Seropositive Myasthenia Gravis Research Articles

Seropositive Myasthenia Gravis Associated with Small-Cell Lung Carcinoma

BackgroundLambert-Eaton myasthenic syndrome is well known to be a classical paraneoplastic syndrome of small cell lung carcinoma (SCLC). Three cases of seronegative myasthenia gravis (MG) and SCLC were previously reported.Case ReportA 65-year-old man developed a severe progressive respiratory failure with clinical features of MG. Tests showed a decremental response in the repetitive nerve stimulation test, abnormal single-fiber electromyography, and positive acetylcholine receptor antibody. SCLC was confirmed by the lung biopsy.ConclusionsThis case represents the first case of seropositive MG and SCLC.

Frequency of Autoimmune Diseases in Myasthenia Gravis: A Systematic Review

ABSTRACTThe course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%–14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and anti-acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Unusual association of seronegative, nonparaneoplastic limbic encephalitis and relapsing polychondritis in a patient with history of thymectomy for myasthenia: a case study

Limbic encephalitis (LE) associated with other autoimmune disorders is relatively rare. There is an evidence of LE with relapsing polychondritis [1, 2] or Sjogren’s syndrome [3], and also with myasthenia gravis [6]. We present a case of LE with an unusual association of different autoimmune conditions. A 73-year-old man developed headache and fever over 2 weeks and a transitory loss of consciousness. His wife reported episodes of confusion over the previous 2 months. He had a medical history of seropositive myasthenia gravis in 1996 requiring artificial ventilation, plasmapheresis, immunotherapy and thymectomy. Removed thymus showed atrophy without histopathological finding of thymoma or thymic hyperplasia. After 2 years, the patient was asymptomatic and decided to stop all treatment and follow up. His medical history also included acute myocarditis in 1972, asthma, gastric ulcer. He was followed up for bladder carcinoma without signs of activity since the operation in 1994 and recent biopsy revealed prostatic microcarcinoma. On admission, he was disoriented in place and person and was confabulating. He had painful erythema of his right auricle, which he had experienced in the past. Neurological examination was unremarkable except for slight gait instability. Laboratory results showed mild inflammatory changes (hyperleucocytosis, higher erythrocyte sedimentation rate 20 mm/h, and raised C reactive protein 20.3 mg/l). Thyroid function was normal. Serum auto-antibodies ANA, ANCA, GBMi and dsDNA were negative; only anti-striatal muscle antibodies were slightly positive. Cerebrospinal fluid analysis showed mild protein-cytological association (hyperproteinorachia 0.657 g/l and 89 mononuclear cells). Serology for HIV, Borrelia, HSV1,2, CMV, EBV, VZV and neurosyphilis was negative. Onconeural antibodies anti-Yo, Hu, Ri, anti-VGKC antibodies, anti-GAD, antiamphiphysin and anti-NMDA receptor antibodies were negative in serum and cerebrospinal fluid. MRI showed FLAIR and T2 hippocampal temporal hyperintensities, vascular white matter lesions and moderate atrophy (Fig. 1). EEG repeatedly showed slow waves in the temporal regions. Whole body PET scan was negative. Progressively, myoclonic jerks, cerebellar signs, aphasia and hallucinations appeared with worsening of cognitive impairment. Bilateral auricle swelling occurred with softening and loss of cartilage contour. Biopsy revealed nonspecific cartilage inflammation without signs of an acute vasculitis (Fig. 2b), compatible with criteria for relapsing chondritis. Parenteral bolus of methylprednisolone 1,500 mg over 3 days led to partial and transitory improvement, therefore a month later bolus of 3,500 mg was repeated followed by permanent treatment with oral methylprednisolone 24 mg daily. Painful swelling extended to elbows and knees, and partial complex seizures with orofacial automatisms developed. A third bolus of 1,500 mg methylprednisolone was administered and four cycles of plasmapheresis were performed with only limited effect, moreover, massive eruptions of herpes labialis required intravenous acyclovir. Finally, IVIG was added. The patient’s condition worsened K. Storey (&) R. Rusina Department of Neurology, Thomayer Teaching Hospital and Institute for Postgraduate Education in Medicine, Videňska 800, 14059 Prague 4, Czech Republic e-mail: katerina.storey@gmail.com

Serological and Clinical Features of Patients with Myasthenia Gravis in North Indian Population

