| Description |
This case, previously reported in 2007, is published courtesy of John Newsom-Davis, M.D., FRCP, FRS, CBE. Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford. This patient was unusual in presenting in early childhood and the development of persistent facial muscle and tongue atrophy. At age 3 years, she presented with severe facial weakness and partial bilateral ptosis. When she was 14 years old, single fiber EMG (SF-EMG) detected a disorder of neuromuscular transmission at the neuromuscular junction and a diagnosis of myasthenia gravis (MG) was made. To establish whether she had an acquired form of myasthenia she underwent plasma exchange, resulting in clear clinical improvement. She was then started on corticosteroid treatment. As soon as her condition stabilized, she was weened off steroids but at the age of 15 her symptoms relapsed with profound facial weakness and moderate axial and limb weakness. Steroids were re-introduced and she was started on azathioprine as a steroid-sparing agent, but she failed to respond to the latter so this was switched to cyclosporin together with prednisolone, and she responded well. Although her axial and limb problems had been, up to 2007, in remission, her severe facial weakness persisted and she developed marked nasal speech, although no dysphagia for solids or liquids. A striking clinical finding was severe wasting of the tongue with a triple furrowed appearance. MRI of the facial and tongue muscles confirmed muscular atrophy and an abnormal high signal replaced most of the intrinsic tongue musculature. Antibody studies: The patient tested seronegative for anti-acetylcholinesterase antibodies (AChR) and positive for antibodies to the muscle specific tyrosine kinase (MuSK). MuSK is another protein of the post synaptic membrane of the neuromuscular junction, and plays a role in agrin-induced AChR clustering. In the original report of this child, the authors described altogether four AChR antibody negative-MuSK antibody positive patients to illustrate the phenotypes of this neurological rarity. The four cases had typical features of MuS-MG. The patients are young females presenting between 10 and 40 years of age. However, about 1 in 8 patients are male and, with increased awareness of this disorder by neurologists, older cases are now being identified. Patients often present with bulbar and ocular symptoms, but profound neck or respiratory weakness without other signs may occur. Limb and axial muscle involvement may be present in the acute phase of the disease but is seldom severe and usually responds readily to treatment. These patients can deteriorate rapidly, relatively frequently requiring ventilatory and nutritional support. Dysphagia and weight loss may at first suggest motor neuron disease, and some patients may not complain of typical myasthenic fatigue. In contrast to AChR antibody-positive patients, the tensilon test may be only weakly positive. SF-EMG studies on limb muscles may be normal at presentation, and this has been noted frequently in MuSK patients studied following treatment. Muscle atrophy particularly of the facial and bulbar muscles, seems to be a relatively common long-term consequence of the disease perhaps because the condition is relatively difficult to treat effectively, frequently responding poorly to steroids and azathioprine and sometimes requiring other immunosuppressive agents as in this case. It has also been noted that the patients may not respond well to acetylcholinesterase inhibitors such as pyridostigmine (mestinon), although ambenonium chloride (mytelase) may be tolerated better and can be helpful in some patients. None of the four reported cases were treated with thymectomy, which is of doubtful benefit in MuSK antibody-positive cases. Two studies reported in 2005 have shown that the histology of the MuSK-MG thymus is normal or near normal. Conclusions: MuSK phenotype •MuSK-myasthenia gravis often presents with predominantly bulbar and ocular symptoms. •Facial muscle atrophy is relatively common in long-standing MuSK-MG •The age range at onset is wide although to date most patients are young adult females •There is no substantial thymus pathology •Limb symptoms may remit with treatment while facial and bulbar weakness persists. •Patients are seronegative for AChR antibodies. There are no other diagnostic serum markers for this disorder. •Neurophysiological studies usually show evidence of a transmission defect in facial muscles but may be normal in the limb muscles. •Response to plasma exchange is usually very good. Response to conventional treatments with prednisolone and azathioprine can be poor, and additional immunosuppressive drugs may be required. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/359 |
