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    Myasthenia Gravis

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    AliMalik
    Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies against acetylcholine receptors at the neuromuscular junction. This results in muscle fatigue and weakness. It commonly affects eye muscles initially and can then progress to other muscles. Symptoms vary in severity and can include drooping eyelids, difficulty speaking, swallowing and breathing. Diagnosis involves testing for acetylcholine receptor antibodies and responding to treatment with acetylcholinesterase inhibitors. Management focuses on immunosuppression and crisis prevention. Prognosis depends on disease severity and response to treatment.

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    Myasthenia Gravis

    Uploaded by

    AliMalik
    72 views24 pages
    Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies against acetylcholine receptors at the neuromuscular junction. This results in muscle fatigue and weakness. It commonly affects eye muscles initially and can then progress to other muscles. Symptoms vary in severity and can include drooping eyelids, difficulty speaking, swallowing and breathing. Diagnosis involves testing for acetylcholine receptor antibodies and responding to treatment with acetylcholinesterase inhibitors. Management focuses on immunosuppression and crisis prevention. Prognosis depends on disease severity and response to treatment.

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    Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies against acetylcholine receptors at the neuromuscular junction. This results in muscle fatigue and weakness. It commonly affects eye muscles initially and can then progress to other muscles. Symptoms vary in severity and can include drooping eyelids, difficulty speaking, swallowing and breathing. Diagnosis involves testing for acetylcholine receptor antibodies and responding to treatment with acetylcholinesterase inhibitors. Management focuses on immunosuppression and crisis prevention. Prognosis depends on disease severity and response to treatment.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    72 views24 pages

    Myasthenia Gravis

    Uploaded by

    AliMalik
    Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies against acetylcholine receptors at the neuromuscular junction. This results in muscle fatigue and weakness. It commonly affects eye muscles initially and can then progress to other muscles. Symptoms vary in severity and can include drooping eyelids, difficulty speaking, swallowing and breathing. Diagnosis involves testing for acetylcholine receptor antibodies and responding to treatment with acetylcholinesterase inhibitors. Management focuses on immunosuppression and crisis prevention. Prognosis depends on disease severity and response to treatment.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 24

    Myasthenia Gravis

    (Goldflam disease)
    Haider Ali Malik
    20130180
    Definition
    • Myasthenia gravis is a chronic disease caused
    by autoantibodies that block the function of
    postsynaptic acetylcholine receptors at motor
    end plates, which results in the degradation
    and depletion of the receptors.

    • This results in rapid fatigability of striated


    muscles
    Epidemiology
    • The disease is not hereditary
    • Incidence of approx. 3 in 100,000
    • Can manifest at any age
    • More common in women under 20-30 yrs
    • More common in men over 40-60 yrs
    • Disease can be transferred to animals with
    serum
    Pathophysiology
    Pathology

    • IgG and T cell dependent antibody is produced against the


    acetylcholine receptors and fixes to receptor sites, blocking
    the binding of acetylcholine.
    • Thus, immunotherapeutic strategies directed against either
    the antibody-producing B cells or helper T cells are effective in
    this antibody-mediated disease
    Pathophysiology
    In MG, the fundamental defect is a decrease in the number
    of available AChRs at the postsynaptic muscle membrane.
    In addition, the postsynaptic folds are flattened, or
    “simplified.” These changes result in decreased efficiency of
    neuromuscular transmission.
    Therefore, although ACh is released normally, it produces
    small end-plate potentials that may fail to trigger muscle
    action potentials.
    Failure of transmission at many neuromuscular junctions
    results in weakness of muscle contraction.
    What is Presynaptic rundown?
    • Amount of Ach released per impulse normally declines on
    repeated activity.

    Decreased
    efficiency of
    NMT
    Myasthenia
    Myasthenia fatigue
    gravis
    Normal
    presynapatic
    rundown
    Autoimmune response
    • Mediated by specific anti AchR ab
    • How do they act ?

    RAPID
    CROSS
    LINKING,ENDOCYTOSIS TURNOVER OF
    AchRs

    AntiAch Receptor
    Ab BLOCKADE OF
    Decreased
    ACTIVE SITE OF
    AchRs efficacy

    DAMAGE TO
    COMBINED WITH
    COMPLEMENT
    POST SYNAPTIC
    MEMBRANE
    Pathophysiology
    • An immune response to muscle-specific
    kinase (MuSK), a protein involved in AChR
    clustering at neuromuscular junctions,
    can also result in MG, with reduction of
    AChRs demonstrated experimentally.
    Anti-MuSK antibody occurs in about 40%
    of patients without AChR antibody.

