Myasthenia gravis is an autoimmune disorder mainly caused by
antibodies to the muscle acetylcholine receptors (AChRs) at the
neuromuscular Junction. Loss of these receptors leads to a defect in
neuromuscular transmission with muscle weakness and fatigue. AChR
antibody tests are widely available and overall incidence and
prevalence of the disorder seem to be rising, especially in elderly
people. The disease is heterogeneous with respect to age at onset,
thymic changes and distribution of muscle weakness, but the roles
of immunogenetic factors and thymic abnormalities in the causes of
the different forms are unclear. Most patients are now effectively
treated with cholinesterase inhibitors and immunosuppressive druge,
and in younger patients by thymectomy. In about 15% of patients with
myasthenia gravis, AChR antibodies are absent, and many of these
patients have antibodies to another neuromuscular junction protein,
muscle specific kinase (MuSK). Myasthenia needs to be distinguished
from other rarer but rqually well characterised autoimmune, genetic,
and toxic disorders of neuromuscular transmission by clinical and
laboratory tests.
Myasthenia gravis (my: muscle,
asthenia: weakness, gravis: severe) has been recognised as a disease
since the Oxford physician Thomas Willis described a woman with
dysarthria in 1672, and is a prototype for borth synaptic and
sutoimmune disorders. In most patients, it is caused by
autoantibodies specific for the human nicotinic acetylcholine
receptor (AChR), which is concentrated at the post-synaptic region
of the neuromuscular junction. These antibodies reduce the number of
AChRs, causing impaired neuromuscular transmission and muscle
weakness. Clinical and experimental findings from the 1970s showing
that myasthenia gravis was an autoimmune disease, established the
ideas that have been applied to other autoimmune disorders of the
neuromuscular junction.
Additionally, the subsequent
identification of AChR mutations in a large proportion of patients
presenting myasthenic signs at birth or neonatally has led to the
definition of inherited or congenital myasthenic syndromes. Thus
several myasthenic disorders are now recognised (figure 1 ). Here,
we will focus mainly on myasthenia gravis, the most common disorder
of neuromuscular transmission.
THE
LANCENT . VOL 357. June 30,2001 |
