Intradural vasculitis and hemorrhage in full sibling Welsh springer spaniels

Abstract

Two, full sibling, Welsh springer spaniels presented at 8 and 18 mo of age with rapidly progressive ataxia, recumbency, and pyrexia. The spinal cord contained extensive subdural hemorrhage and, in 1 dog, suppurative and necrotizing arteritis in the dura. The findings suggest a familial form of canine juvenile polyarteritis syndrome.

An 8-month-old, spayed female, Welsh springer spaniel (case 1) was examined at the Ontario Veterinary College for progressive neurological signs of 12 h duration, and recumbency, lethargy, depression, slight mucoid diarrhea, and anorexia of 72 h duration. Clinical signs were first noted 3 d after ovariohysterectomy. On general physical examination, the dog was depressed, pyrexic (40.9°C), tachypneic (90 breaths/min), and anxious. Scleral hemorrhage was present. Cranial nerve examination was normal. The dog was ambulatory on the forelimbs, with normal proprioception and reflexes. Examination of the hind limbs revealed proprioceptive deficits, no purposeful movement, and absence of deep pain sensation. The left patellar reflex was weak and the muscle tone in the left hind leg was decreased. The cutaneous trunci muscle reflex was absent caudal to the 2nd lumbar vertebra (L2), and hyperaesthesia was present over the T5 to L2 vertebrae. Clinical pathologic findings included leukocytosis (32.2 × 10⁹/L; reference range 6.0 to 17.0 × 10⁹/L), attributable to a neutrophilia (22.9 × 10⁹/L; reference range 3.0 to 11.5 × 10⁹/L), with a left shift (bands 1.3 × 10⁹/L; reference range 0 to 0.9 × 10⁹/L), and monocytosis (3.9 × 10⁹/L; reference range 0.2 to 1.4 × 10⁹/L). Mild toxic changes were noted in the neutrophils.

The neurological signs suggested a multifocal asymmetric lesion of the spinal cord between T3 and L6, based on the hind limb proprioceptive deficits, thoracolumbar pain, hypotonia, and weak left patellar reflex. The differential diagnoses were meningomyelitis, congenital malformation, and a space-occupying spinal cord lesion. The dog was euthanized. Necropsy findings included spinal subdural hemorrhage from C3 to L7, with softening of the spinal cord at T2 to L2. Histologic lesions of the spinal cord were minimal. Rare swollen axons were present in the thoracic cord. The dura mater was not examined.

An 18-month-old, neutered male, Welsh springer spaniel (case 2) was examined at the Ontario Veterinary College for lethargy, depression, anorexia of 48 h duration, and progressive neurological deficits. The dog was a full sibling to case 1. The breeder claimed that no other siblings had been affected.

On general physical examination, the dog was pyrexic (39.7°C), tachycardic (120 beats/min), tachypneic, and reluctant to move. Bilateral scleral hemorrhage was present. The dog was unable to stand without support and had proprioceptive deficits in both hind limbs. The patellar and withdrawal reflexes in the right hind limb were absent, and the left hind limb withdrawal reflex was decreased. Forelimb reflexes, pain sensation, and the cutaneous trunci muscle reflex were normal. There was marked neck pain with extreme reluctance to move. One day prior to admission, there was leukocytosis (39.5 × 10⁹/L; reference range 6.0 to 16.9 × 10⁹/L) attributable to neutrophilia (36.4 × 10⁹/L; reference range 3.3 to 12.0 × 10⁹/L), and thrombocytopenia (57 × 10⁹/L; reference range 175 to 500 × 10⁹/L). Activated clotting time was within normal limits at 120 s.

The multifocal neurological deficits including depression, cervical pain, hindlimb proprioceptive deficits, and decreased hind limb reflexes suggested a lesion in the brainstem, cervical spinal cord, and/or lumbar enlargement of the spinal cord. The differential diagnoses included infectious meningoencephalomyelitis, granulomatous meningoencephalomyelitis, and steroid-responsive suppurative meningitis. The dog was euthanized.

Necropsy findings included extensive subdural hemorrhage from C1 to L6. Histologically, there was vasculitis in a single 400-μm diameter artery in the dura mater of the lumbar spinal cord (Figure 1). This lesion was characterized by deposition of periodic acid Schiff (PAS)-positive fibrinoid material, cellular debris, and low numbers of neutrophils in the tunica media. The tunica intima was segmentally thickened by mesenchymal cells and matrix, but the internal elastic lamina was preserved. The adventitia and surrounding tissue contained extensive infiltration of neutrophils, and many of these cells were necrotic. Fibrillar strands of fibrin were present in the lumen of the artery. Infectious agents were not identified in sections stained with PAS or methenamine silver. Immunohistochemical studies, performed by the Immunology Laboratory of Prairie Diagnostic Services, did not reveal deposition of IgM, IgG, or complement (C3). Histologic lesions were not present in the brain.

