Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis

Amelia Evoli, Pietro A. Tonali, Luca Padua, Mauro Lo Monaco, Flavia Scuderi, Anna P. Batocchi, Mariapaola Marino, Emanuela Bartoccioni

Research output: Contribution to journalArticle

Abstract

The term seronegative myasthenia gravis (SNMG) refers to the generalized disease without detectable antiacetylcholine receptor (anti-AChR) antibodies. In these patients, IgG antibodies against the muscle-specific kinase (MuSK) have been described, which reduced agrin-induced AChR clustering in vitro. We have assayed anti-MuSK antibodies in 78 patients with SNMG, who have been followed for many years in our Institution. Here we describe the clinical phenotype of the 37 patients whose results were positive on this assay. MG with anti-MuSK antibodies was characterized by a striking prevalence of female patients (eight men and 29 women). Age of onset ranged from 6 to 68 years, with 56.8% of patients presenting under 40 years of age. All these patients shared a similar pattern of muscle weakness, with prevalent involvement of cranial and bulbar muscles and a high frequency of respiratory crises; the involvement of limb muscles was comparatively less severe and inconsistent. Single-fibre-EMG confirmed the most sensitive examination in the EMG diagnosis of MuSK-positive disease, while, owing to weakness topography, repetitive nerve stimulation in limb muscles was diagnostic in 56.8% of cases. The effect of edrophonium (or neostigmine) injection was equivocal or negative in 11 of 37 patients (29.7%), and the response to oral pyridostigmine was even more unsatisfactory, ranging from mild benefit to overt intolerance. In thymectomized patients, thymus was normal for age or atrophied, and no benefit from surgery was noticed. Thirty-five of 37 patients were given immunosuppressive therapy and 22 received plasmaexchange. The course of the disease was often characterized by periodic exacerbation phases requiring hospitalization and even assisted ventilation; plasmaexchange produced marked improvement in these cases. At the end of the observation period, most patients, although improved, were still symptomatic, having developed permanent facial and pharyngeal weakness together with some atrophy of facial muscles. MuSK-negative disease was comparatively more heterogeneous. Most patients were affected with mild to moderate symptoms and responded well to pharmacological treatment; however, a few subjects in this group had severe refractory disease, poorly responsive to both acetylcholinesterase inhibitors and immunosuppressants.

Original languageEnglish
Pages (from-to)2304-2311
Number of pages8
JournalBrain
Volume126
Issue number10
DOIs
Publication statusPublished - Oct 2003

Keywords

  • MuSK
  • Myasthenia gravis
  • Plasma exchange
  • Seronegative myasthenia gravis
  • SF-EMG

ASJC Scopus subject areas

  • Neuroscience(all)

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    Evoli, A., Tonali, P. A., Padua, L., Lo Monaco, M., Scuderi, F., Batocchi, A. P., Marino, M., & Bartoccioni, E. (2003). Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain, 126(10), 2304-2311. https://doi.org/10.1093/brain/awg223