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:

Enlargement of the calf muscles

To get up from the ground, the child associated with weakness, a
'walks up' his thighs with his hands. phenomenon termed
This is mainly because of weak pseudohypertrophy, is an
thigh muscles. 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.

 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.

 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.
 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.
 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.