Myastenia gravis 2 dengan thymoma pada penderita anak usia

DISKUSI KASUS

MYASTENIA GRAVIS DENGAN
THYMOMA PADA PENDERITA
ANAK USIA 5 THN

Kemala Hayati

Moderator : Dr. Maimun, ZA, M.Kes. SpPK

Patologi Klinik Laboratorium Sentral RSSA
MALANG
Powerpoint Templates
Page 1

DATA DASAR
• An. MM, 4 thn, perempuan
• Anamnesa :
• Keluhan utama : mata seperti
mengantuk
• Mata seperti mengantuk sjk 3 minggu
SMRS. Saat bangun tidur mata dpt
membuka lebar,tp siang hari / setelah
aktifitas mata kembali tampak spt
mengantuk.
• Riwayat keluarga dengan penyakit
serupa disangkal
Page 2

PEMERIKSAAN FISIK
• Pemeriksaan umum : Tampak sakit
• KU : Cukup
• Vital sign : Nadi : 88x/mnt, R : 28X/mnt,
t : 36.5 C
• Kepala :
• Mata kiri : kelopak mata menutupi
separuh mata Konjungtiva anemi : -/-,
Sklera ikterik : -/-
• Thorax : taa
• Abdomen : taa
• Antropometrik : PB : 105 cm,TB : 14,5
kg Powerpoint Templates
Page 3

Darah Lengkap 3-1-2010 15-1-2010

Hemoglobin (11.0-16.5 11.5 12.4
mg/dl) 6.900 9.600
Lekosit (3500-10.000 /µL)
LED 34
Trombosit (150.000 - 283.000 351.000
200.000/µL) 35.3
Hmt
7/-/-/49/38/5/6
Hit.Jenis 81 86
MCV (80-99 µm3) 26.6 27.7
MCH (26.5-33.5 pq) 32.6 32.4
MCHC (31.5-35.0 g/dl) 14.2 13.6
RDW (10-15 µm3)
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LABORATORIUM 5-1-2010
Imunologi
L Total T3 (0.79-1.49 ng/dl) 1.09
A Free T4 (0.71-1.85 ng/dl) 0.91
TSH (0.49-4.67 µIU/ml) 2.517
B
0 Elektrolit
R Natrium (136-145 mmol/l) 140
Kalium (3.5-5.0 mm0l/l) 4.54
A 111
Chlorida (98-106 mmol/l)
T Kalsium (7.6-11.0 mmol/l) 8.5
O Fosfor (2.5-7-0 mmol/l) 4.84
R
Kimia Darah
I GDS (60-110 mg/dl) 96
U Ureum (10-50 mg/dl) 28.4
Kreatinin (0.7-1.5 mg/dl) 0.37
M
Page 5

Kimia Darah 3/1 5/1 14/1 21/1

GDS 96 EMG CT Scan
(60-110 mg/dl) Kesimpulan : Kesimpulan :
Menyokong Massa soft
Ureum 28.4 suatu tissue pd
(10-50 mg/dl) myastemia mediastinum
gravis ant. Suspek
Kreatinin 0.37 Thymoma dg
(0.7-1.5 mg/dl) DD
retrosternal
goiter dan
limfoma

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JAWABAN
• INTERPRETATIF &
Pada pemeriksaan laboratorium klinik
didapatkan hasil normal, dengan klinis
Electromyography (EMG) serta CT Scan
Thorax mengesankan suatu Myasthenia
Gravis dan suspek Thymoma, DD: 1.
retrosternal goiter, 2. limfoma
• Saran : pemeriksaan Acetylcholine Receptor
Antibodi ( AChR Ab) & Muscle Specipic
kinase (Anti MuSk Ab)

Page 7

DISKUSI
1. Penegakan diagnosa
2. Laboratorium Myasthenia
Gravis dan Thymoma

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1. PENEGAKAN DIAGNOSA
• Myasthenia Gravis (MG)
• an acquired autoimmune disorder in which
the postsynaptic AChRs are reduced in
number or function, leading to muscle
fatigue and weakness.
• characterized by a fluctuating pathological
weakness with remissions & exacerbations
involving one or several skeletal muscle
groups, mainly caused by antibodies to the
acetylcholine receptor (AChR) at the post-
synaptic site of the neuromuscular junction
Page 9

