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PURPOSE: Intramedullary spinal cord tumors are an uncommon pathology in adults and children. Most descriptive studies of intramedullary spinal cord tumors have not focused on a possible association with future brain lesions. To the best of our knowledge, few reports describe this potential relationship. This is one of the most extensive case series of secondary brain lesions of intramedullary spinal cord tumors in the pediatric population. METHODS: Retrospective chart review was performed on pediatric patients (21 years old and younger) who underwent resection of an intramedullary spinal cord tumor at two tertiary care hospitals from 2001 to 2020. Patients previously treated or diagnosed with spinal cord tumor, and subsequent development of intracranial manifestation of the same or different tumor, were included. Data regarding epidemiology, surgical intervention, and clinical and follow-up course were gathered. Data analysis was performed according to a standardized clinical protocol with a literature review. RESULT: More than 500 patients underwent intradural spinal tumor resection surgeries at participating hospitals from 2001 to 2020. After excluding adult patients (older than 21 years old) and those with extramedullary lesions, 103 pediatric patients were identified who underwent resection of an intramedullary spinal cord tumor. Four underwent resection of an intermedullary tumor and later in their follow-up course developed a secondary intracranial neoplasm. In every case, the secondary neoplasm had the same pathology as the intramedullary tumor. Three of the patients had tumors at the cervico-thoracic junction, and one patient had a high cervical tumor. These patients had a negative primary workup for any metastatic disease at the time of the presentation or diagnosis. Complete and near complete resection was performed in three patients and subtotal in one patient. CONCLUSION: Secondary brain tumors disseminated after initial spinal cord tumor are extremely rare. This study aims to allow specialists to better understand these pathologies and treat these rare tumors with more certainty and better expectations of unusual associated lesions and conditions.
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Neoplasias Encefálicas , Neoplasias da Medula Espinal , Humanos , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/epidemiologia , Criança , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/epidemiologia , Adolescente , Pré-Escolar , LactenteRESUMO
The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome ("global" ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles ("local" ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.
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Doença de Alzheimer/genética , Apolipoproteína E4/genética , Negro ou Afro-Americano/genética , Hispânico ou Latino/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Variação Genética , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Masculino , Porto Rico/etnologia , Fatores de RiscoRESUMO
BACKGROUND: Multiple sclerosis (MS) affects millions of people worldwide. The estimates for MS incidence are difficult to obtain but are important for understanding MS etiology, developing prevention strategies, and service planning. This study is aimed at estimating the 2014 incidence of MS in Puerto Rico (PR). METHODS: The PR MS Foundation's registry was used as the data source. Neurologists, specialty pharmacies, MRI centers, health insurance companies, and the PR Department of Health identified MS cases missed by the registry. MS patients were 18 years and older and met the 2010 revised McDonald criteria. Age-standardized MS incidence rates and their corresponding 95% CIs were computed. RESULTS: A total of 144 new MS cases were diagnosed in 2014. The age-standardized MS incidence rate was 5.1/100,000 (95% CI 4.3-5.9). The incidence rate was 7.1/100,000 (95% CI 5.7-8.5) for females and 2.9/100,000 (95% CI 2.0-3.8) for males. MS cases were mostly females (72.9%) with a mean age of 41.0 years (±1.0). CONCLUSION: According to the country estimates, PR has a higher MS incidence than other Caribbean and Latin American countries, but a lower incidence compared to countries at higher latitudes. Our findings provide insights into the MS etiology in the Hispanic population that require additional research.
