[Early Clinical Diagnosis of Anti-NMDA Receptor Encephalitis: Case Series and Literature Review]. / Diagnóstico clínico temprano de la Encefalitis Anti-Receptor NMDA: Serie de casos y revisión bibliográfica.

Autoimmune encephalitis refers to a group of pathologies described in the last two decades, characterized by neuropsychiatric symptoms of subacute presentation, mediated by antibodies directed against neuronal membrane proteins. Within this group, encephalitis mediated by antibodies against the NMDA receptor of glutamate is a particular clinical entity, given that its expression is dominated by psychiatric symptoms that usually occur at the onset of the disease. In this paper we describe five cases of NMDA encephalitis in adult patients followed up in the last four years in a public hospital in the City of Buenos Aires, Argentina. We also include a review of the current literature. We emphasize the clinical description of the psychiatric symptoms of presentation, since these lead to the patient's first contact with the health system. Given the difficulty in our environment to implement the determination of autoantibodies, the ability to clinically recognize this pathology becomes paramount to establish an early preliminary diagnosis and not to delay immunosuppressive therapy, thus allowing for a better prognosis.

TNFRSF1A [corrected] R92Q mutation, autoinflammatory symptoms and multiple sclerosis in a cohort from Argentina.

Systemic autoinflammatory diseases are genetic disorders characterized by seemingly unprovoked inflammation, without major involvement of the adaptive immune system. Among them it is recognized the TNF receptor associated periodic syndrome (TRAPS) caused by mutations in the TNFRSF1A gene and characterized by symptoms such as recurrent high fevers, rash, abdominal pain, arthralgia and myalgia. Recent studies have recognized the potential role of TNFRSF1A mutations in Multiple Sclerosis (MS). Our aim was to investigate the role of TNFRSF1A R92Q gene mutation in a cohort of 90 Argentinean MS patients, where we determined the frequency of the TNFRSF1A R92Q mutation. We also compared autoinflammatory symptoms, MS clinical characteristics and treatment response and tolerability in R92Q carriers and non-carriers. Also, we used a case-control study design to obtain the genotypes of 78 healthy controls and assess the role of this mutation as a risk factor for MS. We found that five patients (5.5%) carried the R92Q mutation, four reported autoinflammatory symptoms previous to MS onset. We found no differences in MS clinical features, treatment response and tolerability between carriers and non-carriers. R92Q mutation was more frequent in MS patients as compared to controls. This increases the risk to develop MS in about 4.5 times. The TNFRSF1A R92Q mutation is a common finding in Argentinean MS patients. This genetic variant might be a risk factor for MS.

Acute optic neuritis: What do complementary tests add to diagnosis?

INTRODUCTION: Optic neuritis (ON) is the inflammation of the optic nerve due in many cases, to a pathological immune response. Since its symptoms can be subtle, diagnosis is sometimes challenging. The value of complementary tests for diagnosis and prognosis of ON was demonstrated in retrospective analysis, but their utility in the acute period of ON has been scarcely studied. The aim of this study is to determine the usefulness of clinical assessment, optical coherence tomography (OCT), visual evoked potentials (VEP) and orbit magnetic resonance imaging (MRI) for making diagnosis and prognosis of acute ON (AON). MATERIALS AND METHODS: A cross-sectional study was conducted including patients with ON within 90 days of symptom onset. A complete neuro-ophthalmological evaluation, OCT, VEP and MRI were carried out, determining in each case its sensitivity, specificity and predictive values in the diagnosis of ON and the assessment of its severity. RESULTS: 75 eyes of 34 patients with ON were included. Regarding diagnosis, low contrast visual acuity (LCVA) displayed the highest sensitivity (100%), being superior than the sensitivity of all complementary tools, always below 80%. Orbit MRI abnormal findings has a Specificity of 100% to confirm diagnosis. Regarding severity assessment and prognosis, Ganglion cell +inner plexiform layer (GCIP) thickness, but not retinal nerve fibre layer (RNFL), correlates significantly with patients' visual acuity (VA) (p < 0.05). Furthermore, both P100latency and VEP's amplitude showed to be significantly associated with VA (p < 0.05) in the acute period. The combination of two predictors (measurement of RNFL and GCIP) are capable of explaining 60% of the variation of the patient's visual acuity, with statistical significance (p = 0.02) CONCLUSIONS: In depth neuro-ophthalmological assessment during the acute phase of ON, including contrast sensitivity measurement, proved to be superior to complementary tests for diagnosis, surpassing the performance of OCT and VEP. However, these tools can add to prognosis, as GCIP thickness and VEP's amplitude correlate with disease severity and its findings could encourage prompt aggressive treatments in AON.

