Prognosis in occult thymomas in myasthenia gravis following transcervical thymectomy.

Thymomas were noted in 239 (11%) of 2097 myasthenic patients followed up at our institution. Among 996 patients who had undergone thymectomy, 191 patients (19%) had thymomas compared with 48 (4%) of 1101 patients treated without surgery. A definitive diagnosis of thymoma was not made until after thymectomy in 61 patients (35%); in patients not treated with thymectomy, 23% of associated tumors were diagnosed at autopsy. Patients with occult thymomas treated with the transcervical approach had a clinical course superior to those with tumors diagnosed prior to surgery and treated with the transsternal approach. Most of the advantage could be attributed to the association of occult thymomas with small tumor size and to the association of the latter with absence of invasiveness. Small tumor size was significantly associated with higher remission and lower mortality as shown in a proportional hazards analysis. Occult thymomas were accessible through the transcervical approach, with some operations necessitating a complementary mediastinotomy. Thymectomy, through the transcervical approach if technically feasible, is of benefit to all patients, has minimal morbidity, and should be performed early in the course of the disease as a diagnostic and therapeutic intervention since the risk of occult thymomas in patients with myasthenia gravis is high.

Effects of thymectomy in myasthenia gravis.

Factors influencing onset of remission in myasthenia gravis were evaluated in 2062 patients, of whom 962 had had thymectomy. Multivariate analysis showed that appearance of early remissions among all patients was significantly and independently influenced by thymectomy, by milder disease, and by absence of coexisting thymomas. Patients with mild generalized symptoms treated with thymectomy reached remission more frequently, even when compared with those with ocular myasthenia treated without surgery. Short duration of disease before thymectomy in mild cases was another factor associated with earlier remissions. Mortality for all patients was significantly and independently influenced by severity of symptoms, age, associated thymomas, and failure to remove the thymus. Patients without thymectomy and with thymomas had, in addition, earlier onset of extrathymic neoplasms. Morbidity after the transcervical approach was minimal. This study demonstrates that early thymectomy by the transcervical approach, when technically feasible, has significant clinical advantages over the transthoracic approach and should be advocated for all patients with myasthenia gravis, including those with ocular disease.

Clinical experience in more than 2000 patients with myasthenia gravis.

The vast strides in terms of pathophysiologic understanding which have been made in the past 25 years of research in myasthenia gravis are remarkable. This period of time has also seen the evolution of many applicable technological advances to better our care of these patients. Myasthenia's place in the autoimmune family of diseases has been demonstrated. No clear-cut strategy resulting from these discoveries has, however, been more than one of temporary relief or clinical improvement. In our center over these years the performance of early thymectomy in all cases of generalized myasthenia seems to be the one demonstrably reliable technique available. The effect of this procedure on coexisting neoplasia and other autoimmune disease suggests continuing avenues of investigation.

Analysis of false negative results in the immunoassay for anti-acetylcholine receptor antibodies in myasthenia gravis.

Possible causes for the failure of immunoassays to detect anti-acetylcholine receptor activity in serum from confirmed myasthenia gravis (MG) patients were investigated. A more sensitive assay, using Protein A to trap immune complexes (ARIA), was applied to 65 MG sera which were negative in the usual assay and to 42 normal human sera. Normal and negative MG sera had antibody (Ab) activity in the same range (50-70 pM). Titers present in 70% of normal sera appeared to be specific antireceptor antibodies as defined by tests for antigen specificity. Thus, higher sensitivity assays did not improve discrimination of MG from normals. In a second group of 108 MG sera studied, 48 were negative by the usual assay criteria in a rat acetylcholine receptor immunoassay. Further detailed analysis of this negative group showed that 3/48 had IgG3 antibody not detectable in the test, 14/48 had Ab's recognizing human receptor determinants exclusively, 29/48 had toxin blocking Ab's not determined by immunoassays, and 6/48 were negative in all tests. The results indicate that the exclusive occurrence of toxin-blocking antibodies in MG subjects is a major factor contributing to false negatives in the ARIA test. Estimates of the amount of Ab's with this functionality indicated that they are present in very much smaller amounts than other classes of anti-receptor Ab's. Degree of blocking activity in patient serum showed a fair correlation with severity of disease. Thus, blocking antibodies appear capable of causing all degrees of disease severity in the absence of other types of antireceptor Ab's. The development of a sensitive and quantitative in vitro assay for blocking antibodies combined with the usual immunoassay would be a major improvement for a MG diagnostic test, with greater than 94% positivity predicted.

