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MGA News

Spring 2002

Effectiveness of Thymectomy in MG

Professor Nick Willcox

The Trial being Planned by our President,

Professor Newsom-Davis

Thymectomy -- why and what?

The thymus sits just behind the breastbone. Its main job is to produce and export the white blood “T cells” that control most immune responses; nearly all these T cells protect against infections, but rare rogues can be harmful, as in MG.

[Why remove it? We don’t really understand, but, abnormally, in most young myasthenics, the thymus gets colonised by mature immune cells from the circulation. Some infiltrating “B cells” are busy making the antibodies to the muscles’ ‘ignition system’ (its “AChR”) that cause the myasthenic weakness. They seem to be proliferating there, and ‘learning’ to make a richer mix of more damaging antibodies, before being exported (eg to the bone marrow).]

Thymectomy means removing the thymus, and is a major operation. In a specialist centre, under a general anaesthetic, the breastbone is split, and the thymus is removed totally. The patient is usually fit to go home about one week later. Thymectomy does not create an immune vacuum, because vast numbers of T cells have already been exported, even in young children. Nearly all Neurologists agree that thymomas should normally be removed (to prevent spread), but that thymectomy is not suitable for pure eye-muscle weakness, or in the elderly whose thymus has usually almost disappeared.

The need for a trial

There is no hard proof that thymectomy really is reliably helpful, and there is still much disagreement about it, especially in the USA. From past experience, most European Neurologists believe that about 1 in 4 patients gets completely better, ~1 in 2 improves significantly and ~ 1 in 4 continues as before. The difficulties are that:- previous reports haven’t all compared like with like, and they don’t all agree: at best, any benefits seem modest in many cases: MG can fluctuate unpredictably/without provocation, so we need to compare larger numbers of well-matched patients and we need to assess them by more hard and standardised measures. That inevitably means a multi-centre trial – to provide enough patients without long delays.

In an ideal trial, patients are ‘randomised’ into different groups and then treated identically apart from the operation. They are also assessed ‘blind’ – i.e. the assessor doesn’t know which group they are in. It is not fair on patients to do the scientifically perfect ‘control’ – a sham operation – i.e. opening up but not actually removing anything.

A realistic trial

After much thought, John and his team now propose to compare outcomes after steroids-plus-thymectomy with steroids alone. In detail, they plan to:-

The trial’s current status

John’s applications are under review by both the Medical Research Council (UK) and the National Institutes of Health (USA), who have asked for refinements of details. He is hoping for the necessary funding (~ £650,000) to cover salaries plus back-up over~ 4 years. Say your prayers.

The proposed centres include:-

Webmaster's Note:

21st March 2003     - The funding for this trial is still under review.
14th June 2003       - There is still no funding for this trial.

27th January 2005 - The trial has now been funded and is proceeding.

MGA NEWS Spring 2002
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