The Myasthenic Syndromes

Kaminski, Henry J.; Ruff, Robert L.

doi:10.1007/978-1-4613-1143-0_28

Cited by 13 publications

(13 citation statements)

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The secondary synaptic folds, which mostly house the NaChs, are also simplified due to loss of endplate membrane 10,14,16–18 . MG is inducible in rats by immunization with foreign or self AChRs (EAMG) or by passive transfer of myasthenogenic AChR‐binding IgG (PTMG) 8,14,19–22 . In both models of EAMG, complement is paramount in driving disease pathology.…”

Section: Introductionmentioning

confidence: 99%

Factors contributing to failure of neuromuscular transmission in myasthenia gravis and the special case of the extraocular muscles

Serra

Ruff

Kaminski

et al. 2011

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Acetylcholine receptors (AchRs) and Na(+) channels (NaChs) are concentrated on neuromuscular junction (NMJ) postsynaptic folds; both are depleted in myasthenia gravis (MG), reducing the safety factor (SF) for neuromuscular transmission, especially in extraocular muscles (EOM). Studies of human myasthenic nerve-muscle preparations indicate that loss of endplate AChRs accounts for 59%, and NaChs for 40%, of SF reduction. Rodent models of MG indicate that NaChs and AChRs losses are due to complement-mediated destruction of postsynaptic folding. Saccades in MG show stereotyped, conjugate initial components, similar to normal but different from early disconjugacy with ocular nerve palsies. Loss of AChRs, NaChs, and postsynaptic folding all contribute to SF reduction in MG. EOM seem more susceptible to MG because of poor postsynaptic folding, lower baseline SF, and lower levels of intrinsic complement inhibitors. Initial conjugacy of saccades in MG reflects selective sparing of neuromuscular transmission of fast, pale global fibers, which have better developed postsynaptic folding.

show abstract

Section: Introductionmentioning

confidence: 99%

Factors contributing to failure of neuromuscular transmission in myasthenia gravis and the special case of the extraocular muscles

Serra

Ruff

Kaminski

et al. 2011

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…The secondary synaptic folds are simplified due to loss of endplate membrane (Engel, 1994; Engel et al, 1977; Engel and Santa, 1971; Maselli et al, 1991; Santa et al, 1972). The serum level of AChR binding antibodies does not predict the severity of weakness (Drachman, 1994; Engel, 1994; Kaminski and Ruff, 1996), but the postsynaptic membrane area correlates with the size of the endplate potentials (EPP) miniature endplate potentials (MEPP) and with the patient’s clinical signs of weakness (Engel et al, 1977). …”

Section: Introductionmentioning

confidence: 99%

“…MG is inducible in rats by immunization with foreign or self AChR (EAMG) or by passive transfer of myasthenogenic AChR-binding IgG (PTMG) (Drachman, 1994; Engel, 1994; Kaminski and Ruff, 1996; Lennon and Lambert, 1980; Lindstrom et al, 1976a; Lindstrom et al, 1976b). Weakness in PTMG begins about 12 hours after antibody injection and peaks at 48 hours (Lennon and Lambert, 1980; Lindstrom et al, 1976b).…”

Section: Introductionmentioning

confidence: 99%

How myasthenia gravis alters the safety factor for neuromuscular transmission

Ruff¹,

Lennon

2008

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

Myasthenia gravis (MG), the most common of autoimmune myasthenic syndromes, is characterized by antibodies directed against the skeletal muscle acetylcholine receptors (AChRs). Endplate Na+ channels ensure the efficiency of neuromuscular transmission by reducing the threshold depolarization needed to trigger an action potential. Postsynaptic AChRs and voltage-gated Na+ channels are both lost from the neuromuscular junction in MG. This study examined the impact of postsynaptic voltage-gated Na+ channel loss on the safety factor for neuromuscular transmission. In intercostal nerve-muscle preparations from MG patients, we found that endplate AChR loss decreases the size of the endplate potential, and endplate Na+ channel loss increases the threshold depolarization needed to produce a muscle action potential. To evaluate whether AChR-specific antibody impairs the function of Na + channels, we tested omohyoid nerve-muscle preparations from rats injected with monoclonal myasthenogenic IgG (passive transfer model of MG [PTMG]). The AChR antibody that produces PTMG did not alter the function of Na + channels. We conclude that loss of endplate Na + channels in MG is due to complement-mediated loss of endplate membrane rather than a direct effect of myasthenogenic antibodies on endplate Na + channels.

show abstract

“…rected toward the skeletal muscle acetylcholine receptor (AChR), 3,7 and in 10-15% of patients development of MG is related to an underlying thymoma. Thymoma-associated MG has a more severe clinical course, and patients often have antibodies directed against skeletal muscle proteins other than the AChR.…”

mentioning

confidence: 99%