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
  Nerves
    Intramuscular
    Sciatic
    Terminal
  ALS course
    Early
    Rapidly progressive
    Slowly progressive
    Late
Spinal cord
  Historical images

ALS-HTT
ALS-SOD1
  Muscle
  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 atrophy: Features in ALS
    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
    Number: Many small groups of small muscle fibers
  Larger muscle fibers: Often mildly hypertrophied

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


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: 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: 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

NCAM stain


Acid phosphatase stain
Acid phosphatase positive cells: Scattered in the endoneurium


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."



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

ALS: SOD1

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)

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: HTT

Spinal Cord: Histiocyte (CD163) stain

From: R Bucelli; R Schmidt

Lateral corticospinal tract: Histiocyte (CD163) stain

From: R Bucelli; R Schmidt

TDP43 aggregates

From: R Bucelli; R Schmidt

HTT (PolyQ) aggregates
  Not in nuclei; Motor cortex

From: R Bucelli; R Hickman (Columbia, NY)
p62 aggregates
  Intranuclear; Hippocampus

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6/24/2021