Srovnávací studie pa­cientů s myastenií České a Slovenské republiky

A comparative study of myasthenic patients in the Czech and Slovak Republics

Aim: Exist­­ing epidemiological studies of myasthenia feature dif­ferences in incidence, prevalence, age- and gender-specific incidences, mortality rate, and even the prevalence of myasthenia subtypes. The aim of this study was to compare the over­all management of patients with myasthenia, the severity of the dis­ease, and a number of clinical and laboratory characteristics and ther­apy approaches amongst patients in the Czech Republic and the Slovak Republic.

Patients and methods: Data were retrospectively col­lected from two registries in the Czech Republic (Brno) and the Slovak Republic (Bratislava). Data were randomly matched by age of onset of myasthenia and gender. The result­­ing groups consisted of 152 patients each.

Results: There was almost no significant dif­ference between the matched groups. The clinical form, positivity of antibodies to acetylcholine receptor, Myasthenia Gravis Composite Score, time to dia­gnosis, and percentage of thymomas and thymectomy were not significantly dif­ferent. There were significant dif­ferences only in the occur­rence of limb weakness at the onset of dis­ease and in the choice of treatment modality.

Conclusions: Our data suggest that at least part of previously observed heterogeneity between populations might be based on dif­ferent age and gender distribution.


myasthenia gravis – population characteristics – comparison – registries

Autoři: M. Horáková 1;  I. Martinka 2;  S. Voháňka 3;  P. Špalek 2;  J. Bednařík 3
Vyšlo v časopise: Cesk Slov Neurol N 2019; 82(2): 171-175
Kategorie: Původní práce
doi: 10.14735/amcsnn2019171


Cíl: Stávající epidemiologické studie vykazují rozdíly v incidenci, prevalenci, incidenci specifické dle věku a pohlaví pacientů, mortalitě, a dokonce i v prevalenci jednotlivých subtypů myastenie. Cílem této studie bylo porovnat celkovou péči o pacienty s myastenií, závažnost onemocnění, celou řadu klinických a laboratorních charakteristik a terapeutický přístup mezi pacienty v České a Slovenské republice.

Soubor a metody: Data byla hodnocena retrospektivně ze dvou registrů v České republice (Brno) a Slovenské republice (Bratislava). Pacienti byly náhodně spárováni dle pohlaví a věku v době prvních příznaků myastenie. Výsledné skupiny sestávaly ze 152 pacientů.

Výsledky: Mezi spárovanými skupinami nebyl téměř žádný signifikantní rozdíl. Klinická forma, pozitivita protilátek proti acetylcholinovým receptorům, Myasthenia Gravis Composite skóre, doba do stanovení diagnózy, procentuální zastoupení tymomů a tymektomie se významně nelišily. Významný rozdíl byl ale ve zvolené terapii a také v zastoupení oslabení končetin v úvodu onemocnění.

Závěr: Naše výsledky svědčí pro fakt, že alespoň část dříve pozorované heterogenity mezi skupinami pacientů s myastenií může být vysvětlena rozdílným zastoupením mužů a žen a různou věkovou distribucí.

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Klíčová slova:

myastenie – charakteristiky populace – srovnání – registry


Myasthenia gravis (MG) is a typical autoim­mune disorder, since the pathogenic role of auto-reactive antibodies is evident. Detection of muscle-bind­­ing antibodies in patients’ sera [1] led to the autoim­mune theory of MG in the early 1960s [2]. Further studies described antibodies to several compounds derived from muscle membrane [3] that led to symp­toms typical of MG if pas­sively transfer­red to mice, notably acetylcholine receptor (AChR) and muscle specific kinase (MuSK). [4,5]. Thus, the pathogenesis of MG is clear.

Nevertheles­s, the trigger­­ing factors and the natural course of the dis­ease remain to be elucidated. As the monozygotic twin concordance rate in MG is 35.5% [6], it is certain that genetics plays at least a partial role. Nevertheles­s, the remain­­ing percentage leaves options open for other factors, such as the environment. Accord­­ing to one systematic review, the incidence and prevalence rates vary greatly depend­­ing on where the study took place. The incidence rate ranges from 1.7 to 21.3 cases per mil person-years and the prevalence rate ranges from 15 to 179 per mil [7]. The reason for this marked heterogeneity remains unclear. As dif­ferent populations have variable access to neurological healthcare, the numbers may by slightly biased by under-dia­gnosis. However, genetic and environmental factors are very likely to play key roles.

Epidemiological studies revealed still more dif­ferences. In European countries, the dis­ease af­fects mainly adults, while child-onset MG (at under 14 years old) accounts for almost 45% of the MG population in China [8]. Even in European countries, age- and gender-specific incidences are significantly dif­ferent between populations [7]. Although detailed population-based data on serological subtypes of MG are lacking, the prevalence of MG subtypes does not cor­relate with over­all prevalence. Accord­­ing to unpublished data from Prof. Vincent of Oxford University in the United Kingdom, the reported number of MuSK-MG patients indicates a north-south decline in Europe [9]. Published data on ther­apy approach and severity expres­sed by specific outcome mea­sures across dif­ferent populations are scarce, but the mortality rates (defined as MG-related deaths) range from 0.06 to 0.89 per mil person-years [7].