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Esclerose Múltipla/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Porto Rico/epidemiologia , Sistema de RegistrosRESUMO
BACKGROUND: The incidence of multiple sclerosis (MS) has been increasing worldwide over the past decades. However, this upward trend has not been examined at the country level in Latin America and the Caribbean (LAC). The aims of this study are to examine trends of MS incidence over 4 years and to provide age- and gender-standardized incidence rate estimates for a Caribbean island. METHODS: Data from the Puerto Rico (PR) MS Foundation's registry was used to identify all newly diagnosed MS cases between 2013 and 2016. MS patients were 18 years and older and met the 2010 revised McDonald criteria. Age- and gender-standardized incidence rates were estimated. RESULTS: A total of 583 new MS cases were diagnosed in PR from 2013 to 2016. The age- and gender-standardized MS incidence rate for PR increased from 6.1/100,000 in 2013 to 6.7/100,000 in 2016. The annual age-standardized MS incidence rates for females rose from 8.4/100,000 in 2013 to 9.8/100,000 in 2016 and were higher than males, which remained around 3.7/100,000. CONCLUSION: Incidence estimates for PR were higher than other LAC countries but consistent with MS increases in other world regions. Our findings tend to rule out several prior potential environmental explanations for high MS incidence rates.
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Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Porto Rico/epidemiologia , Sistema de Registros , Adulto JovemRESUMO
Neurosurgical management of basilar invagination (BI) has traditionally been aimed at direct cervicomedullary decompression through transoral dens resection or suboccipital decompression with supplemental instrumented fixation. Dr. Goel introduced chronic atlantoaxial dislocation (AAD) as the etiology in most cases of BI and described a technique for distracting the C1-C2 joint with interfacet spacers to achieve reduction and anatomic realignment. We present our modification to Goel's surgical technique, in which we utilize anterior cervical discectomy (ACD) cages as C1-C2 interfacet implants. A young adult male presented to our institution with BI, cervicomedullary compression, occipitalization of C1, and Chiari 1 malformation. There was AAD of C1 over the C2 lateral masses. This reduced some with preoperative traction. He underwent successful C1-C2 interfacet joint reduction and arthrodesis with anterior cervical discectomy (ACD) cages and concomittant occiput to C2 instrumented fusion. BI can be effectively treated through reduction of AAD and by utilizing ACD cages as interfacet spacers.
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Articulação Atlantoaxial , Luxações Articulares , Adulto Jovem , Masculino , Humanos , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Descompressão Cirúrgica/métodosRESUMO
Multiple Sclerosis (MS) is a complex disease where genetic and environmental factors have been implicated. The onset of symptoms occurs in individuals from twenty to fifty years of age, producing a progressive impairment of motor, sensory and cognitive functions. MS is more frequent in females than in males with a ratio of 4:1. The prevalence of the MS varies among ethnics groups such as Europeans, Africans and Caucasians. The estimated prevalence of MS in Puerto Rico is 42 for each 100,000 habitants, which is more than the prevalence reported for Central America and the Caribbean. In spite of this prevalence, the genetic component of MS has not been explored in order to know the alleles' expression of Puerto Rican MS patients and compare it with the allele expression in other ethnic groups. Thirty-five patients and 31 control subjects were genotyped. The allele frequencies expressed in this sample were similar to those expressed for Puerto Ricans in the National Marrow Donor Program Registry (n = 3,149). The most prevalent alleles for MS patients were HLA-DRB1*01 and *03. HLA-DQB1*04 was the most frequent in the control group and HLA-A*30, in MS patients. These findings are in agreement with published data. HLA-DQB1*04 was a marginal protector in this sample and this role has not been described before. The accuracy of the results is limited due to the sample size. After performing a statistical power analysis it showed that by increasing the sample the values would be significant.
