicio, y estimar la sensibilidad, especificidad y valor predictivo positivo (VPP) para el diagnóstico de EM. Se trata de un análisis retrospectivo de historias clínicas. Se registraron los siguientes datos: pacientes con diagnóstico de EM acorde a los criterios diagnósticos correspondientes, tipo de síntoma de inicio, tiempo hasta la segunda recaída, presencia de bandas oligoclonales en el líquido cefalorraquídeo (LCR) y de banderas rojas radiológicas en la Resonancia Magnética de encéfalo (RMN). Se realizó un análisis descriptivo e inferencial utilizando la prueba de chi cuadrado y se calcularon la sensibilidad, la especificidad y el VPP. Seiscientos dos pacientes tuvieron un diagnóstico final de EM, de los cuales 22 (3.7%) tuvieron una presentación clínica atípica. El 54.5% eran mujeres. La edad promedio fue de 29 años (DE ± 11.7). El síntoma atípico más frecuente fue parálisis facial periférica aislada (6/22). El VPP para el inicio atípico fue de 6.1%; p < 0001. La sensibilidad y especificidad de estos síntomas al diagnóstico de EM fueron del 3.7% y 19%, respectivamente. En nuestra cohorte, demostramos que la presencia de síntomas atípicos como presentación de la EM es poco frecuente. Es mandatorio la exclusión de otras enfermedades, teniendo en cuenta su baja sensibilidad, especificidad y VPP.

Manifestaciones clínicas atípicas como forma de presentación de la esclerosis múltiple / Atypical clinical manifestations as a form of presentation in multiple sclerosis

Resumen Las manifestaciones clínicas atípicas al inicio de la esclerosis múltiple (EM) son poco frecuentes y sugieren la posibilidad de un diagnóstico alternativo. El objetivo fue describir las características clínicas en la EM con síntomas atípicos al inicio, y estimar la sensibilidad, especificidad y valor predictivo posi tivo (VPP) para el diagnóstico de EM. Se trata de un análisis retrospectivo de historias clínicas. Se registraron los siguientes datos: pacientes con diagnóstico de EM acorde a los criterios diagnósticos correspondientes, tipo de síntoma de inicio, tiempo hasta la segunda recaída, presencia de bandas oligoclonales en el líquido cefalorraquídeo (LCR) y de banderas rojas radiológicas en la Resonancia Magnética de encéfalo (RMN). Se realizó un análisis descriptivo e inferencial utilizando la prueba de chi cuadrado y se calcularon la sensibilidad, la especificidad y el VPP. Seiscientos dos pacientes tuvieron un diagnóstico final de EM, de los cuales 22 (3.7%) tuvieron una presentación clínica atípica. El 54.5% eran mujeres. La edad promedio fue de 29 años (DE ± 11.7). El síntoma atípico más frecuente fue parálisis facial periférica aislada (6/22). El VPP para el inicio atípico fue de 6.1%; p < 0001. La sensibilidad y especificidad de estos síntomas al diagnóstico de EM fueron del 3.7% y 19%, respectivamente. En nuestra cohorte, demostramos que la presencia de síntomas atípicos como presentación de la EM es poco frecuente. Es mandatorio la exclusión de otras enfermedades, teniendo en cuenta su baja sensibilidad, especificidad y VPP.

Abstract The atypical clinical features in multiple sclerosis (MS) have been rarely reported and suggest the possibility of an alternative diagnosis. The aim was to describe the clinical and demographic characteristics of MS patients who debuted with atypical symptoms and to estimate the sensitivity, specificity and positive predictive value (PPV) for MS diagnosis. A retrospective analysis of clinical records was performed. The following data were recorded: patients with MS diagnosis according to current diagnostic criteria at the time of diagnosis, type of symptom at the onset, time to second relapse, presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and radiological red flags on MRI. A descriptive and inferential analysis was performed using the chi square test, and sensitivity, specificity and PPV were calculated. Six hundred two patients were diagnosed with MS, of which 22 (3.65%) had an atypical clinical presentation. 54.5% were women. The mean age was 29 years (SD ± 11.7). The most common atypical symptom was peripheral facial palsy (27%). The PPV for atypical onset was 6.14%; p < 0.001. Sensitivity and specificity of these symptoms to MS diagnosis were 3.65% and 19%, respectively. In our research, the presence of atypical symptoms at the onset of MS was very low. Other diseases must be excluded, taking into account their low sensitivity, specificity and PPV.

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

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 RelevarEM (NCT03375177). 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). CONCLUSION: 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 lesions on MRI at clinical presentation all had higher odds of having aMS.

Upper Limb Dexterity in Patients with Multiple Sclerosis: An Important and Underrated Morbidity.

BACKGROUND: Scales to assess disability in multiple sclerosis (MS) rarely provide reliable data on actual global impairment. Upper limb dysfunction is usually overlooked, which has a negative effect on patient well-being. We sought to analyze associations among upper limb dexterity, lower limb speed, and Expanded Disability Status Scale (EDSS) score; the difference in upper limb dexterity between patients with EDSS scores less than 5 and 5 or greater; and the associations that upper limb dexterity, lower limb speed, and EDSS score have with health-related quality of life measurements and depression. METHODS: A total of 140 adults with MS were evaluated using the Nine-Hole Peg Test, Timed 25-Foot Walk test, EDSS, Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire, and Beck Depression Inventory. Thorough descriptive-analytical research was conducted using the Spearman correlation, multiple linear regression, and structural equation modeling. RESULTS: Upper limb dexterity was more closely related to EDSS score than lower limb speed (r = 0.43 vs 0.29, R 2 = 0.38) and was greatest in patients with EDSS scores less than 5 (P < .01). Moreover, upper limb dexterity was negatively associated with EDSS score and the MusiQoL questionnaire (rS = -0.557 to -0.321, P < .05). The correlation that depression has with upper limb dexterity loss was higher than the one it has with lower limb speed (0.098 vs 0.066, t > 1.96). CONCLUSIONS: Upper limb dexterity is associated with global disability, depression, and health-related quality of life. We advocate for the assessment of upper limb dexterity in patients with MS to adopt a better approach to their functional impairment.

Usage trend of oral drugs for multiple sclerosis patients in Argentina.

INTRODUCTION: Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina. METHODS: A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time. RESULT: The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p <0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p<0.01) were independently associated with choice of oDMTs. CONCLUSION: This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina.

Absence of latitudinal gradient in oligoclonal bands prevalence in Argentina.

BACKGROUND: Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient. METHODS: For each province, an average latitude was calculated, and OCB frequency was investigated. Multivariate logistical regression analysis and linear correlation were performed. Statistical analysis was repeated after excluding patients from centers using isoelectric focusing (IEF) in less than 95% of patients (CwIEF<95). RESULTS: We included 2866 patients. OCB where positive in 73.9% of patients. No association or correlation were found between OCB and latitude of residence, even after excluding patients from (CwIEF<95). CONCLUSION: OCB positivity does not follow a latitudinal gradient in Argentina. Also, OCB positivity is lower than described in other world regions.