Topic 14: Myopathy

What is the definition of myopathy?

Myopathy refers to diseases causing structural or functional impairment of skeletal muscle fibers.

What is the typical clinical presentation of myopathy?

Symmetrical, proximal muscle weakness (shoulder and pelvic girdles), difficulty with stairs, rising from chairs, combing hair; no sensory loss.

How can myopathy be distinguished from neuropathy?

Myopathy causes weakness without sensory loss; neuropathy usually includes sensory changes and distal weakness.

What percentage of body mass is skeletal muscle, and what are its functions?

~40% of body mass; functions include movement and joint stabilization.

What event initiates skeletal muscle contraction?

Calcium release from the sarcoplasmic reticulum in response to an action potential.

Describe excitation-contraction coupling in skeletal muscle.

AP spreads along sarcolemma → enters T-tubules → Ca²⁺ released from terminal cisternae → Ca²⁺ binds troponin → tropomyosin shifts → actin sites exposed → myosin binds and contracts via sliding filament mechanism.

What is the sliding filament (walk-along) mechanism?

Myosin heads bind actin, tilt for a power stroke, pull actin toward center, detach, reset, and repeat.

What is the role of ATP in muscle contraction?

ATP is required for both contraction (crossbridge cycling) and relaxation (detachment of myosin).

How does neural (neurogenic) pathology differ from myopathic pathology?

Neural pathology: nerve damage → distal weakness, sensory changes, fasciculations, denervation EMG. Myopathic pathology: intrinsic muscle defect → proximal weakness, sensation preserved.

What blood test is often elevated in myopathy?

Creatine kinase (CK).

What pattern of weakness is typical in myopathy?

Progressive, symmetric, proximal > distal weakness.

What sensory findings are expected in myopathy?

Sensation is usually normal (no numbness or tingling).

What is Gower's sign, and what does it indicate?

Patient uses hands to "walk up" thighs to stand → indicates proximal muscle weakness.

What is Trendelenburg sign, and what does it indicate?

Pelvic drop on contralateral side when standing on one leg → weakness of gluteus medius.

What is pseudohypertrophy?

Enlargement of muscle due to fat and fibrous replacement, seen in Duchenne muscular dystrophy.

What is typically seen in muscle tone in myopathy?

Usually normal or mildly reduced.

What blood marker is often elevated in myopathy?

Creatine phosphokinase (CPK).

What is the most common muscular dystrophy?

Duchenne muscular dystrophy (dystrophin gene defect, calf pseudohypertrophy).

How does Becker muscular dystrophy differ from Duchenne's?

Becker is less severe, later onset, and partially functional dystrophin is present.

Name other hereditary myopathies besides Duchenne and Becker.

Emery-Dreifuss, Limb-girdle, Myotonic dystrophy.

What are some acquired causes of myopathy?

Drugs/toxins (statins, corticosteroids, alcohol), inflammatory myopathies (polymyositis, dermatomyositis), endocrine/metabolic (thyroid, Cushing's), paraneoplastic syndromes, and rare infections (trichinosis, HIV).

What EMG pattern is seen in myopathy?

Small, brief, polyphasic motor unit potentials (myopathic pattern).

How do nerve conduction studies appear in myopathy?

Usually normal.

What does muscle biopsy show in myopathy?

Muscle fiber necrosis/regeneration, fibrosis, or absence of dystrophin (Duchenne's).

What is the role of genetic testing in myopathy?

Confirms inherited types of muscular dystrophy.

In myopathy, is weakness proximal or distal?

Proximal > distal.

In neuropathy, is weakness proximal or distal?

Distal > proximal.

Is sensory loss present in myopathy?

No (sensation spared).

Are reflexes affected in myopathy?

Usually normal or mildly reduced.

What is the atrophy pattern in myopathy vs neuropathy?

Myopathy = mild-moderate; Neuropathy = marked.

Are fasciculations seen in myopathy?

No (absent).

Is creatine phosphokinase (CPK) elevated in myopathy or neuropathy?

Elevated in myopathy, normal in neuropathy.

When should you suspect myopathy clinically?

Painless, progressive, proximal weakness without sensory loss.

What pediatric condition is a classic cause of myopathy?

Duchenne's muscular dystrophy.

What signs are classic for proximal weakness in myopathy?

Gower's sign and Trendelenburg sign.

Does myopathy cause sensory loss?

No—any sensory loss suggests neuropathy.

What history is important to consider when evaluating suspected myopathy?

Medication/toxin history (e.g., statins, steroids, alcohol).

What is the inheritance pattern of Duchenne and Becker muscular dystrophies?

Both are X-linked recessive.

What protein is defective in Duchenne and Becker muscular dystrophies?

Dystrophin.

What is the difference in dystrophin defect between Duchenne and Becker MD?

Duchenne = absent or near-absent dystrophin (frameshift mutation).

Becker = reduced or abnormal dystrophin (non-frameshift mutation).

Which form is more severe: Duchenne or Becker MD?

Duchenne.

At what age does Duchenne MD typically present?

Early childhood (before age 5).

At what age does Becker MD typically present?

Later onset (teens to adulthood).

What is the life expectancy in Duchenne MD?

Death usually by 20s-30s (respiratory or cardiac failure).

What is the life expectancy in Becker MD?

Often survives into mid-to-late adulthood.

What clinical sign is classic in Duchenne MD?

Gower's sign (child uses hands to "walk up" legs when rising).

What other physical sign is characteristic of Duchenne MD?

Pseudohypertrophy of calves (fat/fibrous tissue replaces muscle).

Do both Duchenne and Becker MDs cause cardiomyopathy?

Yes, both can lead to dilated cardiomyopathy, but it is more severe and earlier in Duchenne.

What are the two major causes of skeletal muscle fiber degeneration?

1. Primary muscle disease (myopathy)

2. Secondary to LMN lesion (denervation)

In LMN lesions, are all or only some muscle fibers in a motor unit affected?

All muscle fibers in the motor unit are affected.

In myopathy, are all or only some muscle fibers in a motor unit affected?

Only some fibers are affected; degeneration is random within motor units.

What happens to muscle fibers in an LMN lesion (denervation)?

They atrophy, membrane potential rises toward threshold, leading to spontaneous firing.

What are fasciculations, and are they visible?

Synchronous firing of all fibers in a motor unit; visible as twitches.

What are fibrillations, and are they visible?

Asynchronous firing of individual muscle fibers; not visible, detected only on EMG.

What EMG changes are seen in chronic denervation?

Enlarged motor units with large-amplitude, long-duration, polyphasic motor unit potentials (from collateral reinnervation).

What EMG changes are seen in myopathy?

Small-amplitude, short-duration, polyphasic motor unit potentials.

What is the recruitment pattern in neuropathic processes?

Reduced recruitment with gaps in the interference pattern.

What is the recruitment pattern in myopathic processes?

Early recruitment, producing a full interference pattern even with mild contraction.

What visible sign is typical in neuropathic lesions but not in myopathy?

Fasciculations (visible twitches).

What is the key clinical difference between neuropathy and myopathy in terms of sensation?

Sensation is preserved in myopathy, but often affected in neuropathy.