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Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Adulto , Alelos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Porto RicoRESUMO
BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab. METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined by local laboratory severe acute respiratory syndrome coronavirus-2 qualitative immunoglobulin G assays. Assay No. 1 was ≥14 days after the second or third vaccine dose. Assay No. 2 was 90 days thereafter. RESULTS: Of the 26 patients enrolled (median [range] age: 42 [27-54] years; median [range] ofatumumab treatment duration: 237 [50-364] days), HIR was achieved by 53.9% (14/26; 95% CI: 33.4 - 73.4%) at Assay No. 1 and 50.0% (13/26; 95% CI: 29.9 - 70.1%) at Assay No. 2. Patients who received 3 vaccine doses had higher HIR rates (Assay No. 1: 70.0% [7/10]; Assay No. 2: 77.8% [7/9]) than those who received 2 doses (Assay No. 1: 46.7% [7/15]; Assay No. 2: 42.9% [6/14]). Of patients aged <40 years without previous anti-CD20 therapy, HIR was achieved by 90.0% (9/10) at Assay No. 1 and 75.0% (6/8) at Assay No. 2. No serious adverse events were reported. CONCLUSION: Patients with RMS treated with ofatumumab can mount HIRs following COVID-19 vaccination. A plain language summary, infographic and a short video summarizing the key results are provided in supplementary material. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04847596 (https://clinicaltrials.gov/ct2/show/NCT04847596).
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COVID-19 , Esclerose Múltipla , Humanos , Adulto , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunidade Humoral , Projetos Piloto , Estudos Prospectivos , Recidiva , Vacinas de mRNA , Anticorpos AntiviraisRESUMO
INTRODUCTION: Multiple sclerosis (MS) clinical trials have included low numbers of patients from racial and ethnic minority populations; therefore, it is uncertain whether differences exist in response to disease-modifying therapies. We evaluated the real-world safety and effectiveness of dimethyl fumarate (DMF) treatment over 5 years in four patient cohorts: Black, non-Black, Hispanic, and non-Hispanic people with relapsing-remitting MS. METHODS: ESTEEM is an ongoing, 5-year, multinational, prospective study evaluating the long-term safety and effectiveness of DMF in people with MS. The analysis included patients newly prescribed DMF in routine practice at 393 sites globally. RESULTS: Overall, 5251 patients were analyzed (220 Black, 5031 non-Black; 105 Hispanic, 5146 non-Hispanic). Median (min-max) months of follow-up was 32 (0-72) for Black, 29 (1-77) for Hispanic, and 41 (0-85) for both the non-Black and non-Hispanic populations. In total, 39 (18%) Black and 29 (28%) Hispanic patients reported adverse events leading to treatment discontinuation versus 1126 (22%) non-Black and 1136 (22%) non-Hispanic patients; gastrointestinal disorders were the most common in all subgroups. Median lymphocyte counts decreased by 37% in Black, 40% in non-Black, 10% in Hispanic, and 39% in non-Hispanic patients in the first year, then remained stable and above the lower limit of normal in most patients. Annualized relapse rates (ARRs) (95% confidence intervals) up to 5 years were 0.054 (0.038-0.078) for Black, 0.077 (0.072-0.081) for non-Black, 0.069 (0.043-0.112) for Hispanic, and 0.076 (0.072-0.081) for non-Hispanic populations, representing reductions of 91-92% compared with ARR 12 months before study entry (all p < 0.0001). CONCLUSION: The safety profile of DMF in these subgroups was consistent with the overall ESTEEM population. Relapse rates remained low in Black and Hispanic patients, and consistent with non-Black and non-Hispanic patients. These data demonstrate a comparable real-world treatment benefit of DMF in Black and Hispanic patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02047097.
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This article review the results of a study conducted by the Puerto Rico Multiple Sclerosis Foundation. It presents the results of the first continuous patient registry of the Puerto Rico Multiple Sclerosis (MS) Foundation in the Island between the years 2003 and 2008. It describes the profile of patients with MS and the estimated prevalence. Based on the database of the registry, the estimated prevalence at the present time is estimated to be 52 of 100,000. This population-based study analyzed data of 698 surveyed individuals diagnosed with MS. This study examines demographic factors (age distribution, gender and age at onset), other MS related variables such as the most common symptoms at the onset and after the onset of MS, psychological manifestations, family history, most common treatments, comorbid medical conditions, childhood diseases, use of assistive equipment and patients needs. MS is a chronic demyelinating disease affecting the Central Nervous System, typically manifesting itself in patients between the ages of 30 and 40 years old, causing considerable disability in a significant proportion of afflicted individuals. To date, there has only been one study conducted on the condition of the disease in Puerto Rico.
