What Is Your Neurologic Diagnosis?

Lauren Kmieciak Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Devon Wallis Hague Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Zachary L. Neumann Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Stephen Joslyn Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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A 3-year-old 5.05-kg (11.11-lb) castrated male domestic shorthair cat was evaluated at a local emergency clinic because of sudden-onset anisocoria of the left eye. The cat's behavior, appetite, and water consumption were all considered normal by the owner. Physical examination revealed marked mydriasis of the left pupil and unresponsive direct and indirect pupillary light reflexes of this eye. Results of testing for FeLV antigen and FIV antibody were negative. Abnormalities detected by clinicopathologic analyses included mild leukopenia and neutropenia. The next morning, the cat was brought to the University of Illinois Veterinary Teaching Hospital for further evaluation of the anisocoria. On physical examination, mild upper airway noise in the area of the left nares was heard during inspiration. Both thoracic and pelvic limbs had a normal withdrawal response and the pelvic limbs had intact myotactic reflexes. Results of a cranial nerve examination seemed indicative of normal function with the exception of absent direct and indirect pupillary light reflexes in the left eye. The cat had an intact oculocephalic reflex bilaterally (so-called doll's eye). Other physical and neurologic examination findings were unremarkable.

Neurologic examination

What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.

Assessment

Anatomic diagnosis

ProblemRule out location
Severe mydriasis of the left eye (nonresponsive to light)Suspected efferent pathway deficiency to oculomotor nerve of the left eye

Likely location of 1 lesion

These signs are best described by a lesion of the efferent left oculomotor nerve affecting the general visceral efferent parasympathetic preganglionic neurons that innervate the iris constrictor muscle.

Etiologic diagnosis—Given that the mydriasis of the left pupil developed suddenly and the neurologic signs did not progress, vascular and idiopathic nerve injury were the most likely differential diagnoses. For such a young cat, an inflammatory disease process was possible but considered less likely owing to lack of progression. A degenerative process, congenital anomaly, and neoplasia were also considered less likely, but still possible. Because of the asymmetry of the lesion, toxin exposure and metabolic diseases were also considered unlikely. The diagnostic plan included repeated clinicopathologic analyses (to rule out underlying systemic disease), an ophthalmologic examination (to identify any other ocular abnormalities), and MRI examination of the brain (to evaluate any structural abnormalities).

Diagnostic test findings—Results of the repeated clinicopathologic analyses were unremarkable. The ophthalmologic examination did not reveal any primary ophthalmic cause for the pupillary light reflex abnormalities. The cat was anesthetized and underwent MRI examination of the head with a 0.25-T scanner.a The following sequences were obtained in sagittal, dorsal, and transverse planes and with a slice thickness of 3.8 mm: T2-weighted series (repetition time, 5,670 milliseconds; echo time, 120 milliseconds) and T1-weighted series with and without contrast agent administrationb (repetition time, 710 milliseconds; echo time, 16 milliseconds). A transverse fluid attenuated inversion recovery (FLAIR) sequence was also obtained (repetition time, 7,000 milliseconds; echo time, 100 milliseconds). Magnetic resonance imaging revealed a large homogenous mass lesion ventral to the base of the skull (Figure 1). The mass was larger on the left side (approximately 35 mm in length × 14 mm in depth [left] × 26 mm in width).

Figure 1—
Figure 1—

Sagittal T2-weighted (A), transverse T2-weighted (B), and transverse T1-weighted images (before [C] and after [D] IV contrast agent administration) obtained from a 3-year-old domestic shorthair cat with sudden-onset anisocoria of the left eye. In panel A, the vertical lines from left to right denote the level of the transverse images in panels B, C, and D, respectively. A midline hyperintense mass lesion dorsal to the nasopharynx is visible; the boundaries (arrowheads) of the dorsal midline nasopharyngeal mass lesion indicate slight left lateral extension. The left optic nerve (arrow) is enhanced following contrast agent administration (D).

Citation: Journal of the American Veterinary Medical Association 248, 6; 10.2460/javma.248.6.613

The mass was hyperintense, compared with muscle, on T1-weighted, T2-weighted, and FLAIR sequences and had homogeneous contrast enhancement. The mass extended from the pterygoid process dorsal to the nasopharynx mucosa and terminated at the level of the tympanic bullae. There was infiltration of the mass into the left and right pterygoid muscles (Figure 2), left optic nerve, and left extraocular muscles and widening of both the optic canal and orbital fissure. There was potentially soft palate extension along the left lateral aspect; however, the close proximity of the endotracheal tube obscured this region. Consolidation of both tympanic bullae with hyperintense (on T1-weigthed, T2-weighted, and FLAIR images) non–contrast-enhancing material was evident. The nasal cavity and cribriform plate were considered normal, and the retropharyngeal lymph nodes were not included in images. On the basis of the MRI findings, the differential diagnoses for the infiltrative mass lesion include neoplasia (eg, squamous cell carcinoma or lymphoma), nasopharyngeal granuloma, or, less likely, a polyp. The diagnostic interpretation for the abnormal tympanic bullae included secondary obstructive otitis media or effusion and, less likely, infiltrative nasopharyngeal disease (neoplasia or polyp). A fine-needle aspirate specimen of the mass was obtained (via the oral cavity through the soft palate). Cytologic examination of the specimen revealed it to be highly cellular with minimal hemodilution. A large number of round cells, which appeared most consistent with intermediate to large lymphocytes, was observed. These cells had a scant basophilic rim of cytoplasm, a round nucleus that measured 1.5 to 2 times the diameter of an erythrocyte, and occasional prominent nucleoli. Epithelial atypia was observed with aberrant cytoplasmic keratinization or cytoplasmic vacuoles, and binucleate cells containing prominent nucleoli. The findings were most consistent with malignant neoplasia (lymphoma), and moderate epithelial dysplasia was also noted; thus, a carcinoma could not be ruled out. Results of immunocytochemical analysis were inconclusive because of low cellularity.

