Type I vs Type II Fibers
| Feature |
Type I (Slow Twitch) |
Type II (Fast Twitch) |
| Color |
Red (high myoglobin) |
White (low myoglobin) |
| Metabolism |
Oxidative (aerobic) |
Glycolytic (anaerobic) |
| Mitochondria |
Many |
Few |
| Fatigue resistance |
High (endurance) |
Low (quick fatigue) |
| Function |
Sustained activity, posture |
Rapid, powerful movements |
| ATPase staining |
Light at pH 9.4 |
Dark at pH 9.4 |
Clinical Relevance of Fiber Type
| Fiber Type Affected |
Conditions |
| Type I atrophy |
Myotonic dystrophy type 1, congenital myopathies |
| Type II atrophy |
Disuse, steroids, cachexia, aging (sarcopenia) |
| Type I predominance |
Endurance athletes, central core disease |
💎 Board Pearl
Type II fiber atrophy = steroid myopathy, disuse. These are the “expendable” fibers lost first in catabolic states. Type I fibers are preserved because they’re needed for posture and breathing.
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ATP Sources in Muscle
| Source |
Duration |
Clinical Defect |
| Phosphocreatine |
Seconds (immediate) |
Rare |
| Glycolysis/Glycogenolysis |
Minutes (short burst) |
Glycogen storage diseases |
| Fatty acid oxidation |
Hours (prolonged) |
Lipid storage myopathies |
| Oxidative phosphorylation |
Sustained |
Mitochondrial myopathies |
Glycogen Storage Diseases
| Disease |
Enzyme Defect |
Key Features |
Hallmark |
| McArdle’s (GSD V) |
Myophosphorylase |
Exercise intolerance, cramps, myoglobinuria |
“Second wind” phenomenon; no lactate rise on forearm test |
| Pompe’s (GSD II) |
Acid maltase (α-glucosidase) |
Proximal weakness, respiratory failure, cardiomyopathy (infantile) |
Diaphragm weakness out of proportion to limbs; ERT available |
| Tarui’s (GSD VII) |
Phosphofructokinase |
Similar to McArdle’s |
“Out of wind” phenomenon (worse with glucose); hemolysis |
💎 Board Pearl
McArdle’s = second wind (feels better after 10-15 min as fatty acids kick in). Tarui’s = out of wind (glucose makes it worse by blocking fatty acid use). Both have no lactate rise on forearm exercise test.
Lipid Storage Myopathies
| Disease |
Defect |
Key Features |
Hallmark |
| CPT II Deficiency |
Carnitine palmitoyltransferase II |
Recurrent myoglobinuria with prolonged exercise, fasting, cold, infection |
Most common cause of recurrent myoglobinuria in adults; normal strength between attacks |
| Primary Carnitine Deficiency |
Carnitine transporter (OCTN2) |
Cardiomyopathy, weakness, hypoglycemia |
Low serum carnitine; responds to carnitine supplementation |
Mitochondrial Myopathies
| Syndrome |
Key Features |
Hallmark |
| CPEO (Chronic Progressive External Ophthalmoplegia) |
Ptosis, ophthalmoplegia (no diplopia), proximal weakness |
Ptosis + ophthalmoplegia WITHOUT diplopia |
| KSS (Kearns-Sayre) |
CPEO + retinitis pigmentosa + cardiac conduction defects; onset <20 years |
Heart block – needs monitoring/pacemaker |
| MELAS |
Stroke-like episodes, seizures, lactic acidosis, myopathy |
Strokes not following vascular territories; often occipital |
| MERRF |
Myoclonus, epilepsy, ataxia, ragged red fibers |
Myoclonic epilepsy |
💎 Board Pearl
Ragged red fibers on Gomori trichrome = mitochondrial myopathy. CPEO has no diplopia because both eyes move together (symmetric). Always screen KSS for heart block. MELAS strokes are non-vascular distribution.
