Neuromuscular

SPINAL MUSCULAR ATROPHY (5q)

SMA: General pathology
SMA, Congenital (Type 0)
SMA, Type 1
SMA, Type 2
SMA, Type 3
  Age 2 years
  Age 6 years
  Age 27 years

Also see
  Spinal muscular atrophy
H&E stain
  XBSMA pathology


SMA: Mechanisms Underlying Pathology


SMA 5q: General Features


H&E stain
Grouped atrophy
  Small muscle fibers: Often rounded
  Pyknotic nuclear clumps: None
Large muscle fibers: Hypertrophy

VvG stain

Gomori trichrome stain
Larger muscle fibers
  Hypertrophied
  Commonly type I
  Clustered

Smaller muscle fibers
  Round
  Commonly type II,
    May also be I or IIC
  Clustered


ATPase pH 9.4 stain

ATPase pH 4.3 stain


SMA, Congenital (Type 0)


H & E

H & E
Only small muscle fibers are present.
Small fibers have moderate variation in size.


VvG

SMA0: Fiber type properties

Many small fibers are Type 2C. (Intermediate stained at ATPase pH 4.3)

ATPase pH 4.3

Most muscle fibers are dark (Like type 2) on ATPase pH 9.4

ATPase pH 9.4

Most muscle fibers are intermediate stained (Like type 2C) on ATPase pH 4.3

ATPase pH 4.3

Muscle fibers are variably intermediate stained (Like type 2B) on ATPase pH 4.6
  There are no 2A muscle fibers

ATPase pH 4.6


COX
Mitochondrial stains are pale

SDH

SMA, Type 1


H & E

H & E
Many muscle fibers are small.
A few hypertrophied fibers are present

NADH

Some large & small muscle fibers have reduced or absent glycogen

PAS

SMA Type 2, Age 9 months


H&E stain
Large groups of atrophic muscle fibers

H&E stain

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)

H&E stain


Esterase

Esterase
Neuromuscular junctions on large (Left) and small (Right) muscle fibers.


VvG

Intramuscular nerves: Unremarkable


Toluidine blue
Sensory nerve
  Normal numbers of axons
  Thinly myelinated axons consistent with young age.

VvG


NADH

NADH
Small muscle fibers stain darkly on NADH

SMA 2: Fiber type properties


ATPase, pH 9.4

ATPase, pH 9.4

ATPase, pH 4.3
Small muscle fibers: May be varied types (Left) or mostly type II (Middle)
Large muscle fibers: Clustered; Type I or Abnormal intermediate staining
Many small fibers are type 2C

ATPase, pH 4.3

Incomplete Fiber Type Switching (Abnormal fiber types): ATPase doesn't entirely correspond to COX & PAS

ATPase, pH 9.4
Large muscle fibers: Mostly type I (Intermediate staining)
Small muscle fibers: Mostly type II (Dark staining)


ATPase, pH 4.3
Large muscle fibers: Mostly type I (Dark staining)
Small muscle fibers (Bottom left): Many type IIC (Varied degrees of intermediate staining)


ATPase, pH 4.6
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)


Cytochrome oxidase
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


PAS
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


H & E
Grouped atrophy.
Larger muscle fibers are not promiently hypertrophied.


ATPase pH 9.4

NADH
Variable involvement of fascicles.
  Top: Scattered small fibers. Large fibers are type 1.
  Bottom: Few small fibers. Type 2 predominance.
        Abnormal intermediate-staining fibers.
Variable involvement of fascicles.
  Top: Scattered small fibers. Most fibers are dark-stained.
  Bottom: Few small fibers. Most fibers are pale-stained.



VvG
Grouped atrophy.
Larger muscle fibers: Not promiently hypertrophied.
Intramuscular nerves: Mildly reduced axon numbers.


Esterase
Neuromuscular junctions.
Present on large and small muscle fibers.
Shape: Large; Increased extent around muscle fibers; Not multi-segmented.

SMA Type 3, Age 6 years

Same patient as above

H & E stain
Grouped atrophy: Variable among fascicles
Large muscle fibers: Hypertrophied


VvG stain


H & E stain
Small muscle fibers: Rounded; Grouped

H & E stain

H & E stain

Gomori trichrome stain
Grouped atrophy: Varied degrees in different fascicles

VvG stain

VvG stain

Small muscle fibers: Dark-stained
Large fibers: Irregular internal architecture


NADH stain


ATPase pH 9.4 stain
Large muscle fibers: Type I predominance

ATPase pH 9.4 stain

Small muscle fibers: Type II predominance

ATPase pH 4.3 stain

SMA Type 3, Age 27 years


H&E stain
Regions of grouped atrophy have
  Very small muscle fibers & pyknotic nuclear clumps
  Increased connective tissue & fat

H&E stain


Gomori trichrome stain
Region of grouped muscle fiber atrophy
  Very small muscled fibers
  Increased connective tissue & fibrils between muscle fibers

VvG stain


H&E stain
Less involved region
  Hypertrophic muscle fibers
  Small regions of grouped muscle fiber atrophy
  Pyknotic nuclear clumps

VvG stain


ATPase pH 4.3 stain
Fiber types
  Large fibers: Type I predominance
  Small muscle fibers: Many 2C

ATPase pH 9.4 stain

ATPase pH 9.4 stain

Small muscle fibers, individually & in region of grouped atrophy stain for esterase

Esterase stain

Also see
  Active Denervation
  Fiber type grouping


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3/6/2017