Two Cases of Myasthenia Gravis Showing Fatigibility Presenting with Decreased Gain of Smooth Pursuit / 대한평형의학회지

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies to the acetylcholine receptors of the neuromuscular junction characterized by weakness and abnormal fatigability of the muscles. Therefore, the diagnosis of MG depends on the recognition of this distinctive pattern of fatigable weakness. Previous studies presented the diagnostic efficacy of saccadic eye movements in patients with ocular MG. We here in report 2 patients of ocular MG showing the fatigue effects during repetitive sustained smooth pursuit, and the effects of the administration of edrophonium on myasthenic smooth pursuit. Changes in smooth pursuits reflecting peripheral and secondary central mechanisms were demonstrated.

Efficacy of Gaze Photographs in Diagnosing Ocular Myasthenia Gravis

BACKGROUND AND PURPOSE: The various tests that are routinely used to diagnose generalized myasthenia gravis, such as the edrophonium test, serum anti-acetylcholine-receptor antibodies (AChR-Ab), and repetitive nerve stimulation (RNS) tests, have lower diagnostic sensitivity in ocular myasthenia gravis (OMG). Diagnosing OMG becomes even more difficult when the clinical symptoms are subtle. There is no gold-standard diagnostic test available for OMG patients, and so this study compared the diagnostic sensitivity of gaze photographs with conventional tests in OMG. METHODS: Records of gaze photographs were available for 25 of 31 consecutive patients diagnosed with OMG. Each patient underwent a neuro-ophthalmologic examination, serum AChR-Ab, RNS, edrophonium test, ice tests, and the acquisition of gaze photographs. The margin reflex distance 1 (MRD1) was measured on each of the gaze photographs, with MRD1 < 2 mm or an interlid MRD1 difference of ≥2 mm on any of the gaze photographs defined as a positive sign of OMG. The diagnostic sensitivities of the tests were assessed. RESULTS: The mean age at onset was 38.5 years (range, 2–76 years), and 13 patients (52%) were men. The diagnostic sensitivities of the RNS test, AChR-Ab test, gaze photographs, and ice test were 56%, 64%, 80%, and 73%, respectively. CONCLUSIONS: The diagnostic sensitivity was higher for gaze photographs than for the other tests applied to OMG patients.

Bulbar Myasthenia Gravis Superimposed in a Medullary Infarction Diagnosed by a Fiberoptic Endoscopic Evaluation of Swallowing With Simultaneous Tensilon Application

In the elderly, myasthenia gravis (MG) can present with bulbar symptoms, which can be clinically difficult to diagnose from other neurological comorbid conditions. We describe a case of a 75-year-old man who had been previously diagnosed with dysphagia associated with medullary infarction but exhibited aggravation of the dysphagia later on due to a superimposed development of bulbar MG. After recovering from his initial swallowing difficulties, the patient suddenly developed ptosis, drooling, and generalized weakness with aggravated dysphagia. Two follow-up brain magnetic resonance imaging (MRI) scans displayed no new brain lesions. Antibodies to acetylcholine receptor and muscle-specific kinase were negative. Subsequent electrodiagnosis with repetitive nerve stimulation tests revealed unremarkable findings. A diagnosis of bulbar MG could only be established after fiberoptic endoscopic evaluation of swallowing (FEES) with simultaneous Tensilon application. After application of intravenous pyridostigmine, significant improvement in dysphagia and ptosis were observed both clinically and according to the FEES.

Análisis de impacto presupuestal del uso de anticuerpos bloqueadores de acetilcolina receptores, comparado con la prueba de Tensilon, de estímulo repetitivo, electromiografía con electrodo de fibra única e I CE test para pacientes con miastenia gravis / Budget impact analysis of the use of acetylcholine receptor blocking antibodies, compared to the Tensilon test, repetitive stimulus, electromyography with single fiber electrode and IEC test for patients with myasthenia gravis

