DISEASES OF SKELETAL

MUSCLES
DENERVATION (NEUROGENIC) ATROPHY

Caused by damage of anterior horn

cells or their axons and

manifests clinically as muscle

weakness that varies form mild,
localized weakness to severe,
generalized weakness with
respiratory compromise
Denervated: muscle fibers appear

Smaller than normal (atrophic), and .1

(Roughly triangular (angulated .2

Both type I (slow twitch) and type II (fast twitch) fibres are
.affected

Re-inervation : is followed by

Return of fiber size to normal, and .1

Appearance of aggregates of muscle fibers of the same .2

(histochemical type (fiber type grouping
SPINAL MUSCLE ATROPHY (INFANTILE MOTOR
:(NEURONE DISEASE

A group of autosomal recessive diseases

resulting from idiopathic loss of anterior horn cells
.in infancy

.The responsible gene is located on chromosome 5

The most common form isWerdnig - Hoffman

disease (SMA 1) which presents at birth or
appears in the first 4 months of life and leads to
death within the first 3 years of life
 MUSCLE DYSTROPHIES

Genetically determined (inherited) myopathies, often

.beginning in childhood

:I. X-LINKED MUSCLE DYSTROPHIES

:Duchenne muscle Dystrophy.1

Thecommonest , themost severe and themost rapidly

progressive . of all inherited myopathies

Incidence: 1/10,000 live borne males

Inheritence: An X-linked recessive disease but
.about 30% of cases arise by mutation

The responsible gene is located on the short arm of

.(X-chromosome (Xp-21

Its protein product, dystrophin, is a structural

.component of the sarcolemma

Absence of dystrophin leads to dysfunction of the

.sarcolemma with influx of excessive calcium ions
:Clinical Features

:Affected boys present before the age of 5 years by

A waddling gait .1
Inability to run, and .2
Inability to rise easily from the ground (weak pelvic girdle .3
(muscles

Eventually, they become confined to a wheel chair by the age

of 13 years

to die in the early twenties due to respiratory failure,

pneumonia or cardiac arrythmias
:Pathological changes in a muscle biopsy

Marked random variation in muscle fiber size .1

Degeneration, necrosis & hyalinization of muscle .2

fibers

Regeneration of muscle fibers .3

Replacement of muscle fibers by fat & fibrous .4

tissue in late stages
:Becker’s muscular dystrophy .2

:Differs from Duchenne muscle dystrophy as follows

a) Less common

b) Much less severe

c) More slowly progressive

d) Appears at a later age (late childhood or

(adolescence
:II. AUTOSOMAL DYSTROPHIES

Present at a later age than Duchenne muscle

dystrophy and are more slowly progressive

:The most important are

.1Occulo-pharyngeal muscle dystrophy

.2Fascio-scapulo-humeral muscle dystrophy

.3Limb-girdle muscle dystrophy

:III. MYOTONIC MUSCLE DYSTROPHY

An autosomal dominant disease resulting

from a mutation on chromosome 19

The main clinical presentation ismyotonia

i.e delayed relaxation of muscle after
contraction
 OTHER MYOPATHIES
:I. CONGENITAL MYOPATHIES

A group of myopathies, most of which are inherited and

become manifest in early life, distinguished by the presence
ofspecific histologic changes within the affected
muscles. They are associated with only mild to moderate
.muscle weakness

:The most important congenital myopathies are

Centronuclear (myotubal) myopathy .1

Nemaline myopathy .2

Central core disease .3

II. MYOPATHIES ASSOCIATED WITH INBORN ERRORS
:OF METABOLISM

Glycogen storage diseases .1, types II and IV

Mitochondrial myopathies (oxydative phophorylation .2

:(diseases

A group of disorders resulting from mutation in mitochondrial

.DNA

Characterized by abnormally appearing mitochondria

producing“ragged red fibres” in sections stained by the
Gomori – trichrome stain
:III. INFLAMMATORY MYOPATHIES

Infectious myositis : .1 Viral, bacterial,

parasitic

Non-infectious .2 inflammatory muscle

diseases: Polymyositis, dermatomyositis
:IV. TOXIC MYOPATHY

:May be caused by

Toxins: Snake venom, alcohol .1

Drugs: Glucorticoids, chloroquine, .2

halothane

Thyrotoxicosis .3
 MYASTHENIA GRAVIS

An autoimmune disorder of neuromuscular

transmission characterized by progressive
muscle weakness

:Incidence

Occurs in 3/100,000 persons-

:Seen predominantly in-

a) Young females with thymic hyperplasia
b) Middle aged males with thymoma
:Clinical features

Abnormal fatiguability of muscles manifested as .1

weakness on exercizing and recovery on
resting

(Ptosis and diplopia (weak ocular muscles .2

Difficulty in swallowing, chewing and speaking .3

((weak facial muscles

(Respiratory distress (weak respiratory muscles .4

:Prognosis

:The course is variable and can be either

Rapidly progressive with death in a few .1

months mostly due to aspiration
pneumonia

Slowly progressive .2 over years with

fluctuations in severity
:Pathogenesis

.An autoimmune disorder

Auto-antibodies against acetyl choline

receptors on the sarcolemma either
injure these receptors or inhibit the
binding of acetyl choline to the
.receptors