SPINAL MUSCULAR ATROPHY (5q)
SMA: Mechanisms Underlying Pathology
- Initial innervation
- By reduced nubers of motor axons
- Functional axons
- Innervate, & maintain size of, larger muscle fibers
- Abnormal patterns of activity produce
- Hypertrophy: Larger muscle fibers have
- Very increased size for age
- Type 1 fiber predominance
- Atrophy
- Some muscle fibers may be innervated by non-functioning axons
- Esterase stain: NMJs are preserved with Strongly staining on some small & large muscle fibers
- Younger patients: Many 2C fibers
- ATPase pH 4.6: No 2A fibers; Many degrees of staining of 2B fibers
- Abnormal fiber types
- Type I fibers by ATPase: May be pale on COX or dark on PAS
- Darker fibers on COX: May also be dark on PAS
- Disease progression
- Axon loss: Not proven
- Axons may become progressively dysfunctional or lost
SMA 5q: General Features
![](../pics/biopsy/denervation/SMA/smavvgmp.jpg)
VvG stain
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Muscle fibers
Small fibers: Large groups
Large fibers: Clustered; Hypertrophied, especially for age
![](../pics/biopsy/denervation/SMA/sma3bhe.jpg)
H&E stain
Grouped atrophy
Small muscle fibers: Often rounded
Pyknotic nuclear clumps: None
Large muscle fibers: Hypertrophy
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![](../pics/biopsy/denervation/SMA/sma3bvvg.jpg)
VvG stain
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![](../pics/biopsy/denervation/SMA/sma3bgthp.jpg)
Gomori trichrome stain
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![](../pics/smahe3.jpg)
H&E stain
Larger muscle fibers
Hypertrophied
Commonly type I
Clustered
Smaller muscle fibers
Round
Commonly type II, May also be I or IIC
Clustered
![](../pics/smaatp942.jpg)
ATPase pH 9.4 stain
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![](../pics/biopsy/denervation/SMA/sma3batp43.jpg)
ATPase pH 4.3 stain
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SMA, Congenital (Type 0)
![](../pics/biopsy/denervation/SMA/SMAvsevlp.jpg)
H & E
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![](../pics/biopsy/denervation/SMA/SMAvsevhp.jpg)
H & E
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Only small muscle fibers are present.
Small fibers have moderate variation in size.
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![](../pics/biopsy/denervation/SMA/sma0vvg.jpg)
VvG
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SMA0: Fiber type properties
Many small fibers are Type 2C. (Intermediate stained at ATPase pH 4.3)
![](../pics/biopsy/denervation/SMA/sma0atp43.jpg)
ATPase pH 4.3
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Most muscle fibers are dark (Like type 2C) on ATPase pH 9.4
![](../pics/biopsy/denervation/SMA/sma5q0atp94.jpg)
ATPase pH 9.4
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Most muscle fibers are intermediate stained (Like type 2C) on ATPase pH 4.3
![](../pics/biopsy/denervation/SMA/sma5q0atp43.jpg)
ATPase pH 4.3
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Muscle fibers are variably intermediate stained (Like type 2B) on ATPase pH 4.6
There are no 2A muscle fibers
![](../pics/biopsy/denervation/SMA/sma5q0atp47.jpg)
ATPase pH 4.6
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![](../pics/biopsy/denervation/SMA/sma0cox.jpg)
COX
Mitochondrial stains are pale
![](../pics/biopsy/denervation/SMA/sma0sdh.jpg)
SDH
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SMA, Type 1
![](../pics/biopsy/denervation/SMA/SMAsevlp.jpg)
H & E
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![](../pics/biopsy/denervation/SMA/SMAsevmp.jpg)
H & E
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Many muscle fibers are small. A few hypertrophied fibers are present
|
|
![](../pics/biopsy/denervation/SMA/sma1nadh2.jpg)
NADH
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Some large & small muscle fibers have reduced or absent glycogen
![](../pics/biopsy/denervation/SMA/sma1pas.jpg)
PAS
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SMA Type 2
Age: 9 months
![](../pics/biopsy/denervation/SMA/SMAmp3.jpg)
H&E stain
Large groups of atrophic muscle fibers
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![](../pics/biopsy/denervation/SMA/sma2lphe.jpg)
H&E stain
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Patterns of fiber size changes: Varied among fascicles
Hypertrophic muscle fibers with scattered small angular fibers (Top; Left)
Intermediate, variably sized fibers (Bottom; Left)
Very small fibers: No pyknotic nuclear clumps (Middle)
Large & Small fibers with grouped atrophy (Right)
![](../pics/biopsy/denervation/SMA/sma2lp.jpg)
H&E stain
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![](../pics/biopsy/denervation/SMA/SMA5q2nmjlgfibest.jpg)
Esterase
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![](../pics/biopsy/denervation/SMA/SMA5q2nmjsmfibest.jpg)
Esterase
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Neuromuscular junctions on large & small muscle fibers.
