Neurology Book

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Myasthenia Gravis

Aka: Myasthenia Gravis
  1. Pathophysiology
    1. Neuromuscular Autoimmune Disease
    2. Antibodies form to nicotinic acetylcholine receptors
      1. Affects post-synaptic mambrane of the neuromuscular junction
    3. Results in fluctuating and variable, progressive weakness and true fatigability
    4. Associated with thymoma in up to 25% of cases
  2. Epidemiology
    1. Annual Incidence: 10-20 new cases per million
    2. Prevalence: 150-200 cases per million
    3. Age of onset (multimodal)
      1. Neonatal Myasthenia Gravis (transient related to maternal antibodies)
      2. Ages 20-30 (predominantly female)
      3. Ages 50-80 (predominantly male)
  3. Types
    1. Ocular Myasthenia Gravis
      1. Eyelid weakness (Ptosis)
      2. Extraocular Muscle Weakness (Diplopia)
      3. Seronegative in 50% of cases
      4. Progresses to generalized Myasthenia Gravis within 2 years in 50% of cases
    2. Generalized Myasthenia Gravis
      1. Includes ocular Muscle Weakness as above AND
      2. Bulbar weakness (Dysarthria, Dysphagia, fatigable chewing)
      3. Extremity weakness
      4. Respiratory Muscle Weakness
      5. Seronegative in 10% of cases
    3. Other forms
      1. Thymoma-associated Myasthenia Gravis
  4. Associated Conditions
    1. Neuromyelitis optica
    2. Autoimmune Thyroid disease
    3. Systemic Lupus Erythematosus
    4. Rheumatoid Arthritis
  5. Presentations
    1. Early course
      1. Typically transient with symptom free intervals lasting days to weeks
    2. Ocular Myasthenia Gravis (50%)
      1. Ptosis
      2. Diplopia (vertical or horizontal)
    3. Bulbar symptoms (15%)
      1. Dysarthria
      2. Dysphagia
      3. Fatigable chewing
    4. Isolated motor weakness (<5%)
      1. Proximal limb weakness
      2. Other sites of isolated Muscle Weakness are less common presentations (neck weakness, distal limb weakness, respiratory Muscle Weakness)
  6. Symptoms
    1. Muscle Weakness provoked by exertion
    2. May be precipitated by infection, fever, stress and other acute factors
    3. Ocular weakness
      1. Eyelid Muscle Weakness resulting in Ptosis (unilateral or bilateral)
        1. May increase with sustained upward gaze
      2. Extraocular Muscle Weakness resulting in binocular Diplopia (vertical or horizontal)
        1. Resolves with covering one eye
      3. Pupil reaction is always spared in ocular myasthenia
    4. Bulbar weakness
      1. Fatigable chewing (often mid-way through a meal)
        1. Patient may need to use their fingers to lift the jaw, and close the mouth
      2. Dysarthria
        1. Nasal quality or low intensity voice
      3. Dysphagia
        1. Difficulty Swallowing liquids and solids
        2. Aspiration may occur with myasthenia crisis
      4. Nasal regurgitation
        1. Occurs if Palate weak
    5. Facial Muscle Weakness
      1. Loss of expression (especially loss of smile, or sneer appearance)
    6. Neck Muscle Weakness
      1. Neck flexor Muscle Weakness
      2. Neck extensor Muscle Weakness
        1. May give "dropped head" appearance with head flexed over chest later in the day
    7. Extremity Muscle Weakness (asymmetric)
      1. Arms affected more than legs
      2. Proximal Muscle Weakness are typically more affected than distal muscles
      3. Distal wrist extensors and foot dorsiflexors are most often involved
    8. Respiratory Muscle Weakness
      1. Respiratory insufficiency may progress to Respiratory Failure (myasthenia crisis)
  7. Signs
    1. See symptoms above
    2. Muscle Weakness as above
    3. Deep Tendon Reflexes normal
    4. Specific Tests
      1. Ice Pack Test
        1. Cold pack applied to eye with Ptosis for 2 minutes
        2. Myasthenia Gravis related Ptosis improves with cold applied
      2. Tensilon Test (Edrophonium Test)
        1. Cholinesterase Inhibitor given and Motor Strength improves in Myasthenia Gravis
  8. Labs: Specific Antibody
    1. Seronegative Myasthenia Gravis occurs in 6-12% of cases (most frequently ocular Myasthenia Gravis)
    2. Acetylcholine Receptor Antibody (AChR-Ab)
