My Op At Hies

2nd BPT

Myopathies Dr. Ghaith J. Al-Eyd M.B.Ch.B., M.Sc., Ph.D.

GMC / Department of Pathology

Reaction of Muscle Cells to Injury:  Atrophy; occurs with disuse, ischemia & denervation.  Hypertrophy; in response to increased load, or to compensate for loss.  Necrosis of muscle fiber.  Phagocytosis of dead muscle fibers by macrophages.  Regeneration takes place from the population of stem cells (satellite cells).  Fatty infiltration & Fibrosis.  Primary inflammation.

Muscle Diseases (Sign & Symptoms):  Clinical manifestations:  Progressive muscle weakness.  Muscle wasting.  Stiffness or myotonia.  Fasciculation (abnormal involuntary contractions giving a twitching sensation).  Cramping, aching, tenderness.  Easy fatigability.

Muscle Diseases:  Muscular dystrophies: These are inherited diseases of muscle, which generally result in progressive degeneration. They are classified according to inheritance pattern, clinical pattern of muscle groups involved and, as the genes responsible become characterized, increasingly by molecular genetic technique.  Myopathies: These are a group of conditions of diverse etiology, grouped together because of a predominant impact of disease on the muscle; there are four main sub-groups:  Inflammatory myopathies (primary inflammation. of muscle amenable to therapy), very common.  Secondary myopathies (a systemic disease process causes pathology in muscle, often amenable to therapy), these are common.  Metabolic myopathies (primary metabolic problem has a major impact on muscle function), these are uncommon.  Congenital myopathies (the are distinguished from the dystrophies in that they are generally non-progressive), these are rare.

 Neurogenic disease: Particularly diseases of peripheral nerves or motor neurons, cause secondary atrophy of skeletal muscle.

Muscle Diseases (Diagnosis):  Clinical examination.  EMG (electromyography).  ECG (electrocardiography).  Muscle enzymes can be estimated to investigate a muscle disease (e.g. serum creatine kinase level estimates the level of activity of muscle fiber necrosis).  Biopsy of muscle (open & needle biopsy) is an important investigation in certain neuromuscular diseases in which there are clinical features of weakness, muscle wasting, or muscle pain.  Use of special stains, electron microscopy, genetic studies.

Skeletal muscle has limited pathological responses; atrophy, hypertrophy, change in fiber type distribution, necrosis, phagocytosis of dead muscle fibers by macrophages following necrosis, fibrosis, fatty infiltration and inflammation.

Muscular Dystrophies:  These are a group of genetically determined degenerative diseases of muscle, pathologically they are characterized by the destruction of single muscle cells over a prolonged period of time with fiber regeneration and fibrosis.  They are classified according to the pattern of muscle groups involved, the pattern of inheritance and, molecular genetic abnormalities: Type of dystrophy

Inheritance

Muscle involved in initial stages

Duchenne

X-linked recessive

Pelvic girdle

Becker

X-linked recessive

Pelvic girdle

Limb girdle

AR

Pelvic girdle

Fascioscapulohumeral

AD

Face, shoulder girdle, arm

Scapulhumeral

AR

Shoulder girdle & arm

Oculopharyngal

AD

External ocular & pharynx

Myotonic dystrophy

AD

Face, respiratory, limbs

Duchenne Dystrophy:  It is the most common form of muscular dystrophy in childhood, and it is a x-linked recessive disorder, hence it is almost exclusively seen in males.

 It is caused by mutation in the gene coding for dystrophin (a protein that normally helps anchor the internal cytoskeleton of muscle fibers through the cell membrane and to the extracellular matrix). Lack of dystrophin renders fibers liable to tearing with repeated contraction.

 The onset of clinical features is early in childhood, affected children showing muscle weakness with high a high S. CK level (caused by necrosis), and clinical calf hypertrophy (due to fatty replacement of muscle).

 the disease has a very poor prognosis, most affected individuals dying in their late teens. Heart muscle is also affected, leading to cardiomyopathy.

 Histologically, there is muscle fibers necrosis, phagocytosis of dead fibers, and replacement of muscle by fibrous & fatty tissue.

Duchenne Muscular Dystrophy (DMD):

Normal muscle stained for Dystrophin

Absence of Dystrophin in DMD

Diagram showing the relationship between the cell membrane (sarcolemma) and the sarcolemmal associated proteins

Duchenne Muscular Dystrophy (DMD) – Clinical Course:  Mostly affects boys (rarely girls).  Often brothers or male relatives have same problem. First signs appear around ages 3 to 5: the child may seem awkward or clumsy, or he begins to walk 'tiptoe' because he cannot put his feet flat.  Runs strangely; falls often.  Problem gets steadily worse over the next several years. Muscle weakness first affects feet, fronts of thighs, hips, belly, shoulders, and elbows. Later, it affects hands, face, and neck muscles.  Most children become unable to walk by age 10.  May develop a severe curve of the spine.  Heart and breathing muscles also get weak.  Child usually dies before age 20 from heart failure or pneumonia.

