Major causes of myopathy

Inflammatory Drugs and toxins

Polymyositis Illicit drugs - cocaine, heroin

Dermatomyositis Alcohol

Inclusion body myositis Corticosteroids

Juvenile dermatomyositis Other - colchicine, antimalarial drugs,

HMG-CoA reductase inhibitors,
Vasculitis
penicillamine, zidovudine
Overlap syndromes - lupus,
Infections
scleroderma, rheumatoid arthritis,
Sjögren's syndrome Viral - influenza, parainfluenza, Coxsackie,
HIV, cytomegalovirus, echovirus,
Rheumatoid arthritis, Sjögren's
adenovirus, Epstein-Barr virus
syndrome
Bacterial - pyomyositis, lyme myositis
Endocrine disorders
Fungal
Hypothyroidism
Parasitic - trichinosis, toxoplasmosis
Cushing's syndrome (or exogenous
steroid administration) Rhabdomyolysis

Electrolyte disorders Crush trauma

Hypokalemia Seizures

Hypophosphatemia Alcohol abuse, including hyperkinetic state

with delirium tremens
Hypocalcemia
Exertion, especially with environmental
Hypernatremia or hyponatremia
heat illness
Metabolic myopathies
Vascular surgery
Disorders of carbohydrate, lipid, and
Malignant hyperthermia
purine metabolism
Inherited myopathies

Acid maltase deficiency

Muscular dystrophy
INTRODUCTION Distinguishing true muscle weakness from lassitude or motor impairment not due
to loss of muscle power ●Localizing, within the neuromuscular system, the site of the lesion that is
producing weakness ●Determining the cause

systemic disorders may interpret difficulties performing certain tasks as weakness. Included in this group
are cardiopulmonary disease, joint disease, anemia, cachexia from malignancy or chronic infectious or
inflammatory disease, and/ordepression. Patients with any of these conditions may be functionally
limited but not truly weak. Patients with lassitude often complain that they are weak. In comparison,
those with true muscle weakness typically complain that they are unable to perform specific tasks, such
as climbing stairs or combing hair, or that they have a feeling of "heaviness" or "stiffness" in their limbs.
Muscle pain is relatively uncommon in patients with many types of myopathy and true weakness, but it
is often reported by patients with overexertion, cramps, or fibromyalgia. Similarly, patients with
polymyalgia rheumatica, are limited by pain and stiffness but have normal muscle strength. (

Physical examination — ●Despite advanced generalized muscle atrophy, muscle strength is relatively
preserved in patients with cachexia.●Mus cle tenderness is usually not associated with one of the
causes of true muscle weakness. There are, however, exceptions to this general rule including infectious
myopathies such as trichinellosis and viral myositis, certain drug-induced myopathies, thyroid
myopathy, and the inherited metabolic myopathies.

True muscle weakness is documented by formal muscle testing. The strength of each muscle can be
assessed by determining how much force is required by the examiner to overcome maximal contraction
by the patient.

●Zero – No muscle contraction ●One – Flicker or trace of muscle contraction ●Two – Limb or joint
movement possible only with gravity eliminated ●Three – Limb or joint movement against gravity
only ●Four – Power decreased but limb or joint movement possible against resistance ●Five –
Normal power against resistance

LOCALIZING THE SITE OF THE LESION — motor cortex and proceeds through the corticospinal tracts,
anterior horn cells, spinal nerve roots, peripheral nerves, neuromuscular junction, and finally muscle

Generalized weakness occurs in some cases of myasthenia gravis, long-standing periodic paralysis,
advanced disuse atrophy from prolonged bed rest, muscle wasting from malignancy, or longstanding
motor neuron disease

If the weakness is not generalized, it can be characterized as symmetric or asymmetric. Asymmetric

weakness most likely reflects disease of the central or peripheral nervous System
Symmetric patterns of weakness can be divided into distal, proximal, or specific distributions.

●Distal weakness is characterized by decreased grip strength, weakness of wrist flexion or

extension, decreased plantar flexion strength, and foot drop. These patients have difficulty
walking on their heels or toes. Foot drop can be detected by opposing the patient's attempt to
dorsiflex the ankle. Distal symmetric weakness is characteristic of early motor neuron disease or
peripheral neuropathy.

●Proximal weakness involves the axial muscle groups, deltoids, and hip flexors. Affected patients
may have difficulty flexing or extending the neck against resistance. One way to detect the
 presence of neck flexor weakness is to observe the patient sitting up from the supine position. In
this setting, the head will lag behind as the patient sits up. Sitting up may be difficult or even
impossible in patients with more severe proximal muscle weakness or, at times, may be the only
objective evidence of weakness. Deltoid muscle strength can be assessed by pressing down on the
patient's fully abducted arms with the elbows flexed. The examiner should not be able to
overcome the patient's resistance if strength is normal.

The patient with quadriceps weakness may be unable to rise from a seated position without the
use of the upper extremities and is usually unable to perform a deep knee bend. These individuals
may suddenly drop into the chair when trying to sit down slowly. Patients with proximal leg
weakness may rise from sitting on the floor by "climbing up their legs with their hands." This is
termed Gower's sign and is characteristic of, but is not specific for, Duchenne muscular dystrophy.
Proximal muscle weakness is typically seen in the various myopathies), certain muscular
dystrophies, and myasthenia gravis.

●Specific distributions of weakness are characteristic of certain neuropathies or muscular

dystrophies. Examples of localized disorders include facioscapulohumeral dystrophy,
scapuloperoneal dystrophy, and scapulohumeral dystrophy.

DETERMINING THE CAUSE OF THE LESION — Once the neuromuscular site of the lesion causing
weakness has been identified, the disorders at each site can be categorized as
genetic, inflammatory/immunologic, infectious, neoplastic, toxic, or metabolic in origin.

Lesions of upper motor neurons — Upper motor neuron impairment can occur with the common acute
stroke syndromes, space occupying lesions of the central nervous system, and lesions of the spinal cord.
Spinal cord lesions can be related to trauma, infection, tumor, vascular anomalies, hypertrophic
degenerative skeletal changes, demyelinating diseases, and congenital leukodystrophies.

Anterior horn cell lesions — Weakness due to involvement of the anterior horns cells is seen in motor
neuron disease, familial spinal atrophy, lead poisoning, and poliomielitis. West Nile and other virus
infections represent additional causes of lower motor neuron disease.

Lesions of the peripheral nervous system — typically presents in one of two patterns:

●A symmetric polyneuropathy with weakness and sensory symptoms is a frequent sequela of

diabetes mellitus. Other etiologies toxic or metabolic insults, as well as heritable disorders

●Mononeuropathy may be the result of nerve compression (eg, carpal or tarsal tunnel syndrome,
ulnar neuropathy, radial neuropathy). Mononeuropathy multiplex (ie, asymmetric
polyneuropathy) occurs in diabetes mellitus or one of the vasculitic syndromes such as
polyarteritis nodosa.

