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107]

Original article  699

Intravenous immunoglobulin vs. plasma exchange as

preoperative preparations before thymectomy in myasthenia
gravis patients
Mohamed S. Abdelmotaleb

Department of Cardiothoracic Surgery, Faculty Objective

of Medicine, Menoufia University, Menoufia,
To investigate the efficacy of intravenous immunoglobulin (IVIG) vs. plasma exchange (PLEX)
Egypt
as a preparation before thymectomy in patients with myasthenia gravis (MG).
Correspondence to Background
Mohamed S. Abdelmotaleb, MD,
MG is an autoimmune disorder. Besides medications, thymectomy is usually used to manage
Department of Cardiothoracic Surgery, Faculty
of Medicine, Menoufia University, Yassin MG patients. Some studies investigated the role of IVIG or PLEX in the preparation of
Abdelghafar Street, Shebin Elkoum, Menoufia, thymectomy in MG patients to control perioperative and postoperative complications. The
Egypt. clinicians have met with a lack of adequate knowledge about superiority of IVIG or PLEX in
Postal Cod: 32511; preoperative preparation before thymectomy.
Fax: 0482317502-0482317508;
Tel: +00966549763808;
Patients and methods
e‑mail: m.sabry82@yahoo.com This is retrospective study that was conducted on 14 patients with MG referred for thymectomy.
Patients were assigned to two groups. The IVIG group (n = 7) received IVIG. The PLEX
Received 15 March 2022
Revised 05 April 2022
group (n = 7) underwent PLEX. Both methods were considered as preoperative preparation
Accepted 10 April 2022 before the thymectomy.
Published 27 July 2022 Results
Menoufia Medical Journal 2022, 35:699–703 The duration of hospitalization preoperatively was significantly different between the two groups.
The mean duration of hospitalization preoperatively of IVIG group was 1.86 ± 1.21 days vs.
4.43 ± 2.30 days for PLEX group (P value 0.02).
Conclusion
The interpretation of the results of the current study is limited by the retrospective design and
low number of patients. However, patients in the IVIG group had less preoperative hospital
length of stay.

Keywords:
intravenous immunoglobulin, myasthenia gravis, plasma exchange, thymectomy, video‑assisted
thoracoscopy

Menoufia Med J 35:699–703

© 2022 Faculty of Medicine, Menoufia University
1110‑2098

azathioprine, and cyclosporine, but the stabilizing

Introduction
Myasthenia gravis  (MG) is an autoimmune
disorder [1]. This disorder is caused by autoantibodies
against nicotinic acetylcholine postsynaptic receptors
at the neuromuscular junction of the skeletal
muscles or the muscle‑specific tyrosine kinase in
most patients  [2]. The antiacetylcholine receptor
antibody  (AchRAb) damages the postsynaptic
membrane and induces reduction in the number of
acetylcholine receptors. The most common affected
muscles include the extrinsic ocular muscles, causing
eyelid ptosis and diplopia with fluctuating generalized
weakness  [3]. Myasthenic crisis is a complication of
MG characterized by worsening muscle weakness,
resulting in respiratory failure that requires intubation
and mechanical ventilation. A  more comprehensive
definition of myasthenic crisis also includes postsurgical
patients, in whom exacerbation of muscle weakness
from MG causes a delay in extubation [4]. Treatments
of MG include anticholinesterase medications and
immunosuppressive agents such as corticosteroids,
therapies are plasma exchange (PLEX) and intravenous
immunoglobulin  (IVIG). These could be utilized
in cases of exacerbation  [5]. Surgical removal of the
thymus has been an alternative treatment for this disease
since Blalock performed a successful thymectomy in a
26‑year‑old woman with MG and thymus cysts. Then,
Blalock [6] published the study about 20 patients with
MG treated with transsternal thymectomy. In the next
decade, a many number of studies investigating the
role of thymectomy in MG have been reported from
the United States and the United  Kingdom. Over
time, with improvements in perioperative care, results
of thymectomy have improved, and thymectomy has
found its place in the treatment integrity of MG [7].
Patients with significant myasthenic weakness require
preoperative optimization of their clinical strength
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
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1110-2098 © 2022 Faculty of Medicine, Menoufia University DOI: 10.4103/mmj.mmj_84_22

