|Year : 2020 | Volume
| Issue : 3 | Page : 1077-1081
Predictors of response to plasmapheresis in patients with myasthenia gravis
Wafik M El-Sheikh1, Mohammed A Okda1, Rasha A El-Kabany1, Aktham I Al-Emam1, Ibraheim Al-Ahmer1, Hany Taher2
1 Department of Neuropsychiatry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Neuropsychiatry, Nasser Institute for Research Hospital, Cario, Egypt
|Date of Submission||02-Mar-2019|
|Date of Decision||18-Apr-2019|
|Date of Acceptance||26-Apr-2019|
|Date of Web Publication||30-Sep-2020|
Department of Neurology, Nasser Institute for Research Hospital, Cario
Source of Support: None, Conflict of Interest: None
To measure the clinical responses, after plasmapheresis, in patients with moderate to severe degree of myasthenia gravis (MG), then correlate these responses with the initial clinical picture, acetylcholine receptor antibodies (AChR-Ab) level, and thymus gland changes.
Plasmapheresis is used for acute management of MG exacerbations and when rapid clinical responses are needed. It is effective in reducing the quantitative myasthenia gravis (QMG) score for disease severity in patients with moderate to severe MG. However, little is known about factors that predict response to plasmapheresis, and knowing these clinical factors may help in giving information to clinicians about patient outcome after plasmapheresis.
Patients and methods
A total of 81 patients participated in this study. They had full clinical examination primarily on the first date of plasmapheresis and after 1 month (14 days after finishing plasmapheresis). Disease severity was determined according to QMG scale.
The scores of QMG scales had significantly improved two weeks after plasmapheresis. The improvement in QMG scores had a good correlation with initial severity, presence of AChR-Ab and their levels, thymectomy, and thymus gland pathology.
Initial severity, presence of AChR-Ab, and thymectomy are good predictors of improvement after plasmapheresis in patients with MG.
Keywords: myasthenia gravis, plasmapheresis, quantitative myasthenia gravis score
|How to cite this article:|
El-Sheikh WM, Okda MA, El-Kabany RA, Al-Emam AI, Al-Ahmer I, Taher H. Predictors of response to plasmapheresis in patients with myasthenia gravis. Menoufia Med J 2020;33:1077-81
|How to cite this URL:|
El-Sheikh WM, Okda MA, El-Kabany RA, Al-Emam AI, Al-Ahmer I, Taher H. Predictors of response to plasmapheresis in patients with myasthenia gravis. Menoufia Med J [serial online] 2020 [cited 2020 Oct 22];33:1077-81. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/1077/296710
| Introduction|| |
Myasthenia gravis (MG) is characterized by fluctuating muscle weakness and fatigability, with great interindividual variability ,,. Owing its fluctuating course and clinical heterogeneity, many approaches to evaluate the clinical profile and treatment outcomes had been discussed .
Many variables may affect patients with MG such as (a) age at onset and disease duration, (b) presence of acetylcholine receptor antibodies (AChR-Ab) and its titer, and (c) thymectomy and thymus gland pathology.
Therapeutic plasmapheresis is almost a safe and effective adjuvant treatment for several diseases especially autoimmune diseases, like MG, and achieves immediate improvement of MG symptoms .
The aim of this study was to measure the clinical responses, after plasmapheresis, in patients with moderate to severe degree of the disease, and then correlate these responses with the initial clinical picture, AChR-Ab level, and thymus gland changes.
| Patients and Methods|| |
The current study is a prospective study, in which 98 patients were included, diagnosed as having moderate to severe MG, from September 2016 to July 2018, aged from 18 to 60 years old, recruited from Menoufia University Hospital, Neurology Department in Nasser Institute Hospital and outpatient clinics in these hospitals. The protocol was approved by the ethical committee of the Menoufia medical school and an informed written consent was obtained from the participants.
Patients with MG should fulfill at least two of the following four diagnostic criteria: (a) clinical manifestations of MG, (b) positive AChR-Ab, (c) positive response to anticholinesterases, and (d) abnormal neurophysiological findings.
Patients were divided into two groups: the first group had patients with moderate to severe MG who were admitted for a worsening of the disease (81 patients) and received plasmapheresis sets (five plasmapheresis procedures, performed every second day). The other group (control group) comprised patients with moderate to severe MG who had monthly follow-up schedule in outpatient clinic (17 patients) and did not receive plasmapheresis sets and were only on medical treatment.
