1. MYOPATHIES,MYOTONIA, CARDIOMYOPATHIES.
Presenter: Dr Eva F. Mujuni (Resident-Internal Medicine) Facilitator: Dr B.L. Mtinangi

2. Overview 1.Introduction 2.Myopathies Definition Causes Classification
Pathophysiology
Clinical presentation
Diagnosis
Treatment

3. Overview… 3.Myotonia 5.References 4.Cardiomyopathies Definition
Causes
Types
Pathophysiology
Clinical Presentation
Diagnosis
Treatment
5.References
Definition
Causes
Treatment

4. Myopathies
A myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness.
It can occur in heart muscle, skeletal muscles, or muscles of various organs (for example, the stomach or intestines).

5. Myopathies Winged scapulae

6. Myopathies… Depending on the causes Myopathies can be classified as:
Genetic
Inflammatory
Endocrine
Toxic
Idiopathic

7. Myopathies… Classification of Myopathies… Genetic myopathies
Caused by a genetic defect.
The most common muscular dystrophies, Duchenne and Becker muscular dystrophy, result from a genetic defect on the X chromosome.

8. Myopathies… Classification of Myopathies…
Other Genetic Myopathies include:
Central core disease
Centronuclear (myotubular) myopathy
Myotonia congenita
Nemaline myopathy
Paramyotonia congenita
Periodic paralysis (hypokalemic and hyperkalemic forms)
Mitochondrial myopathies

9. Myopathies… Classification of Myopathies… Inflammatory myopathies
They are autoimmune disorders
Healthy muscle fibres are attacked by the body's immune system and become inflammed , this in turn damages the muscle.
Example in:
Polymyositis (PM)
Dermatomyositis (DM) is characterised by a skin rash as well as muscle symptoms of PM

10. Myopathies… Classification of Myopathies… Endocrine myopathies
Caused by the over or underproduction of hormones.
Examples are:
Hyperthyroid myopathy is caused by the thyroid gland producing too much thyroxine.
Hypothyroid myopathy is caused by the underproduction of thyroxine.

11. Myopathies… Classification of myopathies… Endocrine myopathies…
Cushing's disease, characterized by overproduction of hormones produced by the pituitary and adrenal glands.
Excess parathyroid hormone results in hypercalcemia, which causes proximal muscle pain and weakness.
Hormone-secreting tumors can also cause endocrine disorders that cause myopathies.

12. Myopathies… Classification of myopathies… Toxic myopathies
They are caused by exposure to certain medications and chemicals.
Excessive alcohol intake .
Drugs and chemicals - Anesthetics (eg. lidocaine, mepivacaine, ethyl chloride)
Cholesterol lowering medication (eg. clofibrate, genfibrozil, lovastatin, simivastatin, niacin)

13. Myopathies… Classification of myopathies… Toxic myopathies…
Glucocorticoids (eg. triamcinolone, dexamethasone, betamethasone)
Narcotics (eg. cocaine, heroin, meperidine)
Other drugs (eg. zidovudine, D-penicillamine, procainamide, chloroquine, gallamine)
Herbicides, insecticides

14. Myopathies… Clinical Presentation of Myopathies
Symmetric proximal muscle weakness
Malaise
Fatigue
Patient may note dark colored urine and/or fever.
No sensory complaints or paresthesias are noted with myopathies.
Atrophy and hyporeflexia are very late findings in most patients with myopathy. The early presence of these findings usually implicates neuropathies.

15. Myopathies… Diagnosis of Myopathies Medical history
Thorough physical exam
CK with isoenzymes
Electrolytes- calcium, magnesium
Serum myoglobin
Serum creatinine and BUN

16. Myopathies… Diagnosis of Myopathies…
Urinalysis: Myoglobinuria is indicated by positive urinalysis with few RBCs on microscopic evaluation.
Complete blood count
Erythrocyte sedimentation rate
Thyroid function tests

17. Myopathies… Diagnosis of Myopathies… Muscle tissue biopsy
Electromyogram

18. Myopathies… Treatment: Corticosteroids.
Immunosuppressive drugs - cyclosporine, tacrolimus , mycophenolate mofetil and rituximab .
Physical therapy.
Treating the underlying condition

19. Myotonia A symptom of several muscular disorders characterized by:
Increased muscular irritability and contractility
Slow relaxation of the muscles after voluntary contraction or electrical stimulation.

20. Myotonia… Causes of Myotonia
Abnormality in the muscle membrane—specifically, the ion channels that controls the contraction of muscle fibers.
Examples are:
myotonic muscular dystrophy
myotonia congenita

21. Myotonia… Myotonia congenita
This disease is caused by mutations in the gene for a chloride channel that is necessary for shutting off the electrical excitation that causes muscle contraction.
The Becker type is inherited in an autosomal recessive pattern.
The Thomsen type is autosomal dominant.

22. Myotonia… Treatment of Myotonia Mexelitine Quinine Phenytoin
Physical therapy

23. Cardiomyopathies
Cardiomyopathy is a chronic disease of the heart muscle (myocardium), in which the muscle is abnormally enlarged, thickened, and/or stiffened.

