BACKGROUND: Myasthenia gravis is a rare chronic autoimmune neuromuscular disorder mainly caused by autoantibodies to the nicotinic acetylcholine receptor. Cholesterol is an essential molecule that affects the distribution and proper functioning of this receptor. Several reports have described the potential worsening of myasthenia gravis in patients treated with statins. CASE PRESENTATION: The patient was an obese 72 years old man, past smoker, diagnosed with ischaemic heart disease, type 2 diabetes mellitus and lipid metabolism disorder. Statin treatment was not implemented because of chronic myasthenia gravis and PCSK9i monotherapy [Repatha (evolucamab), 140 mg] was implemented to treat dyslipidaemia. Within 24 h after the first dose of PCSK9i the patient developed severe muscle weakness, joint pain, fever, and general discomfort, lasting for several days. Despite strong advice against the second dose administration, this was self-administered approximately 2 weeks later, leading to report significant worsening of the muscle problems, leading to the patient admittion to the neurology department where he was being treated for myasthenia gravis attack. CONCLUSION: Based on the neurologist's conclusion, it can be assumed that in this case, treatment with PCSK9i resulted in significant worsening of the patient's chronic disease.

3rd Department of Internal Medicine 1st Faculty of Medicine Charles University Prague Czechia

Department of Nephrology 1st Faculty of Medicine Charles University Prague Czechia

Department of Preventive Cardiology Institute for Clinical and Experimental Medicine Prague Czechia

Experimental Medicine Centre Institute for Clinical and Experimental Medicine Prague Czechia

Faculty of Biomedical Engineering Czech Technical University Prague Czechia

Zobrazit více v PubMed

Sinning D, Leistner DM, Landmesser U. Einfluss der lipidstoffwechselparameter auf die entstehung und progression der koronaren herzerkrankung: ein update [impact of lipid metabolism parameters on the development and progression of coronary artery disease: an update]. Herz. (2016) 41:273–80. 10.1007/s00059-016-4430-8 Article in German. PubMed DOI

Ali AH, Younis N, Abdallah R, Shaer F, Dakroub A, Ayoub MA, et al. Lipid-lowering therapies for atherosclerosis: statins, fibrates, ezetimibe and PCSK9 monoclonal antibodies. Curr Med Chem. (2021) 28:7427–45. 10.2174/0929867328666210222092628 PubMed DOI

Seidah NG, Garçon D. Expanding biology of PCSK9: roles in atherosclerosis and beyond. Curr Atheroscler Rep. (2022) 24:821–30. 10.1007/s11883-022-01057-z PubMed DOI PMC

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. (2020) 41:111–88. 10.1093/eurheartj/ehz455 Erratum in: Eur Heart J. 2020;41:4255. PubMed DOI

Roth EM, Davidson MH. PCSK9 Inhibitors: mechanism of action, efficacy, and safety. Rev Cardiovasc Med. (2018) 19:S31–46. 10.3909/ricm19S1S0002 PubMed DOI

Attardo S, Musumeci O, Velardo D, Toscano A. Statins neuromuscular adverse effects. Int J Mol Sci. (2022) 23:8364. 10.3390/ijms23158364 PubMed DOI PMC

Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. (2006) 114:2788–97. 10.1161/CIRCULATIONAHA.106.624890 PubMed DOI

Vrablik M, Zlatohlavek L, Stulc T, Adamkova V, Prusikova M, Schwarzova L, et al. Statin-associated myopathy: from genetic predisposition to clinical management. Physiol Res. (2014) 63(Suppl 3):S327–34. 10.33549/physiolres.932865 PubMed DOI

Geng Q, Li X, Sun Q, Wang Z. Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials. Cardiol J. (2022) 29:574–81. 10.5603/CJ.a2021.0110 PubMed DOI PMC

Gürgöze MT, Muller-Hansma AHG, Schreuder MM, Galema-Boers AMH, Boersma E, Roeters van Lennep JE. Adverse events associated with PCSK9 inhibitors: a real-world experience. Clin Pharmacol Ther. (2019) 105:496–504. 10.1002/cpt.1193 PubMed DOI PMC

Gilhus NE. Myasthenia gravis. N Engl J Med. (2016) 375:2570–81. 10.1056/NEJMra1602678 PubMed DOI