In addition, weakness may result from involvement of the neuromuscular junction. This can be induced
by anti-acetylcholine receptor antibodies in myasthenia gravis or drug-induced myasthenia, inhibition of
acetylcholinesterase by organophosphate poisoning, or interference with presynaptic calcium channel
function in Lambert-Eaton syndrome.

Myopathy — inflammatory disorders, endocrinopathies, metabolic myopathies, drugs and toxins,

infections, and the various causes of rhabdomyolysis .
 ●A history of recurrent episodes of exertion-related pigmenturia and weakness suggests a
metabolic myopathy. However, many metabolic myopathies have a slowly progressive rather than
episodic course. ●Medication, alcohol, or substance-abuse may be a clue to drug-induced
myopathy. ●Endocrinopathy, such as thyroid dysfunction (hypo or hyperthyroidism) or Cushing's
syndrome, may be the cause of true muscle weakness. ●Inflammatory myopathy should be
suspected if there is symmetric proximal muscle weakness and no evidence of an alternative
explanation for the weakness or if there are other features of a systemic rheumatic disease such
as rash, interstitial lung disease, polyarthritis, or Raynaud phenomenon.

Elevations of plasma muscle enzymes (creatine kinase, aldolase, lactate dehydrogenase, and the
aminotransferases) are highly suggestive of muscle diseases. They can, however, also be elevated
in motor neuron disease or can be induced by strenuous exercise, intramuscular injections, or
muscle trauma in the absence of generalized muscle disease A positive test for urine blood, in the
absence of red blood cells in the sediment, is suggestive of myoglobinuria.

●Serologic tests – Serologic tests including antinuclear antibodies, antibodies against extractable
nuclear antigens (anti-Ro/SSA,anti-La/SSB, anti-Sm, and anti-RNP), and "myositis specific" antigens
(eg, anti-histidyl-t-RNA synthase [anti-Jo-1]) should be obtained if an inflammatory myopathy or
associated connective tissue disease is suspected. Anti-neutrophil cytoplasmic antibody (ANCA)
titers, hepatitis B and C serologies, and cryoglobulins should be obtained in patients with
suspected vasculitis.

Electrophysiologic studies — Nerve conduction and electromyographic (EMG) studies are used when
the site of the lesion causing weakness is suspected to be in the peripheral nervous system, the
neuromuscular junction, or the muscle itself. The EMG is also of value in directing the site of muscle
biopsy. Magnetic resonance imaging — Magnetic resonance imaging (MRI) may be useful in selecting a
muscle for biopsy and has an advantage over EMG in cases of suspected inflammatory myopathy in that
the actual muscle to be biopsied can be identified, rather than the muscle contralateral to one with
EMG abnormalities Muscle biopsy — Muscle biopsy may be necessary to determine the precise form of
myopathy. Characteristic changes of dermatomyositis, polymyositis, inclusion body myositis, certain
drug-induced myopathies, the muscular dystrophies, or vasculitis may be seen on routine light
microscopy. Electron microscopic examination may be useful in some cases (eg, to confirm inclusion
body miositis . Special stains can demonstrate enzyme deficiencies and abnormal accumulations of
glycogen or lipid in the metabolic myopathies .

UPPER MOTOR Leukodystrophies Vasculitis Brain tumor B12 Radiation

Anterior horn cell : polio, spinal muscle atrophy, amyotrophic lateral sclerosis, paraneoplàstic,
lead

Peripheral nerve; diabetis, lead , guillain barre,leprosy,myeoloma

NM junction: myathenia,butulism, eaton lamberg, organopho poison

Muscle hypothyroid, steroids,HIV, malignancy.myo

Causes of neuromuscular disease
Spinal cord
Demyelinating disease (multiple sclerosis)
Disc compression
Epidural abscess
Hemorrhage
Infarction
Syringomyelia
Tetanus
Transverse myelitis
Trauma
Tumor

Motor nerves
Amyotrophic lateral sclerosis (ALS)
Cervical spondylosis
Critical illness neuromyopathy
Poliomyelitis
Diphtheria
Guillain-Barre syndrome
Lymphoma
Metabolic (porphyria, diabetes)
Mononeuritis multiplex
Phrenic nerve injury
Sarcoidosis
Toxins (heavy metals)
Vasculitis

Neuromuscular junction
Botulism
Hypermagnesemia
Lambert Eaton syndrome
Myasthenia gravis
Medications (neuromuscular blocking agents, aminoglycosides, anticholinesterase
inhibitors)
Organophosphate poisoning
Scorpion sting
Shellfish poisoning
Snake venom

Muscles
Acid maltase deficiency
Metabolic abnormalities (hypokalemia, hypophosphatemia)
Malnutrition
Mitochondrial myopathy
Muscular dystrophy
Myotonic dystrophy
Polymyositis/dermatomyositis
Rhabdomyolysis
Thyroid disease

Respiratory muscle weakness due to neuromuscular disease

Respiratory muscle weakness is common among patients who have neuromuscular

disease . It can be acute (eg, Guillain-Barré syndrome), chronic and relapsing (eg,
multiple sclerosis, myasthenia gravis), or relentlessly progressive (eg, amyotrophic lateral
sclerosis [ALS]).

It is estimated that 15 to 28 percent of patients with myasthenia gravis and 20 to 30

percent of patients with Guillain-Barré will require invasive mechanical ventilation

Respiratory muscle (inspiratory, expiratory, upper airway) weakness due to

neuromuscular disease can cause insufficient ventilation, nocturnal hypoventilation, or
ineffective cough. It can also be associated with bulbar dysfunction.
●Insufficient ventilation may induce dyspnea, orthopnea, rapid shallow breathing
(tachypnea plus decreased tidal volume), accessory respiratory muscle use,
thoracoabdominal paradox (inward motion of the abdomen during inspiration),
hypercapnia, or hypoxemia.

●Nocturnal hypoventilation may induce choking, insomnia, daytime hypersomnolence,

morning headaches, fatigue, or impaired cognition.

●Bulbar dysfunction may induce difficulty swallowing, dysarthria, dysphagia, weak

mastication, facial weakness, nasal speech, or a protruding tongue.

●Ineffective cough predisposes patients to aspiration, retention of secretions

The principal cause of insufficient ventilation is weakness of the inspiratory muscles

(diaphragm, external intercostals, scalenes, sternocleidomastoids, and trapezii). The
weak inspiratory muscles cause tidal volume to decrease. Respiratory frequency
increases in an effort to compensate for the diminished tidal volume and maintain
alveolar ventilation. However, the tidal volume may eventually fall to such a degree that
the increased respiratory rate is insufficient to maintain alveolar ventilation and arterial
carbon dioxide tension (PaCO2) begins to rise. To maintain the best possible tidal
volume, patients with inspiratory muscle weakness use accessory inspiratory muscles
and rely on gravity to assist diaphragmatic movement. As a consequence, orthopnea,
accessory respiratory muscle use, and thoracoabdominal paradox develop.
●Insufficient ventilation itself can cause hypoxemia ●Patients with inspiratory muscle
weakness breathe shallowly (low tidal volumes) and have an ineffective sigh, a maneuver
essential for maintaining patency of alveoli. As a result, atelectasis develops and creates
a physiologic right-to-left shunt. Such patients can get caught in a vicious cycle because
chronic atelectasis reduces respiratory system compliance, which increases the work of
breathing and predisposes the patient to worsening respiratory muscle fatigue. Early in
the course of the disease, the symptoms and signs described above may exist only when
carbon dioxide production is elevated (eg, fever, infection). In such patients, ventilation
may be adequate to maintain a normal PaCO2 when carbon dioxide production is at its
baseline, but cannot be sufficiently increased to maintain a normal PaCO2 when carbon
dioxide production is elevated.

