AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

March 2017

N-P11

 

Signalment (JPC 1857020):  A horse

 

HISTORY:  This horse developed ataxia and head pressing.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebellum:  Multifocally, primarily within the white matter and less frequently in the granular and molecular layers, generally centered on blood vessels, there are areas of loss of neural architecture (necrosis) and replacement by eosinophilic cellular and karyorrhectic debris, foamy gitter cells, and astrocytes with prominent eosinophilic cytoplasm and an eccentric nucleus (gemistocytes).  Moderate numbers of macrophages, lymphocytes, plasma cells, eosinophils, and fewer neutrophils and multinucleated giant cells (Langhans and foreign-body type) expand Virchow-Robin spaces of adjacent blood vessels as well as the leptomeninges.  Blood vessels are often lined by reactive endothelium.  Affected areas of the white matter are often bounded by many dilated myelin sheaths and swollen, degenerate eosinophilic axons (spheroids).  Within the affected areas, there are numerous tangential and cross sections of larval and adult rhabditid nematodes. Adults are 15-25 um in diameter with a smooth cuticle, platymyarian-meromyarian musculature, a rhabditiform esophagus with terminal bulb, and numerous deeply basophilic 2-3 um internal structures within the pseudocoelom.  Developing larvae are approximately 10um in diameter with a similar rhabditiform esophagus and tapered tail and are occasionally found within egg shells.  Multifocally, the meninges are mildly congested.

 

MORPHOLOGIC DIAGNOSIS:  Cerebellum:  Meningoencephalitis, granulomatous, eosinophilic, and necrotizing, multifocal, moderate, with few adult and rare larval rhabditid nematodes, etiology consistent with Halicephalobus gingivalis, breed not specified, equine.

 

ETIOLOGIC DIAGNOSIS:  Encephalitic nematodiasis

 

SYNONYMS:  H. deletrix, Micronema deletrix, Rhabditis gingivalis, Tricephalobus gingivalis, Trilabiatus gingivalis

 

CAUSE:  Halicephalobus gingivalis

 

GENERAL DISCUSSION:

·         Free-living nematodes (order Rhabditata) of soil and decaying organic matter

·         “Accidental” (facultative) parasite causing disease in man and horses

·         In the horse, causes granulomatous and eosinophilic meningoencephalitis, myelitis, polyradiculitis, and one case of cauda equine neuritis 

·         In tissues, only female adults, larvae, and eggs identified (no males)

·         Granulomas in the nasal cavity, kidney, prepuce, gingiva, and testicle may also occur

·         Rare cause of osteomyelitis in horse

 

PATHOGENESIS:

·         Pathogenesis, life cycle, and route of infection are poorly understood

·         Life cycle thought to be asexual with parthenogenetic females; hypothesized sexual cycle with free-living male and female worms

·         Likely involves entrance through contaminated wounds, via ingestion, or inhalation, with hematogenous dissemination

·         Nematode thought to access the brain via migration along vessels; continued migration within the brain causes necrosis and inflammation

 

TYPICAL CLINICAL FINDINGS:

·         Lethargy, loss of condition, hyperesthesia, opisthotonos, nystagmus, ataxia, progressive neurologic signs, recumbency, multiorgan dysfunction

·         Abnormal clinical pathology values and clinical tests depending on organs affected and extent of disseminated lesions

·         Hyperglobulinemia, hyperfibrinogenemia (chronic inflammation); elevated creatine kinase (muscle injury from parasites, trauma, or recumbency); elevated creatinine (postrenal obstruction due to lower motor neuron disease if cauda equina neuritis)

 

TYPICAL GROSS FINDINGS:

·         Most commonly affected organs in horses:  Brain, kidneys, lymph nodes, spinal cord, adrenal glands, oral and nasal cavities; less commonly heart, stomach, liver, ganglia, bones

·         Multifocal to diffuse, proliferative, firm, gray-white, granulomatous lesions in the brain or spinal cord; thickening and opacity of the leptomeninges; parenchymal hemorrhage and malacia

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

·         Perivascular granulomatous and eosinophilic inflammation with numerous adult and larval parasites; necrosis, vasculitis, and hemorrhage

·         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 adult and larval nematodes

·         Adult females:  15-20 um diameter; 250-430 um length; thin, smooth cuticle; tapered, pointed tail; platymyarian-meromyarian musculature; pseudocoelom; rhabditiform esophagus composed of a corpus, isthmus, and bulb; intestinal tract lined by uninucleate, low cuboidal cells; single genital tube with a dorsoflexed ovary and a ventroflexed uterus at the vulva

·         Larvae:  10 um diameter; rhabditiform esophagus (characteristic); tapered, pointed tail

·         Eggs:  15x35 um; embryonated; ovoid

 

ADDITIONAL DIAGNOSTIC TESTS: 

·         Cerebrospinal fluid (CSF) pleocytosis (erythrocytes and leukocytes) and elevated protein level; possibly parasites in CSF sample