Figure 2—
Figure 2—

Transverse T2-weighted image obtained at the level of the pterygoid muscles in the cat in Figure 1. Notice the markedly increased signal of both pterygoid muscles (arrowheads) consistent with mass extension or infiltration.

Citation: Journal of the American Veterinary Medical Association 248, 6; 10.2460/javma.248.6.613

Comments

On the basis of the cytologic findings, the cat was suspected to have either nasopharyngeal carcinoma or lymphoma. Additional diagnostic testing, including collection of additional aspirate specimens for immunocytochemical analysis or biopsy specimens for histologic examination and concurrent immunohistochemical analysis, was discussed with the owner. Alternatively, a treatment trial with l-asparaginase was proposed. L-asparaginase, a chemotherapy agent, is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. Some tumor cells, including lymphoma cells, are unable to synthesize the nonessential amino acid asparagine. Thus, depleting the circulating concentration of asparagine should result in death of lymphoma cells, whereas, epithelial cells should not be affected.1 A treatment trial with L-asparaginase (10,000 U/m2, SC, once) and prednisolone (2 mg/kg [0.91 mg/lb], PO, q 24 h) was commenced, and the cat responded very well (consistent with a diagnosis of nasopharyngeal lymphoma).

Lymphoma is the most common neoplasm of cats, accounting for almost 30% of all tumors in that species.2,3 However, nasopharyngeal lymphoma is relatively rare, accounting for < 1% of all tumors in cats. Nasal, paranasal, and nasopharyngeal forms of nasopharyngeal lymphoma in cats have been described.4 Although rare, nasopharyngeal lymphoma is the most common tumor of the nasal cavity in cats; results of 1 study5 indicated that approximately 49% of all nasopharyngeal diseases in cats were nasopharyngeal lymphomas. Other studies2,6 of cats with lymphoma revealed that castrated males were overrepresented. Lymphoma can be classified as B cell or T cell in origin on the basis of immunohistochemical analysis to identify the lymphocyte-specific markers CD3 (T cell) and CD79a (B cell). Traditionally, lymphoma has been associated with FeLV- and FIV-positive status, especially in younger cats. More recently, it has been reported that only 7.4% of cats with lymphoma are FeLV positive.3 Although there has been a decrease in the FeLV-associated lymphoma cases among cats over the past few decades, an increase in the incidence of lymphoma has been documented, especially with regard to the atypical (nasopharyngeal) and abdominal forms.7,8 Nasopharyngeal lymphoma typically develops in older cats (median age, 8 to 9 years)9,10; the cat of the present report appears to be an exception to this generalization because it was 3 years old.

In cats, clinical signs of nasopharyngeal lymphoma are similar to those associated with chronic rhinitis, including epistaxis, stertor, facial swelling, nonhemorrhagic nasal discharge, sneezing, and other location-specific clinical signs.4,5,9,11 To our knowledge, there have been no reports of nasopharyngeal lymphoma causing peripheral nerve signs in cats, and the clinical findings for the cat of this report were unique. Nasopharyngeal lymphoma may cross the cribriform plate and involve the CNS, as identified in 23 of 100 (23%) cases in one study8 and 3 of 17 (17.6%) cases in another study.7 Although the cribriform plate was breached and the CNS was involved in those cats, no neurologic clinical signs were reported.

Nasopharyngeal lymphoma is an extranodal neoplasm that tends to be locally invasive with a low rate of involvement of other areas of the body and is highly sensitive to the effects of radiation therapy.6,7 No prognostic factors have been described specifically for cats with nasopharyngeal lymphoma, although in 1 study,6 anemia at the time of diagnosis was associated with significantly decreased survival time. Without treatment or with treatment with prednisolone alone, the prognosis for cats with nasopharyngeal lymphoma is very poor (median survival time, 28 to 60 days).10,11 Fortunately, nasopharyngeal lymphoma does respond to treatment, and the disease-free period is greatest for cats with nasal or peripheral lymphomas (358 and 378 days, respectively).3 There is 1 report12 of a cat that was treated with a chemotherapy protocol consisting of cyclophosphamide, vincristine, doxorubicin, and prednisone, which was successful at maintaining remission for 21 months even with extension of the nasopharyngeal lymphoma into the brain. Additionally, cats that do not achieve complete remission have a much poorer prognosis than those that do achieve complete remission.3,6 Although reported ranges of median survival time vary, increasing the total dose of radiation with or without chemotherapy was shown to achieve the longest median survival time.6

The cat of the present report underwent a treatment trial with L-asparaginase and prednisolone and responded favorably to the medications. Two days after the L-asparaginase and prednisolone treatment trial, the cat was started on a chemotherapy protocol involving vincristine,c doxorubicin,d and cyclophosphamide.13,e Prior to week 7 of the protocol, clinical signs (halitosis and upper airway stertor with decreased nasal airflow) returned and a CT scan of the head revealed recurrence of the nasopharyngeal mass. Radiation therapy consisting of 3-Gy exposure daily (Monday through Friday) for a total exposure of 45 Gy was initiated. Within the first week of treatment, the clinical signs of halitosis and upper airway stertor resolved. At the last follow-up examination (18 months after radiation therapy), the cat remained in complete clinical remission determined by physical examination and clinicopathologic findings.

Footnotes

a.

Esaote Vet MR Grande, Genoa, Italy.

b.

Omniscan (gadodiamide), Nycomed, Santa Monica, Calif.

c.

Hospira, Lake Forest, Ill.

d.

Pfizer, New York, NY.

e.

Baxter Healthcare Corp, Deerfield, Ill.

References

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