Nocturnal hypoventilation — Inadequate ventilation may first manifest during sleep in

patients who have chronic neuromuscular disease. This results from upper airway
obstruction due to bulbar dysfunction, as well as decreased accessory respiratory muscle
activity during rapid eye movement (REM) sleep. The symptoms and signs of nocturnal
hypoventilation due to neuromuscular disease are the same as those due to obstructive
sleep apnea, including choking, insomnia, daytime hypersomnolence, morning
headaches, fatigue, or impaired cognition.

Bulbar dysfunction is due to impairment of the upper airway muscles: the lips, tongue,
palate, pharynx, and larynx. Symptoms include difficulty swallowing, dysarthria,
dysphagia, weak mastication, facial weakness, abnormal secretion clearance, nasal
speech, or a protruding tongue. Patients with bulbar dysfunction have an increased risk
of aspiration. In addition, they are predisposed to upper airway obstruction during
inspiration, which may induce or exacerbate nocturnal hypoventilation.

Ineffective cough — Poor cough is caused by weakness of the upper airway, inspiratory,
and expiratory muscles – internal and external obliques, rectus abdominis, transverse
abdominis, and internal intercostals. Patients with a poor cough are predisposed to
aspiration, pneumonia, and respiratory failure

In neuromuscular disease, the degree of respiratory muscle weakness cannot be

accurately predicted by the degree of peripheral muscle weakness. Significant
respiratory muscle dysfunction can exist in the presence of mild (or no) peripheral
muscle weakness. Therefore, tests of respiratory muscle function are essential to identify
the patient who is at risk for respiratory failure.

Confirm respiratory muscle weakness — Respiratory muscle weakness is confirmed by

pulmonary function testing. No single abnormality is diagnostic of respiratory muscle
weakness; rather, diagnosis is based on a constellation of abnormalities. The use of
single tests tends to overdiagnose respiratory muscle weakness, whereas use of
combinations of tests increase diagnostic accuracy .Typical abnormalities include:

●A pattern of restriction: reduced forced expiratory volume in one second (FEV1, less
than 80 percent of predicted), reduced forced vital capacity (FVC, less than 80 percent of
predicted), normal FEV1/FVC ratio (greater than 70 percent of predicted), and reduced
total lung capacity (TLC, less than 80 percent of predicted). Patients with predominantly
expiratory muscle weakness also demonstrate an increased residual volume (RV)
●FVC measured in the supine position is more than 10 percent lower than that
measured in the upright position.
●Vital capacity (VC) measured in the supine position is more than 10 percent lower than
that measured in the upright position.
 The VC is the maximum volume of gas that can be expelled from full inspiration. The
FVC is also the maximum volume of gas that can be expelled from full inspiration, but it
is measured when the patient is exhaling with maximal speed and effort. The VC is
usually higher than the FVC, with the difference being directly related to the degree of
obstruction. The VC may be a more reliable indicator of respiratory muscle weakness
because it is not affected by coexisting obstructive airway disease.

●Maximum voluntary ventilation (MVV) is reduced.

●Maximal inspiratory pressure (MIP) or maximal expiratory pressure (MEP) is reduced.
The MIP reflects the strength of the diaphragm and other inspiratory muscles, while the
MEP reflects the strength of the abdominal muscles and other expiratory muscles.
●Diffusing capacity for carbon monoxide (DLCO) is normal in the absence of coexisting
pulmonary parenchymal or vascular involvement.

Regardless of the measures used, the degree of perturbation generally correlates with
the severity of the respiratory muscle weakness. As an example, a MIP of -20 cm H2O
indicates more severe respiratory muscle weakness than a MIP of -40 cm H2O.

Another approach to assessment of inspiratory muscle function is measurement of

diaphragmatic thickness by ultrasound.

Assess cough — ●Peak cough flow – The peak cough flow (PCF) is measured by having
the patient inspire fully and then cough forcibly through a mask or mouthpiece attached
to a peak flow meter. A PCF less than 160 L/min identifies patients with an ineffective
cough. Patients with a PCF between 160 and 270 L/min are at risk for respiratory tract
infections, which can further reduce muscle strength ●MEP — A MEP less than 60 cm
H2O suggests that the patient's cough is ineffective

Patients who present with cardiorespiratory arrest, respiratory distress, marked blood
gas abnormalities, severe bulbar dysfunction with aspiration, or impaired consciousness
need immediate mechanical ventilation. For all other patients, mechanical ventilation
should be initiated on the basis of their overall clinical status. Serial measures of
pulmonary function (instead of using one measure at one point in time) can be used as
rough guidelines, especially when the respiratory decline is acute:

Ventilatory support is indicated when the FVC is less than 50 percent of predicted
● when the MIP is less negative than -30 cm H2O (eg, -20 cm H2O) or the MEP is below
40 cm H2O The diminished MIP indicates a high risk for hypercapnia, while the low MEP
indicates inadequate cough strength and risk for secretion retention. ● when
the VC falls below 15 to 20 mL/kg, 60 percent of predicted, or 1 L. It may also be
indicated if the VC falls more than 30 to 50 percent compared to a prior measurement.
The normal VC is 60 to 70 mL/kg

the measures are generally considered in combination. A "20-30-40 rule" has been
proposed. The rule advocates the initiation of ventilatory support when the VC is less
than 20 mL/kg, the MIP is less negative than -30 cm H2O (eg, -20 cm H2O), or the MEP
is less than 40 cm H2O.

Once it is determined that mechanical ventilation is necessary, options include

noninvasive positive pressure ventilation (NIV) or invasive positive pressure

NIV may benefit patients who require: ●Continuous mechanical ventilation for a short
duration (ie, days), such as patients with an acute neuromuscular disease (eg, Guillain-
Barré syndrome)

●Intermittent mechanical ventilation for a long duration (ie, years), such as patients with
nocturnal hypoventilation or early chronic respiratory failure

NIV is not used for continuous long-term mechanical ventilation because of the
potential for local skin breakdown at the patient-mask interface.

The likelihood that NIV will be unsuccessful or cause a complication is increased when
any of the following exist: severe bulbar dysfunction, upper airway obstruction, retention
of respiratory secretions, inability to achieve a satisfactory interface, poor cooperation,
or inadequate cough.