Tecnologías evaluadas: -Tecnologías actuales: electromiografía con electrodo de fibra única e ICE test;\r\n-Tecnología nueva: anticuerpos bloqueadores de acetilcolina receptores, prueba de Tensilon, prueba de estímulo repetitivo. Población: Esta prueba se puede aplicar a todas las edades y a todos los sexos, ya que la aparición de la enfermedad puede presentarse en toda la población. Perspectiva: Tercer pagador - Sistema General de Seguridad en Salud (SGSSS) colombiano. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Solo se tuvieron en cuenta los costos de las pruebas: -Electromiografía con electrodo de fibra única: $71.262,1; -Ice test: $26.223,3; Prueba completa de Tensilon: $24.000; -Prueba de estímulo repetitivo: $46.219,1; -Test de anticuerpos contra receptor de acetilcolina por RIA (ACRA): $45.416. Fuente de costos: Para todas las pruebas diagnósticas se utilizó el promedio ponderado estimado desde los registros de uso de servicios de 2014 SISPRO (módulo de prestación de servicios, mediante conexión OBDS), teniendo como corte de búsqueda la fecha del desarrollo de este impacto (20/10/2015). Todos los costos de las pruebas son ponderados por el número de unidades utilizadas que reporta la misma base de datos. Además, todas\r\nlas tecnologías son costeadas desde bases de aseguradores, para confirmación de precios. Resultados: Actualmente, el mercado se encuentra dominado por la electromiografía con electrodo de fibra única, la cual se encuentra dentro del plan de beneficios, pero por opinión de los realizadores, una vez que la prueba de acetilcolina receptores y de Lambert entre al plan de beneficios, se aumentará su participación, lo cual repercutirá en un ahorro al sistema, dado que dichas pruebas son menos costosas.(AU)

Some current challenges in research on air pollution and health / Desafíos actuales de la investigación sobre contaminación del aire y salud

This commentary addresses some of the diverse questions of current interest with regard to the health effects of air pollution, including exposure-response relationships, toxicity of inhaled particles and risks to health, multipollutant mixtures, traffic-related pollution, accountability research, and issues with susceptibility and vulnerability. It considers the challenges posed to researchers as they attempt to provide useful evidence for policy-makers relevant to these issues. This commentary accompanies papers giving the results from the ESCALA project, a multi-city study in Latin America that has an overall goal of providing policy-relevant results. While progress has been made in improving air quality, driven by epidemiological evidence that air pollution is adversely affecting public health, the research questions have become more subtle and challenging as levels of air pollution dropped. More research is still needed, but also novel methods and approaches to address these new questions.

Este comentario aborda algunos de los temas de interés actual en relación con los efectos de la contaminación del aire sobre la salud, tales como las relaciones exposición-respuesta, la toxicidad y riesgos para la salud de las partículas inhaladas, las mezclas de contaminantes múltiples, la contaminación relacionada con el tráfico, la investigación sobre responsabilidad, y los problemas de susceptibilidad y vulnerabilidad. Considera los retos que se presentan a los investigadores que intentan proporcionar evidencia para los responsables políticos en estas cuestiones. Este texto acompaña otros trabajos con resultados del proyecto ESCALA, un estudio en varias ciudades de América Latina que tiene como objetivo general proporcionar resultados relevantes para la política pública. Aunque ha habido avances para mejorar la calidad del aire, gracias a la evidencia epidemiológica de que la contaminación aérea está afectando negativamente a la salud pública, las preguntas de investigación se han vuelto más sutiles y difíciles a medida que los niveles de contaminación se reducen. Se necesita más investigación, pero también nuevos métodos y enfoques capaces de enfrentar estas preguntas.

A Patient with Coexisting Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome

BACKGROUND: The coexistence of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) is very rare and remains controversial. CASE REPORT: A 48-year-old woman initially presented with noticeable right ptosis and intermittent diplopia. She then developed fluctuating proximal limb weakness and difficulty in swallowing. The serum titer of anti-acetylcholine-receptor antibody was elevated and the edrophonium (Tensilon) test was positive. However, repetitive nerve stimulation revealed abnormalities typical of LEMS. The patient exhibited a good response to treatment with anticholinesterase inhibitors and steroids, and long-term evaluation disclosed that she presented with the clinical, electrophysiological, and immunological characteristics of both diseases. CONCLUSIONS: The reported clinical and electrophysiological features suggest that this patient was a very rare case of combined MG and LEMS.

