Category: Entertainment

Presentation Description

No description available.


By: ornwanya (116 month(s) ago)

thank you

Presentation Transcript




2 PLAN OF DISCUSSION Definition Pathophysiology Diagnosis History, Physical exam, Labs Differentials Treatment Conclusion


3 dEFINITION I s a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles D ecrease in the number of available acetylcholine receptors ( AChRs ) at neuromuscular junctions D ue to an antibody-mediated autoimmune attack

Normal physiology:

4 Normal physiology Ach is synthesized in the motor nerve terminal and stored in vesicles (quanta) Action potential travels down a motor nerve and reaches the nerve terminal ACh from 150–200 vesicles is released Combines with AChRs

Slide 5:

5 Ach combines with the binding sites on the alpha subunits of the AChR Channel in the AChR opens Rapid entry of cations, chiefly sodium Produces depolarization at the end-plate region of the muscle fiber


6 PAthophysiology

Slide 7:



8 PATHOPHYSIOLOGY OF MG Decrease in the number of available AChRs at the postsynaptic muscle membrane Postsynaptic folds are flattened, or "simplified” Results in decreased efficiency of neuromuscular transmission


9 Pathophysiology Presynaptic rundown :- Amount of ACh released per impulse normally declines on repeated activity Myasthenic fatigue :- Decreased efficiency of neuromuscular transmission + Rundown Neuromuscular abnormalities are brought about by an autoimmune response mediated by specific anti- AChR antibodies

Anti AChR Antibodies:

10 Anti AChR Antibodies Reduce the number of available AChRs at neuromuscular junctions Three mechanisms

Slide 11:


Role of Thymus:

12 Role of Thymus Abnormal in ~75% of patients In ~65% the thymus is “ hyperplastic “ An additional 10% of patients have thymic tumors ( thymomas )

Role Of Thymus:

13 Role Of Thymus Myoid(Muscle like) cells within the Thymus Bear AChRs on their surface May serve as a source of autoantigen and trigger the autoimmune reaction within the thymus


14 Incidence 1–7 in 10,000 Affects individuals in all age groups Peaks of incidence :- Women :- 2 nd and 3 rd decade Men :- 5 th and 6 th decade Women are affected more frequently than men ~3:2 Association with HLA B8 and DRW3

Cardinal Features:

15 Cardinal Features Weakness and fatigability of muscles Weakness increases on repeated use Improves following rest or sleep Relapsing and remitting course during the early years


16 MUSCLE WEAKNESS- DISTRIBUTION Ptosis , Diplopia - lids and extraocular muscles, often involved early Snarling Expression – Facial weakness Weakness in chewing – After pronlonged effort Speech Nasal timbre (weakness of palate) Dysarhtric mushy quality ( weakness of tongue)

Slide 17:

17 Difficulty in swallowing - weakness of the palate, tongue, or pharynx Nasal regurgitation / Aspiration

Slide 18:

18 Weakness becomes generalized affecting limb muscles in ~85% Proximal, Asymmetric DTR preserved, Pupillary sparing Weakness of respiration becomes severe requiring ventilator - Crisis


19 OCULAR MG When the weakness remains restricted to the extra ocular muscles for 3 years Unlikely to become generalized

Diagnosis of mg:



21 history Diplopia, ptosis, weakness Weakness in characteristic distribution Fluctuation and fatigue: worse with repeated activity, improved by rest

Physical exam:

22 Physical exam Ptosis, Diplopia Motor power survey: Quantitative testing of muscle strength Forward arm abduction time (5 min) Vital capacity-SBC upto 30 Chest expansion-5-8 cms Absence of other neurologic signs

Slide 23:



24 LAB Anti- AChR radioimmunoassay Electro diagnostic testing Acetylcholinesterase Test Exclude intracranial lesions by CT or MRI - For ocular or cranial MG

Anti-AChR radioimmunoassaY:

