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158 Cards in this Set

  • Front
  • Back
What does this slide show? How do you know?
What does this slide show? How do you know?
Normal Muscle w/ H&E Stain:
- Peripheral nuclei
- Bee-hive pattern is normal
Normal Muscle w/ H&E Stain:
- Peripheral nuclei
- Bee-hive pattern is normal
What does this slide show? How do you know?
What does this slide show? How do you know?
Normal Muscle - ATPase stain
- Checkerboard pattern is NORMAL in muscle (all stains)
- Grouping would be abnormal - indicating denervation w/ reinnervation
- Dark contains more mitochondria (type 1)
- Lighter (type 2)
Normal Muscle - ATPase stain
- Checkerboard pattern is NORMAL in muscle (all stains)
- Grouping would be abnormal - indicating denervation w/ reinnervation
- Dark contains more mitochondria (type 1)
- Lighter (type 2)
What are the basic pathologic reactions of muscle?
- Hypertrophy
- Degeneration / necrosis
- Regeneration
- Denervation atrophy (neurogenic atrophy)
- Reinnervation
What causes hypertrophy of muscle?
Secondary to increased load d/t exercise or pathologic condition

(picture shows pathologic hypertrophy)
Secondary to increased load d/t exercise or pathologic condition

(picture shows pathologic hypertrophy)
What causes degeneration/necrosis of muscle?
Destruction of all or part of a myofiber; stimulates infiltration by macrophages
Destruction of all or part of a myofiber; stimulates infiltration by macrophages
What causes regeneration of muscle? Appearance?
- Satellite cells around degenerated fiber proliferate
- Regenerating fiber has a bluish color
- Satellite cells around degenerated fiber proliferate
- Regenerating fiber has a bluish color
What does this slide show? How do you know?
What does this slide show? How do you know?
Myopathy: fiber atrophy and hypertrophy
Myopathy: fiber atrophy and hypertrophy
What does this slide show? How do you know?
What does this slide show? How do you know?
Degeneration
- Destruction of all or part of a myofiber; stimulates infiltration by macrophages
Degeneration
- Destruction of all or part of a myofiber; stimulates infiltration by macrophages
What does this slide show? How do you know?
What does this slide show? How do you know?
Regeneration
- Satellite cells around degenerated fiber proliferate
- Regenerating fiber has a bluish color
Regeneration
- Satellite cells around degenerated fiber proliferate
- Regenerating fiber has a bluish color
What causes denervation atrophy (neurogenic atrophy) of muscle?
- Clusters of fibers (of one type) become smaller and develop angular contours (group atrophy)
- Lack of neural input results in breakdown of myosin and actin, resorption of myofibrils, decreased cell size
- Both type 1 and type 2 fiber clusters are found
What does the lack of neural input in denervation atrophy result in?
- Breakdown of myosin and actin
- Resorption of myofibrils
- Decrease in cell size
What causes reinnervation of muscle?
- Neighboring axons sprout and reinnervate denervated myocytes 
- Fiber assumes fiber type conferred by the neighboring axon
- This causes FIBER TYPE GROUPING (pathological)
- Neighboring axons sprout and reinnervate denervated myocytes
- Fiber assumes fiber type conferred by the neighboring axon
- This causes FIBER TYPE GROUPING (pathological)
What does this slide show? How do you know?
What does this slide show? How do you know?
Fiber type grouping (d/t reinnervation) and group atrophy
Fiber type grouping (d/t reinnervation) and group atrophy
What are the characteristics of neurogenic pathology?
- Bimodal size distribution
- ANGULATED fibers
- Apparent increase in nuclei (nuclear clumps)
- NO necrosis, regeneration, fibrosis, or inflammation
- Bimodal size distribution
- ANGULATED fibers
- Apparent increase in nuclei (nuclear clumps)
- NO necrosis, regeneration, fibrosis, or inflammation
What are the characteristics of myopathic pathology?
- Random size variation
- ROUND fibers
- Centralization of nuclei
- Necrosis, regeneration ± fibrosis, inflammation
- Random size variation
- ROUND fibers
- Centralization of nuclei
- Necrosis, regeneration ± fibrosis, inflammation
How does the distribution differ for neurogenic vs myopathic pathology?
- Neurogenic: bimodal size distribution
- Myopathic: random size variation
- Neurogenic: bimodal size distribution
- Myopathic: random size variation
How does the shape of the fibers differ for neurogenic vs myopathic pathology?
- Neurogenic: angulated fibers
- Myopathic: round fibers
- Neurogenic: angulated fibers
- Myopathic: round fibers
How do the nuclei differ for neurogenic vs myopathic pathology?
- Neurogenic: apparent increase in nuclei (nuclear clumps)
- Myopathic: centralization of nuclei
- Neurogenic: apparent increase in nuclei (nuclear clumps)
- Myopathic: centralization of nuclei
How does the presence of necrosis, regeneration, fibrosis, or inflammation differ for neurogenic vs myopathic pathology?
- Neurogenic: not present
- Myopathic: necrosis, regeneration, ± fibrosis, or inflammation can be present
- Neurogenic: not present
- Myopathic: necrosis, regeneration, ± fibrosis, or inflammation can be present
How do you classify skeletal muscle disease?
- Neurogenic atrophy
- Muscular dystrophy
- Inflammatory myopathies
- Metabolic myopathies
- Toxic myopathies
What are the types of motor neuron disease?
Amyotrophic Lateral Sclerosis (ALS)
- Aka Lou Gehrig's Disease
- Motor neuron disease

