short course of health partitionner, students and the general public for general knowledge, on muscle atrophy, definition, pathophysiology, clinical presentation, clinical forms and treatment

1. Amyotrophic Diseases
By TSAMO NDOMO V. MD,MPH

2. Objectives
• Define amyotrophy
• Describe the pathophysiology of post inflammatory amyotrophy
• Describe the diagnostic pathway of a patient with muscle atrophy
• Describe the keys paraclinical investigations for a patient presenting
with muscle atrophy
• Give the principle of management for a patient with amyotrophy

3. Outline
• Introduction
• Pathophysiology
• Clinical presentation and diagnostic strategy
• Clininical presentations of someamyotrophic conditions
• Paraclinical investigations
• Conclusion
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4. Introduction (1/2)
• As the most abundant tissue in the human body, muscle occupies
around 40% of the body weight.
• In response to physical or pathological stimuli, muscle tissue
changes fiber content, capillary distribution, and the components of
intracellular connective tissue.
• All these changes may finally lead to pathologic consequences like
atrophy or hypertrophy.
• Our analysis will be centered around muscle atrophy (amyotrophy).
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5. Introduction (2/2)
• Skeletal muscle weakness, defined as a reduction in force or power in
the absence of prior exercise.
• It’s a major problem for many individuals afflicted with chronic
inflammatory diseases including several types of cancer, rheumatoid
arthritis, chronic heart failure, and chronic obstructive pulmonary
disease (COPD).
• Weakness can interfere with basic activities of daily living, limit
productivity in the workplace, impair one's mobility and range of
motion, predispose individuals to fall-related injuries, and even
restrict breathing.
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6. Pathophysiology (1/4)
• Muscle atrophy is characterized by the decrease in muscle mass due to
the imbalance between protein synthesis and degradation.
• The literature shows that weakness is not simply an indirect product of
illness caused by physical inactivity, poor nutrition, or physical
discomfort.
• Rather, chronic inflammatory diseases appear to have direct,
deleterious effects on skeletal muscles of the trunk and limbs.
• In muscle atrophy, myofiber size and muscle mass are reduced.
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7. Pathophysiology (2/4)
• These changes reflect an overall loss of myofibrillar protein that
depresses force.
• Contractile dysfunction is characterized by loss of specific force, i.e.,
force per cross-sectional area, and may cause weakness in the
absence of muscle atrophy.
• human studies suggest contractile dysfunction is common in chronic
diseases that range from chronic obstructive pulmonary disease or
COPD to heart failure to rheumatoid arthritis or RA
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8. Pathophysiology (3/4)
• The process that contributes to weakness is contractile dysfunction.
• proinflammatory cytokines are released from diseased tissues into
the systemic circulation where they function as humoral mediators,
exerting endocrine effects on skeletal muscle.
• Primary candidates for these endocrine stimuli include interleukin-6,
C-reactive protein, sphingomyelinase, and tumor necrosis factor (TNF)
with TNF being implicated most robustly.
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9. Pathophysiology (4/4)
• Studies of cellular mechanism have led to the working hypothesis that
TNF is a primary endocrine stimulus for contractile dysfunction in
chronic inflammatory disease.
• Muscle-derived ROS and NO participate in post-receptor signaling
events that depress specific force.
• In parallel, evidence of oxidative and nitrosative stress suggests that
reactive oxygen species (ROS) and nitric oxide (NO) derivatives also
play an important role.
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10. Clinical conditions associated with amyotrophy, Richard Y et Al, Muscle Atrophy: Present and Future 2018
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11. Clinical presentation of amyotrophy (1/10)
• Classical findings in patients with muscles atrophy include:
• Symmetrical muscle weakness,
• wasting,
• normal sensation,
• normal stretch reflexes.
• Aching muscle cramps can also occur.
• In order to have an etiologic diagnosis, a complete history and proper
physical exam is mandatory.
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12. Clinical presentation of amyotrophy(2/10)
• History
• Weakness is a common complaint with different interpretations by
patients.
• The aim of history taking is to try to define what the patient means by
“weakness.”
• In these patients there is usually a long-standing history of a chronic
disease.
• It’s essential to find out whether this weakness is localized to certain
areas.