All patients underwent history taking to determine the presence of any of the exclusion criteria, such as (a) drug-induced myasthenia-like syndromes and (b) patients who are contraindicated to plasmapheresis, for example, presence of a hemorrhage or surgical bleeding, tumors, acute inflammatory and infectious processes, extreme degree of heart failure, and significant hypotension.
Full clinical examination was done primarily in the first interview, in the two groups, and repeated after 1 month (14 days after finishing plasmapheresis). Disease severity was determined according to quantitative myasthenia gravis (QMG) scale (patient group who had plasmapheresis, and the other group who underwent follow-up without plasmapheresis).
All patients underwent neurophysiological evaluation in the form of repetitive nerve stimulation (RNS). RNS was considered abnormal when a 'decremental pattern' was observed. When RNS gave normal results, single-fiber electromyography was performed on orbicularis oculi (four cases). In all cases, EMG was performed on proximal muscles of the limbs (deltoid, biceps brachii, and rectus femoris) to exclude myopathy.
All patients prepared to undergo plasmapheresis were investigated for AChR-Ab and computed tomography of the mediastinum.
Before plasmapheresis sets, a comprehensive explanation of both clinical efficacy and adverse effects of plasmapheresis was provided for ethical consideration, and to reduce the patients' anxiety to this procedure.
Central venous access was performed using a temporary dual-lumen catheter (Mahukar).
Each patient received up to five plasmapheresis procedures. Plasmapheresis volumes of one plasma volume per procedure were used. Five percent albumin or fresh frozen plasma used as replacement fluids.
Data were collected, revised, coded, and entered to the Statistical Package for the Social Science (IBM Corp., Armonk, New York, USA), version 23. The quantitative data were presented as mean, SDs, and ranges when their distribution was found to be parametric and median with interquartile range for nonparametric. The comparison between two independent groups with quantitative data and parametric distribution was done by using independent t test, whereas with nonparametric data was done by using Mann–Whitney test.
The local ethics committee approved this study.
| Results|| |
A total of 98 patients were enrolled in this case–control study. The patient group that underwent plasmapheresis (81 patients) had 58 (71.6%) females and 23 (28.4%) males. Their age ranged from 18 to 60 years (mean, 35.69 ± 12.46 years), and the duration of illness ranged from 12 to 96 months (mean, 36.59 ± 20.18 months). However, the control group (17 patients) had 10 (58.8%) females and seven (41.2%) males. Their age ranged from 18 to 60 years (mean, 35.29 ± 11.65 years), and the duration of illness ranged from 18 to 80 months (mean, 42.47 ± 18.19 months).
We found no significant differences (P = 0.125) between the initial QMG scores in both groups, with high significant QMG score changes (P < 0.001) after 1 month between both groups, as median change was − 26.67 (percentage of improvement of 26.67%) in the patient group, whereas the median change was 8 (percentage of worsening of 8%) in the control group [Table 1].
|Table 1: Comparison between control group and patients group regarding quantitative myasthenia gravis score at initial and after 1 month and with respect to percentage of quantitative myasthenia gravis changes|
Click here to view
The coefficient correlation (r) was 0.103 between the age of the studied patients and the initial QMG score, 0.402 with QMG score after 1 month, and 0.330 with QMG changes, with highly significant QMG score changes (P = 0.003).
The coefficient correlation (r) was 0.127 between duration of disease of the studied patients and the initial QMG score, 0.425 with QMG score after 1 month, and 0.270 with QMG changes, with significant QMG changes (P = 0.015).
In the patient group, 16 (19.8%) patients did not have AChR-Abs, whereas 65 (80.2%) patients had AChR-Abs in their serum, with AChR-Ab titer ranging from 4.6 to 80.6 (median, 13.4). However, in the control group, three (17.6%) patients did not have AChR-Abs, whereas 14 (82.4%) patients had AChR-Abs in their serum, with AChR-Ab titer ranging from 4.3 to 16.3 (median, 8).
On observing the relation of QMG with the presence of AChR-Abs, Z test showed (Z = −8.59 and P < 0.0001) more significant changes after plasmapheresis in antibodies-positive group, with median QMG improvement in antibodies-negative group was 14.86% and 32% in antibodies-positive group [Table 2].
|Table 2: The relation between acetylcholine receptor antibodies of the studied patients and initial quantitative myasthenia gravis scores, quantitative myasthenia gravis scores after 1 month, and percentage of quantitative myasthenia gravis changes|
Click here to view
The coefficient correlation (r) was 0.371 between AChR-Ab titer of the studied patients and the initial QMG score, −0.155 with QMG score after 1 month, and − 0.306 with QMG changes, with high significant relation between AChR-Ab titer and QMG changes (P = 0.006).
