Measuring the economic burden of neuromyelitis optica spectrum disorder in Colombia.

OBJECTIVE: To assess the economic burden of neuromyelitis optica spectrum disorder (NMOSD) in the Colombian context. METHODS: Analyses were conducted from a societal perspective using the prevalence-based approach. Costs were expressed in 2022 US dollars (1 USD = $3,914.46 COP). Direct medical costs were assessed from a bottom-up approach. Indirect costs included loss of productivity of the patient and their caregivers. The economic burden of NMOSD in Colombia was estimated as the sum of direct and indirect costs. RESULTS: The direct cost of treating a patient with NMOSD was USD$ 8,149.74 per year. When projecting costs nationwide, NMOSD would cost USD$ 7.2 million per year. Of these costs, 53.5% would be attributed to relapses and 34.4% to pharmacological therapy. Indirect costs potentially attributed to NMOSD in Colombia were estimated at USD$ 1.5 million per year per cohort. Of these, 78% are attributable to loss of patient productivity, mainly due to reduced access to the labor market and premature mortality. CONCLUSIONS: The NMOSD has a representative economic burden at the patient level, with direct costs, particularly related to relapses and medicines, being the main component of total costs. These findings are useful evidence that requires attention from public policymakers in Colombia.

Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Therapeutic Plasma Exchange as a Treatment for Autoimmune Neurological Disease.

INTRODUCTION: Therapeutic plasma exchange (TPE) is commonly used as treatment of certain autoimmune neurological diseases (ANDs), and its main objective is the removal of pathogenic autoantibodies. Our aim was to describe the clinical profile and the experience with the usage of TPE in patients with ANDs at our institution. METHODS: This is an observational retrospective study, including medical records of patients with diagnosis of ANDs who received TPE, between 2011 and 2018. Characteristics of TPE, such as number of cycles, type of replacement solution, and adverse effects, were evaluated. The modified Rankin Scale (mRS) was applied to measure the clinical response after the therapy. RESULTS: 187 patients were included with the following diagnoses: myasthenia gravis (MG), n = 70 (37%); Guillain-Barré syndrome (GBS), n = 53 (28.3%), neuromyelitis optica spectrum disorders (NMOSD), n = 35 (18.7%); chronic inflammatory demyelinating polyneuropathy (CIDP), n = 23 (12.2%); and autoimmune encephalitis (AE), n = 6 (3.2%). The most used types of replacement solution were albumin (n = 131, 70%) and succinylated gelatin (n = 45, 24%). All patients received a median of five cycles (IQR 5-5). Hypotension and hydroelectrolytic disorders were the main complications. After TPE, 99 patients (52.9%) showed improvement in the mRS scores and a statistical significance (p < 0.05) was seen between the admission score and after TPE for every diagnosis except for CIDP. CONCLUSION: TPE has an adequate safety profile, and improvement in functionality in treated patients reflects its effectiveness.

Case Report: Rapid Eye Movement Sleep Behavior Disorder as the First Manifestation of Multiple Sclerosis: A Case Report and Literature Review.

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by brief recurrent episodes of loss of muscle atonia during rapid eye movement sleep, with enacted dreams that cause sleep disruption. Patients with multiple sclerosis (MS) have an increased risk compared with the general population to be affected by a sleep disturbance, including RBD. Patients affected, however, uncommonly can present RBD as the first clinical manifestation of MS without other neurologic deficits. These clinical presentations have usually been attributed to inflammatory lesions in the pedunculopontine nuclei, located in the dorsal pons. We present a case of RBD in a 38-year-old woman who was later diagnosed as having MS due to imaging findings and development of focal neurologic deficits. MS should be considered among the differential diagnoses in patients who present with symptoms of RBD, particularly if they are young and female.

Cerebral toxoplasmosis in an MS patient receiving Fingolimod.

Multiple Sclerosis (MS) is an autoimmune disease in which lymphocytes target putative myelin antigens in the CNS, causing inflammation and neurodegeneration. Fingolimod (FTY720) is an immunosuppressive drug used as a second line therapy for relapsing forms of MS due to its safety profile and good response to treatment. Despite its safety, there are still concerns about the possibility of Fingolimod being linked to the development of opportunistic infections like disseminated varicella zoster infections and herpes simplex encephalitis. In this case report, we describe one patient with past medical history of MS in current treatment with Fingolimod for the last year which presents herself with hemiparesis, fever and fatigue. The initial MRI showed multiple demyelinating-like lesions that could have corresponded to the tumefactive form of MS relapse. The blood work up revealed leukopenia with lymphopenia and a CD4+ count of 200 cell/mm3. Treatment for acute relapse was initiated with little to no response. Further examination was carried by the clinicians, a lumbar puncture was performed and it showed pleocytosis with increased protein levels. Later, several serologic studies were performed and both IgM and IgG antibodies for Toxoplasma were positive. Diagnosis of cerebral toxoplasmosis was made and there was no evidence of HIV infection or other causes of secondary immunodeficiency in this patient, except the use of fingolimod. Evidence of decreased levels of CD4+ due to Fingolimod use is concerning. The risk of opportunistic infections in these patients must be considered in order to start or continue therapy with these agents. Further studies are needed to determine the percentage of the population at risk of immunosuppression and its long-term consequences as well as new actions to prevent infections.

