Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.

Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.

Use of foot-to-foot bioelectrical impedance analysis in children.

The aim of this study was to compare two methods of measuring body composition in children aged 6-10 years: with a traditional bioelectrical impedance analyser and a foot-to-foot impedance device. In 117 subjects (55 girls, 62 boys), bioelectrical impedance was measured using a Xitron 4000 device and a foot-to-foot impedance instrument (Rowenta); body fat mass and fat-free mass were then calculated and comparisons between means were performed using appropriate statistical tests.

Thymoma in patients with MG: characteristics and long-term outcome.

OBJECTIVE: To examine the characteristics of thymoma when associated with MG and to evaluate those conditions that can complicate management and affect survival. METHODS: The study includes 207 myasthenic patients who were operated on for thymoma, with at least 1-year follow-up from surgery. MG severity and response to treatment, the occurrence of paraneoplastic diseases and extrathymic malignancies, thymoma histologic types and stages, adjuvant therapy, tumor recurrences, and causes of death were recorded. RESULTS: MG-associated thymoma was predominantly of B type and was invasive in the majority of patients. MG was generally severe, and most patients remained dependent on immunosuppressive therapy. Other paraneoplastic disorders and extrathymic malignancies were found in 9.66 and 11.11% of patients. Thymoma recurrences occurred in 18 of 115 patients with invasive tumors (15.65%) and were often associated with the onset/aggravation of autoimmune diseases. On completion of the study, MG and thymoma accounted for a similar mortality rate. CONCLUSIONS: Thymoma should be considered as a potentially malignant tumor requiring prolonged follow-up. The presence of myasthenic weakness can still complicate its management. Thymoma-related deaths are bound to outnumber those due to MG in the future.

Therapeutic options in ocular myasthenia gravis.

The term ocular myasthenia gravis refers to the disease clinically restricted to extrinsic ocular muscles. It can be disabling as ptosis, and to a greater extent diplopia, both interfere with daily activities. Although ocular disturbances are the most frequent initial complaints in myasthenic patients, symptoms usually progress to generalized disease and only 15% of patients complain of purely ocular weakness for the entire course of their illness. Secondary generalization occurs with the highest frequency in the first 2 years from the onset. Both the severity of symptoms and the risk of generalization should be taken into account when devising a therapeutic plan for these patients. Anticholinesterases are of limited efficacy and a considerable proportion of patients require additional therapy. Corticosteroid therapy, generally prednisone on an alternate-day schedule, is very effective, but a reason for concern is represented by the frequent need for long-term administration with increased risk of severe complications. In patients unresponsive to prednisone or requiring too high dosages, immunosuppressive drugs like azathioprine should be used with the same criteria applied in generalized myasthenia. As corticosteroids and immunosuppressants reduce the chance of generalization, their use is justified in patients with recent-onset disabling disease. In long-standing cases with low risk of generalization, treatment is aimed at the relief of symptoms and pharmacological therapy should be reduced to the minimum effective dosage. The indication for thymectomy in ocular myasthenia remains highly controversial and should be reserved for disabled patients in the early stages of the disease.

Clinical characteristics and prognosis of myasthenia gravis in older people.