Among patients with neuromuscular disease who receive intermittent long-term

mechanical ventilation for early chronic respiratory failure or nocturnal hypoventilation,
NIV may prevent or delay progression of chronic respiratory failure . It may also prolong
survival, at least among patients with amyotrophic lateral sclerosis (ALS)

Tracheostomy should be considered in the following types of patients with

neuromuscular disease:●Patients who have difficulty clearing their secretions.●Patients
who require intermittent long-term mechanical ventilation, but in whom noninvasive
positive pressure ventilation (NIV) is contraindicated (eg, severe bulbar
dysfunction).●Patients whose chronic respiratory failure has worsened and intermittent
long-term NIV is no longer sufficient.●Patients who fail to wean from invasive
mechanical ventilation.

Monitoring gas exchange in patients with neuromuscular disease and respiratory muscle
weakness is important to detect the onset of nocturnal hypoventilation and the need for
nocturnal mechanical ventilation. As an example, nocturnal monitoring of
transcutaneous PCO2 (PtcCO2), conducted at home and without supervision, identified
nocturnal hypoventilation in neuromuscular patients who had daytime normocapnia

Monitoring is also critical for patients receiving NIV to determine ventilator settings
designed to avoid hypercapnia. In patients with chronic respiratory failure on long- term
NIV, noninvasive monitoring of PtcCO2 was shown to accurately reflect PaCO2 . In
patients with chronic neuromuscular respiratory failure, PtcCO2 detected alveolar
ventilation, while SpO2 alone could not reliably do so

Invasive mechanical ventilation is indicated for patients who require continuous

mechanical ventilation for longer than a few days, or those who have contraindications
to NIV. Invasive mechanical ventilation should be initiated early (ie, before it is needed
emergently) in patients with increasing neuromuscular weakness for the following
reasons:●Intubation itself has risks that are best managed in a controlled setting.
Specifically, dysautonomia increases the risk of severe hypotension and bradycardia
during and following the intubation, while denervated muscle increases the likelihood
that succinylcholine will induce life-threatening hyperkalemia. These risks can be
decreased by avoiding depolarizing neuromuscular blocking agents, emphasizing
topical anesthesia instead, and minimizing the use of vasoactive sedative agents ●Early
intubation may decrease the risk of early-onset pneumonia, defined as pneumonia that
occurs within five days of intubation .

Even with timely intubation, patients with neuromuscular disease tend to have relatively
poor outcomes ●Among intubated patients with Guillain-Barré syndrome, mortality is
12 to 20 percent and the median duration of mechanical ventilation is 18 to 29 days
●Among intubated patients with myasthenia gravis, mortality is 4 to 8 percent and the
median duration of mechanical ventilation is 14 days (one week longer than patients
without neuromuscular disease) ●Among intubated patients admitted to ICU, 64
percent have diaphragmatic dysfunction. When compared to patients with normal
diaphragm function, those with diaphragm dysfunction had a higher mortality (26 versus
5 percent)
Interventions that may be useful for improving cough and secretion clearance include
mechanical insufflation-exsufflation, manually-assisted coughing, hyperinflation
maneuvers, and secretion mobilization techniques. Mechanical insufflation-exsufflation is
generally the preferred intervention . Insufflation-exsufflation can be delivered via a
mechanical device to patients who are spontaneously breathing or mechanically
ventilated. During insufflation, positive pressure is applied (usually +40 cm H 2O), which
results in an inspired tidal volume. Exsufflation rapidly follows as the pressure becomes
negative (usually -40 cm H2O). The device is generally well tolerated, with few
complications.

Mechanical insufflation-exsufflation may be less effective in patients who have an

expiratory airflow limitation (eg, chronic obstructive pulmonary disease) because it is
associated with worse expiratory airway collapse. Studies in such patients demonstrate
either no improvement or a decrease in the peak cough flow

Manually-assisted cough — The manually-assisted cough (also called quad cough) is an

abdominal thrust that is provided by a caregiver and timed to occur at the same time as
the patient's voluntary cough effort. It is probably effective in all patients who have
expiratory muscle weakness, although it has only been proven in patients with spinal
cord injury. In patients who have inspiratory muscle weakness, the manually-assisted
cough is insufficient and should be combined with hyperinflation maneuvers.

Hyperinflation maneuvers — Hyperinflation maneuvers increase the inspiratory tidal

volume. This provides a greater volume of gas to be forced out during a cough, thereby
improving cough effectiveness. These maneuvers require intact bulbar function for the
patient to retain the delivered tidal volume .Hyperinflation maneuvers
include:●Glossopharyngeal breathing (ie, repetitive air gulping)●Delivery of stacked
breaths (ie, initiation of inspiration before the completion of expiration) using a
resuscitation bag with a one-way valve and mouthpiece ●Mechanical inspiration using
a mechanical insufflator or a volume cycled ventilator

Secretion mobilization techniques — High frequency chest-wall oscillation and

intrapulmonary percussive ventilation are two techniques that can mobilize secretions
from the airways

correct electrolyte abnormalities (eg, hypophosphatemia, hypokalemia) and avoid

factors that may further compromise respiratory muscle function, including
neuromuscular blocking agents, aminoglycosides, and glucocorticoids. An adequate
nutritional status should be maintained, but overfeeding must be avoided as the
associated increase in carbon dioxide production can worsen hypercapnia

Critically ill patients with neuromuscular disease are at increased risk for developing
superimposed critical illness myopathy or polyneuropathy

Muscle enzymes in the evaluation of neuromuscular diseases

The measurement of serum levels of muscle enzymes is a critical part of the

evaluation of patients presenting with weakness or myalgias, and it is important in
monitoring the course and response to therapy of certain muscular disorders. Creatine
kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and aldolase are the serum enzymes that are measured in
clinical practice.

Creatine kinase (CK) is the most widely used enzyme to diagnose and follow muscle
disease. It is present in the highest concentrations in serum in response to muscle injury,
is the most sensitive indicator of muscle injury, and is the best measure of the course of
muscle injury

Aldolase is another glycolytic pathway enzyme that is found in all tissues but
predominantly in skeletal muscle, liver, and brain. While increased aldolase levels are
not as specific or sensitive for muscle disease as CK levels, aldolase concentrations are
occasionally elevated in patients with myositis who have normal CK levels

Lactate dehydrogenase (LDH) increased serum levels are found in a great variety of
disease states.

Aminotransferases — Both enzymes are found widely in many tissues, and increased
serum levels are a nonspecific indicator of disease. Serum concentrations are highest in
various hepatic disorders, but increased values are also seen in skeletal muscle,
myocardial disease, and hemolysis.

In general, marked elevation of serum muscle enzymes is seen in myopathies. Thus,

serum creatine kinase (CK) activity >1000 units/L helps to distinguish muscle disease
from neurogenic causes of weakness and muscle atrophy. More modest elevation of CK
may occur in some primary neurologic disorders, particularly motor neuron disease.