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Major Muscular Dystrophies
| Dystrophy |
Gene/Protein |
Inheritance |
Key Features |
Hallmark |
| Duchenne (DMD) |
Dystrophin (absent) |
X-linked |
Onset 2-5 yrs; calf pseudohypertrophy; cardiomyopathy; wheelchair by 12 |
Gowers’ sign; CK >10,000 |
| Becker (BMD) |
Dystrophin (reduced/abnormal) |
X-linked |
Later onset; milder; ambulation into adulthood; cardiomyopathy can be severe |
Cardiomyopathy out of proportion to skeletal weakness |
| Myotonic Dystrophy Type 1 (DM1) |
DMPK (CTG repeat) |
AD |
Distal weakness, myotonia, cataracts, cardiac conduction defects, frontal balding, testicular atrophy |
Grip myotonia; “hatchet face” |
| Myotonic Dystrophy Type 2 (DM2/PROMM) |
CNBP (CCTG repeat) |
AD |
Proximal weakness, myotonia (milder), muscle pain, no congenital form |
Proximal > distal (opposite of DM1); muscle pain prominent |
| FSHD |
D4Z4 contraction (chr 4) |
AD |
Face, scapular, humeral weakness; scapular winging; asymmetric |
Can’t whistle, smile, or close eyes tightly; scapular winging |
| LGMD |
Multiple genes (>30 types) |
AD or AR |
Proximal limb-girdle weakness; variable age of onset |
Heterogeneous group; need genetic testing |
| Emery-Dreifuss |
Emerin or Lamin A/C |
X-linked or AD |
Humeroperoneal weakness; early contractures (elbow, Achilles, neck) |
Cardiac conduction defects (sudden death risk); contractures before weakness |
| Oculopharyngeal (OPMD) |
PABPN1 (GCG repeat) |
AD |
Onset >40 yrs; ptosis, dysphagia, proximal weakness |
Late-onset ptosis + dysphagia; French-Canadian or Hispanic ancestry |
💎 Board Pearl
DM1 = distal, DM2 = proximal. DM1 has anticipation (worse in successive generations); congenital form has profound hypotonia. Always screen DM1 and Emery-Dreifuss for cardiac conduction disease. FSHD is very asymmetric.
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Comparison of Inflammatory Myopathies
| Feature |
Dermatomyositis (DM) |
Polymyositis (PM) |
Inclusion Body Myositis (IBM) |
| Age |
Any (children or adults) |
Adults >18 |
>50 years |
| Weakness pattern |
Proximal, symmetric |
Proximal, symmetric |
Distal (finger flexors) + proximal (quads); asymmetric |
| Skin findings |
Heliotrope rash, Gottron’s papules, shawl sign, mechanic’s hands |
None |
None |
| CK |
Elevated (10-50x) |
Elevated (10-50x) |
Normal or mildly elevated |
| Pathology |
Perifascicular atrophy; perivascular inflammation (B cells, CD4) |
Endomysial inflammation (CD8 T cells invading non-necrotic fibers) |
Rimmed vacuoles; CD8 T cells; congophilic inclusions |
| Cancer association |
Yes (screen!) |
Possible (less than DM) |
No |
| Treatment response |
Good (steroids, IVIG) |
Good (steroids) |
Poor (no effective treatment) |
| Dysphagia |
Can occur |
Can occur |
Common (60%) |
Key Antibodies
| Antibody |
Association |
| Anti-Jo-1 (and other anti-synthetases) |
Antisynthetase syndrome: myositis + ILD + arthritis + mechanic’s hands + Raynaud’s |
| Anti-Mi-2 |
Classic DM with good prognosis |
| Anti-MDA5 |
Amyopathic DM with rapidly progressive ILD |
| Anti-TIF1-γ (p155/140) |
DM with high cancer risk |
| Anti-NXP2 |
DM with calcinosis (children) or cancer (adults) |
| Anti-SRP |
Necrotizing myopathy; severe, cardiac involvement |
| Anti-HMGCR |
Statin-associated necrotizing myopathy (persists after stopping statin) |
| Anti-cN1A (Mup44) |
IBM (not specific but supportive) |
💎 Board Pearl
IBM = elderly male + finger flexor + quad weakness + doesn’t respond to steroids. Pathology shows rimmed vacuoles. DM has perifascicular atrophy; PM has endomysial CD8 invasion. Anti-TIF1-γ = screen hard for cancer.
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Common Drug-Induced Myopathies
| Drug/Toxin |
Mechanism |
Clinical Features |
Key Points |
| Statins |
Toxic myopathy; or immune-mediated (anti-HMGCR) |
Myalgias, weakness, elevated CK, rhabdomyolysis (rare) |
Most resolve with discontinuation; anti-HMGCR requires immunotherapy |
| Corticosteroids |
Type II fiber atrophy |
Proximal weakness; normal CK; no myalgias |
Fluorinated steroids worse (dexamethasone, triamcinolone) |
| Colchicine |
Microtubule disruption |
Proximal weakness; may have neuropathy |
Risk increases with renal failure, CYP3A4 inhibitors |
| Chloroquine/Hydroxychloroquine |
Lysosomal dysfunction |
Proximal weakness; cardiomyopathy |
Curvilinear bodies on EM; may have neuropathy |
| Alcohol |
Direct toxicity |
Acute: rhabdomyolysis; Chronic: proximal weakness |
Most common toxic myopathy; Type II fiber atrophy |
| Zidovudine (AZT) |
Mitochondrial toxicity |
Proximal weakness; ragged red fibers |
Reversible with discontinuation |
| Immune checkpoint inhibitors |
Autoimmune |
Myositis, myasthenia, myocarditis |
Can be severe; may overlap with MG |
💎 Board Pearl
Steroid myopathy = normal CK. Distinguish from underlying inflammatory myopathy flare (elevated CK). Statin myopathy usually resolves, but anti-HMGCR necrotizing myopathy persists and needs immunosuppression.
