Muscle Diseases PDF

 Myopathy  Definition   Myopathy is a common term for a muscle disease that is unrelated to any disorder of innervation or neuromuscular junction, with a wide range of possible etiologies. Practically all types of myopathy result in weakening and atrophy of...

 Myopathy  Definition   Myopathy is a common term for a muscle disease that is unrelated to any disorder of innervation or neuromuscular junction, with a wide range of possible etiologies. Practically all types of myopathy result in weakening and atrophy of skeletal muscles (the proximal muscles), such as the thigh and shoulder muscles.  General Classifications   A) Hereditary myopathies (primary)  Hereditary myopathies are inherited disorders primarily affecting the skeletal muscle tissue. These are caused by mutations in different genes- encoding proteins that play important roles in muscle structure and function.  1) Muscular dystrophies   represent a heterogeneous group of hereditary illnesses affecting both children and adults, with at least 30 different genes responsible for the disease development.  The most common muscular dystrophies are Duchenne and Becker muscular dystrophy results from a genetic defect on the X chromosome. These diseases are characterized by muscle wasting and weakness, with elevated levels of creatine phosphokinase (CPK).    A group of diseases of the skeletal muscles characterizes by gradual progressive degeneration of these muscles (Muscle fiber degeneration). When this degenerative process is genetically determined, it is termed “progressive muscular dystrophy” M.D  2) Congenital myopathies (present at birth)  no necrotic or degenerative changes are present in congenital myopathies (in contrast to muscular dystrophy) and CPK levels are often normal.  This group of myopathies includes some well- established conditions such as nemaline myopathy, central core disease, X-linked myotubular myopathy and centronuclear myopathy.  3) Metabolic myopathies   Comprise a diverse group of disorders which arise as a result of defects in cellular energy metabolism, including the vital breakdown of fatty acids and carbohydrates to generate adenosine triphosphate.  Reduction or ATP  4) Mitochondrial myopathies   are also a large group of disorders resulting from primary dysfunction of the mitochondrial respiratory chain and subsequently causing muscle disease. This group of illnesses has genetic etiologies and can frequently present with multi-system dysfunction.  5) Genetic defects   In the genes that code for calcium, sodium, potassium and chloride channels in skeletal muscles result in the periodic paralyses and the nondystrophic myotonias. Hence this group of diseases now includes myotonia congenita, paramyotonia congenita, hyper and hypokalemic periodic paralysis, potassium- aggravated myotonia. B) Acquired myopathies (Secondary)   1) The idiopathic inflammatory  myopathies  Polymyositis (PM) causes muscle aches, cramping, and tenderness. The muscle weakness is severe and may fluctuate over weeks to months. It is often worse in the neck, arms, and thighs, making it difficult to stand up from a sitting position. Many patients also experience fever and loss of appetite.  Dermatomyositis (DM) is characterised by a skin rash as well as muscle symptoms of PM. The rash is a purple discoloration around the eyes and on the cheeks but may also appear on other parts of the body. Eventually the skin becomes thin and fragile. DM most commonly develops in children between the ages of 5 and 14 years.  2) Endocrinologic myopathy   Steroid myopathy is the most common endocrine muscle disease. Steroid excess, whether caused by an adrenal gland disorder (eg. Addison disease) or chronic administration of steroids, causes muscle weakness and wasting.  Hyperthyroid myopathy is caused by the thyroid gland producing too much thyroxine. Its symptoms include weakening and wasting of the muscles, especially in the shoulders and hips, and sometimes the eyes.  Hypothyroid myopathy is caused by the underproduction of thyroxine and results in muscle weakening in the legs and arms. The muscles may become enlarged.  2) Endocrinologic myopathy   Cushing's disease, characterized by overproduction of hormones produced by the pituitary and adrenal glands, causes myopathy. These conditions can develop in children and adults and usually respond well to treatment.  Excess parathyroid hormone results in hypercalcemia, which causes proximal muscle pain and weakness.  3) Toxic myopathies   are caused by exposure to certain medications and chemicals. It is also included among the potential side-effects and toxicities associated with the certain lipid lowering agents, Anesthetics, Cholesterol lowering medication, Narcotics (eg. cocaine, heroin, meperidine), corticosteroids or Excessive alcohol intake can also damage skeletal muscle.  Genetic classifications  1) Muscular Dystrophy:  X linked psdudohypertrophic  -a) Duchenne Muscular Dystrophy  (DMD)  is the most common childhood form of MD accounts for 50% of cases in 1st decade of life.  