Eficacia de la movilización de células madre en pacientes con Polineuropatía Desmielinizante Inflamatoria Crónica refractaria / Efficacy of mobilization of stem cells in patients with Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Introducción: La polineuropatía desmielinizante inflamatoria crónica (CIDP) es una enfermedad desmielinizante e inflamatoria de mediación autoinmune. El tratamiento convencional es basado en la inmunomodulación e inmunosupresión. El uso de células madre es una terapia novedosa en los trastornos autoinmune, siendo incluida como terapia. Objetivo: Determinar la eficacia de la movilización de células madre mediante la aplicación del factor estimulador de colonias granulocíticas (F-ECG) en pacientes con CIDP que han recibido otras líneas de tratamiento. Material y Métodos: Se realizó un estudio aleatorizado, doble ciego sobre una cohorte de 45 pacientes con CIDP, donde se administró el (F-ECG) en 25 pacientes y 20 continuaron con el tratamiento habitual, tratados anteriormente con otras variantes terapéuticas por más de tres años, sin respuesta satisfactoria. Resultados: Predominio de los hombres para 64,4 por ciento, la Diabetes Mellitus tuvo mayor asociación y la medicación más usada fueron los esteroides. Los síntomas y signos clínicos mejoraron significativamente tras el tratamiento. Los valores de la puntuación del TCSS al mes y 3 meses después del tratamiento disminuyeron significativamente; pero este decremento no se mantuvo al final del estudio. La velocidad de conducción y el potencial de acción de los nervios sensoriales y motores mejoraron considerablemente después del tratamiento. Conclusiones: La efectividad de la aplicación del (F-ECG) para la mejoría de los síntomas clínicos y resultados de estudios neurofisiológicos evolutivamente son mayores que otras variantes terapéuticas en los primeros meses, con buena seguridad y tolerabilidad, por lo que se puede incluir en la terapéutica convencional para la CIDP(AU)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune demyelinating disease. Conventional treatment is based on immunomodulation and immunosuppression. The use of stem cells is a novel therapy in autoimmune disorders, so it is included as therapy. Objective: To determine the efficacy of mobilization of stem cells by applying granulocyte colony-stimulating factor (G-CSF) in patients with CIDP who have followed other lines of treatment. Material and Methods: A randomized, double-blind study was carried out on a cohort of 45 patients with CIDP. G-CSF was administered to 25 patients and 20 of them continued with the usual treatment. These patients were previously treated with other therapeutic variants for more than three years without satisfactory response. Results: There was a prevalence of men (64.4 percent), Diabetes Mellitus had a greater association, and the most used medications were steroids. Clinical symptoms and signs improved significantly after treatment. TCSS scores significantly decreased at one and three months after treatment, but this decrease was not maintained at the end of the study. The conduction velocity and action potential of sensory and motor nerves improved considerably after treatment. Conclusions: The effectiveness of the use of G-CSF shows an improvement of clinical symptoms. The results of neurophysiological studies have a better course than other therapeutic variants during the first months, with good safety and tolerability, so it can be included in the conventional therapy for the CIDP(AU)

Estudo do perfil de citocinas inflamatórias das doenças desmielinizantes adquiridas na faixa etária pediátrica em ambulatório especializado no estado do Rio de Janeiro / Study of the inflammatory cytokine profile of acquired demyelinating diseases in the pediatric age group in a specialized outpatient clinic in the state of Rio de Janeiro