Spinal Muscular Atrophy (SMA)
Amyotrophic Lateral Sclerosis (ALS)
- Aka Lou Gehrig's Disease
- Motor neuron disease

Spinal Muscular Atrophy (SMA)
What nerves degenerate in Amyotrophic Lateral Sclerosis (ALS)?
- Upper Motor Neurons
- Lower Motor Neurons
What are the characteristics of Amyotrophic Lateral Sclerosis (ALS)?
- Progressive
- Neurodegenerative (UMN and LMN)
- Normal sensation
When does Amyotrophic Lateral Sclerosis (ALS) typically present? Inherited?
50-60 years
- 5-10% are familial types of ALS
What are the symptoms of Amyotrophic Lateral Sclerosis (ALS)?
- Weakness (loss of α-MN): muscle atrophy of affected body part and dysphagia, dysarthria
- Fasciculations / twitches (affected body part, tongue)
- Hyperreflexia and positive Babinski
- Spasticity
- Pseudobulbar palsy (emotions are inappropr...
- Weakness (loss of α-MN): muscle atrophy of affected body part and dysphagia, dysarthria
- Fasciculations / twitches (affected body part, tongue)
- Hyperreflexia and positive Babinski
- Spasticity
- Pseudobulbar palsy (emotions are inappropriate for situations)
- Executive dysfunction: difficulty taking care of yourself, personality changes
- Atrophy of tongue (picture)
What does Amyotrophic Lateral Sclerosis (ALS) look like pathologically?
- Anterior view: anterior horn cells (nerve roots) coming out of spinal cord are thin compared to the posterior roots (healthy)
- Lateral corticospinal tracts are no longer myelinated (degenerating)
- Anterior view: anterior horn cells (nerve roots) coming out of spinal cord are thin compared to the posterior roots (healthy)
- Lateral corticospinal tracts are no longer myelinated (degenerating)
When does Spinal Muscular Atrophy typically present?
Childhood >> Adulthood
What kind of disease is Spinal Muscular Atrophy?
Degenerative LMN disease
How is Spinal Muscular Atrophy inherited? Gene?
- 2nd most common autosomal recessive disorder
- Panethnic
- Homozygous deletion of exon 7 of SMN1 (survival motor neuron) gene
What are the symptoms of Spinal Muscular Atrophy?
- Proximal muscle weakness >> distal
- Dysphagia → GT
- Respiratory weakness → hypercapnia → death (diaphragm failure, intercostal weakness)
- Normal intellect
- Areflexic on exam
What are the subtypes of Spinal Muscular Atrophy?
- Infantile
- Older infant
- Childhood
- Adult onset
What does this slide show? How do you know?
What does this slide show? How do you know?
Spinal Muscular Atrophy and Werdnig Hoffman Disease
- Large groups of rounded atrophic fibers (panfascicular atrophy - dotted black line)
- Sparse scattered markedly hypertrophic fibers (arrows)
- Differs from typical pattern of neurogenic atro...
Spinal Muscular Atrophy and Werdnig Hoffman Disease
- Large groups of rounded atrophic fibers (panfascicular atrophy - dotted black line)
- Sparse scattered markedly hypertrophic fibers (arrows)
- Differs from typical pattern of neurogenic atrophy see in adults
What are the histologic changes that occur in Werdnig Hoffman Disease (Spinal Muscular Atrophy)?
- Large groups of rounded atrophic fibers (panfascicular atrophy - dotted black line)
- Sparse scattered markedly hypertrophic fibers (arrows)
- Differs from typical pattern of neurogenic atrophy see in adults
- Large groups of rounded atrophic fibers (panfascicular atrophy - dotted black line)
- Sparse scattered markedly hypertrophic fibers (arrows)
- Differs from typical pattern of neurogenic atrophy see in adults
What are the types of muscular dystrophies? How do they compare based on inheritance pattern?
X-linked muscular dystrophy:
- Duchenne MD (DMD)
- Becker MD (BMD)

Autosomal recessive muscular dystrophy:
- Myotonic MD (DM)
What is the function of the Dystrophin proteins?
Stabilizes muscle membranes
- Takes cytoskeleton and stabilizes membrane and attaches it to ECM
Stabilizes muscle membranes
- Takes cytoskeleton and stabilizes membrane and attaches it to ECM
What mutation causes Duchenne / Becker Muscular Dystrophies? Inheritance?
Mutation in Xp21 (X-linked, but 1/3 are new mutations)
- Deletion of ≥1 exons in DMD, duplications, stop codons
- Largest gene in humans!
If both Duchenne and Becker Muscular Dystrophy have the same mutation (Xp21 in Dystrophin gene), how do they differ?
- Duchenne (DMD): 99% have none/nearly no dystrophin
- Becker (BMD): 85% have abnormal dystrohin in reduced quantity (15% have normal dystrophin in reduced quantity)
What is more important the size or the quantity of dystrophin? Implications?
Size of dystrophin does NOT matter as much as the quantity of dystrophin

