Myasthenia Gravis –  a Critical Assessment of the Contribution of Muscle Biopsy Performed During Thymectomy

Authors: J. Zámečník 1;  J. Piťha 2;  J. Schützner 3;  D. Veselý 1,4;  B. Jakubička 1
Authors‘ workplace: Ústav patologie a molekulární medicíny, UK 2. LF a FN v Motole, Praha, 2Neurologická klinika, UK 1. LF a VFN, Praha, 3III. chirurgická klinika, UK 1. LF a FN v Motole, Praha, 4I. infekční klinika, UK 2. LF a FN Bulovka, Praha 1
Published in: Cesk Slov Neurol N 2009; 72/105(2): 147-154
Category: Original Paper


Surprisingly, structural changes o utside the ne uromuscular juncti ons were reported in limited seri es of myastheni a gravis (MG) muscles previ o usly –  mainly small collecti on of interstiti al lymphocytes and atrophy of type II muscle fibers. However, the pathophysiological mechanisms remained uncle ar. We performed a systematic study on MG muscle bi opsi es to contribute to understanding of the associ ation to MG and to demonstrate possible prognostic value.

Sternothyro id muscle bi opsies from 207 MG patients taken during thymectomy were analyzed histopathologically and by histochemistry and morphometry and correlated to the clinical fe atures and the o utcome of MG pati ents.

In 143 MG pati ents, no obvi o us pathological changes were observed in muscle bi opsi es. In 20 pati ents we observed an interstiti al infiltrati on by mature naive CD45RA+lymphocytes. The lymphocytic infiltrati on associ ated with the thymus pathology, mainly with thymoma. The morphometry disclosed selective atrophy of type II muscle fibers in 35 cases. The atrophy of type II muscle fibers was related to long‑term corticostero id tre atment and the potenti al prognostic value co uld be demonstrated for its detecti on: the MG pati ents with type II fibers atrophy presented slower tendency to re ach remissi on. Further, in 12 cases we demonstrated mild changes in mitochondri al metabolism, in 34 cases we disclosed angular atrophic fibers; no prognostic value was demonstrated for these changes.

Conclusi ons:
The previ o usly reported histopathological changes in MG muscle are rare and mostly do not represent a fe ature of the MG, rather a consequence of the thymic disorder or of the long‑term stero id therapy. The value of muscle bi opsy performed during thymectomy for the particular MG pati ent remains controversi al.

Key words:
myasthenia gravis – muscle biopsy – thymectomy – prognosis


1. Romi F, Gilhus NE, Aarli JA. Myastheni a gravis: clinical, immunological, and therape utic advances. Acta Ne urol Scand 2005; 111(2): 134– 141.

2. Engel AG, Hohlfeld R. Acquired a uto immune myastheni a gravis. In: Engel AG, Franzini‑Armstrong C (eds). Myology. 3rd ed. New York: McGraw- Hill Inc. 2004: 1755– 1790.

3. Engstrom JW. Myastheni a gravis: di agnostic mimics. Semin Ne urol 2004; 24(2): 141– 147.

4. Fenichel GM. Muscle lesi ons in myastheni a gravis. Ann N Y Acad Sci 1966; 135(1): 60– 67.

5. Russell DS. Histological changes in the striped muscles in myastheni a gravis. J Pathol Bacteri ol 1953; 65(2): 279– 289.

6. Engel WK, McFarlin DE. Muscle lesi ons in myastheni a gravis. Ann N Y Acad Sci 1966; 135(1): 68– 78.

7. Havlíček F, Šmat V. Histometrická analýza svalové atrofi e u myastheni a gravis. Čas Lék Česk 1980; 119(22): 629– 632.

8. Dubowitz V, Sewry CA. Myastheni a gravis. In: Dubowitz V, Sewry CA (eds). Muscle Bi opsy: A practical appro ach. 3rd ed. London: Sa unders 2007: 512– 520.

9. Weller RO, Cumming WJK, Mahon M, Ellison DW. Dise ases of Muscle: Myastheni a gravis. In: Graham DI, Lantos PL (eds). Greenfi eld‘s Ne uropathology. 7th ed. London: A Hodder Arnold Publicati on 2002: 715– 716.

10. Schützner J, Šmat V. Myastheni a gravis –  komplexní pojetí a chirurgická léčba. Praha: Galén 2005.

11. Zámečník J, Veselý D, Jakubička B, Šimková L, Piť ha J, Schützner J et al. Muscle lymphocytic infiltrates in thymoma-associated myasthenia gravis are phenotypically different from those in polymyositis. Neuromuscul Disord 2007; 17(11–12): 935-942.

12. Zámečník J, Veselý D, Jakubička B, Cibula A, Piť ha J, Schützner J et al. Atrophy of type II fibers in myasthenia gravis muscle in thymectomized patients: steroid-induced change with prognostic impact. J Cell Mol Med 2009: In press.

13. Osserman KE, Genkins G. Studi es in myastheni a gravis: revi ew of a twenty- ye ar experi ence in over 1200 pati ents. Mt Sinai J Med 1971; 38(6): 497– 537.

14. Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS et al. Myastheni a gravis: recommendati ons for clinical rese arch standards. Task Force of the Medical Sci entific Advisory Bo ard of the Myastheni a Gravis Fo undati on of America. Ne urology 2000; 55(1): 16– 23.

15. Sheehan DC, Hrapchak BB. The ory and practice of histotechnology. 2nd ed. Columbus, Ohi o: Mosby 1987.

16. Bro oke MH, Engel WK. The histographic analysis of human muscle bi opsi es with regard to fiber types. 1. Adult male and female. Ne urology 1969; 19(3): 221– 233.

17. Vogel H, Zámečník J. Diagnostic immunohistology of muscle diseases. J Neuropathol Exp Neurol 2005; 64(3): 181-193.

18. Hoffacker V, Schultz A, Ti esinga JJ, Gold R, Schal ke B, Nix W et al. Thymomas alter the T- cell subset compositi on in the blo od: a potenti al mechanism for thymoma‑associ ated a uto immune dise ase. Blo od 2000; 96(12): 3872– 3879.

19. Martignago S, Fanin M, Albertini E, Pegoraro E, Angelini C. Muscle histopathology in myastheni a gravis with antibodi es against MuSK and AChR. Ne uropathol Appl Ne urobi ol 2009; 35(1):103– 110.

20. Polla B, Bottinelli R, Sandoli D, Sardi C, Reggi ani C. Cortisone‑induced changes in myosin he avy chain distributi on in respiratory and hindlimb muscles. Acta Physi ol Scand 1994; 151(3): 353– 361.

21. Rostedt Punga A, Ahlqvist K, Bartocci oni E, Scude ri F, Marino M, Suomalainen A et al. Ne urophysi ological and mitochondri al abnormaliti es in MuSK antibody seropositive myastheni a gravis compared to other immunological subtypes. Clin Ne urophysi ol 2006; 117(7): 1434– 1443.

22. Shichijo K, Mitsui T, Kunishige M, Kuroda Y, Masuda K, Matsumoto T. Involvement of mitochondri a in myastheni a gravis complicated with dermatomyositis and rhe umato id arthritis: a case report. Acta Ne uropathol 2005; 109(5): 539– 542.

23. Lambert AJ, Brand MD. Rese arch on mitochondri a and aging, 2006– 2007. Aging Cell 2007; 6(4): 417– 420.

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