1. Myasthenia gravis is an autoimmune disease causing muscle weakness and fatigability due to antibodies blocking acetylcholine receptors at the neuromuscular junction. 2. Diagnosis involves eliciting a history of fluctuating weakness and physical exam findings of rapidly fatigable weakness, as well as repetitive stimulation tests and tensilon tests. 3. Treatment includes acetylcholinesterase inhibitors, immunosuppressive drugs, thymectomy, and management of myasthenic crisis with IV immunoglobulin or plasma exchange. Long-term management requires balancing medication side effects in children.

1. Case

2. Approach to myasthenia gravis in childhood
Presented by
DR: alsalheen elraied
DR: maraie altopoly
Under supervistion of
DR amal
DR: halima benamer
Dr :wariada bashoon – consultant pediatric neurology

4. •Myasthenia gravis
(MG)
•is an autoimmune
disease in which
antibodies are
directed at the
postsynaptic
membrane of the
neuromuscular
junction,
•leading to varying
degrees of muscle
weakness and
fatigability.

5. History and examinations of
myasthenia case
•The weakness in usualy in cranial in characteistic pattern.
•Weakness in characteristic distribustion ( exaocular muscle , muscle of face
produce snarling expression when smiling . Speech has nasal timbre caused by
weakness in palatine muscle. Difficlt in swallowing which give rise to nasal
regurgitation and aspiration of liquid and solid )
•The weakness in muscle of limb usualy in proximal asyemitrical fasion but with
peserved deep tendon reflexes.
•Fluctuation and fatigue: worse in repeated activity improved by rest
•Effect of previous treatment .
•Examinations
•Ptosis , diplopaia
•On motor examination normal power but on repeated stimulation there is
decrease in response .
•Normal or slightly dimminshed reflexs
•Special testing forward arm abduction (5min)
•Also counting number theres disphonia
•On raising eye lid up by concentration in up fingers

7. Investigation
•AntiACH immunoassay 85% +ve in generilized MG 50% in ocular MG
. But if negative doesn’t exclude the diagnosis.
•About 40% of antiACHR negative pt having anti-MUSK positive in
which the most prominent feature is bulbar symptom( dysarthria-
dysphagia).
•Repetive nerve stimulation : decremental response.
•Single fiber electromyography : blocking and jitter.
•Edrophonium chloride ( tensilon) 2mg iv highly probable diagnosis.
•For ocular or cranial MG : must exclude intralcranial lesion by CT OR
MRI.

8. Recommended investigation for
associated MG diseases.
•Ct or MRI FOR mediastinum for disorder of thymus ,
hyperplasis
•Test for SLE ANA RF antithyroid antibodies
•
•Thyroid function test ( becuaese of association and they may
•exacerbate MG symptom.
•PPD testing because they may interfere with treatment.
•Fasting blood glucose HBA1C because with treatment.

9. CLINICAL TYPES
•Generalised MG: CRANIAL+PROXIMAL LIMB
weakness
•Ocular mysthenia : ocular mainly symptom for
3consequetive years.
•MG crisis: when the weakness affecting
respiratory muscle.

10. Childhood MG
classifications according to age
•Congenital MG
•NEONATAL ( transient MG)
•Familial infantile MG
•Juevenile MG

11. 1-Congenital type :
Maternal MG usually not present
Onset at birth with ocular or generalized
weakness
The course of weakness usually fixed
Family history often present
Anti Ach R antibodies not present

12. Congenital myasthenia syndrome
•CMS comprise heterogenous groupe of disorder that are not
autoammune but rather due genetic mutation incomponent of
neuromuscular junction.
•Share many clinical feature of autoimmune MG but negative
antibodies usually present in the first years of childhood with
variable disability.
•There is often a positive family history, and diagnosis is aided
primarily by electrophysiology and DNA analysis and occasionally by
muscle biopsy .
•With the exception of the autosomal dominantly inherited slow
channel syndrome, the CMS are inherited by autosomal recessive
mutations, which result in loss of function at the neuromuscular
junction

13. 2-neonatal(transient) MG:
-10-20% of infants born to mother with
autoimmune MG
-less common when myasthenia of the mother
treated with immunosuppression
-high anti-ACHR antibody titer
-clinically : present with local or generalized
weakness---respiratory depression----
symptoms subsided over 1 to 4 weeks

14. 3-Familial infantile type:
Maternal MG usually not present
Onest from birth to 1year age
Present with respiratory depression or generalized
weakness
The course of the disease either fatal or enter
improvement over 2years of age
Family history usually present
Ant ChR antibodies not present

15. 4-Juvenile MG
Has the same presentation and response to
therapy as adult type
It is Autoimmune
Antibodies directed against AChR in skeletal
muscle
Cell and complement mediated process
This leads to a reduced number and function
of AChRs
Almost never occurs before 1 year of age.