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Esclerose Múltipla/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Porto Rico/epidemiologia , Estudos RetrospectivosRESUMO
A link between intractable hiccups, as the initial symptom, and a possible neuromyelitis optica spectrum disorder (NMOSD) diagnosis is confusing but vital and may not be made by health care providers (HCPs) if they are not aware of the 2015 NMOSD criteria. Early diagnosis and adequate treatment are essential to prevent disease progression. We report the case of a 46-year-old Puerto Rican female who presented intractable hiccups when she was 31 (in 2004). Almost 15 years passed since the initial symptom, and after two severe relapses, she received a formal NMOSD diagnosis in March 2019. Treatment started with rituximab 1000 mg IV in April 2019. However, a lack of response to treatment led to a switch to eculizumab therapy in August 2019. The patient had cervical and brain magnetic resonance imaging (MRI) conducted in June 2020, which depicted a remarkable decrease in swelling and hyperintensity within the cervical spinal cord with no enhancing lesions when compared with the first MRI from February 2019. In addition, the patient suffered no new relapses, an improvement regarding disability, and a reduction of the cervical spinal cord lesion size. Nonetheless, this substantial decrease does not occur on all NMOSD patients, but more awareness of the disease is needed, especially in Puerto Rico. This case illustrates the efficacy of eculizumab therapy and the importance of differentiating the clinical, histopathological, and neuroimaging characteristics that separate demyelinating autoimmune inflammatory disorders, such as NMOSD and multiple sclerosis (MS).
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BACKGROUND: Previous studies have demonstrated higher multiple sclerosis (MS) incidence and prevalence in Puerto Rico (PR) than in other Caribbean and Latin American countries. Our objectives are to update the epidemiologic trends in MS incidence and prevalence rates for PR from 2017 through 2020 and compare them to prior rate data from 2013 to 2016. METHODS: We used the Puerto Rico MS Foundation's registry (PRMS Registry) data to identify all newly diagnosed MS cases between January 2017 and December 2020. The study population included 568 MS patients, 406 women and 162 men living in PR. All individuals were 18 years and older and met the 2017 revised McDonald criteria for MS diagnosis. In addition, age- and sex-standardized incidence rates were estimated. RESULTS: A total of 568 new MS cases were diagnosed in Puerto Rico between 2017 and 2020. The 2020 MS cumulative prevalence for Puerto Rico was 95.3/100,000 (95% CI: 91.6, 99.1), higher than previously reported. The age- and sex-standardized MS incidence rate for Puerto Rico decreased from 6.5/100,000 (2017) to 6.3/100,000 (2020). The annual age-standardized MS incidence rates declined for females: from 9.5/100,000 (2017) to 8.2/100,000 (2020) but increased for males from 3.6/100,000 to 4.6/100,000 during the same period. CONCLUSION: These incidence and prevalence rates are among the highest reported among Caribbean and Latin American countries. A peak in the age- and sex-standardized MS incidence rate was observed after hurricane María (2018) and a decline during the first year of the COVID-19 pandemic (2020). Further investigation is needed to determine whether there was a causal relationship between the fluctuations observed and those natural events.
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COVID-19 , Esclerose Múltipla , Masculino , Humanos , Feminino , Porto Rico/epidemiologia , Esclerose Múltipla/epidemiologia , Pandemias , COVID-19/epidemiologia , IncidênciaRESUMO
The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.