The aim of this study was to compare the over­all management of patients with MG, the severity of the dis­ease, and a number of clinical and laboratory characteristics and ther­apy approaches in the Czech and Slovak Republics. The Czech and Slovak Republics are neighbour­­ing countries in central Europe that once constituted a single federal republic, known as Czechoslovakia, until 1993. Even though each country has a separate healthcare system now, they share similar systems of compulsory general healthcare insurance, largely acces­sible to the general population.

Patients and methods

Data were retrospectively col­lected from two registries in the Czech Republic (Brno, a regional capital city) and the Slovak Republic (Bratislava, the national capital city). The Slovak registry is nationwide (from a state with 5.4 mil inhabitants [10]), and data have been col­lected since 1977 [11]. The registry in Brno is more local, gather­­ing data from the south-eastern part of the Czech Republic (a region with 1.2 mil inhabitants [12]) since 2001. The fol­low­­ing characteristics were retrieved from visits dur­­ing the January– December 2016 period: age of onset, gender, clinical form, Myasthenia Gravis Composite (MGC) score at the last visit, Myasthenia Gravis Foundation of America (MGFA) clas­sification at the maximum severity of the dis­ease, first symp­toms refer­red to neurologist, time to dia­gnosis, AChR antibody positivity, history of thymoma, thymectomy, thyreopathy, and modality of treatment at the last visit. The drugs were grouped into cholinesterase inhibitors (ChEI), cortico­steroids, azathioprin, ciclosporin, and other im­munosuppres­sants (cyclophosphamide, mycophenolate mofetil). The term “early--onset MG” was defined as that occur­r­­ing at the age under 50 years at first manifestation. All patients who had visited in the period of January– December 2016 were included. The criteria were fulfil­led by 189 patients from Brno and 508 from Bratislava.

Patients from each group dif­fered significantly both in age of onset and gender. Therefore, the data were randomly matched by age of onset and gender to enable comparison of all characteristics. The result­­ing groups consisted of 152 patients each. In consideration of the lack of data normality, the Man­n-Whitney U test was employed to compare dif­ferences in continuous variables. Fisher’s exact test or Pearson chi-squared test (χ2) was used to compare categorical variables. Statistical­ly significance was set at P < 0.05. Bonfer­roni cor­rection for multiple test­­ing was used as required. Data analysis was performed us­­ing IBM-SPSS software (Version 22, SPSS Inc., Chicago, IL, USA) and Statistica (Version 12, StatSoft Inc., Tulsa, OK, USA).


The basic characteristics of the two groups appear in Tab. 1. There was a statistical­ly significant dif­ference between groups in both age of onset (P = 0.001) and gender (P = 0.008), as appears in Fig. 1 A, B. As above, data were then matched by age of onset and gender to enable comparison of all characteristics. Both groups consisted of 152 patients, of whom 44.7% were female. The average age of onset was 57 years in both groups.

Distribution of age of onset (in years) in the Czech Republic (A) and the Slovak Republic (B).<br>
Obr. 1. Rozdělení podle věku v době nástupu onemocnění (v letech) v České republice (A) a ve Slovenské republice (B).
Obr. 1. Distribution of age of onset (in years) in the Czech Republic (A) and the Slovak Republic (B).
Obr. 1. Rozdělení podle věku v době nástupu onemocnění (v letech) v České republice (A) a ve Slovenské republice (B).

Tab. 1. Basic characteristics of Czech and Slovak groups (unmatched data).
Basic characteristics of Czech and Slovak groups (unmatched data).
AChR – acetylcholine receptor; CI – confidence interval; n – number

Clinical characteristics

There was almost no significant dif­ference in clinical characteristics between the two groups (Tab. 2), apart from initial occur­rence of limb weaknes­s, the proportion of which was higher in the Slovak group. The most com­mon initial symp­toms in both groups were diplopia and ptosis (ocular). Furthermore, the ocular symp­toms were the only ones present in more than half the patients at the onset of dis­ease; however, only about a quarter of patients sustained with pure ocular form. Half the patients with initial­ly pure ocular symp­toms, therefore, developed generalized MG. Even though the average MGC score was higher in the Slovak group, the proportion of patients without symp­toms (MGC zero) was also higher in the Slovak group.

Tab. 2. Clinical characteristics.
Clinical characteristics.
CI – confidence interval; MGC – Myasthenia Gravis Composite; MGFA – Myasthenia Gravis Foundation of America; n – number

Time to dia­gnosis

In 88.8% of patients from the Czech group and 84.8% of patients from the Slovak group, the dia­gnosis was made within one year of initial manifestation. The mean and median were similar (Tab. 3) and the dif­ference was not statistical­ly significant.

Tab. 3. Time to diagnosis.
Time to diagnosis.