O grupo de Doenças Desmielinizantes Adquiridas (DDA) acomete o Sistema Nervoso Central (SNC) com base imunopatológica com produção de anticorpos à bainha de mielina. O diagnóstico é baseado em critérios clínico-radiológicos, sendo importante a busca por novas tecnologias para melhores diagnóstico e terapêutica. A avaliação da resposta inflamatória pode ser preditiva do curso evolutivo, sendo pouco explorada em pediatria. A proposta foi avaliar parâmetros clínico-neurológicos e perfis imunológicos nas DDA pediátricas para identificar biomarcadores dos quatro subtipos de DDA: Encefalomielite Disseminada Aguda (ADEM), Esclerose Múltipla Pediátrica (EMP), Síndrome Clínica Isolada (CIS) e Espectro da Neuromielite Óptica (NMOSD). Foi realizado um estudo prospectivo, longitudinal com portadores de DDA com até 18 anos de idade no Ambulatório de Doenças Desmielinizantes do IFF no período de 2012 a 2016. Os pacientes foram submetidos a exame neurológico evolutivo, Ressonância Magnética (RM) e coleta de sangue para pesquisa de citocinas. Foram admitidos 30 pacientes com 12 exclusões e 3 perdas totalizando 15 pacientes avaliados. O diagnóstico mais encontrado foi ADEM seguido de EMP. Os painéis de citocinas foram comparados através de análise estatística e categorizados de acordo com as comparações. Os resultados foram descritos em gráficos Heatmap, Boxplot e árvore de decisões. Foi relatado um caso sobre a evolução do diagnóstico de CIS para EMP. O perfil de citocinas séricas foi realizado por análise de microarranjo líquido (Luminex) totalizando 64 amostras de sangue avaliadas. A coorte apresentou cinco pacientes ADEM, cinco EMP, dois CIS e três NMOSD. No relato de caso da paciente ALAPL, não foi encontrada sincronia temporal entre a alteração do perfil de citocinas, da RM e da avaliação neurológica concluindo que avaliações inflamatória e clínica não anteciparam eventos de desmielinização e evolução para EMP. A correlação entre dosagens de citocinas mostrou um padrão multifuncional, com a participação de moléculas associadas ao perfil inflamatório Th1, Th2, Th17, Treg, e expressão aumentada de quimiocinas e citocinas envolvidas com proliferação de diversos tipos celulares. O padrão inflamatório mais abrangente e polifuncional, com 20 citocinas significativamente mais expressas, foi entre a EMP comparadas à ADEM. Na análise de citocinas entre ADEM e MNOSD houve uma diferença estatisticamente significativa para IL-7, IL-10 e GM-CSF, com uma expressão maior nas amostras de NMOSD. Entre CIS e ADEM, apenas MIP-1b se apresentou com uma diferença estatística nos dois grupos. A IP-10 se mostrou diferencialmente expressa em EMP quando comparada a CIS. Entre EMP e NMOSD, encontramos a eotaxina aumentada em EMP. Foram criadas quatro árvores classificatórias para o diagnóstico de DDA, definindo o perfil mínimo de citocinas capazes de identificar cada tipo de DDA. Concluímos que do ponto de vista diagnóstico as citocinas IL-2, IL-7, IL-13, Basic-FGF, MIP-1b, VEGF, Eotaxina, IP-10 e TNF- seriam capazes de classificar todos os pacientes DDA em seus grupos específicos. Estudos multicêntricos que permitam aumentar o número de pacientes com DDA poderão auxiliar na validação dos achados desse trabalho e definir pontos de cortes mais precisos para cada nível de citocina sérica visando ao diagnóstico diferencial de DDA em pediatria.

