Miastenia gravis y su asociación con trastornos linfoproliferativos: casos clínicos / Myasthenia gravis and its association with lymphoproliferative disorders: a case series

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we identified four patients who developed different lymphoproliferative disorders: two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all cases classified as type IIa according to the definition proposed by the MG Foundation of America. The neoplasia appeared two to 36 years after the onset of MG. These cases provide additional evidence of the association between MG and lymphoproliferative disorders.

Clinical and genetic basis of congenital myasthenic syndromes / Bases clínicas e genéticas das síndromes miastênicas congênitas

ABSTRACT Neuromuscular junction disorders represent a wide group of neurological diseases characterized by weakness, fatigability and variable degrees of appendicular, ocular and bulbar musculature involvement. Its main group of disorders includes autoimmune conditions, such as autoimmune acquired myasthenia gravis and Lambert-Eaton syndrome. However, an important group of diseases include congenital myasthenic syndromes with a genetic and sometimes hereditary basis that resemble and mimick many of the classic myasthenia neurological manifestations, but also have different presentations, which makes them a complex clinical, therapeutic and diagnostic challenge for most clinicians. We conducted a wide review of congenital myasthenic syndromes in their clinical, genetic and therapeutic aspects.

RESUMO Distúrbios da junção neuromuscular representam um grupo amplo de doenças neruológicas caracterizadas por fraqueza, fadigabilidade e graus variados de envolvimento das musculaturas apendicular, ocular e bulbar. Os principais grupos de doenças deste grupo incluem condições auto-imunes, como a miastenia gravis auto-imune adquirida e a síndrome de Lambert-Eaton. Entretanto, um outro grupo importante de doenças incluem as sindromes miastênicas congênitas com uma base genética e eventualmente hereditária que lembra e mimetiza muitas das manifestações neurológicas clássicas das miastenias, mas também se apresentam de diferentes formas tornando um desafio clínico, terapêutico e diagnóstico complexo para a maioria dos clínicos. Realizamos ampla revisão sobre as síndromes miastênicas congênitas em seus aspectos clínicos, genéticos e terapêuticos.

Reporte de dos casos de miastenia gravis en el embarazo / Report of two cases of myasthenia gravis in pregnancy

La miastenia gravis es un trastorno autoinmune de la trasmisión neuromuscular que involucra la producción de autoanticuerpos dirigidos contra receptores músculo-esqueléticos, en la gran mayoría de los casos de acetilcolina. El curso de la miastenia gravis en el embarazo es impredecible. Pueden registrarse remisiones, exacerbaciones, recaídas o que no se modifique durante el curso de la gestación. El 30% de las pacientes empeoran durante el embarazo. El 10 a 20% de los recién nacidos de madres miasténicas pueden tener una miastenia neonatal .Se presentan dos casos de la Cátedra de Gineco Obstetricia de la FCM/UNA que se caracterizaron por una evolución favorable de la madre aunque los recién nacidos presentaron síntomas de miastenia gravis transitoria.

Myasthenia gravis is an autoimmune disorder of neuromuscular transmission involving the production of autoantibodies directed against musculoskeletal receptors, in the vast majority of cases acetilcolina. The course of myasthenia gravis in pregnancy is unpredictable. Remissions can be registered, exacerbations, relapses or no change to occur during the course of gestation. 30% of patients worsen during pregnancy. The 10-20% of infants born to myasthenic mothers may have neonatal myasthenia. Two cases from the Department of Obstetrics and Gynecology FCM/UNA where characterized by a favorable development of the mother although newborns had symptoms of transient myasthenia gravis

Miastenia gavis ocular en pediatría. Clínica y evolución a largo plazo / Ocular myastenia gravis in children. Clinical features and long - term outcome

Objetivo: Reportar cuadro clínico, patologías asociadas y evolución a largo plazo en pacientes con MGO. Material y Métodos: De 74 pacientes con miastenia gravis juvenil atendidos durante el período 1987-2003, se reportan 29 con MGO. Se incluyeron: a) menores de 16 años con debilidad de músculos extraoculares (MGO), elevador y orbicular de los párpados, durante un período mínimo de 6 meses; b) con una de las siguientes pruebas positivas: prueba farmacológica (PF); prueba de estimulación repetitiva (PER); anticuerpos contra receptor de acetilcolina (ACRA) positivo y/o respuesta a inmunosupresores. Resultados: Edad media de inicio de síntomas: 3,6 años, con una relación mujer/varón 2.2/1. Cuadro clínico inicial: ptosis palpebral 100 por ciento (bilateral 62 por ciento); paresia de MEO 86 por ciento; diplopía 17 por ciento; disminución de la agudeza visual (AV) 27 por ciento; ritmo miasténico 89 por ciento. Estudios complementarios: PF (más)100 por ciento (n=25); PER (más)74 por ciento (n=23) y ACRA (más) 52 por ciento (n=21). Evolución: se incluyeron 21 pacientes con seguimiento mayor a un año (media de 8 años). Tres pacientes tuvieron remisión completa estable (1 espontánea y 2 con corticoides); 8 manifestaciones mínimas (5 con piridostigmina y 3 corticoides) y 10 persistencia clínica (3 con piridostigmina y 7 corticoides). Tres (14 por ciento) casos presentaron recurrencias. Cuatro niños quedaron con marcada disminución de la AV y 4 con mirada congelada. Enfermedad asociada: patologías tiroideas (38 por ciento); diabetes (5 por ciento). Conclusiónes: Pacientes con MGO tienen características propias que difieren de las formas generalizadas. Estas son: inicio precoz, mayor positividad de PF, pero menor de la PER y ACRA; elevado porcentaje de pacientes que persisten sintomáticos y con secuelas visuales. Nuevas modalidades terapéuticas deberían ser intentadas, teniendo en cuenta los efectos colaterales de los inmunosupresores a una edad temprana y el riesgo de sec...