Muscle-Specific Receptor Tyrosine Kinase Antibody Positive Myasthenia Gravis Current Status

Muscle-specific tyrosine-kinase-antibody-positive myasthenia gravis (MuSK-MG) has emerged as a distinct entity since 2001. This disease has been reported worldwide, but with varying rates among patients with generalized acetylcholine-receptor-antibody-negative MG. MuSK-MG was detected in approximately 37% of generalized acetylcholine receptor antibody-negative MG. MuSK-MG patients were predominantly female with more prominent facial and bulbar involvement and more frequent crises. Disease onset tended to be earlier. Patients tended to have a relatively poor edrophonium response but showed prominent decrement in the repetitive nerve stimulation test in the facial muscles. Patients were more likely to display poor tolerance of, or a lack of improvement with, anticholinesterase agents. Somewhat better response was observed with steroids and plasma exchange. Most were managed successfully with aggressive immunomodulatory therapies, although a higher proportion of MuSK-MG patients had a refractory course when compared with other forms of generalized MG. I present here an up-to-date overview on MuSK-MG based on our experience at the University of Alabama at Birmingham and the existing literature.

pattern and presentation of myasthenia gravis in Al-Shaab and Omdurman Teaching Hospitals

Myasthenia gravis [MG] is the most common acquired autoimmune disorder of neuromuscular transmission. It has different patterns of presentation.to study the pattern and mode of presentation of Myasthenia Gravis in Al-Shaab and Omdurman Teaching Hospitals, Khartoum Sudan. The demographic and clinical characteristics of 50 patients of myasthenia gravis [MG] were reviewed in Alshab and Oumdrman Teaching Hospitals for five months period from May to October 2008. Out of 2400 patients attending neurology clinics 50 were found to have Myasthenia Gravis [MG] with female; male ratio of 2.5:1. The age at presentation was the second decade of life in 34%. Most of the patients [42%] were from Khartoum State followed by North Kordofan State [14%]. High occurrence of late onset fatigability and weakness was seen in 92% of our patients. Ocular muscles involvement was detected in 78%. MG was aggravated by hot weather and fever in 12% of the patients. Quinine represented the most common drug which aggravated the myasthenia symptoms in 4%. Diabetes mellitus and thyroid diseases were the most associated auto immune diseases seen in 12% and 4% respectively. The diagnosis was made by classic history and neurological examinations in 88% and positive neostigmin test in64%. The majority of patients were treated with steroids. Thymectomy was done in 10% patients. The outcome was excellent as 82% improved and only one [2%] patient died. Going with literature diagnosis of MG was made depending on classical history, full neurological examination and confirmed by tensilon test. Because of different reasons more sophisticated tests were not done in our patients. Only patients with malaria who were treated with quinine showed deterioration of their symptoms in our study. Strikingly, myasthenia crisis which were reported in 27% of patients were not seen in our population. Because of lack of usage of steroid sparing agents the vast majority [96%] of our patients were treated with steroids. Generalized myasthenia gravis with ocular involvement is common in our patients. However, pure OMG was not seen. Thymectomy was done in a small number of our patients with reference to other studies

Comparison of Antiallodynic Effects between Intrathecal Cholinesterase Inhibitors and NMDA Antagonists on Two Neuropathic Pain Rat Models / 대한마취과학회지

