myastenia gravis 2 dengan thymoma pada penderita anak usia
DESCRIPTION
TRANSCRIPT
Powerpoint TemplatesPage 1
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
DISKUSI KASUS
Powerpoint TemplatesPage 2
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
Powerpoint TemplatesPage 3
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 TemplatesPage 4
Darah Lengkap 3-1-2010 15-1-2010
Hemoglobin (11.0-16.5 mg/dl)Lekosit (3500-10.000 /µL)LED Trombosit (150.000 - 200.000/µL)Hmt
Hit.JenisMCV (80-99 µm3)MCH (26.5-33.5 pq)MCHC (31.5-35.0 g/dl)RDW (10-15 µm3)
11.56.900
283.00035.3
8126.632.614.2
12.49.600
34351.000
7/-/-/49/38/5/68627.732.413.6
Powerpoint TemplatesPage 5
LABORATORIUMImunologi 5-1-2010
Total T3 (0.79-1.49 ng/dl)Free T4 (0.71-1.85 ng/dl)TSH (0.49-4.67 µIU/ml)
ElektrolitNatrium (136-145 mmol/l) Kalium (3.5-5.0 mm0l/l)Chlorida (98-106 mmol/l)Kalsium (7.6-11.0 mmol/l)Fosfor (2.5-7-0 mmol/l)
Kimia DarahGDS (60-110 mg/dl)Ureum (10-50 mg/dl)Kreatinin (0.7-1.5 mg/dl)
1.090.912.517
1404.541118.54.84
9628.40.37
LAB0RATORIUM
Powerpoint TemplatesPage 6
Kimia Darah 3/1 5/1 14/1 21/1
GDS (60-110 mg/dl)
Ureum (10-50 mg/dl)
Kreatinin (0.7-1.5 mg/dl)
28.4
0.37
96 EMGKesimpulan : Menyokongsuatu myastemia gravis
CT ScanKesimpulan :Massa soft tissue pd mediastinum ant. Suspek Thymoma dg DD retrosternal goiter dan limfoma
Powerpoint TemplatesPage 7
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)
Powerpoint TemplatesPage 8
DISKUSI1. Penegakan diagnosa
2. Laboratorium Myasthenia Gravis dan Thymoma
Powerpoint TemplatesPage 9
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
Powerpoint TemplatesPage 10
• 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.
Powerpoint TemplatesPage 11
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
Powerpoint TemplatesPage 12
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.
Powerpoint TemplatesPage 13
Powerpoint TemplatesPage 14
Powerpoint TemplatesPage 15
….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.
Powerpoint TemplatesPage 16
….pathophysiology Myasthenia Gravis
• the fundamental defect is a decrease in the 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
Powerpoint TemplatesPage 17
…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.
Powerpoint TemplatesPage 18
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.
Powerpoint TemplatesPage 19
..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 rests.
Powerpoint TemplatesPage 20
….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.
Powerpoint TemplatesPage 21
DIAGNOSIS & EVALUATIONHistory• 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
Powerpoint TemplatesPage 22
…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
Powerpoint TemplatesPage 23
…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
Powerpoint TemplatesPage 24
1 . PENEGAKAN DIAGNOSA PASIEN
• Ptosis (+) • Gejala bertambah dgn
aktifitas• CT Scan thorax : suspek
thymoma• EMG : menyokong suatu
Myastenia Gravis
TEORI• Ptosis,diplopia,dysphagia• Dysharthria• Myasthenic crisis (paralysis
of respiratory) • 75% have an abnormality of
the thymus• 10% have a thymoma • single fiber
electromyography (SFEMG)• AChR Ab • Edrophonium test
Myasthenia Gravis dgn thymoma
Powerpoint TemplatesPage 25
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.
Powerpoint TemplatesPage 26
… 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.
Powerpoint TemplatesPage 27
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.
Powerpoint TemplatesPage 28
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.
Powerpoint TemplatesPage 29
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.
Powerpoint TemplatesPage 30
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.
Powerpoint TemplatesPage 31
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.
Powerpoint TemplatesPage 32
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.
Powerpoint TemplatesPage 33
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.
Powerpoint TemplatesPage 34
THANKS A LOT
THANKS FOR YOUR
ATTENTION
kemala