25 Anti- AChR radioimmunoassaY ~85% positive in generalized MG 50% in ocular MG Definite diagnosis if positive Negative result does not exclude MG


26 ELECTRODIAGNOSTIC TESTING Repetitive nerve stimulation :- Decrement of >15% at 3 Hz: highly probable Single-fiber electromyography


27 ANTICHOLINESTERASE TEST (TENSILON TEST) Edrophonium is used most commonly Rapid onset (30 s) and short duration (~5 min) of its effect IV 2 mg of edrophonium Improvement No improvement Positive Additional 8mg

Adverse reactions:

28 Adverse reactions Nausea, diarrhea, salivation, fasciculations, and rarely with severe symptoms of syncope or bradycardia Atropine (0.6 mg) should be drawn up in a syringe ready for IV administration if these symptoms become troublesome

Congenital myasthenic syndromes:

29 Congenital myasthenic syndromes Heterogeneous group of disorders of the neuromuscular junction that are not autoimmune but rather are due to genetic mutations CMS should be suspected when symptoms of myasthenia have begun in infancy or childhood and AChR antibody tests are consistently negative

Differential diagnosis:

30 Differential diagnosis Drug-induced myasthenia-penicillamine Lambert-Eaton Myasthenic Syndrome (LEMS) Neurasthenia Hyperthyroidism Botulism Intracranial mass lesions Progressive external ophthalmoplegia


31 Lems Have depressed or absent reflexes Presynaptic disorder Experience autonomic changes such as dry mouth and impotence Have incremental rather than decremental responses on repetitive nerve stimulation Most patients with LEMS have an associated malignancy most commonly small cell carcinoma of the lung


32 botulism Due to a potent bacterial toxin produced by Clostridium botulinum Patients present with bulbar weakness (Dysarthria, Dysphagia, Diplopia) but lack sensory symptoms and signs Deep tendon reflexes are preserved early in the disease course


33 dd Neurasthenia - myasthenia-like fatigue syndrome without an organic basis Hyperthyroidism – TFT Cobra bite

associated disorders:

34 associated disorders Disorders of the thymus : Thymoma Hyperplasia Other autoimmune disorders : Hashimoto's thyroiditis Graves' disease Rheumatoid arthritis Lupus erythematosus Disorders or circumstances that may exacerbate myasthenia gravis : Hyperthyroidism or Hypothyroidism Occult infection Medical treatment for other conditions-drugs

Associated disorders:

35 Associated disorders Disorders that may interfere with therapy : Tuberculosis Diabetes Peptic ulcer Gastrointestinal bleeding Renal disease Hypertension Asthma Osteoporosis Obesity

Recommended lab tests or procedures :

36 Recommended lab tests or procedures CT or MRI of mediastinum Tests for lupus erythematosus , antinuclear antibody, rheumatoid factor, antithyroid antibodies Thyroid-function tests PPD skin test Chest radiography Fasting blood glucose measurement, hemoglobin A1c Pulmonary-function tests


37 PRINCIPLES OF TREATMENT Maximize activity of Ach at remaining receptors in NM junction Decrease immunological attack on motor end plates


38 TREATMENT Anticholinesterase medications Immunosuppressive agents-intermediate(steroids) and long term(AZT,MM) Thymectomy Plasmapheresis or intravenous immunoglobulin (IVIg)- immediate


39 ANTICHOLINESTERASE Pyridostigmine - most widely used 30 – 60 mg three to four times daily Initially Long-acting pyridostigmine may occasionally be useful to get the patient through the night Beneficial action begins within 15-30 mts and lasts for 3-4 hrs. Overdosage :- Increased weakness Muscarinic side effects (diarrhea, abdominal cramps, salivation, nausea)- controlled by propanthelene


40 MYASTHENIC Vs CHOLINERGIC CRISIS Onset acute Pupil normal/dilated Sweating absent Heart rate normal Respiration-hurried Tensilon test- improves Hyper acute Constricted Increased Bradycardia Increased secretion Worsening


