APY29 br Patients and methods The

Patients and methods The severity of disease documented at each outpatient visit was graded according to the modified Osserman classification: grade I, focal disease (e.g. restricted to ocular muscles); grade II, generalised disease that is mild (IIa) or moderate (IIb); grade III, severe generalised disease; and grade IV, myasthenic crisis with life – threatening respiratory impairment [13]. Seven to 10days preoperatively, patients routinely received either 3 plasma exchanges on alternate days or intravenous APY29 (IVIG) 2g/kg over 24–48h, with the aim of minimising myasthenic weakness during the perioperative period. A transternal approach with complete removal of the thymus gland was performed in all patients. The histopathological reports of the thymus specimens were available in 16 patients. Most patients were reviewed within one month of surgery, and 3monthly thereafter for the first year. Medication dosages were recorded for each clinic visit. The response to thymectomy and clinical outcome was graded using the myasthenia scale of Millichap and Dodge [16]: A=complete remission, and all drug therapy was discontinued; B=good improvement, both objective and subjective, but continuation of drug therapy required in the same or lower dosage; C=slight subjective and/or objective improvement, but large doses of medication necessary; D=no change or worse; and E=patient died.
Results Key clinical and demographic features of our cohort are summarized in Table 1. All patients were AChR antibody-positive, with levels ranging from 7 to 499nM/L, without correlation to disease severity, throughout our cohort graded as IIb or above prior to thymectomy according to the modified Osserman classification. Five patients had received intensive care treatment for myasthenic crises, of whom four required invasive ventilation. At the time of thymectomy, in addition to treatment with pyridostigmine (20/20) and oral prednisolone (14/20), patients had either elective plasma exchange (15/20), or received IVIG (5/20) preoperatively. In 3 patients, thymectomy was performed following emergency admission for myasthenic crisis. The median age at thymectomy was 11year 1month, with a dominant median interval of 9months from disease onset to thymectomy. 90% of patients underwent thymectomy less than 2years after disease onset. Five children had thymectomy performed below the age of 10years, including two children younger than 3years. Only 2 patients required more than 24h of postoperative intensive care support; one patient was electively extubated on the second postoperative day, while another had been intubated preoperatively for severe bulbar symptoms and aspiration pneumonia, and required ongoing ventilation for airway protection postoperatively. Mainly minor infective episodes occurred postoperatively in 4 patients on steroid therapy, all responding promptly to antibiotic treatment. 15/20 patients were discharged home within 7days following thymectomy. From the 16 available histopathology reports, thymic hyperplasia was found in 9 (one associated with thymolipoma), thymoma (grade B1) in one, and normal findings in 6 patients. However, all patients with apparently normal thymus had had prior steroid therapy. The intervals between thymectomy and last follow-up ranged from 10months to 10years 11months (median: 2year 8months). At the last follow-up, 19/20 patients demonstrated improvement. Using the MG scale of Millichap and Dodge, six (30%) patients had achieved grade A response (complete remission). However, the time required for the patients to discontinue all medications varied considerably, ranging from 5months to 4years (median: 14months) in 5 patients; one other patient had been symptom free 3years postoperatively but only agreed to discontinue low dose pyridostigmine after 8.5years. Twelve (60%) patients achieved grade B response (with ongoing or weaning regimes of medical therapy), and one patient demonstrated slight clinical improvement (grade C response). No sustained clinical benefit was observed in the patient (Nr 6) with thymoma (grade D response). Of the 9 patients with thymus hyperplasia, 4 were graded A, and 5 were graded B in the response to thymectomy; by contrast, of the 6 patients with normal thymus, one was graded A, 4 were graded B and 1 was graded C.