Difficulties of diagnostic testing and therapy in seronegative myasthenia gravis with oculobulbar symptoms

The muscle-specific receptor tyrosine kinase (MuSK) antibody (ab) positive myasthenia gravis is a distinctive subgroup of the myasthenia gravis population. The clinical features are very variable with mostly severe oculobulbar involvement. The following case report should illustrate the complexity of diagnostic testing and therapy in this rarely subgroup of myasthenia gravis.

A 69 year old female patient suffered from bulbar symptoms as dysarthria and dysphagia since 2 weeks. The patient developed ocular symptoms as left sided ptosis, horizontal and vertical double vision. The bulbar weakness got worse with dysarthrophonia and severe dysphagia. Limbs and neck muscles were never involved. Cranial and thoracal MRI showed a normal brain and no thymoma.

All the diagnostic testing provided no evidence for myasthenia gravis (no decrement, negative Tensilon Test, no acetylcholin receptor antibodies).

Because of progressive clinical deterioration we started intravenous immunglobuline (25mg/d) for 5 days concomitant with oral medication of corticosteroids (40mg/d). The treatment showed no improvement. Under the medication of corticosteroids the clinical features even got worse after about 10 days. The patient developed a respiratory insufficiency with restricted vital capacity, deteriorated dysphagia and worsened dysarthrophonia. There were no need for intubation at no time. We started pyridostigmine bromide 330mg/d without positive effects but severe cholingergic side effects.

About more than 10 days later the test result of the MuSK Ab arrived which showed highly elevated Titers. FinallyMuSK positive myasthenia gravis could be diagnosed. After all the patient was transferred to a closed home town hospital and a plasma exchange was initiated.

Conclusion: This case report illustrates the diagnostical and therapeutical difficulties of MuSK positive myasthenia gravis in the clinical daily routine. Especially by the severe clinical pattern with undinstinguished oculobulbar symptoms and the commonly negative diagnostic results for the diagnosis of Myasthenia gravis the diagnosis can be delayed due to the prolongated processing of laboratory-testing.