The group of Acquired Demyelinating Diseases (DDA) affects the Central Nervous System (CNS) with immunopathological basis with production of antibodies to the myelin sheath. The diagnosis is based on clinical-radiological criteria, being important the search for new technologies for better diagnosis and therapeutics. The evaluation of the inflammatory response can be predictive of the evolutionary course, being little explored in pediatrics. The purpose of this study was to evaluate clinical and neurological parameters and immunological profiles in pediatric ADIs to identify biomarkers of the four ADD subtypes: Acute Disseminated Encephalomyelitis (ADEM), Pediatric Multiple Sclerosis (EMP), Isolated Clinical Syndrome (CIS) and Optical Neuromyelitis Spectrum ). A prospective, longitudinal study was conducted with patients with ADD up to 18 years of age at the IFF Demyelinating Diseases Clinic in the period from 2012 to 2016. The patients were submitted to evolutionary neurological examination, EDSS, Magnetic Resonance (MRI) and collection to detect cytokines. Thirty patients with 12 exclusions and 3 losses totaling 15 patients were admitted. The most common diagnosis was ADEM followed by EMP. The cytokine panels were compared between the DDAs by statistical analysis and categorized according to the comparisons. The results were described in Heatmap, Boxplot and decision tree charts. A case has been reported on the evolution of the diagnosis of CIS to PMS. Serum cytokine profile was performed by liquid microarray analysis (Luminex), totalizing 64 blood samples. The cohort presented five ADEM, five EMP, two CIS and three NMOSD patients. In the case report of the ALAPL patient, no temporal synchrony was found between the alteration of the cytokine profile, MRI and neurological evaluation, concluding that inflammatory profile evaluations and clinical examination did not anticipate events of demyelination and evolution to PMS. The correlation between cytokine dosages and ADI in pediatrics showed a multifunctional pattern with the participation of molecules associated with the inflammatory profile Th1, Th2, Th17, Treg, and increased expression of chemokines and cytokines involved with proliferation of several cell types. The most comprehensive and multifunctional inflammatory pattern, with 20 significantly more expressed cytokines, was seen among PMS compared to ADEM. In the analysis of cytokines between ADEM and MNOSD there was a statistically significant difference for IL-7, IL-10 and GM-CSF, with a greater expression in the samples of patients with NMOSD. Between CIS and ADEM, only MIP-1b presented a statistical difference in the two groups. IP-10 was differentially expressed in EMP when compared to CIS patients. Among patients with EMP and NMOSD, we found increased eotaxin in EMP. Four classification trees were created for the diagnosis of ADI, defining the minimum profile of cytokines capable of identifying each type of ADI. We conclude that IL-2, IL-7, IL-13, Basic-FGF, MIP-1b, VEGF, Eotaxin, IP-10 and TNF-γ could be classified as diagnostic groups. Multicentric studies that allow an increase in the number of patients with ADD can help to validate the findings of this study and define more precise cutoff points for each level of serum cytokine aiming at the differential diagnosis of AD in pediatrics.

Diagnósticos, resultados e intervenções de enfermagem em pacientes com esclerose múltipla / Diagnósticos, resultados e intervenciones de enfermería en pacientes con esclerosis múltiple / Diagnostics, results and nursing interventions in patients with multiple sclerosis

RESUMO Introdução: a esclerose múltipla (EM) é uma Doença desmielinizante de etiologia autoimune, e está entre as principais causas de incapacidade neurológica não traumática nos adultos jovens. Objetivo: identificar os principais diagnósticos, resultados e intervenções de enfermagem e validar uma proposta de plano de cuidados para pacientes com Esclerose Múltipla. Métodos: estudo metodológico, realizado com 16 enfermeiros especialistas e 68 pacientes em uma unidade de Neurologia de um Hospital Escola, seguindo quatro etapas: elaboração dos Diagnósticos de Enfermagem; proposta inicial de resultados e intervenções de enfermagem; elaboração de um plano de cuidados; validação do plano por especialistas. Para a análise da concordância aplicou-se a escala do Coeficiente Kappa. Resultados: identificou-se quatro diagnósticos com frequência acima de 50 porcento, elencou-se quatro resultados de enfermagem e foram propostas 14 intervenções que alcançaram índice de concordância ≥ 0,8 entre os experts. Conclusão: o estudo permitiu identificar os diagnósticos, resultados e intervenções de enfermagem para aplicação na prática clínica, além de validar a proposta do plano de cuidados para pacientes com Esclerose Múltipla(AU)

