Lec.

46

MEDICINE
Neurology

Dr.Zuhair

Lec 3

2017/2/28

Done by : Noor Ali Majeed

‫ﻣﻛﺗب اﺷور‬
‫ﻟﻼﺳﺗﻧﺳﺎخ‬
2016-2017
 Dr.Zuhair 21/2/2017

Myopathies
Note: This lecture has been extensively edited by the students and contains
much more information than the one presented by the doctor.

Objectives

• To recognize existence of muscle diseases

• To differentiate them from other disorders.
• To know about various causes of myopathy.
• To know of basic investigations of myopathy.

Definition
Myopathy: is a muscular disease in which the muscle fibers do not function for
any reason, resulting in muscular weakness. "Myopathy" simply means muscle
disease (myo- Greek "muscle" + -pathy Greek "suffering"). This meaning implies
that the primary defect is within the muscle, as opposed to the nerves
("neuropathies" or "neurogenic" disorders).

Muscle disease, either hereditary or acquired, is rare. Most typically, it presents

with a proximal symmetrical weakness.

Diagnosis is dependent on recognition of clinical clues, such as cardiorespiratory

involvement, evolution, family history, exposure to drugs, the presence of
contractures, myotonia and other systemic features, and on investigation
findings, most importantly EMG and muscle biopsy.

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Types
There are many types of myopathy; generally it is classified as either hereditary
or acquired and each of these is sub classified into many other types.

Hereditary syndromes include the

• Muscular dystrophies: characterized by muscle degeneration and

regeneration. Clinically, muscular dystrophies are typically progressive,
because the muscles' ability to regenerate is eventually lost, leading to
progressive weakness, often leading to use of a wheelchair, and
eventually death, usually related to respiratory weakness.
• Muscle channelopathies: Inherited abnormalities of the sodium, calcium
and chloride ion channels in striated muscle produce various syndromes
of familial periodic paralysis, myotonia and malignant hyperthermia,
which may be recognised by their clinical characteristics and potassium
abnormalities.
• Metabolic myopathies: which result from defects in biochemical
metabolism that primarily affect muscle, this includes Mitochondrial
myopathies, which are due to defects in mitochondria, which provide a
critical source of energy for muscle.
• Congenital myopathies: do not show evidence for either a progressive
dystrophic process (i.e., muscle death) or inflammation, but instead
characteristic microscopic changes are seen in association with reduced
contractile ability of the muscles.
• Again each of these sub classifications is further classified as shown in the
• boxes below which were taken from Davidson’s Principles and Practice of
Medicine 22ed 2014.

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Please note that you don’t need to memorize all the boxes’
information below as it contains much more information than the
doctor discussed or wanted for the exam!

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Muscular dystrophies

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These are inherited disorders with progressive muscle destruction, and may be
associated with cardiac and/or respiratory involvement and sometimes non-
myopathic features (Box 26.107). Myotonic dystrophy is the most common,
with a prevalence of about 12/100 000.

Clinical features The pattern of the clinical features is defined by the specific
syndromes. Onset is often in childhood, although some patients, especially
those with myotonic dystrophy, may present as adults.

• Wasting and weakness are usually symmetrical,

• No fasciculation or sensory loss
• Tendon reflexes are usually preserved until a late stage.
• Weakness is usually proximal, except in myotonic dystrophy type 1, when
it is distal.

Investigations The diagnosis can be confirmed by:

• Creatine kinase (Most important) is markedly elevated in the

dystrophinopathies (Duchenne and Becker) but is normal or moderately
elevated in the other dystrophies.
• EMG and muscle biopsy if necessary
• Specific molecular genetic testing.
• Screening for an associated cardiac abnormality (chest x-ray for
cardiomyopathy or ECG for dysrhythmia) is important.

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Management
There is no specific therapy for most of these conditions but physiotherapy and
occupational therapy help patients cope with their disability. Steroids are used
in Duchenne muscular dystrophy. Treatment of associated cardiac failure or
arrhythmia (with pacemaker insertion if necessary) may be required; similarly,
management of respiratory complications (including nocturnal hypoventilation)
can improve quality of life. Improvements in non-invasive ventilation have led
to significant improvements in survival for patients with Duchenne muscular
dystrophy. Genetic counselling is important.

Inherited metabolic myopathies: (Mitochondrial disorders & Channelopathies)

There are a large number of rare inherited disorders that interfere with the
biochemical pathways that maintain the energy supply (adenosine
triphosphate, ATP) to muscles. These are mostly recessively inherited
deficiencies in the enzymes necessary for glycogen or fatty acid (β-oxidation)
metabolism

Box 26.108). They typically present with muscle weakness and pain.)

Mitochondrial disorders
Mitochondria are present in all tissues and dysfunction causes widespread
effects, on vision (optic atrophy, retinitis pigmentosa, cataracts), hearing
(sensorineural deafness), and the endocrine, cardiovascular, gastrointestinal
and renal systems. Any combination of these should raise the suspicion of a
mitochondrial disorder, especially if there is evidence of maternal transmission.

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Mitochondrial dysfunction can be caused by alterations in either mitochondrial

DNA or genes encoding for oxidative processes. Genetic abnormalities or
mutations in mitochondrial DNA may affect single individuals and single tissues
(most commonly muscle). Thus, patients with exercise intolerance, myalgia and
sometimes recurrent myoglobinuria may have isolated pathogenic mutations in
genes encoding for oxidation pathways.

Inherited disorders of the oxidative pathways of the respiratory chain in

mitochondria cause a group of disorders, either restricted to the muscle or
associated with non-myopathic features (Box 26.109). Many of these
mitochondrial disorders are inherited via the mitochondrial genome, down the
maternal line. Diagnosis is based on clinical appearances, supported by muscle
biopsy appearance (usually with ‘ragged red’ and/or cytochrome oxidase
negative fibres), and specific mutations either on blood or, more reliably,
muscle testing. Mutations may be due either to point mutations or to deletions
of mitochondrial DNA.

A disorder called Leber hereditary optic neuropathy (LHON) is characterized by

acute or subacute loss of vision, most frequently in males, due to bilateral optic
atrophy. Three point mutations account for more than 90% of LHON cases.

Channelopathies (has been discussed above)

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Differential Diagnosis of myopathy

Ø Lower motor neuron disorders
Ø Neuropathy, How to differentiate?
Ø Peripheral neuropathy associated with autonomic changes (fecal and
urinary incontinence, bradycardia and dry mouth)
Ø Reflexes are absent (not useful to differentiate only in late or severe
cases)
Ø Neuromuscular (bizarre, asymmetric, variable)
Ø Anterior horn cell (reflexes are absent)

Limb-girdle

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Oculo-pharyngeal

Periodic Paralysis:
Ø Hypokalemic:
Ø Na, Ca channel
Ø After heavy carbohydrate meals, salt
Treament: Low sugar\salt diet, rich K diet
Ø Acetazolamide
Ø Hyperkalemic:
Ø Na channel
Ø After K rich meals
Treatmen: low K diet

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