Celebrating the 70 years of pyridostigmine on therapy of Myasthenia Gravis: historical aspects of the preliminary trials / Celebrando os 70 anos da piridostigmina no tratamento da Miastenia Gravis: aspectos históricos dos ensaios clínicos preliminares

Abstract Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients.

Resumo Atualmente, o brometo de piridostigmina é um indispensável agente anticolinesterásico usado em todo o mundo no tratamento de pacientes com Miastenia Gravis (MG). Contudo, o brometo de piridostigmina não foi bem-sucedido, em seus "ensaios clínicos pioneiros", no tratamento de uma série de pacientes com MG. Existem importantes marcos históricos antes do brometo de piridostigmina se tornar útil, seguro e indispensável no tratamento da MG. Após 70 anos desses "ensaios clínicos pioneiros", este artigo revisa alguns aspectos históricos a eles relacionados, bem como a outros estudos preliminares que usaram o brometo de piridostigmina como um tratamento para pacientes com MG.

Miastenia Gravis: reporte de dos casos y revisión de la literatura / Myasthenia Gravis: two case reports and review

Myasthenia gravis is an acquired autoimmune disorder of the neuromuscular junction characterized by fluctuating weakness and fatigability of skeletal muscles. The diagnosis can be established by clinical and serologic testing, with predominance of autoantibodies against the acetylcholine receptor, and Muscle-specific kinase antibodies. We report two cases of Myasthenia gravis, the first one is a 31 year old patient with a debut of the disease, mainly with bulbar symptoms, and the second one is a 29 year old patient diagnosed with generalized Miasthenia Gravis also mainly with bulbar symptoms with worsening of symptomatology. In this report treatments alternatives and management approaches are discused

Gluten and Neuroimmunology. Rare association with Myasthenia Gravis and Literature Review

SUMMARY As the celiac disease (CD), the non-celiac gluten sensitivity (NCGS) has also been associated with several autoimmune manifestations. It is rarely associated with myasthenia gravis (MG). This paper shall introduce the case of a young female patient, initially presenting a peripheral neuropathy framework. During clinical and neurological follow-up, she began to present symptoms of various immune-mediated morbidities. Diseases related to gluten represent a clinical spectrum of manifestations with a trigger in common, the ingestion of gluten. CD is the most well-known and serious disease of the spectrum, also called gluten-sensitive enteropathy. The NCGS is diagnosed from clinical evidence of improvement in symptoms followed by a Gluten Free Diet (GFD) in patients without signs of enteropathy in duodenal biopsy. There are indications that, although rare, with a prevalence of 1 in 5000, myasthenia gravis (MG) may occur more often when CD is also present. Between 13 to 22% of the patients with MG have a second autoimmune disorder. However, it is often associated with dermatomyositis or polymyositis, lupus erythematosussystemic lupus erythematosus, Addison's disease, Guillain-Barré syndrome and juvenile rheumatoid arthritis. Thus, the symptoms of neuromuscular junction involvement may give a diagnostic evidence of this rare association.

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.

Use of pyridoxine and pyridostigmine in children with vincristine-induced neuropathy.

Four children with vincristine (VCR)-induced neuropathy are being reported. All cases were followed with the diagnosis of acute lymphoblastic leukemia. Two were boys aged between 2 and 13 year. Electromyographic examination consisted of sensoriomotor polyneuropathy with axonal involvement in three patients. In another patient, it consisted of motor axonal polyneuropathy. In all patients, pyridoxine and pyridostigmine were successfully used in the treatment of VCR-induced neuropathy. They recovered completely with this drug combination. Recovering period of symptoms was between 1-2 week.

Intestinal pseudo-obstruction as initial presentation of thymoma.

A 45-year-old-man presented with severe vomiting, constipation, abdominal distention and bilateral ocular abductor palsy. Evaluation revealed diffuse autonomic dysfunction characterized by intestinal pseudo-obstruction, xerophthalmia, xerostomia, postural hypotension, erectile dysfunction and loss of sinus arrhythmia. Paraneoplastic work-up revealed thymoma. Most symptoms resolved after surgical removal of the thymoma. Six weeks later he developed worsening of external ophthalmoparesis with ptosis, responding to acetylcholinesterase inhibitor, confirming myasthenia gravis.

Vincristine induced cranial polyneuropathy.

We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

Myasthenia gravis accompanied with hypokalemic periodic paralysis.

Myasthenia gravis and hypokalemic periodic paralysis are commonly related with hyperthyroidism but rarely occur together. Here, the authors reported a case of hypokalemic periodic paralysis in a Northeastern Thai woman accompanied with myasthenia gravis. She had motor weakness despite a normal level of serum potassium. Prostigmine test was positive. She dramatically improved after pyridostigmine treatment. Autoantibodies to nicotinic AchR-Ab and dihydropyridine receptor or L-type voltage gated calcium channel were postulated to explain these associated diseases.

The effect of use of pyridostigmine and requirement of vecuronium in patients with myasthenia gravis.

