Myasthenia gravis in children: a longitudinal study

BACKGROUND: Juvenile myasthenia gravis (JMG) is an uncommon disease. Unlike adults, clinical characteristics and outcomes of myasthenia gravis (MG) are not well studied in children. PATIENTS AND METHODS: Case records of 77 patients with MG who were 15 years of age or less at disease onset, evaluated over a period of 34 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. Their clinical characteristics and response to therapy was compared with 290 patients with MG onset after 15 years of age. RESULTS: Median age at onset was 8 years and mean period of follow-up was 6.2 years (range 6 months to 25 years). At presentation, 30% of patients had ocular myasthenia and the rest had generalized disease. Twenty-one patients (27%) had disease confined to ocular muscles throughout the course and three had limb girdle myasthenia. Familial myasthenia was more common than adult onset disease, 10 patients had positive family history. Unlike adults, none of the patients had associated autoimmune disease. Fifty-two patients (67%) received corticosteroids, and azathioprine was added in five patients. Thymectomy was performed in 11 patients, six below the age of 15 years. Thymic histology was normal in one and showed hyperplasia in eight and thymoma in one. Four patients had crisis. At the end of follow-up, 25 patients were asymptomatic, 28 had partial improvement, and nine remained unchanged or worsened and two died. Ten patients achieved complete stable remission. CONCLUSIONS: This study shows some distinctive characteristics of JMG, such as higher frequency of ocular myasthenia, benign course, better long-term outcome and lack of association of thymoma and other autoimmune disorders.     

Thymectomy: its role in the management of myasthenia gravis

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) for thymectomy over a 66 month period were reviewed. There were 53 patients, 20 male and 33 female, mean age 35.2 years (18–74) and median ITU stay of 5 days (2–30). Indications for thymectomy were thymic enlargement on computed tomography (34%), persistence of generalized symptoms (38%), a combination of both (20%), steroid side effects or dependency (4%) and progressive bulbar symptoms (4%). Following thymectomy, thymic histology revealed thymic follicular hyperplasia (26/53; 49%), atrophy (11/53; 21%), thymoma (12/53; 23%) and normal thymus (4/53; 8%). Post-operatively 23% required prolonged intubation (> 48 hrs); two patients required a tracheostomy 10 and 13 days post-operatively. Plasma exchange was required for two patients (3.8%) due to persistent severe myasthenic weakness. Three patients (6%) developed a post-operative chest infection and one pseudomembranous colitis. There were no post-operative mortalities during the study period. After 2 years, 35% of patients were in remission and 46% had ocular or mild generalized symptoms only. Thymectomy for myasthenia gravis is followed by sustained clinical improvement in the majority of patients. The appropriate post-operative management of these patients is best undertaken in a specialized neuro-intensive care setting.     

Disease-specific measure of quality of life for myasthenia gravis

In 2000 a Task Force of the Myasthenia Gravis Foundation of America recommended development of a quality of life (QOL) measure specific for myasthenia gravis (MG). Extant investigations have relied solely on assessment of physical aspects of daily living in conceptualizing QOL, despite research that emphasizes the importance of including psychological factors. In the present study we developed a QOL questionnaire specific to MG (MG-QOL) that assesses both physical and psychological aspects of function. The MG-QOL questionnaire was administered as a secondary measure of efficacy in a recently completed prospective trial of mycophenolate mofetil involving 80 MG patients. Comparisons indicated that the MG-QOL performed better than a nondisease-specific measure of QOL, the SF-36, in demonstrating disease change as assessed by the primary measure, the Quantitative MG score (QMG). The MG-QOL correlated highly with the SF-36, and demonstrated stronger associations with independent physical ability ratings. Results from this study support the use of this new measure of QOL, both clinically and in treatment trials of MG.     