Inflammatory myopathies — nearly universal elevation of at least one of the muscle

enzymes at some time during the course of active myositis . CK is the most commonly
measured, although at times aldolase, lactate dehydrogenase (LDH), or the
aminotransferases will be elevated in the absence of an elevated CK . Rarely, clinical
muscle disease with weakness and abnormal electromyography (EMG) and muscle
biopsy findings occurs in the absence of muscle enzyme elevation. It has been
suggested in these cases that an inhibitor of CK is present causing a false negative CK
level. Slight elevation or normal levels of serum CK activity may be present in patients
with inclusion body myositis.
In other patients, the rash of dermatomyositis is present without clinical muscle disease
or elevated muscle enzymes, termed "amyopathic dermatomyositis" or
"dermatomyositis sine myositis". The degree of CK elevation in dermatomyositis and
polymyositis varies greatly, reaching as high as 100 times normal.

Patients with myopathy presenting with nonspecific arthralgias, myalgias, or

constitutional symptoms that may overshadow the presence of muscle weakness are
commonly evaluated with a multichannel chemical analyzer in which elevated LDH and
aminotransferases may first suggest the presence of liver disease. In this setting, a
careful assessment of muscle strength and measurement of CK and aldolase should lead
to the correct diagnosis of muscle disease and avoidance of an unnecessary liver biopsy

Other exceptions include:●Very early disease in which children present with rash and
fever, but before muscle weakness and enzyme elevation occur ●Very advanced disease
in which there are marked muscle atrophy and normalization of enzymes

Muscle enzyme elevation in patients with other connective diseases including

rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and
scleroderma suggests an associated myositis which may be subclinical or marked by
mild muscle weakness. The enzyme elevations in these disorders are usually mild and,
in a patient with systemic lupus or scleroderma, are suggestive of mixed connective
tissue disease or scleroderma/polymyositis overlap; these disorders are associated with
the specific autoantibodies anti-U1 RNP and anti-PM/Scl, respectively.

●A group of disorders classified as localized myositis presents with focal muscle

involvement and variable degrees of muscle enzyme elevation . Etiologies include
infections, focal presentations of polymyositis, insect bites, and idiopathic cases

.●Serum CK elevations occur in about 80 percent of patients with inclusion body

myositis. The elevations are mild, less than 10 times the normal range

●Other inflammatory conditions associated with myositis and elevated muscle enzymes
include the systemic vasculitides (polyarteritis nodosa , Churg-Strauss vasculitis , and
granulomatosis with polyangiitis [Wegener’s]), polymyositis associated with chronic
graft-versus-host disease, Behçet syndrome, and sarcoidosis .

Infectious myopathies — Infectious myopathies with elevated serum enzyme

concentrations can follow viral, bacterial, spirochetal, mycobacterial, fungal, and
parasitic infections. Muscle involvement in these infections may be either localized or
generalized. CK elevations in viral myositis may reach levels greater than 1000 times
normal

Dystrophinopathies — Elevated serum muscle enzyme concentrations occur in the sex-

linked recessive muscular dystrophies (Duchenne's and Becker's), the limb-girdle
dystrophies, facioscapulohumeral dystrophy, and myotonic dystrophy. CK levels are
elevated in patients with Duchenne and Becker muscular dystrophy from the newborn
period, before any clinical signs of the disease appear. CK levels peak by age two and
then progressively fall, often to the normal range, as more and more muscle is replaced
by fat and fibrosis . CK levels are increased in approximately 70 and 50 percent of
Duchenne and Becker female carriers, respectively .The elevations are usually mild, up
to three times the upper limit of normal.

Rhabdomyolysis — Acute, massive muscle injury due to trauma, prolonged muscle

compression, seizures, electrolyte imbalances, infections or drugs is associated with
marked elevations of muscle enzymes. The degree of CK elevation correlates with the
risk of acute renal failure

Drugs — Muscle enzymes are elevated in various drug-induced myopathies including

those due to colchicine, antimalarials, cholesterol-lowering drugs (statins, gemfibrozil,
nicotinic acid, and clofibrate), cocaine, and alcohol .Serum CK concentrations range
from mild elevations of three to four times normal with antimalarial neuromyopathy to
10- to 20-fold elevations in colchicine neuromyopathy and to massive elevations and
rhabdomyolysis with cocaine use or acute alcoholic myopathy. Massive elevations of
CK have also been reported in patients on mechanical ventilators treated with
nondepolarizing muscle blocking agents and high dose glucocorticoids

Neuroleptic malignant syndrome — change in mental status and the presence of

rigidity, fever, and dysautonomia. Elevation of CK is a variable feature, and otherwise
typical cases of NMS have occurred in the absence of CK elevation. This syndrome is
most often seen with either traditional or "atypical" neuroleptic agents (eg, haloperidol,
fluphenazine, and chlorpromazine; clozapine, risperidone, and olanzapine) and has also
occurred in the setting of use of antiemetic drugs (eg, metoclopramide and
promethazine

Metabolic myopathies — Inherited disorders of carbohydrate, lipid, and purine

metabolism are associated with episodic muscle damage ranging from myalgias and
mild muscle enzyme elevation to frank rhabdomyolysis. While these conditions
represent a very small percentage of cases of rhabdomyolysis, they should be suspected
in cases where no obvious precipitating factors are present, particularly when there is a
history of recurrent episodes.

Carnitine palmitoyltransferase (CPT) and muscle phosphorylase deficiency are the most
common metabolic myopathies. Muscle phosphorylase deficiency, or McArdle's
Disease, is inherited in an autosomal recessive pattern. Affected individuals typically
have a history of exercise intolerance in childhood followed by recurrent cramps,
fatigue, and myoglobinuria in adolescence or early adulthood. CK levels do not
completely return to normal between episodes of rhabdomyolysis.
In contrast, individuals with CPT deficiency have normal CK levels during interictal
periods. Thus, serum muscle levels should be measured when the individual is
symptomatic.

Malignant hyperthermia — fever, generalized muscular contraction and rigidity,

metabolic acidosis, and rhabdomyolysis, most commonly after the use of inhalational
anesthetic agents in susceptible individuals. CK levels may rise several hundred times
greater than normal during an episode and may remain persistently elevated in those
individuals who recover. Malignant hyperthermia may occur sporadically or may be
familial.
Endocrine myopathies — Hypothyroidism is frequently accompanied by myalgias,
stiffness, mild muscle weakness, and mild to moderate elevations of CK and other
muscle enzymes. Rarely, rhabdomyolysis and myoglobinuria occur after vigorous
exercise. Muscle enzymes return to normal levels after one to two months of thyroid
replacement therapy.
Muscle enzymes are typically normal in patients with hyperthyroidism.
Gradually progressive proximal muscle weakness with or without muscle wasting
occurs in some patients with acromegaly. Mild myopathic changes may be seen on
muscle biopsy, and mild elevation of muscle enzymes has been reported. However,
weakness may be a manifestation of peripheral neuropathy.
Cushing's syndrome, glucocorticoid-induced myopathy, and hyperparathyroidism may
all be associated with muscle weakness. However, muscle enzyme levels remain normal
in these conditions.
Diabetic muscle infarction is a rare complication of diabetes mellitus. Patients with
poorly controlled type I disease appear to be at highest risk of developing this otherwise
rare disorder. The sudden onset of pain and localized swelling in the thigh or calf
muscles that characterize muscle infarction must be distinguished from pyomyositis or
other causes of localized myositis. The serum CK level may be normal or elevated. The
erythrocyte sedimentation rate (ESR) is usually increased. Gradual resolution of pain
and swelling is expected over several weeks to months, but recurrences may occur.
Periodic paralyses — The periodic paralyses are characterized by unpredictable
recurrent episodes of muscle weakness lasting generally from a few hours to a few days
and then spontaneously resolving. The periodic paralyses have been classified as
primary or secondary depending upon whether there is a family history or an underlying
condition such as thyrotoxicosis and, on the basis of serum potassium levels during an
attack, as hypokalemic, hyperkalemic, or normokalemic. The common mechanism of
these conditions appears to be an intermittent unexcitability of the muscle fiber
membrane related to electrolyte shifts across the membrane. Muscle enzyme levels rise
rapidly during an attack and may remain slightly elevated between attacks. The degree
of enzyme elevation varies widely among patients with these disorders.

