Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: a study from the RelevarEM registry

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients

Assessing attacks and treatment response rates among adult patients with NMOSD and MOGAD: data from a nationwide registry in Argentina

We aimed to examine treatment interventions implemented in patients experiencing neuromyelitis optica spectrum disorders (NMOSD) attacks (frequency, types, and response). METHODS: Retrospective study. Data on patient demographic, clinical and radiological findings, and administered treatments were collected. Remission status (complete [CR], partial [PR], no remission [NR]), based on changes in the EDSS score was evaluated before treatment, during attack, and at 6 months. CR was analyzed with a generalized estimating equations (GEEs) model. RESULTS: A total of 131 patients (120 NMOSD and 11 myelin oligodendrocyte glycoprotein-antibody-associated diseases [MOGAD]), experiencing 262 NMOSD-related attacks and receiving 270 treatments were included. High-dose steroids (81.4%) was the most frequent treatment followed by plasmapheresis (15.5%). CR from attacks was observed in 47% (105/223) of all treated patients. During the first attack, we observed CR:71.2%, PR:16.3% and NR:12.5% after the first course of treatment. For second, third, fourth, and fifth attacks, CR was observed in 31.1%, 10.7%, 27.3%, and 33.3%, respectively. Remission rates were higher for optic neuritis vs. myelitis (p < 0.001). Predictor of CR in multivariate GEE analysis was age in both NMOSD (OR = 2.27, p = 0.002) and MOGAD (OR = 1.53, p = 0.03). CONCLUSIONS: This study suggests individualization of treatment according to age and attack manifestation. The outcome of attacks was generally poor

Neuromyelitis optica: Association with paroxysmal painful tonic spasms

Introduction: Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. Patients and methods: We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. Results: Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. Conclusions: PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results. Resumen: Introducción: Los espasmos tónicos paroxísticos dolorosos (ETPD) fueron descritos inicialmente en la esclerosis múltiple (EM) pero serían más frecuentes en la neuromielitis óptica (NMO). El objetivo es comunicar su presencia en una serie de casos de NMO y su espectro (NMOSD), determinar la frecuencia y las características clínicas. Métodos y pacientes: Se evaluaron retrospectivamente historias clínicas de pacientes con NMO/NMOSD en 2 centros de la Ciudad de Buenos Aires (Hospital Durand y Hospital Álvarez) durante el periodo 2009-2013. Resultados: De 15 pacientes con NMOSD (7 con NMO definida y 8 con NMO limitada), 4 presentaron ETPD (26,66%). En los pacientes con NMO definida la frecuencia fue del 57,14% (4/7). De 9 (9/15) pacientes con mielitis longitudinal extensa (LETM) 44,44% presentó ETPD. Edad: media 35 años (rango: 22-38 años). Cien por cien sexo femenino. Tiempo desde el diagnóstico de NMO: media 7 meses (rango: 1-29 meses) y con respecto a la última recaída de LETM: media 30 días (rango: 23-40 días). El 100% presentó LETM (cervicodorsal 75% y dorsal 25%) en resonancia magnética (RM). El 100% presentó control de los espasmos y el dolor con carbamazepina (uno asociado a gabapentin) sin una respuesta adecuada a pregabalina, gabapentin y fenitoína. Conclusiones: Los ETPD son frecuentes en la NMO. Aparecen aproximadamente al mes de una recaída de LETM con lesiones cervicodorsales extensas en RM. Tienen excelente respuesta a carbamazepina y poca o nula a pregabalina y gabapentin. Estos resultados deberán ser confirmados con estudios prospectivos con mayor número de pacientes. Keywords: Multiple sclerosis, Paroxysmal painful tonic spasms, Neuromyelitis optica, Neuromyelitis optica spectrum disorders, Longitudinally extensive transverse myelitis, Palabras clave: Esclerosis múltiple, Espasmos tónicos paroxísticos dolorosos, Espectro de la neuromielitis óptica, Mielitis transversa longitudinal extensa, Neuromielitis óptic

Neuromielitis óptica: asociación con espasmos tónicos paroxísticos dolorosos

Resumen: Introducción: Los espasmos tónicos paroxísticos dolorosos (ETPD) fueron descriptos inicialmente en la esclerosis múltiple (EM) pero serían más frecuentes en la neuromielitis óptica (NMO). El objetivo es comunicar su presencia en una serie de casos de NMO y su espectro (NMOSD), determinar la frecuencia y las características clínicas. Métodos y pacientes: Se evaluaron retrospectivamente historias clínicas de pacientes con NMO/NMOSD en 2 centros de la Ciudad de Buenos Aires (Hospital Durand y Hospital Álvarez) durante el periodo 2009-2013. Resultados: De 15 pacientes con NMOSD (7 con NMO definida y 8 con NMO limitada), 4 presentaron ETPD (26,66%). En los pacientes con NMO definida la frecuencia fue del 57,14% (4/7). De 9 (9/15) pacientes con mielitis longitudinal extensa (LETM) 44,44% presentó ETPD. Edad: media 35 años (rango: 22-38 años). Cien por cien sexo femenino. Tiempo desde el diagnóstico de NMO: media 7 meses (rango: 1-29 meses) y con respecto a la última recaída de LETM: media 30 días (rango: 23-40 días). El 100% presentó LETM (cervicodorsal 75% y dorsal 25%) en resonancia magnética (RM). El 100% presentó control de los espasmos y el dolor con carbamazepina (uno asociado a gabapentin) sin una respuesta adecuada a pregabalina, gabapentin y fenitoína. Conclusiones: Los ETPD son frecuentes en la NMO. Aparecen aproximadamente al mes de una recaída de LETM con lesiones cervicodorsales extensas en RM. Tienen excelente respuesta a carbamazepina y poca o nula a pregabalina y gabapentin. Estos resultados deberán ser confirmados con estudios prospectivos con mayor número de pacientes. Abstract: Introduction: Paroxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. Patients and Methods: We conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. Results: Out of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. Conclusions: PPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results. Palabras clave: Esclerosis múltiple, Espasmos tónicos paroxísticos dolorosos, Espectro de la neuromielitis óptica, Mielitis transversa longitudinal extensa, Neuromielitis óptica, Keywords: Multiple sclerosis, Paroxysmal painful tonic spasms, Neuromyelitis optica, Neuromyelitis optica spectrum disorders, Longitudinally extensive transverse myeliti

