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PUBLISHED DATE: - 21-08-2024
https://doi.org/10.37547/TAJMSPR/Volume06Issue08-03
PAGE NO.: - 13-20
MYASTHENIA GRAVIS PRESENTS AS BULBAR
PALSY WITHOUT THYMOMA
Gulomova Nozimakhon
School of Medicine, Central Asian University, Tashkent, Uzbekistan
Nigora Kadyrkhodjayeva
Department of Neurology, AKFA Medline University Hospital, Tashkent, Uzbekistan
INTRODUCTION
When the div's immune system mistakenly
targets its own postsynaptic acetylcholine
receptors (AChR) and leads to fatigue that
improves with rest goes by the name of myasthenia
gravis (MG) [1]. Thymoma and thymic hyperplasia
are associated with MG [2]. The clinical
classification
system
established
by
the
Myasthenia Gravis Foundation of America (MGFA)
divides MG into 5 primary classes, depending on
the severity and specific clinical features. Although
the most common form of MG is ocular (50%),
manifested with ptosis, class IIb is characterized by
a predominant involvement of the oropharyngeal
and respiratory muscles [3]. There is a strong
connection between the existence of AChR
antibodies and the severity of MG, suggesting that
individuals who test positive for these antibodies
may have a more difficult clinical experience, as
occurred in a patient who was wrongly diagnosed
with motor neuron disease (MND), demonstrating
the challenges of identifying bulbar palsy. The
patient's experience, marked by worsening bulbar
symptoms and puzzling upper motor neuron signs,
emphasizes the importance of conducting
thorough clinical assessments, especially in older
individuals [4-6].
Our case report details the clinical progression of
MG and the importance of emphasizing the
significance of timely and accurate diagnosis.
RESEARCH ARTICLE
Open Access
Abstract
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Case presentation:
Case 1
A 56-year-old male presented with difficulty
swallowing and feeling of a lump in the throat,
choking, hoarseness, dyspnea, and dizziness, which
persisted for a month. Initially, the patient had
hoarseness and nasal voice; the general
practitioner (GP) treated it as a common cold.
Following 10 days, his condition got worse, and
new symptoms such as choking, inability to
swallow, and shortness of breath started to appear.
GP referred this patient to the neurologist, where
he was diagnosed with motor neuron disease
(MND) in Surkhandarya, a region of Uzbekistan.
The treatment plan with 15mg of corticosteroids
showed no improvement. Due to the deficiency of
nutrients, he experienced a general weakness,
which eventually led him to AKFA Medline
University Hospital.
He has no allergy history. Type 2 Diabetes Mellitus,
managed with insulin twice daily, was notable in
his medical history. The patient’s general condition
during the examination was satisfactory, with clear
consciousness and orientation in time and place.
Neurological examination revealed regular and
round pupils with full eyeball movement, no
nystagmus or diplopia, normal convergence and
accommodation, and sufficient photoreactions.
Prominently, the patient exhibited dysphagia and
dysphonia. The absence of tremor with no change
in muscle tone was considered. Deep tendon
reflexes (Biceps, Radial brachialis, Triceps, Distal
finger flexors, Quadriceps knee jerk, Ankle jerk) are
intact with the negative plantar reflex (Babinski
sign). Sensory loss and meningeal signs are not
detected. Romberg test and further coordination
tests were performed confidently. He was referred
to undergo a comprehensive analysis consisting of
blood tests, electroneuromyography (ENMG),
nerve conduction test (NCT), and chest Computed
Tomography (CT).
Prior to the patient’s arrival at our hospital for the
comprehensive assessment, he was unable to
undergo a blood test for antidiv detection
because it was not accessible in his previous
healthcare setting. Upon arrival, he underwent
serological testing, where blood test results
showed normal anti-skeletal muscle antibodies
(IgG), elevated (0.78 units/ml) muscle-specific
tyrosine kinase antidiv (MuSK, IgG), and
significantly elevated level (2.34 nmol/l) of
acetylcholine receptor antidiv (Table 1).