41 THYMECTOMY 85% of patients experience improvement after thymectomy The advantage of thymectomy :- - It offers the possibility of long-term benefit - Can diminish or eliminate the need for continuing medicines


42 Immunosuppression Gluccocorticoids Azathioprine Mycophenolate mofetil Cyclosporine Tacrolimus Cyclophosphamide

Glucocorticoid therapy:

43 Glucocorticoid therapy Prednisone :- Initial low dose 15 – 25 mg / d Dose is increased stepwise (usually by 5 mg/d at 2- to 3-day intervals) until there is marked clinical improvement or a dose of 50–60 mg/d is reached This dose is maintained for 1 – 3 months and tapered

Mycophenolate mofetil:

44 Mycophenolate mofetil Effectiveness and relative lack of side effects 1–1.5 g bid Inhibition of purine synthesis by the de novo pathway Inhibits proliferation of lymphocytes but not proliferation of other cells Delayed improvement Expensive


45 azathioprine 2–3 mg/kg total body weight Initial dose of 50 mg/day Increased gradually until the white blood count falls to ~3000–4000/µL Adequacy of dosage :- - Reduction of the lymphocyte count to <1000/ L and/or an - Increase of the mean corpuscular volume of red blood cells Beneficial effects:- 3-6 months SE-idiosyncratic reactions,BM failure,alt LFT

Calcineurine inhibitors:

46 Calcineurine inhibitors Cyclosporine - 4–5 mg/kg per day Tacrolimus - 0.1 mg/kg per day given in two equally divided doses Side effects - Hypertension and Nephrotoxicity Therapeutic range Cyclosporine :- 150–200 ng/L Tacrolimus :- 5–15 ng/L


47 Plasmapheresis Plasma, which contains the pathogenic antibodies, is mechanically separated from the blood cells, which are returned to the patient A course of five exchanges (3–4 L per exchange) is generally administered over a 10- to 14-day period Produces a short-term reduction in anti- AChR antibodies

IV Immunoglobulin:

48 IV Immunoglobulin 2 g/kg, which is typically administered over 5 days (400 mg/kg per day) Improvement occurs in ~70% of patients Adverse reactions :- Headache, Fluid overload. Rarely Aseptic meningitis or Renal failure, Hyperviscosity leads to arterial and venous thrombosis

Myasthenic crisis:

49 Myasthenic crisis Exacerbation of weakness sufficient to endanger life Respiratory failure caused by diaphragmatic and intercostal muscle weakness Most common cause of crisis is intercurrent infection

Drugs to avoid:

50 Drugs to avoid Antibiotics Aminoglycosides : Streptomycin, Tobramycin, Kanamycin Quinolones : Ciprofloxacin, Levofloxacin, Ofloxacin, Gatifloxacin Macrolides : Erythromycin, Azithromycin, Telithromycin

Drugs to avoid:

51 Drugs to avoid Nondepolarizing muscle relaxants for surgery D- Tubocurarine (curare), Pancuronium , Vecuronium , Atracurium Beta-blocking agents Propranalol , Atenolol , Metoprolol Quinine derivatives Quinine, Quinidine , Chloroquine , Mefloquine Penicillamine :- May cause MG Magnesium :- Decreases ACh release

Slide 52:


Patient assessment:

53 Patient assessment Forward arm abduction time (up to a full 5 min) Forced vital capacity Range of eye movements Time to development of ptosis on upward gaze AChR antibody level


54 Conclusion 85% of patients experience improvement after thymectomy Myasthenic patient with fever and early infection should be treated aggressively AChR antibody level helps determining progress Negative result of Anti-AChR radioimmunoassay does not exclude MG Thyroid function tests :- should be carried out routinely in patients with suspected MG

Slide 55:


authorStream Live Help