- Duchenne (DMD): 99% have none/nearly no dystrophin → more severe
- Becker (BMD): 85% have abnormal dystrohin in reduced quantity (15% have normal dystrophin in reduced quantity) → less severe b/c they still have some
What is the largest gene in humans?
Dystrophin
What are the symptoms of Duchenne Muscular Dystrophy?
- Proximal muscle weakness
- Intact milestones or slightly delayed
- Slower movements than peers (wheelchair bound by 11-12y)
- Large calves
- Waddling
- Scapular winging
- Gower's maneuver: climb up your body to stand up
- Face/eyes spared...
- Proximal muscle weakness
- Intact milestones or slightly delayed
- Slower movements than peers (wheelchair bound by 11-12y)
- Large calves
- Waddling
- Scapular winging
- Gower's maneuver: climb up your body to stand up
- Face/eyes spared
- Contractures
- Dilated cardiomyopathy
- Intellectual impairment (average IQ 85, although many are normal)
- CK ↑↑↑ → >10,000 (↑ creatinine kinase indicates muscle fiber damage)
What are the symptoms of Becker Muscular Dystrophy?
- Later onset
- Near normal lifespan (mid 60s)
- Still have weakness
What does this slide show? How do you know?
What does this slide show? How do you know?
Duchenne Muscular Dystrophy
- Producing a random occurrence of fibers tearing themselves apart because they are not stabilized enough
- Not going to be grouped/focal (just which fiber has bad luck), ALL RANDOM
- Ongoing b/c people are always mo...
Duchenne Muscular Dystrophy
- Producing a random occurrence of fibers tearing themselves apart because they are not stabilized enough
- Not going to be grouped/focal (just which fiber has bad luck), ALL RANDOM
- Ongoing b/c people are always moving: new and old damage w/ regeneration in different area
- New damage: macrophages
- Old damage: fibrosis/scarring
- Regeneration: basophilia
What immunostaining could you do on a muscle biopsy (not done that often)?
- Dystrophin: lacking in DMD
- Spectrin: indicates if it is alive
- Utrophin: related to dystrophin and upregulated in dystrophy and other myopathic processes (normally it is only in capillaries and nerves)
- Dystrophin: lacking in DMD
- Spectrin: indicates if it is alive
- Utrophin: related to dystrophin and upregulated in dystrophy and other myopathic processes (normally it is only in capillaries and nerves)
What immunostain results would you expect for Dystrophin in DMD?
Dystrophin: lacking in DMD
Dystrophin: lacking in DMD
What immunostain results would you expect for Spectrin in DMD?
Spectrin: indicates if it is alive
Spectrin: indicates if it is alive
What immunostain results would you expect for Utrophin in DMD?
Utrophin: related to dystrophin and upregulated in dystrophy and other myopathic processes (normally it is only in capillaries and nerves)
Utrophin: related to dystrophin and upregulated in dystrophy and other myopathic processes (normally it is only in capillaries and nerves)
What results on Western Blot for Dystrophin would you expect for Becker MD and Duchenne MD?
- Becker MD: dystrophin reduced in size and amount (lane 1, 2)
- Duchenne MD: essentially no dystrophin present (lane 4)
- Becker MD: dystrophin reduced in size and amount (lane 1, 2)
- Duchenne MD: essentially no dystrophin present (lane 4)
What is the most common muscular dystrophy in adults?
Myotonic Dystrophy
How do you inherit Myotonic Dystrophy? When does it present?
- Autosomal dominant
- Presents in adults
What is the genetic cause of Myotonic Dystrophy?
DM1 - Dystrophia Myotonica Type 1
- CTG repeat expansion in DMPK gene on chromosome 19
- Normally 5-37 repeats
- Full mutation: >80 repeats
- Genetic anticipation in subsequent generations
What does this slide show? How do you know?
What does this slide show? How do you know?
Myotonic Dystrophy
- Some fibers are smaller than others
- More nuclei in the centers than normal (usually there are 3 in the center for every 100 fibers) = Increased Internal Nucleation
Myotonic Dystrophy
- Some fibers are smaller than others
- More nuclei in the centers than normal (usually there are 3 in the center for every 100 fibers) = Increased Internal Nucleation
What is the histologic presentation of Myotonic Dystrophy?
- Some fibers are smaller than others
- More nuclei in the centers than normal (usually there are 3 in the center for every 100 fibers) = Increased Internal Nucleation
- Some fibers are smaller than others
- More nuclei in the centers than normal (usually there are 3 in the center for every 100 fibers) = Increased Internal Nucleation
What are the symptoms of Myotonic Dystrophy? Why?
* Difficulty releasing grip → myotonia (impaired Cl- conduction → slow repolarization → impaired relaxation)
- Weakness (distal hands and feet → grip and foot drop)
- Elongated face (myopathic face)
- Temporal wasting
- Endocrine abnor...
* Difficulty releasing grip → myotonia (impaired Cl- conduction → slow repolarization → impaired relaxation)
- Weakness (distal hands and feet → grip and foot drop)
- Elongated face (myopathic face)
- Temporal wasting
- Endocrine abnormalities (testicular atrophy → balding; insulin resistance → diabetes)
- Premature cataracts
- Cardiac arrhythmias (90%)
