Disorders of Skeletal Muscle

Department of Neurology
Anatomy

Skeletal muscle is made up of large numbers of multinucleated

muscle fibers, which have an outer membrane and cytoplasm and
in which lie the contractile components of the muscle. The fibers
are separated by connective tissue and arranged in bundles. Each
fasciculus has a connective tissue sheath. The muscle is made up of
a number of fasciculi bound togather and surrounded by a
connective tissue sheath. There aer two broad types of muscle
fiber, which are functionally different:
 Type 1---rich in myoglobulin, with low
metabolism, and low in sarcoplasm.

 Type2---low in myoglobin, with high mitabolism

and little sarcoplasm.
Clinical features of muscle disease

Muscle has rather uniform structure and function and

thus diseases of muscle from a variety of cause can produce
similar clinical features. The general features of muscle
disease will therefore be discussed prior to discussion of the
most common and important specific diseases.
Weakness

Weakness of muscles is a characteristic finding in

myopathies. Each muscle disease exhibits a particular pattern
of involvement, which is an important diagnostic clue.
Careful examination of all muscle groups is important to
classify a myapathy, and to differentiate it from a neuropathy
or central nervous system discorder.
Changes in muscle contractility

Myotonia—persistence of contraction, often for several

seconds, during attempted relaxation—is found in myotonic
dystrophy, paramyotonia congenita, hyperkalaemic penodic
paralysis, and congenital myatonia. On electromyography, the
characterristic findings consist of rhythmic discharges. This
phenomenon may also be elicited by a sharp tap on the muscle
belly. Myotonin must be differentiated from neuromyotonia,
which is derived from nerve abnormality.
Change in muscle tone

There may be a loss of tone secondary to

disease of muscle.
Changes in muscle bulk

Atrophy result with muscular dystrophies or is

caused by a lower motor neuron lesion.

Enlargement of muscle may be result of

overactivity or an early sign in certain dystrophies,
caused by infiltration of fat, exacerbating the
weakness.
Pain

Pain is a rare complaint in primary muscle

disease except in deficiencies of certain enzymes of
glycolytic or fat pathways or when the disease
involves blood vessels within the muscle.
 Family history

Many muscle diseases are inherited an therefore a full family

history is essential. Inherited muscles diseases include:

X-linked—Duchenne muscular dystrophy, Becker’s muscular

dystrophy, Emery-Dreifuss dystrophy.

Autosomal domiant—facio-scapulo-humeral dystrophy,

scapuloperoneal dysprothy, myotonic dystrophy.

Autosomal recessive---limb-gride dystrophy, all deficiencies

of enzymes of glycolytic and lipid metabolism.
Investigation of muscle disease

The diagnosis may be possible from the clinical features

in some causes of muscle disease. Additionally, helpful test
include:

Serum creatine phosphokinase (CPK) , this is often

highly raised in many dystrophies and in inflammatory
muscle disorders.

EMG---needle examination will reveal myopathic units.

There may be evidence of myotonic discharges in myotonias.
 Muscle biopsy----this can yield information
about fibre bype, inflammation, and dystrophic and
histo-chemical changes. Electron microscopy is
sometimes required.
Hereditary myopathies

Muscular dystrophies:

Duchenne muscular dystrophy

Becker’s muscular dystrophy

Duchenne muscular dystrophy

Duchenne musclar dystrophy is an X-linked

recessive condition caused by an absent of dystrophin,
occurring in 20-30/1000000 liveborn males. It attacks
skeletal and cardiac muscle.
Clinical feature

With Duchenne muscular dystrophy, there is no

abnormality at birth, but the condition is apparent
by the fourth year. The boy is usually wheelchair-
bound by 10 years old, and death is usual by the age
of 20, from respiratory failure or cardiomyopathy.
 There is initially proxiaml muscle weakness
with pseudohypertrophy of the calves. The
weakness then spreads. When rising to an erect
position, there is a characteristic manoeuver in
which the patient has to climb his legs with his
hands------Gower’s sign
Diagnosis

The diagnosis of Duchenne muscular dystrophy is

often made clinically. However, the CK is grossly
elevated often more than 10000U/L. The EMG is
myopathic, and muscle biopsy shows fatty infiltration
and absence of staining for dystrophin.
Management

There is no cure for Duchenne muscular dystrophy,

so the management is supportive. Steroids may provide
short-term improvement. Genetic counselling is
important-in carrier females, the CK is often raised
and the EMG may be myopathic, although there are no
clinical signs. There is also an accurate and rapid DNA
prode available, so accurate carrier and prenatal
diagnosis can be made and acted upon.
Becker’s muscular dystrophy

Becker’s muscular dystrophy is also an X-linked

recessive condition, with similar characteristic to
Duchenne muscular dystrophy, but it has a much
milder cause. Dystrophin is altered rather than
absent.
Clinical feature

The symptoms of Becker’s muscular dystrophy

begin in the first decade, although often are not noticed
until later. Boys continue to walk into their teens and
early adult life. Cramps associated with exercise are
common. Cardiomopathy can be worse than the
weakness.
Hypokalaemic periodic paralysis

Hypokalaemic periodic paralysis is an autosomal

dominant condition that results in abnormalities of L-
type calcium channels.

It becomes apparent between 10 and 20 years of age

and may remit after 35 years of age. Attacks of
generalized weakness develop after a heavy
carbohydrate meal or after a period of rest following
strenuous exertion.
 During an attack, the serum potassium falts to
below 3mmol/L. Attacks may last from 4 to 24 hours.
The weakness responds to treatment with potassium
chloride.

The condition is rarely fatal, as the diaphragm

and respiratory muscles tend to be spared. Similar
weakness with hypokalaemian may occur in
thyrotoxicosis.
Acquired myopathies

Polymyositis and dermatomyositis

Polymyositis and dermatomyositis are conditions in

which there is inflammation within the muscle. There
may be associated connective tissue disease (25%) or
underlying carcinoma (10%), especially if skin changes
are present .
Clinical feature

Polymyositis and dematomyositis usually present

in the fourth to fifth decade, with women more
commonly affected than men. Proximal muscle
weakness is the cardinal symptom. Pain and
tenderness of muscles occurs in less than half the
patients.
The associated skin changes include:

 Macular erythema on the face---especially in the

periorbital area, where it is heliotrope in colour.

 Erythematous plaques over the dorsal aspects of the

fingers,

 Nail-fold haemorrhages

 Photosensitivity
 As the disease progresses, there may be
widespread wasting and weakness, with bulbar
dysfunction and respiratory muscle weakness.
 Investigation

Investigations for polymyositis and dermatomyositis include the

following

ESR----raised

CK---usually raised

EMG---myapathic picture but may include fibrillations

 Muscle biospy----muscle fibre necrosis with inflammatory
infiltrate

 Autoantibodies ---present in up to 25% of patients.

 Investigation for underlying carcinoma

Treatment

Corticosteroids and other immunosupressive drugs

reduce the symptoms in about 75% of cases that not
associated with malignancy. Removal of an associated
tumour may cause complete remission.
 There is full recovery in about 10% of patients.
The remainder have varying degrees of disability ,
and the disease may become inactive after a few years.
When associated with connective tissue disease, the
prognosis is linked to the course of this disease.