      1. Binding AChR-Ab is typically used as it has best efficacy
        1. Blocking AChR-Ab may be indicated in some cases due to its high Specificity
        2. Modulating AChR-Ab may slightly increase Test Sensitivity but at the risk of False Positives
      2. Present in 50% of Ocular Myasthenia Gravis
      3. Present in 80-90% of generalized Myasthenia Gravis
    3. Muscle-Specific Receptor Tyrosine KinaseAntibody (MuSK-Ab)
      1. Absent in most cases of ocular Myasthenia Gravis
      2. Present in 38-50% of generalized Myasthenia Gravis patients who are AChR-Ab negative
  9. Labs: Other testing
    1. Electromyogram (EMG)
      1. Decremental response to repetitive nerve stimulation
    2. CT neck or MRI neck
      1. Thymoma evaluation
    3. Thyroid Function Test
      1. Hyperthyroidism (3-8%)
    4. Rheumatoid Factor (RF)
    5. Antinuclear Antibody (ANA)
  10. Differential Diagnosis
    1. Ocular Myasthenia Gravis mimics
      1. Hyperthyroidism (including Thyroid ophthalmopathy)
      2. Kearns-Sayre Syndrome
      3. Brainstem lesions
    2. Generalized Myasthenia Gravis mimics
      1. Amyotrophic Lateral Sclerosis (ALS)
      2. Lambert-Eaton Syndrome
        1. Associated with cancer, and typically affects proximal extremity Muscle Weakness
      3. Botulism
      4. Neurasthenia
      5. Intracranial Mass lesion with extraocular affect
    3. Drug-induced Myasthenia
      1. Penicillamine
      2. Polymyxin
      3. Tetracycline
      4. Aminoglycosides
      5. Procainamide
      6. Propranolol
      7. Phenothiazine
      8. Lithium
  11. Complications
    1. Aspiration Pneumonia
    2. Myasthenia Crisis
      1. Respiratory compromise
    3. Cholinergic crisis (excessive Acetylcholinesterase Inhibitor)
      1. See Cholinergic Toxicity
  12. Management: Medication
    1. Anticholinesterase (Cholinergic)
      1. Provides symptomatic relief
        1. Most effective on extremity weakness and bulbar symptoms
        2. Less effective on Ptosis
        3. Least effective on Diplopia
      2. Pyridostigmine Bromide (Mestinon)
        1. Child: 0.5 - 1 mg/kg every 4-6 hours up to 7 mg/kg/day
        2. Adult: 30 mg three times daily (may be increased to maximum of 120 mg every 4 hours while awake)
        3. Onset: 15-30 minutes
        4. Peaks: 2 hours
        5. Duration: 3-4 hours
      3. Neostigmine
        1. Less commonly used
    2. Immunosuppressive therapy
      1. Prednisone
        1. Start at 20 mg qd
        2. Increase gradually by 5 mg every 3 days to 60mg
        3. Continue for 3 months OR
          1. Until clinical improvement stops or declines
        4. Taper gradually to every other day
      2. Azathioprine (Imuran)
        1. Dosing
          1. 2 mg/kg/day
        2. Efficacy
          1. Effective when given with Prednisone
          2. Effect not seen for 6 months or more
        3. Monitoring
          1. Complete Blood Count (CBC)
          2. Liver Function Tests (LFT)
    3. Plasmapheresis (Plasma Exchange) and IVIg
      1. Indicated for emergent worsening/crisis
      2. Response rate: 70%
  13. Management: Thymectomy
    1. Indications
      1. Age <60 years
      2. Inadequately controlled on Pyridostigmine
      3. Thymoma discovered
    2. Effect
      1. Clinical improvement after thymectomy in 80%
      2. Benefits may not be seen for 6 months
      3. Transcervical thymectomy may be preferred
    3. References
      1. Calhoun (1999) Ann Surg 230:555-61 [PubMed]
  14. Precautions
    1. Avoid antibiotics that significantly exacerbate neuromuscular weakness
      1. Aminoglycosides
      2. Fluoroquinolones
      3. Telithromycin (Ketek)
      4. Macrolides (Erythromycin, Azithromycin) - less effect than other agents above
    2. Avoid miscellaneous agents that exacerbate neuromuscular weakness
      1. Magnesium
      2. Class Ia Antiarrhythmics (e.g. Quinidine, Procainamide, Amiodarone)
      3. High-dose Corticosteroids
      4. Iodinated Contrast Dye (seen primarily with older contrast dyes)
    3. References
      1. Hayes in Herbert (2015) 15(9):14
  15. References
    1. Bird (2013) Myasthenia Gravis, in Shefner and Targoff, UpToDate, Wolters Kluwer
    2. Keesey (2004) Muscle Nerve 29:484 [PubMed]

