Presence Of Thymoma Research Articles

No sex-based differences in odds of starting or time to treatment of generalized myasthenia gravis: A single center cohort study.

Females with generalized myasthenia gravis (gMG) report lower quality of life (QoL) and have more severe disease than males. Sex differences in disease characteristics exist, however whether there are sex differences in the treatment of gMG that may contribute to QoL disparities is unknown. Our objective is to determine whether there are sex differences in the treatment of gMG. We performed a single-center retrospective study of people diagnosed with gMG at the University of Calgary between 1997 and 2021. Primary outcome was proportion starting treatment and secondary outcome was time from diagnosis to treatment initiation. Treatments included pyridostigmine, prednisone, steroid sparing therapies (azathioprine, mycophenolate mofetil [MMF], methotrexate [MTX], or tacrolimus), intravenous immunoglobulin (IVIg), plasmapheresis, rituximab, eculizumab, cyclosporine, stem cell transplantation, and thymectomy. Multivariable logistic and Cox proportional hazards regression models were used to examine treatment associations with sex, adjusted for time from onset to diagnosis, age at diagnosis, presence of thymoma, and antibody status. A total of 179 people with gMG were included (41.9% female). Odds of starting treatment were not statistically associated with sex after adjustment for confounders and correction for multiple testing. Results of the secondary analysis using time to treatment initiation as the outcome were similar. We found no sex differences in odds of starting treatment or time to treatment initiation that might explain previously observed sex-based differences in QoL. Future work should capture physician and patient treatment preferences that may influence disease management.

Prevalences of Other Non-Thyroid Autoimmune Diseases and Factor Associated with Their Presence in Ocular Myasthenia Gravis.

To report the prevalences of other non-thyroid autoimmune diseases and identify factors associated with their presence in ocular myasthenia gravis (OMG) subjects. A total of 208 subjects with OMG diagnosis were included. Demographic data, clinical characteristics, the ice-pack test, the acetylcholine receptor (AChR) antibody test, electrophysiology tests (single-fiber electromyography and repetitive nerve stimulation), the presence of thymoma, generalized myasthenia gravis conversion, and the presence of other non-thyroid autoimmune diseases (defined as the presence of at least one other non-thyroid autoimmune disease) were retrospectively reviewed. Factors associated with the presence of other non-thyroid autoimmune diseases were analyzed by univariate and multivariate logistic regression. Of the total 208 subjects, 21 (10.10%) exhibited the presence of other non-thyroid autoimmune diseases (19 subjects (9.14%) and 2 subjects (0.96%) had one and two other non-thyroid autoimmune diseases, respectively), and systemic lupus erythematosus (SLE) was diagnosed in 9 subjects, followed by Sjogren's syndrome (7 subjects), rheumatoid arthritis (6 subjects), and ankylosing spondylitis (1 subject). Therefore, the prevalences of SLE, Sjogren's syndrome, rheumatoid arthritis, and ankylosing spondylitis in OMG subjects were estimated to be 4.33% (95% confidence interval (CI): 2.29-8.02%), 3.37% (95% CI: 1.64-6.79%), 2.88% (95% CI: 1.33-6.14%), and 0.48% (95% CI: 0.08-2.67%), respectively. Positivity of the AChR antibody was the only significant factor associated with the presence of other non-thyroid autoimmune diseases (odds ratio 4.10, 95% CI: 1.11-15.21, p = 0.035). The presence of other non-thyroid autoimmune diseases was found in approximately 10% of OMG patients, with SLE displaying the highest prevalence. We recommend screening and monitoring for other non-thyroid autoimmune diseases in OMG patients, particularly those with positivity of the AChR antibody.

Personality factors in patients with myasthenia gravis: A prospective study.