• Prevalence MG : 85–125 permillion,
• The disease has 2 peaks: 1. 20 - 40 years
( ), 2. 60 - 80 years ( , )
• the fetus acquire immune proteins (Ab) from
a mother affected with MG.
• Generally, cases of neonatal MG temporary
& child's symptoms disappear 2-3 months
after birth.
• MG in juveniles is uncommon.
• MG frequently associated with thymic
abnormalities, called thymitis, 60% &
thymoma 10% of patients.
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THYMOMA
• Thymoma is an uncommon neoplasm from
the epithelial cells of the thymus.
• Well known for association with MG,
histologic variability, & heterogeneity of
malignant behavior.
• Thymoma occurs in 10% patients MG
• MG occurs in 33% of patients thymoma

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PATHOPHYSIOLOGY
• Acetylcholine (ACh) synthesized in the
motor nerve terminal & stored in vesicles
• ACh from 150–200 vesicles released &
combines with AChRs that densely packed
at the peaks of postsynaptic folds.
• Structure of the AChR fully elucidated;
consists 5 subunits (2α, 1β, 1δ, & 1γ or ε )
arranged around a central pore.

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Page 13

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….pathophysiology
Normal
• ACh combines with the binding sites on
the subunits of the AChR
• channel in the AChR opens, entry cations,
chiefly sodium, produces depolarization at
the end-plate region muscle fiber.
• Depolarization triggering muscle
contraction.
• Process terminated by hydrolysis of ACh
by acetylcholinesterase (AChE), present
within the synaptic folds, & by diffusion of
ACh away from the receptor.
Page 15

….pathophysiology in the
Myasthenia Gravis
• the fundamental defect is a decrease
number of available AChRs at the
postsynaptic muscle membrane.
• postsynaptic folds flattened, or simplified.
• These changes result in decreased
efficiency of neuromuscular transmission
• although Ach released normally, it produces
small end-plate potentials that may fail to
trigger muscle action potentials
• results in weakness of muscle contraction
Page 16

…pathophysiology
Anti-AChR Ab reduce the number of AChRs
by 3 mechanisms:
(1) accelerated turnover of AChRs by a
mechanism involving cross-linking & rapid
endocytosis of the receptors;
(2) blockade of the active site of the AChR,
i.e., the site that normally binds ACh;
(3) damage to the postsynaptic muscle
membrane by the antibody in collaboration
with complement.

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CLINICAL FEATURE
• Presents between 15-50 years.
• affected > in younger ages & reverse
at older ages.
• It has relapsing / remitting course, esp
during the early years.
• The cardinal symptom is abnormal
fatigable weakness of the muscles;
movement is initially strong but rapidly
weakens.
• Worsening towards the end of the day or
following exercise is characteristic.
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..clinical feature
• No sensory signs or signs of CNS
involvement, although weakness of the
oculomotor muscles may mimic a central
eye movement disorder.
• The 1st symptoms usually intermittent
ptosis or diplopia, weakness of chewing,
swallowing, speaking or limb movement
• Any limb muscle may be affected, most
commonly those of the shoulder girdle;
unable to undertake tasks above shoulder
level, as combing the hair, without frequent
Page 19
rests.

….clinical feature
• Respiratory muscles may be involved &
respiratory failure is a not uncommon
cause of death & may be 1st presentation,
in which case the dx is difficult if not
thought of.
• Aspiration may occur if the cough is
ineffectual.
• Sudden weakness from a cholinergic or
myasthenic crisis may require ventilatory
support.
Page 20

DIAGNOSIS & EVALUATION
History
• Diplopia, ptosis, weakness
• Weakness in characteristic distribution
• Fluctuation & fatigue: worse with repeated
activity, improved by rest
• Effects of previous treatments
Physical examination
• Ptosis, diplopia
• quantitative testing of muscle strength
• Forward arm abduction time (5 min)
• Vital capacity
• Absence of other neurologic signs Page 21

…diagnosis & evaluation
Laboratory testing
• Anti-AChR radioimmunoassay: ~85%
positive in generalized MG; 50% in ocular
MG; negative result does not exclude
MG. ~40% of AChR Ab negative patients
with generalized MG have anti-MuSK Ab.
• Repetitive nerve stimulation; decrement
of >15% at 3 Hz: highly probable
diagnosis if unequivocally positive

Page 22

…diagnosis & evaluation
• Single-fiber electromyography: blocking
& jitter, with normal fiber density;
confirmatory, but not specific
• Edrophonium chloride (Tensilon) 2 mg
+ 8 mg IV; highly probable diagnosis if
unequivocally positive
• For ocular or cranial MG: exclude
intracranial lesions by CT or MRI

