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Gravis
Kinds of Gravis Selected AbstractsMyasthenia Gravis and Related DisordersEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2009K. A. Jellinger No abstract is available for this article. [source] Dysphagia and Unexpected Myasthenia Gravis Associated with Primary Biliary Cirrhosis, Ulcerative Colitis and VitiligoJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2004Peter McCann MRCP No abstract is available for this article. [source] Successful Mitral Valve Surgery in a Patient with Myasthenia GravisJOURNAL OF CARDIAC SURGERY, Issue 2 2009Cüneyt Narin M.D. Most of the patients die because of a respiratory failure toward the end of the disease. A 49-year-old male patient with MG in whom a thymectomy operation had been performed five years ago had dyspnea, palpitation, and chest pain during his admission. After his examination, a severe mitral regurgitation was detected, and he underwent a successful mitral valve replacement. A general anesthesia management was performed using sufentanyl and propophol without any muscle relaxant agent. He was extubated seven hours after the surgery. He had difficulty in swallowing at postoperative day three, and his medication doses were increased. He was discharged from the hospital at postoperative day seven without any complication. MG is a rare disease and may cause morbid complications during the cardiac surgery, but can be successfully managed. [source] Less is more, or almost as much: A 15-item quality-of-life instrument for myasthenia gravisMUSCLE AND NERVE, Issue 2 2008Ted M. Burns MD Abstract We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the "gold standard," the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG. Muscle Nerve, 2008 [source] Plasmapheresis Does Not Affect Polysomnographic Parameters in Patients With Myasthenia Gravis: A Case Series StudyARTIFICIAL ORGANS, Issue 6 2010Jiann-Horng Yeh Abstract The purpose of this study was to evaluate the influence of plasmapheresis on sleep in patients with generalized myasthenia gravis and no respiratory symptoms. Seven myasthenia gravis patients, four women and three men, aged 24,52 years, underwent plasmapheresis treatment because of recent worsening of clinical weakness and poor response to previous treatments. We prospectively recorded the myasthenia gravis score, measured acetylcholine-receptor antibody concentration, performed polysomnography, and checked the Epworth Sleepiness Scale at baseline and 1 day after completion of the last session of plasmapheresis. Myasthenic weakness was ameliorated following plasmapheresis in all patients with a median decrease in myasthenia gravis score of 2 points (P = 0.0002) and a median clearance of 43.3% of acetylcholine-receptor antibody. However, there was no significant change in polysomnographic parameters, except for a trend toward shorter duration of the longest apnea period (P = 0.0763) following the treatment. Plasmapheresis did not affect polysomnographic parameters despite improved clinical weakness along with decreased myasthenia gravis score and acetylcholine-receptor antibody concentration. [source] Isolation and characterization of human anti-acetylcholine receptor monoclonal antibodies from transgenic mice expressing human immunoglobulin lociEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2005Evdokia Protopapadakis Abstract The isolation of human antibodies against muscle acetylcholine receptor (AChR), the autoantigen involved in myasthenia gravis (MG), is important for the development of therapeutically useful reagents. Monovalent antibody fragments from monoclonal antibodies against the main immunogenic region (MIR) of AChR protect the receptor from the destructive activity of MG autoantibodies. Human anti-AChR ,-subunit antibody fragments with therapeutic potential have been isolated using phage display antibody libraries. An alternative approach for obtaining human mAb has been provided by the development of humanized mice. In this report, we show that immunization of transgenic mouse strains with the extracellular domain of the human AChR ,-subunit results in antibody responses and isolation of hybridomas producing human mAb. Four specific IgM mAb were isolated and analyzed. mAb170 recognized the native receptor the best and was capable of inducing AChR antigenic modulation, suggesting its specificity for a pathogenic