BACKGOUND: Cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists reduce the mechanical allodynia in neuropathic pain models. In this study our aim was to compare the antiallodynic effects between intrathecal cholinesterase inhibitors and NMDA antagonists on two well-characterized neuropathic pain rat models. METHODS: Male Sprague Dawley rats were anesthetized and either had the left L5 and L6 spinal nerves ligated (SNL group) or Freund complete adjuvant (FCA) administrated to the sciatic nerve (FCA group) in order to cause neuropathic pain. A catheter was implanted into the intrathecal space for drug administration. After obtaining baseline values, edrophonium (3-100microgram), neostigmine (0.3-10microgram), AP-5 (0.3-3microgram) and MK-801 (1-30microgram) were administered intrathecally to each group. The allodynic left hind paw withdrawal thresholds to von Frey hairs were assessed and converted to % MPE. Antiallodynic effects on the two groups were compared by analyzing dose-response curves and ED 50 values. Motor weakness was also checked. RESULTS: Intrathecal edrophonium, neostigmine, AP-5 and MK-801 had a dose-dependent antiallodynic effect on the two neuropathic pain models. Comparing the antiallodynic effect dose response curves, intrathecal cholinesterase inhibitors had lower ED 50 with steep slopes in the SNL model, whereas intrathecal NMDA antagonists had lower ED 50 in the FCA model, but there were no statistically significant differences between the two models. CONCLUSIONS: Intrathecal cholinesterase inhibitors and NMDA antagonists have relatively better antiallodynic effects on the SNL and FCA neuropathic pain rat models, respectively.

Papel dos testes provocativos esofagianos na investigação de pacientes com dor torácica de origem indeterminada / Role of esophageal provocative tests in the investigation of patients with chest pain of undetermined origin

RACIONAL: As dores de origem esofagiana e coronariana são bastante semelhantes do ponto de vista clínico, havendo necessidade de exclusão desta última, que ocasiona risco de morte. A investigação esofagiana tradicional de pacientes com dor torácica de origem indeterminada, envolve emprego de endoscopia digestiva alta, esofagomanometria e pHmetria esofagiana prolongada. Esses métodos, embora de grande importância diagnóstica, muitas vezes, revelam alterações, em sua maioria, potenciais para a origem da dor. Os testes provocativos de dor esofagiana, ao reproduzirem-na em laboratório, apontam com segurança a sua origem.OBJETIVOS: Determinar a positividade dos testes de perfusão ácida, do edrofônio e da distensão esofagiana com balão em pacientes com dor torácica de origem indeterminada, e correlacionar os resultados com os testes habitualmente empregados, estabelecendo o ganho no diagnóstico da dor esofagiana comprovada...

A case of myasthenia gravis aggravated and diagnosed after repeat cesaerian section / 대한산부인과학회지

Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. It may considerably affect the course of the pregnancy and cause serious compications in both the mother and the infant. Antibodies to nicotinic acetylcholine receptors are the cause of the disturbant nerve impulse transmission to muscle fibers. The clinical state at the beginning of pregnancy does not predict the occurrence of exacerbations or remissions. Each pregnancy has its effect on myasthenia gravis symptoms and does not predict the course of subsequent pregnancies. We experienced a patient received respiratory support because of poor ventilation after repeat caesarean section, but she recovered without complications soon. Two days later after operation, she complained of dysphasia, dysarthria. Then, Tensilon test and acetylcholine receptor antibody test were done. She was diagnosed as myasthenia gravis and administered pyridostigmine as therapeutic dose. We present this case with brief review of the concerned literatures.

The Usefulness of Ice Test for Diagnosis of Myasthenia Gravis in Patients with Ptosis

PURPOSE: To compare the results of the ice test with other diagnostic tests for the diagnosis of myasthenia gravis in patients with ptosis. METHODS: The patients included in this study presented with suspicious myasthenic blepharoptosis and visited the Department of Ophthalmology, Guro Hospital, Korea University between March 2003 and February 2004 for diagnosis. All patients received "myasthenic ptosis workup" including the ice test, edrophonium test, RNS EMG, and anti-acetylcholine receptor antibody (anti-AchR) titer test. The tests were compared for specificity, sensitivity, ease of performance, economic benefits and observed complications. RESULTS: The patients included six men and nine women with an average age of 36.9+/-2.4 yrs. Positive test results were obtained as follows: Ice test 80%, edrophonium test 66.7%, RNS EMG 53.3%, and anti-AchR titer test 86.7%. Adverse effects of edrophonium test were encountered in two patients who had nausea, vomiting, and dizziness. CONCLUSIONS: The authors found that the ice test was simpler, faster, more economic, and safer than the others for diagnosing blepharoptosis caused by myasthenia gravis. Considering its relative high sensitivity and specificity, the ice test should be the first screening test given to patients with suspicious myasthenic ptosis.