In myasthenia gravis (MG), depression and anxiety have frequently been reported as comorbidities. However, little is known about personality characteristics in MG patients. We aimed to characterise personality traits in MG and to correlate them with disease severity and disease course. The Big Five Inventory data questionnaire was used to investigate personality traits in 44 MG patients and 45 healthy controls similar in age and gender. In 28 MG patients, a caregiver was also available for patient assessments to limit bias associated with social desirability in patients' responses. Patients were assessed with regard to premorbid personality (before manifestation of MG) and to present condition. In addition, anxiety and depression scales (Hospital Anxiety and Depression Scale and Beck Anxiety Inventory) were applied. Compared to controls, MG patients showed significantly higher levels of neuroticism, whereas openness and extraversion were significantly lower. Agreeableness and conscientiousness did not differ between groups. Neuroticism was influenced by disease severity such as generalization of weakness, presence of thymoma, and bulbar involvement as well as disease duration. Neuroticism correlated with premorbid level of neuroticism but also with depression and anxiety scores. A personality profile of increased neuroticism and lower openness and extraversion in MG patients may contribute considerably to the perception of disease severity. It may also be related to frequent comorbidities such as anxiety and depression. Although premorbid levels of neuroticism were increased, this characteristic may also increase considerably during the course of the disease. The data indicate that muscle weakness in MG is accompanied or even complicated by psychological aspects. Therefore, a psychological and behavioral intervention in addition to the specific pharmacological therapy might be of particular value.

Significance of Acetylcholine Receptor Antibody Titers in Acetylcholine Receptor Antibody-Positive Ocular Myasthenia Gravis: Generalization and Presence of Thyroid Autoimmune Antibodies and Thymoma.

To evaluate the association in acetylcholine receptor (AChR) antibody-positive ocular myasthenia gravis (OMG) subjects between AChR antibody titers and conversion to generalized myasthenia gravis (GMG), the presence of thyroid autoimmune antibodies, and the presence of thymoma. A total of 118 subjects with AChR antibody-positive OMG were included. Demographic data, clinical characteristics, serology tests, presence of thymoma, treatment, and conversion to GMG were retrospectively reviewed. The presence of thyroid autoimmune antibodies was defined as the presence of at least one of the following: (1) thyroid peroxidase antibody; (2) thyroglobulin antibody; (3) thyroid-stimulating hormone receptor antibody. Univariate and multivariate logistic regression analyses were used as methods of evaluating association. AChR antibody titers were determined in all subjects with a median of 3.33 (0.46-141.09) nmol/L. The median follow-up period was 14.5 (3-113) months. At the final follow-up time-point, 99 subjects (83.90%) remained with a diagnosis of pure OMG, while 19 subjects (16.10%) had converted to GMG. An AChR antibody titer ≥8.11 nmol/L was associated with the conversion to GMG (odds ratio (OR) 3.66, 95% CI: 1.19-11.26; p = 0.023). Of the 79 subjects with available thyroid autoimmune antibodies data, 26 subjects (32.91%) displayed the presence of thyroid autoimmune antibodies. An AChR antibody titer ≥2.81 nmol/L was associated with the presence of thyroid autoimmune antibodies (OR 6.16, 95% CI: 1.79-21.22; p = 0.004). Finally, of the 106 subjects with available thoracic computed tomography (CT) data, only 9 subjects (8.49%) demonstrated the presence of thymoma. An AChR antibody titer ≥15.12 nmol/L was associated with the presence of thymoma (OR 4.97, 95% CI: 1.10-22.48; p = 0.037). AChR antibody titers should be considered in AChR antibody-positive OMG patients. Those with AChR antibody titers ≥8.11 nmol/L, who are at a greater risk of conversion to GMG, should be closely monitored and encouraged to be aware of early clinical signs of life-threatening GMG. In addition, serum thyroid autoimmune antibodies and thoracic CT screening for thymoma should be performed in AChR antibody-positive OMG patients, particularly in those with AChR antibody titers ≥2.81 nmol/L and ≥15.12 nmol/L, respectively.

Pattern of Ocular Myasthenia Gravis in a Tertiary Eye Care Hospital, Bangladesh

Purpose: The purpose of this study was to evaluate pattern of ocular myasthenia gravis patients in a tertiary eye care hospital in Bangladesh.
 Methodology: This observational study was conducted in National Institute of Ophthalmology and Hospital (NIOH), Dhaka from January 2019 to December 2019. A total of 33 cases were purposively selected among ocular myasthenia gravis patients attending in the Department of neuro ophthalmology of NIOH irrespective of age, gender, residence. Study variables wereage, gender, clinical features, presence of thymoma, clinical, pharmacological and serological test findings. A proforma was prepared to record the data on particulars of the patients.
 Results: Among the cases, 45.5% were male and 54.5% were female where the mean age was 38.7 years. All patients presented with ptosis (100.0%) and most of them had fatigability(87.9%), cogan twice sign (81.8%) andorbicularis weakness (81.8%) while 63.6% had diplopia. Diabetes mellitus was observed in 18.2%patients and 15.1% had thyroid associations. Most of them had positive ice test(87.9%), 51.5% had positive serological test and 6.1% had positive neostigmine test. Thymoma was present in 6.1% cases.
 Conclusion: Ptosis was the most common clinical presentation for ocular myasthenia. Clinical diagnosis was confirmed by ice pack test and neostigmine test. Ocular myasthenia gravis patients may be have other systemic diseases.
 J. Natl. Inst. Ophthalmol. 2022;5(1):16-20

