Objective: To present a case of comorbid Parkinson’s disease(PD) and Myasthenia Gravis(MG) and review the literature about the underlying pathogenesis mechanisms and potential treatments.

Background: Coexistence of PD and MG is rare, and the subjacent mechanism is unknown. Some symptoms may overlap and the treatment adjustment can be challenging.

Method: We conducted a systematic on PubMed with “Parkinson’s disease” and “Myasthenia Gravis” along with a new case report from our center.

Results: A 76-year-old woman developed tremoric akinetic rigid syndrome at 66, consistent with idiopathic PD. Treatment included trihexyphenidyl(THP), pramipexole, rasagiline and levodopa. MG was diagnosed after 9 years, leading to THP withdrawal and pyridostigmine initiation, with tremor worsening. Despite adjusting levodopa dose, adding pregabalin and zonisamide, tremor persisted.

Conclusion: PD affects 6.1 million globally, and MG 2.4 per 100,000(1,2). Co-occurrence is rare, with limited cases reported since 1987(3). Most cases involve males aged 55-95, with PD preceding MG by 8 months to 20 years. Most MG cases start with ocular symptoms, and comorbid cases exhibit higher head drop incidence than each condition alone(4-10). Dysphagia, dysarthria and fatigue, common symptoms in PD and MG, are reported in comorbid cases(11-13).

The underlying mechanism is unknown(14), with uncertain overlap or age-related MG incidence increase in older PD patients(13). Initial hypotheses involve anticholinergic PD treatments like THP(15). Pyridostigmine may disturb the dopamine-acetylcholine balance, potentially causing parkinsonism. Unable to penetrate the blood-brain barrier, an altered barrier is hypothesized(16-18).

The hypothesis of immune pathogenesis arises from the documented associations of MG and PD with other autoimmune diseases(19-22). It is suggested that immune dysregulation triggers PD neurodegeneration, T cell dysregulation, and neuroinflammation induced by misfolded α -synuclein. LRRK2 mutations in PD might also imply immune regulation alteration(23-36).

Treatment evidence for comorbid MG and PD is scarce. Corticosteroids and pyridostigmine may worsen tremor, and antitremor medications may exacerbate MG symptoms.

Our case reflects the challenges of managing comorbid MG and PD, exploring shared symptoms, potential etiology and treatment difficulties.

