myasthenia gravis with thymoma
TRANSCRIPT
Dr.Azad A Haleem AL.MezoriDCH, FIBMS
Lecturer University Of DuhokColleg of Medicine
Pediatrics Department2016
Childhood-onset Myasthenia Gravis with
Thymoma
Case Summary
Eight years old boy ………• presented with difficulties chewing, swallowing and
Drooling + • weakness of the limbs muscles, • Fluctuating and generally minimal symptoms are
present on awakening in the morning and gradually worsen as the day progresses.
• No others GIT, Respiratory and GUS … No fever ?• Past History : IDA ….. • F.H & D.H: nothing significant
• They consulted many doctors and many investigations done for him?
• Heevi pediatric teaching hospital complete history taken and general and systemic examination done for the patient which revealed;
Lethargic with Drooling Afebrile Vital signs:Bp-130/95, pulse-105bpm, RR-17
cpm, temp.-36.8oC, Spo2-92% room air. On Examination
CNS; Neurologic examination revealed masticatory and bulbar muscle weakness,proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs.
chest; harsh vesicular breathing with good air entry.
Heart: Audible S1 & S2with systolic murmur in the apex.
Abdomen: liver and spleen just palpable.
Case SummaryOn Examination
o CBC & ESR, RFTs, LFTs,RBS: within normal limits.
o CK; Normal.o TFT: within normal limits. o ANA: Normalo Brain CTScan: normal.o Repetitive nerve stimulation (RNS) ?o Serum antiacetylcholine receptor antibodies?
Case Summary Investigations
Differential Diagnosis?
Brainstem tumourAcute disseminated encephalomyelitisGuillain-Barr´e syndromeNeurotoxins ; For example, botulism, venomsMyopathiesHypothyroidismDrugs Adverse effectsSomething Else?
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o Repetitive nerve stimulation (RNS): a decremental response on repetitive nerve stimulation, and
o increased titers of serum antiacetylcholine receptor antibodies.
Myasthenia gravis (MG)
?Diagnosis…..
Treatment
o The patient received anticholinesterases: Pyridostigmine (Mestinon)
• On further enquiry… Farther investigations done for the patient to know the cause of Myasthenia gravis focusing on Thymus.
• MRI of the Upper Chest: 55X25 mm enhancing soft tissue lesion seen in the upper Anterior mediastinum, the lesion look adherent to the Aortic Arch, finding suggestive of Thymoma.
Case Summary
Myasthenia gravis (MG) & Thymoma
?Diagnosis…..
Surgical Treatment
• Thymectomy done ……• A pathohistologic analysis of the thymus gland
indicated Thymoma. • Now the patient is totally normal and on
follow up.
Before treatment After medical treatment After Surgery
Myasthenia gravis (MG) & Thymoma
Some theory …..
Myasthenia gravis (MG)
• Myasthenia gravis (MG) is an autoimmune disease.
• Clinically characterized by: Weakness of skeletal muscles Fatigability on exertion.• Where MG presents before 19 years of age, it
is termed juvenilemyasthenia gravis (JMG).
Neuromuscular Junction (NMJ) Components: Presynaptic membrane Postsynaptic membrane Synaptic cleft Presynaptic membrane contains vesicles with
Acetylcholine (ACh) which are released into synaptic cleft ACh attaches to ACh receptors (AChR) on postsynaptic
membrane. The Acetylcholine receptor (AChR) opens when bound by
ACh
Anatomy & Physiology
Pathophysiology• In MG, antibodies are directed
toward the acetylcholine receptor at the neuromuscular junction of skeletal muscles.
• Results in: • Decreased number of nicotinic
acetylcholine receptors at the motor end-plate
• Reduced postsynaptic membrane folds
• Widened synaptic cleft
Classification o Childhood myasthenias encompass JMG, which
is the subject of this paper; o congenital myasthenic syndromes, a
heterogeneous group of genetically inherited disorders of the neuromuscular junction;
o transient neonatal myasthenia, which results from placental transfer of maternal AChR (or very occasionally MuSK antibodies) to infants of mothers with autoimmune MG.
Epidemiology and Clinical Features
• JMG is a rare disorder of childhood, but its incidence and prevalence vary geographically. Precise data on incidence and prevalence are not known.
• peak age at presentation of 5–10 years.
Clinical Features The most frequent clinical
presentation of JMG is with ptosis, which is often associated with other ocular symptoms namely unilateral or asymmetric ophthalmoplegia, strabismus, and lid twitch, which may only be elicited after sustained upgaze .
Most children also develop generalised muscle weakness, which presents as painless fatigability of the bulbar and limb musculature, with resultant dysphonia, dysphagia, and proximal limb weakness
Clinical Features Weakness is often
fluctuating and usually becomes more pronounced through the day and improves with rest.
Children are at risk of choking or aspiration and are at increased risk of chest infection.
Occasionally, impairment of the respiratory muscles necessitates ventilatory support. This is known as “myasthenic crisis”.
distinct clinical features
• Prepubertal children presenting with JMG have some interesting and distinct clinical features compared with those who present around or after puberty.
• Prepubertal JMG is more likely to manifest as ocular myasthenia .
• There is an equal male: female ratio , in contrast to the female predominance that is seen in peri-/postpubertal children, and a
• better prognosis, with a higher rate of spontaneous remission in prepubertal presenters.
Diagnosis of JMG• JMG is primarily a clinical diagnosis • A number of diagnostic tools are available to aid with diagnosis: Serology. Detection of antibodies to the AChR supports the
diagnosis of JMG. Pharmacological Investigation. The Tensilon test involves
intravenous infusion of edrophonium, a fast-acting, shortduration cholinesterase inhibitor.
Electrophysiology: Repetitive nerve stimulation in JMG will show a decrement in the
compound motor action potential stimulation. Single fibre EMG (SFEMG) is especially useful in diagnosis of
seronegative MG and congenital myasthenic syndromes. Imaging. Although thymoma in children is rare, the thymus must be
imaged (usually by CT) once JMG has been diagnosed.
Management
• Management of children with JMG should be delivered by a multidisciplinary team comprising;
• paediatrician with support from a • paediatric neurologist, • physiotherapist, • occupational therapist, • psychologist, • speech therapist and dietician.
Treatment Notes
Acetylcholinesterase inhibitors First line therapy.May be sufficient in ocular JMG or mild generalised JMG
Thymectomy Recommended to increase remission rates in postpubertal, seropositive children
Steroids Often used in combination with steroid sparing agents. Significant side-effect profile if used long-term at high dose
Steroid sparing agents Azathioprine, Cyclosporin, Cyclophosphamide, Tacrolimus, Rituximab.
IVIG/Plasma exchange
Management
Thymoma• Thymoma is an uncommon and slow-growing neoplasm. • It is derived from thymic epithelial cells and comprises
about 20% to 30% of mediastinal masses in adults, but only about 1% in pediatric patients.
• Patients usually present with:• mass-associated respiratory symptoms, superior vena
cava syndrome, or • paraneoplastic syndrome : Seventy percent of
thymomas are associated with paraneoplastic syndromes such as:
myasthenia gravis (MG), red cell aplasia, pemphigus, and immunoglobulin (Ig) deficiency.
• As many as 50% of patients with thymoma have MG, and
• approximately 15% of patients with MG have thymoma.
• Due to the limited number of cases, knowledge, and experience with thymoma in pediatric patients, the diagnosis and treatment are very challenging for this age group.
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