ABSTRACTMyasthenia gravis (MG) is a disorder of neuromuscular junction associated with presence of antibodies against nicotinic acetylcholine receptors (nAChRs). Here, we compared the clinical and serological profile of seropositive myasthenia gravis (SPMG) and seronegative myasthenia gravis (SNMG) patients. Anti-AChR antibody was measured using radio receptor immunoassay and correlated with clinical phenotype in 250 MG patients over 2004 and 2006. Out of 250 MG patients, 161 (64.4%%) were males (male:female == 1.8:1). SNMG patients formed 40%% (n == 101) of our MG patients which is much higher as compared to Caucasian and Oriental population (15%%–20%%). The median age of disease onset in SPMG was significantly higher than SNMG patients (43 years; range 8–74 vs. 35 years; range 4–72, p == .022). A bimodal peak of age of disease onset in both genders was observed (first peak in second–third decades and second one in fifth–sixth decades). Among the MG patients with late-onset of disease, male were significantly higher compared to Caucasian and Oriental MG population (p == .047). MG patients with thymoma were significantly older and consisted of higher percent of males. Bulbar symptoms and severe grade (IIB++ III++ IV) at disease onset were more frequent in SPMG than SNMG patients.

Multifocal Paraneoplastic Cortical Encephalitis Associated With Myasthenia Gravis and Thymoma

To report a case of multifocal cortical encephalitis associated with thymoma and to establish an association of this thymoma-related paraneoplastic syndrome with voltage-gated potassium channel antibodies. Case report. University hospital. A 43-year-old woman with a history of seropositive myasthenia gravis and successfully treated invasive thymoma. Four years after thymectomy, she presented with seizure and rapidly progressive confusion and aphasia. Myasthenia gravis remained in pharmacological remission. Magnetic resonance imaging of the brain showed innumerable cortically based signal abnormalities as well as extensive left mesial temporal lobe abnormality with minimal enhancement. Chest computed tomography showed abnormal pleural thickening of the left lung, which proved to be recurrent metastatic thymoma. Results of serological evaluation were positive for acetylcholine receptor, striational, and voltage-gated potassium channel antibodies. She showed partial improvement in response to immunotherapy and chemotherapy but ultimately died 2 months later of tumor complications. Thymoma and myasthenia gravis may be associated with other autoimmune neurological disorders including paraneoplastic encephalitis. This second case of thymoma-associated multifocal cortical encephalitis demonstrates that autoimmune encephalitis can extend to cortical regions outside the limbic system. Autoimmune encephalitis should be considered in the differential diagnosis of patients with myasthenia gravis or thymoma who develop new cognitive symptoms.

SEROPOSITIVE MYASTHENIA GRAVIS: A NATIONWIDE EPIDEMIOLOGIC STUDY

Few cohort epidemiologic myasthenia gravis (MG) studies have been published,1,2 most of them with data from multiple databases and varying inclusion criteria. A review from 1996 reported an increasing MG incidence and prevalence.3 Studies from the last 10 years refer to a yearly incidence between 4 and 11 per million1,2,4 and a prevalence ranging from 70 to 150 per million.1,2,4,5 There is only one laboratory in Norway offering acetylcholine receptor (AChR) antibody testing and all samples are sent to this laboratory. Presence of AChR antibodies is nearly 100% specific for MG in individuals with symptoms.6 The aims of this study were to determine the incidence and prevalence of AChR antibody-positive (seropositive) MG, to describe its gender-specific characteristics, and to examine epidemiologic trends during the last decades. ### Methods. Norway had a population of 4,737,171 inhabitants on January 1, 2008, our chosen MG prevalence day (Statistics Norway-SSB, www.ssb. no). Since the start of our AChR antibody …

Juvenile seropositive myasthenia gravis with anti-MuSK antibody after thymectomy

We report the case of a 17.5-year old girl with generalized myasthenia gravis (MG). When she was 13, she started to complain of episodic diplopia, ptosis and mild fatigability of upper and lower extremity muscles. She was diagnosed with MG 3 years later, after exacerbation of her limb muscle weakness. Acetylcholine receptor antibody was positive (2.56 nmol/l, n < 0.4 nmol/l), anti-MuSK antibodies were not tested at that time. She was treated with a thymectomy. After the operation a gradual worsening of her MG was seen; she reported pirydostygmine intolerance. On retesting, acetylcholine receptor antibodies were negative and she was positive for anti-MuSK antibodies. She received immunosuppressive treatment with prednisone and azathioprine with clinical improvement. She is the third reported patient diagnosed with acetylcholine receptor antibody-positive MG, who became MuSK-positive after thymectomy. Recognition of such clinical patterns may be important for decision making in myasthenia gravis patients.

