

MuSK-myasthenia gravis in a patient with overlap syndrome — Bickerstaff encephalitis and pharyngo-cervico-brachial variant of Guillain-Barré syndrome
https://doi.org/10.30629/2658-7947-2025-30-4-22-31
Abstract
This is the fi rst clinical report of a patient with MuSK-myasthenia gravis combined with Bickerstaff ’s brainstem encephalitis and a pharyngo-cervico-brachial variant of Guillain-Barré syndrome. There were observed previously unreported and rare symptoms in Bickerstaff ’s brainstem encephalitis: palinopsia, allesthesia, derealization, and depersonalization states; in the pharyngo-cervico-brachial variant of Guillain-Barré syndrome, there was involvement of peripheral structures of the visual pathway and the peripheral autonomic nervous system. Manifestations of Bickerstaff ’s brainstem encephalitis included pronounced somnolence, pyramidal and cerebellar symptoms, and psychiatric disturbances; a notable feature was its development following a coronavirus infection and a relapsing course. The diagnosis of the pharyngo-cervico-brachial variant of Guillain-Barré syndrome was based on fi ndings such as hyporefl exia, results of electroneuromyography, elevated protein levels in cerebrospinal fl uid, and involvement of peripheral segments of the optic nerve and autonomic nervous system.
About the Authors
T. V. MatveevaRussian Federation
Kazan, Russia
I. F. Khafizova
Russian Federation
Kazan, Russia
N. A. Popova
Russian Federation
Kazan, Russia
References
1. Cao M, Koneczny I., Vincent A. Myasthenia Gravis With Antibodies Against Muscle Specifi c Kinase: An Update on Clinical Features, Pathophysiology and Treatment. Front. Mol. Neurosci. 2020;13:159. doi: 10.3389/fnmol.2020.00159
2. Evoli A, Alboini PE, Iorio R, Damato V, Bartoccioni E. Pattern of ocular involvement in myasthenia gravis with MuSK antibodies. J Neurol Neurosurg Psychiatry. 2017 Sep;88(9):761–763. doi: 10.1136/jnnp-2017-315782. Epub 2017 Jun 10. PMID:28601810.
3. Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E. Clinical correlates with antiMuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003 Oct;126(Pt 10):2304–11. doi: 10.1093/brain/awg223. Epub 2003 Jun 23. PMID: 12821509.
4. Martignago S, Fanin M, Albertini E, Pegoraro E, Angelini C. Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR. Neuropathol Appl Neurobiol. 2009 Feb;35(1):103–10. doi: 10.1111/j.1365-2990.2008.00965.x. PMID: 19187062
5. Rodolico С, Bonanno С, Antonio Toscano А and Vita G. MuSKAssociated Myasthenia Gravis: Clinical Features and Management. Front Neurol. 2020;11:660. Published online 2020 Jul 23. doi: 10.3389/fneur.2020.00660
6. Farrugia ME, Robson MD, Clover L, Anslow P, Newsom-Davis J, Kennett R, Hilton-Jones D, Matthews PM, Vincent A. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain. 2006 Jun;129(Pt 6):1481–92. doi: 10.1093/brain/awl095. Epub 2006 May 3. PMID: 16672291.
7. Arsen’ev A. Immunnye nejropatii. MEDACH. PRO. 2023. — 31 s. https://medach.pro/post/2914,
8. Pegg E.J., Chhetri S.K., Lekwuwa U.G., Majeed T. An Overlapping Case of Miller Fisher Syndrome, Bickerstaff ’s Encephalitis, and the ASMAN Variant of Guillain-Barre Syndrome. Case Rep Neurol Med. 2016;2016:1596850. doi: 10.1155/2016/1596850. Epub 2016 Nov 6. PMID: 27974981; PMCID: PMC5128697.
