Myasthenia Gravis

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