Research Article ISSN 2641-4333

Neurology - Research & Surgery

Investıgatıon of Motor End Plate Functıons in Indıvıduals wıth Incıdentally

Detected Thymoma
Vural Gonul1,2* and Gumusyayla Sadiye1,2

*
Correspondence:
Department of Neurology, Faculty of Medicine, Ankara Yildirim
1
Gonul Vural, Ankara Yildirim Beyazit University, Faculty of
Beyazit University, 06800, Ankara, Turkey. Medicine, Department of Neurology, Ankara City Hospital,
Universiteler District, 1604th Street, No: 9, Cankaya, Ankara,
2
Department of Neurology, Ankara City Hospital, Ankara 06800, 06800, Turkey, Tel: +90 5055764221, Fax: 0312 552 60 00.
Turkey.
Received: 01 Mar 2024; Accepted: 05 Apr 2024; Published: 12 Apr 2024

Citation: Vural Gonul, Gumusyayla Sadiye. Investıgatıon of Motor End Plate Functıons in Indıvıduals wıth Incıdentally Detected
Thymoma. Neurol Res Surg. 2024; 7(2): 1-4.

ABSTRACT
Purpose: Thymoma is a mediastinal tumor that is frequently associated with Myasthenia Graves (MG) and develops
from thymic epithelial cells. In our study, we aimed to determine whether there is a neuromuscular transmission
defect in individuals with incidentally detected thymoma and to show whether these individuals have subclinical
involvement without any clinical findings.

Materials and Methods: Single fiber electromyography (SFEMG) records made between March 2019 and January
2024 were examined, individuals who underwent SFEMG due to thymoma and structural ptosis were identified and
detailed file record information of the patients was accessed. Individuals with any other disease or neurological
complaint were excluded from the study. Asymptomatic individuals who underwent SFEMG were divided into two
groups: individuals with thymoma and individuals with structural ptosis, and the demographic information and
SFEMG findings of the two groups were compared with each other.

Results: Maximum jitter mean, minimum jitter mean and mean consecutive difference (MCD) values were found to
be significantly higher in asymptomatic individuals with incidentally detected thymoma compared to patients with
structural ptosis.

Discussion: Patients with thymoma may have subclinical neuromuscular transmission abnormalities even when they
are asymptomatic in terms of MG. This is important for early diagnosis of MG and understanding the pathological
processes in thymoma.

Keywords postsynaptic muscle end plate components. MG is a disease

Thymoma, Myasthenia graves, Single fiber electromyography. characterized by clinical findings caused by local or generalized
muscle fatigue resulting from a defect in neuromuscular
Introduction transmission. MG associated with thymoma is a paraneoplastic
Dysfunction at the neuromuscular junction underlies a variety disease. MG is by far the most commonly reported autoimmune
of disorders characterized by skeletal muscle weakness, often disease associated with thymoma [1-3]. Thymomas are rare
affecting some but not all muscle groups. Myasthenia gravis (MG) tumors located in the mediastinal region and developing from
constitutes the largest disease group of neuromuscular junction thymic epithelial cells. Approximately 50% of patients with
disorders and is caused by pathogenic autoantibodies against thymoma develop MG, while thymoma is detected in 10-15%

