Form Of Myasthenia Research Articles

Generalized form and duration of myasthenia gravis as predictors of cognitive impairment

We performed a clinical, neurological, neuropsychological and laboratory examination of 30 patients with a confirmed diagnosis of myasthenia gravis, aged 25 to 69 years (49.0 ± 14.6 years), 11 men and 19 women. Among the examined patients, the generalized form of myasthenia was diagnosed in 20 (66.7%) patients: 4 (20.0%) cases of severe and 16 (80.0%) of moderate forms. The ocular form of myasthenia was found in 10 (33.3%) cases. Neuropsychological testing revealed memory impairment in 15 (50.0%), attention – 11 (36.7%), emotional disturbances – 13 (43.3%) patients with myasthenia gravis. A significant decrease in the concentration of brain-derived neurotrophic factor (BDNF) in the blood serum of patients with myasthenia was noted, compared with the control group (p < 0.01). When comparing the data of neuropsychological testing, the level of BDNF and the history of the disease, it was found that patients with a generalized form of myasthenia gravis and a disease duration of more than three years have a lower level BDNF, which has a reliable correlation with lower cognitive function scores.

The diagnosis and management of ocular myasthenia gravis

Ocular myasthenia is not the most severe form of myasthenia but it might cause certain difficulties to diagnose. In this article, we shall discuss the clinical presentations of ocular myasthenia, its differential diagnostics, examinations and management. Keywords: ocular myasthenia gravis, diagnosis, examination, management.

COMORBIDITIES IN PATIENTS WITH MIASTENIA GRAVIS

The purpose of this work was to study comorbid conditions in patients with myasthenia gravis. Materials and methods: 182 patients with myasthenia gravis aged from 18 to 83 were examined. 147 (80.8%) of then were diagnosed to have generalized form of myasthenia and 35 (19.2%) had ocular form myasthenia. Clinical and neurological examination included present complaints, past medical history, social history, neurological examination. To evaluate the clinical form of myasthenia, the MGFA classification was used. For data processing, the methods of parametric and non-parametric statistics were applied. Among the patients there were 128 (70.3%) women and 54 (29.7%) men, the women to men ration was 2.37: 1. Median age was 52.0 (34.0; 65.0) years. The proportion of patients who, in their routine practice, had CT or MRI of the anterior mediastinal system, made up 74.2% of the total sample and did not differ significantly depending on the form, class or subclass of myasthenia.
 Results: Among patients with the class I of myasthenia gravis, there were no individuals who had thymoma and/or thymectomy, unlike the patients with generalized myasthenia. A significant proportion of thymic and/or thymectomy was recorded in patients with class II (28.9% and 25.0% respectively). The proportion of thymoma and thymectomy in the patients significantly differed based on the myasthenia form (significantly more in patients with generalized form compared to those with ocular form, p = 0.003 and p = 0.009, respectively). The proportion of thymoma and thymectomy history significantly differed among patients with different classes of generalized myasthenia (class II-IV (p = 0.008 and p = 0.018 respectively) and their subclasses (p = 0.006 and p = 0.009, respectively), while they were registered in each class and subclass of generalized myasthenia.
 Attention should be paid to the fact that the proportion of thymoma in the general sample was greater than the proportion of thymectomy (19.2% versus 15.9%). This suggests an inadequate level of surgical care for myasthenia patients, even to those who are shown with such treatment (patients with thymoma).
 The proportion of autoimmune diseases among patients with myasthenia class I (ocular form) significantly exceeded the corresponding level in patients with generalized myasthenia - 45.7% vs. 15.0% (p <0.001).
 The incidence of total concomitant pathology among all patients was 130.8% (95.0% CI 121.6-140.0%) and was slightly higher in the generalized form of myasthenia (134.7% (95.0% CI 123.6 -145.7%)) compared with the ocular form - 114.3% (95.0% CI 100.9-127.7%), p> 0.05.
 One patient had from 0 to 6 concomitant diseases, on the average of 1.0 (0; 2.0) by the median value.
 Cardiovascular diseases, 34.1% (95% CI 27.2 - 41.0), rank the first place in the frequency of the concomitant diseases among the examined patients. The diseases of the gastrointestinal tract (namely, gastritis, ulcers of the stomach and duodenum, chronic holistic, chronic pancreatitis at the stage of remission, etc.) and autoimmune thyroiditis (20.9% (95% CI 15, 0-26.8) have the second highest rate, eye diseases (not related to the myasthenia) are (15.9% (95% CI 10.6 - 21.3)) ranked the third.
 No differences in the incidence of concomitant pathology, apart from autoimmune diseases, between forms, classes and subclasses of myasthenia were detected (p> 0.05).
 Conclusions. The proportion of visualization of the anterior mediastinum in patients with myasthenia gravis is far from being sufficient. This test is supposed to be done for absolutely all patients with myasthenia gravis for early detection of pathological changes of thymus. In the structure of the comorbidities in patients with myasthenia gravis cardiovascular, gastrointestinal and autoimmune thyroiditis have been found out to prevail. This should be taken into account when selecting treatment. Autoimmune thyroiditis was recorded in 45.7% of patients with ocular and in 20.9% of patients with generalized myasthenia that may indicate a systemic autoimmune disorder whose causative relationships require further in-depth study.