Figure 1. Histologic lesions of necrotizing arteritis in the dura mater of the lumbar spinal cord of a dog. Numerous neutrophils are present in the adventitia (large arrow) with fewer in the tunica media. There is deposition of fibrinoid material in the tunica media (small arrow), and thickening of the tunica intima. The internal elastic lamina is indicated by arrowheads, the lumen of the artery is denoted by the asterisk, and the ampersand marks the subarachnoid space. Movat pentachrome stain, Bar = 100 μm.

The clinical findings in these 2 full sibling Welsh springer spaniels included pyrexia, dullness or depression, bilateral scleral hemorrhage, proprioceptive defects, reduced spinal reflexes in the hind limbs, hyperaesthesia, and neutrophilia. Extensive, intradural, extra-medullary hemorrhage was present in the spinal cord of both dogs. Histologic examination revealed severe suppurative and necrotizing vasculitis affecting a single artery in the dura mater of case 2. Vasculitis was not apparent in case 1, but its dura mater was not examined histologically. The presence of similar clinical and necropsy findings in both dogs suggests that spinal meningeal vasculitis was the cause of the subdural hemorrhage in both dogs.

Canine juvenile polyarteritis syndrome (JPS, previously termed beagle pain syndrome) is the most likely cause of suppurative and necrotizing arteritis in the spinal meninges of a young dog. The differential diagnoses include hematogenous mycotic infection, ehrlichiosis, Rocky Mountain spotted fever (RMSF), drug-induced vasculitis, and immune-complex vasculitis (1,2,3). Fungal hyphae were not identified on special stains. Ehrlichiosis and RMSF are expected to incite lymphoplasmacytic and lymphohistiocytic inflammatory responses, respectively, and were considered unlikely in dogs that had not travelled outside Ontario (1,2). The only association with drug administration was the anaesthetic agents administered in case 1, 3 d prior to the onset of clinical signs. Vasculitis restricted to the meninges would be unusual in immune complex vasculitis (2,3), and neither immunoglobulins nor complement was detected in the vessel walls by immunohistochemical staining. Thus, the clinical and pathologic features of this case are consistent with previous reports of JPS.

The cause of JPS is unknown. An immune-mediated disease is suggested; however, as in this case, immunoglobulin or complement cannot be detected in the vessels in most cases (4). Antineutrophil cytoplasmic antibodies (ANCA), which are useful diagnostic markers of specific forms of vasculitis in humans, were identified in the serum of 2 out of 3 dogs with JPS (5). Further investigation of the potential for ANCA to serve as a diagnostic indicator of JPS is warranted. A heritable tendency is suggested by a higher prevalence in certain kennels or bloodlines (4,6), and a test breeding between 2 affected dogs resulted in 1 affected dog from a litter of 7 (7). The present case is the first report of JPS in full siblings. Juvenile polyarteritis syndrome is most commonly reported in laboratory beagles, but sporadic cases have been described in a variety of other breeds. Most cases occur in 6- to 24-month-old juvenile dogs, and rarely in older animals. Clinical signs include pyrexia, reluctance to move, neck pain, and either a hunched posture or an extended head and neck. Neurological signs range from proprioceptive deficits to quadriplegia, hemiplegia, paraplegia, and paresis. The clinical signs of JPS may follow a relapsing course and tend to become less severe and frequent as the dog matures. Mild cases improve dramatically when treated with prednisone, but clinical signs may recur when treatment is discontinued. In cases with severe neurologic deficits, the response may be poor, and euthanasia is justified on humane grounds (7,8,9,10).

Although recurrent bouts of cervical hyperesthesia, fever, and mild proprioceptive deficits may result directly from the meningeal arteritis, the acute onset of severe neurologic impairments in these cases is probably the sequela of hemorrhage into the subarachnoid space. The arteritis in cases of JPS is variable in distribution, affecting the small to medium sized arteries of the spinal meninges, epicardium, and cranial mediastinum, and, uncommonly, the small intestine, testes, thymus, thyroid, lymph nodes, diaphragm, esophagus, urinary bladder, and cerebral meninges (8,9). In the cases described in this report, arteritis was not present in the sections of myocardium, and mediastinal lesions were not grossly apparent. As there is no specific marker for the disease, the diagnosis of JPS requires exclusion of other causes of meningoencephalitis (7,9). The relationship between steroid-responsive suppurative meningitis and JPS is uncertain, since histologic evaluation of the spinal cord is not feasible in cases that respond well to corticosteroids. Nevertheless, clinical and epidemiologic similarities suggest that some cases of steroid-responsive suppurative meningitis are identical to JPS (7). The presence of spinal intradural hemorrhage and meningeal arteritis in full sibling Welsh springer spaniels supports the suggestion that there is a genetic predisposition to JPS. CVJ