Childhood Myasthenia Gravis MG - PowerPoint PPT Presentation

Loading...

PPT – Childhood Myasthenia Gravis MG PowerPoint presentation | free to download - id: 143eb1-OTI0Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Childhood Myasthenia Gravis MG

Description:

Ocular symptoms occur in 90% of cases. ... Seroconversion may occur within 12 months of onset in 15% of cases. ... Severe muscle weakness may occur with IVMP. ... – PowerPoint PPT presentation

Number of Views:773
Avg rating:3.0/5.0
Slides: 47
Provided by: CCRI5
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Childhood Myasthenia Gravis MG


1
Childhood Myasthenia Gravis
(MG)
  • Roula al-Dahhak, M.D.
  • Assistant Professor of Pediatrics and Neurology
  • Columbus Childrens Research Institute
  • Neuromuscular Program

2
Introduction
  • MG is a neuromuscular disorder that affects
    skeletal muscles
  • MG was first described in the year1672
  • Onset in childhood was recognized by Erb in 1879
  • MG in childhood comprises 10-20 of all
    myasthenic patients

3
Types
  • Autoimmune MG (Juvenile) (JMG)
  • Congenital MG (CMG)
  • Neonatal (transient) MG 10

4
Juvenile MG (JMG)
  • Autoimmune
  • Antibodies directed against AChR in skeletal
    muscle
  • Cell and complement mediated process
  • This leads to a reduced number and function of
    AChRs

5
Juvenile MG (JMG)
  • The severity of the symptoms parallels the
    reduction in AChRs.
  • Factors that starts the process ??

6
JMG (epidemiology)
  • Almost never occurs before 1 year of age.
  • It is more common in Oriental than Caucasian
  • In North America 10-15 (1.1 per
    million total
  • population/ year)
  • In China and Japan 43

7
JMG (epidemiology)
  • Pre-puberty Incidence is higher in black as
    compared to white
  • Pre- puberty white patients show an equal sex
    ratio female are more affected among black
    population.
  • Post-puberty Females are more commonly affected
    than males.
  • Possible genetic and environmental trigger
    factors.

8
JMG (pathology)
  • Pathogenic mechanisms are similar to adult.
  • Age, sex hormones influence the incidence of JMG.
  • Female sex hormones enhance while the male sex
    hormones inhibit the thymus function.
  • Certain HLA types are linked to earlier age of
    onset.

9
JMG ( Presentation)
  • Fluctuating and fatigable weakness
  • Symptoms are worse through the day.
  • Worsening of symptoms may occur after febrile
    illness or insect bites or certain medications.

10
JMG ( Presentation)
  • Extraocular, bulbar and limb weakness.
  • Ocular symptoms occur in 90 of cases.
  • MG remains ocular in only 10-15 of cases
    (usually with prepubertal onset)

11
JMG ( Presentation)
  • The maximal disease severity is within 2 years of
    onset.
  • 50 of cases with ocular MG will become
    generalized within 2 years and 75 within 4
    years.

12
JMG (presentation)
  • Bulbar symptoms affect 75 of patients
    dysphagia, dysarthria, facial weakness.
  • Limb weakness (proximal), fluctuating.
  • Systemic weakness may affect the diaphragm and
    other muscles of respiration.

13
JMG (presentation)
  • Thymoma is rare
  • Other autoimmune disease are common diabetes,
    thyroid dx and JRA.
  • Spontaneous remission is more common among young
    patients (up to 30 of cases within 15 years of
    disease onset in one study)

14
JMG (diagnosis)
  • Fluctuating weakness
  • Positive edrophonium (tensilon) test negative in
    8 of children. Non-specific.
  • Electrophysiological test is age limited
  • RNS
  • SFEMG
  • AChR antibodies

15
JMG (diagnosis) RNS
  • Studies on pediatric population are limited
  • One study of 12 children with all forms of MG
    showed RNS is positive in
  • 75 of neonatal MG
  • 88 of JMG
  • Sensitivity increases with proximal muscle
    evaluation.

16
JMG (diagnosis) RNS
  • Decrementgt10 indicates a NMJ disorder.
  • RNS does not discriminate between CMG and JMG.
  • SF-EMG most sensitive methode
  • Absence of jitter on SFEMG of a weak muscle r/o
    NMJ d/o.
  • SFEMG cant discriminate between CMG and JMG.