RESUMEN Introducción: la esclerosis múltiple es una enfermedad desmielinizante de etiología autoinmune, y está entre las principales causas de incapacidad neurológica no traumática en los adultos jóvenes. Objetivo: identificar los principales diagnósticos, resultados e intervenciones de enfermería y validar una propuesta de plan de cuidados para pacientes con esclerosis múltiple. Métodos: estudio metodológico, realizado con 16 enfermeros especialistas y 68 pacientes en una unidad de Neurología de un Hospital Escuela, siguiendo cuatro etapas: elaboración de los Diagnósticos de Enfermería; Propuesta inicial de resultados e intervenciones de enfermería; Elaboración de un plan de cuidados; Validación del plan por expertos. Para el análisis de la concordancia se aplicó la escala del Coeficiente Kappa. Resultados: se identificaron cuatro diagnósticos con frecuencia por encima del 50 por ciento, se enumeraron cuatro resultados de enfermería y se propusieron 14 intervenciones que alcanzaron índice de concordancia ≥ 0,8 entre los expertos. Conclusión: el estudio permitió identificar los diagnósticos, resultados e intervenciones de enfermería para aplicación en la práctica clínica, además de validar la propuesta del plan de cuidados para pacientes con esclerosis múltiple(AU)

ABSTRACT Introduction: Multiple sclerosis (MS) is a demyelinating disease of autoimmune etiology and is one of the main causes of non-traumatic neurological disability in young adults. Objective: to identify the main nursing diagnoses, results and interventions and to validate a proposal for a care plan for patients with multiple sclerosis. Methods: a methodological study, carried out with 16 specialist nurses and 68 patients in a Neurology unit of a School Hospital, following four stages: elaboration of Nursing Diagnoses Initial proposal of results and nursing interventions; Preparation of a care plan; Validation of the plan by specialists. Kappa coefficient scale was used to analyze the agreement. Results: four diagnoses were identified with frequency above 50 percent, four nursing outcomes were listed and 14 interventions were proposed that reached a concordance index ≥ 0.8 among the experts. Conclusion: the study allowed to identify nursing diagnoses, results and interventions for application in clinical practice, in addition to validating the proposal of the care plan for patients with Multiple Sclerosis(AU)

Possível associação entre doença desmielinizante e neoplasias oligodendrogliais: relato de caso / Possible association between demyelinating disease and oligodendroglial tumors: a case report

Desde o primeiro relato de doença desmielinizante associada a tumores cerebrais por Scherer em 1938, inúmeros outros relatos de casos foram publicados fazendo associação desta doença com diferentes tumores primários do sistema nervoso central. Nosso trabalho descreve o caso de uma paciente de 23 anos com duas lesões encefálicas biopsiadas, mostrando inicialmente processo inflamatório desmielinizante que no seguimento desenvolve um oligodendroglioma anaplásico. A partir deste caso, realizamos uma revisão da literatura dessa associação específica, primeiramente publicada por Barnard e Jellinek em 1967, e ressaltamos a importância da diferenciação entre a forma desmielinizante tumefativa de uma neoplasia cerebral verdadeira. (AU)

Since the first report of demyelinating disease associated with brain tumors by Scherer in 1938, several other case reports have been published making association of this disease with different primary tumors of the central nervous system. Our paper describes the case of a 23 year old patient with two brain lesions, biopsied, initially showing a demyelinating inflammatory process that in the follow up develops an anaplastic oligodendroglioma. From this case, we conducted a literature review of this specific association, first published by Barnard and Jellinek in 1967, and emphasize the importance of difference in a tumefactive demyelinating lesions between of true brain neoplasm. (AU)

The profile of patients followed at the Neuroimmunology Clinic at UNIFESP: 20 years analysis / O perfil de pacientes atendidos no setor de Neuroimunologia da UNIFESP: análise de 20 anos

Objective To describe the clinical activities at the Neuroimmunology Clinic of the Universidade Federal de São Paulo (UNIFESP) from 1994 to 2013. Method The final diagnosis of all patients that attended the center was reviewed and established upon specific guidelines for each disease. The number of total appointments and extra clinical activities (reports and prescriptions) were also analyzed, as are part of routine activities. Results 1,599 patients attended the Clinic from 1994 to 2013: 816 with multiple sclerosis (MS), 172 with clinical isolated syndromes, 178 with neuromyelitis optica (NMO), 216 with other demyelinating disease, 20 with metabolic disorder, 42 with a vascular disease and 155 with other or undetermined diagnosis. A mean 219 outpatient visits and 65 extra clinical activities were performed monthly. Conclusion We identified that 15% of patients seen have NMO. As patients with NMO have a more severe disease than MS, this data may be important for planning local health care policies. .