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Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade , Esclerose Múltipla , Humanos , Alelos , Frequência do Gene , Haplótipos , Cadeias HLA-DRB1/genética , Desequilíbrio de Ligação , Complexo Principal de Histocompatibilidade/genética , Esclerose Múltipla/etnologia , Esclerose Múltipla/genética , Risco , População Europeia/genética , População Africana/genéticaRESUMO
BACKGROUND: Health communication tools like film are capable of reducing health disparities and could be effective in addressing negative illness perceptions of MS in Hispanics/Latinx. OBJECTIVE: To test the feasibility of using a culturally appropriate short narrative film to examine illness perceptions overtime and attitudes in Hispanics/Latinx affected with MS. METHODS: Participants were assigned to view a short narrative film (n = 130) or not (n = 106). The Brief Illness Perception Questionnaire (BIPQ) was used to examine illness perceptions at baseline, one and three months. Focus groups were conducted at 6 months. Measures of sociocultural integration were obtained. Individual group BIPQ domains were evaluated over time using paired sample t-test. Multivariate linear regression was used to examine predictors of BIPQ change. RESULTS: A more positive perception of treatment (p < 0.0001) and understanding (p = 0.0003) were seen at 3 months for those exposed to film. Focus groups were effective in highlighting that the perceived disease prognosis, family support and awareness of MS contributes to attitudes. Exposure to film was found to be the strongest predictor (Beta:6.31, p = 0.01) of BIPQ change at three months. CONCLUSION: Our results provide support that a short narrative film of MS in Hispanics/Latinx is a feasible intervention to change perceptions of MS to a more positive view.
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The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.
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Doença de Alzheimer/genética , Cromossomos Humanos Par 9/genética , Ligação Genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Proteína C9orf72/genética , Hispânico ou Latino/genética , Humanos , Proteínas do Tecido Nervoso/genética , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Alemtuzumab efficacy and safety were established in phase 3 randomized trials. We characterize vital signs during and after the first alemtuzumab infusion course. METHODS: Patients with relapsing-remitting multiple sclerosis commercially prescribed alemtuzumab 12 mg/day on 5 consecutive days (initial course) were enrolled in this prospective, observational study. Preinfusion medications included methylprednisolone, antihistamine, and antipyretics. Primary end point: change from precourse baseline in vital signs during and 2 hours after each alemtuzumab infusion. Secondary end points: infusion duration and serious adverse events (AEs) starting within 24 hours and within 7 days after infusion (AEs collected up to 15 days after treatment). Potentially clinically significant vital sign abnormalities were based on predefined thresholds from literature review. RESULTS: In the 304 patients treated, minimal increases in mean systolic (≤8 mm Hg) and diastolic (≤3 mm Hg) blood pressures from precourse baseline were observed on infusion days 3 to 5. An increase in mean heart rate (20 beats per minute) during the first infusion day normalized by day 2, and smaller increases (5 beats per minute) occurred during subsequent infusions. Serious AEs occurred in two patients (0.7%) during or within 24 hours after infusion and in three patients (1.0%) within 7 days. Mean/median infusion duration was 4 hours. Vital sign abnormalities with potential clinical significance occurred in 62.5% of patients. CONCLUSIONS: Although most patients had potentially clinically significant vital sign abnormalities, mean changes from baseline during and after infusion of the first alemtuzumab course were clinically insignificant. No new safety signals were detected.
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INTRODUCTION: Compared with the non-Hispanic/non-Latino population, Hispanic/Latino patients with multiple sclerosis (MS) are reported to exhibit greater disease severity. Geographical location and genetics play a role in differences observed across Hispanic/Latino subpopulations. We evaluated real-world safety and effectiveness of dimethyl fumarate (DMF) on MS disease activity in Hispanic/Latino patients. METHODS: ESTEEM is an ongoing, 5-year, multinational, prospective study evaluating long-term safety and effectiveness of DMF in patients with MS. This interim analysis included patients newly prescribed DMF in routine practice at 394 sites globally. RESULTS: Overall, 4986 non-Hispanic/non-Latino and 98 Hispanic/Latino patients were analyzed; median (range) follow-up was 18 (2-37) months. Unadjusted annualized relapse rates (ARRs) for 12 months before DMF initiation versus 36 months post DMF initiation, respectively, were: non-Hispanic/non-Latino patients, 0.82 (95% CI 0.80-0.84) versus 0.10 (95% CI 0.09-0.10), 88% lower ARR (P < 0.0001); Hispanic/Latino patients, 0.80 (95% CI 0.65-1.00) versus 0.09 (95% CI 0.06-0.14), 89% lower ARR (P < 0.0001). In total, 28 (29%) Hispanic/Latino patients reported adverse events leading to treatment discontinuation; gastrointestinal (GI) disorders (n = 10, 10%) were the most common, consistent with the non-Hispanic/non-Latino population (8%). Median lymphocyte counts decreased by approximately 24% in the first year (vs 36% decrease in non-Hispanic/non-Latino patients) then remained stable and above the lower limit of normal in most patients. CONCLUSIONS: Relapse rates remained low in Hispanic/Latino patients, consistent with non-Hispanic/non-Latino patients. The safety profile of DMF in Hispanic/Latino patients was consistent with safety findings from the non-Hispanic/non-Latino ESTEEM population, demonstrating the real-world treatment benefit of DMF in the Hispanic/Latino patient cohort.