- ↓ Intelligence (higher repeat #)
What is the pathophysiology responsible for Myotonic Dystrophy?
Impaired Cl- conduction → slow repolarization → impaired relaxation
What is the characteristic sound of Myotonic Dystrophy on EMG?
"Divebomber" (sounds like a fart)
What are the endocrine abnormalities in Myotonic Dystrophy? Implications?
- Testicular atrophy → balding
- Insulin resistance → diabetes
What muscles are affected by weakness in Myotonic Dystrophy?
- Distal hands and feet → grip and foot drop
- Proximal muscles
- Face - hatchet face
- Distal hands and feet → grip and foot drop
- Proximal muscles
- Face - hatchet face
Which dystrophy has genetic anticipation?
Myotonic Dystrophy 
- More CTG repeats in subsequent generations
Myotonic Dystrophy
- More CTG repeats in subsequent generations
What are the metabolic myopathies?
- Mitochondrial myopathies
- Glycogen storage diseases
What mutations cause mitochondrial myopathies?
Mutations in nuclear or mitochondrial DNA involved in oxidative phosphorylation
What causes glycogen storage diseases?
Hereditary deficiency of enzyme involved in synthesis or degradation of glycogen
What tissues are affected by mitochondrial myopathies?
Depends which cells have more mitochondria that are affected (heteroplasmy: mitotic segregation of mtDNA)
Depends which cells have more mitochondria that are affected (heteroplasmy: mitotic segregation of mtDNA)
What is MELAS? Mutation?
Mitochondrial myopathy, encephalopathy, lactic acidosis, & stroke-like episodes
- MtDNA mutation: in mt-tRNA (Leu)
What do these slides indicate?
What do these slides indicate?
Mitochondrial myopathy, encephalopathy, lactic acidosis, & stroke-like episodes (MELAS)
What are the diagnostic criteria for Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, & Stroke-like episodes (MELAS)?
- Stroke like episodes < 40 years
- Encephalopathy
- Lactic acidosis, ragged-red fibers, or both
What are the symptoms of Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, & Stroke-like episodes (MELAS)?
- Stroke like episodes (<40 y) → dementia d/t progressive cognitive impairment (not vascular)
- Encephalopathy (seizures, stroke-like episodes, neurodeneration)
- Lactic acidosis, ragged-red fibers, or both (myopathy, proximal, eyes)
- Sensor...
- Stroke like episodes (<40 y) → dementia d/t progressive cognitive impairment (not vascular)
- Encephalopathy (seizures, stroke-like episodes, neurodeneration)
- Lactic acidosis, ragged-red fibers, or both (myopathy, proximal, eyes)
- Sensorineural hearing loss
- Migraines
- Cardiomyopathy
- WPW
- Short stature
What are the three major subgroups of glycogen storage diseases?
- Hepatic forms
- Myopathic forms
- Generalized storage (may organs)
What causes myopathic forms of glycogen storage disease? Example?
- Phosphorylase deficiency
- Type V glycogenosis
- McArdle's Disease
What causes generalized storage forms of glycogen storage disease? Example?
- Acid maltase deficiency
- Type II glycogenosis
- Pompe's Disease
What kind of disease is Mcardle's Disease? Deficiency? Symptoms?
- Myopathic form of glycogen storage disease
- Phosphorylase deficiency (type V glycogenosis)
- Glycogen derived from glycolysis is main source of energy (glycogen accumulates in muscle if enzyme in glycolytic pathway is deficient)
- Clinical syndrome: exercise intolerance w/ cramps and intermittent myoglobinuria
What kind of disease is Pompe's Disease? Deficiency? Symptoms?
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
How can you diagnose glycogen storage diseases?
Measure enzyme concentration in skeletal muscle
What is this pathology?
What is this pathology?
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
What is this pathology?
What is this pathology?
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
Is this normal or pathologic?
Is this normal or pathologic?
Normal muscle EM
Normal muscle EM
Is this normal or pathologic?
Is this normal or pathologic?
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
Pompe Disease
- Generalized storage form of glycogen storage disease in many organs (most prominently in heart)
- Acid Maltase deficiency (type II glycogenosis)
- Death early in life
What are the types of inflammatory myopathies? How are they all similar?
All 3 types have inflammation on the muscle biopsy (T cells and macrophages)
- Inclusion Body Myositis
- Dermatomyositis
- Polymyositis
What are the clinical symptoms of Polymyositis? When does it present?
- Symmetric proximal muscle weakness
- No rash
- Adults; F > M
What is Polymyositis associated with?
- Association with other auto-immune diseases (eg, SLE, polyarteritis nodosa, systemic sclerosis)
- Not associated w/ malignancy
What kind of inflammation occurs in Polymyositis?
Inflammation is predominantly T cells (CD8+)
- Cell-mediated injury
- Cells are endomysial (intermingled among muscle fibers)
Inflammation is predominantly T cells (CD8+)
- Cell-mediated injury
- Cells are endomysial (intermingled among muscle fibers)
What pathology is this? How do you know?
What pathology is this? How do you know?
Polymyositis
- Inflammation is predominantly T cells (CD8+)
- Cell-mediated injury