![](../pics/biopsy/denervation/SMA/sma2nmjest.jpg)
Esterase stain
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![](../pics/biopsy/denervation/SMA/sma2nervevvg.jpg)
VvG
Intramuscular nerves: Unremarkable
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![](../pics/biopsy/denervation/SMA/sma5qnervetb.jpg)
Toluidine blue
Sensory nerve
Normal numbers of large & small myelinated axons
Thinly myelinated larger axons: Consistent with young age.
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![](../pics/biopsy/denervation/SMA/smavvgnv.jpg)
VvG
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![](../pics/biopsy/denervation/SMA/SMA5qnadh.jpg)
NADH
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![](../pics/biopsy/denervation/SMA/smanadh.jpg)
NADH
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Small muscle fibers
Stain darkly on NADH
Large muscle fibers
Coarse internal architecture
![](../pics/biopsy/denervation/SMA/sma2nadh.jpg)
NADH
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SMA 2: Fiber type properties
![](../pics/biopsy/denervation/SMA/sma2atp94lp.jpg)
ATPase pH 9.4
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Small muscle fibers: May be varied types or mostly type II
Large muscle fibers: Hypertrophied; Clustered; Type I or Abnormal intermediate staining
![](../pics/biopsy/denervation/SMA/sma2atp43lp.jpg)
ATPase pH 4.3
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![](../pics/biopsy/denervation/SMA/SMAatp94mp.jpg)
ATPase, pH 9.4
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![](../pics/biopsy/denervation/SMA/SMAatp94tp2atr.jpg)
ATPase, pH 9.4
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![](../pics/biopsy/denervation/SMA/SMAatp43mp.jpg)
ATPase, pH 4.3
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Small muscle fibers: May be varied types (Left) or mostly type II (Middle)
Large muscle fibers: Clustered; Type I or Abnormal intermediate staining
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Many small fibers are type 2C
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![](../pics/biopsy/denervation/SMA/sma2-atp43.jpg)
ATPase, pH 4.3
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Incomplete Fiber Type Switching (Abnormal fiber types): ATPase doesn't entirely correspond to COX & PAS
![](../pics/biopsy/denervation/SMA/sma5qftgatp94.jpg)
ATPase, pH 9.4
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Large muscle fibers: Mostly type I (Intermediate staining)
Small muscle fibers: Mostly type II (Dark staining)
![](../pics/biopsy/denervation/SMA/sma5qftgatp43.jpg)
ATPase, pH 4.3
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Large muscle fibers: Mostly type I (Dark staining)
Small muscle fibers (Bottom left): Many type IIC (Varied degrees of intermediate staining)
![](../pics/biopsy/denervation/SMA/sma5qftgatp46.jpg)
ATPase, pH 4.6
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Large muscle fibers: Mostly type I (Dark staining)
Small muscle fibers (Bottom left): Many type IIB (Varied degrees of intermediate staining); Few, or no IIA (Pale staining)
![](../pics/biopsy/denervation/SMA/sma5qftgcox.jpg)
Cytochrome oxidase
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COX: Clusters of larger fibers that have Type I staining on ATPase are pale (Usual Type II pattern)
Large muscle fibers
Clusters of type I (Dark staining) & Type II (Pale staining)
Some pale stained fiber clusters (Type II pattern) are Type I patterns on ATPase
Small muscle fibers: Intermediate & Pale staining
![](../pics/biopsy/denervation/SMA/sma5qftgPAS.jpg)
PAS
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PAS: Similar to, instead of opposite of, COX stain in larger fibers
Large muscle fibers
Clusters of abnormal type II pattern (Dark staining) in type I fibers on ATPase & COX
Some clusters have Type I pattern (Pale staining)
Fiber types are opposite of COX pattern
Small muscle fibers: Type 2 pattern (Darker staining)
SMA Type 3, Age 2 years
![](../pics/biopsy/denervation/SMA/SMA5q3he.jpg)
H & E
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Grouped atrophy. Larger muscle fibers are not promiently hypertrophied.