Transcervical thymectomy for thymoma in myasthenia gravis.

The results of thymectomy performed through a transcervical approach in 37 myasthenic patients with thymomas is reported and compared with results in 97 patients who had thymomas removed through a transsternal approach. In 29 of the former patients the thymomas were unsuspected and found at the time of thymectomy, and in 8 a preoperative chest roentgenogram was suspicious for the presence of a tumor. In the transcervical group there were only 4 invasive thymomas, while in the transsternal group there were 32. In the transcervical group there was no evidence of recurrence in the patients with unsuspected thymomas, and one recurrence in the group with suspected thymomas. In the transsternal group eight patients had known recurrence or persistent disease. The transcervical approach seems appropriate for the removal of small thymomas discovered at the time of thymectomy or suspected from the preoperative work-up.

Acetylcholine receptor antibodies in myasthenia gravis.

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24- to 30-month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.

Autoimmunity in ocular and generalised myasthenia gravis.

Restricted ocular myasthenia gravis (OMG) and generalised myasthenia gravis (GMG) have been shown to differ in a number of respects. In OMG, antiacetylcholine receptor, antistriational and antinuclear antibodies were rare relative to their frequency in GMG. In contrast, antithyroid antibodies and a history of thyroid disease were much more prevalent in OMG than in GMG, OMG was not associated with the female predominance seen in GMG and appeared to be relatively common in some races rather than others. It is suggested that different pathogenetic mechanisms are responsible for these two forms of MG.

Plasmapheresis in refractory generalized myasthenia gravis.

A group of 16 patients with severe generalized myasthenia gravis (MG) (five with thymoma) that was resistant to anticholinesterases, thymectomy, and corticosteroids were treated by plasmapheresis. Twelve patients showed an excellent clinical response. Plasmapheresis is an effective treatment modality for many patients with severe generalized MG resistant to other forms of therapy. Unfortunately, the beneficial results are only transient and periodic plasmapheresis treatments are necessary.

Current concepts in the surgical treatment of patients with myasthenia gravis.

Patients undergoing surgical treatment often have concurrent diseases. An in-depth understanding of such diseases permits the dentist to initiate treatment with minimal risk to the patient. Myasthenia gravis (MG) is one such disease; it is characterized by various degrees of muscle weakness and fatigue. Many of the physical signs and symptoms affect the oral and facial musculature. A review of the symptoms, etiology, and treatment of myasthenia gravis, with special reference to the patient undergoing surgical treatment, is presented.

Multiple forms of anti-acetylcholine receptor antibody in myasthenia gravis.

Sera of patients with myasthenia gravis (MG) contain anti-acetylcholine receptor (AChR) IgG antibodies (Ab) which have different antigenic specificities. Three Ab types were detected: (1) MG-I, which forms immune complexes with AChR; (2) MG-C, which decreases binding of AChR to concanavalin A; and MG-B, which blocks alpha-bungarotoxin binding to AChR. Sera from 152 MG patients were screened for the Ab types. Sixty-one percent contained MG-I, 26% contained MG-C, 10% contained MG-B, and 5% contained both MG-C and MG-B. The latter Ab types were associated with more severe forms of MG but showed no other clinical correlations. IgG antibodies of defined type were purified, and their interaction with unlabeled and toxin-prelabeled AChR from denervated rat muscle was studied in detail. Receptors are homogeneous with respect to determinants recognized by MG-I, but heterogeneous with respect to determinants recognized by MG-C (3 subpopulations, 22%, 28%, and 50% of AChR) and by MG-B (2 subpopulations, 30% and 70% of AChR). The stoichiometry of AChR interaction with the antibodies indicates that for each toxin-binding site, the receptor is divalent as an antigen for MG-I and MG-C but is tetravalent for MG-B. Denervated muscle AChR appears to be a mixture of at least 3 molecular forms of AChR, each of which has distinct immunological features as well as components common to all the receptor subpopulations.