Quality of life and well-being of patients with myasthenia gravis

The cardinal symptom of myasthenia gravis (MG) is weakness of voluntary muscles, a feature that may restrict full participation in life activities. In turn, such limitations may negatively affect quality of life (QOL) and well-being among individuals with the disease. In the present study, we administered a measure of QOL to 27 patients with generalized MG. Results revealed that functional status was negatively impacted in the domains of physical functioning, energy, and general health. However, a clinically meaningful difference was evident only on perceived ability to accomplish physical tasks. The results suggest that although MG requires accommodations in physical activities, general QOL and well-being does not differ markedly from the general population.     

Fatigue is a relevant outcome in patients with myasthenia gravis

Introduction: Patients with myasthenia gravis often experience fatigue, but its effect on quality of life (QoL) is underestimated, and fatigue is rarely measured in clinical trials. Methods: Two hundred fifty‐seven myasthenic patients completed the Neuro‐QoL‐Fatigue and measures of disease severity and QoL. We studied the relationship between fatigue and clinical and demographic variables. Finally, we studied the responsiveness of the Neuro‐QoL‐Fatigue in 95 patients receiving treatments for myasthenia and estimated the minimal important difference (MID). Results: Fatigue correlated with greater disease severity (r = 0.52–0.69, P < 0.0001) and worse QoL (r = 0.65–0.75, P < 0.0001). Patients in remission, with minimal manifestations, and pure ocular symptoms reported minimal fatigue. Regression modeling showed that, in addition to its relationship with disease severity, fatigue was worse in females, patients with generalized disease, and those with anxiety/depression. Fatigue improved after immunomodulation (P < 0.0001), and the MID was 5.3 points. Discussion: Fatigue in myasthenia correlates with disease severity, affects QoL, and can improve after treatment. Muscle Nerve 58 : 197–203, 2018     

Surrogate therapeutic outcome measures in patients with myasthenia gravis

Treatment of acquired myasthenia gravis (MG) with immunotherapies successfully relieves symptoms and improves strength as documented by the Quantitative Myasthenia Gravis Score for disease severity (QMGS). Neuromuscular function, as demonstrated by the surrogate measures of repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG), is sensitive for diagnosis and staging disease severity. This study of 51 patients treated with immunomodulation confirmed that RNS and SFEMG are useful to stage disease severity, but found that clinical measures such as the QMGS are more sensitive to change than electrophysiological parameters. The presence of blocking on SFEMG did predict responsiveness to intravenous immunoglobulin (IVIG) treatment, providing clinicians with an objective, reliable, quantitative measure to help determine which patients will benefit from this costly treatment.     

Quality of life in 188 patients with myasthenia gravis in China

Myasthenia gravis (MG) is a kind of chronic autoimmune disease which can weaken patients' motor function and, furthermore, produce negative impact on the health-related quality of life (HRQoL). The primary purpose of this research was to evaluate factors that might affect the HRQoL of MG patients. A cross-sectional clinical research was carried out including 188 successive patients with MG. Myasthenia Gravis Foundation of America (MGFA) classification and Quantitative Myasthenia Gravis (QMG) score were applied to assess the severity of the disease. The Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36) was used to estimate the HRQoL. Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were utilized to measure the depression and anxiety symptom. Factors may influence the HRQoL of MG patients include age, educational level, occupation, the situation of the thymus, the type of MG and generalized myasthenia gravis (GMG), the severity of the disease and the psychological disorder. Higher QMG and HARS scores were two significant factors that can prognosticate lower Physical Composite Score (PCS) and Mental Composite Score (MCS), while older age was just a significant factor which has prognostic value for lower PCS. The results of this research may have a potential guiding significance for the clinical treatment strategy and improve the quality of life in patients with MG consequently. In addition to the treatment of physical symptoms, the psychological symptoms such as anxiety and depression should be concerned as well.     

Thymectomy in myasthenia gravis a review

The role of thymectomy in the management of myasthenia gravis is reviewed in the light of the published data and of a personal series. The patients in whom the operation is most successful are non thymomatous patients aged between 10 and 40 years with an MG history of less than 3 years. There is no sex prevalence. Lasting improvement may be expected. There are no proven correlations between biological indices like the germinal centers in the thymus and/or AChR antibody titers and the postoperative course of the disease. Complete removal of the thymus seems to be crucial and hence the transsternal approach is preferred. The operation, less effective in patients with thymona than in those with an active thymus, is nonetheless necessary to in these patients prevent putative damage to surrounding organs from thymona infiltration. Why thymectomy should be effective in patients with an active thymus and not in those with a thymona may be revealed by in vitro studies of the interactions between thymic cells and peripheral B cells, now in progress.

