Comparison of clinical and biochemical parameters of patients with Guillain-Barré syndrome and Myasthenia gravis: A retrospective single center experience

Introduction: Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are common neurological autoimmune diseases. In this study, we aimed to compare the patients’ complaints, clinical course, and laboratory parameters of both diseases. Methods: This study was carried out as a retrospective file scan. The study covers the dates between April 1, 2017, and April 20, 2020. The GBS and MG patients were compared in terms of sociodemographic characteristics, application complaints, clinical course, laboratory findings, treatments, and outcomes. Results: In this study, 51 patients from both groups were included. The mean age of GBS and MG patients was 52.1 ± 19.4 and 43.6 ± 15.8 years, respectively. Respiratory involvement of the patients was 23.5% in GBS and 17.6% in MG. When the treatments of the patients were compared, it was observed that 78.4% of GBS patients and 98% of MG received intravenous immunoglobulin (IVIG) treatments. Only two patients from GBS group were found to be excluded. When the laboratory results were compared, it was found that lactate, vitamin D, transferrin, and total iron binding capacity results were lower in GBS patients, whereas, vitamin B12 and ferritin results were lower in MG patients and this difference was statistically significant

to GBS patients, are weakness in the hands and feet and inability to walk. However, proximal muscle weakness is more prominent in MG patients. Electrophysiological examination has an important role in the diagnosis of both diseases and rapid diagnosis should be made. 6,9 In the treatment, intravenous immunoglobulin (IVIG) and plasmapheresis should be started as soon as possible supportive therapy should be applied concomitantly. 2,6,10 The most common cause of mortality in both diseases is respiratory failure. 1 In this study, we aimed to compare the arrival complaints, clinical course, and laboratory parameters of GBS and MG patients.

Study design and adjustment
This study retrospectively analyzed the sociodemographic data, application complaints, laboratory results, clinical course, and treatments of GBS and MG patients from the electronic data system of a university affiliated hospital between April 1, 2017, and April 20, 2020. This study was done in a third level university hospital.

Patient selection
Patients diagnosed with "Guillain-Barre syndrome (G61.0)" and Myasthenia gravis (G70.0) with International Disease Classification (ICD) diagnostic codes were screened from the hospital electronic data system. In the hospital data system, patients diagnosed with GBS and MG were examined and patients with suspected and undiagnosed definitions were excluded from the study. Patients older than 18 years old and without diabetes were included in the study. Patients under 18 years of age, druginduced polyneuropathy, radiation, and chemotherapeutic and diabetic polyneuropathy were excluded from the study.
Within the scope of our study, in the last 3 years, newly diagnosed and hospitalized GBS patients in our hospital were screened and 51 patients were identified in accordance with the study criteria. Furthermore, 51 MG patients, whether newly diagnosed or admitted to the hospital for acute flame attack in the last 3 years were included in our study by randomization method. The laboratory findings for all patients were included and analyzed by checking the test results taken bloods in the first hospital visits.
The demographic data of the patients, complaints of application, predisposing factors, physical examination, laboratory and electroneuromyography (EMG) findings, clinical course, treatments, and ventilation needs were evaluated and compared in terms of morbidity and mortality.

Evaluation of variables
The history of upper and lower respiratory tract infection, acute gastroenteritis, and previous surgery were examined from the electronic files of the patients with GBS diagnosis.
Possible pathogens and biochemical parameters were recorded from patient files. The treatments of the patients were evaluated only for IVIG and plasmapheresis. Other symptomatic and specific treatments were ignored.
EMG studies of the patients were taken according to standard EMG technique with Nihon Kohden Neuropack MEB-9102 and Dantec ™ Keypoint® G4 EMG devices. EMG results of the patients were obtained by scanning from the hospital EMG archive. EMG examinations of all patients consisted of four motor nerves (median, ulnar, peroneal, and tibial), two sensory nerves, (ulnar and sural) and two F waves (ulnar and tibial). According to EMG results, GBS subtype definition was made.

Statistical analysis
In our study, statistical analyses were performed using IBM SPSS 25.0 package program. Kolmogorov-Smirnov test was used for normal distribution assessment. Categorical data were presented as frequency and percentage, mean and standard deviation was given if data is normally distributed, median and interquartile ranges (IQR) if it is not normally distributed.
In the statistical analyses, Student t test was used when the two groups are normally distributed, if the distribution is not normal, Mann-Whitney U test was chosen. When the compared group is three or more and it is normally distributed, one way ANOVA variance test was used, whereas, if the distribution is not normal, Kruskal Wallis variance test was used. The statistical significance of the study was taken as P < 0.05.