- Cells are endomysial (intermingled among muscle fibers)
Polymyositis
- Inflammation is predominantly T cells (CD8+)
- Cell-mediated injury
- Cells are endomysial (intermingled among muscle fibers)
What are the signs/symptoms of Dermatomyositis?
- Shawl sign
- Heliotrope (violaceous) rash around eyes
- Nail bed w/ thrombi and hemorrhages
- Subcutaneous calcifications - painful, more common in juvenile Dermatomyositis
- Gottron's papules - erythematous lesions over knuckles
- Shawl sign
- Heliotrope (violaceous) rash around eyes
- Nail bed w/ thrombi and hemorrhages
- Subcutaneous calcifications - painful, more common in juvenile Dermatomyositis
- Gottron's papules - erythematous lesions over knuckles
What is the pathologic appearance of Dermatomyositis?
- Microvasculature attacked by antibodies and complement
- B cells predominante
- Ischemic atrophy and necrosis of fibers (perifascicular atrophy)
- Microvasculature attacked by antibodies and complement
- B cells predominante
- Ischemic atrophy and necrosis of fibers (perifascicular atrophy)
What pathology is this? How do you know?
What pathology is this? How do you know?
Dermatomyositis
- Microvasculature attacked by antibodies and complement
- B cells predominante
- Ischemic atrophy and necrosis of fibers (perifascicular atrophy)
Dermatomyositis
- Microvasculature attacked by antibodies and complement
- B cells predominante
- Ischemic atrophy and necrosis of fibers (perifascicular atrophy)
What is the clinical presentation of Inclusion Body Myositis (IBM)?
- Severe and early quad atrophy
- Medial forearm atrophy - deep finger flexors
- Severe and early quad atrophy
- Medial forearm atrophy - deep finger flexors
What is the histologic appearance of Inclusion Body Myositis (IBM)?
Inclusion Body Myositis (IBM)
- Endomysial infiltrates (CD8)
* Rimmed vacuoles
- Amyloid deposits
- Invasion of non-necrotic fibers
* Tubulofilamentous inclusions
Inclusion Body Myositis (IBM)
- Endomysial infiltrates (CD8)
* Rimmed vacuoles
- Amyloid deposits
- Invasion of non-necrotic fibers
* Tubulofilamentous inclusions
What test can you do to confirm Inclusion Body Myositis (IBM)?
Amyloid deposits (congo red w/ polarized light birefringence
Amyloid deposits (congo red w/ polarized light birefringence
What is the electron microscope appearance of Inclusion Body Myositis (IBM)?
Cytoplasmic inclusions of tuberofilaments
Cytoplasmic inclusions of tuberofilaments
What is this pathology?
What is this pathology?
Inclusion Body Myositis (IBM)
Inclusion Body Myositis (IBM)
What is this pathology?
What is this pathology?
Inclusion Body Myositis (IBM)
Inclusion Body Myositis (IBM)
How do the inflammatory myopathies compare for gender predisposition and age of onset?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: F>M, childhood & adult
- Polymyositis: F>M, adult
- Inclusion Body Myositis: M>F, older adult (>50y)
- Dermatomyositis: F>M, childhood & adult
- Polymyositis: F>M, adult
- Inclusion Body Myositis: M>F, older adult (>50y)
How do the inflammatory myopathies compare for the presence of rash?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: yes
- Polymyositis: no
- Inclusion Body Myositis: no
- Dermatomyositis: yes
- Polymyositis: no
- Inclusion Body Myositis: no
How do the inflammatory myopathies compare for the pattern of weakness?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: proximal
- Polymyositis: proximal
- Inclusion Body Myositis: proximal = distal, deep finger flexors and quads, and dysphagia
- Dermatomyositis: proximal
- Polymyositis: proximal
- Inclusion Body Myositis: proximal = distal, deep finger flexors and quads, and dysphagia
How do the inflammatory myopathies compare for CK (creatinine kinase)?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: ↑↑ CK
- Polymyositis: ↑ CK
- Inclusion Body Myositis: Normal or mildly ↑ CK
- Dermatomyositis: ↑↑ CK
- Polymyositis: ↑ CK
- Inclusion Body Myositis: Normal or mildly ↑ CK
How do the inflammatory myopathies compare for Muscle Biopsy?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: perivascular, perimysial and endomysial infiltrates; perifascicular atrophy and focal necrosis, microangiopathy
- Polymyositis: endomysial infiltrates (CD8+), invasion of non-necrotic fibers
- Inclusion Body Myositis: endomysi...
- Dermatomyositis: perivascular, perimysial and endomysial infiltrates; perifascicular atrophy and focal necrosis, microangiopathy
- Polymyositis: endomysial infiltrates (CD8+), invasion of non-necrotic fibers
- Inclusion Body Myositis: endomysial infitlrates (CD8), rimmed vacuoles, amyloid deposits, invasion of non-necrotic fibers, tubulofilamentous inclusions
How do the inflammatory myopathies compare for response to immunosuppression?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: Yes
- Polymyositis: Yes
- Inclusion Body Myositis: No
- Dermatomyositis: Yes
- Polymyositis: Yes
- Inclusion Body Myositis: No
How do the inflammatory myopathies compare for associated conditions?
- Dermatomyositis
- Polymyositis
- Inclusion Body Myositis
- Dermatomyositis: myocarditis, interstitial lung disease, malignancy, vasculitis
- Polymyositis: SLE, PAN, scleroderma
- Inclusion Body Myositis: -