·         Nematode has been recovered from semen and urine of horses

 

DIFFERENTIAL DIAGNOSIS: 

·         Histomorphology of the nematode, specifically the unique reproductive tract, differentiates H. gingivalis from other metazoan encephalitides (e.g. Hypoderma bovis, Hypoderma lineatum, Parastrongylus (Angiostrongylus) cantonensis, Setaria sp., Strongylus vulgaris, and Draschia megastoma

 

COMPARATIVE PATHOLOGY:

Parasitic migration through the CNS in other species:

·         Nematodes:

o   H. gingivalis disseminated disease reported in a Grevy’s zebra (Equus grevyi)

o   Parastrongylus (Angiostrongylus)cantonensis:  Rat metastrongylid (lungworm) with occasional aberrant CNS migration in humans, dogs, horses, and macropods; granulomas most numerous and severe in spinal cord

o   Parelaphostrongylus tenuis: Cervid (white-tailed deer, Odocoileus virginianus) metastrongylid with aberrant CNS migration in wild ungulates(red deer, elk, moose) and sheep

o   Elaphostrongylus panticola, E. rangifera:  Similar to P. tenuis, affects deer in northern Europe and Russia

o   Elaeophora schneideri:  Filarid, develops in leptomeningeal arteries of cervids, sheep, and goats; may cause ischemic necrosis in brain

o   Setaria digitata:  Filarid; adults found in peritoneal cavity of cattle and buffalo in Asia; aberrant CNS migration of larvae in horses, camels, sheep and goats (disease name “kumri”)

o   Others: Gurltia paralysans (spinal veins of cats); Angiostrongylus vasorum (hemorrhagic malacia in brains of dogs); ascarids (e.g. Baylisascaris procyonis (raccoon ascarid) or B. columnaris (skunk ascarid)); Stephanurus dentatus (invasion or spinal canal, meningeal cysts in pigs); Strongylus sp. (horses)

·         Arthropods:  Oestrus ovis in sheep, Hypodermis bovis in cattle, Cuterebra sp. in dog and cat

·         Cestodes:  Coenuris cerebralis (Taenia multiceps) (definitive hosts are carnivores; intermediate hosts are sheep and other ruminants); Cysticercus cellulosae (Taenia solium) in pigs, dogs, and humans; Cysticercus bovis (Taenia saginata)

·         Trematodes:  Troglotrema acutum (may invade brain from paranasal sinuses); Paragonimus sp. (have been reported in brains of dogs, possibly via embolization)

 

References:

1.     Anderson RC, Linder KE, Peregrine AS. Halicephalobus gingivalis (Stefanski, 1954) from a fatal infection in a horse in Ontario, Canada with comments. Parasite. 1998;5:255-261.

2.     Bryant UK, Lyons ET, Bain FT, Hong CB. Halicephalobus gingivalis-associated meningoencephalitis in a thoroughbred foal. J Vet Diagn Invest. 2006;18(6):612-615.

3.     Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:390.

4.     Dunn DG, Gardiner CH, Dralle KR, Thilsted JP. Nodular granulomatous posthitis caused by Halicephalobus (syn. Micronema) sp. in a horse. Vet Pathol. 1993;30(2):207-208.

5.     Foster RA, Ladds PW. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 5th ed. Philadelphia, PA: Elsevier; 2007:587.

6.     Isaza R, Schiller CA, Stover J, Smith PJ, Greiner EC. Halicephalobus gingivalis (Nematoda) infection in a Grevy’s zebra (Equus grevyi). J Zoo Wildl Med. 2000;31(1):77-81.

7.     Johnson JS, Hibler CP, Tillotson KM, Mason GL. Radiculomeningomyelitis due to Halicephalobus gingivalis in a horse. Vet Pathol. 2001;38(5):559-561.

8.     Kinde H, Mathews M, Ash L, St. Leger J. Halicephalobus gingivalis (H. deletrix) infection in two horses in southern California. J Vet Diagn Invest 2000;12:162-165.   

9.     Muller S, Grzybowski M, Sager H, Bornand V, Brehm W. A nodular granulomatous posthitis caused by Halicephalobus sp. in a horse. Vet Dermatol 2008;19(1):44-48.

10.  Ruggles AJ, Beech J, Gillette DM, Midla LT, Reef VB, Freeman DE. Disseminated Halicephalobus deletrix infection in a horse. J Am Vet Med Assoc. 1993;203(4):550-552.

11.  Sponseller BT, Plattner BL, Hostetter JM, J Am Vet Med Assoc. 2011; 238(10):1265-1267

12.  Wilkins PA, Wacholder S, Nolan TJ, Bolin DC, Hunt P, Bernard W, Acland H, Del Piero F. Evidence for transmission of Halicephalobus deletrix (H gingivalis) from dam to foal. J Vet Intern Med. 2001;15:412-417.

13.  Zachary JF. Nervous system. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Mosby; 2017:846.

 

 

 

 

 

 

 

 


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