Incidence and Ocular Features of Pediatric Myasthenias

To report the incidence, demographics, and ocular findings of children with myasthenia. Retrospective cohort study. The medical records of all children (<19 years) examined at Mayo Clinic with any form of myasthenia from January 1 1966, through December 31, 2015, were retrospectively reviewed. A total of 364 children were evaluated during the study period, of which 6 children were residents of the Olmsted County at the time of their diagnosis, yielding an annual age- and sex-adjusted incidence of 0.35 per 100 000<19 years, or 1 in 285 714<19 years. The incidence of juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS) was 0.12 and 0.23 per 100 000, respectively. Of the 364 study children, 217 (59.6%) had JMG, 141 (38.7%) had CMS, and 6 (1.7%) had Lambert-Eaton syndrome, diagnosed at a median age of 13.5, 5.1, and 12.6 years, respectively. A majority of the JMG and CMS patients had ocular involvement (90.3% and 85.1%, respectively), including ptosis and ocular movement deficits. Among children with at least 1 year of follow-up (JMG; median, 7.1 years, CMS; median, 7.0 years), improvement was seen in 88.8% of JMG patients (complete remission in 31.3%) and in 58.3% of CMS patients. Although relatively rare, myasthenia gravis in children has 2 predominant forms, CMS and JMG, both of which commonly have ocular involvement. Improvement is more likely in children with the juvenile form.

Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia

The incidence of myasthenia gravis which is characterized by progressive muscular weakness on the background of structural disorders of the thymus, has increased. Myasthenia gravis is a multifactorial autoimmune disease, it has a pronounced clinical heterogeneity, and therefore the standard diagnostic and treatment protocol is not always effective. To substantiate an individual approach to the treatment of various clinical forms of myasthenia, we conducted a study of mechanisms and markers of loss of central and peripheral self-tolerance in thymus-independent myasthenia (M) and thymus-dependent myasthenia gravis with thymus hyperplasia (MH) and thymoma (MT), involving a total of 427 patients examined. In patients with different phenotypes of myasthenia, we used the methods of spectrophotometry, flow cytometry, enzyme immunoassay. In patients with MH on the background of lymphofollicular thymus hyperplasia we revealed a pronounced humoral sensitization in comparison with the reference values: the concentration of C4 complement, C-reactive protein, circulating immune complexes and the initiation of an indirect autoimmune reaction a reliable increase in autoantibodies (AAbs) to the α1 and α7 subunit of subunit of nicotinic receptors (nAChR). In M and MT groups a high similar titer of AAbs to other epitopes was revealed: DNA, β2-glycoprotein I, membranes of intestinal and stomach cells, lung, liver, kidney cells. A pronounced blast-transforming response to the presence of the mitogen PHA was revealed in the MT group. In the MT group, a decrease in the content of CD4+ CD28+ co-stimulatory molecules and in the MH group, a decrease in СD4+ CD25+ Treg lymphocytes was revealed. Individual methods for correcting the loss of self-tolerance in patients with different clinical phenotypes of myasthenia were justified taking into account the use of immunosuppression, specific viral-neutralizing immunoglobulins and massive IgG immunoglobulin therapy, and the application of anti-inflammatory recombinant interleukins.

