JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
February 2023
N-P11
Signalment (JPC# 4068726): Adult, thoroughbred gelding (Equus caballus)
HISTORY: A mature racehorse started to develop neurologic signs. When presented to the veterinarian, the horse showed severe ataxia and incoordination. The horse was also colliding with the box walls and displayed head pressing behavior. No significant changes were identified on hemogram or serum biochemistry. Blood collected for Flavivirus ELISA testing was negative. After unsuccessful treatment with dexamethasone and DMSO, the horse was humanely euthanized.
HISTOPATHOLOGIC DESCRIPTION: Cerebellum: Multifocally infiltrating the white matter and, to a lesser extent, gray matter are perivascular aggregates of inflammatory cells composed of many epithelioid macrophages, multinucleated giant cells (Langhans and foreign body types), and fewer lymphocytes and plasma cells that often surround and expand Virchow-Robin spaces and are admixed with eosinophilic cellular and karyorrhectic debris with loss or architecture and rarefaction of the neuropil (liquefactive necrosis). Within and adjacent to inflammatory foci are multiple cross and tangential sections of larval and few adult female rhabditid nematodes and embryonated eggs. Adults are 15-20µm in diamer with a thin, 1µm smooth eosinophilic cuticle, platymyarian-meromyarian musculature, a rhabditiform esophagus composed of a corpus, isthmus, and bulb, an intestinal tract lined by uninucleate, low cuboidal cells, and a single genital tract. Larva are 6-10µm in diameter with a rhabditiform esophagus and tapered tail. Eggs are ovoid, 10-15µm and embryonated. Adjacent white matter is vacuolated (spongiosis) with dilated myelin sheaths that contain swollen, eosinophilic axons (spheroids).
MORPHOLOGIC DIAGNOSIS: Cerebellum: Encephalitis, granulomatous and necrotizing, multifocal, perivascular, moderate, with numerous rhabditid nematode adults, larvae, and eggs, thoroughbred, Equus caballus.
ETIOLOGIC DIAGNOSIS: Encephalitic nematodiasis
CAUSE: Halicephalobus gingivalis (formerly known as: Micronema deletrix)
GENERAL DISCUSSION:
- Free-living rhabditiform nematode of soil and decaying organic matter
- “Accidental” (facultative) parasite causing disease in horse
PATHOGENESIS:
- Pathogenesis, life cycle, and route of infection are poorly understood; hypothesized to be ingestion, wound contamination, or direct penetration of skin and mucous membranes, followed by hematogenous distribution or transmission from infected dam to foal
- Females are parthenogenic in tissue (no males present)
TYPICAL CLINICAL FINDINGS:
- Blindness, abnormal mentation, anterior uveitis, and other signs or clinical pathology abnormalities related to the affected organ and extent of dissemination
TYPICAL GROSS FINDINGS:
- Granulomatous tan-white multifocal to diffuse lesions in the CNS, kidneys, mandibular gingiva, nasal cavity, bones, skin, mammary glands, eyes, testes, adrenal glands, liver, and/or other organs
- Anterior uveitis
- Focal arachnoid hemorrhages and patchy meningeal thickening
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Perivascular granulomatous and eosinophilic meningoencephalitis, myelitis, polyradiculitis, and/or caudal equina neuritis with numerous life stages of rhabditiform nematodes, necrosis, vasculitis, and gitter cells
- Adult females: 13-20 µm diameter; thin eosinophilic smooth cuticle; tapered, pointed tail; platymyarian musculature; rhabditiform esophagus composed of a corpus, isthmus, and bulb; single genital tube with a dorsoventrally reflected (dorsoflexed) ovary and ventroflexed uterus
- Larvae: 6-10 µm diameter; rhabditiform esophagus (characteristic); tapered, pointed tail
- Eggs: 10x35 µm; embryonated; ovoid
- +/- parasitic granulomas and granulomatous inflammation in the gingiva, kidney, eye (uvea, optic nerve, lens), other organs; normal tissue architecture may be replaced by dense collagen and fibroblasts with infiltration of tissue by lymphocytes, plasma cells, epithelioid macrophages, multinucleated giant cells, eosinophils, and nematodes/eggs
ADDITIONAL DIAGNOSTIC TESTS:
- Nematode has been recovered from semen, CSF, urine, and aqueous and vitreous humor of horses
DIFFERENTIAL DIAGNOSIS:
- Eosinophilic encephalitides – fungal or other parasites, including Sarcocystis neurona, Neospora hughesi, and Angiostrongylus catonensis; diagnosis is often presumptive due to organisms being not present in histologic section, but can be confirmed via rt-PCR (Zoll et al, JVDI 2018)
- Histomorphology of the nematode, specifically the unique reproductive tract, differentiates H. gingivalis from other metazoan encephalitides
COMPARATIVE PATHOLOGY:
- Grevy’s zebra: reported in a blind, abnormally behaving female with bilateral uveitis and anemia; found disseminated granulomatous inflammation with rhabditiform nematodes within the eyes, heart, kidney, uterus, lymph nodes
- Rarely seen in cattle and humans
References:
- 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, Inc; 2016:390.
- Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier, Inc; 2016:443-444.
- Craig LE, Dittmer KE, Thompson KG. Bone and Joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier, Inc; 2016:98.
- Duncan M. Perissodactyls. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press: 2018: 450.
- Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier, Inc; 2016:487.
- Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:963.
- Pillai VV, Mudd LJ, Sola MF. Disseminated Halicephalobus gingivalis infection in a horse. J Vet Diagn Invest. 2022; online ahead of print.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier, Inc; 2016:19.
- Zoll WM, Prakoso D, Dark M, Stockdale-Walden H, Long MT. Histologic characterization of eosinophilic encephalitis in horses in Florida. J Vet Diagn Invest. 2018;30(3):442-446.