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13. Clinical presentation of amyotrophy (3/10)
• Symmetrical weakness occurs in large number of diseases including
inflammatory myositis, inherited muscle dystrophy, endocrine
disorders, and neuromuscular junction diseases.
• it is important to know if the weakness is proximal (muscles of the
trunk, shoulders, and thighs) or distal.
• The patient with proximal amyotrophy will have difficulty combing
hair, difficulty climbing up the stairs, difficulty standing from a sitting
position, and/or difficulty in getting up from bed.
• In distal myopathy, the patient will complain about difficulties while
performing fine work like handling the objects by hands and driving.
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14. Clinical presentation of amyotrophy (4/10)
• These patients may also present with wrist drop or foot drop.
• It must be noted that there are diseases affecting proximal muscles in
an asymmetrical fashion like diabetic amyotrophy.
• We can have diseases with both proximal and distal muscle weakness
in symmetrical and/or asymmetrical fashion like in systemic lupus
erythematosus (SLE), or vasculitis respectively.
• An extensive review of rheumatologic symptoms should follow.
• Detailed history of joint pain, skin rashes, fever, recent infections,
should be noted.
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15. Clinical presentation of amyotrophy (5/10)
• Detailed history of joint pain, skin rashes, fever, recent infections,
should be noted.
• There are life-threatening symptoms should be identified and
promptly as they need urgent medical intervention.
• We can have:
• dysphagia and nasal regurgitations,
• chest pain and heart failure
• Breathlessness
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16. Clinical presentation of amyotrophy (6/10)
• Physical examination
• The first step is to observe the patient doing certain activities like raising
arms, standing up from a chair, or writing.
• This will determine if the weakness is proximal, distal, or combined.
• Perform a complete objective neurological exam, with a detailed motor
examination.
• This starts with inspection of the muscle bulk and determining whether if it is
normal, atrophied, or hypertrophied.
• Clear distinctions between signs of upper motor neuron disease (UMND):
hypertonia, hyperreflexia, and upgoing plantar response
• signs of LMND : hypotonia, normal or low or absent reflexes, and equivocal or
downgoing plantar response.
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17. Assessment of muscle strength. Diaz G, 2018
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18. Clinical presentation of amyotrophy (8/10)
• The last step in the neurological examination in this case is examining
sensory level.
• In peripheral neuropathy loss of sensation is parallel to the weakness.
• After comprehensive neurological examination, a search for
extramuscular signs should follow.
• The examination of the face, hands, lower limbs, chest, and abdomen
is important, since any abnormality can help in the differential
diagnosis.
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19. Symptoms associated with muscles weakness, Hani L et AL, 2021
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20. Clinical presentation of amyotrophy (10/10)
• Check for associations in signs and symptoms as they may easily
reveal the diagnosis.
• Changes in the mental status, for example, with muscle weakness may
indicate electrolyte imbalance.
• Cardiovascular assessment may reveal signs of cardiomyopathy, which is
associated with some inflammatory and hereditary myopathies.
• Small joint examination is essential as well to detect any tenderness and/or
swelling suggestive of rheumatoid arthritis (RA) and/or systemic lupus
erythematosus (SLE).
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21. Clinical approach to a patient with muscle weakness. Hani L et AL, 2021 21

22. Some Clinical presentations of amyotrophy(1/4)
• Postoperative
• Associated with micrometallic artifact or other evidence of surgical intervention
• Atrophy, such as in rotator cuff, may have preceded surgery
• Surgical resection of muscle may have occurred as in treatment for malignancy
• Immobilization
• General immobility from debilitating condition, such as coma, stroke, prolonged
hospitalization.
• Immobilization limited to joint or extremity for posttraumatic, postsurgical treatment
• Muscle atrophy begins after 10 days of immobilization/immobility
• Atrophy from prolonged immobilization/immobility (> 4months) may be irreversible,
especially in elderly patients
• With generalized immobility, other changes occur, such as dependent subcutaneous
edema, pressure ulcers
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23. Some Clinical presentations of amyotrophy(2/4)
• Sarcopenia
• Age-related loss of muscle
• Inactive individuals lose 3-5% muscle mass/year
• Starts in 3rd decade and accelerates with advancing age.