Results
The data of 51 patients from both groups were evaluated for the study. The mean age of the GBS group was 52.1 ± 19.4 years and 56.9% (n = 29) of the patients were women. The mean age of the MG group was 43.6 ± 15.8 years and 66.7% (n = 34) of the patients were women (Table 1).
When these data were evaluated, it was found that GBS patients were older, more hospitalized, more intubated, and these conditions were statistically significant compared to MG patients (P < 0.05). It was found that female gender, respiratory and bulbar involvement, discharge from hospital and excitus were not statistically significant in both groups (P > 0.05).
When predisposing factors are investigated in GBS patients; pre-determined disease rates of patients with upper respiratory tract infection, lower respiratory tract infection, acute gastroenteritis, surgical operation and Hashimoto thyroiditis, were 27.5%; 13.7%; 9.8%; 9.8% and 3.9%, respectively. No predisposing factor was found in 35.3% of the patients (Figure 1).
The diagnoses of GBS patients according to EMG examinations; acute inflammatory demyelinating polyradiculoneuropathy, acute motor and sensory axonal neuropathy, acute motor axonal neuropathy and Miller-Fisher syndrome were found to be 41.2%; 39.2%; 15.7% and 3.9%, respectively ( Figure 2).
Hospital admission complaints of both patient groups were examined in Table 2. Accordingly, 80.4% (n=41) of GBS patients had weakness in the feet, 17.7% (n=9) had gait disturbance, and one patient (2%) complained of double vision. MG patients were most frequently referred to the hospital with the complaint of weakness in the arms and legs (56.9%). When comparing the most frequent hospital admission complaints of GBS and MG patients, GBS patients complained of weakness and inability to walk, whereas MG patients presented with complaints of weakness in the eyelid and bulbar complaints, and this was statistically significant (P < 0.05).
The comparisons of patients' laboratory test results are given in Table 3. The attained results show that lactate, vitamin D, transferrin and total iron binding capacity (TIBC) test values were lower in GBS patients; whereas, vitamin B12 and ferritin values were lower in MG patients and these differences were statistically significant (P < 0.05). It was determined that there were no statistically significant differences in other tests such as serum electrolytes, CRP, procalcitonin, folate and TSH values (P >0.05).

Discussion
In this study, general characteristics and the laboratory test results of the patients with GBS and MG diseases were compared. Although their etiology and pathogenesis are different, these diseases should be considered in the differential diagnosis, since patients are presented with similar symptoms. As a result of our study, it was revealed that both diseases show similar features in some aspects and differ in other aspects.
As a result of this study, GBS and MG patients were differed significantly from each other in terms of the patients age, deep tendon reflex, low eyelid complaints, the level of vitamin D, Vitamin B12, lactate, ferritin, and transferrin were significantly differed in assay results (P <0.05).
Similar points of both patient groups that we detected in our study were female gender, respiratory and  In our study, vitamin D levels were found at lower rates in both GBS and MG patients. In the literature, a study comparing vitamin D levels of MG patients and healthy control group, a significant decrease in the vitamin D was found in MG patients similar to our study. 13 In a study investigating immune-dependent peripheral neuropathies and vitamin D levels, vitamin D levels were found to be significantly low. 14,15 In an another study comparing vitamin D levels between GBS and MG patients conducted   There are no studies comparing the vitamin B12 levels in GBS and MG patients in the literature. Vitamin B12 deficiency should be kept in mind in differential diagnosis of GBS. 6,11 Muscle weaknesses due to the vitamin B12 deficiency can occur in gastrointestinal system disorders and therefore, it can be confused with both diseases. 12 In our study, although normal levels of the vitamin B12 were determined in both patient groups (the normal level of homocysteine in both groups supports this situation), on a small number of patients, it was found that a lower vitamin D was found in GBS patients, which was similar to our results. 16 However, interestingly, they found that there were high vitamin D levels in MG patients compared to the healthy group. Vitamin D levels in our study were found to be quite low in both GBS and MG patients compared to this study.
In our study, ferritin, transferrin, and TIBC assays of GBS and MG patients were compared for the first time in the literature. Ferritin levels were higher in patients with GBS, while transferrin and TIBC tests were lower than the MG patients. Since ferritin is a positive acute phase reactant and GBS has an acute inflammatory pathogenesis, it was evaluated that ferritin was found to be meaningfully higher. However, since the CRP and procalcitonin assays are both acute markers of infection but they were not statistically differed between these groups, the usability of the ferritin test in the differential diagnosis of GBS becomes more apparent.
Mortality in neuromuscular diseases generally depends on the respiratory involvements. Respiratory and blood gas parameters should be closely monitored in these patients. 2 In respiratory involvements, blood lactate level due to hypoxia increases. 17 In our study, the lactate levels of GBS and MG patients were compared for the first time in the literature, and it was found that MG patients had statistically higher blood lactate levels. Although respiratory involvement and intubation rates were lower in MG patients, it was concluded that respiratory functions should be closely monitored in the follow-up of MG patients, due to the relationship of blood lactate levels with body oxygenation.
In a study by Vellipuram et al, it was found that there was a higher need for intubation in MG patients. 2 However, in our study, it was found that the need for intubation was higher in GBS patients than MG, which was an interesting result and should be linked with the timing of the treatments.
Studies have shown that IVIG follows plasmapheresis treatment has no advantage over IVIG alone or plasmapheresis only. 18 In the treatments, IVIG and plasmapheresis and supportive treatment should be started as soon as possible before irreversible nerve damage occurs. Although plasmapheresis is cheaper, IVIG treatment is preferred by most centers because it is more accessible, easier to apply and has fewer side effects. 6,18,19 In our study, it was observed that the majority of patients were given IVIG treatment.

Limitations
Our study had some limitations. First of all, our study was a retrospective study and patients in the last 3 years were included in the study using ICD codes. Since 51 GBS patients were detected in the last 3 years, 51 MG patients were selected by a randomization method. Therefore, the number of patients included in the study was partially small. The second limitation was that patients' treatments were compared only in terms of IVIG and plasmapheresis. Other treatments were not included in the study because they differed between the groups. Another point is that since the study is retrospective, not all assay results were available in all patients, and some comparative assay data have been made in relatively few patients, since these missing assays cannot be compensated.

Conclusion
The clinical presentation of GBS and MG patients are heterogeneous and the prognosis can vary significantly among patients. In differential diagnosis, both diseases can be confused with each other. In scope of this, the general features and laboratory findings of GBS and MG patients were compared, and similar and different aspects of these two patient groups were revealed in our study. It was concluded that detailed anamnesis and laboratory analyzes are necessary and useful for the differential diagnosis of these two diseases.