Myasthenia Gravis

Myasthenia Gravis was first described by Thomas Willis in 1672.
“Myasthenia Gravis” literally means “muscle weakness”.
MG is often called the “snowflake disease” because it differs so much from person to person.
Definition
Myasthenia gravis (MG) is an autoimmune disease that causes chronic, progressive damage of the neuromuscular junction.
The underlying defect is a decrease in the number of available acetylcholine receptor (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack.
Clinical Features
Eye muscles
Drooping of one or both eyelid (Ptosis)
Double vision (diplopia)
Face and throat muscles
Dysarthria
Dysphasia
Problem in chewing
Limited facial expression
Snarling expression
Respiratory symptoms
Weakness of intercostal muscle and diaphragm.
Weakness of pharyngeal muscles
Palate muscle weakness
Nasal voice
Nasal regurgitation
Swallowing may be difficult and regurgitation of food can occur.
Coughing and chocking while drinking
Limb muscle weakness in MG is often proximal and may be asymmetric.
In ~85% o patients, the weakness becomes generalized, affecting the limb muscles as well.
If weakness remains restricted to the extra ocular muscles for 3 years, it is likely that it will not become generalized, and these patients are said to have ocular MG.

1. Myasthenia Gravis By – Anumeha Sharma MPT I st Year (Neurology)

2. Table of Contents Introduction Epidemiology Aetiology Pathophysiology Clinical features Clinical classification Diagnosis Management

3. Introduction Myasthenia Gravis was first described by Thomas Willis in 1672. “Myasthenia Gravis” literally means “muscle weakness”. MG is often called the “snowflake disease” because, it differs so much from person to person.

4. Definition Myasthenia gravis (MG) is an autoimmune disease that causes chronic, progressive damage of the neuromuscular junction. The underlying defect is a decrease in the number of available acetylcholine receptor (AChRs ) at neuromuscular junctions due to an antibody-mediated autoimmune attack.

5. Epidemiology The estimated prevalence of MS is approx. 77 to 150 cases per 100,000 population . Incidence increases with advancing age, and incidence distribution is bimodal. All age groups Women in 20-30’s Men in 40-60’s W:M – 3:2

6. Aetiology Autoantibodies that destroys acetylcholine receptors. Autoantibodies against MuSK protein. Thymus tumour found in 15% of patients. Rare hereditary form of MG.

7. Pathophysiology

8. Clinical features Eye muscles Drooping of one or both eyelid (Ptosis) Double vision (diplopia) Face and throat muscles Dysarthria Dysphasia Problem in chewing Limited facial expression Snarling expression

9. Contd. Respiratory symptoms Weakness of intercostal muscle and diaphragm. Weakness of pharyngeal muscles Palate muscle weakness Nasal voice Nasal regurgitation

10. Swallowing may be difficult and regurgitation of food can occur. Coughing and chocking while drinking Limb muscle weakness in MG is often proximal and may be asymmetric. In ~85% o patients, the weakness becomes generalized, affecting the limb muscles as well . If weakness remains restricted to the extra ocular muscles for 3 years, it is likely that it will not become generalized , and these patients are said to have ocular MG .

11. Peek Sign

12. Clinical C lassification

13. Physical Examination Sustained up gaze (60 to 180 seconds); results in fatigable ptosis in one or both eyes. Sustained tight closure of the eyelids can induce fatigue of the orbicularis oculi muscles resulting in the white sclera of the eye slowly becoming apparent under the partially open eye. This is called the “peek sign.” Sustained abduction of the arms (120 seconds); patient can no longer hold arms up, or weakness becomes apparent with subsequent manual testing.

14. Contd. Counting aloud (1 to 50): Enhances dysarthria (nasal, lingual, or labial) and results in dyspnoea. Patient may sound relatively clear on speaking initially but will become increasingly dysarthric to the point of becoming unintelligible . Weakness of the laryngeal muscles results in hoarseness. This can be elicited by asking the patient to make a high-pitched (“eeee”) sound.

15. Single breath counting aloud (1 to 20) may elicit not only dysarthria but dyspnoea and gives an approximate idea of the vital capacity . Sustained elevation of leg while lying supine (90 seconds): Patient can no longer hold leg up, or weakness becomes apparent with subsequent manual testing. Repeated arising from chair without use of arms (up to 20 repetitions): Fatigues after several attempts. Early/mild weakness may cause exaggerated lean-forward and ‘‘buttocks-first’’ manoeuvre.

