Background

Acetylcholine receptor antibody (anti-AChR) antibodies are detected in 75–80% of patients with generalised myasthenia gravis (MG). Among patients without anti-AChR antibodies, antimuscle-specific receptor tyrosine kinase (anti-MuSK) antibodies are detected in 40% of cases.1

Anti-MuSK-positive MG has a marked female preponderance. When comparing to anti-AChR-positive MG the age of onset is in average 10 years later, in the fourth decade.2–5 Although bulbar symptoms have been reported to be more common in this subtype of disease, three phenotypes have recently been described: oculopharyngeal weakness, with occasional profound tongue and facial atrophy; neck, shoulder and respiratory weakness without ocular weakness; and a phenotype indistinguishable from anti-AChR-positive MG. Another striking feature of anti-MuSK-positive MG is the poorer response to medical treatment, with a lower rate of complete remission.6–8

Since these antibodies were described for the first time, there have been multiple cases reported in literature allowing for a better understanding of the clinical features and appropriate management of these patients. However, few cases of anti-MuSK-positive MG during pregnancy have been described. We report the diagnosis and management of the disease in a pregnant woman, highlighting the importance of a multidisciplinary approach of these patients.

Case presentation

A 39-year-old patient, gravida 3, para 1, with irrelevant medical or familial history, was diagnosed with generalised immune-mediated MG with oculobulbar predominance during the first trimester of pregnancy.

The patient referred a 6-month history of bilateral ptosis, horizontal diplopia and dysphagia. On examination she presented bilateral ptosis, bilateral limitation of eye abduction, diplopia in all directions of gaze, dysphonia, facial diparesis, limited cervical flexion and bilateral superior limb proximal fatigable weakness. There was no evidence of respiratory compromise. Neurophysiological examination with repetitive nerve stimulation of radial, accessory and facial nerves was normal. Thoracic CT showed residual thymic tissue in the anterior mediastinum. Radioimmunoprecipitation assay revealed negative anti-AChR antibodies and positive anti-MuSK antibodies.

After clinical diagnosis of MG the patient initiated treatment with pyridostigmine (60 mg per os four times a day) with partial benefit on bulbar weakness. At 15 and 19 weeks of pregnancy, she presented two episodes of worsening of myasthenic symptoms, namely dysphagia, diplopia, cervical weakness and ptosis, requiring hospitalisation. Intravenous immunoglobulin (IvIG) 0.4 g/kg body weight per day, 5 days per month was introduced. The symptoms improved but did not resolve. After the second episode of exacerbation, 125 mg intravenous methylprednisolone was associated during hospitalisation. Immediately following the corticoid administration, the patient developed an anaphylactic reaction which resolved after intravenous treatment with clemastine. Corticosteroid therapy was suspended and IvIG administration was increased to 0.4 g/kg body weight per day, 3 days every 3 weeks. There was no repercussion in the fetal well-being in none of the episodes. Owing to the patient's poor response to treatment, desensitisation therapy was performed at 21 weeks of pregnancy and methylprednisolone was resumed at a dosage of 64 mg per os per day. Medication was maintained until delivery.

Obstetric surveillance was performed according to the hospital protocol, with normal laboratory and ultrasound scan routines. Third trimester ultrasound scan showed a fetus growing in the 25th centile, with normal amniotic fluid and no signs of fetal akinesia.

The patient presented to the emergency room at 34 weeks and 4 days with preterm premature rupture of membranes (PPROM). On admission amniotic fluid was clear, Bishop score was 5 and cardiotocography was reassuring, demonstrating irregular contractility. The patient presented a discrete bilateral ptosis and facial diparesis. Intravenous ampicillin protocol for PPROM was initiated. On re-evaluation 5 h 30 min after admission, Bishop score was 7 and the patient maintained a reassuring cardiotocography. Intravenous infusion of oxytocin (5 IU in 500 mL 5% glucose solution) was initiated to regularise uterine contractility. After discussion of the case with the neurology team it was decided that, given the patient's clinical stability, there was no contraindication to vaginal delivery. Ambulatory medication was maintained until delivery. With the beginning of the active phase of labour, intravenous hydrocortisone protocol for prophylaxis of adrenal insufficiency was initiated and, after anaesthetic evaluation, epidural anaesthesia was performed. During labour there was no exacerbation of myasthenic symptoms.

Eutocic delivery was performed uneventfully at 12 h 30 min after rupture of membranes. A lively male infant (weight: 2360 g; APGAR score 9/10/10) was born, showing no signs of muscular weakness.

Outcome and follow-up

Both the mother and the newborn went from the delivery room to the puerperium ward. Breastfeeding was initiated in the first hour postpartum, according to the hospital protocol. The newborn presented no signs of neonatal disease, neither initially nor in the course of time. The mother showed no immediate signs of worsening of myasthenic symptoms. Prepartum MG medication was maintained. Postpartum care was performed according to the hospital protocol and both the mother and the newborn were discharged on the second day.

Three months after, the patient presents only with mild facial diparesis; she is now with prednisolone 20 mg daily per os, in a reducing dosage schedule, and monthly IvIG (0.4 g/kg body weight).