AssessmentsLambert-Eaton myasthenic syndrome
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 60-year-old man presents to the office because of complaints of a persistent cough, shortness of breath, and weakness. These symptoms have been ongoing for the past six months, and he says that his muscle weakness now seems to be worsening. He reports that the weakness seems to be at its worst when he is sitting down and resting, and improves when he gets up and moves around for awhile. He has a 50-pack-year history of cigarette smoking and currently smokes two packs per day. He has a medical history of hypertension and chronic obstructive pulmonary disease (COPD), and is irregularly-compliant with follow-up office visits. A chest radiograph shows flattening of the diaphragm and elongation of the mediastinum, and there is an irregularly shaped 2 cm nodule near the hilum on the right. Which of the following is the most likely diagnosis?
Lambert-Eaton myasthenic syndrome is a rare autoimmune disease that attacks the peripheral nervous system, causing muscle weakness, and actually improves temporarily after repeated use of the muscle.
The nervous system is divided into the central nervous system, which is the brain and spinal cord, and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs.
The peripheral nervous system can then further be divided into the somatic nervous system, which controls voluntary movement of our skeletal muscles, and the autonomic nervous system, which is even further divided into the sympathetic and the parasympathetic, and controls the involuntary movement of the smooth muscles and glands of our organs.
Now, to better understand Lambert-Eaton myasthenic syndrome, let’s review normal skeletal muscle contraction at the cellular level.
First you’ve got your motor neurons, which have voltage-gated calcium channels in their membranes.
Whenever a motor neuron receives an electrical impulse from the brain, these channels open up and let calcium inside.
The increased intracellular calcium concentration triggers the release of small vesicles that contain the neurotransmitter acetylcholine into the neuromuscular junction.
Acetylcholine goes from the neuron over to the nicotinic receptors on muscle cell membranes.
When acetylcholine binds the nicotinic receptors it leads to muscle contraction.
The parasympathetic division of the autonomic nervous system also has motor neurons that work in the same way; the main difference from the somatic nervous system is that they work on smooth muscle, so the muscle cell membranes have muscarinic receptors for acetylcholine, and they’re not called neuromuscular junctions.
In Lambert-Eaton myasthenic syndrome there’s an autoimmune response against the voltage-gated calcium channels on the motor neurons, mostly affecting the somatic nervous system, but also the parasympathetic part of the autonomic nervous system.
More specifically, it’s a type II hypersensitivity reaction, meaning that the body produces antibodies against its own proteins. In this case, B cells inappropriately make antibodies that recognize, bind to and block voltage-gated calcium channels on the motor neurons, which leaves only a few unbound channels that are available to open and allow calcium in.
Unfortunately, when only a few of the channels are working, they can only generate a low level of calcium within the neuron, and it’s insufficient to trigger the release of acetylcholine into the neuromuscular junction.
When there’s no release of acetylcholine, there’s no contraction of the attached muscle fiber. However, with repeated stimulation by electrical impulses from the brain, enough calcium might get through the few free calcium channels, resulting in acetylcholine release and muscle contraction.
The majority of Lambert-Eaton cases are associated with small cell lung cancer, because the small cell lung cancer cells express the same calcium channels that are found on motor neurons.