Acetylcholinesterase inhibitors in MG: To be or not to be?

Myasthenia gravis (MG) is an autoimmune disorder usually caused by antibodies against either the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) at the neuromuscular junction. Neuromuscular transmission failure results in muscle fatigue and weakness that can be treated symptomatically with acetylcholinesterase inhibitors (AChEIs). Long-term treatment with nonselective AChEIs may have considerable drawbacks; thus, this medication is ideally tapered when strength improves. Patients with AChR antibodies respond beneficially to treatment, whereas patients with MuSK antibodies generally do not. Recently, the selective AChEI EN101, which specifically targets the isoform of "read-through" AChE (AChE-R), has been developed and may be of importance for symptomatic relief in AChR-antibody seropositive MG. This article is a review of the mechanisms, therapeutic effects, and drawbacks, with both old and new AChEIs in MG.

Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR

We compared myopathological features in myasthenia gravis (MG) patients with antibodies against AChR (seropositive) and muscle-specific tyrosin-kinase (MuSK). While the immunopathogenesis of seropositive MG is well known, there is a lack of pathological studies in anti-MuSK antibody-positive (MuSK+) MG. We analysed skeletal muscle biopsy features of 13 MG patients: 6 MuSK+ (all women) and 7 anti-AchR antibody-positive (AChR+) (2 women and 5 men). In our histopathological examination, we quantified the atrophy factor of both fibre types, and the extent of minicores, myofibrillar disarray, cytochrome c oxidase (COX)-negative fibres, mitochondrial aggregates and fibre type grouping. Mean muscle fibre atrophy factor was higher in AChR+ MG than MuSK+ MG, both in type I fibres (494 vs. 210) and particularly in type II fibres (1023 vs. 300). Fibre type grouping was observed in AChR+ MG whereas COX-negative fibres were common in MuSK+ MG. Bulbar muscles were more severely affected in MuSK+ MG and the disease was more severe: the onset was usually earlier (39 years) with Myasthenia Gravis Foundation of America score III in MuSK+ MG, and score II was found in AChR+ MG (62 years). Muscle biopsies of MuSK+ MG show myopathic signs with prominent mitochondrial abnormalities, whereas neurogenic features and atrophy are more frequently found in AChR+ MG. The mitochondrial impairment could explain the oculo-bulbar involvement in MuSK+ MG.

A comparison of long-term post-thymectomy outcome of anti-AChR-positive, anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis

Objective: A single-centre, non-randomized, non-controlled study was designed to compare the long-term post-thymectomy clinical outcome in anti-AChR-positive, anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis (MG). Methods: A total of 331 consecutive patients with seropositive MG, 55 with seronegative MG and 10 with anti-MuSK-positive MG underwent extended transsternal thymectomy (T-3b according to Myasthenia Gravis Foundation of America). The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients with and without anti-AChR and anti-MuSK antibodies. Results: The mean follow-up was 218.3 (SD 128.1) months in the seropositive MG group, 149.8 (SD 131.1) in the seronegative group and 169.9 (SD 116) in the anti-MuSK-positive group. In the seropositive MG group, the probability of obtaining CSR at 5 years post-thymectomy was 51.1% for the seropositive group compared with 40 for the seronegative group (p = 0.05) and 20 for the anti-MuSK-positive group (p = 0.03). Differences between the seronegative and anti-MuSK-positive groups were not observed. The estimated median follow-up to obtain a CSR was 17.8 months (95% confidence interval [CI] 15.7 – 19.8 months) in seropositive MG patients, 22.1 (95% CI 16.7 – 27.4 months) in seronegative MG patients and 20.6 (95% CI 13.3 – 27.9 months) in anti-MuSK-positive MG patients (long-rank test, p = 0.07). Conclusions: Long-term post- thymectomy clinical outcome was better in patients with conventional anti-AChR antibodies than in those with seronegative disease. In seronegative anti-MuSK-positive MG, thymectomy seems to be less effective than in anti-MuSK-negative MG but this study cannot answer the question of whether thymectomy should be undertaken in anti-MuSK-positive patients.