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700  Menoufia Medical Journal, Volume 35 | Number 2 | April-June 2022
to avoid prolonged respiratory insufficiency and
ventilation after surgery  [8]. This approach reduces
perioperative complications, duration of hospital stay,
and overall morbidity  [9]. Some studies investigated
the role of IVIG or PLEX in the preparation of
thymectomy in MG patients to control perioperative
and postoperative complications  [10]. The clinicians
have met with a lack of adequate knowledge about
superiority of IVIG or PLEX in preoperative
preparation before thymectomy [11].
The aim of this study was to compare the efficacy of
IVIG vs. PLEX as a preparation before thymectomy in
patients with MG.
Patients and methods
After approval by the local Research Ethics Board, we
conducted a retrospective study including all patients
who underwent thymectomy for MG from 2017 to
2021 in our tertiary university institute.
The diagnosis of MG was established by a
neuromuscular expert, abnormal electrophysiological
testing on single‑fiber electromyography, and
response to acetylcholinesterase and other treatments.
Abnormal repetitive nerve stimulation studies
supported the diagnosis, and elevated AchRAb or
anti–muscle‑specific Kinase  (anti‑MuSK) antibody
levels, when available, confirmed the diagnosis.
Routine management of patients with generalized
MG at this clinic mandates thymectomy for patients
without contraindications to surgery. The charts of all
patients referred for thymectomy from 2017 to 2021
were reviewed.
A total of 14  patients were assigned to two groups.
The IVIG group  (n  =  7) received IVIG. The PLEX
group (n = 7) underwent PLEX. The IVIG group (n = 7)
prepared by administration of 1 g/kg/day of IVIG as a
single dose and some cases received second dose in two
consecutive days according to neurologist assessment.
To control the possible allergic side effects of IVIG,
patients received diphenhydramine 50  mg and
acetaminophen 650  mg tablets before infusion. The
PLEX group (n = 7) prepared by two or three sessions
of 1  L PLEX with 5% albumin replacement fluid
every other day according to neurologist assessment.
Both methods were considered as preoperative
preparations before the thymectomy started direct
before operation in same admission. Required data
for this study were extracted from the patients’
files. Gathered information included demographic
characteristics  (age and sex), duration of the disease,
and significant medical history and pathology report
of the thymus tissue samples. The outcomes of the
study were duration of hospitalization (day), length of
intensive care unit (ICU) stay after surgery, and need
for postoperative mechanical ventilation.
Surgical technique of video‑assisted
thoracoscopy (VATS)
The patients received general anesthesia with
double‑lumen endotracheal intubation that was
confirmed by fiber‑optic bronchoscopy. The patient
was placed in a 30‑degree semisupine position angled
with a bump under the right side. Three ports were
planned for the right VATS. The 30° thoracoscopic
camera was introduced and the entire hemithorax
was evaluated. Carbon dioxide  (CO2) insufflation at
a pressure of 10  mmHg was used. Complete radical
thymectomy was achieved by en‑bloc removal of the
thymus, perithymic fat and tissue from the thoracic
inlet to the diaphragm, and from phrenic nerve to
phrenic nerve. Once VATS intervention was complete
and complete hemostasis achieved, two chest tubes
were placed through the intercostal access sites under
the vision to facilitate proper drainage. The thoracic
cavity was then closed in layers and the aseptic dressing
was done.
Statistical analysis of the data
Analysis was performed by Statistical Package for Social
Sciences  (SPSS) Computer Software  (Version  20;
IBM Software, Chicago, Illinois, USA). To compare
the quantitative variables, data were assessed regarding
normality and homogeneity of variances. We compared
with independent samples t test if these assumptions
were met; otherwise, Mann–Whitney U test was
performed. Fischer’s exact test was used to compare the
two groups for categorical variables due to sample size.
All statistical tests were conducted with a significant
level less than 0.05.
Results
Fourteen patients were included in the study, seven
patients in the IVIG group and seven patients in the
PLEX group. No significant difference was observed
between the two groups in terms of age and sex. The
mean age of IVIG group was 32.17 ± 4.17 years and
the mean age of PLEX group was 41.71 ± 5.10 years
and all patients were female. The median duration of
disease was 36 months in IVIG group and 24 months
in PLEX group with no significant difference observed
between the two groups. Regarding form of disease
preoperatively, there was one patient in IVIG group
and no patients in PLEX group with ocular symptoms,
and six patients in IVIG group and seven patients
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in PLEX group with generalized symptoms with no
significant difference. AchRAb before initial treatment