Test
Result
s
Norma
Units
Striated Muscle Antidiv,
IgG
16
up to 20
Muscle-specific
tyrosine
kinase antidiv (MuSK), IgG
0.78
up to 0.40
U/mL
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Acetylcholine
Receptor
(ACHR) Antidiv
2.34
less than 0.45 nmol/L
Table 1. Antidiv testing results in Case 1.
ENMG demonstrated a weakly positive decrement
test following pyridostigmine administration, with
normal muscle unit (MU) action potentials and no
spontaneous activity in needle EMG of the deltoid
and general extensor muscles of the hand. Post-
administration of 2 ml of neostigmine showed no
clinical changes and a negative decrement in
ENMG. No signs of motor neuronal processes or
neuromuscular conduction disorders were
expressed, indicating compensated myasthenic
syndrome. Obtained results ultimately exclude the
initial diagnosis he arrived with and allow us to
come to a more accurate treatment strategy.
In a clinical evaluation, a chest CT scan (Figure 1)
was performed as part of the standard diagnostic
procedure for a patient with MG to check for
thymoma. The absence of any abnormalities in the
thymus allows us to focus more on addressing the
autoimmune aspect of MG without having to
manage complications related to a thymic tumor.
Moreover, a comprehensive chest CT scan
effectively eliminated the possibility of small-cell
lung carcinoma.
Figure 1: Chest CT in Case 1
Arrows show a normal appearance of the thymus
in the anterior mediastinum. (A) Axial CT, (B)
Coronal CT, (C) Sagittal CT.
A treatment plan focuses on managing neurological
symptoms
and
addressing
his
diabetes.
Pyridostigmine 60 mg was initiated every 8 hours.
The doses are scheduled precisely at 8 AM, 4 PM,
and midnight to ensure optimal concentration in
the bloodstream and effectiveness in managing
muscle
weakness
and
jaw
movements.
Additionally, the patient's diabetes is being
managed with insulin, which is administered at 12
AM and 8 PM.
The coexistence of diabetes may have influenced
the progression of neuromuscular symptoms.
Long-term follow-up and management focusing on
both neuromuscular and diabetic control enhances
results for the patient.
Case 2
A 66-year-old female experienced worsening
speech and swallowing issues, as well as severe
joint pain that had been developing for the past 9
months. Her medical background included
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confirmed rheumatoid arthritis (RA) through high
levels of anti-cyclic citrullinated peptide (A-CCP)
antibodies, characteristic of this autoimmune
condition. Although there was no widespread
muscle weakness usually seen in myasthenia
gravis, the ongoing presence and particular nature
of her bulbar symptoms raised concerns about MG
as a possible alternative diagnosis.
Therapeutic interventions aimed at managing RA
did not help with her bulbar symptoms, and using
pyridostigmine, a common treatment for MG, did
not lead to any notable improvement. This lack of
response required a thorough diagnostic
assessment to rule out other potential causes and
issues.
Ultrasonography (USG) Doppler examination of the
brachiocephalic arteries showed no major
abnormalities except for kinking of the internal
carotid artery, indicating that vascular factors were
unlikely contributors to her symptoms.
Blood tests showed normal levels in a complete
blood count (CBC), but C-reactive protein (CRP)
was three times higher (15.05 mg/l) than normal,
pointing to ongoing inflammation. Rheumatoid
factor (RF) level was seven times above (97.48
U/ml) the normal range (Table 2), confirming the
RA diagnosis and hinting at heightened
autoimmune activity that could potentially overlap
with other conditions like MG.
Test
Results Normal range Units
C-reactive protein
(CRP)
15.05
0-5
mg/l
Rheumatoid Factor 97.48
0-14
U/ml
Table 2
.
Acute Phase Proteins in Case 2
.
MRI of submandibular soft tissues (Figure 2) and
CT (Figure 3) scans were conducted to rule out
thymoma and squamous cell carcinoma (SCC), only
showing signs of chronic bronchitis without any
significant issues or masses.
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Figure 2. Neck MRI in Case 2.
No structural alterations in the soft tissues of the
neck were identified through imaging.