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Myopathic vs Neurogenic Patterns
| Feature |
Myopathic |
Neurogenic |
| MUP amplitude |
Low (small) |
High (large) |
| MUP duration |
Short |
Long |
| Recruitment |
Early (many small units for weak effort) |
Reduced (few units firing fast) |
| Polyphasia |
Increased |
Increased |
| Fibrillations |
May be present (inflammatory, necrotic myopathies) |
Present (denervation) |
Specific EMG Findings by Disease
| Disease |
Characteristic EMG Finding |
| Myotonic dystrophy |
Myotonic discharges (“dive bomber” sound); waxing-waning frequency and amplitude |
| Inflammatory myopathies (DM, PM) |
Fibrillations, PSWs + myopathic MUPs; “irritable myopathy” |
| IBM |
Mixed myopathic AND neurogenic features |
| Muscular dystrophies |
Myopathic MUPs; fibs/PSWs in actively necrotic dystrophies |
| Steroid myopathy |
Myopathic MUPs; NO fibrillations (no membrane irritability) |
| Critical illness myopathy |
Low CMAP amplitudes; fibs; myopathic MUPs; reduced muscle membrane excitability |
💎 Board Pearl
Myopathic = small, short, polyphasic MUPs with early recruitment. Fibrillations in myopathy indicate membrane instability (inflammation, necrosis, DM1). IBM is unique: mixed pattern due to its dual pathology (inflammation + degeneration).
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Metabolic Myopathy Presentation Patterns
| Presentation |
Think Of |
| Exercise intolerance with “second wind” |
McArdle’s disease |
| Recurrent myoglobinuria with prolonged exercise/fasting |
CPT II deficiency |
| Proximal weakness + respiratory failure (adult) |
Pompe’s disease (late-onset) |
| Ptosis + ophthalmoplegia without diplopia |
Mitochondrial myopathy (CPEO) |
| Stroke-like episodes + seizures + lactic acidosis |
MELAS |
Dystrophy Quick Recognition
| Clinical Clue |
Diagnosis |
| Boy + calf pseudohypertrophy + Gowers’ sign |
DMD |
| Distal weakness + grip myotonia + cataracts + frontal balding |
DM1 |
| Can’t whistle + scapular winging + asymmetric |
FSHD |
| Early contractures + cardiac conduction defects |
Emery-Dreifuss |
| Late-onset ptosis + dysphagia |
OPMD |
Inflammatory Myopathy Quick Recognition
| Clinical Clue |
Diagnosis |
| Heliotrope rash + Gottron’s papules + proximal weakness |
Dermatomyositis |
| Elderly + finger flexor weakness + quad weakness + doesn’t respond to steroids |
IBM |
| Myositis + ILD + mechanic’s hands + arthritis |
Antisynthetase syndrome (anti-Jo-1) |
| Persistent weakness after stopping statin |
Anti-HMGCR necrotizing myopathy |
Red Flags
⚠️ Urgent Situations
- Rapidly progressive weakness + respiratory decline: Check FVC urgently; may need ICU
- Myoglobinuria (dark urine): Rhabdomyolysis risk; aggressive hydration, monitor renal function
- New dermatomyositis in adult: Screen for malignancy (especially with anti-TIF1-γ)
- Cardiac symptoms in muscular dystrophy: DMD/BMD, DM1, Emery-Dreifuss all have cardiac risk
- Dysphagia in myopathy: Aspiration risk; may need modified diet or feeding tube
- Late-onset Pompe’s with respiratory symptoms: Diaphragm weakness; start ERT
Key Clinical Pearls
🔍 High-Yield Points
- Type II fiber atrophy = steroid, disuse, cachexia
- McArdle’s = second wind; Tarui’s = out of wind
- CPT II = most common cause of recurrent rhabdomyolysis in adults
- DM1 = distal; DM2 = proximal
- IBM = mixed EMG pattern + doesn’t respond to immunotherapy
- Perifascicular atrophy = dermatomyositis; rimmed vacuoles = IBM
- Normal CK in weakness = consider steroid myopathy, endocrine, or non-organic
- Always screen DM for malignancy; KSS/Emery-Dreifuss/DM1 for cardiac conduction
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