revealed no significant difference between IVIG group
(six patients, 86%) and PLEX group (six patients, 86%)
in terms of the ratio of positive patients.
The preoperative dosage of Mestinon was mean
310.00  ±  62.77 for IVIG group and mean
180.00  ±  22.68 for PLEX group. The postoperative
dosage of Mestinon was mean 310.00 ± 24.08 for IVIG
group and mean 274.29 ± 34.29 for PLEX group. The
preoperative dosage of steroids was mean 5.00 ± 3.16
for IVIG group and mean 5.71  ±  3.17 for PLEX
group. The postoperative dosage of steroids was mean
2.50  ±  1.71 for IVIG group and mean 6.43  ±  2.10
for PLEX group. The preoperative dosage of Imuran
was mean 154.17 ± 13.57 for IVIG group and mean
103.57  2  ±  3.42 for PLEX group. The postoperative
dosage of Imuran was mean 137.50 ± 19.09 for IVIG
group and mean150.00 ± 14.43 for PLEX group with
no significant difference observed between the two
groups regarding medication.
One of the seven patients in each group required
postoperative intubation and mechanical ventilation.
The duration of hospitalization preoperatively was
significantly different between the two groups. The
mean duration of hospitalization preoperatively of IVIG
group was 1.86 ± 1.21 days vs. 4.43 ± 2.30 days for PLEX
group  (P  value 0.02). The duration of hospitalization
postoperatively and ICU length of stay did not show any
significant difference between the two groups. The most
common pathology was follicular hyperplasia in four
patients in IVIG group and five patients in PLEX group.
Other pathological results were as thymoma one patient
in IVIG group and in one patient in PLEX, thymolipoma
found in one patient in IVIG group and one patient in
PLEX, and Hodgkin’s lymphoma one patient in IVIG.
There was no statistical difference between both groups
in thymus gland pathology (Table 1).
Discussion
Both medications and thymectomy are usually used
to manage MG patients. Surgery in the first years of
MG has a great impact on the consequences of the
disease, especially in maintaining remission  [1]. The
immunomodulation for preparation of surgery can be
achieved by either PLEX or IVIG but PLEX is the
usual method [2].
This study showed that administration of IVIG in
comparison with PLEX before thymectomy has
similar outcomes as there is no significant difference
regarding to postoperative crisis, ICU stay, mechanical
Thymectomy  in myasthenia gravis patients Abdelmotaleb  701
ventilation and medication doses, but there are
significant differences regarding the duration of
hospitalization preoperatively as it was less in those
receiving IVIG (P value 0.02).
The significant difference regarding the duration
of hospitalization preoperatively is due to IVIG
administrated as one dose preoperative or two doses in
2 consecutive days so only 1 or 2 days are needed before
operation but in PLEX group  6 or 4  days are needed
before operation as two or three sessions of PLEX were
needed and the frequency of sessions was every other day.
Thymic abnormalities are a common finding in MG
in form of thymic hyperplasia and thymoma. We had
a rare case of coexisting primary thymic Hodgkin’s
disease and thymoma with background thymic
epithelial hyperplasia in female patient known to have
MG. The immunohistochemistry of this case is that of
classical Hodgkin’s disease. Moreover, there was strong
reactivity for CK19 and p63 with focal positivity for
pan‑CK‑denoted background thymoma.
Alipour‑Faz et  al. [1] conducted randomized clinical
trial that investigated the efficacy of IVIG vs. PLEX
as a preparation before thymectomy in patients with
MG. Their study showed that in the PLEX group,
postoperative outcomes  (duration of hospitalization,
ICU length of stay after surgery, intubation period, and
duration of surgery) were longer than those in the IVIG
group. There was significant difference in intubation
period and duration of surgery between the PLEX and
IVIG groups. They concluded that administration of
IVIG in comparison with PLEX can be more effective
in the preparation before thymectomy in MG patients.
Jensen and Bril conducted a retrospective chart review
to determine if PLEX and IVIG had comparable
effectiveness in the preoperative preparation of patients
with MG. Their results showed that IVIG may have
comparable efficacy in the preoperative preparation
of patients with MG and this therapy is a reasonable
alternative to PLEX in this clinical setting.
Heatwole et al. [12] made comparative
cost‑minimization analysis of IVIG vs. PLEX as a
primary immunomodulating treatment for MG crisis
was performed. They concluded that the use of IVIG
for MG may be a short‑term cost‑minimizing therapy
compared with PLEX.
Furlan et al. [13] compared the cost of IVIG with the
cost of PLEX in treatment of patients with moderate
to severe MG. Their study included 32  cases treated
with IVIG and 38  cases treated with PLEX. They
concluded that treatment with PLEX is a better
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702  Menoufia Medical Journal, Volume 35 | Number 2 | April-June 2022