In the patient group, 52 (64.2%) patients had thymectomy (thymectomy-positive group), and their thymus pathology was normal in 31 (59.6%) patients, thymic hyperplasia was seen in 15 (38.8%) patients, and six patients had thymoma (11.6%). However, in the control group, 10 (58.8%) patients had thymectomy, and their thymus pathology was normal in five (50%) patients, thymic hyperplasia was seen in five (50%) patients, and no patients had thymoma.
The mean initial QMG score was 23.34 in thymectomy-negative group, and 26.92 in thymectomy-positive group, with median percentage of QMG change of −19.23% in thymectomy-negative group and −32.07% in thymectomy-positive group [Table 3].
|Table 3: The relation between thymectomy of the studied patients and initial quantitative myasthenia gravis scores, quantitative myasthenia gravis scores after 1 month, and percentage of quantitative myasthenia gravis changes|
Click here to view
Regarding thymus gland pathology, the mean initial QMG score was 25.10 in normal thymus patients, 28.87 in patients with thymus hyperplasia, and 31.50 in patients with thymoma, with median percentage of improvement of QMG change was 34.62% in normal thymus patients, 31.25% in patients with thymus hyperplasia, and 15.08% in patients with thymoma [Table 4].
|Table 4: The relation between thymus gland pathology of the studied patients and quantitative myasthenia gravis scores|
Click here to view
| Discussion|| |
Plasmapheresis is widely used in the treatment of MG, as it removes pathogenic antibodies, and results in short-term improvement of MG . However, despite the increasing availability of immunomodulatory treatments, little is known about factors predicting response to plasmapheresis .
In our study, regarding the demographic distribution, no significant changes were observed between the two groups regarding male to female ratio, which is similar to previous studies ,.
We found that younger patients had better improvement after plasmapheresis. This is in contrary to previous studies that analyzed the relation between age and clinical response to plasmapheresis ,,. However, our results are similar to a previous study , which stated that fair responders had a higher percentage of young patients. This improvement may be owing to lack of comorbid diseases that affect the general condition of the patients.
We found that the duration of the disease had no significant correlation with the initial QMG, but patients with shorter duration of the disease have significant improvement in QMG score after plasmapheresis. These results are similar to previous two studies ,. This may be owing to patients with short disease duration have less structural affection in AChR at the motor end plate. On the contrary, two studies stated that there was no correlation between the duration of illness and plasmapheresis responsiveness ,.
In our tested group, patients with AChR-Abs had significantly higher initial QMG scores than AChR-Ab negative patients, and elevation of the AChR-Ab titer also highly correlated with the improvement in QMG scores after plasmapheresis (as plasmapheresis produces rapid improvement by temporarily reducing circulating AChR-Abs). Similar results were found during studying the predictors of response to immunomodulation in patients with MG, and it was noted that patients with AChR-Abs were good responders, but the study also noted that the presence of higher titers does not predict better response .
In a recent study, thymic abnormality was found to play a key role in the pathogenesis of MG, and 50–60% of patients with MG have concomitant thymic hyperplasia and 10–20% have thymoma . Recent numerous retrospective studies noted that thymic lymphoid hyperplasia is generally regarded as a more favorable prognostic indicator over thymoma ,,,. On the contrary, several recent studies have shown some differences and found that the patients with thymomatous MG had a much more promising prognosis than those with hyperplastic MG ,,, and also the role of thymectomy in the management of MG is still matter of debate .
We found in this study that patients who had thymectomy operation had significantly higher initial QMG scores compared with the nonthymectomy patients, but also showed significant improvement in QMG in patients with thymectomy compared with nonthymectomy patients. Moreover, regarding thymus pathology in the present study, the initial clinical picture was more severe in patients with thymoma compared with thymic hyperplasia and normal thymus patients, and also associated with significantly less improvement after plasmapheresis. This may be owing to the aggressive nature of thymoma over thymic hyperplasia.
| Conclusion|| |
In our study of clinical changes after plasmapheresis in patients with moderate to severe degree of MG, we found significant improvement in patients' QMG scores in the patient group.