Myasthenia Gravis (C0026896)

Definition (MEDLINEPLUS)

Myasthenia gravis is disease that causes weakness in the muscles under your control. It happens because of a problem in communication between your nerves and muscles. Myasthenia gravis is an autoimmune disease. Your body's own immune system makes antibodies that block or change some of the nerve signals to your muscles. This makes your muscles weaker.

Common symptoms are trouble with eye and eyelid movement, facial expression and swallowing. But it can also affect other muscles. The weakness gets worse with activity, and better with rest..

There are medicines to help improve nerve-to-muscle messages and make muscles stronger. With treatment, the muscle weakness often gets much better. Other drugs keep your body from making so many abnormal antibodies. There are also treatments which filter abnormal antibodies from the blood or add healthy antibodies from donated blood. Sometimes surgery to take out the thymus gland helps.

For some people, myasthenia gravis can go into remission and they do not need medicines. The remission can be temporary or permanent.

If you have myasthenia gravis, it is important to follow your treatment plan. If you do, you can expect your life to be normal or close to it.

NIH: National Institute of Neurological Disorders and Stroke
Definition (NCI_NCI-GLOSS) A disease in which antibodies made by a person's immune system prevent certain nerve-muscle interactions. It causes weakness in the arms and legs, vision problems, and drooping eyelids or head. It may also cause paralysis and problems with swallowing, talking, climbing stairs, lifting things, and getting up from a sitting position. The muscle weakness gets worse during activity, and improves after periods of rest.
Definition (NCI) A chronic autoimmune neuromuscular disorder characterized by skeletal muscle weakness. It is caused by the blockage of the acetylcholine receptors at the neuromuscular junction.
Definition (MSH) A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)
Definition (CSP) disease characterized by progressive weakness and exhaustibility of voluntary muscles without atrophy or sensory disturbance and caused by an autoimmune attack on acetylcholine receptors at the neuromuscular junction.
Concepts Disease or Syndrome (T047)
MSH D009157
ICD9 358.0
ICD10 G70.0, G70.00
SnomedCT 193208002, 155092009, 91637004
LNC LA15158-1
Dutch myasthenia gravis paralytica, gravis; myasthenie, myasthenie; gravis, myasthenia gravis, Myasthenia gravis
French Myasthénie grave pseudo-paralytique, Myasthénie grave, Myasthénie, Myasthénie auto-immune, Myasthénie autoimmune
German Myasthenia gravis paralytica, Myasthenia gravis
Italian Miastenia gravis paralitica, Miastenia gravis, Miastenia grave
Portuguese Miastenia grave paralítica, Miastenia Grave, Miastenia grave, Miastenia Gravis
Spanish Miastenia gravis paralítica, miastenia gravis, SAI, miastenia gravis, SAI (trastorno), enfermedad de Erb - Goldflam, miastenia grave, miastenia gravis (trastorno), miastenia gravis, Miastenia gravis, Miastenia Gravis
English Myasthenia Gravis, MYASTHENIA GRAVIS, MG, myasthenia gravis (diagnosis), myasthenia gravis, Myasthenia gravis paralytica, Myasthenia gravis NOS, Myasthenia Gravis [Disease/Finding], myasthenia gravis (MG), myasthenia gravis disorder, Myasthenia gravis NOS (disorder), Erb-Goldflam disease, Myasthenia gravis, MG - Myasthenia gravis, Myasthenia gravis (disorder), Erb-Goldflam, Goldflam-Erb, gravis; myasthenia, myasthenia; gravis, Myasthenia gravis, NOS
Japanese 麻痺性重症筋無力症, ｼﾞｭｳｼｮｳｷﾝﾑﾘｮｸｼｮｳ, ﾏﾋｾｲｼﾞｭｳｼｮｳｷﾝﾑﾘｮｸｼｮｳ, 重症筋無力症, 筋無力症, 筋無力症-重症
Swedish Myasthenia gravis
Czech myasthenia gravis, Myasthenia gravis, Myastenia gravis, myastenie gravis
Finnish Myasthenia gravis
Russian MIASTENIIA GREVIS, MIASTENIIA TIAZHELAIA PSEVDOPARALITICHESKAIA, ERBA-GOL'DFLAMA BOLEZN', MIASTENIIA, MYASTHENIA GRAVIS, МИАСТЕНИЯ, МИАСТЕНИЯ ГРЭВИС, МИАСТЕНИЯ ТЯЖЕЛАЯ ПСЕВДОПАРАЛИТИЧЕСКАЯ, ЭРБА-ГОЛЬДФЛАМА БОЛЕЗНЬ
Korean 중증 근육무력증
Croatian MIASTENIJA GRAVIS
Polish Nużliwość mięśni rzekomoporaźna, Miastenia
Hungarian Myasthenia gravis paralytica, Myasthenia gravis
Norwegian Myasthenia gravis
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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