Table 1 Comparison of evaluated variables between the two study groups

Variable IVIG (n=7) PLEX (n=7) P*
Age (mean±SD, years) 32.17±4.17 41.71±5.10
Sex
Male (%) 0 (0) 0 (0) 1
Female (%) 7 (100) 7 (100)
Median duration of the disease in months (IQR) 36.00 (45.00) 24.00 (55.00) 0.45
Serology
AchRAb positive (%) 6 (85.7) 6 (85.7) 1
AchRAb negative (%) 1 (14.3) 1 (14.3)
Preoperative myasthenic crisis (%) 2 (28.6) 5 (71.4) 0.29
Postoperative myasthenic crisis (%) 1 (14.3) 5 (71.4) 0.10
MG medication
Preoperative Mestinon (mg) 310.00±62.77 180.00±22.68 0.26
Postoperative Mestinon (mg) 310.00±24.08 274.29±34.29 0.31
Preoperative steroids (mg) 5.00±3.16 5.71±3.17 0.90
Postoperative steroids (mg) 2.50±1.71 6.43±2.10 0.38
Preoperative Imuran 154.17±13.57 103.57 2±3.42 0.42
Postoperative Imuran 137.50±19.09 150.00±14.43 0.44
Preoperative symptoms
Ocular (%) 1 (14.3) 0 (0) 1
Generalized (%) 6 (85.7) 7 (100) 1
Postoperative ICU stay (days) 1.29±0.49 1.14±0.38 0.55
Postoperative mechanical ventilation (h) 1 1 1
Preoperative hospital stay (days) 1.86±1.21 4.43±2.30 0.02*
Postoperative hospital stay (days) 4.29±0.49 4.71±0.95 0.31
Thymus enlargement in CT (%) 2 (28.6) 2 (28.6) 1
Histopathology of the thymus
Follicular hyperplasia (%) 4 (57.1) 5 (71.4)
Thymoma (%) 1 (14.3) 1 (14.3)
Thymolipoma (%) 1 (14.3) 1 (14.3)
Hodgkin’s lymphoma (%) 1 (14.3) 0 (0)
AchRAb, antiacetylcholine receptor antibodies; CT, computed tomography; ICU, intensive care unit; IQR, interquartile range; IVIG,
intravenous immunoglobulin; MG, myasthenia gravis; PLEX, plasma exchange. *P value: categorical variables were calculated with
Fischer’s exact test, and independent samples t test and Mann–Whitney U test were used for continuous variables. Significance level was
P=0.05.

short‑term cost‑minimizing therapy for patients with
MG exacerbation in comparison with IVIG therapy
if their body mass index is >15.7 kg/m2. But hospital
administrators working with more rigid institutional
budget may prefer IVIG therapy as it is a more
financially attractive option in comparison with PLEX
treatment due to the costs of the blood products.
In ocular MG, since the early report of Keynes’
comprehensive early analysis  [14], most researchers
have found a significant advantage in performing
thymectomy early. They believe that patients with
ocular AchRAb‑positive MG and thymic hyperplasia
can be good candidates for surgery, as in these cases,
the ocular symptoms often represent the early phase of
a form of generalized MG [15,16].
Zhu et  al. [17] published a recent meta‑analysis
based on 26 publications that analyzed the course
of 684  patients with ocular MG and thymectomy.
The pooled rate of completely stable full remission
was comparably high at 51%. They concluded that
thymectomy clearly represents an effective treatment
for patients with nonthymomatous ocular MG.
The limited body of data relating to the effectiveness of
thymectomy in MuSK‑ab‑positive MG is contradictory.
In a study conducted by Leite et al. [18], typical thymic
pathologies (thymoma, thymic hyperplasia) have been
observed only in exceptional cases, the significance
of which is still unclear. They concluded that these
variations may explain some apparent differences in
responses to thymectomy in seronegative.
Another extensive narrative review was published
in 2005 by Oh  [19], presenting an overview on
MuSK‑ab‑positive MG based on his experience at the
University of Alabama at Birmingham and review of
literature. Oh stated that there were reports of remission
in a few patients: four of nine thymectomized patients
in Lavrnic’s series [20], and two of four thymectomized
patients in Kostera‑Pruszczyk’s series  [21]. In their
published results, one patient  (out of five patients)
achieved pharmacological remission after thymectomy.
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They concluded that these data would argue against
performing thymectomy.
For such contradicting data, some authors’ opinion is
that for seronegative patient and MuSK‑ab‑positive
MG patients, thymectomy should be performed
for individual cases of severe treatment‑refractory
disease [22].
The limitations of this study were small sample size
and being retrospective study and, therefore, studies
with a larger sample size and long‑term follow‑up are
recommended.
Conclusion
The current study is limited by the retrospective design
and low numbers of patients. These concerns need to
be addressed in a prospective, randomized, controlled
study that is adequately powered to provide definitive
comparisons. Despite these limitations, the results
suggest that PLEX or IVIG could be particularly used
for preparation before thymectomy. The outcome of
both methods was similar in the case management of
these patients. However, IVIG has less preoperative
hospital stay.
Acknowledgements
The manuscript has been read and approved by the
author; the author believes that the manuscript
represents honest work.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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