Dynamic nomogram for predicting generalized conversion in adult-onset ocular myasthenia gravis

PurposeTo explore the factors and risk mapping model of progression from ocular myasthenia gravis (OMG) to generalized myasthenia gravis (GMG) in adult-onset patients.MethodsA retrospective, observational cohort study was performed for 435 OMG patients with onset age older than 14 years old. Multivariate Cox regression was used to identify the independent factors affecting generalized conversions that then were incorporated into the construction of the nomogram.ResultsTwo hundred thirty-seven patients (54.5%) had transformed into GMG after a median of 1.1 years (range 0.1-–9.1 years). The 6-, 12-, and 24-month generalized conversion rates were 31.7%, 49.8%, and 65.4%, respectively. Multivariable analysis showed that the early-onset age, male sex, concomitant autoimmune diseases (AID), positive results of anti-acetylcholine receptor antibodies, repetitive nerve stimulation abnormalities, the presence of thymoma, and prednisone treatment were significantly associated with the generalized conversions (hazard ratio [HR] = 0.598, 0.686, 1.554, 1.541, 2.020, 2.510, and 0.556, respectively). A nomogram was established to predict the possibility of generalization-free survival (GFS) in adult-onset OMG patients, and the model demonstrated good predictive performance with a C-index of 0.736 (95% confidence interval 0.703 ~ 0.769). Moreover, subgroup analyses were performed based on the presence or absence of prednisone therapy, and the results indicated that prednisone therapy has better prevention of generalized conversions in male, non-thymoma patients, and patients without other AID.ConclusionA new predictive nomograph and web-based survival calculator we developed show favorable applicability and accuracy in predicting long-term GFS in adult-onset OMG patients.

Clinical picture and treatment of myasthenia gravis in the adult population

Introduction and purpose: Myasthenia gravis (MG, myasthenia gravis ) is a classic example of an autoimmune disease caused by antibodies against acetylcholine receptors ( AChR) , muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle membrane leading to characteristic muscle weakness.
 Description of the state of knowledge: It is not fully known why the body begins to produce antibodies that act against its own acetylcholine receptors. The main role in producing these antibodies is played by the thymus gland, a gland located in the chest. The thymus gland is normally present in children, while it atrophies in adults. In about 60% of myasthenia gravis patients, however, it is present (we say they have a persistent thymus), and 15% of patients have a thymic neoplasm called a thymoma.
 Summary: Myasthenia gravis is the most common neuromuscular junction disorder. Myasthenia gravis is a rare disease that involves muscle weakness of the eyes, pharynx, larynx, respiratory muscles and limbs. Clinical manifestations vary depending on the type of autoantibody and the presence of thymoma. The diagnosis of the disease should be confirmed by electrodiagnostic and laboratory tests in addition to the typical symptoms. Myasthenia gravis can manifest at any age, both in men ( peak incidence 50-60 years of age) and women ( peak incidence 20-30 years of age). Muscle fatigue intensifies after any exercise, even small ones. The patient feels best in the morning hours, right after waking up. As time passes, the symptoms of muscle fatigue intensify and the patient becomes less and less fit. For this reason, patients should rest frequently.

Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients

BackgroundMyasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome.MethodsWe examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation.Results815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange.ConclusionsMC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients.Graphical

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

Клініко-нейрофізіологічні особливості у хворих на міастенію залежно від структурних змін тимуса

Для вивчення особливостей клінічного перебігу й порушення нервово-м’язової передачі в пацієнтів з міастенією залежно від структурних змін тимуса були проаналізовані результати клініко-нейрофізіологічного обстеження 78 хворих. Матеріали та методи. Залежно від структурних змін тимуса всі хворі були поділені на 3 групи. Перша група — 29 пацієнтів з міастенією без змін структури тимуса. Друга група — 30 пацієнтів, у яких міастенія супроводжувалася гіперплазією тимуса. Третя група — 19 хворих з міастенією на фоні тимоми. Ступінь тяжкості захворювання оцінювався за допомогою кількісної шкали тяжкості клінічних проявів міастенії (QMGS) та клінічної класифікації Myathenia Gravis Foundation of America (MGFA), 2001. Оцінка нервово-м’язової передачі проводилася на підставі аналізу результатів декремент-тесту та амплітуди негативної фази М-відповіді при низькочастотній непрямій супрамаксимальній стимуляції m. abductor digiti minimi та m. orbicularis oculi. Результати та висновки. Зміни структури тимуса негативно впливають на перебіг міастенії, про що свідчать показники за шкалою QMGS та класифікацією MGFA. Найбільша тяжкість захворювання (з переважанням ураження бульбарної групи м’язів) поєднувалася із наявністю у хворих тимоми, а найменша відзначалась у хворих з нормальною структурою тимуса. Переважання пацієнтів жіночої статі в групі хворих з міастенією на тлі гіперплазії тимуса може свідчити про вплив гормонального статусу як на структуру вилочкової залози з розвитком її гіперплазії, так і на перебіг міастенії, що потребує подальшого вивчення. Простежена пряма залежність між структурними змінами в тимусі та зниженням амплітуди негативної фази М-відповіді, що свідчить про негативний вплив морфологічних порушень тимуса на нервово-м’язову передачу імпульсів. Значне зниження амплітуди негативної фази М-відповіді на фоні високих показників декремент-тесту можна вважати маркером тяжкого перебігу захворювання.

Myasthenia gravis and arrhythmias in COVID-19: a case report

Background: Myasthenia Gravis (MG) is an autoimmune disorder, which autoantibodies against postsynaptic (muscle) nicotinic acetylcholine receptors (nAChR). MG patients have a higher prevalence of cardiac manifestations in the presence of thymoma. It is not known whether Coronavirus disease 2019 (COVID-19) can cause more severe illness in patients with chronic neuromuscular disorders such as MG, which can cause respiratory muscle weakness, or in those who are immunosuppressed. This case report will discuss patient with MG, thymoma, atrial fibrillation, and COVID-19.Case presentation:Â A 60-year old man came to the hospital with difficulty of swallowing. He had nasal voice and dropping of eyelids. These complaints were happened repeatedly, worsened at night and got better in the next morning. From the neurological examination, it was also obtained Wartenberg test (+), counting test (+), and prostigmine test (+). Atrial fibrillation was found with normal ventricular response and decreased systolic left ventricular function on the electrocardiogram and echocardiography. On the chest MSCT, a lobulated homogeneous solid mass was found in anterior mediastinum which supported the image of thymoma, and there was the imaging of typical viral pneumonia. The patient also had the positive result of COVID-19 PCR test.Conclusion: MG patients have been shown with abnormal manifestations of heart rhythm. This may reflect as a complication of myocarditis or autonomic nervous system dysfunction. COVID-19 infection in MG can be challenging for many reasons. Current guidelines recommend continuing the current standard care treatment of MG during hospitalization.

Acetylcholine receptor antibody positivity rate in ocular myasthenia gravis: a matter of age?

Anti-acetylcholine receptor antibodies (AChR Abs) are detected in 85% of myasthenia gravis (MG) patients, at higher rates in patients with late-onset disease. AChR Ab frequency is generally thought to be much lower in ocular MG (OMG), although recent studies reported positivity rates higher than 70%. We hypothesized that the improved AChR Ab diagnostic yield in OMG could be related to an increased frequency of late-onset disease, as observed in generalized MG. We compared OMG patients, with disease onset before or after 1998, for the age of onset, sex, presence of thymoma, immunosuppressive therapy rate, AChR Ab positivity, and follow-up duration. All patients had a follow-up ≥ 2years. AChR Abs were tested by radioimmunoassay. The study included 133 patients. Disease onset occurred before 1998 in 54/133 cases (41%). Age of onset, the proportion of late-onset patients, and AChR Ab positivity rate were significantly increased in the more recent population. Thymoma frequency was similar in the two series. On multivariate analysis, the only variable predicting AChR Ab positivity was the age at onset ≥ 50years (OR = 6.50, 95% CI = 2.70-15.63, p < 0.0001). Our results confirm that current AChR Ab positivity in OMG may be higher than generally thought. In our population, this finding was associated with an increased frequency of late-onset cases.