epitope. Moreover, the recombinant antigen-binding (Fab) fragment of this mAb competed with an anti-MIR mAb, revealing that its antigenic determinant lies in or near the MIR. Finally, Fab170 was able to compete with MG autoantibodies and protect the AChR against antigenic modulation induced by MG sera. This approach will be useful for isolating additional mAb with therapeutic potential against the other AChR subunits. [source] Myasthenia gravis and proximal limb weaknessEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006K. Papadopoulos No abstract is available for this article. [source] Seronegative myasthenia gravis: comparison of neurophysiological picture in MuSK+ and MuSK, patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006L. Padua The aim of this study was to compare the neurophysiological and clinical pictures of a large sample of seronegative myasthenia gravis (SNMG) patients with and without anti-MuSK antibodies. Fifty-two consecutive SNMG patients were retrospectively evaluated. They had undergone an extended neurophysiological evaluation: repetitive nerve stimulation (RNS), single fiber EMG (SFEMG), and electromyography (EMG) with nerve conduction study. A muscle biopsy was performed in 11 of 52 patients, the edrophonium test in 44 of 52 patients and anti-AChR antibodies and anti-MuSK antibodies were tested in all patients. Anti-MuSK antibodies were detected in 25 SNMG patients (48.1%). The number of women in the MuSK+ group was significantly higher (P = 0.01) than in the MuSK, group. Seronegative MuSK+ patients are more severely affected and the deficit often involves the bulbar and the respiratory muscles. No statistically significant differences were observed in the edrophonium test between MuSK+ and MuSK, groups. The RNS test was abnormal in a significantly higher number of MUSK, patients than MUSK+ patients (P < 0.00001). With regard to SFEMG data, MuSK, patients were characterized to have more severe neurophysiological pattern. Our observations showed several differences between the clinical and neurophysiological pictures of MUSK+ and MUSK, patients. [source] Seronegative myasthenia gravis: disease severity and prognosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2005F. Romi Around 10,20% of myasthenia gravis (MG) patients do not have acetylcholine receptor (AChR) antibodies (seronegative), of whom some have antibodies to a membrane-linked muscle specific kinase (MuSK). To examine MG severity and long-term prognosis in seronegative MG compared with seropositive MG, and to look specifically at anti-AChR antibody negative and anti-MuSK antibody negative patients. Seventeen consecutive seronegative non-thymomatous MG patients and 34 age and sex matched contemporary seropositive non-thymomatous MG controls were included in a retrospective follow-up study for a total period of 40 years. Clinical criteria were assessed each year, and muscle antibodies were assayed. There was no difference in MG severity between seronegative and seropositive MG. However, when thymectomized patients were excluded from the study at the year of thymectomy, seropositive MG patients had more severe course than seronegative (P < 0.001). One seropositive patient died from MG related respiratory insufficiency. The need for thymectomy in seronegative MG was lower than in seropositive MG. None of the seronegative patients had MuSK antibodies. This study shows that the presence of AChR antibodies in MG patients correlates with a more severe MG. With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies. [source] Crystal structure of Fab198, an efficient protector of the acetylcholine receptor against myasthenogenic antibodiesFEBS JOURNAL, Issue 13 2001Konstantinos Poulas The crystal structure of the Fab fragment of the rat monoclonal antibody 198, with protective activity for the main immunogenic region of the human muscle acetylcholine receptor against the destructive action of myasthenic antibodies, has been determined and refined to 2.8 Å resolution by X-ray crystallographic methods. The mouse anti-lysozyme Fab D1.3 was used as a search model in molecular replacement with the amore software. The complementarity determining regions (CDR)-L2, CDR-H1 and CDR-H2 belong to canonical groups. Loops CDR-L3, CDR-H2 and CDR-H3, which seem to make a major contribution to binding, were analyzed and residues of potential importance for antigen-binding are