Neuromuscular

Small Vessel Pathology (Capillaries or Endoneurial Microvessels) 2

Capillaries
  Muscle: Normal
  Endoneurial Microvessels
Capillary pathology
  Microvasculopathy
    C5b-9 Deposits
    HIEM (Nerve)
    Muscle
  Enlargement
    Pipestem
    SRP Myopathy
    TS-HDS neuropathy
  Hemosiderin
  Endoneurial inflammation
    Ipilimumab
    Perineuritis
  Loss
    DM-VP
    GvHD
  Systemic Sclerosis
    Minimal myopathy
      Ultrastructure
    Myopathy + Capillary Δ
  Subperineurial edema
  Thick vessel walls
ELS vessels
Endomysial Capillary: Normal

ENDOMYSIAL CAPILLARIES: NORMAL

Capillary: Normal
  Endothelial cell = E: Inside basal lamina
  Pericyte = P: Within basal lamina

Capillary Structure

Basement membrane
  Around & outside endothelial cell layer
  May be homogeneous or layered
  Contains pericytes (P)
  Composition
    Collagen IV
    Laminin
    Glycoproteins: Fibronectin, Nidogen-1, Nidogen-2 (Entactin)
    Proteoglycans (as HSPG): Perlecan, Agrin
  Thickening: Differential diagnosis
Endothelial cells (E)
  Surround lumen
  Stains: Ulex Europaeus Agglutinin I (UEAI); CD31
Pericytes (P)
  Location: Within basal lamina of vessel wall
  Contractile
  Frequency vs Endothelial cells: 1:10 to 1:100
  Stain: PDGRFβ
Smooth muscle
  Stain: Smooth muscle actin

Muscle Capillaries: Features

Anatomy Plasticity

Endomysial Capillaries: Normal


UEA I stain
Endomysial capillaries: Normal
  Normal number: Every muscle fiber has at least one adjacent capillary
  Orientation: Run parallel to muscle fiber length; Cut in cross-section

UEA I stain
All muscle fibers have at least one adjacent capillary

UEA I stain

There are few or no capillaries immediately adjacent to the perimysium

UEA I stain

Endomysial Capillaries: Reduced numbers

Some muscle fibers have no adjacent capillary

UEA I stain

Endomysial Capillaries: Partial Denervation


UEA I stain
Endomysial capillaries
  Orientation: May be circumferential around muscle fibers (Above); Cut in cross-section
  Number: Every muscle fiber has several adjacent capillaries

UEA I stain

Endomysial Capillaries: Dermatomyositis with Vascular pathology (DM-VP)

Endomysial capillaries
  Orientation: Normal
  Number: Reduced or absent Endothelium (Ulex stain) in regions with small muscle fibers (Arrow)
    Endothelium is lost but basal lamina is still present
      & may have C5b-9 deposition
  Size: Increased in regions neighboring muscle fiber atrophy

UEA I stain

Endomysial Capillaries: Enlarged


UEA I stain

UEA I stain
Patient history: Cardiac failure & Interstitial lung disease

NERVE: Endoneurial Microvessels


H&E stain
Endoneurial Microvessel (Arrow)
  Orientation: Along length of nerve


Toluidine blue stain

Endoneurial Microvessel

Endomysial & Endoneurial Capillaries: Thickened Walls


Ultrastructure: From Robert E Schmidt MD


Ultrastructure: From Robert E Schmidt MD
Diabetes
Endoneurial vessel in Nerve
Basal lamina: Multiple layers
Non-diagnostic muscle
Endomysial vessel in Muscle
Thickened wall: Homogeneous


From: Chunyu Cai

Basal lamina of Endoneurial microvessels
  Thickened; Homogeneous (Arrows)
Basal lamina of Endoneurial microvessel
  Normal (Arrow)

Capillaries: Walls have varied thickness
Capillaries with homogeneous thick walls

Humoral Immune Endoneurial Microvasculopathy (HIEM) 28

Microvessels
  C5b-9 deposition on Microvessels
  C5b-9 around Endotheial cells
  Endoneurial Microvascular Endothelial cells: Large
Nerve
  Histology
  Axon loss
    Varied: Toluidine blue
    Large > Small

Associated Clinical Syndrome

C5b-9 stain
HIEM Nerve
C5b-9 Stains Most Endoneurial Microvessels
Disease Control Nerve
C5b-9 Stains Perineurium & Epineurial vessels but not Endoneurial microvessels

C5b-9 stain

HIEM Nerve
C5b-9 Stains Endoneurial Microvessels

C5b-9 stain


C5b-9 stain

Endoneurial Microvasculopathy
  HIEM: C5b-9 stains Endoneurial microvessels

C5b-9 stain
Disease Control Nerve
  C5b-9 does not stain Endoneurial microvessels

C5b-9 stain


C5b-9 (Green) + UEAI (Red) stain
HIEM: C5b-9 stain (Green) around Endoneurial Microvessel endothelium (Red)

C5b-9 (Green) + UEAI (Red) stain

C5b-9 (Green) + UEAI (Red) stain


Toluidine blue stain
Endoneurial Microvessel Pathology
  Vessel size: Normal or Large
  Vessel wall: Thick
  Endothelial cells: Large
  Basal lamina: Multi-layered

Toluidine blue stain

Endothelial cells in HIEM Microvessels: Multiple, Large

Toluidine blue stain   From R Schmidt

HIEM: Nerve anatomic pathology

H&E stain
HIEM nerve: No lymphocytic inflammation


VvG stain
HIEM: Differential fascicular involvement
  Myelinated axon loss: Varied (Above)
  Endoneurial ATPase stain: Varied (Below)

ATPase pH 4.3 stain


Toluidine blue stain
HIEM sural nerve
  Moderate loss of large & small myelinated axons
  Regeneration: Clusters of small myelinated axons
  Endoneurial microvessels
    Basal lamina: Thick
    Endothelial cells: Large

Toluidine blue stain


Toluidine blue stain
HIEM sural nerve
  Large & small myelinated axons: Severe loss (Above)
  Small unmyelinated axons: Relatively preserved (Below)

Neurofilament stain

Control sural nerve
  Large & Small axons are present

Neurofilament stain

Muscle: Endomysial Capillary Vasculopathy

Muscle: C5b-9 Deposits
  On Endomysial capillaries
Microvasculopathy
Control Muscle
Microvasculopathy: C5b-9 Deposits on many endomysial capillaries

Go to Moderate & large vessel vasculitis
Return to Neuromuscular Home Page
Return to Vasculitis

References
1. Acta Neuropathol 2000;100:445-450
2. Am J Physiol Heart Circ Physiol 2016 Jul 1

6/27/2021