Thymoma-associated myasthenia gravis

A 25-year-old HIV-negative woman presented to our hospital with a 6-week history of progressive generalised muscle weakness. Her main complaints were limb weakness, blurred vision, difficulty in swallowing and a change in her voice. She was previously healthy and had a normal vaginal delivery 5 months previously. She had no family history of any neuromuscular disease.

On neurological examination she had bilateral ptosis, bilateral asymmetrical facial weakness (with involvement of the forehead) and generalised proximal muscle weakness which was characterised by fatigability. Her reflexes were generally brisk, but her tone, sensation and co-ordination were normal and her plantar responses were downgoing. Her swallowing was impaired and she had a hypophonic dysarthria. The rest of the physical examination was unremarkable.

On examination the following morning, most of her muscle weakness had resolved and she was able to swallow her breakfast with ease. However, later on during the day her ptosis, dysphasia and limb weakness became evident again.

Her serum thyroid-stimulating hormone (TSH), calcium, magnesium, phosphate and creatinine kinase were normal. Her forced vital capacity was 2 litres. A chest X-ray showed an anterior mediastinal mass with calcification (Fig. 1) and on computed tomography (CT) scan this mass was assessed as most likely being a thymoma.

Neostigmine and ice-pack tests were performed and each confirmed a diagnosis of myasthenia gravis (MG). She was started on oral pyridostigmine 60 mg 6-hourly and prednisone 20 mg daily. She responded well to treatment and had a thymectomy 2 months after presentation.

Discussion

MG is a construct of the Greek words myo (muscle) + asthenia (weakness) and a Latin adjective gravis (severe). It is an uncommon autoimmune syndrome caused by failure of the neuromuscular junction as a result of formation of antibodies against acetylcholine nicotinic postsynaptic receptors. MG has an incidence of 10 - 20 new cases per million persons per year and a prevalence rate of 200 - 400 cases per million persons.¹ The incidence is the same in the Cape Town metropolis as the rest of the world.2 It has a bimodal distribution with an early peak of the disease in the 2nd and 3rd decades with female predominance and a late peak in the 6th and 8th decades with male predominance.

MG may affect the ocular muscles alone or cause a generalised muscle weakness. Fluctuating fatigable skeletal muscle weakness is usually diagnostic of MG. Pain and wasting are typically absent. The reflexes are preserved and usually brisk but may be fatigable. The asymmetry of skeletal muscle weakness and brisk reflexes might cause the diagnosis to be confused with that of motor neuron disease. However, bilateral ptosis in a young female patient should always make MG a priority diagnosis.

A thymoma is found in 10% of patients with MG and 99% of these patients will be seropositive. Thymoma-associated MG is generally a severe disease whose current good prognosis depends mainly on immunosuppressive therapy. A thymoma is an obvious indication for surgery because there may be an underlying malignancy. Although thymectomy improves the prognosis for thymoma it does not significantly improve the course of MG.3

The common diagnostic test is using the anticholinesterase edrophonium (tensilon test) or neostigmine for reversal of muscle weakness. Other simple tests that are cheap are the ice-pack test and sleep test for reversal of ptosis. Criteria for these tests are poorly defined. Serum assays for anticholinerase antibodies may be positive in approximately 80 - 90% of patients with generalised MG and 30 - 50% of patients with ocular MG. Repetitive stimulation of peripheral nerves with electromyography (EMG) may also demonstrate progressively diminished action potentials or fatigability in up to 90% of cases of generalised MG.1

Management

Management of MG ranges from symptomatic treatment with oral anticholinesterases to chronic immunomodulating drugs for patients who remain symptomatic on anticholinesterases.4 , 5

Lindisa Mbuli, MB ChB, DOH

Registrar, Department of Medicine, New Somerset Hospital, Cape Town

Muhammed S Moosa, MB ChB, FCP

Consultant, Department of Medicine, New Somerset Hospital, Cape Town

Correspondence to: M S Moosa (shiraz.moosa@gmail.com)

References

1. Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present and future. J Clin Invest 2006;116(11):2843-2854.

2. Heckmann J, Owen EP, Little F. Myasthenia gravis in South Africans: racial differences in clinical manifestations. Neuromuscul Disord 2007;17:929-934.

3. Avoli A, Minisci M, di Schino MD, et al. Thymoma in patients with MG: characteristics and long term outcome. Neurology 2002;59:1844-1850.

4. Heckmann J, Rawoot A, Bateman K, et al. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurology 2011;11:97.

5. Hart IK, Sharshar T. Immunosuppressant drugs for myasthenia gravis. J Neurol Neurosurg Psychiatry 2009;80:5-6.