Myasthenic Synd vs Myas Gravis: Sx

Advanced, Clinical - Neuromuscular Diseases and Disorders, Organ-Based and Clinical Sciences

Myasthenic syndrome and myasthenia gravis are two disorders of neuromuscular transmission that result in muscle weakness and fatigue. They differ in pathophysiology and their symptoms. Myasthenia gravis (MG) is an autoimmune disorder caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction (NMJ).  MG has early signs of ocular and bulbar nerve involvement followed by extremity weakness. This results in a rapid decline in the number of action potentials and overall contractile strength with repeat use of said muscle. Medication that improves strength in myasthenia gravis includes anticholinesterases inhibitors such as neostigmine and pyridostigmine. These patients are very sensitive to NMBAs.

Myasthenic syndrome (sometimes referred to as Lambert-Eaton syndrome) is an autoimmune disorder where there are antibodies formed against the voltage-gated calcium channels in the NMJ.  Roughly 60% of patients with LEMS have an underlying malignancy, most commonly SCLC making this a “paraneoplastic syndrome.” Symptoms of LEMS improve with successful treatment of the underlying malignancy. Weakness in LEMS involves the arms and legs; with leg involvement more pronounced than in MG. Proximal musculature (hip and shoulder girdle) is predominately affected making climbing stairs difficult. Unlike MG eye muscle weakness is uncommon. 75% of LEMS patients have involvement of the autonomic nervous system resulting in ataxia, impaired sweating, orthostatic hypotension, and metallic taste in the mouth. A key difference between LEMS and MG is that the weakness and reflexes on neurologic examination improves with repeated testing.

Updated definition 2020:

Myasthenia gravis (MG) and myasthenic syndrome, also known as Lambert-Eaton Myasthenic Syndrome (LEMS) are two different autoimmune conditions that result in weakness and muscle fatigue.

Myasthenia gravis is an autoimmune disorder characterized by easy fatiguability of the skeletal muscle and weakness. The weakness seen in patients with MG is related to the autoimmune destruction or inactivation of the postsynaptic acetylcholine receptors at the neuromuscular junction (NMJ), which then leads to reduced numbers of receptors, and eventually complement system mediated destruction of the postsynaptic endplate. The course of MG is marked by a series of exacerbations and remissions. The patient’s ocular muscles are most commonly affected; patients often report diplopia and ptosis. Patients with bulbar involvement may report dysarthria, difficulty with chewing and/or swallowing, problems with managing secretions, and/or frank pulmonary aspiration. Those with severe disease demonstrate proximal muscle weakness and involvement of respiratory muscles. Generally, MG patients experience improvement in muscle strength following a period of rest. Exacerbations may follow infection, stress, surgery, pregnancy and can have variable effects. There is a lengthy list of medications which may potentiate MG weakness (see below). MG is primarily treated using anticholinesterase drugs (most commonly pyridostigmine), which function by increasing the amount of acetylcholine in the NMJ. Excessive administration can precipitate cholinergic crisis.

Lambert-Eaton Myasthenic Syndrome is a paraneoplastic syndrome that is characterized primarily by proximal muscle weakness that generally begins in the lower extremities but may spread to include the upper limbs, bulbar, and respiratory muscles. Autonomic dysfunction including male impotence and dry mouth are common. LEMS is typically associated with small cell carcinoma of the lung but can be seen with other malignancy variants or as an idiopathic autoimmune disease. LEMS results from a presynaptic defect in neuromuscular transmission in which antibodies to the voltage-gated calcium channels result in a reduced release of acetylcholine at the motor end plate. Unlike MG, muscle weakness with LEMS improves with repeated efforts and demonstrates less marked improvement with the administration of anticholinergic medications. LEMS may demonstrate significant improvement with guanidine hydrochloride or 3,4-dyaminopyridine (DAP), which increase presynaptic acetylcholine release. Patients may derive benefit from corticosteroids, immunosuppression, or plasmapheresis.

74%

Answered correctly

2020

Year asked

72%

Answered correctly

2014

Year asked

64%

Answered correctly

2011

Year asked

Author
Cait Tourje, MD