16. Differential diagnosis of JMG.
• muscular dystrophies
• Neurotoxins For example, botulism,
• Guillain-Barré syndrome Acute disseminated
encephalomyelitis Multiple sclerosis
Brainstem
• tumour
• Hypothyroidism

17. Classification according to antibodies
•the various subgroups of autoimmune MG respond
differently to treatment.
•USUALY defined according to subgroups.
•[1)early-onset MG
•(3)thymoma-associated MG;
•(4)MG with anti-MuSK antibodies;
•(5)ocular MG: symptoms only from periocular muscles;
•(6)MG with no detectable AChR and MuSK antibodies;

18. Juvenile mysthenia gravis
•In the majority of cases MG is caused by antibodies to the nicotinic
acetylcholine receptor (AChR).
•
•Antibodies to the AChR are found in over 80% adults with
generalised disease but only in 55% of adults with
•weakness confined to the oculomotor muscles. Patients with AChR
antibodies are often referred to as seropositive.
•AChR antibodies are probably less frequent in prepubertal
•patients than in adolescent and adult patients
•.
•Antibodies to muscle-specific kinase (MuSK) and to Leucine rich
protein 4 (LRP4) have been reported in some seronegative patients

19. Cont..
•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.
•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”.

20. •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 .
•Peri- or postpubertal patients presenting with JMG
share more similarities with adult-onset MG .

21. Diagnosis
•JMG is primarily a clinical diagnosis with classical
patterns of fluctuating weakness and fatigability
as described above.
•A number of diagnostic tools are available to aid
with diagnosis.
•In very young children it is particularly
important to distinguish between autoimmune
myasthenia and congenital myasthenic
syndromes (CMS)
•as the treatment options, prognosis, and genetic
implications are very different .

22. Cont..
•As conclusion the diagnosis must always be confirmed
by investigation :
•Because
•
•1- other treatable condition may resemble MG
•2- treatment of myasthenia may involve surgery and
prolonged use of drugs of potentially advers side
effects
•Investigation include:
•Antibodies
•Electrodiagnostic study
•Anticholinesterase test.

24. Treatment Principles
•The clinical response and evaluation is most important, but
there tends to be a correlation between MG severity/activity
and AChR antibody concentration in the individual
patientpolicy regarding full drug withdrawal is recommended.
•A low-dose prednisolone, azathioprine, or other immunoactive drugs can in such
patients be sufficient to maintain the stable condition, but also necessary to avoid
new exacerbations.
•Younger patients in particular, not least after thymectomy, can obtain a full clinical
remission without any need for continued drug treatment
•The prognosis has improved srikely as result of advances of treatment which
conisst of
•Anticholinesterase inhibitor
•Thymectomy
•Immunosupression
•Ttt of maysthenic crisis

25. Acetylcholinesterase Inhibitors
•Acetylcholinesterase inhibitors are first-line treatment in
JMG and provide symptomatic relief.
•In mild cases and in some cases of ocular MG,
acetylcholinesterase therapy may be sufficient.
•Pyridostigmine is a long-acting cholinesterase inhibitor
that is commonly used. Dosing is usually 4–6 times per day
and is tailored to effects.
•Overdosage with anticholinesterase medication may cause
increase weakness and other side effects
•With muscarinic side effect (diarrhea-abdominal cramp-
salivations-nausea) so atropine (diphenoxylate) –
lepromide for GI symptoms.
•Cautious use in MuSK-positive children is advised due to
risk of acetylcholine hypersensitivity .

26. Thymectomy
•Recent studies says : thymectomy increases the probability of remission or
improvement of symptoms in AChR seropositive, nonthymomatous, autoimmune
MG .
•More recent reviews of children including prepubertal patients, also suggested
increased remission rates after thymectomy .
•Current evidence suggests that thymectomy should not be recommended in
MuSK-positive disease as it is unclear whether it confers any benefit .
•Thymectomy in pure OMG remains controversial. Whereas OMG is not life
threatening, patients may be dependent on long-term immunosuppressant
medications, including corticosteroids, with the resultant side effects which can be
substantial in children..
•Thymectomy is not proven to reduce risk of progression of OMG to generalised
JMG and is not routinely indicated in pure OMG in children but has been
performed in refractory cases.
•A variety of surgical methods for thymectomy have been described: full or partial
sternotomy, thorascopic, or transcervical approaches
•After thymectomy there is increased risk of antimuscarinic side effects of
cholinesterase inhibitors, and they should therefore be used under close