Determinants of Suboptimal Outcome Following Thymectomy in Myasthenia Gravis.

Response to thymectomy in myasthenia gravis (MG) is influenced by various patient-, disease-, and therapy-related factors. Retrospective analysis of 128 patients with MG who underwent maximal thymectomy over 15 years was done to identify the determinants of suboptimal clinical outcome. Among the 128 patients, 62 (48.4%) were females with a mean age of 38.97 (12.29) years. Thymomatous MG occurred in 66 (51.6%). Overall improvement from preoperative status was noted in 88 (68.8%) patients after mean follow-up of 51.68 (33.21) months. The presence of thymoma was the major predictor of suboptimal clinical outcome (P = 0.001), whereas age, gender, preoperative disease severity, and seropositive status did not attain significance. Patients with better outcome had received higher steroid dose preoperatively (P = 0.035). Suboptimal response after thymectomy occurred in one-third of MG patients, more commonly with thymomatous MG. Relationship of preoperative steroid therapy to remission merits evaluation.

Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review.

Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its' severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.

MYASTHENIA & RELATED DISORDERS: P.33 Clinical features and evolution of juvenile myasthenia gravis in an Israeli cohort

Myasthenia Gravis (MG), an autoimmune neurological disease, is more frequently found amongst adults than amongst children. Our research provides data on the clinical symptoms, forms of MG, effective treatment, the presence of thymoma and the effect of thymectomy in children with MG in Israel. The database of a tertiary pediatric medical center was retrospectively reviewed for patients under 18 years of age diagnosed between the years 2000-2020 with either ocular or systemic acquired myasthenia gravis.

Clinical features and treatment status of antiacetylcholine receptor antibody-positive ocular myasthenia gravis.

To clarify the factors predictive of progression from ocular myasthenia gravis (OMG) to generalized MG (GMG) among patients with positive antiacetylcholine receptor antibodies (AChRAb) and to evaluate the efficacy of our OMG treatment protocol including tacrolimus (TAC). Retrospective study. Fifty-two patients with AChRAb positivity and ptosis and/or eye movement disturbance showing diurnal fluctuation and fatigability were included. First, we compared the clinical characteristics of patients without OMG progression (p-OMG) with those of patients whose OMG transformed to GMG (TMG). Second, we subdivided the p-OMG patients according to the time of approval of TAC into the Before group and the After group. We compared the dosage and period of prednisolone administration (PSL) of the 2 groups. Third, we evaluated the responses to OMG treatment using the Myasthenia Gravis Foundation of America Postintervention Status (MGFA-PS) scale. Forty-one patients were classified into the p-OMG group, and 11, into the TMG group. The AChRAb level (P = 0.0006) and prevalence of thymoma (P = 0.001) were significantly higher in the TMG group than in the p-OMG group. In the p-OMG group, the MG composite score (P ≤ 0.0001) and AChRAb level (P = 0.005) improved after treatment. The periods of PSL administration at ≥ 20mg/day (P = 0.009) and at 10 to 19mg/day (P = 0.002) were significantly shorter in the After group. At the last follow-up, 78.0% of the p-OMG group patients had achieved MGFA-PS minimal manifestations or better status with PSL ≤ 5mg/day. The TMG cases were characterized by higher AChRAb levels and presence of thymoma. The P-OMG patients could be managed with our treatment protocol. Combined use of TAC was efficacious in patients with steroid-dependent p-OMG.

Thymomatous myasthenia gravis: 10-year experience of a single center.