CONTEXT: Patients with myasthenia gravis receive pyridostigmine, an anticholinesterase agent, as a part of therapy. These patients demonstrate a heightened sensitivity towards non-depolarising muscle relaxants. Continuing pyridostigmine till the day of the surgery or omitting it on the night before surgery could provide variable results with regards to the effect of vecuronium. AIMS: Myographic evaluation of a dose of vecuronium in patients with myasthenia gravis on pyridostigmine therapy. SETTING AND DESIGN: A randomised, double-blind, clinical study conducted in a teaching hospital. SUBJECTS AND METHODS: Medically (oral pyridostigmine) well-controlled adult patients with myasthenia gravis who were posted for thymectomy, were randomly divided into two groups. Patients in Group 1 received their last dose of pyridostigmine on the night before surgery while those in Group 2 received even the morning dose of the drug on the day of surgery. Neostigmine (1-2 mg) intravenously was used as rescue medication. Vecuronium (0.01 mg/kg) was used for intubation and muscle relaxation during trans-sternal thymectomy and its effect was reversed using neostigmine and atropine. RESULTS: Fourteen patients (7 in each group) belonging to both sexes were enrolled in the study. The intubating dose of vecuronium showed quicker onset time (155 sec or 2.7 min approx.) and peak effect (99% T1 suppression) in patients belonging to Group 1, and 3/7 (43%) complained of respiratory discomfort while waiting for surgery. By giving the morning dose of pyridostigmine (Group 2), an identical intubating dose of vecuronium showed relative resistance (peak effect-97% T1 suppression) and delayed onset time (198 sec approx.). However, the reversal was complete at the end of surgery in both the regimens. CONCLUSIONS: Omission of the pyridostigmine dose on the day of surgery predisposed patients with myasthenia gravis to the possibility of respiratory discomfort and sensitivity to vecuronium. Continued administration significantly prolonged the onset time of vecuronium and the patients required a higher dose of vecuronium.

Autosomal recessive limb girdle myasthenia in two sisters.

Limb girdle myasthenic syndromes are rare genetic disorders described under the broad heterogeneous group known as congenital myasthenic syndromes and present with mixed features of myasthenia and myopathy. The familial limb girdle myasthenia has been described as one with selective weakness of pectoral and pelvic girdles, showing a positive response to edrophonium chloride. A report of two sisters affected by this disorder is presented.

Myasthenia gravis in children: analysis of 18 patients

Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 percent of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1). Eleven patients (61 percent) presented moderate or severe generalized disease and 4 (22 percent) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47 percent) out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6 percent (9 out of 11 tested) and the levels had no relation to clinical severity. Nine out of 16 patients (56 percent) worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia). Three patients (75 percent) improved markedly after thymectomy and one (25 percent) worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child

Miastenia Gravis en el Hospital Santo Tomás 1990-1997 / Myasthenia gravis in Santo Tomás Hospital 1990-1997

Myasthenia Gravis is an infrequent disease. Diagnosis and treatment must be done early to avoid high morbidity that can compromise patients lives. Nine cases were identified during the eight year 1990-1997 at the Santo Tomas Hospital of Panama city but one had to be excluded because he refused treatment. Most of the patients (7/8) had symptoms for more than 3 months. The diagnosis of Myasthenia Gravis requires a high index of suspicion and the clinical impressión must be confirmed by various diagnostic studies that include the edrophonium test, the repetitive stimulation test, the therapeutic test with pyridostigmine, the determination of acetylcholine anti-receptor antibodies and a CT Scan of the thorax. Medical treatment consists mainly of anticholinesterase agents and surgical treatment consists of thymectomy by means of an extended transternal ablation. Operative results were excellent, seven out of eight improved

Diagnóstico en Miastenia Gravis / Myasthemia gravis diagnosis

La miastenia gravis (MG) es uno de los desórdenes neuromusculares con involucro oftalmológico inicial más frecuente, por lo que el oftalmólogo debe conocer esta patología. Se debe sospechar de esta entidad en los casos en que se presenta ptosis y estrabismo con limitación en las ducciones; se deben realizar pruebas clínicas y de laboratorio para el diagnóstico de certeza. Se mencionan las pruebas clínicas, serológicas y electromiográficas diagnósticas más importantes, las ateraciones genéticas asociadas a este padecimiento y, brevemente, el tratamiento

Miastenia gravis e gravidez: análise de 9 casos / Myasthenia gravis and pregnancy: analysis of 9 cases

Os autores fazem a análise de nove casos de miastenia gravis associados à gravidez e comparam a evoluçao dos mesmos com a literatura. As possíveis exacerbaçoes para as maes e para os seus recém-nascidos tornam essa associaçao de alto risco. Oito pacientes (88,8 por cento) submeteram-se à timectomia. Todas as pacientes com miastenia gravis devem ser cuidadosamente monitoradas durante toda a gravidez, parto e puerpério. Apenas um recém-nascido apresentou sinais de miastenia gravis neonatal.

Miastenia grave: tratamento clínico e cirúrgico / Myasthenia gravis: clinical and surgical treatment

A indicaçäo da timectomia na miastenia grave ainda é controversa e, na atualidade, é difícil encontrar séries comparando tratamento conservador, devido à indicaçäo generalizada da timectomia. Na presente série foram estudados 65 casos divididos em três grupos: (1) 15 pacientes timectomizados e 50 com tratamento conservador; (2) 15 pacientes timectomizados pareados com 15 pacientes semelhantes clinicamente, mas tratados conservadoramente; (3) 49 pacientes tratados com corticosteróides, com 16 sem corticosteróides. Estes três grupos foram comparados quanto a idade, idade de início dos sintomas, tempo de doença, formas clínicas, escala funcional e intensidade dos sintomas, seguidos durante vários anos, estudando-se o número de remissöes, melhora, estabilidade ou piora dos sintomas e número de óbitos. Somente tiveram melhora dos sintomas (p<0,005) os timectomizados do grupo 1; os demais parâmetros de todos os grupos näo se mostraram estatisticamente significativos. Esses resultados sugerem que o tipo de tratamento pouco interferiu na evoluçäo da miastenia grave neste grupo de pacientes