Patterns and severity of neuromuscular transmission failure in seronegative myasthenia gravis

Nemoto, Yasuo; Kuwabara, Satoshi; Misawa, Sonoko; Kawaguchi, Naoki; Hattori, Takamichi; Takamori, Masaharu; Vincent, Angela

doi:10.1136/jnnp.2004.043125

Cited by 60 publications

(53 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,19 Disease onset is somewhat earlier in the MuSK MG population than for other MG groups. In one study the mean age at onset of MuSK-Ab-positive MG was 36 years, whereas it was 48 years for AChR-Ab-positive MG and 38 years for double-seronegative patients.…”

Section: Discussionmentioning

confidence: 97%

Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

et al. 2009

View full text Add to dashboard Cite

We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

show abstract

Section: Discussionmentioning

confidence: 97%

Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The limb muscles are often relatively unaffected and limb muscle electrophysiology may be normal in MuSK-MG, [60] while facial muscles are abnormal; [61,62] this suggesting that the MuSK antibodies are particularly pathogenic in these muscles, as supported by magnetic resonance imaging (MRI) studies. [54] Further in vitro and animal studies are required to determine the role of MuSK in adult muscle, and to look for differences between facial and limb NMJs.…”

Section: Myasthenia Gravis With Muscle-speciþ C Kinase Antibodiesmentioning

confidence: 99%

Autoimmune disorders of the neuromuscular junction

Lang

Vincent

2009

Current Opinion in Pharmacology

View full text Add to dashboard Cite

The neuromuscular junction (NMJ) is a prototypic synapse although its structure is rather different from those of the central nervous system (CNS). The unmyelinated motor nerve terminals are separated from the postsynaptic membrane by a cleft that contains a basal lamina. This includes many proteins such as collagens, laminins, fibronectin and perlecan which help anchor some of the key elements involved in NMJ The neuromuscular junction (NMJ) is a specialized synapse with a complex structural and functional organization. It is a target for a variety of immunological disorders and these diseases usually respond well to immunotherapies. The understanding of the immunological basis of myasthenia gravis, the most common neuromuscular junction disorder, has improved in the recent years. Most patients have antibodies to the acetylcholine receptor (AChR), but around 10% have AChR antibodies that are only identified by novel methods, and up to 5% have muscle-speciÞ c kinase antibodies which deÞ ne a different subgroup of myasthenia. The spectrum of antibodies and their pathophysiological aspects are being elucidated. Even though less common, Lambert Eaton myasthenic syndrome (LEMS) is important to recognize. The abnormality in LEMS is a presynaptic failure to release enough packets of ACh, caused by antibodies to the presynaptic voltage-gated calcium channels. More than half these patients have a small cell carcinoma of lung. Acquired neuromyotonia (NMT) is a condition associated with muscle hyperactivity. Clinical features include muscle stiffness, cramps, myokymia, pseudomyotonia and weakness. The immune mechanisms of acquired NMT relate to loss of voltage-gated potassium channel function. This review will focus on the important recent developments in the immunemediated disorders of the NMJ.Key words: Gravis, Lambert Eaton myasthenic syndrome, neuromyotonia, neuromuscular junction, autoimmunity, acetylcholine receptor, voltage-gated channel development and function; for instance acetylcholine esterase (AChE) is localized via ColQ, a collagen-like molecule, to the basal lamina. Agrin and neuregulins, secreted from the nerve terminal, are bound by the basal lamina and interact with their receptors, playing an important role in the location of postsynaptic membrane proteins, voltage-gated calcium channels and the dystroglycans. The postsynaptic membrane at the NMJ forms a series of deep folds. The acetylcholine receptors (AChRs) are found at the top one-third of these folds, whereas the voltage-gated sodium channels are anchored at the bottom of the folds. The development of the NMJ is a fascinating area of research [1] and many of the proteins involved are relevant to disease ([ Figure 1] for a simple representation).The nerve action potential opens voltage-gated calcium channels (VGCCs) that are located in the motor nerve terminal [ Figure 1]. The resulting influx of calcium leads to the release of about 30 (in human muscle) individual packets of acetylcholine (ACh). Some of the ACh is hydrolysed by AChE but about 65%...

show abstract

“…9 These factors may also partly explain why MG patients with MuSK antibodies seem to have more evidence of neuromuscular transmission failure of facial muscles, but rarely of limb muscles. 1,12 Thus, there are structural, functional, and immunological differences between extraocular and limb muscles, and it is not clear whether there is a single determining factor that renders ocular muscles particularly more vulnerable to myasthenia. Although SFEMG of the ocular muscles is possible, it is much less practical than SFEMG of OO.…”

Section: Discussionmentioning

confidence: 99%

Correlating extent of neuromuscular instability with acetylcholine receptor antibodies

et al. 2009

View full text Add to dashboard Cite

In a retrospective study of 86 patients with myasthenia gravis (MG), we correlated the acetylcholine receptor (AChR) antibody titers with single-fiber EMG studies to explore whether a relationship exists between these parameters. We found that the AChR antibody titers correlated significantly with the mean of the mean consecutive difference of orbicularis oculi (OO, P<0.0001) and extensor digitorum communis (EDC, P<0.0001). The correlation was found to be stronger in OO. The antibody titers also correlated with the percentage of potential pairs with increased jitter in both muscles and, again, the correlation was more significant in OO (P<0.0001) than in EDC (P=0.001). We speculate that this relationship is stronger in OO than in the limb muscles, because the architectural and immunological differences in the motor unit render OO more vulnerable and sensitive to disturbances in neuromuscular transmission.

show abstract

Patterns and severity of neuromuscular transmission failure in seronegative myasthenia gravis

Cited by 60 publications

References 24 publications

Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

Autoimmune disorders of the neuromuscular junction

Correlating extent of neuromuscular instability with acetylcholine receptor antibodies

Contact Info

Product

Resources

About