The co-occurrence of serologically proven myasthenia gravis and Miller Fisher/Guillain Barré overlap syndrome — A case report

The co-occurrence of myasthenia gravis (MG) and Guillain Barré syndrome (GBS) is uncommon with a few reported cases in the literature. There is only one reported case of MG and Miller Fisher variant of GBS. We described an 84 year old Chinese woman with underlying seropositive myasthenia gravis (MG) who presented with ophthalmoplegia, areflexia and acute neuromuscular weakness. She was proved to have co-occurrence of MG and GBS/Miller Fisher overlap syndrome with positive anti-GQ1b antibody. The unusual finding in this patient raises an interesting question on their pathogenesis with the possibility that prior activation of the immune system may predispose the development of autoantibodies against other antigens within the same set of muscles.

Influence of ectopic thymic tissue on clinical outcome following extended thymectomy in generalized seropositive nonthymomatous myasthenia gravis

We determined the effect of detecting ectopic thymic tissue in thymectomy specimens on the long-term outcome of patients with myasthenia gravis. A total of 83 consecutive patients with generalized seropositive nonthymomatous myasthenia gravis underwent transsternal extended thymectomy (T-3b according to Myasthenia Gravis Foundation of America). Ectopic thymic tissue was only accepted when Hassal's corpuscles in the excised cervicomediastinal fat were documented. The primary endpoint was to assess differences in time to obtain complete stable remission (CSR) according to the presence or absence of ectopic thymus. Thirty-five patients (42.2%) had ectopic thymic tissue. The mean follow-up was 88.4+/-36.3 months (range 20-144). By the Kaplan-Meier analysis method, the estimated median follow-up to obtain a CSR in the group without ectopic thymic tissue was 32.9 months (95% confidence interval [CI] 21.1-44.8 months) and 117.8 months (95% CI 98.0-137.6 months) for the group with ectopic thymic tissue (log-rank test, p=0.0002). The probability over time of obtaining CSR for the groups without and with ectopic thymic tissue was 65% vs 26% at 5 years. After stratification by hyperplasia or involution of the thymus as well as by post-thymectomy immunomodulating regimen (prednisone and prednisone-tacrolimus), the probability over time of obtaining CSR at 5 years was also significantly higher for patients without ectopic thymic tissue than for those with ectopic thymic tissue. The clinical outcome of patients with nonthymomatous seropositive myasthenia gravis is significantly affected by the presence of ectopic thymic tissue in the mediastinal fat.

Thymus and Myasthenia Gravis: What can we learn from DNA microarrays?

This review is dedicated to John Newsom-Davis, who was an exceptional colleague and friend, always exchanging ideas with respect and consideration. We shall not forget his involvement and passion in search for the truth on the role of thymectomy in the management of Myasthenia Gravis (MG). In this short review, we shall summarize what we learnt from DNA microarrays applied to MG thymus. We shall focus on three main comparisons of the thymic transcriptomes: 1) highly hyperplastic MG patients versus non-MG adults; 2) corticosteroid-treated versus untreated seropositive MG patients; and 3) seronegative versus seropositive MG patients.

Atrophy of type II fibres in myasthenia gravis muscle in thymectomized patients: steroid‐induced change with prognostic impact

Selective atrophy of type II muscle fibres has been long recognized as an enigmatic but consistent feature of myasthenia gravis (MG) muscle; however, the pathophysiology and the mechanism of that change have remained obscure. In the present study, the results of histomorphometric analysis performed on muscle biopsies from 207 thymectomized seropositive MG patients were correlated with clinical features of MG to demonstrate possible pathophysiological associations and potential prognostic impact. The atrophy of type II fibres was verified in 35 cases (16.9%), being more pronounced in fibres of IIB subtype. It was neither significantly associated with the duration and severity of MG nor with the age of the patients. On the other hand, we demonstrated that the atrophy associated with long-term treatment with corticosteroids, and correlated with increasing doses. Thus, we suppose that the atrophy of type II muscle fibres in seropositive MG is steroid induced rather than MG-associated event. Although the MG patients with atrophy of type II fibres did not differ from the remaining MG cases in terms of improvement in the disease during the follow-up period, our analysis provides clear evidence that they presented a significantly slower tendency to reach an asymptomatic state after thymectomy. Therefore, the steroid-induced atrophy of type II fibres in MG muscle might be considered to be an unfavourable prognostic factor.

