JPC SYSTEMIC PATHOLOGY

Nervous System

January 2023

N-M03

 

Signalment (JPC #4048842): 5-year-old, 9.3 kg, tricolor, female, intact Beagle mix (Canis familiaris)

 

HISTORY: The patient presented to the Neurology Service with a 3-week history of peracute onset paraplegia. There was no known trauma and no therapy was undertaken. At the time of presentation, the dog was paraplegic with pain sensation and severe extensor rigidity of the hind limbs. She had an MRI performed, which showed a locally extensive intramedullary myelopathy from the level of L2 extending caudally. There was minimal to no contrast enhancement with T2 hyperintensity of the gray matter (irregularly shaped and undulating) from L2 to the conus medullaris. Due to poor prognosis for return to function, the owner elected euthanasia.

 

HISTOPATHOLOGIC DESCRIPTION: Spinal cord, lumbar: Multifocally affecting 75% of the grey matter of the ventral and dorsal horns, there are well-demarcated areas of liquefactive necrosis characterized by cavitation and loss of normal architecture (infarction) with replacement by cellular debris, increased clear space (edema), and numerous foamy macrophages (gitter cells). Multifocally within the necrotic foci and adjacent grey/white matter and leptomeninges are small to medium-sized vessels that are variably occluded by pale amphophilic hyaline material (fibrocartilaginous emboli). Adjacent to necrotic foci there are increased numbers of glial cell (gliosis); elongate microglial cells (rod cells); astrocytes with plump nuclei and swollen eosinophilic cytoplasm (gemistocytes); occasional swollen neurons (degeneration) with central dispersion of Nissl substance and peripheralized nuclei (central chromatolysis); and vacuolation of the neuroparenchyma (spongiosis). Multifocally within the white matter are dilated myelin sheaths (Wallerian degeneration) that often either contain swollen, homogenous eosinophilic axons (spheroids) or have loss of axons with replacement by necrotic debris or gitter cells (ellipsoids/digestion chambers). Ventral spinal nerves are multifocally characterized by myelin sheath dilation (Wallerian degeneration) often with swollen axons (spheroids), as well as hypercellularity due to Schwann cell proliferation (Büngner’s bands), and scattered lymphocytes, macrophages and plasma cells.

 

MORPHOLOGICAL DIAGNOSES: 

1.  Spinal cord, lumbar: Poliomyelomalacia (infarction), multifocal, subacute, severe, with Wallerian degeneration and intravascular fibrocartilaginous emboli, Beagle mix, canine.

2. Spinal nerves, lumbar: Wallerian degeneration, multifocal, subacute, moderate, with Schwann cell proliferation (Büngner’s bands) and mild multifocal lymphoplasmacytic neuritis.

 

ETIOLOGIC DIAGNOSIS: Embolic (ischemic) myelopathy (due to fibrocartilaginous embolism)

 

GENERAL DISCUSSION:  

 

PATHOGENESIS:  

• Fibrocartilagenous embolism of spinal cord vasculature (most commonly ventral spinal artery, vein, and their tributaries) à infarction of spinal cord à posterior paresis or paralysis 
• Mechanism of emboli formation unclear, but these emboli typically overly degenerated intervertebral disks (i.e. herniation of fibrocartilage from the disk); the fibrocartilage is identical to that of the nucleus pulposus
• Theories: (1) direct penetration of nucleus pulposus fragments into damaged veins, venous plexuses, or small arterioles in the area during traumatic events; (2) herniation of the nucleus pulposus into the vertebral body medullary sinusoidal channels with retrograde entrance into the vertebral venous plexus; (3) neovascularization of degenerated disks with chronic inflammation or Schmorl’s bodies (masses of fibrocartilage in vertebrae)

 

TYPICAL CLINICAL FINDINGS:

• Typically middle aged (average age 5 years old), large to giant breed dogs or young Irish wolfhounds
• Sudden onset of spinal cord deficits (e.g. hindlimb paresis) +/- cerebral involvement 
• 60% of cases have history of trauma or exercise associated with event 

 

TYPICAL GROSS FINDINGS:

• Depending on size of the lesion, may see nothing grossly
• Acute focal infarct – red-yellow-brown region of necrosis within the spinal cord 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Intravascular fibrocartilage emboli, completely or partially occluding the vessel
• Acute ischemic necrosis of neurons and oligodenroglia – shrunken, hypereosinophilic cytoplasm, pyknotic nuclei; sharply demarcated zones of pallor; swollen axons; prominent capillaries
• Chronic lesions have neovascularization at periphery with microgliosis and later astrogliosis 

 

ADDITIONAL DIAGNOSTIC TESTS:

• Clinical diagnostics: Myelogram to determine spinal cord swelling, MRI
• Histochemical stains to highlight emboli: Masson’s trichrome, Alcian blue, PAS 

 

DIFFERENTIAL DIAGNOSIS: 

• Cerbrospinal thrombosis or embolism – fibrocartilage (nucleus puposus), bacterial/septic, fat (originating from trauma to bones, soft tissues, or lipid-laden hepatocytes) 
• Rapid paresis/paralysis: IVDD, vertebral/spinal cord trauma 

 

COMPARATIVE PATHOLOGY:  

• Reported in all domestic species, most notably dogs and pigs 
• Swine – 

• Recent case report (J Comp Pathol 2020) of cerebral fibrocartilaginous emboli in neuroparenchymal vessels causing severe multifocal bilateral necrotizing encephalopathy in the midbrain; origin of the embolic material was not found  
• Recent paper (Vet Pathol 2022) found that intervertebral instability due to minor congenital malformations in the vertebral articular facets are suspected to contribute to a high incidence of FCE in finishing pigs

• African hedgehogs – associated with intervertebral disk disease 

 

REFERENCES:

2. Cantile C, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:299, 334.

1. Gal A, Castillo-Alcala F. Cardiovascular system, pericardial cavity, and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby Elsevier; 2022:695.
2. Lin CM, Oglesbee M, Knudsen D, et al. Ischemic myelomalacia and closed spinal dysraphism in multiple finishing swine. Vet Pathol. 2022;online ahead of print. 
3. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby Elsevier; 2022:942-943.
4. Vidana B, Floyd T, Murphy A, et al. Fibrocartilagenous embolic encephalopathy in a pig. J Comp Pathol. 2020;181:58-62. 

 

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