Lambert-Eaton-Myasthenic-Syndrome-Pathogenesis-and-Clinical-Findings

Lambert-Eaton-Myasthenic-Syndrome-Pathogenesis-and-Clinical-Findings

Lambert-Eaton Myasthenic Syndrome: Pathogenesis and Clinical Findings
Authors: Alexandros Mouratidis Dmitriy Matveychuk Ario Mirian Reviewers: Austin Laing Davis Maclean Michal Krawcyzk Harjot Atwal Chris White* Yan Yu* * MD at time of publication
Acquired autoimmunity:
mechanism unknown, possibly associated with other autoimmune diseases
A paraneoplastic syndrome of small cell lung cancer (SCLC) in >50% of patients
Tumour membrane expresses voltage-gated calcium channels (VGCCs), which normally exist on neurons and function in neurotransmission
Note:
A paraneoplastic syndrome is a condition that arises due to cancer elsewhere in the body; possibly an immune response against tumour cells
Positive anti-VGCC IgG on serology
↓ Stimulation of salivary glands à↓ production of saliva
↓ Nitric oxide & prostaglandin production by cavernosal endothelial cellsàImpaired vasodilation of penile arteries
↓ Acetylcholine-induced gastric motility
↓ Acetylcholine available to mediate muscle reflexes
↑ Variability in action potential initiation along muscle fibers
Immune response to foreign cancer cells triggers production of antibodies against VGCCs on the cell surfaces of presynaptic neurons
Antibodies bind VGCCs, blocking Ca2+ Antibodies bind, cross-link, and
from entering presynaptic neurons
↓ Ca2+ influx into the presynaptic neuron during its depolarization
internalize VGCCsà↓ VGCC on neuron surface
Xerostomia (dry mouth)
Erectile dysfunction
Constipation
↓ Deep tendon reflexes
Unstable motor unit action potentials on electromyography
↓ Baseline compound muscle action potentials (CMAPs:
summated action potentials of all motor endplates in one muscle) on nerve conduction studies
Since intracellular Ca2+ mediates neurotransmitter vesicle fusion with the presynaptic membrane, ↓ Ca2+ influx ↓release of neurotransmitters like acetylcholine into the synaptic cleft
However, with repeated stimulation of the presynaptic neuron (e.g. exercise), there is ↑ Ca2+ accumulation within the axon terminal, allowing for more neurotransmitter vesicle fusion with the presynaptic membrane
↑ Acetylcholine available to mediate muscle reflexes
With high frequency repetitive nerve stimulation, ↑ number of compound CMAPS can be generated
↓ Acetylcholine release into synapses leading to autonomic nerves
↓ Acetylcholine release into neuromuscular junction
Autonomic dysfunction
↑ Deep tendon reflex amplitude
Temporary improvement in muscle strength
↓ Number of
muscle fibers activated by each action potential
Post-activation facilitation: Repeated stimulation improves symptoms
Larger proximal muscles involved in movement (i.e. walking) do not recruit sufficient number of muscle fibers for proper function
Can affect any muscle group, but muscles involved in speech, swallowing, and periocular muscles are often afflicted
Gait disturbance
Symmetric skeletal muscle weakness
Dysarthria (difficulty speaking)
Dysphagia (difficulty swallowing)
Ptosis (drooping of upper eyelid)
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Re-Published July 18, 2021 on www.thecalgaryguide.com