{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:20:20Z","timestamp":1780075220420,"version":"3.54.0"},"reference-count":30,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Neurol. Sci."],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic><jats:bold>Background:<\/jats:bold><\/jats:italic> Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which a clinical diagnosis may be confirmed with serological testing. The most common autoantibodies used to support a diagnosis of MG are anti-acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase antibodies. In cases in which both of these autoantibodies are negative (termed double-seronegative [dSNMG]), other autoantibodies such as low-density lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis. <jats:italic><jats:bold>Methods:<\/jats:bold><\/jats:italic> We have undertaken a systematic literature review to identify studies that have assessed the frequency of anti-LRP4 antibodies in dSNMG patients and the characteristics of anti-LRP4+ dSNMG patients (epidemiology, clinical features, electromyographic findings, or management). PubMed, EMBASE, Medline, and Scopus were searched on January 14, 2017, using the medical subject headings \u201cmyasthenia gravis\u201d and \u201clow-density lipoprotein receptor-related protein 4\u201d or \u201cLRP4.\u201d <jats:italic><jats:bold>Results:<\/jats:bold><\/jats:italic> The initial search identified 367 articles. Fourteen publications met the inclusion criteria. There were ten cross-sectional research studies, three were case series, and one was a case report. The majority of studies were limited by small sample sizes of LRP4+ dSNMG. There has been a wide range of frequencies of anti-LRP4 antibodies detected in different MG patient populations, some involving different laboratory techniques. <jats:italic><jats:bold>Conclusions:<\/jats:bold><\/jats:italic> LRP4+ dSNMG is more likely than LRP4\u2013 dSNMG to have a younger onset of disease and occur in females. LRP4+ dSNMG most often is mild in severity and often involves isolated ocular weakness. 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