Objetivo Descrever a casuística de pacientes atendidos no setor de Neuroimunologia da Universidade Federal de São Paulo (UNIFESP) de 1994 a 2013. Método Analisamos o diagnóstico final de todos os pacientes atendidos de 1999 a 2013, sendo o diagnóstico revisado na última consulta e estabelecido de acordo com os critérios específicos para cada doença. O volume de atendimentos clínicos e não clínicos (relatórios e receitas) foram contabilizados para avaliar a carga de trabalho da equipe. Resultados 1.599 pacientes foram avaliados: 816 com esclerose múltipla (EM), 172 com síndromes clínicas isoladas, 178 com neuromielite óptica (NMO), 216 com outras doenças desmielinizantes, 20 com doenças metabólicas, 42 com doenças vasculares e 155 com outros diagnósticos ou diagnósticos indefinidos. Identificamos uma média de 219 consultas e 65 solicitações de relatórios por mês. Conclusão Identificamos que 15% dos pacientes atendidos tem NMO. Por ser uma doença mais incapacitante que a EM estes dados podem ser importantes para o planejamento de políticas de saúde locais. .

Tumefactive demyelinating lesions: A Clinicopathological correlative study.

Tumefactive demyelinating (TDL) lesions are focal zones of demyelination in the central nervous system and they often mimic the neuroimaging features of an intraxial neoplasm. In this report we describe the clinical, neuroimaging and neuropathological features of six cases of TDL. Only in two patients the neuroimaging features in MRI (magnetic resonance imaging) scans were suggestive of TDL while in the other four cases a diagnosis of glioma was suggested. In order to establish a confirmatory diagnosis neuronavigation/stereotactic biopsy was undertaken and the diagnosis of TDL was established in all six cases at histopathology. Two out of six patients did not respond to the conventional corticosteroid therapy and they were treated with plasma exchange. It is being concluded that neuronavigation biopsy, though provide only a small amount of tissue, and is extremely useful in making the diagnosis of TDL.

A Case of Lewis-Sumner Syndrome Showing Dramatic Improvement after Plasma Exchange

We report a patient with Lewis-Sumner syndrome (LSS) who showed an improvement only with plasma exchange (PE). The patient, 32-yr old man, had progressive multifocal motor-sensory deficits with persistent, multiple conduction blocks and marked slowing of NCVs. Nerve pathology supported a diagnosis of demyelinating neuropathy by revealing marked loss of myelinated fibers with inter- and intrafascicular variation. Although the patient was refractory to treatment with corticosteroid and intravenous immunoglobulin, PE produced a dramatic improvement. Our experience strongly proposes that PE should be tried for refractory LSS.

Chronic inflammatory demyelinating polyradiculoneuropathy in two children

Chronic inflammatory demyelinating polyradiculoneuropathy [CIDP] is relatively rare in children. We report two cases diagnosed over a thirteen year period. One patient had a monophasic course resulting in complete recovery while the other case had a slowly progressive relapsing course with significant morbidity

Tumefactive demyelination.

We present a case of 22 year old female who had pulmonary tuberculosis followed by tuberculous meningitis and tuberculomas in past. This time she presented to us with right hemiparesis and altered sensorium. Diagnosis of tumefactive demyelination was made on the basis of typical MRI findings. Patient showed good response to steroids.

Demyelinating disease in patients with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness, caused by impaired neuromuscular transmission. Patients with MG can present other autoimmune diseases in association, commonly hypo or hyperthyroidism. The association of MG to demyelinating disease is rare and has been described before. We report on three Brazilian patients with MG that presented distinct demyelinating diseases, two monophasic and one recurrent neuromyelitis optica, several years after the diagnosis of MG, and discuss their clinical courses.