ELEVATED MUSCLE ENZYMES IN THE ABSENCE OF MUSCLE

DISEASE — Serum muscle enzyme concentrations can be increased in the absence of
muscle disease with exercise, muscle trauma, and motor neuron disease.

Exercise — Serum creatine kinase (CK) concentrations reach peak levels at 8 to 24

hours after exercise, decrease at 24 to 48 hours, and return to baseline by 72 hours
Iatrogenic muscle injury — CK levels follow the same temporal pattern after an
intramuscular injection, major surgery, electromyography (EMG), or muscle biopsy..
Major surgical procedures, particularly orthopedic and spinal surgery, cause serum
enzyme elevation due to direct muscle trauma and to ischemic compression of muscle
due to positioning during the procedure

Motor neuron disease — mild elevations in serum muscle enzymes were found in 75
percent of cases, particularly in the early phases of the disease and more commonly in
men possibly leading to misdiagnosis of an inflammatory myopathy or inclusion body
myositis.

Asymptomatic elevations in creatine kinase — Individuals with persistently elevated

CK but with no or minimal muscle symptoms and no weakness present a diagnostic
dilemma. Muscle biopsies in these individuals are infrequently diagnostic, and in those
patients in whom a specific diagnosis can be made, it is usually a disorder for which
there is no treatment, such as a dystrophy or a metabolic myopathy with a benign
outcome.

An approach to evaluating an asymptomatic patient with an unexplained elevated CK

includes: ●Determine if the elevated CK is high enough to be of clinical significance
based on age, gender, and race. CK levels decrease with age, so elevated levels are more
likely to be due to an identifiable cause in children and adolescents. Serum CK levels
vary between racial groups, being higher in blacks than whites, Hispanics, or Asians
Within racial groups, CK levels are correlated with body size and composition,
including body mass index (BMI) and fat mass, and are higher in males than females.
CK levels 1.5 times the upper limit of normal should be considered abnormal; these
equate to >1200 for black men, >650 for black women, >500 for white men, and >325
for white women.

●Repeat the CK after the patient has refrained from intense exercise for at least three
days if there is any question that the elevation could be due to overexertion. Exclude
recent intramuscular injections. ●Review the medication list and inquire about recent
drug exposures ●Consider the possibility of macro CK, particularly if there is an
unexpected increase in the MB isoenzyme, which can be identified by CK
electrophoresis ●EMG can be performed to exclude motor neuron disease. EMG is not,
however, adequately specific or sensitive to exclude myopathy with certainty.
●A muscle biopsy can be performed only after a discussion with the patient that the
likelihood of making a definite diagnosis of a treatable condition is extremely low and
that the prognosis of an isolated unexplained CK is very good. ●If there is concern for
malignant hyperthermia susceptibility based on the patient’s family history or a
previous reaction to an inhaled anesthetic agent, a muscle biopsy may be done for a
contracture test.

MUSCLE ENZYMES IN MONITORING THE COURSE OF DISEASE

—Dermatomyositis or polymyositis — In adults with dermatomyositis or polymyositis,

serum levels of creatine kinase typically decrease by about 50 percent during the first
month of high-dose therapy with glucocorticoids, and normalization of muscle enzymes
may take up to four months

. Muscle enzyme levels generally decrease before improvement in muscle strength

occurs; normalization of muscle enzymes with therapy is predictive of recovery of
strength.. Failure to normalize muscle enzymes after two months should prompt
consideration of alternative diagnoses such as inclusion body myositis, muscular
dystrophy, or hypothyroidism. However, in some cases of severe disease, serum
enzymes will fail to normalize even with aggressive glucocorticoid and
immunosuppressive therapy. Disease exacerbations are usually preceded by an increase
in muscle enzymes. Thus, serial enzyme measurements are generally useful in assessing
the disease course in an individual patient.
In some cases, the elevations in serum creatine kinase (CK) or aminotransferase
concentrations are within the normal range but are still a harbinger of increased clinical
disease activity. If glucocorticoids are tapered at the time of a mild increase in CK, a
further increase in CK to outside the normal range and relapse of muscle weakness is
likely. By contrast, recurrence of weakness during glucocorticoid treatment with no
increase in serum enzymes is more likely to represent steroid myopathy than increased.

Pathogenesis of inflammatory myopathies

The inflammatory myopathies are a group of disorders sharing the common feature of
immune-mediated muscle injury. The most common of these disorders
include:●Dermatomyositis (DM)●Overlap syndromes (with another systemic rheumatic
disease)●Inclusion body myositis (IBM)●Immune-mediated necrotizing myopathy
(IMNM)●Polymyositis (PM)

No specific environmental factors or infectious causes have known roles in these disorders.
Other subtypes of inflammatory myopathy include eosinophilic myositis and granulomatous
myositis. Many patients with inflammatory myopathies cannot be assigned to any category
and may be classified as having nonspecific myositis

IMMUNE-MEDIATED NECROTIZING MYOPATHY — This uncommon condition, which is

sometimes confused with polymyositis (PM), may occur in several settings, including as a
paraneoplastic disorder or in association with the use of certain drugs, including statins [91]. In
the small number of patients on statins who develop this syndrome, myositis that develops in
association with use of these medications persists despite drug discontinuation, unlike the
more typical statin-related myopathy that resolves after drug discontinuation. The condition
can respond to immunosuppressive therapies, supporting the view that this condition is
immune-mediated, despite the lack of substantial immune cell invasion of muscle.In patients
with autoimmune necrotizing myopathy, which is sometimes classified with PM, scattered
necrotic muscle fibers are present. Necrotizing myopathy is sometimes associated with anti-
signal recognition particle (SRP) antibodies
DRUG ASSOCIATED MYOSITIS — Several drugs appear to contribute to the development of
inflammatory myopathy, including statins, interferon (IFN)-alpha and -beta, tumor necrosis
factor (TNF) inhibitors, L-tryptophan, and others
OTHER MYOPATHIES — Eosinophilic myositis is sometimes classified as a form of polymyositis
(PM). The only distinctive feature is the presence of eosinophils in muscle biopsy sections and,
occasionally, blood eosinophilia. Chronic parasitic infection is one known cause . Remarkably,
some patients with eosinophilic myositis have mutations in calpain-3
●Granulomatous myositis is a clinical syndrome of distal asymmetric weakness and the
presence of granulomas in muscle biopsy sections. It may occur with systemic involvement
leading to a diagnosis of sarcoidosis or graft-versus-host disease, or it can be idiopathic,
without another associated illness
Clinical manifestations and diagnosis of inclusion body myositis

Sporadic inclusion body myositis (IBM) is classified along with polymyositis, dermatomyositis,
and autoimmune necrotizing myopathy as one of the idiopathic inflammatory myopathies.

