Childhood-onset Myasthenia Gravis with Thymoma

2. 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

3. • 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

4. 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 Summary
On Examination

5. o CBC & ESR, RFTs, LFTs,RBS: within normal
limits.
o CK; Normal.
o TFT: within normal limits.
o ANA: Normal
o Brain CTScan: normal.
o Repetitive nerve stimulation (RNS) ?
o Serum antiacetylcholine receptor antibodies?
Case Summary Investigations

6. Differential Diagnosis?
Brainstem tumour
Acute disseminated encephalomyelitis
Guillain-Barr´e syndrome
Neurotoxins ; For example, botulism,
venoms
Myopathies
Hypothyroidism
Drugs Adverse effects
Something Else?
6

7. o Repetitive nerve stimulation (RNS): a
decremental response on repetitive nerve
stimulation, and
o increased titers of serum antiacetylcholine
receptor antibodies.

8. Diagnosis…..

9. Treatment
o The patient received anticholinesterases:
Pyridostigmine (Mestinon)

10. • 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

12. Diagnosis…..

13. Surgical Treatment
• Thymectomy done ……
• A pathohistologic analysis of the thymus gland
indicated Thymoma.
• Now the patient is totally normal and on
follow up.

14. Before treatment After medical treatment After Surgery

15. Some theory …..

16. 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).

17. 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

18. 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

19. 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.

20. 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.

21. 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

22. 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”.

23. 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.

24. 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.

25. 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.

26. 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

27. 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.

28. • 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.

29. THANKS FOR YOUR
ATTENTION