4716 At the last follow up nine

At the last follow-up, nine patients had discontinued pyridostigmine within the first year postoperatively. Only one patient required pyridostigmine at a higher dose, but this was accompanied by successful weaning of prednisolone. None of the 5 patients who were on pyridostigmine treatment alone prior to thymectomy required additional medical treatment postoperatively (median time of follow-up: 5years 9months, range 1year 8months to 10years 2months); these included one patient who presented initially with a myasthenic crisis (grade IV) and 2 patients with grade III disease severity. Three of these 5 patients were in complete remission (grade A response) and 2 had a grade B response. Of the 14 patients treated with prednisolone prior to thymectomy, 5 had discontinued the drug at the time of their last follow-up, with weaning periods ranging from 13months to 42months (median 14months), while 4 patients were on a tapering dose that was at least 50% less than the dose taken preoperatively. Of the remaining 5 patients, only the patient with thymoma had required prednisolone at a higher dose than in the 4716 prior to thymectomy. Six patients had received additional immune therapy postoperatively, starting from between 1.5months to 3years (median 7.5months) following the surgery; these included various combinations of IVIG, plasma exchange, azathioprine, mycophenolate mofetil, and rituximab. Maximum drug (Pyridostigmine, Prednisolone) doses prior to thymectomy, doses at the last follow-up appointment and additional immune-modulating treatment introduced after thymectomy are summarized in Supplementary Table S1. Non-myasthenic features were seen in a patient (Nr 2) who developed persistent microscopic haematuria 8months after thymectomy. Renal biopsy revealed mild, diffuse mesangio-proliferative glomerulonephritis not requiring treatment. Another patient (Nr 18) developed severe nephrotic syndrome 3months postoperatively. Renal biopsy showed mesangio-proliferative glomerulonephritis. She required high dose daily prednisolone, plasma exchange and four doses of rituximab, followed by complete resolution of her nephrotic syndrome, with concomitant improvement in myasthenic symptoms. She later developed alopecia areata. None of our other patients developed other forms of immune-related diseases.
Discussion Although the outcome of thymectomy has not been objectively evaluated with randomised controlled trials in children with JMG, previous case series have suggested that the remission rate following thymectomy in JMG is higher than the remission rate with or without medical treatment. In a study involving 149 children, Rodriguez found cumulative remissions of 38.4% three years after thymectomy, compared with 7.6% of cumulative spontaneous remissions over the same period [17]. More recently, in a study involving a smaller number of patients, the incidence of complete remission was similar in both thymectomised and non-thymectomised groups (31%), but the thymectomised patients were sicker initially, and most had failed medical treatment; there was also a greater portion of thymectomised patients achieving partial remission [13]. The effects of immunotherapy and thymectomy were also recently reported in two series of children and adolescents with JMG [14], [15]. In our centres, children who were not thymectomised generally had either milder disease, good response to initial medical therapy, or were seronegative, thus precluding comparative analysis as representing a different population. The Osserman classification of disease severity has been widely used in previous JMG studies [2], [13], [17], [18], [19], [20], [21], [22]. In our series, the distribution of Osserman disease severity demonstrates a substantial shift toward less severe grades at the last follow-up in comparison to the grades before thymectomy. In grading the outcome of thymectomy, most previous paediatric studies have classified responses into remission/asymptomatic, improved, unchanged, worse or dead following thymectomy [23], [24]; some authors also include change in medication [2], [16], [17], [18], [19], [20], [21], [25]. More detailed classifications such as the Myasthenia Gravis Foundation of America (MGFA) post-intervention classification have been proposed for use in prospective clinical trials [26] but are not validated in children.