The Usefulness of Ice Test for Diagnosis of Myasthenia Gravis in Patients with Ptosis

PURPOSE: To compare the results of the ice test with other diagnostic tests for the diagnosis of myasthenia gravis in patients with ptosis. METHODS: The patients included in this study presented with suspicious myasthenic blepharoptosis and visited the Department of Ophthalmology, Guro Hospital, Korea University between March 2003 and February 2004 for diagnosis. All patients received "myasthenic ptosis workup" including the ice test, edrophonium test, RNS EMG, and anti-acetylcholine receptor antibody (anti-AchR) titer test. The tests were compared for specificity, sensitivity, ease of performance, economic benefits and observed complications. RESULTS: The patients included six men and nine women with an average age of 36.9+/-2.4 yrs. Positive test results were obtained as follows: Ice test 80%, edrophonium test 66.7%, RNS EMG 53.3%, and anti-AchR titer test 86.7%. Adverse effects of edrophonium test were encountered in two patients who had nausea, vomiting, and dizziness. CONCLUSIONS: The authors found that the ice test was simpler, faster, more economic, and safer than the others for diagnosing blepharoptosis caused by myasthenia gravis. Considering its relative high sensitivity and specificity, the ice test should be the first screening test given to patients with suspicious myasthenic ptosis.

Pharmacodynamic and Pharmacokinetic Study on the Neuromuscular Blocking Action of Rapacuronium: a Comparison with Other Muscle Relaxants / 대한마취과학회지

BACKGROUND: We evaluated the pharmacodynamic and pharmacokinetic properties of rapacuronium, a new non-depolarizing muscle relaxant. METHODS: The EC50 and EC95 values of rapacuronium, vecuronium, and rocuronium were determined on rat hemidiaphragm, and reversal effects were determined using edrophonium or pyridostigmine. In 57 healthy adults, neuromuscular transmission was monitored at the adductor pollicis. Patients received a single dose of succinylcholine (1.0 mg/kg), rapacuronium (1.5 mg/kg), rocuronium (0.6 mg/kg), or mivacurium (0.16 mg/kg). Onset time, clinical duration, recovery index (RI), total duration (TD), train of four (TOF) ratio at over 95% recovery of control first twitch height, cardiovascular effect, and intubation scores were measured. RESULTS: By in vitro study, the EC50 and EC95 of rapacuronium were 4 to 10 fold larger than those of vecuronium and rocuronium, and by clinical study, the onset time of rapacuronium was similar to those of succinylcholine. The clinical duration of rapacuronium was not different from those of succinylcholine and mivacurium. RI and TD of rapacuronium (9.6 +/- 3.5 min and 30.9 +/- 10.7 min) were longer than those of succinylcholine (3.5 +/- 1.1 min and 18.1 +/- 4.4 min) and mivacurium (6.5 +/- 0.9 min and 23.0 +/- 4.4 min) for spontaneous recovery, but not different during reversal by pyridostigmine (5.0microgram/kg). The TOF ratio was increased after pyridostigmine than during spontaneous recovery. Intubation conditions of rapacuronium were similar to those of succinylcholine. Heart rates were significantly increased (15% of control) within 2 min, but not mean arterial pressure after rapacuronium was administration. CONCLUSIONS: Rapacuronium can be considered a valid alternative to succinylcholine and had no observed cardiovascular effect.

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.