Weakness in Duchenne Muscular Dystrophy subtype (DMD) sever form  results from the gradual loss of functional muscle fibers which are replaced by fat and connective tissue due to a lack of dystrophin, a protein encoded by the Xp21 gene. Dystrophin is integral within a complex of proteins which stabilizes the integrity of the sarcolemmal membrane, particularly during the stress associated with repeated cycles of contraction and relaxation   -b) Becker MD:   Similar to Duchenne MD with a later onset (2nd decade) and slower progression.  Early symptoms include frequent falls, and difficulty rising from the floor.  Calf muscles may appear large.  Becker Muscular Dystrophy (BMD) subtype benign form  Duchenne and Becker Muscular Dystrophy Duchenne Backer Form Sever Benign Course Progressive Slowly progressive Age of onset First decade Second,third decade Skeletal Present Absent deformities ECG changes Commonly Absent present  Duchenne and Becker Muscular Dystrophy  Duchenne Becker  1st decade of life  2nd decade of life  Progressive   Slowly progressive There is skeletal deformity as Talipus  No skeletal equino varus and scoliosis deformity appeared  Cardiomyopathy  No ECG changes might be present (ECG changes)  2-Autosomal dominant  as facio-scapulo-humeral MD type. Symptoms usually appear by age 20 yr. Symptoms are typically asymmetrical. Initially affects muscles of the face (facio), shoulders (scapulo), and upper arms (humeral) with typically very slow progressive weakness.  3-Autosomal recessive limb  girdle muscular dystrophy type (LGMD): Caused by a mutation in any of at least 18 different genes that affect proteins necessary for muscle function. Onset is anywhere from childhood to adulthood. symmetrical weakness of muscles of the shoulders and around the hips. Typically less severe and progress more slowly. Clinical classifications   Clinical types of progressive muscular dystrophies:   Shoulder girdle type: Scapulo-humeral type Facio- Scapulo-humeral type  Pelvic girdle type: Psudo-hypertrophy type (duchenne, backer) LGMD Atrophic type  Other rare types: Distal type of gower Ocular type Oculo-pharyngeal type Myotonic dystrophy  Signs and symptoms (clinical manifestations)  1- Signs of L.M.N lesion  Weakness Wasting LMNL signs Hypotonia Hyporeflexia  2- The weakness and wasting of the shoulder, pelvic girdle and trunk muscles results in :  A- Exaggerated lumbar lordosis  B- Pot-belly abdomen  C- Gower’s sign  D- Winging of the scapula (meryon’s  sign) E- Sloping of shoulders  F- Gait disorders  3- Selective affection of certain muscles (selectivity)  4- Facio-Scapulo- Humeral type  5- Pseudo hypertrophy   6- Skeletal deformities 7- E.C.G changes Clinical types of progressive  muscular dystrophy 1- Shoulder girdle types 2- Pelvic girdle types 3- Other rare types  Clinical Manifestations (Signs &   MuscleSymptoms): weakness shows affection in functional capabilities (start by shoulder, pelvis and trunk)  Weakness in LMN nature associated with wasting, hypotonia, hyporeflexia.  Fatigue: Muscle Pain (Myalgias), Cramps, and Stiffness.  Pseudo-hypertrophy mainly calf, gluteus maximus, quadriceps, deltoid, supraspinatus and infraspinatus).    Later on there are fibrosis and contractures on the affect of muscles resulting in skeletal deformity as genu recarvatum, talipus equines and pes cavus.  No sensory changes, fasciculation or sphincteric disturbances.  ECG changes and cardiomyopathy at (18 years) may be found especially in duchenne type.  With advancing age there is progressive muscle weakness and wasting leading to severe physical disability.  With advancing age death occur due to chest infections.  Selective affection by atrophy of certain muscles as sparing of sternocledomastoid and clavicular head of pectoralis and while sternal head was affected.   Weakness of shoulder, pelvis and trunk leading to:  Winging of scapula  Pot-belly abdomen  Exaggerated lumber lordosis  The Gowers’ sign  A waddling gait.  Hyperextension of the knee Investigations   Estimation of creatine and creatinine in urine  Estimation of serum enzyme  Creatine tolerance test  E.M.G  Muscle biopsy  Diagnostic investigations   Positive family history and genetic testing.  Urine analysis (presence of creatine).  Elevated serum enzymes: Creatine kinase (CPK).  Nerve conduction: Slower motor conduction velocity due to muscle degeneration.  Electromyogram (EMG): Diseased muscle has less activity.  Muscle biopsy: Muscle degeneration.  Analyze proteins: Lacking of dystrophin.  DNA Analysis: is sufficient to confirm a diagnosis.  What is a creatine kinase (CPK) test?  This test measures the amount of creatine phosphokinase (CPK) in the blood. CPK is a type of protein, known as an enzyme. It is mostly found in skeletal muscles and heart, with lesser amounts in the brain. There are three types of CK enzymes: -CK-MM, found mostly in skeletal muscles -CK-MB, found mostly in the heart muscle -CK-BB, found mostly in brain tissue  If you have higher than normal CK-MM enzymes, it may mean a muscle injury or disease, such as muscular dystrophy If you have higher than normal CK-MB enzymes, it may mean an inflammation of the heart muscle or are having or recently had a heart attack. If you have higher than normal CK-BB enzymes, it may mean a stroke or brain injury.  