Chia R, Saez-Atienzar S, Murphy N, Chiò A. Blauwendraat C, International Myasthenia Gravis Genomics Consortium, et al. Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study. Proc Natl Acad Sci U S A. (2022) 119:e2108672119. 10.1073/pnas.2108672119. Erratum in: Proc Natl Acad Sci U S A. 2022;119(23):e2206754119. PubMed DOI PMC

Paz ML, Barrantes FJ. Cholesterol in myasthenia gravis. Arch Biochem Biophys. (2021) 701:108788. 10.1016/j.abb.2021.108788 PubMed DOI

Pediconi MF, Gallegos CE, De Los Santos EB, Barrantes FJ. Metabolic cholesterol depletion hinders cell-surface trafficking of the nicotinic acetylcholine receptor. Neuroscience. (2004) 128(2):239–49. 10.1016/j.neuroscience.2004.06.007 PubMed DOI

Gale J, Danesh-Meyer HV. Statins can induce myasthenia gravis. J Clin Neurosci. (2014) 21:195–7. 10.1016/j.jocn.2013.11.009 PubMed DOI

Oh SJ, Dhall R, Young A, Morgan MB, Lu L, Claussen GC. Statins may aggravate myasthenia gravis. Muscle Nerve. (2008) 38:1101–7. 10.1002/mus.21074 PubMed DOI PMC

Tsivgoulis G, Spengos K, Karandreas N, Panas M, Kladi A, Manta P. Presymptomatic neuromuscular disorders disclosed following statin treatment. Arch Intern Med. (2006) 166:1519–24. 10.1001/archinte.166.14.1519 PubMed DOI

Xie W, Li J, Du H, Xia J. Causal relationship between PCSK9 inhibitor and autoimmune diseases: a drug target Mendelian randomization study. Arthritis Res Ther. (2023) 25:148. 10.1186/s13075-023-03122-7 PubMed DOI PMC

Li J, Wang F, Zhang C, Li Z, Gao J, Liu H. Genetically predicted effects of physical activity and sedentary behavior on myasthenia gravis: evidence from Mendelian randomization study. BMC Neurol. (2023) 23:299. 10.1186/s12883-023-03343-y PubMed DOI PMC

Nelke C, Stascheit F, Eckert C, Pawlitzki M, Schroeter CB, Huntemann N, et al. Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients. J Neuroinflammation. (2022) 19:89. 10.1186/s12974-022-02448-4 PubMed DOI PMC

Franco DC, Neupane N, Riaz M, Mohammadzadeh S, Sachmechi I. Chronic inflammatory demyelinating polyradiculoneuropathy association with low cholesterol levels: a case report in a patient taking PCSK9 inhibitor. J Neurol Res. (2019) 9:72–4. 10.14740/jnr552 DOI

Jaafar AK, Techer R, Chemello K, Lambert G, Bourane S. PCSK9 And the nervous system: a no-brainer? J Lipid Res. (2023) 64:100426. 10.1016/j.jlr.2023.100426 PubMed DOI PMC

Poirier S, Prat A, Marcinkiewicz E, Paquin J, Chitramuthu BP, Baranowski D, et al. Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system. J Neurochem. (2006) 98:838–50. 10.1111/j.1471-4159.2006.03928.x PubMed DOI

Wang L, Wang Z, Shi J, Jiang Q, Wang H, Li X, et al. Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates neuronal apoptosis following focal cerebral ischemia via apolipoprotein E receptor 2 downregulation in hyperlipidemic mice. Int J Mol Med. (2018) 42:2098–106. 10.3892/ijmm.2018.3797 PubMed DOI PMC

Malong L, Napoli I, Casal G, White IJ, Stierli S, Vaughan A, et al. Characterization of the structure and control of the blood-nerve barrier identifies avenues for therapeutic delivery. Dev Cell. (2023) 58:174–91.e8. 10.1016/j.devcel.2023.01.002 PubMed DOI

Morelli F, Carlier P, Giannini G, De Luigi MC, Dejana AM, Ruzzenenti MR. Hypercholesterolemia and LDL apheresis. Int J Artif Organs. (2005) 28:1025–31. 10.1177/039139880502801010 PubMed DOI