Epidemiologic and populational aspects of myasthenia gravis in the Krasnodar Region

Objective: to study epidemiological and population indicators of myasthenia in the Krasnodar Territory. Materials and methods. 344 patients with a diagnosis of myasthenia living in the Krasnodar Territory underwent a retrospective analysis. Results. On January 1, 2017 the prevalence of myasthenia was 8.1 cases per 100,000 population, morbidity in 2011–2016 ranged from 0.27–0.71 cases per 100,000 population, and the average was 0.52 cases per 100,000. The average age of manifestation of the disease of registered patients was 46.2 ± 0.97 years. The minimum age of debut of the disease was 11 years, the maximum – 80 years. The ratio of men and women among patients with myasthenia was 1:2.5. The peak of the onset of the disease in women falls on the period of 20–40 years. A bimodal pattern of incidence in women was revealed in the period from 20 to 40 years and from 50 to 70 years. After 60 years 35 % of men fell ill. The generalized form of myasthenia was observed in 82.8 % of patients, eye cases in 16.3 %, oculopharyngeal form in 0.9 %. Of the observed patients, rural residents accounted for 58.7 %, urban residents for 41.3 %. Conclusion. The main epidemiological indicators of myasthenia obtained in the course of the study in the Krasnodar Territory are on average comparable with the Russian ones and meet the global trends. Epidemiological monitoring of myasthenia is more effective on the basis of specialized myasthenic centers.

Clinical experience of myasthenic crisis management in Amur region

Background. Management of the myasthenic crisis remains one of the issues in clinical neurology. Objective. Analysis of the timeframes of the myasthenic exacerbation since the disease onset, sex distribution, age predominance, specific clinical features, precipitating factors in order to investigate the efficacy of the management algorithm of the myasthenic crisis. Materials and methods . Medical histories of 33 female and 19 male patients with myasthenia for the period of 2000 to 2003 were analyzed. Results. In comparison with the literature data the number of mysthenic crisis in myasthenic patients was lower and did not exceed 25 %. Sex distribution 1,2 (male): 1 (female). In 70 % worsening of myasthenia appeared in the first two years of the disease: in 6 patients (46.2 %) at the age of 22–35 y. o.; in 5 patients (38.5 %) – at the age of 36–60 y. o. All patients suffered from generalized myasthenia, in three of them ocular and bulbar muscle weakness predominated. In 46.2 % of patients with crisis, thymus abnormalities were present (thymoma / hyperplasia). The most common precipitating factors were: infection (36.9 %), stress (26.3 %), misuse of the anticholinesterase drugs (15.8 %). In 5.2 % the worsening of myasthenia followed the delivery. The crisis triggering factor was not identified in 15.8 % of cases. Conclusion. In order to prevent the exacerbation of myasthenia, generalized forms of myasthenia with poor response to anticholinesterase drugs require special attention towards patients in their first two years of the disease, including patient’s educational program on appropriate mode of drug administration and avoiding initiating factors, as well as thymectomy.

Endogenic Cytotoxic Factors and Formation of the Clinic Forms of Myasthenia

Background: Recently, increased incidence of autoimmune disorders, one of which is myasthenia gravis. The myasthenia is revealed at 3-30 patients out of 100 000 in a year. As it is considered by the most of specialists the central chain in myasthenia development is the formation of antibodies to the nicotinic acetylcholine receptors (nAChR), leading to the blockage of muscle fiber contraction and to the muscle dystrophy. Along with this, there is an assumption of the role of cytotoxic factors in the development of myasthenia gravis. The aim of the present article is to proof working hypothesis about specific role of cytotoxic factors in the formation of various clinical variants of myasthenia gravis. Method: Patients were divided according to the clinical phenotype of myasthenia gravis: myasthenia without thymus lesion (M), myasthenia with thymus hyperplasia (MH) and myasthenia with thymoma (MT). We used methods of light microscopy to determine the serum cytotoxicity using a cell bioindicator Dunaliella viridis. The determination of antibodies to nicotinic acetylcholine receptors (nAChR), thyroperoxidase (TPO) and antibodies to lungs, liver tissues and elastin was performed by ELISA. And fluorescence microscopy used for determination of expression of clusters differentiation of CD3+, CD4+, CD8+, CD16+, CD19+, CD45+. Results: The patients with different clinical phenotypes of myasthenia: myasthenia without thymus lesions (M), myasthenia with thymus hyperplasia (MH), and myasthenia with thymoma (MT), have been investigated. It was discovered that the amount of autoantibodies to the α1 and α7 acetylcholine receptor was different among patients with different clinical types of myasthenia. Drastic differences between forms of myasthenia were also identified using a blood serum thyroperoxidase activity. Additionally, we found that all clinical forms of myasthenia could be characterized by the differences in the amounts of IL4 and IL8, compositions of lymphocyte subpopulations, as well as patterns of autoantibodies to the lung tissue, liver, heart, and DNA. Test culture D. viridis responded differently to the cytotoxic components of the blood serum in different clinical types of myasthenia. Our results suggest that endogenous factors play a primary role in forming of clinical types of myasthenia. Conclusions: 1) development of myasthenia gravis occurs on the background of cytotoxic factors formed in the organism; 2) endogenous cytotoxic factors have nonspecific effects on the various functional systems of the organism, even the plant objects; 3) the organism of patients with myasthenia gravis produce various cytotoxic factors, which influence on different systems of the organism and can lead to the formation of a variety of clinical phenotypes.