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.

Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy. It presents with a course of progression which may be slow and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the only clinical manifestation of this disease. Treatment with interferon beta1a (INF beta1a) has been tried with different results in patients who were refractory to other, more conventional, immunomodulatory therapies. Here we report on a patient who had a relapsing form of pure sensory ataxic CIDP and who failed to respond to intravenous human immunoglobulin. He was put on INF beta1a for 3 years. During this period he suffered no relapses while his condition stabilized.

Investigación de la Asociación entre el Polimorfismo TNFA -376 del gen TNF Alfa y el desarrollo de Esclerosis Múltiple en Argentina

El presente estudio tuvo como objetivo determinar la asociación entre el polimorfismo TNF -376 en el gen que codifica para TNF y un riesgo aumentado de padecer Esclerosis Múltiple en una población de pacientes nativos de argentina, así como también cuantificar el efecto de este polimorfismo sobre la expresión clínica en enfermos de esta patología. Los resultados comunicados en este trabajo no lograron determinar una asociación entre el polimorfismo del promotor del gen de TNF y la susceptibilidad de desarrollar Esclerosis Multiple. Las dos publicaciones comunicadas que demuestran esta asociación, pertenecen a poblaciones de pacientes españoles con EM RR. El mas significativo de estos dos trabajos que corroboro la susceptibilidad a desarrollar EM fue el de Martinez A y colaboradores ( ), quienes constataron en nativos españoles de raza blanca una asociación del alelo buscado con la susceptibilidad a desarrollar EM (p=0.018).

Investigación de la Asociación entre el Polimorfismo TNFA -376 del gen TNF Alfa y el desarrollo de Esclerosis Múltiple en Argentina

El presente estudio tuvo como objetivo determinar la asociación entre el polimorfismo TNF -376 en el gen que codifica para TNF y un riesgo aumentado de padecer Esclerosis Múltiple en una población de pacientes nativos de argentina, así como también cuantificar el efecto de este polimorfismo sobre la expresión clínica en enfermos de esta patología. Los resultados comunicados en este trabajo no lograron determinar una asociación entre el polimorfismo del promotor del gen de TNF y la susceptibilidad de desarrollar Esclerosis Multiple. Las dos publicaciones comunicadas que demuestran esta asociación, pertenecen a poblaciones de pacientes españoles con EM RR. El mas significativo de estos dos trabajos que corroboro la susceptibilidad a desarrollar EM fue el de Martinez A y colaboradores ( ), quienes constataron en nativos españoles de raza blanca una asociación del alelo buscado con la susceptibilidad a desarrollar EM (p=0.018).

Investigación de la Asociación entre el Polimorfismo TNFA -376 del gen TNF Alfa y el desarrollo de Esclerosis Múltiple en Argentina

El presente estudio tuvo como objetivo determinar la asociación entre el polimorfismo TNF -376 en el gen que codifica para TNF y un riesgo aumentado de padecer Esclerosis Múltiple en una población de pacientes nativos de argentina, así como también cuantificar el efecto de este polimorfismo sobre la expresión clínica en enfermos de esta patología. Los resultados comunicados en este trabajo no lograron determinar una asociación entre el polimorfismo del promotor del gen de TNF y la susceptibilidad de desarrollar Esclerosis Multiple. Las dos publicaciones comunicadas que demuestran esta asociación, pertenecen a poblaciones de pacientes españoles con EM RR. El mas significativo de estos dos trabajos que corroboro la susceptibilidad a desarrollar EM fue el de Martinez A y colaboradores ( ), quienes constataron en nativos españoles de raza blanca una asociación del alelo buscado con la susceptibilidad a desarrollar EM (p=0.018).