- Dermatomyositis: myocarditis, interstitial lung disease, malignancy, vasculitis
- Polymyositis: SLE, PAN, scleroderma
- Inclusion Body Myositis: -
What are the toxic, drug-induced myopathies?
- Steroids
- Statin induced
What are the signs of steroid induced myopathy?
- Proximal weakness
- Associated with high dose, prolonged use of steroids
- Proximal weakness
- Associated with high dose, prolonged use of steroids
What pathology is associated with Steroid Induced Myopathy?
Type 2b Atrophy (type 2 fibers are dark)
Type 2b Atrophy (type 2 fibers are dark)
What is this pathology?
What is this pathology?
Necrotizing Immune Mediated Statin Myopathy
Necrotizing Immune Mediated Statin Myopathy
What does the PNS encompass?
Motor, autonomic, and sensory neurons that extend outside the CNS
How does PNS compare to CNS in terms of regeneration?
PNS is able to regeneration (unlike CNS)
What terminology is used to talk about the PNS?
- Motor unit
- Axon
- Schwann cells
- Nerve fiber
- Nerve
- Epi-, peri-, and endometrium
What is this?
What is this?
Peripheral nerve section
- The individual little circles are the large myelinated axons
Peripheral nerve section
- The individual little circles are the large myelinated axons
What is the arrow pointing at?
What is the arrow pointing at?
Large myelinated axon in a peripheral nerve
Large myelinated axon in a peripheral nerve
What are A and B?
What are A and B?
A= myelin
B= neurofilaments and microtubules in axons
A= myelin
B= neurofilaments and microtubules in axons
What happened to these peripheral nerves?
What happened to these peripheral nerves?
Segmental (primary) demyelination
Segmental (primary) demyelination
What happened to these peripheral nerves?
What happened to these peripheral nerves?
Axonal degeneration
Axonal degeneration
What pathologies can occur to peripheral nerves?
Axonal degeneration (two types)
- Neuronopathy or axonopathy (generalized abnormality)
- Wallerian degeneration (focal lesion causing axonal injury)
What does the neuronopathy / axonopathy type of axonal degeneration affect?
GENERALIZED abnormality affecting:
- Neuronal cell body (eg, motor neuron disease)
- Axon ("dying back" from distal territory)
What does the Wallerian degeneration type of axonal degeneration affect?
FOCAL lesion causing axonal injury
- Affects portions of fibers (axon and myelin) distal to focal injury degenerates (eg, transection)
What do these images show?
What do these images show?
Axonal degeneration - digestion chambers (or myelin ovoids)
Axonal degeneration - digestion chambers (or myelin ovoids)
What do these arrows point out?
What do these arrows point out?
Axonal regrowth - clusters of regenerating axons, sprouting
Axonal regrowth - clusters of regenerating axons, sprouting
What does this image represent?
What does this image represent?
Segmental Demyelination - loss of myelin with axonal preservation (teased fiber preparation)
Segmental Demyelination - loss of myelin with axonal preservation (teased fiber preparation)
What are the causes of peripheral neuropathies?
- Inflammatory neuropathies
- Hereditary neuropathies (Charcot-Marie-Tooth disease)
- Metabolic and toxic neuropathies
- Traumatic neuropathies
What is the hereditary neuropathy?
Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy)
What are the inflammatory neuropathies?
- Guillain-Barré Syndrome (Acute Inflammatory Demyelinating Polyradiculoneuropathy = AIDP)
- Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
- Vasculitis = Mononeuritis Multiplex
What is the other name for Guillain-Barré Syndrome?
Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
What is the other term for the inflammatory neuropathy vasculitis?
Mononeuritis Multiplex
What are the characteristics of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)?
- Onset
- Symptoms
- Diagnosis
- Treatment
- Onset: any age, monophasic illness (only get it once)
- Symptoms: rapidly ascending weakness, respiratory weakness, bulbar weakness, autonomic - cardiac rhythm, preceding viral illness
- Diagnosis: areflexia, CSF - high protein; normal cells → cytoalbuminologic dissociation; EMG/NCS - demyelinating features
- Treatment: IVIG or PLEX
What are the characteristics of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)?
- Onset
- Symptoms
- Diagnosis
- Treatment
- Onset: any age, chronic illness
- Symptoms: slowly progressive weakness, proximal → distal, no preceding illness
- Diagnosis: areflexia, CSF - high protein; normal cell → cytoalbuminologic dissociation; EMG/NCS - demyelinating features
- ...
- Onset: any age, chronic illness
- Symptoms: slowly progressive weakness, proximal → distal, no preceding illness
- Diagnosis: areflexia, CSF - high protein; normal cell → cytoalbuminologic dissociation; EMG/NCS - demyelinating features
- Treatment: Prednisone, IVIG, PLEX
How do AIDP and CIDP compare for onset?
- AIDP: any age, monophasic illness
- CIDP: any age, chronic illness
- AIDP: any age, monophasic illness
- CIDP: any age, chronic illness
How do AIDP and CIDP compare for symptoms?
AIDP:
- Rapidly ascending weakness
- Respiratory weakness
- Bulbar weakness
- Autonomic: cardiac rhythm
*Preceding viral illness