Neurol Res Surg, 2024 Volume 7 | Issue 2 | 1 of 4

of patients with MG [4,5]. Epithelial cells have the capacity to (SD), median (M), minimum (min) and maximum (max) values.
express epitopes cross-reactive with skeletal muscle proteins such Normal distribution of the data of numerical variables was
as acetylcholine receptor (AChR), titin, and ryanodine receptor evaluated with the Shapiro Wilk normality test. When comparisons
(RyR) [6,7]. Muscle-like epitopes are presented to T cells together between groups were evaluated, the Independent two-sample t test
with costimulatory molecules [7]. Autoreactive T cells specific was used when the data met the parametric test prerequisites, and
for AChR and titin are found both in thymoma and in the serum the Mann-Whitney U test was used when the data did not meet the
of patients with coexistence of thymoma and MG [8]. Therefore, parametric test prerequisites. Pearson chi-square test was used to
some of the mechanisms related to the responsible pathogenesis compare categorical variables with each other. A value of p<0.05
in patients with MG can be detected in patients with thymoma was considered statistically significant.
but without developing clinical findings of MG. In fact, detecting
these findings in advance may be important in terms of being a Results
predictor of the disease before the disease develops for MG. 98 patients who were asymptomatic in terms of MG, who were
incidentally diagnosed with thymoma, or who were sent to the
Single fiber electromyography (SFEMG) is an electrophysiological clinical neurophysiology laboratory for SF EMG due to structural
method with very high sensitivity in detecting neuromuscular ptosis, were included in the study. These patients were divided into
junction pathologies. SFEMG also has remarkable sensitivity 2 groups. The patients in Group 1 consisted of 62 patients who had
in detecting subclinical neuromuscular conduction disorders. In a thymoma on thorax CT taken for another reason and did not have
some studies, neuromuscular junction dysfunction was detected any neurological symptoms. The patients in Group 2 consisted of
electrophysiologically in the SFEMG studied in extensor 36 patients who did not have any neurological complaints and had
digitorum comminis muscle in patients with isolated ocular MG, structural ptosis. While the average age of the patients in Group 1
even though this muscle was not symptomatically involved [9,10]. was 41.62±12.62, the average age of the patients in Group 2 was
Based on this information, we aimed to determine whether there 52.80±16.41. 38.7% of the patients in Group 1 were female and
is an abnormality in neuromuscular conduction in patients with 61.3% were male. Of the patients in Group 2, 44.4% were female
incidentally detected thymoma, although no clinical findings of and 55.6% were male. Although there was a significant difference
MG were observed. between the two groups in terms of age, there was no difference
between the groups in terms of gender.
Material and Methods
This study included 62 patients who were referred to our hospital's When the SFEMG parameters were examined, the mean minimum
clinical neurophysiology laboratory for SFEMG between March jitter value of the patients in Group 1 was 14.62±3.77, while the
2019 and January 2024, whose thymoma was detected on thorax mean minimum jitter value of the patients in Group 2 was found to
computed tomography (CT) taken for another indication and be 11.25±2.81. While the mean maximum jitter value of the patients
who were asymptomatic in terms of MG, and 36 individuals who in Group 1 was 53.0±14.47, the mean maximum jitter value of the
underwent SFEMG due to structural ptosis. The demographic, patients in Group 2 was 43.55±14.61. While the average MCD
clinical, laboratory, radiological and electrophysiological of the patients in Group 1 was 28.59±4.18, the average MCD
parameters of the individuals in both groups were accessed by of the patients in Group 2 was 23.41±4.79. When Group 1 and
retrospectively examining the records of patients who underwent Group 2 were compared, the minimum jitter, maximum jitter and
SFEMG between March 2019 and January 2024. Individuals with average MCD values in the individuals in Group 1 were found to
insufficient data on SFEMG or with another known disease were be significantly higher than those in the individuals in Group 2
excluded from the study. Neurological examinations and SFEMGs (p<0.001).
of the patients were performed by the researchers in the laboratory