CLINICAL AND NEUROLOGICAL CRITERIA FOR THE DIAGNOSISOF MYASTHENIA GRAVIS

927 patients suffering from myasthenia gravis have been examined. A long-term follow-up analysis of the various forms of myasthenia in its clinical and neurological development has been conducted. Systematization and evaluation of the results have revealed major and frequent diagnostics criteria appropriate of myasthenia gravis. There are fatigable muscular weakness (92,3%), formula motor dis- turbances (91,9%), test with neostigmine (77,5%), generalized muscular weakness (76,3%), “flutter” and «migration» of the symptoms (71,1%), preservation of eye movements downward while it restricts in other directions (68,3%), combination ptosis and lagophthalmos on one side (50,1%). A diagram of clinical diagnostic, which help us to review a patient diagnosis of myasthenia gravis or suspect this exact disease has been developed.

Acetylcholinesterase inhibitor treatment for myasthenia gravis.

In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic transmission. Acetylcholinesterase inhibitors provide temporary symptomatic treatment of muscle weakness but there is controversy about their long-term efficacy, dosage and side effects. This is the second update of a review published in The Cochrane Library Issue 2, 2011. To evaluate the efficacy of acetylcholinesterase inhibitors in all forms of myasthenia gravis. On 8 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE for randomised controlled trials and quasi-randomised controlled trials regarding usage of acetylcholinesterase inhibitors in myasthenia gravis. Two authors scanned the articles for any study eligible for inclusion. We also contacted the authors and known experts in the field to identify additional published or unpublished data and searched clinical trials registries for ongoing trials. The types of studies were randomised or quasi-randomised trials. Participants were myasthenia gravis patients diagnosed by an internationally accepted definition. The intervention was treatment with any form of acetylcholinesterase inhibitor. Types of outcome measures Primary outcome measureImprovement in the presenting symptoms within one to 14 days of the start of treatment. Secondary outcome measures(1) Improvement in the presenting symptoms more than 14 days after the start of treatment.(2) Change in impairment measured by a recognised and preferably validated scale, such as the quantitative myasthenia gravis score, within one to 14 days and more than 14 days after the start of treatment.(3) Myasthenia Gravis Association of America post-intervention status more than 14 days after start of treatment.(4) Adverse events including muscarinic side effects. One author (MMM) extracted the data, which were checked by a second author. We contacted study authors for extra information and collected data on adverse effects from the trials. We did not find any large randomised or quasi-randomised trials of acetylcholinesterase inhibitors in generalised myasthenia gravis either for the first version of this review or this update. One cross-over randomised trial using intranasal neostigmine in a total of 10 participants was only available as an abstract. It included three participants with ocular myasthenia gravis and seven with generalised myasthenia gravis. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase. Lack of detail in the report meant that the risk of bias was unclear. Adverse events were minor. Except for one small and inconclusive trial of intranasal neostigmine, no other randomised controlled trials have been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. The response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in a placebo arm of treatment would be difficult to justify.

Does only thymectomy influence on results of surgical treatment at patients with myasthenia gravis?