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BACKGROUND: There are limited data on multiple sclerosis (MS) patients in underserved groups, including Puerto Rico. In this study, we analyzed the characteristic of MS symptoms and number of relapses in Puerto Rican patients. We then compare these characteristics with MS patients from the US. The number of MS relapses is highly correlated with the treatment onset and adherence. Patients in Puerto Rico have been experiencing lengthy treatment delay. We will discuss the possible causes of such delay and its impact on MS prognosis. METHODS: This retrospective cohort study consisted of the evaluation of 325 medical records from MS patients attending the Caribbean Neurological Center from 2014 to 2019. We gathered symptoms and comorbidities data as binary objects. The treatment delay was calculated based on the mean value of days between diagnosis and treatment onset for these groups of patients. RESULTS: We found that on average, the treatment delay for MS patients in Puerto Rico (PR) to receive their medication was 120 days. The most common MS subtype was relapsing-remitting 72.8%, with a mean of 1.684 relapses per year. Initial symptoms were sensory 54%, visual 33.1%, motor 28.8%, coordination 23.2%, fatigue 9.7%, memory 7.3%, depression 6.5%, urinary 4.9%, gastrointestinal 2.4%, and sexual dysfunction 1.6%. The most common comorbidities were hypertension 18.4%, asthma 13.6%, and thyroid disease 12.8%. When we compared the comorbidities between the two populations, immune thrombocytopenia had the highest percent change with the value of almost 200% (0.001% of US patient vs. 0.8% of Puerto Rican MS patients). CONCLUSION: Patients from Puerto Rico had a 33% higher relapse rate compared to the one reported for MS patients in the US. This higher rate may be related to the long delay in receiving their medications. They also had a higher rate of complex comorbidities such as immune thrombocytopenia or thyroid disease. Our findings provide a proof of concept that delay in receiving medications can increase the number of relapses and complex comorbidities among MS patients.
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INTRODUCTION: Multiple sclerosis (MS) patients of African descent have increased risk for disease progression and may be less responsive to disease-modifying therapy. METHODS: Patients in the CARE-MS studies received alemtuzumab 12 mg/day [initial alemtuzumab treatment (IAT); baseline: 5 days; 12 months later: 3 days] or subcutaneous interferon beta-1a (SC IFNB-1a) 3 ×/week. Core study outcomes were compared between treatment groups. In the extension study CAMMS03409, SC IFNB-1a-treated patients switched to alemtuzumab [delayed alemtuzumab treatment (DAT)]. Data from IAT and DAT arms were pooled to assess outcomes through 6 years post alemtuzumab initiation; IAT patients had an additional 2 years of follow-up in TOPAZ. RESULTS: Of 1200 CARE-MS patients, 43 (4%) were of African descent (35 IAT; 8 DAT) and received alemtuzumab in the 2-year core and/or 6-year extension; 29 (67%) remained on study at the time of analysis (24 IAT patients completed year 8 post alemtuzumab; 5 DAT patients completed year 6 post alemtuzumab). In year 2, annualized relapse rate (ARR; 0.09 versus 0.42), percentage of patients with improved Expanded Disability Status Scale (EDSS; 18% versus 11%), 6-month confirmed disability improvement (CDI; 28% versus 13%), no evidence of disease activity (55% versus 13%), and cumulative brain volume loss (BVL; - 0.55% versus - 1.32%) favored alemtuzumab versus SC IFNB-1a. Alemtuzumab remained efficacious at year 6 (pooled IAT/DAT) and at year 8 (IAT only) post alemtuzumab (ARR: 0.15 and 0.30; improved EDSS: 17% and 25%; CDI: 47% and 55%; BVL: - 1.14% and - 0.70%, respectively). No safety signals were unique to this population. CONCLUSIONS: Alemtuzumab was efficacious in a small cohort of relapsing-remitting MS patients of African descent over 8 years. Safety was consistent with the overall CARE-MS population, although the small sample size may have prevented the detection of known low-frequency adverse events. CLINICALTRIALS. GOV REGISTRATION NUMBERS: CARE-MS I, II, extension, TOPAZ: NCT00530348, NCT00548405, NCT00930553, NCT02255656. FUNDING: Sanofi (Cambridge, MA, USA) and Bayer HealthCare Pharmaceuticals (Leverkusen, Germany).