To summarize the clinical features of thymomatous myasthenia gravis (T-MG), examine the association between MG and thymoma, and identify the related factors or predictors for long-term prognosis of T-MG. A retrospective, observational study was conducted on 100 patients with T-MG and 96 patients with non-T-MG (NT-MG) between January 1, 2009 and December 31, 2019. The baseline characteristics were recorded for each patient. Logistic regression was used to measure the association between all clinical variables and T-MG prognosis. Between the T-MG and NT-MG groups, age at onset (45.66±11.53years vs 39.06±14.39years); age >40years (72.0% vs. 40.6%); AChR-Ab positive rate (100.0% vs. 83.3%); Myasthenia Gravis Foundation of America (MGFA) classification at the worst condition (≥grade III, 61.0% vs. 33.0%); thyroid dysfunction (7.0% vs. 20.8%); and outcome (complete stable remission+pharmacologic remission+improvement, 74.0% vs. 93.7%) were statistically significant (P<.05). Presence of thymoma (OR=0.196, 95%CI=0.076-0.511, P=.001) was a risk factor for MG. Male sex, post-operative complications, higher grade of MGFA classification, and thymoma Masaoka-Koga pathological stage were risk predictors for long-term prognosis of T-MG (P<.1). Use of preoperative anticholinesterase drugs (OR=5.504, 95%CI=1.424-21.284, P=.013) was identified as an independent predictor for T-MG. T-MG is clinically different from NT-MG, and thymoma is considered a risk factor for MG. Preoperative anticholinesterase drug use is a protective factor for long-term prognosis of T-MG. A comprehensive understanding of the characteristics of T-MG will likely help improve its prognosis.

Delayed Diagnosis of Good Syndrome

An 82-year-old man presented with worsening vision in his left eye for 2 weeks. He was found to have cytomegalovirus (CMV) retinitis and was treated with intravenous valganciclovir. He has a history of blindness in his right eye thought to be due to an undiagnosed infectious retinitis in the past. His medical history is otherwise notable for a “mass in his chest,” which was incidentally found on imaging more than a decade prior when he was treated for pneumonia. Records obtained from the outside hospital showed biopsy results consistent with thymoma type AB, a noninvasive tumor with low risk of metastasis. A chest x-ray revealed an anterior mediastinal mass, as shown in Figure 1. Because CMV retinitis is an opportunistic infection that occurs mainly in immunocompromised patients, an immunologic workup was initiated. An HIV test was negative. Lymphocyte subsets revealed normal CD3+ T cells (1754; 84%; ref 760-2130; 58% to 85%), a reduction of CD4+ T-cell subsets (373; 17%; ref 430-1185; 31% to 62%), an elevation of CD8+ T cells (1250; 57%; 180-865; 15% to 36%) with an inverted CD4:CD8 ratio of 0.3 (ref 0.9-3.0), and CD19+ B-cell count of zero (ref 25-285; 1% to 21%). He had normal CD16+CD56+ natural killer cells. Immunoglobulin levels were uniformly low: IgG 183 mg/dL (ref 700-1600 mg/dL), IgA 54 mg/dL (ref 70-400 mg/dL), IgM 13 mg/dL (ref 46-304 mg/dL). The patient was diagnosed with Good syndrome (GS) and started on immunoglobulin replacement, prophylactic antibiotics, and after completion of his CMV retinitis treatment, antiviral prophylaxis. GS is a rare syndrome defined by the presence of thymoma and immunodeficiency. It was first described in 1955 by Robert Good who played a crucial role in identifying the thymus' role in the immune system. Patients with GS usually present after the fourth decade of life. Presenting symptoms may be related to the thymoma, either due to its mechanical effects such as cough, dysphagia, and superior vena cava syndrome, or secondary entities such as myasthenia gravis and pure red cell aplasia. Patients have an antibody deficiency and differ from patients with common variable immunodeficiency (CVID) in that they have very few or absent B cells. GS is also characterized by CD4 lymphopenia, inversion of the CD4:CD8 ratio, and reduced T-cell mitogen proliferation. Similar to patients with CVID, patients with GS may present with recurrent sinopulmonary infections. However, their CD4 lymphopenia also leads to opportunistic infections normally not seen in patients with CVID. Notably, opportunistic infections in GS differ from patients with HIV in several ways: (1) they occur at significantly higher CD4 counts compared with HIV (CMV retinitis is documented in patients with HIV with CD4 counts <50, but occurs in patients with GS at CD4 counts >300), (2) the most common opportunistic infections include CMV retinitis and colitis, and mucocutaneous candidiasis, and (3) there have been no documented cases of cryptococcus or systemic fungal infections, and toxoplasmosis and disseminated tuberculosis are rare in patients with GS. Thymectomy is recommended for patients in whom a margin-negative resection is feasible. However, the immunologic abnormalities leading to immunodeficiency do not correct after thymectomy, and we recommend an immunological evaluation for all patients found to have a thymoma. Treatment of the immunodeficiency consists of immunoglobulin replacement, targeted antimicrobial prophylaxis, and appropriate vaccination with avoidance of live vaccines.1Malphettes M. Gérard L. Galicier L. Boutboul D. Asli B. Szalat R. et al.Good syndrome: an adult-onset immunodeficiency remarkable for its high incidence of invasive infections and autoimmune complications.Clin Infect Dis. 2015; 61: e13-e19Crossref PubMed Scopus (54) Google Scholar,2Multani A. Gomez C.A. Montoya J.G. Prevention of infectious diseases in patients with Good syndrome.Curr Opin Infect Dis. 2018; 31: 267-277Crossref PubMed Scopus (8) Google Scholar