Methods We have analyzed results of surgical treatment of 87 patients having myasthenia gravis. There were 68 (79,2%) female, 19 (21,8%) male. Patients ranged in age from 15 to 64 years. 80 patients (91,9%) had generalized myasthenia, 7 patients (8,1%) had local forms of myasthenia. The most number of patients had IIb – Iva degree of myasthenia according to international clinical classification. All patients underwent extended thymectomy. At 75 patients we have performed thymectomy by median sternotomy, at 10 patients – by VATS. Dissection of mediastinal fat was a mandatory component of operation. The histologic pattern was: thymoma – at 43 patients (49,4%), thymic hyperplasia – at 42 patient (48,3%), thymic atrophy – at 2 patients (2,3%). Additional thymus corpuscles were revealed at 10 patients (11,5%).

Pyridostigmine but not 3,4‐diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle‐specific kinase autoantibody

In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft.

The Role of ADRB2 in Myasthenia: Genetic and Immunological Factors

To examine the possibility of using ADRB2 adrenergic receptor agonists for correction of myasthenia-induced immunological and motor disturbances, a method of anti-ADRB2 antibody assay by ELISA was developed. The haplotype of ADRB2 gene was determined by MLPA-PCR in 34 myasthenia patients; blood sera from 40 patients were examined. The content of antibodies against ADRB2 receptors was elevated in 12 of 30 patients with generalized form of myasthenia. Arg-Arg in position 16 in ADRB2 receptors determines the developmental risk of side effects, while Gly-Gly in the same codon determines tolerance to β2-adrenoceptor agonists and is associated with more severe course of myasthenia and resistance to β2-adrenoceptor agonists treatment with ADRB2 agonists. The study demonstrated the possibility of using ADRB2 obtained gene engineering technique for quantitatively assay the autoantibodies.

Juvenile myasthenia

Juvenile myasthenia is a chronic autoimmune neuromuscular disease characterized by varying degrees of fluctuating, painless muscle weakness and rapid fatigue of any muscles under voluntary control. Juvenile myasthenia is a form of myasthenia appearing in adolescent age, representing 10% to 15% of all cases of myasthenia gravis. Juvenile myasthenia is presented by a defect in the transmission of nerve impulses to muscles, resulting from a breakdown in the normal communication between nerves and muscles. In myasthenia, antibodies produced by the body's own immune system block, alter, or destroy the receptors for acetylcholine. Juvenile myasthenia is neither directly inherited nor is it contagious. The first noticeable symptoms may be eye muscle weakness, difficulty in swallowing, or slurred speech. Juvenile myasthenia usually affects muscles innervated by the cranial nerves (face, lips, tongue, neck and throat), but it can affect any muscle group. Symptoms vary in type and severity with typical periods of exacerbation interspersed with periods of remission. When the muscles necessary for breathing are affected, a patient is said to be in a myasthenic crisis, which is a life-threatening situation. Juvenile myasthenia produces sporadic but progressive weakness and abnormal fatigability of striated (skeletal) muscles, exacerbated by exercise and repeated movement, but improved by rest and anticholinesterase drugs. Juvenile myasthenia follows an unpredictable course of recurring exacerbations and periodic remissions. With current therapies, however, most cases of juvenile myasthenia are not as serious as the name implies. Although there is no known cure, drug treatment has improved prognosis and allows patients to lead relatively normal lives, except during exacerbations.

Clinical features and treatment strategy in myasthenia

20 patients with the various forms of myasthenia were observed for the period from 2 to 10 years. There are trigger factors, features of different forms of disease described. The diagnostic criteria of diagnostics myasthenia and methods of treatment are described.

Antibodies to acetylcholine receptors in patients with different clinical forms of myasthenia and Lambert-Eaton myasthenic syndrome

Increases in the titers of antibodies to acetylcholine receptors (AChR), along with clinical signs of disease, posi­ tive responses to administration of anticholinesterase agents, and electromyographic phenomena reflecting impainnents of neuromuscular transmission are the classical criteria for the diagnosis of myasthenia [1, 6, 9, 14], though most authors emphasize the absence of any cOlTelation between anti-AChR antibody titers and the severity of the clinical manifestations of myasthenia [1, 6,14,19,21]. A group of patients (about 20%) has been identified [19] in whom the antibody titer does not exceed that in healthy subjects; these are patients with seronegative myasthenia. Anti-AChR antibodies are generally not found in patients with Lambert-Eaton myas­ thenic syndrome [7, 1 \, 12, 16]. However, patients with myasthenia accompanied by thymoma and patients with late onset of disease produce antibody to the muscle protein titin, along with antibody to ryanodine receptors [2, 3, 20]. The aim of the present work was to investigate titers of anti-AChR antibodies in patients with different clinical forms of myasthenia and with Lambert-Eaton myasthenic syndrome, as well as in patients with thymoma without clinical signs of myasthenia.