Diagnósticos diferenciales y pronóstico de las mielitis longitudinales extensas en Buenos Aires, Argentina

Resumen: Introducción: Las mielitis longitudinales extensas (LETM) fueron clásicamente relacionadas con los trastornos del espectro de la neuromielitis óptica (NMOSD) tanto definidas como limitadas. Sin embargo, los diagnósticos diferenciales incluyen una amplia gama de etiologías. Objetivo: Comunicar los diagnósticos diferenciales y el pronóstico de LETM observados en un grupo de pacientes en Buenos Aires, Argentina. Pacientes y métodos: Estudio multicéntrico retrospectivo transversal realizado en 2 hospitales de Buenos Aires desde junio del 2008 hasta junio del 2014. Criterios de inclusión: síndrome medular asociado a una lesión en la médula espinal con una extensión de 3 o más segmentos vertebrales contiguos en la resonancia magnética (RM). Datos bioquímicos, radiológicos y clínicos fueron evaluados. Asimismo, se aplicó la escala de discapacidad funcional de Winer-Hughes (WHFDS) a los 3 meses. Resultados: Se evaluó a 27 pacientes, el 74% mujeres, edad (media): 35,22 años. NMO-IgG se realizó en el 66,6% y las bandas oligoclonales en el 71%. NMO-IgG se observó exclusivamente en pacientes con NMOSD (75%). La RM de encéfalo fue normal en el 59,2% y la media de segmentos afectados en RM espinal fue 7,9. Los diagnósticos diferenciales encontrados fueron: NMOSD (37%), idiopática (22,2%), lupus (11,1%), tumores (11,1%), fístula dural (7,4%), encefalomielitis diseminada aguda (7,4%) y esclerosis múltiple (3,7%). Los pacientes con ≥ 7 segmentos afectados tenían peor WHFDS (p < 0,001) y se asoció a etiología tumoral, vascular, lupus e idiopática. Conclusiones: En nuestra cohorte, NMOSD seguidos por idiopática, fueron las causas más frecuentes de LETM. Las LETM tumorales, vasculares, lupus e idiopáticas pueden representar un grupo crítico con diferente pronóstico y tratamiento. Abstract: Introduction: Longitudinally extensive myelitis (LETM) has classically been grouped with the full or limited neuromyelitis optica spectrum disorders (NMOSD). However, differential diagnosis reveals a wide range of aetiologies. Objective: To report on differential diagnosis and prognosis for LETM observed in a group of patients in Buenos Aires, Argentina. Patients and methods: Cross-sectional and retrospective multicentre study in two hospitals in Buenos Aires from June 2008 to June 2014. Inclusion criteria: medullary syndrome associated with spinal cord lesion extending for 3 or more contiguous spinal segments in magnetic resonance imaging (MRI). Clinical, radiological, and biochemical data were collected and subjects were rated on the Hughes functional disability scale (WHFDS) at 3 months. Results: We evaluated 27 patients, 74% of whom were women; mean age was 35.22 years. The NMO-IgG antibody test was performed in 66.6% and oligoclonal band testing in 71%. NMO-IgG seropositivity was found exclusively in NMOSD patients (75%). Brain MRI was normal in 59.2% and revealed a mean of 7.9 affected spinal segments. Differential diagnoses revealed NMOSD (37%), idiopathic LETM (22.2%), lupus (11.1%), tumour (11.1%), dural fistula (7.4%), acute disseminated encephalomyelitis (7.4%), and a single case of multiple sclerosis (3.7%). Patients with lesions to ≥ 7 spinal segments showed poor recovery at 3 months (P < .001); these cases were associated with neoplastic, vascular, idiopathic, and lupus-related aetiologies. Conclusions: The most frequent causes of LETM in our cohort were NMOSD followed by idiopathic cases. Neoplastic, vascular, lupus-related, and idiopathic LETM may constitute a critical group with a distinct prognosis and other treatment needs. Palabras clave: Mielitis transversa longitudinal extensa, Neuromielitis óptica, Anticuerpo antiaquaporina-4, Pronóstico, Diagnósticos diferenciales, Keywords: Longitudinally extensive transverse myelitis, Neuromyelitis optica, Aquoporin-4 antibody, Prognosis, Differential diagnosi