CIDP:
- Slowly progressive weakness
- Proximal → distal
* No preceding illness
AIDP:
- Rapidly ascending weakness
- Respiratory weakness
- Bulbar weakness
- Autonomic: cardiac rhythm
*Preceding viral illness

CIDP:
- Slowly progressive weakness
- Proximal → distal
* No preceding illness
How do AIDP and CIDP compare for diagnosis??
AIDP:
- Areflexia
- CSF: high protein
- Normal cells → cytoalbuminologic dissociation
- EMG/NCS: demyelinating features

CIDP:
- Areflexia
- CSF: high protein
- Normal cells → cytoalbuminologic dissociation
- EMG/NCS: demyelinating f...
AIDP:
- Areflexia
- CSF: high protein
- Normal cells → cytoalbuminologic dissociation
- EMG/NCS: demyelinating features

CIDP:
- Areflexia
- CSF: high protein
- Normal cells → cytoalbuminologic dissociation
- EMG/NCS: demyelinating features
How do AIDP and CIDP compare for treatment?
AIDP:
- IVIG
- PLEX

CIDP:
- Prednisone
- IVIG
- PLEX
AIDP:
- IVIG
- PLEX

CIDP:
- Prednisone
- IVIG
- PLEX
What is this indicative of?
What is this indicative of?
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
What is this indicative of?
What is this indicative of?
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
What happens in Vasculitis (Mononeuritis Multiplex)? Implications?
Infarctions of peripheral nerves
- Distal sciatic → foot drop
- Ulnar in midarm → hand weakness

Immune mediated
Infarctions of peripheral nerves
- Distal sciatic → foot drop
- Ulnar in midarm → hand weakness

Immune mediated
How do you diagnose Vasculitis (Mononeuritis Multiplex)?
Nerve biopsy:
- Inflammation of nerve
- Vascular necrosis
Nerve biopsy:
- Inflammation of nerve
- Vascular necrosis
What does this pathology indicate?
What does this pathology indicate?
Vasculitis (Mononeuritis Multiplex)

Nerve biopsy shows:
- Inflammation of nerve
- Vascular necrosis
Vasculitis (Mononeuritis Multiplex)

Nerve biopsy shows:
- Inflammation of nerve
- Vascular necrosis
What are the types of infectious neuropathy?
Leprosy
- aka Hansen's disease

Varicella Zoster Virus Neuropathy
- aka Herpes Zoster
- aka Shingles
What infection causes leprosy? How is it obtained?
Mycobacterium leprae
- Route of transmission is unknown, may be nasal droplets, infected soil, contact with infected
How long does Mycobacterium leprae incubate? What does it do?
- 5-7 year incubation period
- Bacilli invade nerves and skin → inflammation and granulomas
What are the forms of Leprosy? How do they differ?
- Tuberculoid: host mounts T cell response
- Lepromatous: host is anergic
- Tuberculoid: host mounts T cell response
- Lepromatous: host is anergic
Where does Mycobacterium leprae grow best?
Grows best in cooler regions of the body
- Skin
* Nerves
- Anterior chamber of eye
- Testes
- Upper respiratory tract
How does Mycobacterium leprae affect the skin and nerves?
Skin:
- Hypopigmented lesions that are well-defined, anesthetic, anhidrosis
- Plaques on face, loss of eyebrows

Nerves:
- Enlarged
- Destruction → anesthesia → auto-amputation
Skin:
- Hypopigmented lesions that are well-defined, anesthetic, anhidrosis
- Plaques on face, loss of eyebrows