29. Immunosuppressive therapy
•It include
•Glucocorticoid therapy
•Other agent (cyclophosamide – calcineurin inhibitors)
•Steroid sparing agent( azathioprine and mycophenolate
mofetil)
•Plasmapherisis and IV immunoglobulin
•The indivual choice of drugs should be guided by relative
risk and benefite according to the case :
•For sever cases use IV immunoglobulin and plasmapherisis.
•For intermediate controle ( steroid – cyclosporin-
tacrolimus ).
•For long term controle usualy use of stroid sparing agent

31. Immunosuppressive Therapies
•Corticosteroids are often effective and are the mainstay of
therapy but can worsen symptoms in the first few weeks of
use, particularly if started at high doses , Because of the
numerous adverse effects associated with long-term high-
dose steroids,
•steroids are often used in combination with a steroid-sparing
immunosuppressant, for example, azathioprine.
•Children are at particular risk of steroid side effects, including
growth failure, susceptibility to severe infection, and delay in
receiving live vaccinations.

32. Azathioprine is a purine analogue that suppresses B and T cell
proliferation. It has been found to be effective when used
alone, but is most commonly used in combination with
prednisolone as a steroid-sparing agent.
Beneficial effects may take months to be seen but eventually result in
weaning of steroid doses
Some studies have suggested that azathioprine or corticosteroids
may reduce the likelihood of progression of OMG to the generalised
form of disease .
Studies suggests that cyclosporin either as monotherapy or with
corticosteroids, or cyclophosphamide in conjunction with
corticosteroids, improves symptoms of MG within 1 year
Mycophenolate mofetil (MMF) blocks purine synthesis by selectively
inhibiting proliferation of activated T and B lymphocytes . A recent
retrospective study of AChR seropositive patients, which included
children (age range 11–87 y), concluded some benefit of MMF
when used either as monotherapy or in conjunction with
prednisolone

33. •Tacrolimus inhibits interleukin 2.
•Efficacy studies have been carried out in adults and
postpubertal children and have shown early and
sustained improvement of symptoms with tacrolimus,
allowing dose reduction of prednisolone and in many
cases its complete withdrawal.
•
•A case has also been reported of tacrolimus being
successfully used as adjunctive therapy in refractory
pure ocular myasthenia in a 3-year-old girl .
•Rituximab is a chimeric IgG monoclonal antibody that
depletes B cells and has been used in refractory JMG

34. Plasma Exchange/Intravenous
Immunoglobulin (IVIG)
•Improvement in symptoms after plasma
exchange or administration of IVIG is usually
temporary, 4–10 weeks.
•Their use is therefore largely reserved to optimise
condition for surgery before thymectomy and in
management of myasthenic crisis.
•single randomised controlled trial showed no
evidence for superior benefit of plasma exchange
over IVIG in treatment of myasthenic crisis.

35. management of myasthenic crisis
•Myasthenic crisis is defined as excerbation of weakness
sufficient to endanger life :
•It is uauslay consist of respiratory failure .
•Crisis rarely accure in good managed case
•The most common cause of crisis is intercrrent
infections.
•The myasthenic patient with fever should be treated as
immunoconpromised case in ICU
•With AB and respiratory assestance
•And plasmapherisis and IV immunoglobulin which is
hasten recovery.

37. Patient assesment
•Interval assement form
•Which use clinical assesment by history and
examination to asses the pts response to
treatment. Useful tool for treatment
reevaulation.
•Using AchR antibody titre
•Provide valuable informations about
treatment effectiveness.

39. In summary
• myasthenia gravis Is Rapidly fatigable weakness (characteristic), double vision,
upper airway weakness
• diagnosis and assesment of ttt : Largely on a clinical basis, by eliciting a history of
fluctuating weakness and by physical findings of rapidly fatigable
• Weakness
• other diagnostic tool in repetitive stimulation test : Rapid loss of activity after
repetitive
• stimulation of the same muscles
• Also tensilon test: A very short-acting acetylcholinesterase
• inhibitor administered intravenously
• In myasthenia, Tensilon usually produces
• a rapid, dramatic increase in strength. A
• positive test is consistent with (but does
• not diagnose) myasthenia gravis.
• ttt include;
• Acetylcholinesterase inhibitors (e.g.,
• pyridostigmine); immunosuppressive drugs and thymectomy