Assessment Anatomic diagnosis

Etiologic diagnosis—The neurolocalization of the dog's problem was the peripheral vestibular system on the left side, namely a lesion affecting the vestibular apparatus or vestibulocochlear nerve. The differential diagnosis list for this syndrome included inflammatory and infectious conditions affecting the vestibulocochlear nerve and neoplasia or congenital abnormalities of the vestibular system. Idiopathic vestibular disease is a known cause of peripheral vestibular dysfunction in dogs, but it would be exceptionally rare in a dog of this age, and it typically causes sudden-onset vestibular dysfunction. Lesions affecting the inner ear include otitis media, otitis interna, and neoplasia; hypothyroidism has also been identified in some dogs with peripheral vestibular disease. Finally, a discrete lesion affecting the central components of the vestibular system could result in unilateral signs of vestibular dysfunction without any additional clinical signs. Given the unusual signalment in this case, an MRI examination of the head was considered the most appropriate investigation, with analysis of a CSF sample and further serologic testing if indicated.

Diagnostic test findings—Magnetic resonance imaging^a of the head revealed prominent sulci over the cerebral hemispheres and cerebellum, suggestive of some cerebellar atrophy. The sulci were hyperintense on T2-weighted images, had partial suppression on fluid-attenuated inversion recovery images, and were hypointense on T1-weighted images. There were no clear lesions of the tympanic bullae, vestibular apparatus, or vestibulocochlear nerves on assessment of conventional MRI images. To assess the caudal brainstem in more detail, T1-weighted volume acquisitions (slice thickness, 1 mm) were obtained before and after administration of the contrast agent gadobenate dimeglumine^b; in these images, mild hyperintensity of the vestibulocochlear nerve on the left side was evident (Figure 1).

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Magnetic resonance images of the brain and brainstem of a 1-year-old Labrador Retriever with a head tilt to the left side of 10 weeks' duration. A—Midsagittal plane T2-weighted image of the brain. Notice the abnormally prominent sulci over the surface of the cerebellum with apparent atrophy of the cerebellar parenchyma. B—Transverse plane T2-weighted image of the forebrain at the level of the caudate nuclei. Prominent sulci are evident over the surface of the cerebral hemispheres, which is not apparent in the midsagittal image. C—Fluid-attenuated inversion recovery image at the same level as that in panel B. There is incomplete attenuation of the hyperintense sulci, suggestive of malacia of the surface of the cerebral cortex in addition to widening of the sulci. D—Postcontrast T1-weighted image obtained following reconstruction of transverse-plane volume acquisitions (slice thickness, 1 mm) of the caudal portion of the brainstem. Although not a definitive observation, there appears to be subtle hyperintensity of the vestibulocochlear nerve (arrow) on the left side, which was not evident on conventional 3.5-mm-slice-thickness T1-weighted images.

Citation: Journal of the American Veterinary Medical Association 255, 5; 10.2460/javma.255.5.529

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A cisternal CSF sample was subsequently collected and analyzed; the nucleated cell count (3 nucleated cells/μL; reference interval, < 5 nucleated cells/μL) and protein concentration (26 mg/dL; reference interval, < 30 mg/dL) were within reference intervals. However, cytologic examination of the CSF sample revealed small mature, reactive lymphocytes with rare mature neutrophils and vacuolated phagocytic macrophages. On the basis of these and the MRI findings, a blood sample was obtained for serologic testing, the results of which indicated that the dog had a serum anti-Neospora antibody titer of > 1:12,800 (reference interval, < 1:50).

Given the clinical and imaging findings for the dog, a final diagnosis of neosporosis was made. The vestibular signs were considered most likely a consequence of left-sided vestibulocochlear neuritis rather than of cerebellitis.

Comments

Following confirmation of the neosporosis in the dog of the present report, treatment with a combination of trimethoprim-sulfamethoxazole (15 mg/kg [6.8 mg/lb], PO, q 12 h) and pyrimethamine (1 mg/kg [0.45 mg/lb], PO, q 24 h) was initiated. Folic acid was also provided (5 mg, PO, once weekly) to diminish the bone marrow suppression that can occur with this combination of drugs. The dog was initially treated with both drugs together for 2 months, by which time the nystagmus had resolved, although a head tilt remained at this point and there were no reported balance problems.

During the course of treatment, the dog's serum anti-Neospora antibody titer was measured several times, and it decreased to 1:1,600 within a 2-month period. At this point, the administration of pyrimethamine was stopped, and the trimethoprim-sulfonamide treatment was continued for another 3 months. The dog's serum anti-Neospora antibody titer further decreased during this period, initially to 1:400 (at 3.5 months following diagnosis) and then to 1:200 (at 5 months following diagnosis). An additional serologic test performed 2.5 months following cessation of treatment revealed further reduction of the titer to 1:100. The dog had a persistent slight head tilt, but this is common in dogs with vestibular lesions despite resolution of the underlying condition. The dog had no detectable medication-related adverse effects.

