Denervation: ALS

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
Late
ALS-SOD1
Nerves
Intramuscular
Sciatic
Terminal
Spinal cord
Historical images

ALS-HTT
ALS-SOD1
Neuron Inclusions

ALS Muscle: Denervation, Reinnervation &
Atrophy of some Reinnervated Muscle fibers

ALS: Common patterns of denervation in muscle

H & E stain

Small Muscle fibers: Atrophic, Angular & Grouped
Grouped muscle fiber atrophy: Features in ALS
Number: Many small regions of grouped atrophy
Muscle fibers in regions of grouped atrophy
Small
Angular
Similar size
Fiber types: Mixed
Often contain: Targets
Pyknotic nuclear clumps: Uncommon
Grouped atrophy size: Small; < 20 muscle fibers
Larger muscle fibers
Size: Often mildly hypertrophied
Shape: Rounded/Polygonal

H & E stain

ALS Muscle: Fiber type changes

ATPase stain. pH 9.4

Grouped atrophy: Groups of small fibers contain mixed fiber types

ATPase stain. pH 9.4

ATPase stain. pH 9.4

ATPase stain. pH 4.3

Atrophic muscle fibers in individual groups: Often varied types.
Little type grouping: Except in chronic, slowly progressive cases

Type 2C fibers: Many Large & Small

ATPase stain. pH 4.3

ALS Muscle: Fiber Types

Type 1 fibers: Normal
ATPase: Intermediate color at pH 9.4 & Dark at pH 4.6 & 4.3
All have MYH7, but not MYH2 or MYH1
Type 2 fibers: Variant
All have MYH2 & moderate MYH7
Type 2A fibers
All have MYH2 & Moderate MYH7, but no MYH1
ATPase: Dark at pH 9.4; Pale at pH 4.6 & 4.3
Type 2B fibers
All have MYH2 & Moderate MYH7 & MYH1
ATPase: Dark at pH 9.4; Intermediate at 4.6; Pale at pH 4.3
Type 2C fibers
All have MYH2 & MYH7, but no MYH1
ATPase: Moderately Dark at pH 9.4 & 4.6; Internediate at 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

ALS Muscle: Targets & targetoid structures on many smaller (dark) muscle fibers

NADH stain

Small muscle fibers: Reduced or absent glycogen

PAS stain

Small muscle fibers: Darker on esterase stain

Esterase stain

Esterase stain

ALS: Neuromuscular Junctions
Dark
Compact or multisegmented
May remain on small muscle fibers

Esterase 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

ALS: Late

H&E stain

Grouped Atrophy
Many small and moderate-sized regions with clusters of pyknotic nuclear clumps & very small muscle fibers

H&E stain

Grouped Atrophy, Confluent
Large clusters of pyknotic nuclear clumps & very small muscle fibers

VvG stain

Esterase stain

Small Angular Muscle Fibers
Dark on esterase & NADH stains

NADH stain

ALS SOD1: Muscle

H & E stain

Grouped atrophy: Small regions

H & E stain

Congo red stain

Grouped atrophy: Targets or Targetoid canges in Small fibers

NADH stain

ATPase pH 9.4 stain

Some clusters of small fibers have mixed fiber type

ATPase pH 4.3 stain

Many type 2C fibers

VvG stain stain

Artery: Reduced numbers of fibrils; Increased connective tissue inside the fibril layer

ALS: Intramuscular nerves

VvG stain

ALS: Intramuscular nerves
Loss of myelinated axons, moderate
Nodes of Ranvier: May be widened (Arrows)

VvG stain

Neurofilament stain

ALS: Intramuscular nerves
Abnormal branches & sprouts from intramuscular axons (Arrows)

ALS: Sciatic Nerve

Control Nerve

Neurofilament stain

Neurofilament stain

Myelinated Axons: Moderate loss
Varied among fascicles

Neurofilament stain

H&E stain

Myelinated Axons: Moderate loss

Gomori trichrome stain

Gomori trichrome stain

VvG stain

Myelinated Axons: Moderate loss
Varied among fascicles

VvG stain

ALS Nerve: Non-myelinating Schwann cells
Control

NCAM stain

Non-myelinating Schwann cells: Normally clustered
Myelin: Scattered myelin sheaths with abnormal NCAM staining (Arrow)

NCAM stain

Acid phosphatase stain

Histiocytes: Acid phosphatase positive cells
Scattered in the endoneurium
Some neighbor myelin sheaths (Arrow)

Alkaline phosphatase stain

Endoneurial Microvessels: Normal numbers

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."