examined. The antigen-binding site was found to be a long crescent-shaped crevice. The structure should serve as a model in the rational design of very high affinity humanized mutants of Fab198, appropriate for therapeutic approaches in the model autoimmune disease myasthenia gravis. [source] Mycophenolate mofetil substitution for cyclosporine-dependent myasthenia gravis and nephrotoxicityINTERNAL MEDICINE JOURNAL, Issue 1 2007A. K. H. Lim Abstract Severe autoimmune myasthenia gravis is difficult to manage and may require immunosuppression with cyclosporine. However, cyclosporine dependency is associated with the risk of nephrotoxicity. Mycophenolate mofetil is a non-nephrotoxic alternative which should be considered to rescue cyclosporine-dependent, severe myasthenia gravis sufferers with renal impairment from progression to end-stage renal failure. However, the evidence is limited and studies have not assessed the outcome of a direct substitution in these cyclosporine-dependent patients. We study three such patients who successfully converted to mycophenolate mofetil, and briefly examine the evidence behind this option. We believe that total cyclosporine withdrawal is feasible, but strongly recommend overlapping mycophenolate mofetil treatment with cyclosporine. [source] Autoimmune myasthenia gravis: place of thymectomy and preferred techniqueINTERNAL MEDICINE JOURNAL, Issue 8 2002E. Byrne No abstract is available for this article. [source] Cutaneous granulomas in rheumatoid arthritisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2007Esther J. H. Collaris MD A 57-year-old man with rheumatoid arthritis and myasthenia gravis developed an asymptomatic erythematous plaque on his nose and skin-colored nodules on the elbows. Histopathological examination was suggestive of palisaded neutrophilic granulomatous dermatitis (PNGD). PNGD is a rather uncommon cutaneous finding in different collagen vascular disorders that can manifest with a broad range of clinical symptoms and histological signs. Based on the case report of the patient described here, we briefly discuss what is currently known about this disease. [source] Mucous membrane pemphigoid, thymoma, and myasthenia gravisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2000Haideh Yazdani Sabet In November 1997, approximately 1 year before being evaluated at the Mayo Clinic, Rochester, a 63-year-old woman presented with erosive tongue lesions that were diagnosed by her physician as oral lichen planus. The lesions responded well to 3 months of treatment with systemic and topical corticosteroids and topical antiyeast medication. She stopped taking the medications and had a relapse. A few months after the oral lesions developed, her left eyelid became ptotic. Results of magnetic resonance imaging of her brain were normal, and the ptosis resolved spontaneously after 2 weeks. One year later, her right eyelid began to droop, and the results of edrophonium testing were positive. She was prescribed prednisone, 30 mg daily, and pyridostigmine, as needed. The ptosis improved, but never fully resolved. Radiography revealed a left ,,thyroid nodule,'' but computed tomography did not show a mediastinal mass. She was advised to have the ,,nodule'' removed surgically and came to the Mayo Clinic, Rochester, for a second opinion. Her medical history was significant for the following: tinnitus, glaucoma, early bilateral cataracts, and long-standing hypertension, for which she took losartan, 50 mg twice daily. Other medications included: prednisone, 30 mg daily; pyridostigmine as needed; famotidine, 40 mg daily; and eyedrops for glaucoma. She denied any history of hyperthyroidism or hypothyroidism, head and neck irradiation, family history of thyroid disease, or diplopia. Hepatitis serologic studies revealed hepatitis B exposure and recovery, hepatitis C immunity, and a previous hepatitis A viral infection. On examination at the Mayo Clinic, Rochester, an erosive hypertrophic plaque was noted on the posterior dorsal half of the tongue, and vesicles and erythematous erosions on the hard and soft palates ( Fig. 1a). A lace-like white pattern was seen on the buccal mucosa bilaterally, and a small erosive patch on the left buccal mucosa ( Fig. 1b). Ocular and nasal mucous membranes were normal in appearance, and there were no pertinent skin findings. Dermatopathologic examination of an excisional biopsy specimen from the