Editors' note: Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis

Abstract

In the article “Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis,” Algaeed et al. presented a 73-year-old man who was diagnosed with myasthenia gravis (MG) after receiving pembrolizumab for recurrent melanoma and had positive anti–acetylcholine receptor antibodies (AChRAbs). In response, Robbins et al. note that antibodies like AChRAbs may be less specific for MG after immune checkpoint inhibitor (ICI) therapy and may be a marker for general autoimmunity. They note that AChRAb-positive patients receiving ICI therapy are more likely to develop myositis and that this can clinically resemble MG. In this regard, they note that some reports of ICI-associated MG had normal repetitive nerve stimulation and single-fiber EMG despite severe weakness. Using an illustrative case, they note that the distinction between myositis and MG has important implications for clinical management. In response, Algaeed et al. acknowledge these observations, but note that their patient had unequivocal fatigable ptosis strongly supporting (not pathognomonic in the editor's opinion) the diagnosis of MG. The authors also argue that further understanding of ICI-related autoimmune pathogenesis is needed before concluding that AChRAbs can just be a marker of general autoimmunity. In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.