Antisense Treatment for Myasthenia Gravis

Acetylcholinesterase pre-mRNA is susceptible to alternative splicing. Myasthenia gravis has been shown to be associated with the expression of the readthrough transcript (AChE-R), which, unlike the normal "synaptic" transcript (AChE-S) is not tethered to the post-synaptic membrane, but is a soluble monomer in the synaptic cleft. In rats with experimental autoimmune myasthenia gravis (EAMG), inhibition of production of AChE-R using antisense is associated with a significant reduction in synaptic expression of AChE-R mRNA and protein, with improved muscle strength and stamina and increased survival. Synaptic AChE does not appear to be significantly affected by the induction of EAMG or treatment with antisense to AChE-R. Monarsen (EN101) is a synthetic 20-base antisense oligodeoxynucleotide directed against the human AChE gene. It is modified to achieve stability for oral administration. Sixteen patients with seropositive myasthenia gravis who were responsive to pyridostigmine were withdrawn from it and treated with Monarsen. Fourteen patients experienced a clinically significant response. In some, the improvement was dramatic. Although the dose of pyridostigmine was not optimized before the study, the majority of responders achieved better Quantitative Myasthenia Gravis scores than on pyridostigmine. The response of an individual muscle group to Monarsen was related to the degree of deterioration following the withdrawal of pyridostigmine. Cholinergic side effects were conspicuous by their absence. Monarsen is now being investigated in a phase II study.

Serum matrix metalloproteinase-3 levels are elevated in myasthenia gravis

MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signalling by controlling acetylcholine receptor clustering. The degradation of agrin by MMP-3 may disrupt the neuromuscular junction leading to a failure of neuromuscular transmission and muscle weakness. We have therefore examined the levels of MMP-3 in 116 patients with myasthenia gravis (MG) and 90 healthy controls. A significant elevation in MMP-3 levels was observed in 10% of seronegative and 17% of seropositive MG patients, indicating that MMP-3 may play a pathogenic role in a proportion of MG patients.

Incidence of seropositive myasthenia gravis in Cape Town and South Africa.

Myasthenia gravis (MG) is a treatable autoimmune disease characterised by fatiguable weakness of skeletal muscles. More than 85% of MG patients have antibodies to the acetylcholine receptor (AChR) at the neuromuscular junction or are seropositive for MG (SPMG). In the developed world the incidence of MG has increased, particularly among older individuals, but no epidemiological studies have been done on SPMG in Africa. To determine the annual incidence rate (IR) of SPMG in the Cape Town (CT) municipality, and the crude annual IR of SPMG for the whole of South Africa (SA). Positive AChR antibody tests were identified between 1 January 2003 and 1 January 2005 for patients living in CT, and the age- and sex-specific incidences were calculated. To determine the national crude annual IR over the same period, positive assays were identified from the laboratories that process AChR assays for SA. National Census 2001 population statistics formed the denominators. There were 65 positive assays in CT, and 230 nationwide. Based on these figures the annual IR for CT was 11.2 per million per year (95% confidence interval (CI) 8.7 - 14.3), and for South Africa 2.6 per million/year (95% CI 2.2 - 2.9). After a questionnaire response from CT neurologists regarding the routine use of the AChR antibody assay, the annual IR for CT was adjusted to 12.6 per million (95% CI 9.9 - 15.9) to incorporate those presumed to have SPMG without a confirmatory test. In CT, the IR in females was 15.3 per million/year (95% CI 11.2 - 20.4), and in males, 6.8 per million/year (95% CI 4.1 - 10.7). The CT IRs for blacks, coloureds and whites were not statistically different after adjusting for age and gender. The IR of SPMG in CT was 6 times greater in those presenting after the age of 50 years than in those with earlier disease onset (95% CI 3.7 - 9.7). The annual IR of SPMG in CT is much the same as rates recorded recently in other developed countries, but the rest of SA has a much lower IR. A preponderance of MG starting after the age of 50 years reflects a worldwide trend, although the CT data showed a relatively lower-than-expected incidence for older males. IRs for SPMG vary widely in different regions in SA; this is likely to be related to differences in regional health care delivery, and underdiagnosis.