left dorsum of the tongue demonstrated an ulcer with epitheliomatous hyperplasia and a granulomatous reaction, presumably due to yeast infection. Silver staining showed hyphae and yeast at the base of the tongue ulcer. The results of the direct immunofluorescence study were negative and revealed no lichenoid changes on hematoxylin and eosin staining. Indirect immunofluorescence testing of the serum revealed a 1 : 80 titer of basement membrane zone antibodies, reflecting pemphigoid. This test was positive on repeat study. Salt-split skin on monkey esophagus revealed an epidermal pattern of basement membrane zone antibodies. Treatment included fluocinonide gel applied to the involved areas four times daily and oral antiyeast therapy (fluconazole, 200 mg once daily by mouth) while the rest of the evaluation was being completed. Figure 1(a). Erosive hypertrophic tongue plaque. Figure (b) ,. Erosive patch on the buccal mucosa. As part of the evaluation of the ptosis, a myasthenia gravis antibody panel was performed. It revealed the following abnormalities: striated muscle antibody at 1 : 480 (reference range, <1 : 60), acetylcholine receptor binding antibody at 6.33 nmol/L (reference range, ,,0.02 nmol/L), acetylcholine receptor blocking antibody at 31% (reference range, 0,25%), and acetylcholine receptor modulating antibody at 100% (reference range, 0,20%), suggesting thymoma. Treatment included pyridostigmine, 30,45 mg 3,4 times daily, to control the myasthenia symptoms, while the ill-defined neck mass was being evaluated. A mildly enlarged thyroid was noted on physical examination. Hematology panel revealed thyroid-stimulating hormone (TSH) levels in the low normal range; the thyroid microsomal antibody was normal. Chest radiography showed minor tracheal deviation, and a previous computed tomogram showed what appeared to be a 3-cm enlarged mass in the thyroid. Ultrasonographically guided thyroid biopsy did not show malignancy, but a benign mesenchymal-type tumor was found and surgical excision was planned. Intraoperatively, a thymoma of the left cervical thymic tongue was found. At 6 months' follow-up, the ptosis and oral mucosal lesions had improved significantly, although she continued topical corticosteroid therapy intermittently for minor erosive oral disease. [source] Effect of tacrolimus in a patient with pure red-cell aplasiaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2005S. YOSHIDA Summary A 78-year-old woman has suffered from pure red-cell aplasia (PRCA) associated with generalized myasthenia gravis and thymoma. Cyclosporin A (CyA) with corticosteroid increased numbers of erythroid cells in her bone marrow cells but she required monthly blood transfusions. Administration of tacrolimus as a substitution for CyA inhibited progression of anemia without the need for further blood transfusion. No serious side effects were observed. This case demonstrates that tacrolimus is another option of treatment for PRCA in patients who fail to respond to CyA. [source] T cell lymphocytosis associated with polymyositis, myasthenia gravis and thymomaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2000S.H. Otton Summary Peripheral T cell lymphocytosis is a rare finding in association with malignant thymomas. In the majority of previous cases, the tumours have behaved aggressively with symptoms arising from local invasion. We describe a patient with ocular myasthenia gravis who presented with a rapidly progressive polymyositis and neuropathy and who was subsequently found to have a thymic mass and a mild T cell lymphocytosis. The thymoma did not give rise to local symptoms and showed no evidence of progression over a 14-month period of follow-up. The possibility of an underlying thymic tumour should be considered in any patient with chronic T cell lymphocytosis if the circulating cells show mature morphology and there is no molecular evidence of monoclonality. [source] Starch and albumin mixture as replacement fluid in therapeutic plasma exchange is safe and effectiveJOURNAL OF CLINICAL APHERESIS, Issue 5 2008Gladys P. Agreda-Vásquez Abstract Therapeutic plasma exchange (TPE) is an effective treatment in Myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) and 5% human albumin is the replacement fluid of choice; however, it is expensive. More recently, it has been suggested that starch is a safe and cheaper choice to human albumin. Objective: To