The unusual aspect of the case described in the present report was the neosporosis-associated peripheral vestibular syndrome. This highlighted the fact that an unusual combination of signalment and clinical signs in any patient should prompt further investigation whenever possible. In dogs with peripheral vestibular disease, empirical treatment with glucocorticoids is not uncommon, and the short course that was prescribed initially for the dog of the present report could have resulted in a marked deterioration of the clinical signs had the course been extended. Prompt diagnosis and treatment of neosporosis resulted in a rapid improvement of the dog's condition and almost complete resolution of clinical signs.

Neospora caninum is a protozoal parasite that was first identified in dogs in Norway in 1984; among Boxer puppies, infection with the parasite resulted in progressive and fatal neurologic disease.¹ Two classic clinical syndromes are associated with Neospora infection, of which paraparesis in puppies and juvenile dogs is the most widely recognized form. This syndrome typically results in neuromyopathy with hyperextension of the pelvic limbs, associated postural deficits, and variably severe paresis; additional neurologic deficits may also be present. The other clinical syndrome associated with neosporosis in dogs involves cerebellar and brainstem dysfunction.

This syndrome generally affects adult dogs and is predominantly associated with necrotizing cerebellitis, although the condition is multifocal and lesions are present in other regions of the brain.² For the dog of the present report, the MRI findings were typical of the form of the disease that affects adults, with changes suggestive of cerebellitis; however, there were no signs of cerebellar or brainstem dysfunction, which suggested that the CNS disease was not sufficiently severe to cause clinical signs. Although the presence of a small lesion affecting the central vestibular apparatus was possible, the dog's head tilt seemed more likely attributable to vestibulocochlear neuritis. This speculation could not be definitively confirmed by MRI, although mild equivocal changes detected on the T1-weighted volume acquisitions supported the suspicion. It is known that MRI is relatively insensitive for detection of presumptive vestibulocochlear neuritis, compared with its ability to detect diseases that affect other cranial nerves. The use of a low-field MRI scanner might have been another limitation to the ability to detect changes in the vestibulocochlear nerve.

Confirmation of the diagnosis in the case described in the present report was provided by the results of serologic testing for anti-Neospora antibodies. Indirect fluorescent antibody testing is the most useful diagnostic technique for detection of circulating anti-Neospora antibodies. However, it is important to note that test results for clinically normal dogs can be positive; in such instances, the titer is typically low, with clinically normal dogs rarely having a titer > 1:800.³ It is also possible that dogs with neosporosis can have a low anti-Neospora antibody titer if empirical treatment was commenced prior to testing.⁴ The diagnosis of neosporosis in such cases is facilitated by the performance of a PCR assay on CSF samples, although in a case series⁴ of 5 dogs with neosporosis, the PCR assay result for 1 dog was negative. In dogs with evidence of myositis, immunohistochemical analysis of muscle biopsy specimens might also facilitate diagnosis.³

Treatment options for Neospora infection in dogs include administration of clindamycin and folate synthesis inhibitors. The folate inhibitors most commonly used in veterinary practice are potentiated sulfonamides, in which trimethoprim is combined with a sulfonamide, most commonly sulfamethoxazole or sulfadiazine. For the dog of the present report, sulfonamide-based treatment was administered on the grounds that penetration of the blood-brain barrier by that drug combination is more effective than that of clindamycin. A proprietary trimethoprim-sulfadiazine preparation (15 mg/kg, PO, q 12 h) in combination with pyrimethamine (1 mg/kg, PO, q 24 h) was administered, which has been effective for treatment of neosporosis in dogs in our experience. Bone marrow suppression can occur with this combination of drugs, and some clinicians advocate use of supplemental folinic acid (5 to 10 mg, PO, q 24 h), but there is no convincing evidence to indicate that this is superior to administration of folic acid.

As illustrated by the case described in the present report, further diagnostic investigation of animals with unusual clinical signs or history is essential. Although unilateral vestibular disease is common in dogs, the persistent head tilt in the dog of the present report was considered unusual in a dog of this age that had only mild prior bilateral otitis externa and an absence of other neurologic deficits. This prompted further diagnostic testing, the results of which led to a diagnosis of neosporosis. The dog's clinical signs and MRI findings suggested that the vestibular disease was caused by unilateral vestibulocochlear neuritis, which has not been previously reported for canine cases of neosporosis, to our knowledge. For the dog of the present report, the prompt diagnostic investigation avoided prolonged empirical treatment with glucocorticoids, which could have had catastrophic consequences if not accompanied by appropriate antimicrobial administration.