History

A 14-year-old Morgan–Quarter Horse crossbred gelding presented to a veterinary university ambulatory service for a chief complaint of tail rubbing and inability to move his tail. The clinical signs were observed approximately 2 weeks prior. The patient was up to date on vaccinations against eastern and western equine encephalitis viruses, West Nile virus, tetanus, and rabies. Prior to presentation, the patient had no history of disease or hospitalization and was only seen for routine preventive care.

Clinical and Clinicopathologic Findings

Upon physical examination, temperature, heart rate, and respiratory rate were within normal limits. The patient was generally depressed and exhibited bilaterally symmetrical mild hind limb ataxia when turned in tight circles. Musculoskeletal and neurologic abnormalities included decreased gluteal muscle and anal tone, absent tail tone, absent sensation around perineum and prepuce, and absent perineal reflex. Rectal examination identified severely distended urinary bladder and accumulation of fecal material in the rectum.

Results of CBC and chemistry panel revealed mild mature neutrophilia (8.3 thousand/μL [2.7 to 6.6 thousand/μL]), mild hyperproteinemia (8.6 g/dL on whole blood [5.2 to 7.8 g/dL]; 7.7 g/dL on serum [5.4 to 7.0 g/dL]), moderate hyperglobulinemia (4.8 g/dL [2.3 to 3.8 g/dL]), severely elevated serum amyloid A (710 μg/mL [0 to 8 μg/mL]), moderately low iron (48 μg/dL [95 to 217 μg/dL]) and iron saturation (13% [27% to 56%]). Cytology of CSF from the lumbosacral space showed marked mixed pleocytosis (238 nucleated cells/μL) characterized by 55% nondegenerate neutrophils, 43% small lymphocytes, 2% quiescent macrophages, and protein in the CSF was elevated (470 mg/dL). Borrelia burgdorferi was undetected on PCR of CSF, and Lyme disease multiplex assay on serum was negative for antibodies against OspA, OspC, and OspF. Equine herpesvirus 1 and 4 were undetected on PCR on whole blood and nasal exudate. The Sarcocystis neurona surface antigen 2, 3, 4 serum: CSF ratio was less than 100, inconsistent with clinical EPM. A serum sample was positive for antibodies against myelin protein peptide and myelin P2.

Six days after the initial visit, the patient developed a visibly enlarged right facial nerve (Figure 1), lost sensation in the nares, and became dysphagic. Eight days after the initial visit, the patient developed muzzle deviation to the left (Figure 2), had staggering gait, and was completely anorexic. Due to the decreasing quality of life and poor prognosis, the patient was euthanized.

Enlarged right facial nerve (arrow), 6 days after initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Enlarged right facial nerve (arrow), 6 days after initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Enlarged right facial nerve (arrow), 6 days after initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Nares deviated to the left, 8 days after the initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Nares deviated to the left, 8 days after the initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Nares deviated to the left, 8 days after the initial presentation.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Histopathologic Findings

Possible etiologies of neurologic disease include trauma, neoplasia, or infectious diseases affecting the CNS or PNS. The clinical findings of cauda equina nerve paresis and facial paresis with a visibly enlarged facial nerve made polyneuritis equi the most likely diagnosis although lymphoma and neuroborreliosis were considered as differential diagnoses.

Variable, mild to severe, depending on the section evaluated, granulomatous, lymphoplasmacytic, and eosinophilic polyneuritis with degeneration, necrosis, epineurial and perineurial fibrosis was identified in the following tissues: trigeminal nerve roots, entire spinal cord, right and left pudendal nerves, right and left buccal nerves, right and left trigeminal nerves, right brachial plexus, right and left facial nerve, and vestibulocochlear nerve. The inflammation was most severe in the cauda equina, and it was characterized by macrophages on a background of small lymphocytes with multiple areas of rich eosinophilic infiltrate and numerous giant cells (Figure 3). Masson’s trichrome stain for collagen fibers confirmed fibrosis, Luxol fast blue, and Bielschowsky silver stains confirmed degeneration of axons, characterized by segmentally dilated and fragmented myelin sheaths with central eosinophilic material (spheroids) or pale, eosinophilic, fibrillar debris and a central macrophage (digestion chamber; Figure 3). Immunohistochemistry for CD3 (T-lymphocytes), IBA 1 (histiocytes), and CD20 (B-lymphocytes) revealed a majority of T-lymphocytes in the inflammatory infiltrate, followed by macrophages and small numbers of B-lymphocytes (Figure 3).