24. Cardiomyopathies… Common types: Dilated cardiomyopathy (DCM)
Hypertrophic cardiomyopathy (HCM)
Restrictive cardiomyopathy (RCM)   

25. Dilated cardiomyopathy (DCM)
Dilated cardiomyopathy is a condition characterized by dilatation and impaired systolic function of the left and/or right ventricle.
In majority,the cause is idiopathic

26. DCM

27. Causes of dilated cardiomyopathy
Genetic eg: Autosomal dominant DCM, X-limked cardiomyopathy
Inflammatory eg: Post-infective, autoimmune, connective tissue diseases( such as SLE and systemic sclerosis)
Metabolic eg: Glycogen storage diseases
Nutritional eg: Thiamin and selenium deficiency

28. Causes of dilated cardiomyopathy…
Endocrine eg Acromegaly, Thyrotoxicosis, Diabetes mellitus
Infiltrative eg: Hereditary haemochromatosis
Neuromuscular eg: Muscular dystrophy, mitochondrial myopathies
Toxic eg: Due to Alcohol,cocaine, Cyclophosphamide
Haematological eg: Sickle cell anemia, Thrombotic thrombocytopenic purpura

29. DCM Pathophysiology 25% of the idiopathic cases are familial
In the majority of familial cases the inheritence is autosomal dominant
The responsible genes are the genes encoding cytoskeletal or associated myocyte proteins(dystrophin,actin,desmin,troponin,lamin)

30. DCM Diagnosis Chest x-ray ECG Echocardiography
Testing for cause as indicated
Diagnosis is by history, physical examination, and exclusion of other common causes of ventricular failure (eg, systemic hypertension, primary valvular disorders, MI

31. DCM
Management
Anticoagulation (EF <30%, hx of embolic events,atrial fibrillation)
Limit activity based on functional status
Salt restriction
Fluid restriction
Medical therapy
ACE inhibitors, diuretics
Digoxin
Beta blockers

32. DCM Management… Cardiac transplantation
This disorder is the most common indication for cardiac transplantation
Left Ventricular Reduction Procedures
LV-reshaping

33. Hypertrophic cardiomyopathy (HCM)
Hypertrophic cardiomyopathy (HCM) is a condition in which the heart muscle becomes thick.
Characterized by variable myocardial hypertrophy most commonly involving the interventricular septum
Majority of cases are familial,autosomal dominant

34. HCM
With HCM, the sarcomeres (contractile elements) in the heart increase in size, which results in the thickening of the heart muscle.
In addition, the normal alignment of muscle cells is disrupted, a phenomenon known as myocardial disarray.
HCM is most commonly due to mutations in the genes encoding sarcomeric proteins.

35. HCM
Beta myosin heavy chain mutations cause elaborate ventricular hypertrophy
Troponin mutations cause less hypertrophy but more disarray and abnormal vascular response eg.hypotension,hence liable to sudden deaths.

36. HCM

37. HCM Clinical features : Asymptomatic Echocardiographic findings only
Dyspnea
Chest pain
Fatigue, pre-syncope, syncope
Palpitation, PND, CHF, dizziness
Cardiac arrythmias,Sudden death

38. HCM
Treatment
The primary goal of medications is to relieve symptoms such as chest pain, shortness of breath, and palpitations.
Beta blockers are considered first-line agents, as they can slow down the heart rate.
Nondihydropiridine calcium channel blockers such as verapamil can be used

39. HCM Treatment… Surgical myectomy Alcohol septal ablation
Ventricular pacing
Cardiac transplantation

40. Restrictive cardiomyopathies
It is a disease of the myocardium characterized by restrictive filling and reduced diastolic volume of either or both ventricles, with normal or near-normal systolic function.
May be classified as:
Primary (e.g., endomyocardial fibrosis, Löffler's endocarditis, idiopathic restrictive cardiomyopathy)
Secondary

41. Restrictive cardiomyopathies
Causes of secondary restrictive cardiomyopathy include:
Infiltrative diseases (e.g., amyloidosis, sarcoidosis)
Storage diseases (e.g., hemochromatosis, glycogen storage disorders, Fabry's disease).

42. Restrictive cardiomyopathies
Rigid ventricular wall with impaired ventricular filling
Much less common than DCM or HCM outside the tropics, but frequent cause of death in Africa, India, South and Central America and Asia primarily because of the high incidence of endomyocardial fibrosis in those regions

43. Restrictive cardiomyopathies
The idiopathic form may be familial
Associated with mutations in the sarcomeric protein troponin I

44. Restrictive cardiomyopathies
Clinical manifestations:
Dyspnea
Fatigue
Symptoms of right and left heart failure
Elevated Jugular Venous Pulse

45. Restrictive cardiomyopathy
Management:
No satisfactory medical therapy .
Cardiac failure should be treated.
Cardiac transplantation

46. References Kumar and Clark,Clinical Medicine 6th edition
Review of medical Physiology,W.Ganong 21st edition
Textbook of Medical Physiology,Guyton and Hall,10th edition
Medscape references-Drugs,diseases and procedures
of children.com
Wikipedia