Miastenia gravis (MG) é doença autoimune caracterizada por episódios de fraqueza muscular alternados com melhora, causada por bloqueio da junção neuromuscular. Pacientes com MG podem apresentar outras doenças autoimunes, comumente hipo ou hipertiroidismo, e a associação de MG com doenças desmielinizantes é raramente descrita. Relatamos três pacientes brasileiros com MG que desenvolveram doenças desmielinizantes, dois monofásicos e um neuromielite óptica recorrente, vários anos após o diagnóstico de MG e discutimos seus cursos clínicos.

Central nervous system demyelination associated with etanercept in a 51 years old woman

There are few case reports documenting a new onset of demyelinating processes in patients receiving anti-tumour necrosis factor alpha therapy [anti-TNF alpha] for chronic inflammatory arthropathies. Whether anti-TNF alpha therapy induces new onset demyelination or just exacerbates pre-existing latent multiple sclerosis is not fully understood. We are reporting a 51-year-old woman without a prior history of multiple sclerosis, who developed demyelinating brain lesions three months after starting Etanercept. Her symptoms partially resolved on cessation of the drug. Our case was unusual compared to some previous case reports, as the patient's age at presentation was beyond that for idiopathic multiple sclerosis. This may strengthen the hypothesis of a causal relationship between new onset demyelination and Etanercept; however, exacerbation of pre-existing demyelinating process by Etanercept in this patient still cannot be totally excluded. We recommend doing magnetic resonance imaging [MRI] of the brain before starting patients on anti-TNF alpha therapy to exclude latent demyelination. In addition, new onset demyelination following anti-TNF alpha therapy should be reported and studied thoroughly as this may yield a significant advancement in our understanding of the pathogenesis of multiple sclerosis. Long-term follow-up of these cases is also important to determine the long-term prognosis and the rate of relapse of demyelinating process in this group of patients

Desmielinização tardia da substância branca cerebral devido à intoxicação por monóxido de carbono / Delayed demyelination of the cerebral white matter due to carbon monoxide intoxication

Os autores apresentam um caso de desmielinização tardia da substância branca cerebral devido à intoxicação por monóxido de carbono, discutem os principais diagnósticos diferencias e a importância da anamnese na elucidação do caso.

The authors present a case of delayed demyelination of the cerebral white matter due to carbon monoxide poisoning; discuss the main differential diagnoses and the importance of the anamnesis in the elucidation of the case.

Inflammatory demyelinating pseudotumor

Inflammatory demyelinating pseudotumor [IDP] is a rare inflammatory lesion of unknown etiology, which presents as a space-occupying lesion but responds dramatically to steroid therapy. The objective of this report is to document 2 cases of IDP seen in Kuwait. Two female patients, aged 35 and 27 years presented with the clinical and radiological features of a space-occupying lesion. Radiological investigations showed partial ring-enhancing lesions with insignificant mass effect, which were multiple in patient one, and single in patient 2. Biopsies in each patient showed features of a demyelinating disorder. Both patients remarkably improved clinically on steroid therapy. The report highlights the need for an early and correct diagnosis of IDP for therapeutic purposes

Extra pontine myelinolysis associated with hypophosphatemia

We report a unique association of extra-pontine myelinolysis with severe hypophosphatemia developing in a young lady with a prolonged febrile illness and inadequate oral intake.The late identification of severe hypophosphatemia resulted in extra-pontine myelinolysis. Gradual improvement in clinical status was noticed with phosphate replacement and good supportive care

Pseudobulbar paralysis--a sequelae of cerebral malaria.

Demyelination may be a pathogenic mechanism of post-malarial neurological sequelae. It can cause pseudobulbar palsy, which has not been documented earlier. In the present communication we report two cases of pseudobulbar palsy after cerebral malaria with evidence of demyelination.