9. Murtazina A.F., Naumova E.S., Nikitin S.S., Boriskina L.M., Lagutin A.V. Bickerstaff brainstem encephalitis, acute transverse myelitis, and acute motor axonal neuropathy: diagnostic and treatment challenges in patients with concomitant syndromes. Clinical observation. Neuromuscular Diseases. 2017;7(3):56–62. (In Russ.). https://doi.org/10.17650/2222-8721-2017-7-3-56-62
10. El’chaninov A.P., ZHuravlev P.V., Amosova N.V., Dekan V.S., Mitusova G.M., Pavlov D.G., Kozlova G.A., Grishchenkov A.S. Bickerstaff ’s encephalitis. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(7):84–88. (In Russ.). https://doi.org/10.17116/jnevro20181187184
11. Bickerstaff , E. R., & Cloake, P. C. (1951). Mesencephalitis and rhombencephalitis. British Medical Journal. 2(4723):77–81. https://doi.org/10. 1136/bmj.2.4723.77
12. Al-Din AN, Anderson M, Bickerstaff ER, Harvey I. Brainstem encephalitis and the syndrome of Miller Fisher: a clinical study. Brain. 1982 Sep;105(Pt 3):481–95. doi: 10.1093/brain/105.3.481. PMID: 7104664
13. Piradov M.A. Polyneuropathies: diagnostic and treatment algorithms (Polinejropatii: algoritmy diagnostiki i lecheniya) / M.A. Piradov, N.A. Suponeva, D.A. Grishina. — Moscow: Hotline — Telecom, 2020. — 248 p., ISBN 978-5-9912-0818-5
14. Más-Lázaro C, García-Pastor A, Díaz-Insa S, Moltó-Jordà JM, Lacruz-Ballester L. Variante faringocervicobraquial del síndrome de Guillain-Barré: una entidad clínica bien defi nida con un perfi l inmunológico heterogéneo. Rev Neurol. (2008) 47:579–81. doi: 10.33588/rn.4711.2008074
15. Wakerley BR, Yuki N. Pharyngeal-cervicalbrachial variant of Guillain–Barré syndrome. J NeurolNeurosurg Psychiatry. 2014;85:339–344. PMID: 23804237. doi: 10.1136/jnnp-2013-305397
16. Miyagi T, Higa K, Kido M, Ishihara S, Nakachi R, Suwazono S. The Sequential Ultrasonographic, Electrophysiological and MRI Findings in a Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barré Syndrome from the Acute Phase to the Chronic Phase. Intern Med. 2017;56(10):1225–1230. doi: 10.2169/internalmedicine.56.7807. Epub 2017 May 15. PMID: 28502941; PMCID: PMC5491821
17. Moscona-Nissan A, López-Hernández J, Seidman-Sorsby A, et al. (October 14, 2021) Pharyngeal–Cervical–Brachial Variant of Guillain–Barré Syndrome. Cureus. 13(10): e18788. doi: 10.7759/cureus.18788
18. Luan H, Zhang P, Zhen M, Li M, Wang X, Xu J. Recurrent Guillain-Barré syndrome presenting as pharyngeal-cervical-brachial variant with three species of ganglioside antibodies:case report. BMC Neurol. 2022 Nov 28;22(1):441. doi: 10.1186/s12883-022-02955-0. PMID: 36443698; PMCID: PMC9703836
19. Nagashima T, Koga M, Odaka M, Hirata K, Yuki N. Continuous spectrum of pharyngeal- cervical-brachial variant of GuillainBarré syndrome. Arch Neurol. 2007;64:1519–2
20. Kim JK, Kim BJ, Shin HY, Shin KJ, Nam TS, Oh J, Suh BC, Yoon BA, Park HT, Huh SY, Oh SI, Bae JS; Korean Infl ammatory Neuropathy Consortium. Acute bulbar palsy as a variant of Guillain-Barré syndrome. Neurology. 2016 Feb 23;86(8):742–7. doi: 10.1212/WNL.0000000000002256. Epub 2015 Dec 30. PMID: 26718574
21. Yuki N, Hartung H-P. Guillain–Barré syndrome. N Engl J Med. (2012) 366:2294–304. doi: 10.1056/NEJMra1114525 10.1056/NEJMra1114525
22. Brohi, Hazim; Mustaqeem, Marium; and Khan, Sundus (2017) “Pharygeal Cervicobrachial Variant Of Guillian -barre Syndrome,” Pakistan Journal of Neurological Sciences (PJNS): Vol. 12: Iss. 4, Article 9. Available at: https://ecommons.aku.edu/pjns/vol12/iss4/9
23. Pegg E.J., Chhetri S.K., Lekwuwa U.G., Majeed T. An Overlapping Case of Miller Fisher Syndrome, Bickerstaff ’s Encephalitis, and the ASMAN Variant of Guillain-Barre Syndrome. Case Rep Neurol Med. 2016;2016:1596850. doi: 10.1155/2016/1596850. Epub 2016 Nov 6. PMID: 27974981; PMCID: PMC5128697.,
24. Verboon C, van Berghem H, van Doorn PA, Ruts L, Jacobs BC. Prediction of disease progression in Miller Fisher and overlap syndromes. J Peripher Nerv Syst. 2017 Dec;22(4):446–450. doi: 10.1111/jns.12238. Epub 2017 Nov 15. PMID: 29065229.