17
JMG (Diagnosis) AChR antibodies
  • A Higher percentage of young childrens are
    sero-negative as compared with adults (adults are
    positive is 70-90).
  • Age related
  • Pre-puberty 36-50 are sero-negative
  • peri-puberty 25-30
  • post puberty 0-9

18
JMG (Diagnosis) AChR antibodies
  • Most common AChR Ab are binding Ab.
  • Modulating antibodies are positive in 6 of
    sero-negative adults.
  • Seroconversion may occur within 12 months of
    onset in 15 of cases .

19
JMG (diagnosis) MuSK antibodies
  • MuSK Ab is positive in 40 of seronegative adult
    pts, but it is less positive in children.
  • MuSK is negative in pure ocular cases and in
    patients with thymoma, and in seropositive pts.
  • Mechanism of action of Musk??

20
JMG (diagnosis) MuSK antibodies
  • The disruption of NMJ may not be mediated by
    complement.
  • Thymus role with MuSK is ??
  • The role of cell mediated immunity is ??
  • Thymic hyperplasia is absent among MuSK positive
    patients.

21
JMG (diagnosis) MuSK antibodies
  • Among MuSK ab positive pts, bulbar and facial
    weakness and atrophy are prominent in white
    women.
  • In black women who have positive MuSK ab, neck,
    shoulder, respiratory weakness with less marked
    or absent ocular weakness predominate.
  • Both seronegative and positive pts respond
    similarly to PE and IS therapy.

22
JMG (DDx)
  • Congenital MG
  • CN palsies
  • GBS
  • Myopathies (with ptosis and EOM abnormalities)
  • Botulism
  • LEMS
  • Venoms, toxins, drugs
  • Brain stem lesions.
  • hysteria

23
JMG (DDx)
  • DDx between JMG and CMG

  • JMG CMG
  • Age of onset gt12
    months since birth
  • Weakness
    fluctuating stable
  • Spontaneous remession possible
    no
  • AChR Ab
    varies normal
  • FH
    -
  • Response to IS
    effective non-effective
  • Thymectomy possibly
    effective non-effective
  • Response to AChEI 62
    40
  • MG crisis
    yes no

24
JMG (therapeutic options)
  • Anticholinesterase medications
  • Short-term immunomodulation (PE or IVIG)
  • Long-term immunosuppression
  • Thymectomy

25
Rx(AChEI)
  • Are usually the first treatment for JMG.
  • Pyridostigmine 1 mg/kg q 4-6 hours
  • AChEIs do not influence the autoimmune process
    and do not control all symptoms.
  • Response may diminish with time
  • A drug holiday is recommended to reestablish
    efficacy.
  • SE n/v, abdominal pain, diarrhea, sweating,
    cholinergic crisis (worsening weakness)

26
Rx(Short-term immunomodulation) PE
  • PE removes antibodies and other protein from
    circulation.
  • Improvement within days and may last4-10 weeks.
  • Equally effective in seronegative and
    seropositive patients.
  • A course of 5-6 treatment over 2 weeks. Volume is
    replaced with saline, and close monitoring of
    fluid and electrolytes balance is recommended.
  • Needs to be repeated frequently

27
Rx(Short-term immunomodulation)PE
  • Indication of PE
  • 1) Preoperative period
  • 2) Acute care of very weak patients
  • 3) At initiation of immunosupressive
    therapy
  • It requires double lumen venous catheter under
    general anesthesia in children younger than 7
    years.

28
Rx(Short-term immunomodulation)IVIG
  • IVIG use in pediatrics population is not very
    well documented.
  • Up to 70 of pts improve with IVIG, usually
    within 5 days of onset of treatment.
  • Easier to use for acute therapy in young pts.
  • However, improvement is less than with PE.

29
Rx(Short-term immunomodulation)IVIG
  • The standard dose is 2 gm/kg giving slowly at 400
    mg/kg/ day X 5days.
  • Another approach dose of 1 g/kg daily for 2
    days.
  • Improvement lasts for 3-6 weeks and up to 17
    weeks for pts on long-term immunosuppressants.

30
Rx(Short-term immunomodulation)IVIG
  • Indications for IVIG
  • 1) Preoperative period
  • 2) Pts with severe weakness
  • 3) At the initiation of immunosuppressants
  • IVIG can be repeated as needed.
  • SE headache, aseptic meningitis (in
    migraineurs), flu-like symptoms, hyperactivity,
    (CHF, DVT, ARF in adults)
  • Beware of IgA deficiency

31
Rx(Long-term immunosuppressants steroids)
  • Steroids suppress multiple aspects of the
    humoral, cell-mediated, and other arms of the
    immune system.
  • Are helpful in 80 of adults pts.
  • In children improvement occurs in only 10-61 of
    pts.
  • Steroids do not influence the chance for
    remission after thymectomy.