A study of myasthenia gravis in patients with and without thymoma.

This study was undertaken to compare the clinical, neurophysiological, radiological and prognostic features of myasthenia gravis with and without thymoma. 37 patients with myasthenia gravis (27 males, 10 females), with age range of 4.5 to 72 (mean 39) years, were managed at a tertiary care centre in India. Four patients were below 15 years of age and 6 above 55 years. Most of the patients were in stage II (34). There were 2 patients in stage III and 1 in stage I. 27 patients underwent thymectomy. Thymoma was detected in 10 cases. The decrement in patients with thymoma ranged between 11 and 62% (mean 27.9%) and nonthymoma group 10-75% (mean 28%). CT scan of thorax revealed mediastinal mass in 5 out of 10 cases of thymoma and 2 out of 27 patients without thymoma. Outcome of myasthenia gravis with thymoma was worse than without thymoma at 1 year followup. Severity of illness, extent of decrement, lack of facilitation, duration of illness and age of the patients were not related to the outcome. It is concluded the clinical and neurophysiological changes in myasthenia gravis with and without thymoma do not differ. However, patients with thymoma have a worse outcome.

Invasive medullary thymoma associated with myasthenia gravis: an unusual case

Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome

Miastenia grave e doença de Graves: relato de caso / Myasthenia gravis and Grave's disease: case report

Os autores relatam o caso de uma paciente de 26 anos com miastenia grave, associada à doença de Graves. Neste relato, revisam a literatura e discutem a etiopatogenia, a apresentaçäo clínica, o diagnóstico, e o tratamento clínico e cirúrgico; ressaltando a importância do diagnóstico precoce da doença tireoideana nos pacientes com miastenia grave.

A case of myasthenia gravis proven by ultrastructural study

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.

A case of myasthenia gravis proven by ultrastructural study

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.

Myasthenia gravis crisis

A previously undiagnosed case of myasthenia gravis who presented in Nizwa hospital with severe respiratory distress due to acute myasthenic crisis is reported here. This is a rare form of presentation of myasthenia gravis which requires aggressive treatment with ventilatory support in an intensive care unit

Juvenile myasthenia gravis and thymectomy: report of ten cases

Sao relatados dez pacientes de 7 a 12 anos de idade e com miastenia grave generalizada adquirida: seis tinham forma severa e quatro apresentavam forma moderada. Todos os pacientes evoluiram com piora progressiva e resposta pobre aos tratamentos medicos. Todas as criancas foram submetidas a timectomia mediana transesternal. Os resultados a longo prazo foram favoraveis em 60 por cento dos pacientes que experimentaram melhora importante ou mesmo remissao completa. Um paciente teve remissao completa sem medicacao tendo sido acompanhado por dois anos, enquanto outro assim se manteve com dose minima de anticolinesterasico durante o periodo de sete anos de acompanhamento. Na maioria dos pacientes foi mantida prednisona a longo prazo apos timectomia. Resultados a curto prazo nao foram favoraveis, pois ocorreu um obito e 30 por cento dos pacientes pioraram.

Thymic histology in myasthenia gravis.

Histological features of resected thymuses of 18 patients with myasthenia gravis were evaluated. Thymoma were seen in 16.6% of the patients. In the non-thymomatous group, thymic hyperplasia with follicle formation was seen in 33.3%, involuted thymus with occasional lymphoid follicle formation in 11.1%, thymitis with B cell infiltration in 16.6%, involuted thymus in 11.1% and normal thymus in 11.1% of patients. Immuno-histological staining for B and T lymphocytes delineated the group labelled as thymitis with B cell infiltration. Mast cell and eosinophils were frequently seen in thymuses with thymic hyperplasia with follicle formation and thymitis with B cell infiltration. Thymic hyperplasia with follicle formation was more frequent in young patients and these patients had better prognosis.