Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy.

Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.     

Peer influence on students’ estimates of performance: social comparison in clinical rotations

Context During clinical rotations, students move from one clinical situation to another. Questions exist about students’ strategies for coping with these transitions. These strategies may include a process of social comparison because in this context it offers the student an opportunity to estimate his or her abilities to master a novel rotation. These estimates are relevant for learning and performance because they are related to self‐efficacy. We investigated whether student estimates of their own future performance are influenced by the performance level and gender of the peer with whom the student compares him‐ or herself. Methods We designed an experimental study in which participating students (n = 321) were divided into groups assigned to 12 different conditions. Each condition entailed a written comparison situation in which a peer student had completed the rotation the participant was required to undertake next. Differences between conditions were determined by the performance level (worse, similar or better) and gender of the comparison peer. The overall grade achieved by the comparison peer remained the same in all conditions. We asked participants to estimate their own future performance in that novel rotation. Differences between their estimates were analysed using analysis of variance (anova) . Results Students’ estimates of their future performance were highest when the comparison peer was presented as performing less well and lowest when the comparison peer was presented as performing better (p < 0.001). Estimates of male and female students in same‐gender comparison conditions did not differ. In two of three opposite‐gender conditions, male students’ estimates were higher than those of females (p < 0.001 and p < 0.05, respectively). Conclusions Social comparison influences students’ estimates of their future performance in a novel rotation. The effect depends on the performance level and gender of the comparison peer. This indicates that comparisons against particular peers may strengthen or diminish a student’s self‐efficacy, which, in turn, may ease or hamper the student’s learning during clinical rotations. The study is limited by its experimental design. Future research should focus on students’ comparison behaviour in real transitions.     

Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.     

Masticatory performance in patients with myasthenia gravis

Masticatory muscle electromyograms (EMGs) were recorded while patients with bulbar myasthenia gravis chewed artificial food and compared with those of patients with ocular myasthenia gravis, patients in clinical remission who had previously suffered from bulbar myasthenia gravis and healthy individuals. Masticatory performance and EMGs were significantly smaller in the bulbar group. There were no indications of subclinical masticatory muscle weakness in patients with bulbar myasthenia gravis in remission and in patients with ocular myasthenia gravis. Patients with bulbar myasthenia gravis barely compensated for muscular weakness by chewing at a higher percentage of their maximal EMG. These quantitative findings, when combined with subjective reports of masticatory muscle weakness, show that a need to support the jaw is characteristic of patients with bulbar myasthenia gravis who produce low EMG activity.     

Proximal muscle weakness, depressed tendon reflexes and autonomic dysfunction: the Lambert-Eaton myasthenic syndrome

Three patients with Lambert-Eaton myasthenic syndrome (LEMS), two men aged 61 and 64 and a woman aged 55 years, all developed proximal weakness, depressed tendon reflexes and autonomic dysfunction. Although this clinical triad is highly suggestive for LEMS, the disorder had not been recognized initially. The woman had a small-cell bronchial carcinoma, treated successfully by chemotherapy, whereafter the LEMS symptoms gradually disappeared. The first man was treated with 3,4-diaminopyridine and azathioprine, whereupon his symptoms diminished. The other man had only slight complaints and refused drug treatment. The three cases illustrate that presentation and course of LEMS can vary between patients. Furthermore, clinical and electrophysiological features can suggest myasthenia gravis, myopathy or axonal polyneuropathy. Therapeutic options and the risk of underlying malignancy make early diagnosis important. In conclusion, in every patient presenting with unexplained proximal weakness, LEMS should be considered, especially if depressed tendon reflexes and autonomic dysfunction are found as well.     

Epidemiology of myasthenia gravis with anti-muscle specific kinase antibodies in The Netherlands

The epidemiology of myasthenia gravis subtypes and the frequency of antibodies to muscle-specific kinase (MuSK) was studied in patients with generalised myasthenia gravis without anti-acetylcholine receptor antibodies who had an onset of symptoms between 1990 and 2004 in a well-defined region in The Netherlands. The nationwide prevalence and incidence of myasthenia gravis with anti-MuSK antibodies were also studied. MuSK antibodies were found in 22% of patients with generalised myasthenia gravis without anti-acetylcholine receptor antibodies. Nationwide, 35 patients with MuSK myasthenia gravis were identified, yielding a prevalence of 1.9 per million (95% confidence interval (CI) 1.22 to 2.59) and an annual incidence 0.10 per million person-years (95% CI 0.06 to 0.14).