Post on 19-Nov-2014
description
Myasthenia Gravis (MG)Medical Background
Definition
(O’ Sullivan & Schmitz, 2007) Myasthenia gravis is an autoimmune
d/o often associated with other immunological dse. It is characterized by weakness and extensive fatigability.
Epidemiology
Prevalence: 20/100,000 MG may begin any time in life Onset, two major peaks
› Women: second & third decade› Men: sixth decade
Etiology
Action takes place at the site of the neuromuscular (n.m.) junction & motor endplate.
Risk factors› Thymic d/o› Diabetes› Other Immune d/o› Menstrual period› Pregnancy
Pathophysiology
fundamental defect = n.m. junction Receptors at the motor endplate
normally receive acetylcholine (ACh) from the motor nerve terminal.
Figure 12.7 Neuromuscular junction, Human biology, 7th edition. McGraw-Hills©2001
Figure 9-1. Motor end plate, Electrodiagnosis in disease of nerves and muscles: Principles and Practice, 3rd Edition. Oxford University Press©2001
Pathophysiology
receptors are ↓ & those that remain are flattened = ↓ efficiency of n.m. transmission
Without Ach: nerve impulses fail to pass across the n.m. junction to stimulate muscle contraction
n.m. abnormalities = autoimmune response› specific anti-ACh receptor antibodies
Pathophysiology
Response› blocks the site that normally binds Ach› damage the postsynaptic muscle
membrane› Endocytosis of receptor site
pinching off of regions of the cell's membrane
Pathophysiology
MG & Thymic d/o› cause of the autoimmune response is not
well understood› thymus appears to play a role in the dse
75 % of persons with MG have abnormalities of the thymus
› Cells within thymus bear ACh receptors on their surface
Pathophysiology
› Cells within the thymus bear ACh receptors on their surface
› serve as a source of autoantigen to trigger the autoimmune reaction within the thymus gland when an immunologic abnormality causes a breakdown an autoimmune attack on acetylcholine (ACh) receptors.
MGFA Clinical Classifications
CLASS I any ocular weakness; may have weakness of eye closure; all other muscle strength is normal
CLASS II
mild weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
IIapredominantly affecting limb, axial muscles or both; may also have lesser involvement of oropharyngeal weakness
IIbpredominantly affecting oropharyngeal respiratory muscles, or both; may also have lesser involvement of oropharyngeal weakness
CLASS III
moderate weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
MGFA Clinical Classifications
IIIapredominantly affecting limb, axial muscles or both; may also have lesser involvement of oropharyngeal muscles
IIIbpredominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles or both
CLASS IV
severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
IVapredominantly affecting limb and/or axial muscles
IVbpredominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles or both
MGFA Clinical Classifications
CLASS V
defined by intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of feeding tube without intubation places the patient in class IVb.
Clinical Manifestations
MG encompasses a spectrum of mild to severe (Goodman & Fuller, 2009)
cardinal features› Diplopia; › Ptosis; Unilateral frontalis muscle
contraction due to weak lid elevators on that side
Motor symptoms› Fatigue› Muscle weakness
Clinical Manifestations
Facial Muscles Eyelid closure is almost always weak eyelids are separated against forced eye closure slight involuntary opening of the eyes as the
patient tries to keep the eyes closed Snarling expression on attempted smile Sleepy or sad facial appearance
Neck muscles; causes head bobbing due to weak neck flexors
Intercostal and diaphragm muscles; SOB
Clinical Manifestations
Proximal limb weakness having difficulty raising arms above the head having difficulty climbing up stairs having difficulty arising from a chair
• Speech, voice and swallowing disorders› Oropharyngeal muscles weakness:
Dysphagia, Dysarthria, Dysphonia, voice may be nasal,
› Jaw weakness: prolonged chewing, especially tough, fibrous or chewy food
Clinical Manifestations
Cardiopulmonary function› weak bulbar muscles; aspiration
pneumonia› weak chest wall muscles; respiratory
failure Pattern of Symptoms
› Fatigability of muscles with recovery to the baseline strength after a short period of rest
› Proximal muscles are more affected
Clinical Manifestations
› S/sx fluctuate throughout the day› S/sx are provoked by exertion› Fluctuations occur with superimposed
illness, menses, & air T°› Neurologic findings are normal except for
muscle weakness› No muscular atrophy› Reflexes and sensation normal
Differential Diagnosis
Dse s/sx that mimic MG s/sx that does not mimic MG
MS Onset: 20 & 40 y/oPrimary affected area: nervous systemSpeech impairementFatigue, muscle weakness,
Peak onset: 30 y/oPrimary affected are is CNS white matter in MS and neuromuscular junction in MG,nystagmus
Guilain-Barre syndrome
Affects all age groupsRespiratory involvement
muscular weakness progress from lower extremity-upper extremity
Lambert-Eaton Myasthenic syndrome
Muscle weaknessProximal muscle involvement
autoantibodies directed against the PREsynaptic Ca channels
MGFA Diagnostic Procedures
Edrophonium Chloride Test Auto-Antibodies in MG
› Anti-striational muscle anti-bodies› Acetylcholine receptor antibodies (AChR-
ab)› Anti-musK antibodies› Other auto-antibodies
Anti-titin antibodies Anti-RyR
MGFA Diagnostic Procedures
Electrodiagnostic Testing› Repetitive nerve stimulation› Single fiber EMG
Ocular cooling/Ice Pack test Other studies
› Complete blood count› Thyroid Function Test› Thyroid Antibodies
Prognosis
The prognosis of MG in infancy is usually favorable, although exacerbations may occur in fevers. In sporadic case, a fulminating onset with life-threatening respiratory insufficiency may occur.
Progression to severe disease may be more common in MG with onset after the age of 50.
MGFA Treatment Program
• Medical, Surgical and Pharmacological management› Thymectomy › Plasma exchange (PLEX)› Intravenous Immunoglobulin (IGIv)› Cholinesterase inhibitor drugs (ChI)
Pyridostigmine bromide Neostigmine
MGFA Treatment Program
› Corticosteroid Prednisone
› Immunomodulatory drugs Azathioprine Cyclosporine Mycophenolate mofetil
MGFA Treatment Program
› Miscellanous Ephedrine Terbutaline
• Rehabilitation management› Walking› Stationary ergometer› Weight training› Treadmill› Swimming