JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-M18

 

Signalment (JPC #3155989): 14 year old female American Quarter horse

 

HISTORY: This horse presented for rigidity in the hindlimbs with no anal/tail tone. Neurologic exam revealed muscle fasciculations of the gluteal muscles, decreased panniculus reflex on the right, pain on lumbo-sacral palpation, decreased rectal tone, and flaccid bladder that was easily expressed with manual pressure. The horse subsequently developed rear-limb ataxia and colic, and was euthanized. On necropsy, the nerves of the cauda equina were markedly thickened and firm with multifocal epidural, leptomeningeal, and perineural hemorrhage. 

 

HISTOPATHOLOGIC DESCRIPTION: Spinal cord, spinal nerve roots (cauda equina), and nerve root ganglia: Diffusely, gray and white matter of the spinal cord, spinal nerve roots (cauda equina), and nerve root ganglia are effaced by marked inflammatory infiltrates composed of numerous epithelioid macrophages and multinucleated giant cells (both foreign body and Langhans type) with up to 50 nuclei, further surrounded by many lymphocytes, plasma cells, and abundant fibrous connective tissue. There are occasional areas with central cellular and karyorrhectic debris that is surrounded by abundant viable and degenerate neutrophils, further surrounded by macrophages, lymphocytes and fibrosis (pyogranuloma). Inflammation is frequently centered on dilated myelin sheaths, either containing swollen axons (spheroids) or gitter cells and axonal debris (ellipsoids). The perineurium and epineurium of peripheral nerves are thickened up to 3-4x normal by fibrous connective tissue (fibrosis). The fibrosis is interspersed with small and medium caliber vessels that are congested with occasional perivascular hemorrhage. Within the nerve root ganglia, neurons are often swollen, with rounded edges and loss of Nissl substance (chromatolysis/neuronal degeneration). Within the spinal cord, the central canal contains a fibrinocellular thrombus characterized by pale eosinophilic fibrillar material (fibrin) with enmeshed previously described inflammatory cells. 

 

MORPHOLOGIC DIAGNOSIS: Spinal cord and cauda equina: Polyradiculoneuritis, ganglioneuritis, and myelitis, lymphohistiocytic, chronic, diffuse, severe, with marked perineurial and epidural fibrosis, central canal thrombosis, hemorrhage, and neuronal and axonal degeneration, American quarter horse, equine.

 

ETIOLOGIC DIAGNOSIS: Idiopathic polyradiculoneuritis

 

CONDITION: Cauda equina syndrome

 

SYNONYMS: Neuritis of the cauda equina; polyneuritis equi

 

GENERAL DISCUSSION:

• Granulomatous, fibrotic, and demyelinating disease of unknown etiology, primarily affecting the sacral and caudal spinal nerve roots (cauda equina) in the horse
• Slowly progressive inflammatory condition
• Occasional involvement of cranial nerves and autonomic nervous system
• Adult females predisposed
• Poor prognosis

 

PATHOGENESIS:

• Unknown; suggestions include:

• Primary immune reaction (lesions resemble those of Guillain-Barré syndrome in humans and experimental allergic neuritis in rats)
• Post-infectious origins: EHV-1, equine adenovirus, Streptococcus and Campylobacter spp. bacteria
• Halicephalobus gingivalis reported as a novel cause in one horse

 

TYPICAL CLINICAL FINDINGS:

• Tail and sphincter paralysis
• Hypotonia, hypoalgesia, and hyporeflexia of the tail, anus, and perineal region; urinary bladder paresis with sabulous cystitis, and fecal retention leading to colic
• Rear limb weakness and ataxia; muscle atrophy
• Occasional cranial nerve involvement: primarily VII, VIII, and less frequently V occur 
• Cerebrospinal fluid analysis: Variable and nonspecific results
• Nonspecific neutrophilic leukocytosis, hyperfibrinogenemia, anemia, and increased total protein

 

TYPICAL GROSS FINDINGS:  

• Extradural segments of sacral and caudal spinal nerve roots (cauda equina) are markedly swollen, thickened, usually discolored by hemorrhage 
• Intradural nerve segments are discolored, but not usually enlarged
• Extension through intervertebral foramina into adjacent muscle

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Acute: hemorrhage and marked inflammation of extradural nerves
• Chronic: granulomatous inflammation with extensive fibrosis; hemorrhage, proliferation of epineural tissue, and inflammatory cell infiltrates; granuloma formation with central epithelioid macrophages and multinucleated giant cells
• Abundant epineural and perineural proliferation of extradural root sheaths, demyelination, secondary axonal degeneration
• Inflammation spares the muscles which exhibit secondary changes of neurogenic atrophy

 

DIFFERENTIAL DIAGNOSIS:  

• Sacral or coccygeal trauma
• Equine herpesvirus type 1 myeloencephalitis
• Equine protozoal myeloencephalitis (N-P01): Necrotizing, nonsuppurative encephalomyelitis; schizonts
• Rhodococcus equi myeloencephalitis (secondary to vertebral osteomyelitis)
• Nematode migration (Strongylus vulgaris; Halicephalobus deletrix)
• Rabies (N-V06): Nonsuppurative polioencephalomyelitis with ganglionitis, Negri bodies 

 

COMPARATIVE PATHOLOGY:

• Dogs: Coonhound paralysis (N-M20)
• Rats: Radiculoneuropathy - degenerative disease of spinal nerve roots (demyelination, dilated myelin sheaths, swollen axons, axonal loss) restricted to white matter, most severe in cauda equina; skeletal muscle atrophy in lumbar region and hindlimbs, posterior weakness, paresis
• Humans: Guillain-Barré syndrome 
• Experimental allergic neuritis (EAN) in rats:  Animal model for Guillain-Barré syndrome; autoimmune disorder thought to be due to both T-cell mediated and humoral immune response to myelin.
• Experimental autoimmune encephalomyelitis (EAE) in NHPs: an animal model used to study human idiopathic inflammatory demyelinating diseases (eg. multiple sclerosis) (Stimmer, Vet Pathol. 2018)

 

References:   

1. Aleman M, Nout-Lomas YS, Reed SM. Disorders of the neurologic system. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine. 4^th ed. St. Louis, MO: Elsevier; 2018: 652-3.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016: 154-155.
3. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol1, 6th ed. St. Louis, MO: Elsevier; 2016:394-395.
4. Constable PD. Hinchcliff KW, Done SH, Grunberg W. Veterinary Medicine. 11th ed. St. Louis, MO: Elsevier; 2017:1369-1370.
5. Stimmer L, Fovet CM, Serguera C. Experimental Models of Autoimmune Demyelinating Diseases in Nonhuman Primates. Vet Pathol. 2018; 55(1):27-41.
6. Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1023.
7. Vandevelde M, Higgins RJ, Oevermann, A. Veterinary Neuropathology. Ames, IA: Wiley-Blackwell; 2012: 78, 90-91.

 

 

 

 

 

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