Regarding factors that may predict clinical changes in response to plasmapheresis in MG patients, we found the following:
- The age of the patients was significantly correlated with improvement in QMG scores, as younger patients had better outcome after plasmapheresis
- The patients with shorter duration of the disease have high significant improvement in QMG score after plasmapheresis
- The presence of AChR-Ab had a significant improvement in QMG scores
- The elevation of the AChR-Ab titer is correlated with the improvement in QMG score
- There is significant improvement in QMG in patients with thymectomy compared with nonthymectomy patients
- Patients with thymoma compared with those with thymic hyperplasia and normal thymus patients have significantly less improvement in QMG scores after plasmapheresis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kalb B, Matell G, Pirskanen R, Lambe M. Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden. Neuroepidemiology 2002; 21
Alshekhlee A, Miles JD, Katirji B, Preston DC, Kaminski HJ. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology 2009; 72
Carr AS, Cardwell CR, McCarron PO, McConville J. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol 2010; 18
Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F, et al
. Task force on MG Study Design of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Recommendations for myasthenia gravis clinical trials. Muscle Nerve 2012; 45
Ghonemy TA, Salim EM, Alsayed F, Elokely AM. Outcomes of therapeutic plasma exchange; one year single center experience. Urol Nephrol Open Access J 2016; 3
Zhang L, Liu J, Wang H, Zhao C, Lu J, Xue J, et al
. Double filtration plasmapheresis benefits myasthenia gravis patients through an immunomodulatory action. J Clin Neurosci 2014; 21
Katzberg HD, Barnett C, Bril V. Predictors of response to immunomodulation in patients with myasthenia gravis. Muscle Nerve 2012; 45
El-Medany Y, Hajjar W, Essa M, Al-Kattan K, Hariri Z, Ashour M. Predictors of outcome for myasthenia gravis after thymectomy. Asian Cardiovasc Thorac Ann 2003; 11
Rajesh K, Paul B, Gupta S, Singh G, Kaur A. Therapeutic plasma exchange in the treatment of myasthenia gravis. Indian J Crit Care Med 2015; 19
Mantegazza R, Bruzzone E, Regi B, Peluchetti D, Marconi M, Sirchia G, et al
. Single donor plasma in therapeutic plasma exchange for myasthenia gravis. Int J Artif Organs 1987; 10
Kornfeld P, Fox S, Maier K, Mahjoub M. Ten years' experience with therapeutic apheresis in a community hospital. J Clin Apher 1992; 7
Shibuyna S, Osamem T, Kawanams I. Immunoadsorption therapy for myasthenia gravis. J Neurol Neurosurg Psychiatry 1994; 57
Yeh JH, Chiu HC. Plasmapheresis in myasthenia gravis: a comparative study of daily versus alternately daily schedule. Acta Neurol Scand 1999; 99
DAU PC. Response to plasmapheresis and immunosuppressive drug therapy in sixty myasthenia gravis patients. Ann NY Acad Sci 1981; 377
Fornasari PM, Riva G, Piccolo G, Cosi V, Lombardi M. Short and long-term clinical effects of plasma-exchange in 33 cases of myasthenia gravis. Int J Artif Organs 1985; 8
Zheng Y, Cai YZ, Shi ZY, Qiu Y, Zhang HL, Wang ZH, et al
. Different neurologic outcomes of myasthenia gravis with thymic hyperplasia and thymoma after extended thymectomy: a single center experience. J Neurol Sci 2017; 383
Siwachat S, Tantraworasin A, Lapisatepun W, Ruengorn C, Taioli E, Saeteng S. Comparative clinical outcomes after thymectomy for myasthenia gravis: thoracoscopic versus trans-sternal approach. Asian J Surg 2018; 41
Mao Z, Hu X, Lu Z, Hackett ML. Prognostic factors of remission in myasthenia gravis after thymectomy. Eur J Cardio-Thorac Surg 2014; 48
Yu S, Li F, Chen B, Lin J, Yang M, Fu X, et al
. Eight-year follow-up of patients with myasthenia gravis after thymectomy. Acta Neurol Scand 2015; 131
Marx A, Willcox N, Leite MI, Chuang WY, Schalke B, Nix W, et al
. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 2010; 43
Kim HK, Park MS, Choi YS, Kim K, Shim YM, Han J, et al
. Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma. J Thorac Cardiovasc Surg 2007; 134
Nazarbaghi S, Amiri-Nikpour MR, Mahmodlou R, Arjmand N, Rezaei Y. Clinical outcomes of myasthenia gravis with thymoma and thymic hyperplasia undergoing extended trans-sternal thymectomy: a single-center experience. N Am J Med Sci 2015; 7
Padua L, Evoli A, Aprile I, Caliandro P, Mazza S, Padua R, et al
. Health-related quality of life in patients with myasthenia gravis and the relationship between patient-oriented assessment and conventional measurements. Neurol Sci 2001; 22
[Table 1], [Table 2], [Table 3], [Table 4]