Inclusion body myositis (IBM) is a rare sporadic disorder , it is the most common acquired
idiopathic inflammatory myopathy in individuals over the age of 50 / affects men more often
than women

Patients with inclusion body myositis (IBM) present with the insidious onset of weakness. The
average duration of symptoms before diagnosis is about five years [3,7]. The most common
initial presentation is slowly progressive proximal leg weakness, with difficulty getting up out
of a chair or frequent falls. In some patients, the initial complaint may be with weakness of grip
strength, such as difficulty opening jars. Rarely, patients may present with isolated dysphagia
The characteristic physical exam finding is weakness of the distal finger flexor muscles in
approximately 95 percent of patients . Though often difficult to detect on physical examination
early in the course of disease, weakness and atrophy of quadriceps (knee extensor) muscles
are seen in the majority of patients.
●Compared with patients with polymyositis and dermatomyositis, patients with IBM are more
likely to have asymmetric and distal muscle involvement and a more slowly progressive course.

●Both proximal leg and distal arm muscle groups are usually involved. Involvement of the hip
flexors, quadriceps, tibialis anterior with weakness of the ankle dorsiflexors, and forearm
flexors with grip weakness are characteristic of IBM. Facial muscles (especially muscle
controlling eye closure) may be involved, but the oculomotor muscles are spared.

●Myalgias may accompany the weakness but are usually mild.

●Muscle atrophy progresses in parallel with the duration and severity of weakness and is
greater than would be expected for the same degree of weakness in polymyositis. Deep
tendon reflexes also decrease in parallel with the decline in strength.

●Dysphagia due to involvement of the cricopharyngeal muscle occurs in about one-third to

one-half of patients. It may rarely be the presenting complaint, in some cases preceding the
onset of extremity weakness by up to seven years .

Laboratory abnormalities — Muscle enzymes are typically mildly elevated early in the disease,
but may normalize with disease progression. Creatine kinase (CK) levels are usually less than
10 times normal .An elevation of CK greater than 15 times the upper limit of normal suggests
an alternative diagnosis. Glucocorticoids may dramatically reduce serum CK levels in IBM, and
a normalization of serum CK in the absence of an improvement of weakness is common in
IBM. Measures of the acute phase response, such as the erythrocyte sedimentation rate (ESR)
or the C-reactive protein (CRP), are usually normal. Myositis-specific autoantibodies are
typically absent in patients with IBM.
DIAGNOSIS — The diagnosis of sporadic inclusion body myositis (IBM) generally depends upon
the presence of characteristic clinical and laboratory findings which include slowly progressive
muscle weakness, with early involvement of the quadriceps muscles and wrist/finger flexors,
and elevated muscle enzymes. While a muscle biopsy should be considered in all patients with
suspected IBM, histopathological confirmation is not always possible, and the diagnosis may
still be made based on characteristic clinical findings.

The diagnosis of IBM should be considered in patients over the age of 45 who present with
progressive muscle weakness, even in the absence of an elevated serum creatine kinase (CK). If
patients have proximal leg weakness and distal arm and/or leg weakness on exam, referral to a
neurologist and muscle biopsy should be performed

perform a thorough history with particular attention to the following symptoms:●Insidious

onset of falls due to weakness of knee extensors and/or foot drop, typically in the absence of
sensory complaints ●Difficulty standing from the floor or a low chair●Loss of dexterity of
hands or grip strength due to finger flexor weakness●Dysphagia

ask about exposure to a variety of prescription and illicit drugs that may cause myopathy,
myositis, neuropathy, or other disorders that cause muscle weakness. Among the drug
exposures that should be specifically sought are antimalarial drugs (eg, chloroquine,
hydroxychloroquine), colchicine, glucocorticoids, cholesterol-lowering drugs (eg, HMG-CoA
reductase inhibitors [statins]), alcohol, and cocaine.
Symptoms of associated conditions should be reviewed since as many as 15 percent of IBM
patients have underlying autoimmune disorders such as systemic lupus erythematosus (SLE),
Sjögren's syndrome, systemic sclerosis (scleroderma), Hashimoto thyroiditis, variable
immunoglobulin deficiency, sarcoidosis, and idiopathic thrombocytopenia purpura. However,
unlike other inflammatory myopathies such as polymyositis or dermatomyositis, IBM is not
associated with myocarditis, interstitial lung disease, or an increased risk of malignancy.

A careful family history should be taken, as some hereditary myopathies such as Limb-Girdle
Muscular Dystrophy and hereditary IBM may have proximal and distal weakness as well as
rimmed vacuoles and/or inflammation on muscle biopsy and may be misdiagnosed as IBM. The
physical examination helps to determine the distribution of muscle weakness and atrophy.
Findings of quadriceps (ie, knee extensor) and forearm flexor (ie, wrist and finger flexor)
muscle weakness and wasting are clinical hallmarks of IBM . Many patients also have
significant hip flexion weakness and are typically unable to stand from a chair without pushing
off with their arms. With severe quadriceps weakness, patients may walk with the leg
hyperextended (genu recurvatum). To detect subtle weakness of distal finger flexion (typically
the earliest exam finding), the clinician should isolate and specifically examine flexion at the
distal interphalangeal (DIP) joint. Other muscles that are commonly affected are orbicularis
oculi (leading to weakness with eye closure), triceps (weakness with arm extension), and
tibialis anterior (leading to foot drop)

While many patients with IBM present with symmetric and proximal muscle weakness
suggestive of polymyositis, the finding of more distal, asymmetric involvement with finger and
wrist flexor weakness greater than deltoid weakness and knee extensor weakness greater than
hip flexor weakness would be more typical of IBM.