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![](../pics/biopsy/denervation/SMA/sma5q3atp94.jpg)
ATPase pH 9.4
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![](../pics/biopsy/denervation/SMA/sma5q3nadh.jpg)
NADH
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Variable involvement of fascicles.
Top: Scattered small fibers. Large fibers are type 1.
Bottom: Few small fibers. Type 2 predominance.
Abnormal intermediate-staining fibers.
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Variable involvement of fascicles.
Top: Scattered small fibers. Most fibers are dark-stained.
Bottom: Few small fibers. Most fibers are pale-stained.
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![](../pics/biopsy/denervation/SMA/sma5q3nvvvg.jpg)
VvG
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Grouped atrophy.
Larger muscle fibers: Not promiently hypertrophied.
Intramuscular nerves: Mildly reduced axon numbers.
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![](../pics/biopsy/denervation/SMA/sma5q3nmjest.jpg)
Esterase
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Neuromuscular junctions.
Present on large and small muscle fibers.
Shape: Large; Increased extent around muscle fibers; Not multi-segmented.
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SMA Type 3, Age 6 years
Same patient as above
![](../pics/biopsy/denervation/SMA/sma36yohelp.jpg)
H & E stain
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Grouped atrophy: Variable among fascicles
Large muscle fibers: Hypertrophied
![](../pics/biopsy/denervation/SMA/sma3vvglp.jpg)
VvG stain
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![](../pics/biopsy/denervation/SMA/sma3hemp.jpg)
H & E stain
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Small muscle fibers: Rounded; Grouped
![](../pics/biopsy/denervation/SMA/sma3hehpv.jpg)
H & E stain
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![](../pics/biopsy/denervation/SMA/sma3hehp2v.jpg)
H & E stain
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![](../pics/biopsy/denervation/SMA/sma3gtmp.jpg)
Gomori trichrome stain
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Grouped atrophy: Varied degrees in different fascicles
![](../pics/biopsy/denervation/SMA/sma3vvgmpv.jpg)
VvG stain
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![](../pics/biopsy/denervation/SMA/sma3vvgmp2v.jpg)
VvG stain
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Small muscle fibers: Dark-stained
Large fibers: Irregular internal architecture
![](../pics/biopsy/denervation/SMA/sma3nadh.jpg)
NADH stain
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![](../pics/biopsy/denervation/SMA/sma3atp94.jpg)
ATPase pH 9.4 stain
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Large muscle fibers: Type I predominance
![](../pics/biopsy/denervation/SMA/sma3atp94b.jpg)
ATPase pH 9.4 stain
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Small muscle fibers: Type II predominance
![](../pics/biopsy/denervation/SMA/sma3atp43.jpg)
ATPase pH 4.3 stain
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SMA Type 3, Age 27 years
![](../pics/biopsy/denervation/SMA/sma327help.jpg)
H&E stain
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Regions of grouped atrophy have
Very small muscle fibers & pyknotic nuclear clumps
Increased connective tissue & fat
![](../pics/biopsy/denervation/SMA/sma327hehp.jpg)
H&E stain
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![](../pics/biopsy/denervation/SMA/sma3237gthp.jpg)
Gomori trichrome stain
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Region of grouped muscle fiber atrophy
Very small muscled fibers
Increased connective tissue & fibrils between muscle fibers
![](../pics/biopsy/denervation/SMA/sma327vvghp.jpg)
VvG stain
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![](../pics/biopsy/denervation/SMA/sma327hehp2.jpg)
H&E stain
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Less involved region
Hypertrophic muscle fibers
Small regions of grouped muscle fiber atrophy
Pyknotic nuclear clumps
![](../pics/biopsy/denervation/SMA/sma327vvgmp.jpg)
VvG stain
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![](../pics/biopsy/denervation/SMA/sma327atp43.jpg)
ATPase pH 4.3 stain
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Fiber types
Large fibers: Type I predominance
Small muscle fibers: Many 2C
![](../pics/biopsy/denervation/SMA/sma327atp94b.jpg)
ATPase pH 9.4 stain
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![](../pics/biopsy/denervation/SMA/sma327atp94.jpg)
ATPase pH 9.4 stain
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Small muscle fibers, individually & in region of grouped atrophy stain for esterase
![](../pics/biopsy/denervation/SMA/sma327est.jpg)
Esterase stain
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Also see
Active Denervation
Fiber type grouping
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Hereditary motor syndromes
8/28/2019