MYASTHENIA GRAVIS internal medicine.pptx

Internal medicine topic

1. MYASTHENIA GRAVIS AND OTHER NEUROMUSCULAR DISORDERS. BY GROUP SIX

2. Definition Myasthenia gravis is a chronic auto immune neuromuscular disorder caused by an antibody mediated blockade of neuromuscular transmission resulting into weakness and rapid fatigue of voluntary muscles. It is the most common NM junction disorder of skeletal muscles and The most affected muscles are the ocular, facial and bulbar.

3. Epidemiology It is a rare disease with an estimated prevalence of approximately 20-30 cases per 100,000 people. MG can occur at any age, but it has two peak inset periods. The first peak is in women under 40years of age, and the second one is in both men and women over 60 years of age.

4. the overall female-to-male ratio has been considered to be 3:2, with a female predominance in younger adults ( ie , patients aged 20-30 years) and a slight male predominance in older adults ( ie , patients older than 50 years) Juvenille myasthenia gravis can also occur but it is less common.

5. PATHOPHYSIOLOGY

6. Pathophysiology cont ; MG occurs when the immune system produces antibodies against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles. This results into a blockage 0f the receptor sites for acetylcholine, a neurotransmitter necessary for muscle contraction. This reduces communication between nerves and results into a characteristic pattern of progressive reduction in muscle strength with repeated use and recovery of the muscle strength after a period of rest.

7. Pathophysiology cont ; As a result, there is a Decreased no of the nicotinic ach receptors at the motor end plate, Reduced post synaptic membrane folds and a Widened synaptic cleft all contributing to the transmission dysfunction. Since the action of Ach at the synapse is short lived due to the action of an enzyme Acetylcholinestrase responsible for breakdown of Ach at the synapse, a reduction in the duration of action of the Ach further contributes to the disease symptomology. With decreased Ach at the synapse and increased competitive auto antibody binding to the receptor sites of ach, symptomology of MG worsens with activity.

8. Patients become symptomatic when the AchR reduce to approximately 30% of the normal. NOTE; Due to differences in antigenicity of cholinergic receptors of the cardiac and smooth muscles from those of the skeletal muscles, the latter are not affected in MG

9. CLINICAL FEATURES The hallmark of MG is fluctuating muscle weakness and fatigue of the affected muscle groups. The weakness worsens with activity and improves with rest and involves ocular , bulbar and extremity muscles. Occular muscle weakness Ptosis, diplopia[ often not present in the morning but rather as the day progresses, is often an initial finding and can be unilateral or bilateral, most common symptom ie 50%-85% ]

10. Limb weakeness Proximal muscles affected more than the distal muscles. Isolated limb weakeness is rare ie 5% Bulbar muscle weakness Muscles involved in speaking, chewing and swallowing thus leading to slurred speech, nasal speech, diff swallowing and chewing. Maybe associated with obstructed sleep apnea Others Head and neck extension weakness. Note; These features can progress from mild to severe over weeks to months

11. PTOSIS OF THE LEFT EYELID A myasthenic face appears as a sad looking face or sleepy face impression due the ptosis and weakeness in the facial muscles Myasthenic snarl(from upward movt of the medial portion of the upper lip and horizontal contraction of the corners of the mouth); this appears when an MG pt smiles.

12. Auto antibodies involved; Anti- AChR The serum titer of the acetyl-choline receptor antibodies does not correlate with disease severity. Their value is mainly in the initial diagnosis of myasthenia gravis (MG). Anti- AChR antibodies are predominantly IgG1 and IgG3. Anti- MuSK antibodies( muscle-specific kinase ) About half of the patients with negative results for anti- AChR Ab ( seronegative MG) may have positive test results for anti- MuSK antibodies, a receptor tyrosine kinase that is essential for neuromuscular junction development. Anti- MuSK –positive individuals tend to have more pronounced bulbar weakness and may have tongue and facial atrophy. They are also less likely to respond to acetylcholine esterase ( AChE ) inhibitors, and their symptoms may actually worsen with these medications. Anti–striated muscle antibody The anti-SM Ab refers to a class of antibodies against components of skeletal muscle including titin , the ryanodine receptor, myosin, and alpha-actin 0thers include ; Anti-lipoprotein-related protein 4 (LRP4) antibody, Anti- agrin antibody , etc

13. CLASSIFICATION OF MS MS is classified into 5 classes by Myasthenia Gravis Foundation of America (MGFA) as follows; Class I : Any ocular muscle 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. Class III : Moderate weakness affecting other than ocular muscle; may also have ocular muscle weakness of any severity Class IV : Severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity Class V : Defined by intubation, with or without mechanical ventilation, except when used during routine postoperative management.