25. Tan CY, Ahmad SB, Goh KJ, Latif LA, Shahrizaila N. Overlap of Bickerstaff brainstem encephalitis/Guillain–Barré syndrome simulating brain death. Neurol India. 2018;66:1475–80. doi: 10.4103/0028-3886.241342
26. Kaida R., Ariga T., Yu R.K. Antiganglioside antibodies and their pathophysiological eff ects on Guillain–Barré syndrome and related disorders—A review. Glycobiology. 2009. doi: 10.1093/glycob/cwp027 PMCID: PMID: 19240270
27. Naik GS, Meena AK, Reddy BAK, Mridula RK, Jabeen SA, Borgohain R. Anti-ganglioside antibodies profi le in GuillainBarré syndrome: Correlation with clinical features, electrophysiological pattern, and outcome. Neurol India. 2017 SepOct;65(5):1001–1005. doi: 10.4103/neuroindia.NI_1226_15. PMID: 28879885.
28. Liu JX, Willison HJ, Pedrosa-Domellof F (2009) Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles. Invest Ophthalmol Vis Sci. 50(7):3226–3232. doi: 10.1167/iovs.08-3333 PMID:19255160
29. Sipione S, Monyror J, Galleguillos D, Steinberg N, Kadam V. Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications. Front Neurosci. 2020 Oct 6;14:572965. doi: 10.3389/fnins.2020.572965. PMID: 33117120; PMCID:PMC7574889.
30. Kusunoki S, Chiba A, Kanazawa I (1999) Anti-GQ1b IgG antibody is associated with ataxia as well as ophthalmoplegia. Muscle Nerve. 22:1071–1074. doi: 10.1002/(sici)1097-4598(199908)22:8<1071::aid-mus10>3.0.co;2-0.
31. Yuki N., Yamada M., Koga M., Odaka M., Susuki K., Tagawa Y., et al.. (2001). Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganglioside. Ann. Neurol. 49, 712–720. 10.1002/ana.1012
32. Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, Burwen DR, Cornblath DR, Cleerbout J, Edwards KM, Heininger U, Hughes R, Khuri-Bulos N, Korinthenberg R, Law BJ, Munro U, Maltezou HC, Nell P, Oleske J, Sparks R, Velentgas P, Vermeer P, Wiznitzer M; Brighton Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case defi nitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011 Jan 10;29(3):599–612. doi: 10.1016/j.vaccine.2010.06.003. Epub 2010 Jun 18. PMID:20600491.
33. Burden SJ, Yumoto N, Zhang W. The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol. 2013 May 1;5(5):a009167. doi: 10.1101/cshperspect.a009167. PMID: 23637281; PMCID: PMC3632064
34. Ghazanfari N, Morsch M, Reddel SW, Liang SX, Phillips WD. Musclespecifi c kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction. J Physiol. (2014) 592(Pt 13):2881–97. doi: 10.1113/jphysiol.2013.270207
35. Odaka M., Hirata N.Y.K. Anti-Gq1b IgG antibody syndrome: clinical and immunological range. J Neurology, Neurosurgery, and Psychiatry. 2001. 70:50–55. doi: 10.1136/jnnp.70.1.50 PMID:11118247 PMCD:PMC1763462.,
36. Michev A, Musso P., Foiadelli T. et al. Bickerstaff Brainstem Encephalitis and overlapping Guillain-Barre syndrome in children: Report of two cases and review of the literature. Eur J Paediatr Neurol. 2019 Jan;23(1):43–52. doi: 10.1016/j.ejpn.2018.11.008. Epub 2018 Nov 20. PMID: 30502045
37. Tyrakowska Z, Jakubowicz-Lachowska D, Kułakowska A, Galińska-Skok B, Drozdowski W, Tarasów E. Relapsing-Remitting Severe Bickerstaff ’s Brainstem Encephalitis — Case Report and Literature Review. Pol J Radiol. 2016 Dec 28;81:622–628. doi: 10.12659/PJR.898647. PMID: 28096906; PMCID: PMC5214676.