Immunology of disorders of neuromuscular transmission

The neuromuscular junction (NMJ) is a prototype synapse and myasthenia gravis is the prototypic antibody-mediated disorder. There are now three other disorders of neuromuscular transmission caused by antibodies to other essential components of the NMJ. Antibodies to the muscle-specific kinase, MuSK, are defining a new form of myasthenia that can be associated with muscle atrophy. Antibodies to voltage-gated calcium channels are responsible for muscle weakness and autonomic dysfunction in the Lambert Eaton myasthenic syndrome. Antibodies to voltage-gated potassium channels are found in patients with a range of disorders affecting the NMJ, the autonomic system or the central nervous system. The pathogenic mechanisms probably depend on the IgG subclass of the antibodies and are only partly shared between the diseases.

Immune-mediated slow-channel syndrome: A new form of myasthenia

Immune-mediated slow-channel syndrome: A new form of myasthenia

The clinical limits of myasthenia gravis and differential diagnosis

The question of the limits of the clinical diagnosis of myasthenia gravis is in part one of definitions superimposed on the evolution in our understanding of normal and abnormal neuromuscular junction anatomy, physiology, and pharmacology, complemented by new knowledge of the immunopathogenic events that take place at the neuromuscular junction in the most common form of myasthenia gravis, acquired autoimmune myasthenia gravis. [1,2] In the past, myasthenia gravis was used to describe a series of disorders, most of them quite uncommon or rare, in which there appeared to be a defect in neuromuscular function based on abnormal neurophysiology and on pharmacologic responses to agents that enhanced or inhibited neuromuscular transmission, acting either presynaptically or postsynaptically. In 1982, we still classified myasthenia gravis as generalized vs. ocular, but in the generalized category we included congenital myasthenia gravis. It was recognized that congenital myasthenia gravis comprised several different disorders that did not appear to be immunologically mediated but that did appear to involve the neuromuscular junction based on the clinical picture, neurophysiology, and/or response to cholinesterase inhibitory drugs. [3] Through the work of several investigators, principally Dr. Andrew Engel and his collaborators (reviewed by Dr. Engel in this supplement and elsewhere [4]), we now understand that congenital myasthenia includes several disorders involving different presynaptic and postsynaptic defects. Some of these have very different neurophysiologic findings from those of classic autoimmune myasthenia gravis, even using traditional clinical neurophysiologic testing. It is of interest that we classified the Lambert-Eaton myasthenic syndrome (LEMS) as a clearly different myasthenic syndrome, although some of the congenital forms of myasthenia are just as clearly presynaptic as LEMS, albeit not immunologically mediated, which we now know is true of LEMS. Should we now reserve the term myasthenia gravis for the acquired, immunologically mediated postsynaptic disorder, be it generalized or …

Indications and value of thymectomy in myasthenia gravis

The therapeutic impact of thymectomy on the clinical course of myasthenia gravis is still a matter of debate. Issues in this discussion that are clinically relevant are reviewed. While the surgical procedure is accepted for thymomas its performance is controversial in cases with no thymomatous tissue. Outcome studies show a weak correlation between clinical course and thymus histology, but there is some doubt about the maximum age for thymectomy and about the therapeutic regimen following surgery. Retrospective studies show that thymectomy has a beneficial influence on the natural course of myasthenia. This positive effect is enhanced by appropriate immunosuppressive therapy together with anticholinesterase inhibitor substitution. Unfortunately, the different forms of myasthenia do not all respond in the same manner. Studies have shown that thymoma-associated myasthenia is more difficult to control than non-thymoma-associated myasthenic states. In both groups some patients go into remission after thymectomy alone, and the majority of patients with the institution of additional immunosuppression. In clinically mild cases thymectomy should not immediately be followed by immunosuppression. This will help to identify those patients responding with remission to thymectomy alone. Mostly these are young women with a hyperplastic thymus. Overall, thymectomy is beneficial and should be considered in all patients with generalized myasthenia who are still under 60 years of age.