OBJECTIVES: To investigate the characteristics of myasthenia gravis (MG) in older people and to evaluate the benefits of immunosuppressive treatments at this age. BACKGROUND: Myasthenia gravis in older adults has not been extensively studied. In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present. METHODS: Of 837 myasthenic patients followed since 1978, we identified 172 cases with onset after age 60. All patients were treated with anticholinesterases. In the decade from 1978 to 1988, immunosuppressive therapy was performed mainly with corticosteroids (prednisone); since 1989, azathioprine alone or, more often, associated with prednisone, has been increasingly used in MG patients. Long-term outcome was evaluated in 149 cases with follow-up longer than 1 year. Remission, pharmacological remission, and marked improvement with reduction in drug dosage were considered good results. RESULTS: Patients older than age 60 at onset of the disease were 20.5% of our series, male/female ratio was 1.9, age at onset ranged from 61 to 86 years, 87.2% patients had generalized disease, thymoma was detected in 37 patients (21.5%). Of 149 cases with sufficient follow-up data, 9 were in remission, 111 achieved good results, 3 died of MG, and 120 required immunosuppressive therapy at some time. Sixty-seven patients had been treated with prednisone for 0.5-16 years (mean, 5 years); good results were recorded in 51 patients (76.1%) and severe side effects in 12 (17.9%). Forty-six patients had received combined therapy with prednisone and azathioprine for 1 to 12 years (mean, 3.9 years); good results were recorded in 41 patients (89.1%) and severe side effects in six (19.5%). Seven patients had been treated with azathioprine alone for 1 to 4 years (mean, 2.3 years) with good results in five and with no side effects. CONCLUSIONS: The prognosis of MG in older people seems to be favorable, although full remission is rare and MG weakness, treatment side effects, and associated thymoma can contribute to mortality rate. In our experience, the combined therapy with prednisone and azathioprine was more effective than prednisone alone, and steroid-related side effects were more frequent than those related to azathioprine.

Course and treatment of myasthenia gravis during pregnancy.

OBJECTIVE: To evaluate the influence of myasthenia gravis (MG) on pregnancy and potential treatment risks for infants and mothers. BACKGROUND: MG frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Knowledge of the potential effects of 1) pregnancy on the course of MG and 2) the use of immunosuppressive drugs during pregnancy is limited, rendering decision-making difficult for both patient and physician. METHODS: We studied 47 women who became pregnant after the onset of MG. Immunosuppressive drugs were administered when MG symptoms were not controlled with anticholinesterases. Sixty-four pregnancies resulted in 55 children and 10 abortions. RESULTS: During pregnancy, MG relapsed in 4 of 23 (17%) asymptomatic patients who were not on therapy before conception; in patients taking therapy, MG symptoms improved in 12 of 31 pregnancies (39%), remained unchanged in 13 (42%), and deteriorated in 6 (19%). MG symptoms worsened after delivery in 15 of 54 (28%) pregnancies. Anti-acetylcholine receptor antibody (anti-AChR ab) was positive in 40 of 47 mothers and was assayed in 30 of 55 newborns; 13 were positive and 5 of 55 (9%) showed signs of neonatal MG (NMG). All affected babies were seropositive. CONCLUSIONS: Pregnancy does not worsen the long-term outcome of MG. The course of the disease is highly variable and unpredictable during gestation and can change in subsequent pregnancies. The occurrence of NMG does not correlate with either maternal disease severity or anti-AChR antibody titer. Immunosuppressive therapy, plasmapheresis, and i.v. human immunoglobulins can be administered safely if needed.

Juvenile myasthenia gravis with prepubertal onset.

Juvenile myasthenia gravis (JMG) with prepubertal onset is an uncommon disease. We studied 19 patients with age at onset ranging from 1.5 to 9.2 years and compared their clinical characteristics and response to therapy with 114 cases with MG onset after the prepubertal age, up to 20 years. Neither sex prevalence nor autoimmune diseases other than MG were found in younger patients. Although ocular myasthenia was more frequent than in later-onset JMG, children with generalized symptoms were often severely affected and respiratory involvement was present in 8/19 patients. Anti-acetylcholine receptor antibodies were detected at a lower rate and, in contrast with results in older patients, seronegativity was more frequent among children with generalized disease. Three out of six patients with onset before the age of five showed spontaneous remission. Nine prepubertal patients underwent thymectomy and, as most of them also received immunosuppressive therapy, the influence of surgery on disease outcome remains unclear; in no case was thymoma found. This is in contrast to the good results after thymectomy and the presence of thymoma in the later-onset group. Eleven patients in the prepubertal series were treated with immunosuppressive therapy. At the end of follow-up, most patients were in good condition. The frequency of immunosuppressive therapy and the rate of good therapeutic results did not differ from those observed in older patients.