38. Gersztenkorn D, Lee A.G Palinopsia revamped: a systematic review of the literature. Sury Ophthalalmol. 2015 JanFeb;60(1):1–35. doi: 10.1016/j.survophthal.2014.06.003
39. Grigoryeva VN, Mashkovich KA. Metamorphopsia in neurological practice. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(4):111–116. (In Russ.). https://doi.org/10.14412/2074-2711-2019-4-111-116
40. River Y, Hur T.B., Steiner I. Reversal of Vision Metamorphopsia Clinical and Anatomical Characteristics. Arch Neurol. 1998;55(10):1362–1368. doi: 10.1001/archneur.55.10.1362
41. Hitier M, Besnard S, Smith PF. Vestibular pathways involved in cognition. Front Integr Neurosci. 2014 Jul 23;8:59. doi: 10.3389/fnint.2014.00059. PMID: 25100954; PMCID: PMC4107830.
42. Ango F, Dos Reis R. Sensing how to balance. Elife. 2019 Apr 17;8:e46973. doi: 10.7554/eLife.46973. PMID: 30994456; PMCID: PMC6469924.
43. Giaccari LG, Mastria D, Barbieri R, De Maglio R, Madaro F, Paiano G, Pace MC, Sansone P, Pulito G, Mascia L. Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today. Front Neurol. 2024 Mar 12;15:1387505. doi: 10.3389/fneur.2024.1387505. PMID: 38533411; PMCID: PMC10963475.
44. Shahrizaila N, Yuki N. Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome. J Neurol Neurosurg Psychiatry. 2013 May;84(5):576–83. doi: 10.1136/jnnp2012-302824. Epub 2012 Sep 15. PMID: 22984203
45. Illarioshkin S.N., Rudenskaya G.E., Ivanova-Smolenskaya I.A., Markova E.D., Klyushnikov S.A. Hereditary ataxias and paraplegias. — M.: MEDpress-inform, 2006:416. ISBN 5-98322-196-5
46. Odinak M.M., Litvinenko I.V., Emelin A.Yu., Prokudin M.Yu., Lobzin V.Yu., Skiba Ya.B. Parenchymal cortical cerebellar atrophy: discussion on clinical observation. Bulletin of the Russian Military Medical Academy. 2014;2(46):18–21
47. Mahale R, Mehta A, Hegde S, Buddaraju K, Javali M, Acharya PT, Srinivasa R. Sporadic spinocerebellar ataxia, type 5: First report from India. Neurol India. 2018;66:230–1. doi: 10.4103/0028-3886.222857
48. Al-Chalabi M, DelCimmuto NR, Beran A, Devarasetty PP, Mhanna A, Mahfooz N, Sheikh A. Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies. Mult Scler Relat Disord. 2022 Dec;68:104112. doi: 10.1016/j.msard.2022.104112. Epub 2022 Aug 18. PMID: 36029706.
49. Bradshaw MJ, Pawate S, Koth LL, Cho TA, Gelfand JM. Neurosarcoidosis: Pathophysiology, Diagnosis, and Treatment. Neurol Neuroimmunol Neuroinfl amm. 2021 Oct 4;8(6):e1084. doi: 10.1212/NXI.0000000000001084. PMID: 34607912; PMCID: PMC8495503.
50. Zadorina G.N., Zinov’eva O.E., Safi ulina E.I., Solokha О.А., Lisitsina T.A., Ovcharov P.S., Alekberova Z.S., Yakhno N.N. Neurological signs of Behcet’s disease. Neurological Journal (Nevrologicheskiy Zhurnal). 2017;22(3):148–156. (In Russ.). doi: 10.18821/1560-9545-2017-22-3-148-156.
51. Hermetter C, Fazekas F, Hochmeister S. Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis. Front Neurol. 2018 Sep 5;9:706. doi: 10.3389/fneur.2018.00706 PMID: 30233481; PMCID: PMC6135049.
Review
For citations:
Matveeva T.V., Khafizova I.F., Popova N.A. MuSK-myasthenia gravis in a patient with overlap syndrome — Bickerstaff encephalitis and pharyngo-cervico-brachial variant of Guillain-Barré syndrome. Russian neurological journal. 2025;30(4):22-31. (In Russ.) https://doi.org/10.30629/2658-7947-2025-30-4-22-31