evaluate our 5-year experience using 3% hydroxyethyl starch (HES) and 5% human albumin mixture, as replacement fluid in TPE for these diseases. Materials and methods: Retrospective study carried out from January 2001 through September 2006. We included those patients with MG and GBS undergoing TPE. We analyzed clinical outcome (CO) and adverse events (AE) and our results were compared with a previous study which included similar patients undergoing TPE using just 5% human albumin. Results: Thirty-one procedures were carried out in 26 patients, a total of 147 TPE sessions. In the group of MG we had 57% complete responses (CR) and 86% overall response (OR) while in the group of GBS we had 40% CR and 60% OR. When we analyzed our CO with the previous study no statistical differences were found. Mean processed plasma volume (PPV) was 4.2 in MG and 5.5 in GBS. Twenty patients had AE, being hypotension and catheter dysfunction the most frequent ones, while tachycardia, hypertension and paresthesias were statistically more frequent in the HES/albumin group. Conclusions: TPE with a mixture of 3% HES and 5% human albumin is as effective and safe as 5% human albumin alone for patients with these diseases. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Prethymectomy plasmapheresis in myasthenia gravisJOURNAL OF CLINICAL APHERESIS, Issue 4 2005Jiann-Horng Yeh Abstract Plasma exchange before thymectomy may decrease the time on mechanical ventilation (MV) and shorten the stay in the intensive care unit (ICU) for patients with myasthenia gravis (MG). This study evaluated the effects of prethymectomy plasmapheresis. A total of 29 myasthenic patients, 18 women and 11 men aged 20,73 years, were treated with double filtration plasmapheresis (DFP) for two to five consecutive sessions over a period between 2 and 21 days (mean 8.1 days) before transsternal thymectomy. Acetylcholine receptor antibody (AchRAb) titers, vital capacity (VC), maximal inspiratory pressure (Pimax), and MG score were measured before and after the course of DFP. Three outcome measures including duration of postoperative hospital stay, duration of ICU stay, and duration of MV were analyzed for correlation with clinical variables. The duration of MV ranged from 6 to 93 h, with a median of 21 h. The median ICU stay was one day and the median postoperative hospital stay was 10 days. A higher removal rate of AchRAb was associated with a shorter duration of ICU and postoperative hospital stay (P = 0.001 and 0.019, respectively). Postoperative hospital stay was strongly correlated with post-DFP Pimax (P = 0.010), and marginally correlated with pre-DFP VC (P = 0.047) and to a lesser extent with pre-DFP Pimax (P = 0.063). Univariate analysis using the log rank test revealed that removal rate of AchRAb <30% (P = 0.043) and pre-DFP Pimax <,60 cmH2O (P = 0.024) were significantly associated with prolonged ICU stay. Risk factors for prolonged postoperative stay included post-DFP Pimax <,60 cmH2O (P = 0.017), pre-DFP Pimax <,60 cmH2O (P = 0.031), and post-DFP VC < 1.0 L (P = 0.046). Our results confirmed the efficacy and safety of DFP in prethymectomy preparation for myasthenic patients. J. Clin. Apheresis, 2005 © 2005 Wiley-Liss, Inc. [source] Patients with thrombotic thrombocytopenic purpura commonly develop metabolic alkalosis during therapeutic plasma exchangeJOURNAL OF CLINICAL APHERESIS, Issue 3 2001Marisa B. Marques Abstract Thrombotic thrombocytopenic purpura (TTP) and myasthenia gravis (MG) are category I indications for therapeutic plasma exchange (TPE). This study was based on the hypothesis that the development of metabolic alkalosis during TPE is more common in TTP than in MG, based on our previous observations. In order to test it, we compared the levels of bicarbonate and potassium in both groups of patients undergoing plasmapheresis. Fifteen patients with TTP (190 procedures) and ten MG patients seen concurrently were studied. While baseline bicarbonate levels were similar among all patients, the post-procedure bicarbonate levels in TTP patients were mostly elevated with a mean ± SD of 29.4 ± 3.5 mEq/L, as opposed to decreased or unchanged in MG patients 26.3 ± 3.1 mEq/L (mean ± SD) (P = 1.4 × 10,8). Furthermore, alkalosis in the TTP group persisted throughout subsequent daily treatments. There was also a significant decrease between pre- and post-TPE potassium levels in TTP patients (P = 3 × 10,21) by paired Student's t test. Additionally, samples with levels <3.3 mEq/L were alkalotic 75% of the time. In the MG group, however, potassium was normal in 85% and 83% of the pre- and post-TPE samples, respectively. Consequently, the hypokalemia was significantly more marked in the TTP group (P = 0.0008). These data confirm that plasmapheresis commonly induces metabolic alkalosis in TTP patients, probably due to high citrate in fresh frozen plasma, the frequency of treatments, and perhaps decreased renal clearance due to disease involvement of the kidneys. J. Clin. Apheresis. 