16. Contd. Saccades may undershoot their goal (hypometric saccades ), but may be more rapid than normal . Ptosis may improve after applying ice to the eyelids ( icepack test ), since cold temperatures may f acilitate neuromuscular transmission .

17. The Tensilon Test The Tensilon test uses Edrophonium an acetylcholinesterase inhibitor that inhibits the breakdown of acetylcholine in the neuromuscular junction . Edrophonium increases the availability of acetylcholine in the synapse to activate muscle. Therefore , administering edrophonium can lead to rapid improvement in myasthenic symptoms.

18. Screening or Thymoma CT or MRI of the chest or evaluation of the mediastinum.

19. Management A chE Inhibitors Immunomodulatory Therapies Plasma Exchange Thymectomy

20. Contd. Pyridostigmine is the most commonly used acetylcholinesterase inhibitor. If a patient does not respond to pyridostigmine, immunomodulatory treatment is generally required . Oral steroids are used commonly, although azathioprine and mycophenolate are the most commonly used steroid-sparing agents in patients who cannot tolerate steroids or who will need prolonged immunomodulatory treatment .

21. C ontd. Plasmapheresis Filters out the antibodies IV immunoglobulins Provides body with antibodies

22. Diet & Nutrition Thickened liquids are preferred. Patients are instructed to start a low sodium, low carbohydrate, high protein diet to prevent excessive weight gain. Manage liquids carefully Eat slowly, rest between each bite Have smaller, more frequent meals instead of a big meal Avoid hard to digest food.

23. Myasthenic Crisis This is an acute exacerbation in myasthenia causing respiratory failure requiring intubation. Myasthenic crisis can be triggered by any physiologic stress (e.g., infection, surgery ) or by medications including: Antibiotics : quinolones, macrolides, aminoglycosides Cardiac medications: beta blockers, calcium channel blockers, quinidine , procainamide Magnesium Anaesthetic agents Neuromuscular blocking agents

24. Management Treatment of myasthenic crisis is with S teroids and immunomodulatory therapy (IVIg or plasma exchange) T reatment of any potential triggers (e.g., treating infection , discontinuing any potential medication triggers). M echanical respiratory support until respiratory muscle weakness improves with treatment .

25. Physiotherapy Management History Evaluation Strength measurement Flexibility Mobility assessment Evaluation of balance Gait Endurance/Activity tolerance

26. Goals of Rehabilitation Enhance ability to perform daily life activities Decrease risk of falling M aintenance of independence Maintain or increase muscle strength Improve gait functions Maintain muscle flexibility To improve vital capacity of the patient Improve posture To advise for assistive devices if needed

27. Exercise considerations All stable MG patients who are exercising should consider following points- The dollar per day rule says you should “budget” energy to accomplish daily activities. Exercise at best time of day Exercise at peak dose of pyridostigmine Exercise large, proximal muscle group for short period of time. Exercise should be short in duration and never exceed moderate intensity.

28. Moderate exercise intensity HR should not elevate greater than 30 beats per minute from resting baseline. Does not cause shortness of breath at peak of exercise. MG symptoms should not become worse during exercise (drooping of eyelids). Patient should not still be tired 2 hours after exercise. Patient should not have severe residual muscle soreness day(s) post exercise.

29. Strengthening exercises Should be done progressively Start with less number of repetitions If significant weakness is present, active assisted exercise should be performed In stable or early stages of MG weightlifting and resistance band exercise can also be performed. To avoid muscle fatigue, alternate upper and lower extremity exercise should be done.

30. Postural Exercise Important in assisting with breathing, speaking and swallowing. Keeps body in correct alignment. Prevent fatigue as muscle are being used more efficiently, allowing the body to use less energy .

31. Breathing Exercise Pursed lip & diaphragmatic breathing exercise have been found to be beneficial in MG. These exercise can improve respiratory endurance. Release and reduce muscular tension. Improves vital capacities. Promotes relaxation.

32. Aerobic Exercise Aerobic exercise has shown improvement in balance and gait. Overcoming and enhancing mental and emotional well being. Increase lung volume. Reduce weight gain and improves cardiovascular risk profile.

33. A ctive physical exercise intervention studies in myasthenia gravis (MG)