Nerves:
- Enlarged
- Destruction → anesthesia → auto-amputation
What causes Varicella Zoster Virus Neuropathy?
Reactivation of Varicella Zoster Virus (aka Herpes Zoster)
- VZV travels down the Dorsal Root Ganglion (DRG)
What are the symptoms of Varicella Zoster Virus Neuropathy?
- VZV travels down Dorsal Root Ganglion (DRG) causing a RASH
- Pain in dermatomal distribution → post-herpetic neuralgia
- Immunosuppressed, elderly
- VZV travels down Dorsal Root Ganglion (DRG) causing a RASH
- Pain in dermatomal distribution → post-herpetic neuralgia
- Immunosuppressed, elderly
What does this image show?
What does this image show?
Varicella Zoster Virus Neuropathy
Varicella Zoster Virus Neuropathy
What is the hereditary neuropathy?
Charcot-Marie-Tooth (CMT) type 1A
What causes Charcot-Marie-Tooth (CMT) type 1A?
- Duplication or point mutation in PMP22
- Autosomal dominant inheritance
- Gradual myelin loss leads to axonal degeneration
When does Charcot-Marie-Tooth (CMT) type 1A present? Symptoms?
- Onset: early-mid teens

Longest nerves affected:
- Foot drop
- Inverted champagne bottles, stork legs
- Tripping, falling, clumsy walk
- Claw hands
- Ataxia, loss of proprioception
- Pes cavus, hammer toes
- Onset: early-mid teens

Longest nerves affected:
- Foot drop
- Inverted champagne bottles, stork legs
- Tripping, falling, clumsy walk
- Claw hands
- Ataxia, loss of proprioception
- Pes cavus, hammer toes
What is the histological appearance of Charcot-Marie-Tooth (CMT) type 1A?
Onion bulb formation
Onion bulb formation
What is this pathology? Description?
What is this pathology? Description?
Charcot-Marie-Tooth (CMT) type 1A
- Onion bulb formation
Charcot-Marie-Tooth (CMT) type 1A
- Onion bulb formation
What kind of neuropathy is Diabetic Neuropathy? Cause?
Axonal Degeneration - secondary demyelination
What are the two forms of Diabetic Neuropathy?
- Stocking → globe distribution loss of sensation → motor
- Diabetic amyotrophy - lumbosacral plexus lesion → quad atrophy
- Stocking → globe distribution loss of sensation → motor
- Diabetic amyotrophy - lumbosacral plexus lesion → quad atrophy
What are the symptoms of Diabetic Neuropathy?
- Pain, tingling, numbness
- Foot drop
- Severe proprioceptive loss
What nerve is affected by carpal tunnel syndrome?
Median nerve at wrist
Median nerve at wrist
What are the symptoms of carpal tunnel syndrome?
- Pain, numbness, tingling in median nerve distribution
- Worse at night or when wrist is flexed/extended
- Pain, numbness, tingling in median nerve distribution
- Worse at night or when wrist is flexed/extended
How do you treat carpal tunnel syndrome?
- Wrist splints at night
- Carpal tunnel release surgery
- Wrist splints at night
- Carpal tunnel release surgery
What is a neuroma?
Intraneural scarring
Intraneural scarring
What are the types of neuromas?
Morton's Neuroma and Traumatic Neuromas
What are the causes of Morton's Neuroma and Traumatic Neuromas?
Causes: fracture
- Compression
- Surgical lesion of nerve
What are the symptoms of Morton's Neuroma and Traumatic Neuromas?
Persistent, incapacitating pain, tingling at site of injury
Persistent, incapacitating pain, tingling at site of injury
What is specific about Morton's Neuroma vs Traumatic Neuromas
Morton's Neuroma: occurs between 3rd and 4th metatarsals, pain when bearing weight
Morton's Neuroma: occurs between 3rd and 4th metatarsals, pain when bearing weight
Case: A 40 yo M complains of difficulty walking with unsteadiness and propensity to fall for 1 week. Exam shows inability to stand on toes, walk on heels, squat deeply, diffuse areflexia, but he can walk independently with mild difficulty and guarding. Which of the following is true?
a) Inheritance of disease is autosomal dominant
b) CSF will show high protein and high cell count
c) Nerve biopsy will show nerve inflammation with acute necrosis of vessels
d) Chances of autonomic dysfunction is low
e) Condition is monophasic
Condition is monophasic (Guillain-Barré Syndrome = Acute Inflammatory Demyelinating Polyradiculopathy, AIDP)
Case: Nerve biopsy done on a 40 yo F with foot drop showed the following. What is the most likely diagnosis?
a) AIDP
b) Vasculitis
c) CMT1A
d) Leprosy
e) Diabetic neuropathy
Case: Nerve biopsy done on a 40 yo F with foot drop showed the following. What is the most likely diagnosis?
a) AIDP
b) Vasculitis
c) CMT1A
d) Leprosy
e) Diabetic neuropathy
CMT1A: Charcot-Marie-Tooth type 1A (can tell because of onion bulbs)
CMT1A: Charcot-Marie-Tooth type 1A (can tell because of onion bulbs)