References: 1. Dorsey, E. Ray, Alexis Elbaz, Emma Nichols, Nooshin Abbasi, Foad Abd-Allah, Ahmed Abdelalim, Jose C. Adsuar, et al. ‘Global, Regional, and National Burden of Parkinson’s Disease, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016’. The Lancet Neurology 17, no. 11 (November 2018): 939–53. https://doi.org/10.1016/S1474-4422(18)30295-3.
2. Salari, Nader, Behnaz Fatahi, Yalda Bartina, Mohsen Kazeminia, Reza Fatahian, Payam Mohammadi, Shamarina Shohaimi, and Masoud Mohammadi. ‘Global Prevalence of Myasthenia Gravis and the Effectiveness of Common Drugs in Its Treatment: A Systematic Review and Meta-Analysis’. Journal of Translational Medicine 19, no. 1 (20 December 2021): 516. https://doi.org/10.1186/s12967-021-03185-7.
3. Ueno, S.; Takahashi, M.; Kajiyama, K.; Okahisa, N.; Hazama, T.; Yorifuji, S.; Tarui, S. Parkinson’s disease and myasthenia gravis: Adverse effect of trihexyphenidyl on neuromuscular transmission. Neurology 1987, 37, 832–833.
4. Alshaikh, Jumana T., and Kelly Mills. ‘Coincident Parkinsonism and Myasthenia Gravis: A Case Series’. Parkinsonism & Related Disorders 89 (August 2021): 4–5. https://doi.org/10.1016/j.parkreldis.2021.06.016.
5. Neuman, Leslie A., and Farooq Z. Cheema. ‘Two Cases of Parkinson Disease and Concurrent Myasthenia Gravis, Generalized and Ocular’. The Neurohospitalist 4, no. 3 (July 2014): 117–18. https://doi.org/10.1177/1941874414522498.
6. Fujimoto, Ken-ichi. ‘Dropped Head in Parkinson’s Disease’. Journal of Neurology 253, no. 7 (1 December 2006): vii21–26. https://doi.org/10.1007/s00415-006-7006-3.
7. Puruckherr, Michael, Payam Pooyan, Daniel Dube, Ryland P. Byrd, and Thomas M. Roy. ‘The Dropped Head Sign: An Unusual Presenting Feature of Myasthenia Gravis’. Neuromuscular Disorders: NMD 14, no. 6 (June 2004): 378–79. https://doi.org/10.1016/j.nmd.2004.01.009.
8. Sih, Marvin, Betty Soliven, Nicholas Mathenia, John Jacobsen, and Kourosh Rezania. ‘Head-Drop: A Frequent Feature of Late-Onset Myasthenia Gravis’. Muscle & Nerve 56, no. 3 (September 2017): 441–44. https://doi.org/10.1002/mus.25526.
9. Aiba, Yosuke, Mikihiro Iwakawa, Ryuji Sakakibara, Yohei Tsuyusaki, Fuyuki Tateno, Masahiko Kishi, Hiromi Tateno, and Tsuyoshi Ogata. ‘Myasthenia Gravis Manifesting As Head Drop in an Elderly Adult with Parkinson’s Disease’. Journal of the American Geriatrics Society 64, no. 10 (2016): e120–22. https://doi.org/10.1111/jgs.14359.
10. Fasano, A., A. Evoli, C. Piano, P. A. Tonali, and A. R. Bentivoglio. ‘Myasthenia Gravis: An Unrecognized Cause of Head Drop in Parkinson’s Disease’. Parkinsonism & Related Disorders 14, no. 2 (2008): 164–65. https://doi.org/10.1016/j.parkreldis.2007.02.009.
11. Hogg, Elliot J., Richard A. Lewis, Serguei Bannykh, and Michele Tagliati. ‘Head Drop in Parkinson’s Disease Complicated by Myasthenia Gravis and Myopathy’. Journal of the Neurological Sciences 376 (15 May 2017): 216–18. https://doi.org/10.1016/j.jns.2017.03.026.
12. Albassam, Mohammed S., Salman A. Thabet, Mohammed Hmoud, and Seraj Makkawi. ‘Anti-Muscle Specific Kinase (Anti-MuSK) Positive Myasthenia Gravis Overlapping With Parkinson’s Disease: A Challenging Diagnosis’. Cureus 13, no. 5 (4 May 2021): e14839. https://doi.org/10.7759/cureus.14839.
13. Urban, P. P., and O. Stammel. ‘Bei Morbus Parkinson und progredienter Dysphagie an Myasthenia gravis denken’. Der Nervenarzt 89, no. 4 (1 April 2018): 443–45. https://doi.org/10.1007/s00115-017-0378-z.
14. Sciacca, G., A. Nicoletti, G. Mostile, V. Dibilio, L. Raciti, A. Luca, E. Reggio, and M. Zappia. ‘Is It Just a Coincidence? Three New Cases of Myasthenia Gravis Associated with Parkinson’s Disease’. Parkinsonism & Related Disorders 28 (July 2016): 166–68. https://doi.org/10.1016/j.parkreldis.2016.04.005.
15. Lang, Anthony E. ‘Treatment of Parkinson’s Disease with Agents Other than Levodopa and Dopamine Agonists: Controversies and New Approaches’. Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques 11, no. S1 (February 1984): 210–20. https://doi.org/10.1017/S0317167100046436.
16. Iwasaki, Y., N. Wakata, and M. Kinoshita. ‘Parkinsonism Induced by Pyridostigmine’. Acta Neurologica Scandinavica 78, no. 3 (September 1988): 236–236. https://doi.org/10.1111/j.1600-0404.1988.tb03653.x.
17. Kao, K. P., S. Y. Kwan, K. P. Lin, and Y. C. Chang. ‘Coexistence of Parkinson’s Disease and Myasthenia Gravis: A Case Report’. Clinical Neurology and Neurosurgery 95, no. 2 (June 1993): 137–39. https://doi.org/10.1016/0303-8467(93)90008-5.
18. Gray, Madison T., and John M. Woulfe. ‘Striatal Blood-Brain Barrier Permeability in Parkinson’s Disease’. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 35, no. 5 (May 2015): 747–50. https://doi.org/10.1038/jcbfm.2015.32.
19. Levin, Netta, Dimitrios Karussis, and Oded Abramsky. ‘Parkinson’s Disease Associated with Myasthenia Gravis’. Journal of Neurology 250, no. 6 (1 June 2003): 766–67. https://doi.org/10.1007/s00415-003-1088-y.