Figure 3. Chest CT in Case 2.
Imaging confirms the absence of thymoma and
small cell carcinoma within the examined region.
Patient also went through blood testing to examine
the possible autoimmune origin of her symptoms,
focusing specifically on certain indicators that
could confirm a diagnosis of myasthenia gravis.
The test results indicated MuSK antidiv level of
0.97 U/mL (increased) and antibodies targeting
AChR at a level of 3.2 nmol/L (increased).
Identifying these antibodies provided crucial
evidence confirming the myasthenia gravis
diagnosis alongside her existing rheumatoid
arthritis, underscoring the challenges involved in
managing patients with overlapping autoimmune
conditions.
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Test
Resul
ts
Norma
Units
Striated Muscle Antidiv,
IgG
18
up to 20
Muscle-specific
tyrosine
kinase antidiv (MuSK), IgG
0.97
up to 0.40
U/mL
Acetylcholine
Receptor
(ACHR) Antidiv
3.2
less than 0.45 nmol/L
Table 3. Antidiv testing results in Case 2.
Management plan of neurological symptoms with
Pyridostigmine 60 mg was commenced at intervals
of every 8 hours. The doses are scheduled precisely
at 8 AM, 4 PM, and midnight to ensure optimal
concentration.
Additionally,
the
patient's
rheuemotological symptoms is being managed
with Leflunomide 20 mg once a day.
This kind of approach may result in an overall
enhancement in the quality of life for patients
dealing with overlapping autoimmune and
neuromuscular conditions.
DISCUSSION
The occurrence of MG in Asia is increasingly seen
among older patients who have other health
conditions such as high blood pressure, diabetes,
and cancer [7]. There is a connection between MG
and thymoma [2], which is extensively recorded,
but our case did not have this typical association,
making the diagnosis more complicated. When
thymoma is not present in MG patients, especially
those with bulbar symptoms, it is important to
highlight the importance of comprehensive
serological and neurophysiological testing for
unusual presentations of MG. A considerable
portion of individuals with MG possess
autoantibodies that attack the AChRs, although a
small number exhibit antibodies targeting different
proteins like MuSK [8-11]. The different clinical
presentations of MG, such as those with antibodies
against AChRs or MuSK, present unique challenges
in managing respiratory dysfunction during a
myasthenic crisis [4,12].
As was mentioned above, our patient was initially
misdiagnosed
with
MND,
which
could
subsequently lead to bad consequences, so
comprehensive and detailed diagnostic approaches
are emphasized in cases where there are
overlapping symptoms of MND due to the role of
immune mechanisms in their development [13]. It
is important to be more careful and thorough when
diagnosing MG, especially in patients with
unexplained bulbar symptoms, regardless of their
deep tendon reflexes [6].
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The majority of patients with bulbar palsy in MG
are
recommended
to
start
taking
acetylcholinesterase
inhibitors,
like
pyridostigmine,
which
enhances
the
communication between nerves at the neuro-
muscular
junction
by
preventing
the
acetylcholinesterase enzyme from breaking down
acetylcholine [14,15].
CONCLUSION
MG with the early onset of bulbar palsy may
frequently be undetected or misdiagnosed,
particularly in these two unique instances, in light
of concurrent conditions - diabetes mellitus in the
first case and rheumatoid arthritis in the second.
Highlighting connection between autoimmune
neuromuscular
disorders
and
systemic
autoimmune or metabolic illnesses. Moreover,
patients are unable to obtain proper diagnostic
tools due to shortages and financial limitations in
underdeveloped areas. In these circumstances,
government assistance in healthcare becomes
important for medical diagnosis and treatment.
REFERENCES
1.
Hehir MK, Silvestri NJ. Generalized Myasthenia
Gravis: Classification, Clinical Presentation,
Natural History, and Epidemiology. Neurologic
Clinics.
2018;
36(2):253-60.
https://doi.org/10.1016/j.ncl.2018.01.002
2.