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1 . PENEGAKAN
PASIEN
DIAGNOSATEORI
• Ptosis (+) • Ptosis,diplopia,dysphagia
• Gejala bertambah dgn • Dysharthria
aktifitas • Myasthenic crisis (paralysis
• CT Scan thorax : suspek of respiratory)
thymoma • 75% have an abnormality of
• EMG : menyokong suatu the thymus
Myastenia Gravis • 10% have a thymoma
• single fiber
electromyography (SFEMG)
• AChR Ab
Myasthenia Gravis • Edrophonium test
dgn thymoma Powerpoint Templates
Page 24

2. Laboratorium MG &
• Thymoma
Tensilon test: IV short-acting
anticholinesterase, edrophonium
bromide, is a valuable diagnostic aid; 2
mg initially, with a further 8 mg, half a
minute later if no undesirable side-
effects. Improvement in muscle power
occurs within 30 sec & usually persists
for 2-3 min.
• Ice pack test: simple & less risky than
tensilon test with improvement in
ptosis in 2 mins.
• EMG with repetitive stimulation show
the characteristic decremental
response. Page 25

… laboratorium MG & Thymoma
• Anti-acetylcholine receptor Ab
(AChRA) is found in > 80%, < in purely
ocular myasthenia (50%).
• Anti-MuSK Ab found especially in
AChRA-negative patients with prominent
bulbar involvement.
• Positive anti-skeletal muscle Ab
suggest the presence of thymoma, but
all patients should have a thoracic CT to
exclude this condition, which may not be
visible on plain X-ray.
• Screening for other autoimmune
disorders, particularly thyroid disease, is
important.
Page 26

Anti-AChR Ab
• Anti-AChR Ab detectable in serum of ~85% MG
• 50% patients with weakness confined to the
ocular muscles.
• presence of anti-AChR Ab virtually diagnostic of
MG, but a negative test does not exclude the
disease.
• The measured level of anti-AChR Ab does not
correspond well with the severity of MG in
different patients.
• in an individual patient, a treatment-induced fall
in the Ab level often correlates with clinical
improvement.
Page 27

Anti-AChR antibodi
• Acetylcholine receptor (ACHR) Ab not
detected in healthy individuals or in
patients with neurological disorders or AID
other than MG
• the specificity of these assays approaches
100 %
• The most sensitive of the ACHR Ab assays
is the ACHR binding Ab assay.

Page 28

AChR Ab Measurement
• AChR Ab first measured by
immunoprecipitation of 125I a-BuTx-
labeled AChR in detergent extracts of
human muscle,
• most current assay employ AChRs
extracted from muscle-like cell lines that
express a mixture of fetal & adult AChRs
• Enzyme-linked immunosorbent assay
(ELISA) & other alternative assays not
proved successful.

Page 29

AChR Ab
• Measurement
AChR Ab titers highly variable among
MG patients, (0 to >1000 nm/L),
• between individuals titers do not
correlate well with clinical severity,
• level of Ab within an individual
correlates well with clinical scores after
plasma exchange ,thymectomy,or
immunosuppressive treatment.

Page 30

Interpretasi AChR Ab
• Presence of ACHR Ab confirms a dx MG.
• ACHR-binding Ab titer of ≥ 0.5 Nm
considered positive.
• ACHR-blocking Ab demonstrating ≥ 25%
inhibition/blocking considered positive.
• ACHR-modulating Ab demonstrating ≥ 26%
modulation considered positive.
• Absence of ACHR Ab does not rule out a dx
of MG, as 10–15 % of MG patients lack
detectible ACHR
• Normally, there is no AChr Ab (< 0.05
nmol/L) in the bloodstream.
Page 31

MuSK Antibody
• MuSK Ab found ~40% of AChR Ab negative
patients with generalized MG
• MuSK Ab rarely present in AChR Ab positive
patients or in patients with MG limited to ocular
muscles.
• These Ab interfere with clustering of AChRs at
neuromuscular junctions, as MuSK is known
to do during early development.
• There is also evidence MG patients without
demonstrable Ab to either AChR or MuSK
have other—as yet undefined—Ab that impair
neuromuscular transmission.
Page 32

MuSK Antibody
• About 10–15% of all MG patients with
generalized symptoms do not have
detectable anti-AChRs with AChR
Ab―seropositive‖ generalized MG
• never found, & no HLA association has
been identified.
• on clinical and pathologic grounds, the
disease appears to have several unusual
features.

Page 33

kemala
Page 34

Myastenia gravis 2 dengan thymoma pada penderita anak usia

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