Search

Objective Many myasthenia gravis (MG) patients with anti-muscle-specific tyrosine kinase (MuSK) antibodies have prominent oculobulbar symptoms or weaknesses of the neck and respiratory muscles. An ocular form of MG having anti-MuSK antibodies (MuSK-OMG) is very rare. We review the clinical features of two such cases. Methods We reviewed cases of patients with an ocular form of MG having anti-MuSK antibodies, including two new cases. Results We found seven published cases, plus two cases described in this report. The mean age at onset of these nine patients was 37.0 ± 17.7 years, and the mean disease duration (from ocular MG onset to report) was 47.0 ± 43.1 months. The clinical courses appeared benign, but heterogeneous. Five of the patients responded to pyridstigmine. Four patients received immunotherapy, which resulted in improvement. Our two patients had mild ocular symptoms. One patient was stable with no immunosuppressive treatment, and the other patient was treated with prednisolone and tacrolimus. Conclusions Cases of an ocular form of MG having anti-MuSK antibodies do exist. The benign clinical courses and pharmacological responses to cholinesterase inhibitors imply that the antibodies might have different pathogenicities and specificities from those of MuSK-generalized MG. The presence of anti-MuSK antibodies should therefore be determined in ocular MG patients negative for anti-acetylcholine receptor antibodies.

Some intractable cases of autoimmune autonomic ganglionopathy are treated with diverse combinations of immunomodulatory therapies. However, it is unclear which of the immunotherapies directly contributed to the relief of dysautonomia when several immunotherapies have been utilized. To evaluate which of the immunomodulatory therapies are effective, we describe a 60-year-old man with autoimmune autonomic ganglionopathy who was successfully treated by combined immunomodulatory therapies. The patient showed subacute pure autonomic failure without antecedent infectious symptoms, and was admitted to Yamaguchi University Hospital, Yamaguchi, Japan. He demonstrated involvement of cardiovascular, pupillary, sudomotor, gastrointestinal and bladder functions. Serum ganglionic acetylcholine receptor autoantibody titer was highly elevated. The diagnosis of autoimmune autonomic ganglionopathy was made. Plasma exchange was repeated nine times, resulting in minimal improvement. Subsequently, intravenous immunoglobulin therapy followed by steroid administration was initiated, after which his symptoms gradually improved. Plasma noradrenaline levels showed a stepwise elevation after each treatment, including plasma exchange. Our case adds to the evidence that combining several immunomodulatory therapies is beneficial for some intractable cases of autoimmune autonomic ganglionopathy that do not adequately respond to a single immunomodulatory therapy. Each immunomodulatory therapy should be effective even though they are not enough to show clinical improvement.

Myasthenia gravis (MG) is an autoimmune disorder characterized by skeletal muscle fatigability and muscle weakness resulting from inhibition of neuromuscular transmission by autoantibodies against synaptic apparatus in the neuromuscular junction (NMJ). MG is probably classified into three groups: anti-acetylcholine receptor (AChR) antibody-positive MG; antimuscle-specific kinase (MuSK) antibody-positive MG; and seronegative MG, which is negative for both antibodies. In patients with seronegative MG, pathogenic factors remain elusive. Recently, a new autoantibody against low-density lipoprotein receptor-related protein 4 (Lrp4), which is one of the postsynaptic apparatus and indispensable for the formation of the NMJ, has been identified and has attracted attention as a third MG-related autoantibody. In the present review, we discuss the role of Lrp4 in the formation of NMJ, and the molecular mechanism(s) of pathogenesis for anti-Lrp4 antibody-positive MG.