AChR antibodies

Serology of AChR-antibodies is a routine examination support­­ing the dia­gnosis of MG in both countries. Seronegative results appeared in 10.5 and 14.5% of patients in the Czech and Slovak groups respectively, and the dif­ference was not statistical­ly significant. Positivity of AChR-antibodies in both groups increased with age. Whereas 37% of patients in the early-onset group were seronegative, the proportion decreased to 7% in the late-onset group.

Thymoma and thymectomy

Imag­­ing of the mediastinum represents also a routine procedure in both countries. Thymoma was dia­gnosed in approximately 12% of patients in both groups (Tab. 4). Occur­rence of thymoma did not dif­fer with age in the Slovak group (11.6% in early-onset and 12.8% in late-onset), while in the Czech group thymoma was dia­gnosed in 27.9 and 5.5% of early- and late-onset MG, respectively.

Tab. 4. Thymoma and thymectomy.
Thymoma and thymectomy.


Ther­apy approaches dif­fered (Tab. 5). Patients in the Czech group received cortico­steroids more often compared to ChEI and im­munosuppres­sants.

Tab. 5. Therapy.
ChEI – cholinesterase inhibitors


Our data suggest that at least part of the observed heterogeneity between dif­ferent populations [7] may be based on dif­ferent gender and age distributions. As the basic characteristics of both unmatched groups reveal in Tab. 1, some dif­ferences (particularly in age of onset, gender, and seropositivity of AChR) are obvious. Nevertheles­s, after cor­rection for dif­ferences in age and gender, both groups showed very similar clinical and laboratory characteristics. In particular, MGC score and MGFA clas­sification were not significantly dif­ferent.

The fact that the MGC score was used uniformly in both groups lends weight to this study. It describes the actual severity of symp­toms and thus reflects the patient care and enables more comprehensive comparisons.

As there were only few dif­ferences even in matched groups, they should be mentioned. Patients from the Slovak group presented more often with limb weakness among the first symp­toms. The reason for this distinction is unclear. As limb weakness in elderly patients might be caused by other comorbidities (spinal and intervertebral disc dis­eases, polyneuropathy, ischemia, obesity, etc.), such weakness could have been attributed to other causes in the Czech group and not recorded as an MG symp­tom. Another pos­sible explanation, later dia­gnosis in the Slovak group with more pronounced symp­toms, is not supported by the almost identical time to dia­gnosis. While there was no dif­ference in the total number of patients with histories of thymoma, there was a clearly higher percentage of thymoma in early-onset myasthenia in the Czech group. This find­­ing is not in agreement with published studies [13,14]. In general, MRI was used as a mediastinal imag­­ing modality in the Czech group, while contrast CT was used in the Slovak group. As the sensitivity of MRI and contrast CT is similar for detect­­ing thymoma, the dif­ference in early-onset thymoma is not explained and the reason for it remains unclear. Nevertheles­s, the imag­­ing method used might partly explain the higher percentage of hyperplasia in the Czech group, for which MRI is more accurate [15].

Even though there was a clear dif­ference in the choice of treatment modality (Tab. 5), the MGC score in both groups was similar. Therefore, it seems that particular drug choice is probably based on local practice or insurance coverage and does not af­fect therapeutic response. As more than half the patients were without symp­toms at the last visit and the median time to dia­gnosis was under three months, patient care in both countries appears to be excel­lent.

Our study has a number of limitations. First, the registry in the Czech Republic is not nationwide, since it covers only a part of the country that is not strictly defined (approximately 1.2 mil of 10.6 mil out inhabi­tants [12]). Further, as only patients who had visited in the defined period were included, the entire MG population in the Slovak Republic was not covered. This rendered it impos­sible to calculate and compare prevalence in the two countries. Also, a partial explanation of the observed dif­ferences in age and gender may be found in the fact that some patients in a given area were refer­red to other Czech neuromuscular centres, and dia­gnosed and treated in them.


We report a comparative study of two MG groups from central Europe. Both groups dif­fered significantly both in age of onset and gender. Nevertheles­s, the groups were very similar after cor­rection for these factors. The heterogeneity among MG populations is certainly largely due to genetic and environmental factors, but our study suggests that some of this heterogeneity might be explained by dif­ferent age and gender distributions. This should be taken to account when compar­­ing MG populations.

This publication was written at Masaryk University as a part of the MYO project, ref. MUNI/ A/ 2017, with the support of a Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2017.

Further support was obtained from the Institutional Support of the Ministry of Health, ref. RVO FNBr - 65269705. None of the fund­­ing organizations or sponsors was involved in the design and conduct of the study, or the col­lection, management analysis and interpretation of the data. Tony Long (Svinošice) helped with English style cor­rections.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.

Accepted for review: 12. 12. 2018

Accepted for print: 25. 2. 2019

MUDr. Magda Horáková

Department of Neurology

Faculty of Medicine

Masaryk University

University Hospital

Jihlavská 20 625 00 Brno

Czech Republic



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Dětská neurologie Neurochirurgie Neurologie

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 2

2019 Číslo 2

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