environment. This research was approved by the local ethics A pathological increase in jitter was detected in 1 fiber in 17.7% of
committee (03.13.2024/ TABED 1-24-76). the individuals in Group 1, and a pathological increase in jitter was
detected in 2 fibers in 3.2%. In Group 2, a pathological increase
SFEMG electrode (diameter for recording 2.5 µm) and a in jitter was found in 1 fiber in 5.6% of the individuals, and a
counterpoint EMG instrument (Keypoint. 4ch, Medtronic, pathological increase in jitter was found in 2 fibers in 2.8% of the
Denmark) were used for minimum voluntary contraction SFEMG individuals (p=0.248)
test. Jitter was calculated as mean consecutive difference (MCD).
The criteria for acceptable potential pairs were: Amplitude >200 Discussion
µV; and rise time 50 µs. Pathological increase in jitter was accepted In our study, we found that the minimum jitter, maximum jitter
as MCD>55 µs. and mean MCD values of individuals with no symptoms and
incidentally diagnosed thymoma were significantly higher
Statistical Method than those of patients who had no neurological complaints
The data were evaluated in the statistical package program IBM and underwent SFEMG due to structural ptosis. In addition,
SPSS Statistics Standard Concurrent User V 26 (IBM Corp., the percentage of fibers with pathologically increased jitter in
Armonk, New York, USA). Descriptive statistics were given as individuals with incidentally detected thymoma was found to be
number of units (n), percentage (%), mean ± standard deviation higher than in individuals without thymoma. These findings show
Neurol Res Surg, 2024 Volume 7 | Issue 2 | 2 of 4
that individuals who are asymptomatic for MG but have thymoma with thymoma, even when they are asymptomatic in terms of
have a significantly impaired neuromuscular transmission at the MG. One of the limitations of our study is its retrospective design.
neuromuscular junction. Another limitation is that it did not follow up this patient group
to confirm this information and evaluate whether they would
Histologically, thymomas are epithelial neoplastic cells surrounded develop MG and which patients would convert to MG. Prospective
by maturing T cells. There are a few case reports that detected randomized controlled studies are needed on this subject.
elevated antibodies in patients with thymoma even when MG did
not develop [8,11]. However, there is no study in the literature to References
date that evaluates neuromuscular transmission in patients with 1. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis
thymoma who are asymptomatic in terms of MG. In this study, we emerging clinical and biological heterogeneity. Lancet Neurol.
determined that there is dysfunction in neuromuscular transmission 2009; 8: 475-490.
in individuals with thymoma, even in the asymptomatic period. In 2. Gilhus NE. Myasthenia and neuromuscular junction. Curr
this respect, our study is the first and provides important information Opin Neurol. 2012; 25: 523-529.
to the literature in this context. The relationship between thymoma
3. Oosterhuis HJGH. Myasthenia Gravis. In Clinical Neurology
and MG can be explained by the function of thymic tissues and the
and Neurosurgery Monographs. London: Churchill
connection in the pathogenesis of MG. Immunological maturation
Livingston. 1984; 288.
occurs when T cells interact with cell surface proteins on thymic
tissue cells to distinguish between self and non-self antigens. In 4. Muller Hermelink HK, Marx A, Geuder K, et al. The
the case of thymoma-associated MG, thymomas are hypothesized pathological basis of thymoma-associated myasthenia gravis.
to retain epitopes that can cross-react with certain skeletal muscle Ann N Y Acad Sci. 1993; 681: 56-65.
proteins. These epitopes are ryanodine receptor (RyR), titin and 5. Muller Hermelink HK, Marx A. Pathological aspects of
acetylcholine receptor [12]. The genetic profile of the patient and malignant and benign thymic disorders. Ann Med. 1999; 31:
the ability of the thymus to export autoreactive T cells are equally 5-14.
important in the development of MG [13]. The neuromuscular 6. Marx A, Kirchner T, Hoppe F, et al. Proteins with epitopes of the
conduction abnormalities we found in our study are probably acetylcholine receptor in epithelial cell cultures of thymomas
related to the onset of subclinical involvements even when MG in myasthenia gravis. Am J Pathol. 1989; 134: 865-877.
has not yet developed, and to the fact that these involvements only 7. Romi F, Bo L, Skeie GO, et al. Titin and ryanodine receptor