• Tendon Injury
• Complete tendon tear results in atrophy of associated muscle
• Common, involving rotator cuff and gluteus minimus tendons
• Spinal Cord Injury
• Rapid muscle atrophy below level of injury.
• 18-46% decrease in muscle cross-sectional area 6 weeks after injury.
• Associated findings: Cord atrophy, cord disruption, tethered cord, myelomalacia,
syrinx
• Associated with heterotopic bone formation, especially around hips
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24. Some Clinical presentations of amyotrophy(3/4)
• Peripheral Nerve Injury
• Often possible to identify abnormal nerve based on muscle denervation
pattern.
• Subacute denervation states have increased signal on fluid-sensitive
sequences even as fatty infiltration occurs
• Nerve Entrapment
• Distribution of atrophy depends on location of entrapment
• Search for masses, fibrous bands at sites associated with specific entrapment
syndrome.
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25. Some Clinical presentations of amyotrophy(4/4)
• Neuropathy
• Associated neuropathic changes in joints include distention, debris, disorganization,
deformity, dislocation
• Complications of Corticosteroids
• Myopathy occurs due to high-dose steroid therapy
• Affects proximal muscles > distal muscles
• Weakening of bone leads to increased fractures with resultant immobilization,
worsening muscle atrophy
• Diabetes
• Multiple potential causes for atrophy
• Neuropathy, muscle infarction, increased incidence of fracture leading to
immobilization, infection
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26. Paraclinical investigations :Biology (1/3)
• A thorough history and physical examination is the cornerstone to reach
the diagnosis.
• Investigations should be tailored to screen for reversible causes of a
amyotrophy.
• Muscle enzymes:
• The measurement of serum levels of muscle enzymes is of critical value for
the evaluation and monitoring of muscular disorders.
• Creatine kinase (CK), lactate dehydrogenase (LD), alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and aldolase.
• To diagnose rheumatologic myopathy, erythrocyte sedimentation rate (ESR) C-
reactive protein (CRP), antinuclear antibody assay (ANA), rheumatoid factor, anti-
doublestranded DNA, antiphospholipid antibodies, and anti-centromere antibodies
should be ordered.
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27. Paraclinical investigations: Functional test (2/3)
• Electromyography (EMG) is a test that is used to record muscle
electrical activity and assess the nerves that control the muscles.
• An abnormal electromyogram can indicate a neuropathy or neuromuscular
disease.
• Characteristic EMG findings of myopathy include short duration and
decreased amplitude of action potential unlike neuropathies that are
characterized by increased duration and amplitude of action potential.
• EMG can help distinguish inflammatory from non-inflammatory forms of
myopathy.
• Normal EMG examination, however, would not exclude myopathy.
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28. Paraclinical investigations: Morphology (3/3)
• Muscle Magnetic Resonance Imaging (MRI)
• MRI evaluates deep muscles not readily accessible by EMG and plays
a role in the diagnostic process by identifying subclinical signs of
muscle involvement.
• Can also help to diagnose inflammatory amyotrophy which will be
presented as fat.
• A secondary role for muscle MRI is to provide information about the
best site for muscle biopsy by showing which muscles are involved in
the myopathic process.
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29. Management of muscle atrophy
• Treatable causes should be sought and treated accordingly.
• Aims
• releave the symptoms generally pain
• Treat the underlying cause (RA, connective tissues diseases)
• Prevent the complication (cardiorespiratory failure, pulmonary embolism)
• Methods
• Non pharmacological
• Counceilling
• Elastics stocking
• physioteraphy
• Pharmacological
• Depends of the etiology
• Management of proximal myopathy depends on underlying etiology.
• Corticosteroids are the cornerstone in the treatment of PM and DM
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30. In fine
• Amyotrophy or muscle atrophy can be defined as a reduction in
muscle mass.
• The etiologies varies and a complete physical exam centered on
muscles should be done in order to give clues in the diagnosis.
• Muscles enzymes can be assessed in addition with functional test and
imagery can give a more tailored diagnosis.
• The treatment of amyotrophies fully depends of the underlying cause,
be very careful with complications and alert signs.
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