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Sommario Viene rivisto alla luce dei dati della letteratura e della casistica personale il ruolo della timectomia nella terapia della miastenia. Dei pazienti non portatori di timoma i migliori risultati si ottengono in quelli di età fra i 10 e i 40 anni con una durata della malattia minore di tre anni. Non vi è prevalenza di sesso. Ci si può attendere un miglioramento duraturo. Non vi sono prove di una correlazione tra gli indici biologici germinativi quali i centri germinali nel timo e o il titolo degli anticorpi contro i ricettori acetilcolinici e il decorso post-operatorio della malattia. É fondamentale la completa asportazione del timo e perciò è preferibile la scelta della tecnica di approccio transternale. Nei pazienti con timoma la timectomia è meno efficace ma l'intervento è necessario per evitare danni derivanti dall'infiltrazione del timoma sugli organi circostanti. Il perché della efficacia della timectomia nei pazienti con un timo attivo ma non in quelli con timoma potrà essere chiarito dagli studi in vitro sulle interazioni tra cellule timiche e quelle periferiche B, studi che sono ormai in stadio avanzato.

     

Factors influencing the outcome of transsternal thymectomy for myasthenia gravis

BACKGROUND: Thymectomy is one of the current treatment strategies for patients with myasthenia gravis (MG); however, the selection criteria for surgery remain controversial. METHODS: The demographic data and the surgical results of 168 patients with MG who underwent transsternal thymectomy from June 1986 to December 2000 were retrospectively reviewed. Follow-up information was obtained by review of the hospital records or telephone contact. The postoperative status of MG was assessed at the interval of 1, 3 and 6 months and then annually. The complete remission rate (CRR) between groups was compared. RESULTS: A total of 168 patients, including 69 male patients and 99 female patients, with a mean age of 38.3 years (range 13-80 years), were analyzed. The symptom duration before operations was from 1 to 312 months with a mean of 33.8 months. Complete follow-up information was obtained on 154 patients (91.6%) with a mean follow-up duration of 98.9 months. Complete remission was achieved in 89 of 154 patients (57.8%) and marked clinical improvement in 47 patients (30.5%). Total improvement rate was 88.3%. Seventeen of 24 patients (70.8%) with ocular MG and 18 of 35 patients (51.4%) with thymoma had reached complete remission during the follow-up period. The CRR increased with each consecutive year and reached the plateau in the fourth postoperative year. There was no surgical mortality. The complication rate was 16.6%. Univariate analysis demonstrated that age <35 years old (P = 0.0001), symptom duration before operation <24 months (P = 0.01) and absence of preoperative steroid treatment (P = 0.04) were favorable prognostic factors. Multivariate Cox regression analysis revealed age <35 years old (odds ratio = 3.645, P = 0.001), symptom duration before operation <24 months (2.311, P = 0.041) were favorable prognostic factors for patients having transsternal thymectomy. CONCLUSIONS: Transsternal thymectomy is feasible in the management of patients with MG at all stages with high improvement rate and low surgical morbidity. Those patients aged 35 years or less at operation, with symptoms developed <24 months before operation, may benefit more from thymectomy. MG patients with thymoma did as well as patients without thymoma, and 18 of 35 patients with thymoma had reached complete remission during the follow-up period. Thymectomy seems to be beneficial also for ocular MG.     