Laboratory testing — There is no definitive diagnostic laboratory test for IBM. Mild to
moderate elevations of plasma muscle enzyme levels (serum CK less than 10-fold higher than
normal) are common with IBM, while levels greater than 15-fold suggest other causes.
The purpose of laboratory testing is primarily to exclude an alternative diagnosis that could
lead to weakness and to look for associated conditions. include serum electrolytes, calcium,
magnesium, phosphate, creatine kinase, aldolase, lactate dehydrogenase, serum
aminotransferases, and thyroid-stimulating hormone An elevated alkaline phosphatase level
should prompt evaluation for Paget disease, which can be seen in hereditary IBM. Testing for
autoantibodies directed against cytoplasmic 5'-nucleotidase 1A (cN1A) may be helpful for
distinguishing IBM from other forms of myositis However, anti-cN1A antibodies are also
detected in about 20 percent of patients with SLE and Sjögren's syndrome in the absence of
muscle disease

There is an association of IBM with some autoimmune diseases, such as Sjögren's syndrome
and sarcoidosis, as well as with some lymphoproliferative disorders such as chronic
lymphocytic leukemia (CLL). In addition, IBM has been observed in patients with chronic viral
infections such as HIV and Hepatitis C. As such, screening laboratory testing for antinuclear
antibodies (ANA), anti-Ro(SSA), anti-La(SSB), serum immunofixation, human immunodeficiency
virus (HIV), and hepatitis C may be considered.

Electromyography — Electromyography (EMG) and nerve conduction studies are extremely

useful tests in all patients with suspected muscle disease. EMG in IBM typically reveals an
"irritable myopathy". Fasciculations are not observed. These findings strongly suggest a
diagnosis of inflammatory myopathy; a muscle biopsy is then indicated for pathologic
diagnosis. In some muscles, EMG may show reduced recruitment . This mixed pattern of
myopathic and "neurogenic"-appearing units is more typical of IBM than polymyositis or
dermatomyositis. Nerve conduction studies are usually normal, but may show a concomitant
peripheral neuropathy in some cases.
Magnetic resonance imaging — Magnetic resonance imaging (MRI) is generally reserved for
diagnostically challenging cases. While there are no findings on MRI studies that are diagnostic
for IBM, there are some disease-specific patterns of muscle involvement that may support the
diagnosis and help distinguish IBM from polymyositis. For example, MRI of the thigh typically
shows edema, atrophy, and fatty replacement of the anterior compartment with relative
sparing of the medial and posterior compartments. MRI may be useful in guiding the selection
of a muscle for biopsy, as the diagnostic yield for biopsy is low in muscles with extensive
atrophy and/or fatty replacement.

Muscle biopsy — Muscle biopsy may be diagnostic in IBM and in many cases can distinguish it
from polymyositis and other muscle diseases, which is not always possible on a clinical basis.
We biopsy muscles that are only moderately weak (4 or 4+ on MRC scale) and prefer biceps or
quadriceps muscles. However, in some cases the muscle biopsy in IBM is nonspecific and the
diagnosis depends on a combination of clinical findings and a biopsy consistent with IBM.

A relatively simple and clinically useful set of criteria has been proposed that has 90 percent
sensitivity and 96 percent specificity ●Finger flexor or quadriceps weakness●Endomysial
inflammation●Invasion of nonnecrotic muscle fibers or rimmed vacuoles

several disorders that can resemble inclusion body myositis (IBM) :●Polymyositis – IBM and
polymyositis can in some cases be difficult to distinguish clinically or by muscle biopsy. In the
absence of rimmed vacuoles or protein aggregates found on immunostaining or electron
microscopy, the muscle biopsy in IBM may only demonstrate endomysial inflammation that
closely resembles that seen in polymyositis. The lack of response to high-dose steroids should
lead to a reevaluation of the diagnosis of polymyositis●Hereditable myopathies•Hereditary
inclusion body myositis (hIBM) – These patients present with slowly progressive muscle
weakness (variously labeled familial distal myopathy, autosomal recessive hereditary inclusion
body myopathies, and distal myopathy with rimmed vacuole formation), usually with marked
distal muscle group involvement, and the muscle biopsy shows a vacuolar myopathy with
inclusions . In contrast to sporadic IBM, the onset of weakness is usually in early adulthood and
spares quadriceps muscles. The family history and a paucity of inflammation on histologic
examination help to distinguish these rare heritable disorders from sporadic IBM.

•Multisystem proteinopathy (MSP) – With the advent of whole exome sequencing, it is

becoming increasingly evident that many hIBM families have a pleiotropic degenerative
disorder that may affect muscle, bone, and the nervous system •Muscular dystrophy – Other
inherited myopathies that variably show rimmed vacuoles and/or inflammation of muscle
biopsy can occasionally be misdiagnosed as IBM, in particular oculopharyngeal muscular
dystrophy (OPMD), fascioscapulohumeral dystrophy (FSHD), and limb girdle muscular
dystrophy (LGMD)—particularly the myofibrillar myopathies, dysferlinopathies, and ANO5. The
correct diagnosis can usually be suspected based on the earlier age of onset, the pattern of
weakness, and/or family history. Diagnosis is confirmed by genetic testing. ●Drug-induced
myopathies – Vacuolar changes are also present in drug-induced myopathy due to colchicine
and chloroquine. ●Amyotrophic lateral sclerosis – Patients with IBM who have predominantly
distal or asymmetric involvement may resemble motor neuron disease or peripheral
neuropathies with predominantly lower motor neuron involvement. Electrophysiologic testing
and muscle biopsy may be necessary to establish the correct diagnosis. Electromyography
(EMG) of the forearm flexor muscles may be particularly useful in distinguishing the primarily
myopathic features of IBM from the neurogenic features of ALS

SUMMARY AND RECOMMENDATIONS

●Inclusion body myositis (IBM) is a rare sporadic disorder in adults that causes muscle
weakness with an insidious onset. The distribution of weakness can be either symmetric or
asymmetric, and both proximal and distal muscle groups can be involved. Dysphagia occurs in
about one-third of patients. ●Muscle enzymes are typically normal or mildly elevated in IBM,
with creatine kinase (CK) levels generally being less than 10 times normal●The diagnosis of
sporadic IBM depends upon the presence of characteristic clinical and laboratory findings
which include a slowly progressive muscle weakness with early involvement of the quadriceps
muscles and wrist/finger flexors, and elevated muscle enzymes. ●A muscle biopsy should be
performed in all patients with suspected IBM. However, histopathological confirmation is not
always possible, and the diagnosis may still be made based on characteristic clinical findings.
●Muscle biopsy findings that are highly specific for IBM include the presence of rimmed
vacuoles, mononuclear cell inflammatory infiltrate of non-necrotic muscle fibers, and the
presence of either amyloid deposits or tubulofilaments by electron microscopy. ●Findings on
electromyography (EMG) and magnetic resonance imaging (MRI) may also help support the
diagnosis of IBM when present. EMG typically reveals an "irritable myopathy" . MRI
abnormalities in IBM tend to be localized to the anterior muscle groups.

Inclusion body myositis Polymyositis

Sex Male > female Female > male

Age Uncommon before 50 Common before 50

Onset Insidious Acute or subacute

Course Slowly progressive More rapid

Distribution of Usually asymmetric finger flexor and proximal Proximal, symmetric

weakness leg weakness

Creatine kinase Normal or <10x normal Often >10x normal

EMG Myopathic or mixed myopathic and neurogenic Myopathic

Muscle biopsy Inflammation, rimmed vacuoles, inclusions Inflammation, fiber

necrosis

Response to therapy Generally poor Expected