16:120,124, 2001. © 2001 Wiley-Liss, Inc. [source] The use of desflurane or propofol in combination with remifentanil in myasthenic patients undergoing a video-assisted thoracoscopic-extended thymectomyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009P. GRITTI Background: Although several studies of the use of desflurane in anesthesia have revealed many desirable qualities, there are no data on the use and effects especially on the neuromuscular function of desflurane on myasthenia gravis (MG) patients. The purpose of this study was to evaluate the use of either desflurane or propofol, both combined with remifentanil, in patients with MG undergoing a video-assisted thoracoscopic-extended thymectomy (VATET). Methods: Thirty-six MG patients who underwent VATET were enrolled. Nineteen patients were anesthetized with remifentanil and propofol infused with a target-controlled infusion plasma model, and 17 patients with desflurane and remifentanil. No muscle relaxant was used. The intubating conditions, hemodynamic and respiratory changes, neuromuscular transmission and post-operative complications were evaluated. Results: Neuromuscular transmission was significantly decreased in the desflurane group (6.7%, from 3% to 9% during anesthesia P=<0.05). The intubating conditions were good in all 36 patients and 35 patients were successfully extubated in the operating room. The time-to-awakening, post-operatory pH and base excess were significantly different in the two groups, with a decreasing mean arterial pressure in the group administered with desflurane. No patients required reintubation due to myasthenic or cholinergic crisis, or respiratory failure. No other significant differences between the two groups studied were observed. Conclusion: Our experience indicates that anesthesia with desflurane plus remifentanil in patients with MG could determine a reversible muscle relaxation effect, but with no clinical implication, allowing a faster recovery with no difference in extubation time and post-operative complications in the two groups. [source] Infantile botulism: Clinical and laboratory observations of a rare neuroparalytic diseaseJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2000E Urdaneta-Carruyo Abstract: A 3-month-old male infant was admitted to the University Hospital of Los Andes with a history of constipation, weak crying, poor feeding, flaccidity and later bilateral ptosis and hyporeflexia. The admission diagnosis was septicaemia until an electrophysiological study reported postetanic facilitation with 50 Hz/seg stimulations four days later. The Clostridium botulinum toxin type B was isolated from the infant's stool samples and the organism grew in anaerobic cultures. The patient recovered completely and was discharged 2 months later. Although infant botulism is an uncommon disease in our environment, this diagnosis must be suspected in all afebrile infants with constipation, affected cranial nerves and generalized hypotonia. The principal differential diagnoses are Landry-Guillain,Barré syndrome, poliomyelitis, myasthenia gravis and infant muscular atrophy. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 3JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003F Terenghi Intravenous immunoglobulins (IVIg) are successfully used as immunomodulatory therapy in patients with multifocal motor neuropathy (MMN) but their mechanism of action remains unknown. An anti-idiotypic block of pathogenic autoantibodies has been often postulated even if other possible mechanisms, including a modulation of the release of various cytokines, have been proposed. To evaluate the expression of cytokines in patients with MMN and their possible modulation by IVIg, we determined circulating levels of TNF,, INF,, IL2, IL4, IL10, and IL12 by ELISA in serum samples of 17 patients with