TREATMENT OF HUMAN MYASTHENIA GRAVIS WITH ORAL ANTISENSE SUPPRESSION OF ACETYLCHOLINESTERASE

Antisense oligonucleotides are synthetically manufactured short segments of deoxynucleotide sequences that cause targeted gene transcription inhibition. They are designed to interact with their specific complementary mRNA, thereby interfering with transcript stability and/or translation.1,2 This process activates endogenous RNAse-H, which destroys the target mRNA and releases the antisense molecule to act on another mRNA transcript. EN101 antisense (Monarsen) acts against both the catalytic and noncatalytic contributions of acetylcholinesterase (AChE). It was designed to induce destruction of the read-through splicing variant of AChE3 and has shown promising short- and long-term therapeutic effects in experimental myasthenia gravis (MG), both IV and orally.4The objectives of this open label human study with oral EN101 were 1) to evaluate the safety of short-term administration in seropositive MG and 2) to assess possible efficacy by monitoring changes in patients’ functional status. ### Methods. An open label trial was conducted in 16 patients with stable MG receiving at least 180 mg of pyridostigmine daily (for more details see the Neurology Web site at www.neurology.org). For assessment of MG status, the Quantitative MG (QMG) score …

Microarrays Reveal Distinct Gene Signatures in the Thymus of Seropositive and Seronegative Myasthenia Gravis Patients and the Role of CC Chemokine Ligand 21 in Thymic Hyperplasia

Myasthenia gravis (MG) is an autoimmune disease mainly caused by antiacetylcholine receptor autoantibodies (seropositive (SP) disease) or by Abs against unknown autoantigenic target(s) (seronegative (SN) disease). Thymectomy is usually beneficial although thymic hyperplasia with ectopic germinal centers is mainly observed in SP MG. To understand the role of thymus in the disease process, we compared the thymic transcriptome of non-MG adults to those of SP patients with a low or high degree of hyperplasia or SN patients. Surprisingly, an overexpression of MHC class II, Ig, and B cell marker genes is observed in SP but also SN MG patients. Moreover, we demonstrate an overexpression of CXCL13 in all MG thymuses leading probably to the generalized B cell infiltration. However, we find different chemotactic properties for MG subgroups and, especially, a specific overexpression of CCL21 in hyperplastic thymuses triggering most likely ectopic germinal center development. Besides, SN patients present a peculiar signature with an abnormal expression of genes involved in muscle development and synaptic transmission, but also genes implicated in host response, suggesting that viral infection might be related to SN MG. Altogether, these results underline differential pathogenic mechanisms in the thymus of SP and SN MG and propose new research areas.

The effectiveness of thymectomy on seronegative generalized myasthenia gravis: comparing with seropositive cases

To investigate the efficacy of thymectomy between patients with seronegative myasthenia gravis (SNMG) and seropositive myasthenia gravis (SPMG). We present here the first Taiwanese retrospective paired cohort study comparing the effectiveness of thymectomy among 16 seronegative and 32 seropositive MG patients after matching for age-of-onset and time-to-thymectomy, and following up over a mean of 35 +/- 20 (7-86) months. Clinical characteristics and complete stable remission (CSR) rates were compared and analyzed between the groups. There were no major clinical differences between the two groups except for our finding of a lower percentage of SNMG receiving preoperative plasmapheresis or human immunoglobulin than SPMG (31% for SNMG vs 72% for SPMG, P = 0.007). CSR rates calculated using the Kaplan-Meier method were similar in the two groups (38% for SNMG vs 50% for SPMG, P = 0.709). The median time for CSR was 47.4 months for SNMG and 48.2 months for SPMG. Thymic hyperplasia were the most common pathology (69% for SNMG vs 88% for SPMG, P = 0.24). During the follow-up period, we found no group difference on prednisolone or pyridostigmine dosages. Significant postoperative dosage reductions on pyridostigmine, but not on prednisolone, were found in both groups. Thymectomy has a comparable response among SNMG and SPMG in our study. Thymic hyperplasia is prevalent in our SNMG patients and thymectomy may also be a therapeutic option to increase the probability of remission or improvement in SNMG. More prospective controlled trial will be helpful in the future.