20. Zis, Panagiotis, Vassiliki Argiriadou, Prodromos P. Temperikidis, Lamprini Zikou, Socrates J. Tzartos, and Antonios Tavernarakis. ‘Parkinson’s Disease Associated with Myasthenia Gravis and Rheumatoid Arthritis’. Neurological Sciences 35, no. 5 (1 May 2014): 797–99. https://doi.org/10.1007/s10072-014-1660-5.
21. Wang, Juan, Xiujuan Wu, Wei Wu, Hongliang Zhang, and Kangding Liu. ‘Parkinson’s Disease Associated with Myasthenia Gravis and Rheumatoid Arthritis’. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 36, no. 4 (April 2015): 637–38. https://doi.org/10.1007/s10072-014-1946-7.
22. Iori, Erika, Marco Mazzoli, Alessandra Ariatti, Tiziana Salviato, Vittorio Rispoli, Franco Valzania, and Giuliana Galassi. ‘Myasthenia Gravis Crossing Parkinson’s Disease: A 20 Year Study from Single Italian Center’. The International Journal of Neuroscience, 4 September 2022, 1–7. https://doi.org/10.1080/00207454.2022.2107517.
23. Mosley, R. Lee, Jessica A. Hutter-Saunders, David K. Stone, and Howard E. Gendelman. ‘Inflammation and Adaptive Immunity in Parkinson’s Disease’. Cold Spring Harbor Perspectives in Medicine 2, no. 1 (January 2012): a009381. https://doi.org/10.1101/cshperspect.a009381.
24. Tan, Eng-King, Yin-Xia Chao, Andrew West, Ling-Ling Chan, Werner Poewe, and Joseph Jankovic. ‘Parkinson Disease and the Immune System – Associations, Mechanisms and Therapeutics’. Nature Reviews. Neurology 16, no. 6 (June 2020): 303–18. https://doi.org/10.1038/s41582-020-0344-4.
25. Gerhard, Alexander, Nicola Pavese, Gary Hotton, Federico Turkheimer, Meltem Es, Alexander Hammers, Karla Eggert, Wolfgang Oertel, Richard B. Banati, and David J. Brooks. ‘In Vivo Imaging of Microglial Activation with [11C](R)-PK11195 PET in Idiopathic Parkinson’s Disease’. Neurobiology of Disease 21, no. 2 (1 February 2006): 404–12. https://doi.org/10.1016/j.nbd.2005.08.002.
26. Theodore, Shaji, Shuwen Cao, Pamela J. McLean, and David G. Standaert. ‘Targeted Overexpression of Human Alpha-Synuclein Triggers Microglial Activation and an Adaptive Immune Response in a Mouse Model of Parkinson Disease’. Journal of Neuropathology and Experimental Neurology 67, no. 12 (December 2008): 1149–58. https://doi.org/10.1097/NEN.0b013e31818e5e99.
27. Kannarkat, George T., Jeremy M. Boss, and Malú G. Tansey. ‘The Role of Innate and Adaptive Immunity in Parkinson’s Disease’. Journal of Parkinson’s Disease 3, no. 4 (2013): 493–514. https://doi.org/10.3233/JPD-130250.
28. Allen Reish, Heather E., and David G. Standaert. ‘Role of α-Synuclein in Inducing Innate and Adaptive Immunity in Parkinson Disease’. Journal of Parkinson’s Disease 5, no. 1 (2015): 1–19. https://doi.org/10.3233/JPD-140491.
29. Koutsilieri, E., M. B. Lutz, and C. Scheller. ‘Autoimmunity, Dendritic Cells and Relevance for Parkinson’s Disease’. Journal of Neural Transmission 120, no. 1 (2013): 75–81. https://doi.org/10.1007/s00702-012-0842-7.
30. Jiang, Tianfang, Gen Li, Jun Xu, Shane Gao, and Xu Chen. ‘The Challenge of the Pathogenesis of Parkinson’s Disease: Is Autoimmunity the Culprit?’ Frontiers in Immunology 9 (2018): 2047. https://doi.org/10.3389/fimmu.2018.02047.
31. De Virgilio, Armando, Antonio Greco, Giovanni Fabbrini, Maurizio Inghilleri, Maria Ida Rizzo, Andrea Gallo, Michela Conte, Chiara Rosato, Mario Ciniglio Appiani, and Marco de Vincentiis. ‘Parkinson’s Disease: Autoimmunity and Neuroinflammation’. Autoimmunity Reviews 15, no. 10 (October 2016): 1005–11. https://doi.org/10.1016/j.autrev.2016.07.022.
32. Baird, Jill K., Dennis Bourdette, Charles K. Meshul, and Joseph F. Quinn. ‘The Key Role of T Cells in Parkinson’s Disease Pathogenesis and Therapy’. Parkinsonism & Related Disorders 60 (1 March 2019): 25–31. https://doi.org/10.1016/j.parkreldis.2018.10.029.
33. Garretti, Francesca, Dritan Agalliu, Cecilia S. Lindestam Arlehamn, Alessandro Sette, and David Sulzer. ‘Autoimmunity in Parkinson’s Disease: The Role of α-Synuclein-Specific T Cells’. Frontiers in Immunology 10 (25 February 2019): 303. https://doi.org/10.3389/fimmu.2019.00303.
34. Reale, M., C. Iarlori, A. Thomas, D. Gambi, B. Perfetti, M. Di Nicola, and M. Onofrj. ‘Peripheral Cytokines Profile in Parkinson’s Disease’. Brain, Behavior, and Immunity 23, no. 1 (January 2009): 55–63. https://doi.org/10.1016/j.bbi.2008.07.003.
35. Kustrimovic, Natasa, Cristoforo Comi, Luca Magistrelli, Emanuela Rasini, Massimiliano Legnaro, Raffaella Bombelli, Iva Aleksic, et al. ‘Parkinson’s Disease Patients Have a Complex Phenotypic and Functional Th1 Bias: Cross-Sectional Studies of CD4+ Th1/Th2/T17 and Treg in Drug-Naïve and Drug-Treated Patients’. Journal of Neuroinflammation 15, no. 1 (12 July 2018): 205. https://doi.org/10.1186/s12974-018-1248-8.
36. Dzamko, Nicolas L. ‘LRRK2 and the Immune System’. Advances in Neurobiology 14 (2017): 123–43. https://doi.org/10.1007/978-3-319-49969-7_7

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-and-myasthenia-gravis-a-case-report-and-literature-review/