Enfoque diagnóstico molecular utilizando secuenciación exómica en las distrofias musculares cintura-cadera / Molecular diagnosis approach through the use of whole exome sequencing in limb-girdle muscular dystrophies

Antecedentes. La distrofia muscular cintura-cadera tipo 1B es una enfermedad con herencia autosómica dominante y secundaria a una mutación en el gen LMNA. Esta enfermedad se caracteriza por su afectación a nivel neuromuscular y cardiaco. Objetivo. Realizar diagnóstico clínico y confirmatorio molecular en una paciente con debilidad muscular proximal y sintomatología cardíaca a través de secuenciación exómica. Materiales y métodos. Se presenta el caso de una paciente de 57 años de edad con cuadro de debilidad muscular proximal progresiva principalmente en extremidades y posterior afectación cardíaca; adicionalmente, la paciente tiene múltiples familiares con la misma sintomatología. Se realizó estudio de secuenciación exómica con confirmación, por método de Sanger, de la mutación hallada y posteriormente el análisis bioinformático de esta. Resultados. La detección de la mutación R377L en el gen LMNA por secuenciación exómica con confirmación por Sanger, junto con la sintomatología clínica de la paciente y el análisis bioinformático de la mutación hallada, permitió realizar diagnóstico confirmatorio de distrofia muscular cintura-cadera tipo 1B. Conclusión. Es difícil realizar un diagnóstico clínico debido a la heterogeneidad genética del fenotipo de distrofias musculares cintura-cadera. La aproximación diagnóstica es compleja y requiere clasificar las distrofias musculares según el patrón de afectación y el patrón de herencia de la enfermedad. Adicionalmente, debido a los múltiples genes que pueden generar clínica semejante a las diferentes distrofias musculares, se recomienda realizar secuenciación exómica solicitando especial énfasis en los genes candidatos de distrofias musculares cintura-cadera.

Background. Limb-girdle muscular dystrophy type 1B has a dominant autosomal inheritance pattern and is caused by a mutation in the LMNA gene. This disease has a major neuromuscular and cardiac compromise; furthermore, it belongs to the limb-girdle muscular dystrophies. Objective. To make a clinical and molecular confirmatory diagnosis in a patient with proximal muscular weakness and cardiac symptoms using whole exome sequencing. Materials and Methods. This is the case of a 57 year old patient with a slowly progressive proximal muscular weakness and cardiac compromise; furthermore, the patient has many relatives with the same clinical history. Whole exome sequencing with Sanger confirmation and bioinformatics analysis was performed on the found mutation. Results. The detection of mutation R377L in the LMNA gen by whole exome sequencing with Sanger confirmation, the bioinformatic analysis of the mutation and the symptoms exhibited by the patient allowed the confirmatory diagnosis of limb-girdle muscular dystrophy type 1b. Conclusion. Due to genetic heterogeneity in the phenotype of limb-girdle muscular dystrophies it is difficult to make a clinical diagnosis. The diagnostic approach is complex and requires classification of the muscular dystrophies according to the pattern of muscular weakness and to identify the disease inheritance pattern. Additionally, due to the multiple genes that can generate similar symptoms in the different muscular dystrophies, the authors recommend the use of whole exome sequencing with a special emphasis on the candidate genes for limb-girdle muscular dystrophies.

Mutation in the Prothrombin Gene G20210A as a Cause of Cerebral Venous Thrombosis.

Introduction. Cerebral venous sinus thrombosis (CVST) is a rare form of cerebrovascular disease, which may manifest clinically by a wide variety of signs and symptoms. It has been associated with multiple risk factors including genetic or acquired blood disorders, infections, and trauma. Case Report. Man of 17 years who presented with 10 days of intense global headache with nausea and vomiting and subsequent onset of mild hemiparesis and hypoesthesia in right hemibody. Studies show venous thrombosis of the superior longitudinal sinus. It was identified a gene mutation in prothrombin G20210A as a probable cause of the thrombosis. Conclusions. Substitution of guanine for adenine at nucleotide 20210 in the coding region of the prothrombin gene is the second most common primary thrombophilia. Multiple cases of CVST have been associated with this mutation. In the presence of CVST must be considered the primary studies for thrombophilia gene mutations, including prothrombin G20210A.

Prevalence of multiple sclerosis in Bogotá, Colombia.

Among Latin American countries, Colombia is considered a low-risk area for multiple sclerosis (MS) and no studies on MS prevalence have been conducted in any of the country's large urban settings. To fill this gap and assess the prevalence of MS in Bogotá as of December 31, 2002, this study reviewed the clinical records of patients diagnosed with MS in most Bogotá hospitals. This review produced a sample of 296 patients with an MS diagnosis whose reliability was verified by a neurologist with expertise in MS. The total prevalence rate identified for December 2002 was 4.41/100,000 inhabitants (95% CI 3.9-4.9), including a rate of 5.98/100,000 (95% CI 5.2-6.8) for women and 2.71/100,000 (95% CI 2.2-3.3) for men (differences measured at p < 0.001). The prevalence estimates for Bogotá, confirm the city's status as a low-risk area for MS.