SEARCH RESULTS FOR: 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