Priola AM, Priola SM. Imaging of thymus in
myasthenia gravis: From thymic hyperplasia to
thymic tumor. Clinical Radiology. 2014; 69(5):
230-45
https://doi.org/10.1016/j.crad.2014.01.005
3.
Gilhus NE, Owe JF, Hoff JM, Romi F, Skeie GO,
Aarli JA. Myasthenia gravis: a review of
available treatment approaches. Autoimmune
Diseases. vol. 2011, Article ID 847393, 6 pages,
https://doi.org/10.4061/2011/847393
4.
Gilhus NE, Tzartos S, Evoli A, Palace J, Burns
TM, Verschuuren JJGM. Myasthenia gravis.
Nature Reviews Disease Primers. 2019; 5(1).
https://doi.org/10.1038/s41572-019-0079-y
5.
Gwathmey K, Burns T. Myasthenia Gravis.
Seminars in Neurology. 2015; 35(04):327-39.
https://doi.org/10.1055/s-0035-1558975
6.
Basiri K, Ansari B, Okhovat AA. Life-threatening
misdiagnosis of bulbar onset myasthenia gravis
as a motor neuron disease: How much can one
rely on exaggerated deep tendon reflexes.
Advanced Biomedical Research. 2015; 4(1):58.
https://doi.org/10.4103/2277-9175.151874
7.
Herr KJ, Shen S-P, Liu Y, Yang C-C and Tang C-H.
The growing burden of generalized myasthenia
gravis: a population-based retrospective
cohort study in Taiwan. Frontiers in Neurology.
2023;
14:1203679.
https://doi.org/10.3389/fneur.2023.1203679
8.
Patrick J, Lindstrom J: Autoimmune response to
acetylcholine receptor. Science. 1973; 180:871-
2.
https://www.doi.org/10.1126/science.180.40
9.
McConville J, Farrugia ME, Beeson D, Kishore U,
Metcalfe R, Newsom-Davis J, et al. Detection
and characterization of MuSK antibodies in
seronegative myasthenia gravis. Annals of
Neurology.
2004;
55:580-4.
https://doi.org/10.1002/ana.20061
10.
Pevzner A, Schoser B, Peters K, Cosma N-C,
Karakatsani A, Schalke B, et al. Anti-LRP4
autoantibodies in AChR- and MuSK-antidiv-
negative myasthenia gravis. Journal of
Neurology.
2012;
259:427-35.
https://doi.org/10.1007/s00415-011-6194-7
11.
Zhang B, Shen C, Bealmear B, Ragheb S, Xiong
W-C, Lewis RA, et al. Autoantibodies to agrin in
myasthenia gravis patients. PLoS One. 2014,
9(3):
e91816.
https://doi.org/10.1371/journal.pone.009181
12.
Wendell LC, Levine JM. Myasthenic Crisis.
Neurohospitalist.
2011;
1(1):16-22.
https://doi.org/10.1177/1941875210382918
13.
Tai H, Cui L, Guan Y, Liu M, Li X, Huang Y, et al.
Amyotrophic Lateral Sclerosis and Myasthenia
Gravis Overlap Syndrome: A Review of Two
Cases and the Associated Literature. Frontiers
in
Neurology.
2017;
8:218.
THE USA JOURNALS
THE AMERICAN JOURNAL OF MEDICAL SCIENCES AND PHARMACEUTICAL RESEARCH
(ISSN
–
2689-1026)
VOLUME 06 ISSUE08
20
https://www.theamericanjournals.com/index.php/tajmspr
https://doi.org/10.3389/fneur.2017.00218
14.
Remijn-Nelissen L, Verschuuren JJ, Tannemaat
MR. The effectiveness and side effects of
pyridostigmine in the treatment of myasthenia
gravis: a cross-sectional study. Neuromuscular
Disorders.
2022,
32:790-9.
https://doi:10.7759/cureus.50017
15.
Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I,
Harms L, et al. Guidelines for treatment of
autoimmune neuromuscular transmission
disorders. European Journal of Neurology.
2010,
17:893-902.
https://doi.org/10.1111/j.1468-
1331.2010.03019.x
