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

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

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

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).

Myopathies Winged scapulae

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

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.

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

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

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.

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.

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)

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

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.

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

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

Myopathies… Diagnosis of Myopathies… Muscle tissue biopsy Electromyogram

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

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.

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

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.

Myotonia… Treatment of Myotonia Mexelitine Quinine Phenytoin Physical therapy

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

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

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

DCM

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

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

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)

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

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

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

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

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.

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.

HCM

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

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

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

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

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).

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

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

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

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

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 http:www.health of children.com Wikipedia