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INTRODUCTION: Puerto Ricans, the second largest Latino group in the continental US, are underrepresented in genomic studies of Alzheimer disease (AD). To increase representation of this group in genomic studies of AD, we developed a multisource ascertainment approach to enroll AD patients, and their family members living in Puerto Rico (PR) as part of the Alzheimer's Disease Sequencing Project (ADSP), an international effort to advance broader personalized/precision medicine initiatives for AD across all populations. METHODS: The Puerto Rico Alzheimer Disease Initiative (PRADI) multisource ascertainment approach was developed to recruit and enroll Puerto Rican adults aged 50 years and older for a genetic research study of AD, including individuals with cognitive decline (AD, mild cognitive impairment), their similarly, aged family members, and cognitively healthy unrelated individuals age 50 and up. Emphasizing identification and relationship building with key stakeholders, we conducted ascertainment across the island. In addition to reporting on PRADI ascertainment, we detail admixture analysis for our cohort by region, group differences in age of onset, cognitive level by region, and ascertainment source. RESULTS: We report on 674 individuals who met standard eligibility criteria [282 AD-affected participants (42% of the sample), 115 individuals with mild cognitive impairment (MCI) (17% of the sample), and 277 cognitively healthy individuals (41% of the sample)]. There are 43 possible multiplex families (10 families with 4 or more AD-affected members and 3 families with 3 AD-affected members). Most individuals in our cohort were ascertained from the Metro, Bayamón, and Caguas health regions. Across health regions, we found differences in ancestral backgrounds, and select clinical traits. DISCUSSION: The multisource ascertainment approach used in the PRADI study highlights the importance of enlisting a broad range of community resources and providers. Preliminary results provide important information about our cohort that will be useful as we move forward with ascertainment. We expect that results from the PRADI study will lead to a better understanding of genetic risk for AD among this population.
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Neuromyelitis optica (NMO) is an immune-mediated inflammatory disorder of the central nervous system. It is characterized by concurrent inflammation and demyelination of the optic nerve (optic neuritis [ON]) and the spinal cord (myelitis). Multiple studies show variations in prevalence, clinical, and demographic features of NMO among different populations. In addition, ethnicity and race are known as important factors on disease phenotype and clinical outcomes. There are little data on information about NMO patients in underserved groups, including Puerto Rico (PR). In this research, we will provide a comprehensive overview of all aspects of NMO, including epidemiology, environmental risk factors, genetic factors, molecular mechanism, symptoms, comorbidities and clinical differentiation, diagnosis, treatment, its management, and prognosis. We will also evaluate the demographic features and clinical phenotype of NMO patients in PR. This will provide a better understanding of NMO and establish a basis of knowledge that can be used to improve care. Furthermore, this type of population-based study can distinguish the clinical features variation among NMO patients and will provide insight into the potential mechanisms that cause these variations.