No increased risk of adverse pregnancy outcomes for women with myasthenia gravis: a nationwide population-based study

Background:  This study aims to examine the risk of adverse pregnancy outcomes [low birthweight (LBW), preterm birth, cesarean sections (CS) and babies born small for gestational age (SGA)] in pregnant women with myasthenia gravis (MG), using a 3-year population-based database, taking characteristics of infant and mother into consideration.
Methods:  This study used two nationwide population-based datasets: the Taiwan National Health Insurance Research Dataset and the Taiwan birth certificate registry. We identified 163 pregnant women with MG during 2001–2003 as the study cohort and 815 randomly selected pregnant women as a comparison cohort. Conditional logistic regression analyses were performed.
Results:  The results showed that, although these patterns did not reach a statistically significant level, mothers with MG had higher percentages of LBW (6.8%, vs. 5.6%), SGA (17.8%, vs. 14.1%) and cesarean deliveries (44.8%, vs. 37.4%), except for preterm births (8.1%, vs. 8.1%). After adjusting for highest maternal education level, marital status, family monthly income and infant gender and parity, the odds ratios (OR) of LBW, preterm birth, SGA infants, and cesarean delivery for mothers with MG were 1.19 (95% CI = 0.60–2.38), 1.00 (95% CI = 0.54–1.87), 1.30 (95% CI = 0.83–2.04), and 1.33 (95% CI = 0.94–1.88), respectively, as compared to unaffected mothers.
Conclusions:  We conclude that there were no statistically significant differences in the risk of having preterm, LBW, SGA infants and cesarean deliveries between women with and without MG.     

Factors affecting outcome in ocular myasthenia gravis

Aim of the study: 50%–60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables.

Materials and methods: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients.

Results: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL.

Conclusions: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.     

The cerebrospinal fluid in myasthenia gravis

We examined the number of leucocytes and the concentration of total protein, albumin and IgG in the cerebrospinal fluid (CSF) from 46 patients with myasthenia gravis (MG) and 50 controls. Mean leucocyte number in the MG patients was 1634 cells/ml (controls 1244), mean total protein 0.38 g/l (controls 0.32), mean IgG 0.034 g/l (controls 0.025) and mean albumin 0.199 g/l (controls 0.176). No evidence of intrathecal IgG synthesis was demonstrated. The CSF was normal in most cases. When pathological changes occurred they were slight and could be attributed to associated diseases or to iatrogenic blood contamination of the CSF. We demonstrated that an artificial blood contamination of the CSF, although macroscopically undetectable, increased the CSF albumin concentration and the CSF albumin/serum albumin ratio considerably.     

The management and outcome of patients with myasthenia gravis treated acutely in a neurological intensive care unit

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) over a 66 month period were reviewed. Twenty-seven patients were admitted in myasthenic crisis, eight of whom had multiple admissions. One patient had a cholinergic crisis and a further patient an acute myocardial infarction. A specific aetiological factor precipitating myasthenic crisis was identified in 19 instances: infection (8), reduction in medication (5), menstruation (4), and steroid administration (2). Thirteen patients with crisis had had a previous thymectomy, six with thymoma. Twenty-three out of 35 (66%) patients admitted in crisis required intubation; nine subsequently needed a tracheostomy. Twenty-nine patients received plasma exchange and seven intravenous immunoglobulin. Four patients in myasthenic crisis died in ITU [adult respiratory distress syndrome (1), disseminated intravascular coagulation and cytomegalovirus (CMV) pneumonitis (1), cardiac failure (1) and multiple organ failure (1)]. Appropriate management of myasthenia gravis requires the easy availability of specialised neuro-intensive care facilities.     

Effectiveness of steroid treatment in myasthenia gravis: a retrospective study

The records of 142 patients with generalized autoimmune myasthenia gravis who had been treated with steroids as the single immunosuppressive agent, collected at regular intervals, were employed for a retrospective evaluation. The effectiveness of treatment was assessed after 24 months; the data from the 6th and 12th months were also considered. After 24 months, 63.4% of the whole sample had improved (33.8% were in clinical or pharmacological remission); 13.4% were unchanged or had worsened and 22.3% had moved to a different immunosuppressive treatment. The rate of positive outcome was higher in patients over the age of 40 at disease onset.     

Less is more, or almost as much: a 15-item quality-of-life instrument for myasthenia gravis

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.