14. Myasthenic crisis This is a severe complication of MS characterized by significant respiratory muscle weakeness resulting into resp failure necessitating intubation or mechanical ventilation. Estimated that 15-20% of the MG patients will experience this crisis at some point in their life

15. More common in the first 2years of dx and most common in those with Anti-musk antibodies Symptoms include, labored breathing, difficulty swallowing, increased saliva production. It can be triggered by infections, medication non compliance, or stress

16. DIAGNOSIS History and physical examination Antibody testing or serological testing Anti achR antibodies ; highly specific to MG , More likely to occur in those with generalized MG vs ocular MG Anti musk antibodies, anti agrin , anti lrp4 etc

17. In Seronegative patients repetitive nerve stimulation(RNS) single fibre electromyography(SFEMG) Imaging Plain Chest radiographs ( could show a thymoma) CT scan MRI of the brain and eye orbit( to rule out mass lessions )

18. TREATMENT Anti cholinerastases inhibitors (e.g. pyridostigmine ) to improve neuromuscular transmission [offers symptomatic benefit only]. Immunosuppressive drugs ( e.g. corticosteroids, azathioprine, methotrexate, cyclosporine etc ) Intavenous IgG . Plasmapheresis [removes antibodies from AchR , used if all the all the above fails, or if patient is in respiratory failure]. Thymectomy ( surgical removal of thymus gland) This provides symptomatic benefit and complete remission in many patients even in the absence of a thymoma .

19. PROGNOSIS With appropriate treatment, many individuals with myasthenia gravis can lead relatively normal lives. However, it is a chronic condition, and some patients may experience periods of remission and exacerbation. While there is no known cure, available treatments can control symptoms and allow people to have a relatively high quality of life sever complications, such as respiratory failure, can be life- threatening, particularly in early years of the disease.

20. GUILLAIN-BARRE SYNDROME

21. INTRODUCTION : Definition: Guillain-Barre syndrome is a neurological disorder in which the immune system mistakenly attacks part of the peripheral nervous system It is an acute, autoimmune, progressive and inflammatory demyelination of the peripheral nerves.

22. Cont’n The GBS variants include; Acute inflammatory demyelination polyneuropathy(AIDP) Acute motor axon neuropathy(AMAN) Miller Fisher syndrome Acute motor and sensory axonal neuropathy Polyneuritis cranialis

23. EPIDEMIOLOGY The annual incidence of Guillain-Barre syndrome ranges from 0.5-1.5 cases per 100,000 population in individuals younger than 18years, though it can appear at any age. Males are at a higher risk than females. Occurs 1-6 weeks after a respiratory or gastrointestinal infection

24. RISK FACTORS Gastrointestinal and respiratory infections, for example Campylobacter, influenza, CMV, Epstein bar virus, and mycoplasma pneumoniae . Vaccines for example influenza vaccine, and meningococcal vaccine. Recent surgery Trauma Lymphomas( Hodgkins lymphomas)

25. PATHOPHYSIOLOGY : GBS occurs after an infection, for example campylobacter jejuni . The lipopolysaccharide on the outer membrane of campylobacter mimics the gangliocides of the peripheral nerves so the immune system can not distinguish between the two. The immune system produces antibodies that attack the myelin sheath in the peripheral nerves causing demyelination and damage of the peripheral nerves thus transmission of nerve impulses is slowed or stopped.

26. CLINICAL FEATURES Distal paresthesia and pain preceding muscle weakness. It ascends from the lower to upper limb and it is more marked proximal than distal. Features of respiratory failure due to the ascending weakness which can affect the diaphragm Areflexia or hyporeflexia which can progress to quadriplegia Ptosis, diplopia, facial weakness, dysphagia. Difficulty with facial movements including speaking and chewing. Difficulty with bladder control.

27. DIAGNOSIS Nerve conduction block Electromyography Lumbar puncture, with elevated CSF proteins with no white blood cells

28. MANAGEMENT Plasmaperesis . Intravenous Immunoglobulin therapy. In severe GBS both are started within two weeks of onset to fasten recovery Intubation in cases of respiratory failure. Supportive management which includes monitoring heart beat, breathing and blood pressure.

29. PROGNOSIS Most people recover fully from even the most severe cases although some continue to experience weaknesses. However, even in the best settings a small number of Guillain-Barre syndrome patients die from complications which include paralysis of muscles that control breathing, blood infection, lung clots and cardiac arrest.

30. REFERENCES Oxford Handbook of Tropical Medicine 5th edition Harrison’s Principles of Internal Medicine 21st edition Davidson’s Principles and Practices of Medicine 24th edition