MMN and compared them with 12 patients with amyotrophic lateral sclerosis (ALS), 12 with multiple sclerosis (MS), 6 with chronic inflammatory demyelinating polyneuropathy (CIDP), 5 with myasthenia gravis (MG) and 12 healthy controls (NS). Comparable levels of INF,, IL2, IL4, IL10 and IL12 were detected in patients' sera and controls. Even if TNF, levels did not differ significantly among patients' groups, they were higher than in any healthy control (mean ± SD 1.2 ± 0.5 pg/ml, range 0.7,2.4 pg/ml), in 12 (70%) MMN patients (mean ± SD 3.6 ± 1.9 pg/ml; range 0.2,7.5 pg/ml), all ALS, 3 MS (25%), 2 CIDP (40%) and 2 MG (40%). We then measured the concentration of TNF, before and after IVIg therapy in 9 MMN and 2 ALS patients. In all but one MMN patients, circulating levels of TNF, slightly increased after treatment with IVIg (mean values 4.3 vs. 7.2 pg/ml) and decreased 3 weeks after therapy while in both ALS patients they decreased or remained unchanged. No detectable level of TNF, was found in IVIg preparation. This study shows that, similarly to what previously reported in other autoimmune neuropathy as GBS and CIDP, TNF, serum levels are slightly increased in MMN but, at odds with what reported in these disease, their concentration tend to increase parallel to clinical improvement after IVIg therapy. Further studies are necessary to clarify the pathogenetic implication of this finding and in particular whether a possible deviation from a presumably Th2 to a Th1 immune response may help explaining the effect of IVIg in MMN. [source] Treatment of a Myasthenic Dog with Mycophenolate MofetilJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2000C.W. Dewey DVM, DACVIM (Neurology), DACVS Summary A ten-year-old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side-effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one-month follow-up ACh receptor antibody concentration was normal (0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed. [source] Acetylcholine receptor-, subunit expression in myasthenia gravis: A role for the autoantigen in pathogenesis?MUSCLE AND NERVE, Issue 2 2009Jian Rong Sheng PhD Abstract Previous studies have shown increased expression of acetylcholine receptor-alpha (AChR-,) subunit transcripts in myasthenia gravis (MG) and experimental MG (EAMG), but none examined the functional properties of this overexpression. In this study we examined the mRNA and protein expression of AChR-, as well as the pattern of ,-bungarotoxin labeling in muscle tissue from EAMG mice with varying disease severity. AChR-, expression was increased considerably in endplates from mice with severe EAMG, but it was distinct and greatly in excess of ,-bungarotoxin labeling. This "aberrant expression" occurred in mice with morphologic endplate damage, and the pattern of complement and immunoglobulin deposition in muscle from these mice appeared to mirror the pattern of AChR-, expression. The loss of functional AChR in severe MG increases transcription of AChR-, mRNA, but the expressed protein is "functionally inert," failing to compensate for loss of AChR. This enhanced expression of AChR may play a role in driving the ongoing autoimmune response. Muscle Nerve 40: 279,286, 2009 [source] Less is more, or almost as much: A 15-item quality-of-life instrument for myasthenia gravisMUSCLE AND NERVE, Issue 2 2008Ted M. Burns MD Abstract We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the "gold standard," the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG. Muscle Nerve, 2008 [source] Antigen-specific T-cell activation in hyperplastic thymus in myasthenia gravisMUSCLE AND NERVE, Issue 1 2007Kimiaki Utsugisawa MD Abstract In order to determine whether antigen-specific T-cell activation by dendritic cells (DCs) is accelerated in thymuses exhibiting lymphofollicular hyperplasia (TLFH) among patients with early-onset myasthenia gravis (EOMG), we investigated the expression levels of phosphorylated protein kinase C (PKC), and the local relationship between the presence of phosphorylated PKC, and the homing receptor CD44 or CD83, a marker for mature DCs, in samples taken from EOMG patients with early improvement following thymectomy, in remnant thymuses from late-onset MG patients, and in non-MG control thymuses. Antigen-specific T-cell activation was markedly accelerated in TLFH from EOMG patients. Activated T cells and adjacent DCs appeared to be components