Neuromuscular

AMYOTROPHIC LATERAL SCLEROSIS

Muscle
  Grouped atrophy
    Many small groups
    Mixed fiber types in groups
  2C fibers
    Increased numbers vs other denervation
  Internal architecture
    SR
    Glycogen
    Esterase
  Neuromuscular junctions
  ALS course
    Early
    Rapidly progressive
    Slowly progressive
Spinal cord: Historical images
ALS-SOD1: Inclusions


ALS: Common patterns of denervation in muscle

Muscle fibers: Atrophic, Angular & Grouped
  Many small groups of small muscle fibers
  Fibers within & among atrophic groups have similar size
  Larger muscle fibers: Often mildly hypertrophied
  Pyknotic nuclear clumps are uncommon, but may be present

H & E stain


H & E stain

H & E stain

ALS Muscle: Fiber type changes


Grouped atrophy: Groups contain mixed fiber types

ATPase stain. pH 9.4
Atrophic muscle fibers in one group: Often varied types.
Little type grouping: Except in chronic, slowly progressive cases

ATPase stain. pH 9.4

ATPase stain. pH 4.3

ATPase stain. pH 9.4

Type 2C fibers: Many Large & Small

ATPase stain. pH 4.3

ALS Muscle fibers: Internal architecture


NADH stain

Atrophic muscle fibers
  Many stain darkly
  May have targets or targetoid changes
Larger muscle fibers
  Internal architecture may be
    Normal
    Moth-eaten
  Size: Some are mildly hypertrophied

NADH stain

NADH stain

NADH stain

NADH stain

Small muscle fibers: Reduced or absent glycogen

PAS stain

Small muscle fibers: Darker esterase stain

Esterase stain
Neuromuscular Junctions: Dark, compact

Esterase stain

ALS: Intramuscular nerve with loss of myelinated axons

VvG stain

ALS: Early

Muscle Fiber Atrophy

H&E stain
Smaller fibers
  Scattered
  Intermediate-sized
  Polygonal or Angular
  Very small groups
2C muscle fibers
  Common
  Large & small fibers

Gomori trichrome stain

Small Muscle Fibers
  Angular
  Mildly dark stained

NADH stain

Type 2C Muscle Fibers
  Frequent
  Large & Small size

ATPase pH 4.3 stain

Small Angular Muscle Fibers
  Types I (Interrmediate-stained) and II (Dark-stained)

ATPase pH 9.4 stain

ALS, early: Neuromuscular Junctions
  Compact
  Normal staining density

Esterase stain

Esterase stain

ALS: Slowly progressive

  Grouped atrophy: Larger regions
  Fiber type grouping: More common

H& stain
Grouped atrophy: Regions are often larger

H&E stain


NADH stain
Grouped atrophy: Small muscle fibers stain dark
Targets & Targetoid changes

NADH stain

Type grouping of larger fibers
  Groups often include 2C fibers

ATPase pH 4.3 stain

Type grouping of larger fibers
  Grouped atrophy contains both fiber types

ATPase pH 9.4 stain

ALS: Rapidly progressive


H&E stain
Small angular fibers: Grouped
Nuclei: Irregular shapes

Congo red stain

Congo red stain

NADH stain
Small angular fibers: Very small size; Dark stained

NADH stain


PAS stain
Grouped, atrophic muscle fibers: Reduced PAS stain

ATPase pH 9.4 stain
Fiber types: I = Pale; II = Dark; Abnormal = Intermediate stained


ATPase pH 4.3 stain
Fiber types: Frequent 2C fibers, large and small

Motor axon in ALS: Collateral sprouting of terminal axon




ALS spinal cord pathology: Bramwell & Charcot images


From Bramwell: Atlas of Clinical Medicine

Spinal cord: Reduced number of motor neurons in anterior horn

ALS Spinal cord pathology: Original patients of JM Charcot

Case reports:
  English translation from Google books
  Illustrations from original article


Case 1

From: R Baloh

Legend: "Section of the cord of Catherine A. (Case 1), taken from the superior cervical region.
  In a, one can see the rare cells and cell debris in the anterior horns.
  In b, sclerosis of the lateral columns, determined by the atrophy of a large number of axons."



From: R Baloh
Legend: "Symmetric sclerosis of the posterior part of the
  lateral columns in the dorsal region (Case 2)"

Hyaline conglomerate inclusions (HCI)
    in ALS/SOD motor neurons

From A Hays MD

H & E stain

Neurofilament stain

Peripherin stain

Ubiquitin stain
Large HCI inclusions in motor neurons (Arrows)
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3/8/2017