32
Rx(Long-term immunosuppressants steroids)
  • Always start slow.
  • Starting at higher (therapeutic dose 1-2
    mg/kg/day) will produce weakness in 8 of pts
    within the first 3 weeks of treatment.
  • Improvement begins w/i 4 weeks and maximal by 3-9
    months.
  • Preparatory PE or IVIG is helpful.

33
Rx(Long-term immunosuppressants steroids)
  • SE of chronic steroid use may be serious.
  • 60 of adults experience side effects.
  • SE are more in children due to the effect of
    steroids on development growth retardation, bone
    mineralization and development abnormalities.

34
Rx(Long-term immunosuppressants steroids)
  • High dose IVMP
  • Limited use, limited data.
  • SE can be serious sudden death, atrial fib,
    peptic bleeding, transient psychosis.
  • Severe muscle weakness may occur with IVMP.
  • Typical dose 1gm/day given slowly (1/6th hourly)
    for 5 days.
  • Watch for fluid balance, electrolytes, blood
    pressure, hematuria, ECG, and use ranitidine
    prophylaxis.
  • In less severe cases (ocular MG).

35
Rx(Long-term immunosuppressants others)
  • Azathiprine
  • It metabolizes to a cytotoxic 6-MP.
  • It inhibits DNA and RNA synthesis and interfers
    with T cell function.
  • It is used to limit steroid use for long
    duration.
  • Dose 2mg/kg/day with weekly increments of 0.5
    mg/kg/day

36
Rx(Long-term immunosuppressants others)
  • Azathiprine (cont)
  • Onset of action is slow.
  • Maximum benefit is delayed for 3-12 months.
  • Improvement occurs in 30-90 of adult and
    pediatric pts.
  • SE flu-like symptoms, abnormal LFTs, leukopenia,
    pancytopenia, immunosuppression, late development
    of malignancy.

37
Rx(Long-term immunosuppressants others)
  • Cyclosporin A
  • It inhibits T helper function and T
    cell-dependent antibody responses and activates T
    suppressor functions.
  • In adults, improvement occurs in 40, usually
    within 2 months.
  • Dose 5 mg/kg/day divided in two doses.
  • SE nephrotoxicity, HTN, headache, and cost.

38
Rx(Long-term immunosuppressants others)
  • Cyclophosphamide
  • It inhibits B cell proliferation and IG
    synthesis.
  • Faster action than Azathioprine.
  • Worse side effects immunosuppression, sterility,
    teratogenesis, and malignancy.

39
Rx(Long-term immunosuppressants others)
  • Mycophenolate
  • Newest immunosuppressant.
  • Mild side effects.
  • Rapid onset of therapeutic benefit.

40
Rx(Thymectomy)
  • No controlled studies available.
  • In children with generalized and/or bulbar
    weakness It produces complete remission in
    10-75 and improvement in 57-95.
  • It is more effective within 12 months of disease
    onset.
  • Helpful for pts with bulbar or generalized
    weakness.
  • Ocular MG?????

41
Rx(Thymectomy)
  • Complete excision.
  • It may help in reducing the dose of medications.
  • Relatively safe.
  • Preoperative prep minimizes the complications.
  • Consider it in seropositive (AChR Ab) patients.

42
Rx (Thymectomy) Timing of surgery
  • Pre-pubertal
  • The incidence of JMG is low.
  • Difficult to differentiate from CMG.
  • Spontaneous remission is more common (better in
    white than black) than among older pts.
  • Spontaneous remission (w/o thymectomy) is better
    in younger children with onset before 11 years.

43
Rx (Thymectomy) Timing of surgery
  • Conclusion Among pts with prepubertal onset,
    spontaneous remission is common and thymectomy
    may make little difference to the rate of
    remission.

44
Rx (Thymectomy) Timing of surgery
  • Peri-puberty
  • Response is excellent among white pts who have
    the surgery within 12 months of onset.
  • The only response in black was when the surgery
    occurred within 1 year of disease onset.
  • Conclusion thymectomy is recommended early for
    all peripubertal pts with bulbar or generalized
    weakness.

45
Rx (Thymectomy)
  • Patients with elevated MuSK Ab respond poorly to
    thymectomy
  • (Avoid surgery here).

46
  • Questions????
About PowerShow.com