of a CD44high cell population circulating from the blood to the thymus. Although there is no convincing evidence that thymectomy is of benefit in MG, in some EOMG patients with early improvement following thymectomy, blockade of CD44-associated circulation mechanisms is probably the cause for the early benefits of thymectomy and is a potential alternative to thymectomy. Muscle Nerve, 2007 [source] Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitabilityMUSCLE AND NERVE, Issue 6 2006Paul Maddison MD Abstract Acquired autoimmune neuromyotonia is regarded as part of the spectrum of peripheral nerve hyperexcitability disorders. We aimed to use clinical neurophysiological measurements to study the extent, distribution, and characteristics of spontaneous motor unit potentials in 11 patients with acquired neuromyotonia. Investigations revealed that most spontaneous discharges recorded were motor unit, or partial motor unit potentials of normal size. Bursts of motor unit potentials arose more commonly from distal portions of the peripheral nerve and had abnormal absolute and relative refractory periods. Spontaneous discharges in some patients occurred in semirhythmic bursts in certain muscles. No patient had neurophysiological abnormalities detectable in first-order neurons of the central nervous system when using transcranial magnetic stimulation to estimate the threshold for corticomotor excitation and determine central motor conduction time. Only patients with coexistent myasthenia gravis had neurophysiologically detectable defects in neuromuscular transmission. The pathogenic region of abnormality in peripheral nerve hyperexcitability disorders therefore seems to lie within the terminal branches of peripheral motor nerves. Muscle Nerve, 2006 [source] Single-fiber electromyography in limb and facial muscles in muscle-specific kinase antibody and acetylcholine receptor antibody myasthenia gravis,MUSCLE AND NERVE, Issue 4 2006Maria Elena Farrugia DPhil Abstract We examined the findings from single-fiber electromyography in extensor digitorum communis (EDC) and orbicularis oculi (OOc) in 13 myasthenia gravis (MG) patients with muscle-specific kinase antibodies (MuSK-MG) and 12 MG patients with acetylcholine receptor antibodies (AChR-MG) with similar clinical scores. More than 70% of AChR-MG patients had abnormal jitter in both EDC and OOc, but the majority of MuSK-MG patients had normal jitter in EDC despite abnormal jitter in OOc. These findings demonstrate clear differences between the neurophysiology of MuSK-MG and AChR-MG. Muscle Nerve, 2005 [source] Myasthenia gravis and premature ovarian failureMUSCLE AND NERVE, Issue 2 2004Monique M. Ryan MMed Abstract We describe a patient who developed seropositive myasthenia gravis 16 years after she was diagnosed with autoimmune premature ovarian failure with antibodies to the receptor for follicle-stimulating hormone (FSH). Although thymectomy led to improvement of her myasthenic symptoms, menses did not resume. Such combined seropositivity for antibodies to acetylcholine and ovarian hormone receptors in a patient with myasthenia gravis and premature ovarian failure may reflect common disease mechanisms, although the precise pathogenesis of these disorders remains ill-defined. Muscle Nerve 30: 231,233, 2004 [source] Clinical evaluation and management of myasthenia gravisMUSCLE AND NERVE, Issue 4 2004John C. Keesey MD Abstract Myasthenia gravis (MG) is a syndrome of fluctuating skeletal muscle weakness that worsens with use and improves with rest. Eye, facial, oropharyngeal, axial, and limb muscles may be involved in varying combinations and degrees of severity. Its etiology is heterogeneous, divided initially between those rare congenital myasthenic syndromes, which are genetic, and the bulk of MG, which is acquired and autoimmune. The autoimmune conditions are divided in turn between those that possess measurable serum acetylcholine receptor (AChR) antibodies and a smaller group that does not. The latter group includes those MG patients who have serum antibodies to muscle-specific tyrosine kinase (MuSK). Therapeutic considerations differ for early-onset MG, late-onset MG, and MG associated with the presence of a thymoma. Most MG patients can be treated effectively, but there is still a need for more specific immunological approaches. Muscle Nerve 29: 484,505, 2004 [source] | |||||||||||||||||||||||||||||||