Section of cauda equina infiltrated by abundant macrophages, multinucleated giant cells, lymphocytes, and eosinophils; H&E stain (A). Section of cauda equina with concentric fibrosis surrounding nerve fibers and separating axons; Masson Trichrome stain (B). Severe dilation and fragmentation of myelin sheaths along with replacement by inflammation and necrotic debris; Luxol fast blue stain (C). Severe dilation and fragmentation of myelin sheaths with accumulation of central argyrophilic material in spheroids; Bielschowsky silver stain (D). CD3 marker for T-lymphocytes reveals strong immunolabeling of the majority of infiltrating lymphocytes (E). CD20 marker of B-lymphocytes shows strong immunolabeling in scattered infiltrating cells, predominantly around the periphery of the nerve fibers (F). Bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Section of cauda equina infiltrated by abundant macrophages, multinucleated giant cells, lymphocytes, and eosinophils; H&E stain (A). Section of cauda equina with concentric fibrosis surrounding nerve fibers and separating axons; Masson Trichrome stain (B). Severe dilation and fragmentation of myelin sheaths along with replacement by inflammation and necrotic debris; Luxol fast blue stain (C). Severe dilation and fragmentation of myelin sheaths with accumulation of central argyrophilic material in spheroids; Bielschowsky silver stain (D). CD3 marker for T-lymphocytes reveals strong immunolabeling of the majority of infiltrating lymphocytes (E). CD20 marker of B-lymphocytes shows strong immunolabeling in scattered infiltrating cells, predominantly around the periphery of the nerve fibers (F). Bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Section of cauda equina infiltrated by abundant macrophages, multinucleated giant cells, lymphocytes, and eosinophils; H&E stain (A). Section of cauda equina with concentric fibrosis surrounding nerve fibers and separating axons; Masson Trichrome stain (B). Severe dilation and fragmentation of myelin sheaths along with replacement by inflammation and necrotic debris; Luxol fast blue stain (C). Severe dilation and fragmentation of myelin sheaths with accumulation of central argyrophilic material in spheroids; Bielschowsky silver stain (D). CD3 marker for T-lymphocytes reveals strong immunolabeling of the majority of infiltrating lymphocytes (E). CD20 marker of B-lymphocytes shows strong immunolabeling in scattered infiltrating cells, predominantly around the periphery of the nerve fibers (F). Bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 261, 5; 10.2460/javma.23.01.0045

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Interpretation and Case Summary

Interpretation: Variable, mild to severe, granulomatous, lymphoplasmacytic, and eosinophilic polyneuritis with degeneration, necrosis, epineural and perineurial fibrosis.

Case summary: Histopathology along with clinical presentation confirmed that this was a case of polyneuritis equi (previously known as cauda equina neuritis).

Comments

Polyneuritis equi is a relatively uncommon disease of mature horses characterized by progressive inflammation of the cauda equina and occasionally the cranial nerves.¹ The true incidence of this disease is unknown, in part due to the lack of conclusive diagnostic antemortem tests.¹ The etiology is unknown, but autoimmune and infectious causes have been postulated.^1,2 A prevailing theory is that autoimmunity against myelin P2 causes the inflammation and destruction of nerve fibers commonly seen at histopathology.^1,2 Anti-myelin P2 antibodies have been detected in horses diagnosed with polyneuritis equi.² The pathogenesis has been compared to Guillain-Barré syndrome and experimental allergic neuritis.^1,3 These diseases are characterized by inflammatory response, predominated by T-lymphocytes, and histopathology of polyneuritis equi has revealed similar lesions.³ It has been suggested that various pathogens that can cause neurologic signs, such as EHV-1, Campylobacter spp, equine adenovirus, and Streptococcus spp, may be implicated in the pathogenesis of polyneuritis equi.^1,4 However, any connection between these pathogens and polyneuritis equi has not been definitively proven.

