Juvenile myasthenia gravis associated with autoimmune channelopathy and mixed connective tissue disease

Abstract

Background/Aims: Ion channels are crucial elements in neuronal signaling and synaptic transmission. Autoantibodies against voltage-gated ion channels cause disorders in neuromuscular transmission. Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia and related disorders such as Morvan's syndrome and limbic encephalitis. The symptoms of myasthenia gravis reflect dysfunction of neuromuscular transmission. Methods and results: We present a 15-year-old girl with ptosis, proximal muscle weakness, neuromyotonia, hyperhidrosis, short memory loss and confusion. AntinAChR antibodies were positive. Electromyography showed neuromyotonic discharges. Cerebrospinal fluid analysis revealed oligoclonal bands. The plasma VGKC-antibody titer was elevated (176 pM, controls 100 pM), along with positive antiganglioside antibodies (GM1, asialo GM1, GM2, GD1a,b) and SS-A 211 U/mL, SS-B 157 U/mL, U1-RNP 188 U/mL, DNA-topo 128 U/mL (control <100). Brain magnetic resonance imaging was normal. The girl was treated with pyridostigmine, steroids, intravenous immunoglobulins and azathioprine, and repetitive plasma exchanges. Neurological impairments and myasthenic crisis occurred in periods of 5-21 days. Conclusion: The neuromyotonia and some of the dysautonomic features are likely to be directly related to the VGKC antibodies in the peripheral nervous system. The central nervous system symptoms are very likely to be due to the direct effects of VGKC antibodies, although there can be some other autoantibodies. A severe clinical course might be related to myasthenia gravis associated with autoimmune disease of the central and peripheral nervous system overlapping probably with mixed connective tissue disease