Continuum, Myasthenic Disorders and ALS, February 2009, Volume 15, Issue 1

Acquired myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission that presents clinically as fluctuating skeletal muscle weakness often affecting particular muscle groups preferentially. The target of the autoimmune attack in most cases is the skeletal muscle acetylcholine receptor (AChR), but in others it may be non-AChR components of the neuromuscular junction, such as the muscle-specific receptor tyrosine kinase. The final result remains muscle endplate dysfunction and muscle weakness. The clinical presentation may vary considerably in MG, both for anti-AChR-positive and anti-AChR-negative disease, and accurate diagnosis is dependent on clinical recognition of variant as well as classic disease phenotypes. The primary aim of treatment of MG is induction and maintenance of clinical or pharmacologic remission while minimizing adverse effects of therapy. Treatment decisions must be individualized based on MG severity and coexisting disease, and patient participation in these decisions is essential to successful management.(C) 2009 American Academy of Neurology

Amyotrophic lateral sclerosis (ALS) was first described 134 years ago. While still incurable, significant progress has been made in understanding the pathophysiology of the disease and its management. For example, it is now clear that ALS is not a single disease; there are familial and sporadic subtypes. ALS is not specific for motor neurons; other cell types are involved and in fact may be critical in determining disease progression. A number of options now exist for managing the troublesome symptoms of ALS, and we have a pipeline of potential ALS therapeutics, which is larger and more varied than ever before. Finally, we are on the cusp of a diagnostic test for ALS that will allow us to get these therapies to patients more quickly.(C) 2009 American Academy of Neurology

Paraneoplastic neurologic disorders can affect any part of the nervous system. Rarely, the motor neuron or motor axons may be affected in patients with cancer, leading to clinical signs and symptoms that resemble ALS. Myasthenia gravis (MG) is the prototypic autoimmune disorder of the nervous system. In most cases, MG is an idiopathic disorder, and the events leading to the production of acetylcholine receptor autoantibodies are not known. About 15% of patients have a paraneoplastic form of MG associated with a thymic neoplasm (thymoma). Patients with paraneoplastic MG typically have late-onset generalized MG and require long-term immunosuppression. Another form of neuromuscular junction disorder, the Lambert-Eaton myasthenic syndrome, often occurs as a paraneoplastic manifestation of small cell lung cancer. Together, MG and Lambert-Eaton syndrome are the most common paraneoplastic neurologic disorders.(C) 2009 American Academy of Neurology