    • A small proportion of patients whose


    sera are negative for both AChR and
    MuSK antibodies have antibodies to
    another protein at the neuromuscular
    junction—low-density lipoprotein
    receptorr elated protein 4 (lrp4)—that is
    important for clustering of AChRs
    What is the basis of autoimmune
    response?
    • Unknown
    • Hypothesis –THYMUS plays a role..
    • ABNORMAL in 75% pts with MG.
    – Of them 65% -HYPERPLASTIC (presence of active germinal
    centers histologically)
    – 10% -thymomas.
    Which cells are the initiators?
    • MUSCLE LIKE CELLS (myoid cells) IN THYMUS.
    • Have AchR on surface –autoantigen – autoimmune reaction
    Types

    • Several Types of Myasthenia Gravis


    – Neonatal Myasthenia Gravis: A transient condition in 10%
    to 15% of infants born to mothers with MG.
    – Congenital Myasthenia
    – Juvenile Myasthenia: Onset is around 10 years of age.
    – Ocular Myasthenia
    – Generalized Autoimmune Myasthenia
    Clinical Manifestations
    • Insidious onset
    – May first appear during pregnancy, during the postpartum
    period, or in combination with the administration of anesthetic
    agents.
    • Complaints
    – Most individuals complain of fatigue and
    progressive weakness.
    – The person usually has a history of frequent respiratory tract
    infections.
    Clinical Manifestations
    • trouble talking
    • problems walking up stairs or lifting objects
    • facial paralysis
    • difficulty breathing because of muscle weakness
    • difficulty swallowing or chewing
    • fatigue
    • hoarse voice
    • drooping of eyelids
    • double vision

    Not everyone will have every symptom, and the degree of muscle weakness can
    change from day to day. Symptoms generally worsen with physical activity and
    improve after resting or a good night's sleep.
    Clinical pattern
    • Characteristic pattern

    Early in course Facial Bulbar Respiratory


    lids,EOMs weakness weakness muscles

    Nasal timbre
    voice
    Snarling Nasal
    Ptosis, expression. regurgitation Difficulty in
    aspiration of respiration..
    diplopia liquids and
    Difficulty in Decreased breath
    food holding time
    chewing meat

    Generally progresses over time so that within 2 years of onset of ocular MG, 90% have
    bulbar and proximal symmetric limb weakness
    • Painless
    • Bowel and bladder function preserved
    • The limb weakness in MG is often proximal
    and may be asymmetric
    • Deep tendon reflexes are preserved
    • If weakness remains restricted to the extraocular
    muscles for 3 years, it is likely that it will not
    become generalized, and these patients are said
    to have ocular MG (16% of patients)
    OSSERMAN Classification

    1. Class I Any ocular muscle weakness

    2. ClassII Mild weakness other than ocular


    IIa Predominantly limb,axial, or both
    IIb Predominantly orpharyngeal/respiratory
    3. Class III Moderate weakness other than ocular
    IIIa Predominantly limb,axial, or both
    IIIb Predominantly orpharyngeal/respiratory
    4. Class IV Severe weakness other than ocular
    IVa Predominantly limb,axial, or both
    IVb Predominantly orpharyngeal/respiratory

    5. Class V Intubation with/without ventilation


    CO-EXISTING AUTOIMMUNE DISEASES
     Hyperthyroidism
    – Weakness may not improve simply by treatment of
    patients with MG; with co-existing hyperthyroidism.
     Rheumatoid arthritis
     Scleroderma
     Lupus

     Sjӧgren syndrome
     mixed connective tissue disease
     anticardiolipin antibody
     polymyositis
    Diagnosis
    Complications
    – Myasthenic Crisis happens when extreme muscle weakness
    causes quadriparesis or quadriplegia, difficulty swallowing, and
    shortness of breath. A person in this state is in danger of
    respiratory arrest.
    – Cholinergic Crisis occurs from anticholinesterase drug toxicity.
    This is similar to Myasthenic Crisis, but also includes increased
    intestinal motility with diarrhea and complaints of cramping,
    fasciculation, bradycardia, constriction of the pupils, increased
    salvation, and sweating. A person in this state may also be in
    danger of respiratory arrest.
    • Long-term steroid use may cause or aggravate
    osteoporosis, cataracts, hyperglycemia, weight
    gain, avascular necrosis of hip, hypertension,
    opportunistic infection, and other complications.
    Long-term steroid use also increases the risk of
    gastritis or peptic ulcer disease. Patients on such
    therapy should take an H2 -blocker or antacid as
    well.
    • Infections such as tuberculosis, systemic fungal
    infections, and Pneumocystis carinii pneumonia.
    The risk of lymphoproliferative malignancies may
    be increased with chronic immunosuppression
    Prognosis
    • Prognosis is variable. Remissions sometimes
    occur spontaneously. When myasthenia is
    confined to the eye muscles, the prognosis is
    excellent and disability slight. Young female
    patients with generalised disease have high
    remission rates after thymectomy, whilst older
    patients are less likely to have a remission
    despite treatment. Rapid progression of the
    disease more than 5 years after its onset is
    uncommon.
    References
    • Oxford handbook of clinical medicine 9th Ed.
    • Harrisons principles of internal medicine 19th
    Ed.
    • Ganong review of medical physiology
    • Davidsons principle and practice of medicine

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