Physical therapy Examination:   1) Respiratory assessment:  2) Motor assessment:  -Observation  - Palpation:  a) Individual muscle testing/Group muscle test because all myopathic patient easy fatigability  b) Muscle tone examination: hypotonia  c) Deep reflexes: Hyporeflexia or areflxia  d) ROM examination  3) Sensory assessment: Normal  Exercise-induced myalgia (muscle pain) is more likely to be the presenting complaint of a metabolic or mitochondrial myopathy.  4) Gait and wheel chair assessment.  5) Functional assessment: To asses’ patient’s functional abilities and disabilities.  Treatment:   Medical  In recent years, there is growing evidence that treatment with corticosteroids  Physical Therapy & Rehabilitation  Improving Respiratory function.  Improving transfers and Gait re-education  Reducing risk of falls  Preventing contractures  Maintaining range of movement  Maintaining movement related to daily function  Provide equipment and parents instructions  Avoid resistive ex Physical therapy treatment   Physical Therapy prevention:   walking independent stage  ambulant stage  bound to wheel chair stage Rehnold’s Program for muscular dystrophy   Line of treatment First stage.. Walking Second stage.. Third stage.. bound to independent Ambulant wheel chair 1- Muscle shortening - Active free ex. - Active free ex. - Submaximal stretching  - Submaximal - Active assisted ex. ex stretching ex. - Submaximal stretching ex. 2- Exercises - Breathing ex. Same as first stage - Breathing ex. - Active free - Passive ROM - Active assisted - Passive ROM 3- Heat application - Under water ex. With Same as first stage Same as first stage tem.(34-38) - Paraffin packing 4- Technical application Night splints - Night splints - Splints - Walking aid - Electric wheel chair - Standing table 5- ADL Normal activities Activities within - Wheel chair activities patient’s ability - Respiratory care 6- Parent instruction - Breathing ex. - Breathing ex. - Breathing ex. - Diet rich in vitamins - Diet rich in - Coughing training - Avoid air draft vitamins - Diet rich in vitamins - Avoid air draft - Avoid air draft & wheel - Adaptation of chair complications house for ADL     Providing adaptation and equipment: Prognosis    Bad prognosis because the causes of death in muscular dystrophy are:  Paralysis of respiratory muscle  Infections specially pneumonia  Cardiomyopathy in Duchenne type  Bed sores in late stage of the disease Myasthenia gravis     is a neuromuscular disorder that causes weakness in the skeletal muscles  It is characterized by weakness and rapid fatigue of any of the muscles under voluntary control.  It is caused by a breakdown in the normal communication between nerves and muscles.  Though myasthenia gravis can affect people of any age, it's more common in women younger than 40 and in men older than 60.  Symptoms tend to progress over time, usually reaching their worst within a few years after the onset of the disease.  Pathogenesis:   Immune system produces antibodies that block or destroy many of muscles' receptor sites for a neurotransmitter called acetylcholine.  With fewer receptor sites available, muscles receive fewer nerve signals, resulting in weakness.  Antibodies may also block the function of a protein called a muscle-specific receptor tyrosine kinase. This protein is involved in forming the nerve- muscular junction. When antibodies block the function of this protein, it may lead to myasthenia gravis.  Symptoms of myasthenia  gravis:  Problems walking up stairs or lifting objects  Weakness in neck, arms and legs  Facial paralysis  Difficulty breathing due to muscle weakness  Difficulty swallowing or chewing  Fatigue  Trouble talking  Hoarse voice  Drooping of eyelids (ptosis).  Double vision (diplopia).  Assessment of myasthenia gravis:   Checking reflexes, looking for muscle weakness, checking for muscle tone  Making certain your eyes move properly  Repetitive nerve stimulation test  Blood testing for antibodies associated with MG  Imaging of the chest using CT scans or MRI to rule out a tumor  Treatment   treatment can help relieve signs and symptoms, such as weakness of arm or leg muscles, double vision, drooping eyelids, and difficulties with speech, chewing, swallowing and breathing.  -Medication: Corticosteroids and immunosuppressants  -Thymus gland removal: which is part of the immune system, may be appropriate for many patients with MG.   -Plasmapheresis is also known as a plasma exchange. This process removes harmful antibodies from the blood,  -Intravenous immune globulin (IVIG) is blood product that comes from donors.  -Lifestyle changes: There are some things can do at home to help alleviate symptoms:  Get plenty of rest to help minimize muscle weakness.  If double vision, patient should wear an eye patch.  Avoid stress and heat exposure, as both can worsen symptoms.  Complications of myasthenia  gravis:  One of the most dangerous potential complications of MG is myasthenic crisis. This consists of life-threatening muscle weakness that can include breathing problems.  Individuals with MG are at a higher risk of developing other autoimmune disorders such as lupus and rheumatoid arthritis.  Long-term outlook for  MG:  depends on a lot of factors, some people will only have mild symptoms. Others may eventually become confined to a wheelchair.  Early and proper treatment can limit disease progression in many people.