Sensitivity of Diagnostic Tests and Therapeutic Outcome in Ocular Myasthenia Gravis

PURPOSE: To compare the sensitivity of various diagnostic tests, and to assess the efficacy of therapy in the management of myasthenia gravis (MG). METHODS: Thirty-two patients with ocular findings with MG were examined by Stimulated Single Fiber Electromyograhy (SFEMG), Repetitive Nerve Stimulation (RNS) test, Edrophonium (Tensilon) test, anti-acethylcholine receptor antibody titer. We also studied retrospectively clinical characteristics and efficacy RESULTS: Mean age of patients was 32 years (range 1 to 63 years). Twenty (62.5%) were females and 12 (37.5%) were males. Mean duration of symptoms was 17 months (range 5 months to 10 years). Associated ocular findings were ptosis 31 eyes (97%), diplopia 20 eyes (63%), and ocular limitation 19 eyes (59%). The value of diagnostic sensitivity was 97% in SFEMG, 94% in tensilon test, 75% in RNS test, and 69% in anti-acetylcholine receptor antibody assay. Nine of 10 cases who were treated with thymectomy and pyridostigmine were markedly improved. Eight cases (25%) subsequently developed generalized type of myasthenia gravis. CONCLUSIONS: Ptosis and diplopia were most frequently associated with ocular myasthenia gravis. For diagnosis of ocular myasthenia gravis, SFEMG or tensilon test was the most sensitive test. Thymectomy combined with pyridostigmine bromide seemed to be an effective therapeutic modality.

Effects of Edrophonium and/or Pseudocholinesterase for the Reversal of Mivacurium-Induced Paralysis in vitro / 대한마취과학회지

BACKGROUND: Mivacurium is a nondepolarizing neuromuscular blocking agent hydrolyzed by pseudocholinesterase. Anticholinesterase used in the reversal of mivacurium-induced muscle relaxation may also inhibit plasma pseudocholinesterase, and delay hydrolysis of mivacurium. In this study, the effects of edrophonium and/or bovine pseudocholinesterase (BpChE) in the reversal of mivacurium were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Fifty Sprague-Dawley rats (150 - 200 g) were randomly allocated into 10 groups based on the dosage of edrophonium and BpChE. Each animal was anesthetized with thiopental sodium (40 mg/kg I.P.). The phrenic nerve-diaphragm was dissected and mounted in a bath containing an oxygenated Krebs' solution at 32degreesC. The phrenic nerve was stimulated at supramaximal intensity and the single twitch responses and train of four (TOF) ratio were measured. After stabilization of the twitch responses, mivacurium (1ng/ml) was administered incrementally to obtain more than 95% twitch inhibition. Reversal of the mivacurium-induced block by edrophonium (0.01, 0.1, 1, or 10ng/ml) and/or BpChE (0.1 u, or 1.0 u/ml) were tested. A single twitch height more than 75% of the baseline value was considered an adequate reversal. RESULTS: Mivacurium-induced paralysis was recovered more effectively by BpChE 1.0 u/ml than the other groups. Edrophonium improved a single twitch in a dose dependent manner. CONCLUSIONS: Mivacurium-induced paralysis can be more effectively reversed by BpChE than edrophonium. Inhibition of pseudocholinesterase was not observed by increasing the dose of edrophonium.

Persistent Diplopia after Local Anesthesia

PURPOSE: To determine causative factors of persistent diplopia after local anesthesia for ophthalmic surgery. METHODS: Prism and alternate cover test in the diagnostic positions of gaze and ductions/versions testing were performed in 26 patients with persistent diplopia six months after local anesthesia. Lancaster test, Bielshowsky head tilt test, double Maddox rod test, funduscopic examination for torsion, forced duction test, force generation test, tensilon test, thyroid function test, and/or orbit CT were done when necessary. RESULTS: Most of the patients (24 patients, 92%) did not have diplopia before local anesthesia. Of the thirteen patients with strabismus resulting from trauma to extraocular muscles, eleven patients showed vertical rectus overaction (10 superior recti, 1 inferior rectus) and two patients, mild vertical rectus underaction. Eight patients were presumed to have sensory deviation. In the remaining patients, one patient had childhood esotropia and another, old superior oblique palsy. Three patients showed a small vertical deviation without any specific cause. CONCLUSIONS: Fifty percent of diplopia was related with the surgical trauma to extraocular muscles, in which overactions (42%) were more common than underactions (8%). Thirty-five percent of the patients were presumed to have sensory deviation, which suggested the importance of preoperative examination for strabismus as well as the explanation about the risk of postoperative diplopia before surgery.