Muscular atrophy, dystrophies and myositis

1. Muscular Atrophy

Definition

• Non-specific response in various muscle disorders → abnormally small myofibers.

Causes

1. Neurogenic atrophy

• Loss of innervation → loss of single neuron → affects all muscle fibers in a motor unit.
• Examples: ALS, polio, peripheral neuropathy, spinal cord lesion.
• Histology: grouped atrophy + fiber type grouping (reinnervation).

2. Disuse atrophy

• Minimal physical activity, prolonged bed rest, immobilization (bone cast).
• Primarily type II fibers (fast twitch).
• Random distribution of atrophic myofibers.

3. Glucocorticoid / hypercortisolism

• Exogenous steroids or endogenous Cushing.
• Type II fiber atrophy (similar to disuse).

4. Myopathic atrophy

• Intrinsic muscle disease (e.g., dystrophies).

2. Muscular Dystrophy

Definition

• Inherited disorders (often in childhood).
• Progressive degeneration of muscle fibers → weakness + wasting.
• Advanced: muscle fibers replaced by fibrofatty tissue.

3. X-linked Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD)

• Most common + most severe.
• Evident by age 5, wheelchair by 10–12, death by early 20s.

Becker Muscular Dystrophy (BMD)

• Less common, much less severe than DMD; later onset, slower progression.

Pathogenesis

• Deletion of dystrophin gene on short arm of X chromosome (Xp21).
• Largest gene in human genome.
• Dystrophin: maintains structural + functional integrity of muscle cells by connecting sarcomere to cell membrane (via dystrophin-glycoprotein complex).
• DMD: dystrophin absent.
• BMD: dystrophin truncated/decreased but present.

Morphology

• Variation in fiber size (hypertrophy + atrophy).
• Degenerative changes: fiber splitting, necrosis.
• Adipose tissue infiltration (advanced stages).

Clinical Features

DMD

• Pseudohypertrophy of calf muscles (hypertrophy initially, then degenerates + replaced by adipose/fibrous tissue).
• Proximal muscle weakness → Gowers sign (using hands to climb up legs to stand).
• Heart failure, cardiac arrhythmias, CNS impairment.
• ↑ Creatine kinase (CK) in serum.
• Cause of death: respiratory insufficiency, cardiac decompensation.

BMD

• Symptoms develop later, slower progression, normal lifespan or near-normal.

4. Autosomal Muscular Dystrophies

Limb-Girdle Muscular Dystrophy

• AD (6 subtypes) and AR (10 subtypes) inheritance.
• Affects proximal musculature of trunk + limbs.

Myotonic Dystrophy

• Autosomal dominant.
• CTG trinucleotide repeat expansion on chromosome 19 → codes for dystrophia myotonica protein kinase (DMPK).
• Anticipation: earlier/more severe in successive generations.
• Myotonia = sustained involuntary contraction (difficulty releasing grip on doorknob/handle).
• Presents in late childhood with gait abnormalities → progresses to weakness of intrinsic hand muscles + wrist extensors.
• Associated: cataracts, frontal balding, testicular atrophy, cardiomyopathy.

5. Myositis

Overview

• Inflammation of muscle (umbrella term).
• All forms: muscle weakness initially affecting large muscles of trunk, neck, limbs (proximal weakness).

A) Dermatomyositis

• Inflammation of muscle + skin.
• Antibody-mediated injury (humoral; complement attacks endomysial capillaries → perifascicular atrophy).
• Rash:
  • Heliotrope rash: violet upper eyelids + periorbital edema.
  • Gottron papules: knuckles, elbows, knees.
  • Shawl sign: upper back/shoulders.
• ↑ Risk of visceral cancer (especially in women) — paraneoplastic association.
• Anti-Jo-1, anti-Mi-2 antibodies.

B) Polymyositis

• Autoimmune — CD8⁺ T-cell inflammatory infiltrate → myofiber necrosis → regeneration.
• No skin involvement.
• Adults; symmetric proximal weakness.
• Anti-Jo-1.

C) Inclusion Body Myositis

• Inclusions + vacuoles inside muscle cells (rimmed vacuoles).
• CD8⁺ T-cell mediated.
• Older adults; most common myositis > 50 yr.
• Distal + asymmetric weakness (atypical pattern).
• Treatment-resistant.

6. Summary Table

Disease	Inheritance	Defect	Key features
DMD	X-linked recessive	Dystrophin absent	Calf pseudohypertrophy, Gowers sign, ↑ CK, death early 20s
BMD	X-linked recessive	Dystrophin truncated	Later onset, milder
Myotonic dystrophy	AD	CTG repeat (chr 19, DMPK)	Myotonia, cataracts, frontal balding, testicular atrophy
Dermatomyositis	Autoimmune	Antibody-mediated (humoral)	Heliotrope rash + Gottron papules + visceral cancer; anti-Jo-1
Polymyositis	Autoimmune	CD8⁺ T-cell	Symmetric proximal weakness, no skin; anti-Jo-1
Inclusion body myositis	Autoimmune	CD8⁺ T-cell + rimmed vacuoles	Older, distal + asymmetric, treatment-resistant

💡 High-yield: Atrophy: neurogenic (motor unit, ALS), disuse (type II), steroids, myopathic. DMD = X-linked recessive, dystrophin absent (Xp21), calf pseudohypertrophy + Gowers sign + ↑ CK; wheelchair by 10–12, death by 20s. BMD = milder, truncated dystrophin. Myotonic dystrophy = AD, CTG repeat (chr 19, DMPK), myotonia + cataracts + frontal balding + testicular atrophy. Dermatomyositis = humoral, heliotrope rash + Gottron papules + shawl sign, ↑ visceral cancer risk. Polymyositis = CD8⁺ T-cell, proximal weakness, no skin. Inclusion body myositis = older, distal + asymmetric, rimmed vacuoles.