P.377Myasthenia gravis (MG) anti-musk in Argentina: demographic, clinical findings and therapeutic response in a cohort of 56 patients

MuSK antibody positive Myasthenia Gravis (MuSK-MG) is diagnosed between 0-49% cases with generalized seronegative MG in different populations. Segmental muscular atrophy, frequent bulbar symptoms and a high incidence of myasthenic crisis characterize the disease. The aim of this study is to present a large cohort of MuSK-MG patients from Argentina. We performed a retrospective chart review on 56 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients in nine neuromuscular centers in Argentina. All of them were identified to have MuSK-Ab on commercial laboratory testing. MG severity and response to treatment were assessed according to MGFA classification. We identified 56 patients with diagnosis of Musk-MG. Of them, 66% were female. Mean age at diagnosis was 45,6 and 44,9 years-old in women and men respectively. Initial symptoms were: oculo-bulbar (34,3%), pure ocular (21,8%), pure bulbar (21,8%). 2 patients initiated with ocular and limb weakness, 2 with only limb weakness, 2 showed respiratory symptoms an 1 presented with dropped head. Initial MGFA status was: IIB (62%), I (13,7 %), IIIB (7%), IIA 6,9 % and 27,5% had myasthenic crisis at diagnosis. Peak MGFA was: IIb (20%), IIIB 26,6%, IVB 30 %. 6 (20%) patients had myasthenic crisis Three clinical phenotypes were found: the oculo-bulbar, the respiratory and the pseudo-myopathic. We did not find a clearly female predominance as described in previous reports. The presence of thymoma or thymic pathology was not detected by CT scan or MRI. Most patients respond favorably to immunotherapy. The best clinical response was to rituximab ,corticosteroids and plasma exchange, and the poorest response was to IVIG and anticholinesterase. Long-term outcome is favorable in about 80% of cases. This is the first series of patients with MuSK-MG described in South America and one of the largest worldwide.

Risk Factors for the Exacerbation of Myasthenic Symptoms After Surgical Therapy for Myasthenia Gravis and Thymoma

Extended thymectomy is employed for patients with myasthenia gravis (MG) and/or thymoma with elevated serum antiacetylcholine receptor antibody (AchR) titers. However, MG symptoms occasionally worsen in post-thymectomy patients. We explored the risk factors for exacerbation of MG symptoms after surgical therapy for patients with MG and/or thymoma with an elevated AchR titer. We retrospectively analyzed 90 patients suffering from MG and/or thymoma with an elevated AchR titer who underwent thymectomy in our institute. Patients were classified into Improved, Unchanged, and Exacerbated groups by assessing their postoperative myasthenic symptoms, amount of medication, and incidence of myasthenic crisis. Risk factors for postoperative exacerbation of myasthenic symptoms were assessed by comparing the Exacerbated with the Improved and Unchanged groups. Of the 90 patients, 29 were classified into the Improved group, 47 into the Unchanged group, and 14 into the Exacerbated group. The presence of thymoma and Masaoka stage were significantly different between the Exacerbated and Improved/Unchanged groups. Although preoperative AchR titers did not significantly differ among the groups, the perioperative AchR titers in the Exacerbated group were significantly higher than those in the other groups (P = 0.003). A multiple logistic regression analysis with stepwise forward selection showed that advanced-stage thymoma was a risk factor for postoperative exacerbation of myasthenic symptoms (P = 0.007). Patients with advanced-stage thymoma have a relative risk for exacerbation of myasthenic symptoms after surgical therapy.