Duchenne Muscular Dystrophy (DMD) – Clinical Course:

To get up from the ground, the child 'walks up' his thighs with his hands. This is mainly because of weak thigh muscles.

Enlargement of the calf muscles associated with weakness, a phenomenon termed pseudohypertrophy, is an important clinical finding.

Duchenne Muscular Dystrophy (DMD) – Clinical Course:

Gower’s Sign in DMD

Myotonic Dystrophy:  It is the most common inherited muscle disease of adults that is characterized by muscle weakness, myotonia, and several non-muscle features including cataracts & frontal baldness in males, cardiomyopathy and low intelligence.

 It is inherited as AD disorder and usually becomes apparent in adolescence with facial weakness in the limbs. Death is commonly due to involvement of the respiratory muscles.

 The responsible gene is located on chromosome 19, coding for a protein kinase.

 Histologically, affected muscles show abnormalities of fiber size, with fiber necrosis, abundant internal nuclei, and replacement by fibro-fatty tissue.

Limb Girdle Syndrome:  Patients with this syndrome may have one of several diseases; patients who have weakness in pelvic girdle & proximal leg muscles or in shoulder girdle and proximal arm muscles are said to have a limb girdle syndrome.

 On investigation, most patients with this syndrome have metabolic or neurogenic muscle disease or a late-onset Becker’s dystrophy.

Fascioscapulohumeral dystrophy:  This may be caused by several diseases and the true one presents with weakness in the face & shoulder, and is associated with a slow clinical progression.

 Onset is generally in the third decade and all cases require investigation, as a variety of metabolic, inflammatory, neurogenic and myopathic disorders may be responsible.

Congenital Myopathies:  They usually present in childhood as hypotonia (floppy baby syndrome) or muscle weakness.

 The majority of congenital myopathies are named after the structural abnormalities seen on muscle biopsy, e.g. central core disease, nemaline body myopathy, myotubular myopathy, congenital fiber-type disproportion.

 They are non progressive and this distinguish them from muscular dystrophies.

 Inheritance is variable, with both sporadic & heritable types.

 Although many types are compatible with a long life expectancy , others may cause disability because of secondary skeletal deformities or respiratory muscle involvement.

Inflammatory Myopathies:  The inflammatory myopathies are characterized by primary inflammation of muscle, with resulting fiber necrosis. The inflammatory infiltrate is mainly composed of T-cells and monocytes as part of an abnormal autoimmune response.

 There are 3 main types of inflammatory myopathy:

 Polymyositis: This presents clinically with weakness of proximal limb muscles & facial muscles, ptosis, and dysphagia.  Inclusion body myositis: This is clinically similar to polymyositis, but occurs mainly in elderly patients. Muscle biopsy shows inflammation, necrosis, and the presence of vacuoles & filamentous inclusions in fibers (seen by EM).  Sarcoidosis: may affect muscle, but it is relatively uncommon compared to other types of inflammatory myopathy.

Signs and Symptoms:  Although symptoms depend on the type of myopathy, some generalizations can be made:  Skeletal muscle weakness is the hallmark of most myopathies, with some noticeable exceptions, such as myotonia and paramyotonia congenital.  Pain.  Stiffness (myotonia).  Tenderness.  Fasciculation (abnormal involuntary contractions giving a twitching sensation).  Easy fatigability and Aching.  Cramping.  Muscle wasting.

 Initially, individuals may feel fatigued doing very light physical activity. Walking and climbing stairs may be difficult because of weakness in the pelvic and leg muscles that stabilize the trunk. Patients often find it difficult to rise from a chair. As the myopathy progresses, there may be muscle wasting.

Questions About Muscular Dystrophies: 

How common is it? It is not very common. Rehabilitation centers may see one child with muscular dystrophy for every 30 or 40 with cerebral palsy or polio.

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What treatment is there? None. No medicines help. Special therapy or exercises will not stop the weakness from increasing. Surgery to release tiptoe contractures is at best of temporary benefit.

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The family can, however, do much to help the child make the best of his life and adapt to his limitations as they progress.

 Exercise. To keep as strong as possible and prevent contractures, probably the best therapy, at least at first, is to stay active, to walk, run, and play. While range-of-motion and stretching exercises may help, it is even better to involve the child in games, work, and other activities that keep his joints flexible. 

Also the use braces to prevent contractures may help the child to keep walking longer. If the child sits in a bad position, pillows or supports to help him sit straighter can help prevent deformities.

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If the child sits in a bad position, pillows or supports to help him sit straighter can help prevent deformities.

 Even though he is slow and awkward, encourage him to take part. Feeling sorry for him and just letting him sit is the worst thing you can do.

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If contractures of the knees and hips begin to develop, try resting or sleeping with 'sand bags' to press down the legs and help straighten them.

Other aids. The child will reach a point where he needs to use crutches. Later, (often by age 10) he will not be able to walk. Do not force him when it becomes too hard. Instead, try to obtain or make a wheelchair. At first, the child may be able to roll it himself. But as his weakness progresses, he may need to be pushed.