Due to the primary involvement of the cauda equina, common clinical signs of polyneuritis equi include caudal hyperesthesia followed by anesthesia, decreased caudal muscle and tail tone, inability to urinate or defecate, and penile prolapse.¹ The disease may also involve the cranial nerves. Cranial nerves V, VII, and VIII are most commonly affected, resulting in decreased facial sensation, facial muscle paresis, head tilt, and vestibular signs.^1,4 Caudal neurologic signs are typically symmetric while cranial nerve signs are typically asymmetric.^1,4 Peripheral motor nerves affecting limb function are less commonly affected.⁴ Clinical signs are irreversible and progressive in severity.¹ No breed, age, or sex predilection has been identified, although this is complicated by the relatively low number of cases reported in literature, difficulty of antemortem diagnosis, and associated likelihood of underreporting the true disease incidence.¹

No definitive antemortem diagnostic exists; this is a diagnosis of exclusion that can only be confirmed by postmortem examination and histopathology.¹ However, several antemortem diagnostics can be used to rule up polyneuritis equi as a differential diagnosis. The CSF cytology typically reveals a mixed pleocytosis and elevated protein levels.¹ Detection of circulating anti-myelin P2 antibodies in serum can be suggestive of polyneuritis equi although available tests are not highly specific and may yield positive results with cases of EHV-1 or equine adenovirus infection.^1,2

Grossly, extradural nerve roots, especially sacral and coccygeal nerves, may be thickened, a feature that was not obvious in this case.¹ Histopathology reveals granulomatous inflammation of affected nerves characterized by macrophages, lymphocytes, multinucleated giant cells, plasma cells, and eosinophils, as in this case.^1,3 Degeneration of axons and myelin, as well as epineurial, endoneurial, and perineurial fibrosis, are often observed and were documented in this case.¹

There is no cure for polyneuritis equi, and treatment focuses on palliative care.¹ Anti-inflammatory medications such as corticosteroids can be given to help control the inflammation, but this will not prevent the progression of disease.¹ Manual removal of feces from the rectum and manual evacuation or catheterization of the urinary bladder may be indicated if the patient experiences fecal or urinary retention.¹ Prognosis is poor, and patients are typically euthanized within months.¹ Treatment of this case involved epidural administration of 5 mg dexamethasone at the initial visit and every 48 hours thereafter; dexamethasone IV (0.1 mg/kg, q 24 h) on day 1 and 2; prednisolone (1 mg/kg, PO, q 24 h) starting on day 3; oxytetracycline (6.6 mg/kg, IV, q 24 h for 7 days); selenium (1 mL of E-SE [2.5 mg selenium and 50 mg vitamin E per mL] per 100 lbs, once, IM); and vitamin E (5,000 IU, PO, q 24 h, for 7 days). Feces were manually removed from the patient’s rectum twice daily.

The patient in this case exhibited classical clinical signs and postmortem lesions associated with this disease, thus affirming the current knowledge of this disease presentation. The results of the antemortem diagnostics performed, particularly the serum anti-myelin P2 antibody test, may improve antemortem diagnosis of polyneuritis equi in the future. Another possible antemortem test is the biopsy of the sacrocaudalis dorsalis lateralis muscle.⁵ The negative infectious disease diagnostics aid in ruling out infectious etiologies for polyneuritis equi. The histochemical staining and immunohistochemistry provide greater knowledge of the changes at the cellular level and allow for a more precise understanding of the inflammatory process involved in this disease pathogenesis. Overall, the results of this case contribute to the breadth of knowledge regarding polyneuritis equi and provide rare insight into an uncommon equine disease.