produce clinical findings if they exceed a certain threshold point. epitopes are expressed in cortical thymoma along with
costimulatory molecules. J Neuroimmunol. 2002; 128: 82-89.
MG is a neuromuscular junction disease characterized by muscle
8. Skeie GO, Bentsen PT, Freiburg A, et al. Cell mediated
weakness and fatigue, caused by AChR antibodies in 85% of cases
immune response against titin in myasthenia gravis evidence
[14]. When MG occurs with a thymoma, MG is a paraneoplastic
for the involvement of Th1 and Th2 cells. Scand J Immunol.
disease caused by the presence of a thymoma. MG with thymoma
1998; 47: 76-81.
accounts for approximately 15% of all MG cases [15]. The
immune response against an epitope expressed in thymoma cells 9. Padua L, Stalberg E, Lo Monaco M, et al. SFEMG in ocular
spreads to components of the neuromuscular junction that share myasthenia gravis diagnosis. Clin Neurophysiol. 2000; 111:
the same epitope [16]. Therefore, thymoma is a tumor with a 1203-1207.
very high risk for the development of MG. In the 1970s, Ekstedt 10. Padua L, Caliandro P, Di Iasi G, et al. Reliability of SFEMG
and Stalberg [17,18] introduced SFEMG as an important method in diagnosing myasthenia gravis sensitivity and specificity
for evaluating neuromuscular conduction defects. Since then, its calculated on 100 prospective cases. Clin Neurophysiol.
diagnostic value in MG has been evaluated in many studies in both 2014; 125: 1270-1273.
extraocular muscles and extremity muscles [19-21]. Therefore, 11. Moore HJ, Woods EL. Myasthenia gravis-associated
SFEMG has a very high sensitivity in detecting neuromuscular antibodies in asymptomatic thymoma. J Thorac Cardiovasc
conduction disorder in MG. Based on this information, in our Surg. 1985; 89: 308-310.
study, we investigated whether SFEMG could detect subclinical 12. Meriggioli MN, Sanders DB. Muscle autoantibodies in
involvements in patients with thymoma but no MG symptoms. myasthenia gravis beyond diagnosis Expert Rev Clin
There was no study on this subject in the literature. In our study, Immunol. 2012; 8: 427-438.
the high mean, minimum, maximum jitter and MCD values in
13. Amdahl C, Alseth EH, Gilhus NE, et al. Polygenic disease
patients with thymoma supported the existence of subclinical
associations in thymomatous myasthenia gravis. Arc Neurol.
neuromuscular junction dysfunction, although MG did not develop
2007; 64: 1729-1733.
in patients with thymoma. SFEMG abnormalities studied from the
extremity muscles of patients with pure ocular MG, previously 14. Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis.
reported in the literature, also support this hypothesis [9,10,22,23]. Lancet. 2001; 357: 2122-2128.
15. Romi F, Skeie GO, Aarli JA, et al. Muscle autoantibodies in
Our study is important because it is the first study to show subgroups of myasthenia gravis patients. J Neurol. 2000; 247:
subclinical neuromuscular conduction abnormalities in patients 369-375.
Neurol Res Surg, 2024 Volume 7 | Issue 2 | 3 of 4
16. Albert ML, Darnell RB. Paraneoplastic neurological 21. Rivero A, Crovetto L, Lopez L, et al. Single fiber
degenerations keys to tumour immunity. Nat Rev Cancer. electromyography of extraocular muscles: A sensitive method
2004; 4: 36-44. for the diagnosis of ocular myasthenia gravis. Muscle Nerve.
17. Ekstedt J, Stalberg E. Single fibre electromyography for the 1995; 18: 943-947.
study of the microphysiology of the human muscle. New 22. Cui LY, Guan YZ, Wang H, et al. Single fiber electromyography
Devel in Electro Clini Neuro. 1973; 1: 89-112. in the diagnosis of ocular myasthenia gravis report of 90 cases.
18. Trontelj JV, Stålberg E. Single fiber electromyography in Chin Med J. 2004; 117: 848-851.
studies of neuromuscular function. Adv Exp Med Biol. 1995; 23. Rostedt A, Saders LL, Edards LJ, et al. Predictive value of
384: 109-119. single fiber electromyography in the extensor digitorum
19. Rouseev R, Ashby P, Basinski A, et al. Single fiber EMG communis muscle of patients with ocular myasthenia gravis
in the frontalis muscle in ocular myasthenia Specificity and a retrospective study. J Clin Neuromuscul Dis. 2000; 2: 6-9.
sensitivity. Muscle Nerve. 1992; 15: 399-403.
20. Ukachoke C, Ashby P, Basinski A, et al. Usefulness of single
fiber EMG for distinguishing neuromuscular from other
causes of ocular muscle weakness. Can J Neurol Sci. 1994;
21:125-128.

© 2024 Vural Gonul, et.al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

Neurol Res Surg, 2024 Volume 7 | Issue 2 | 4 of 4