A 6-year-old 3.9-kg (8.6-lb) spayed female indoor-only domestic medium hair cat was evaluated because of stupor, blindness, and a recent onset of seizure-like activity. During the preceding 3 days, the cat had become unsteady when standing, developed increased respiratory rate and effort, and had an episode of vocalization and full-body rigidity. Two months prior to evaluation, the cat had been treated for and recovered from pneumonia; 1 week prior to evaluation, an abdominal mass (tentatively identified as an intra-abdominal lipoma) had been removed surgically. The cat had no history of travel outside of the Pacific Northwest, no longstanding medical conditions, and no known toxin exposure. Other cats in the household were healthy.
Initial physical examination of the cat revealed a stuporous mentation with dehydration (5% to 7%); rectal temperature was 37.9°C (100.2°F), and the cat was laterally recumbent. The cat had a body condition score of 4/9. Cardiac auscultation revealed no abnormalities, and femoral pulses were strong and synchronous with the heartbeat; respiratory rate and effort were mildly to moderately high (48 breaths/min). The ventral midline incision site appeared to be healing well, and no abnormalities were detected via abdominal palpation.
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
| Problem | Rule out location |
|---|---|
| Altered level of consciousness (stuporous) | Cerebrum, thalamus, or brainstem |
| Partial blindness with intact pupillary light reflex | Thalamus or cerebrum (occipital lobe) |
| Seizure-like activity | Cerebrum |
| Vertical downbeat positional nystagmus | Brainstem or cerebellum |
Likely location of one lesion
| Multifocal intracranial localization |
Etiologic diagnosis—Differential diagnoses included infectious CNS disease (feline infectious peritonitis and infection with Toxoplasma spp, Cryptococcus spp, or other fungal organisms), hypoxia, neoplasia (lymphoma), or inflammatory CNS disease. The diagnostic plan included performing a CBC, serum biochemical analysis, and urinalysis (to assess cell counts and metabolic changes); MRI of the brain (to detect structural intracranial abnormalities); CSF analysis (to rule out CNS inflammatory disease or detect infectious organisms or neoplastic cells); and assessment of titers of serum antibodies against Toxoplasma and Cryptococcus (capsular antigen) organisms to further rule out infectious processes.
Diagnostic test findings—The CBC and serum biochemical analysis revealed hyponatremia (138.3 mg/dL; reference range, 146 to 157 mg/dL), hypokalemia (3.27 mg/dL; reference range, 3.5 to 4.9 mg/dL), hypochloremia (102.4 mg/dL; reference range, 116 to 126 mg/dL), hypomagnesemia (1.22 mg/dL; reference range, 1.7 to 2.3 mg/dL), and hyperglycemia (207 mg/dL; reference range, 64 to 118 mg/dL). Results of a diagnostic test for circulating FeLV antigen and anti-FIV antibody were negative.
Magnetic resonance images (T2-weighted, fluid-attenuated inversion recovery, diffusion-weighted images, and T1-weighted [before and after contrast medium administration]) of the brain, including transverse, sagittal, and coronal views, were obtained. Imaging revealed marked, diffuse, generalized meningeal enhancement with multifocal contrast-enhanced parenchymal lesions in the regions of the cerebellum and brainstem. No other abnormalities of the head, the nasal cavity, the tympanic bullae, or soft tissues of the head were evident via MRI.
A sample of CSF was collected from the cerebellomedullary cistern, and analysis revealed high protein concentration (41.9 mg/dL; reference range, < 30 mg/dL), high WBC count (407 cells/μL; reference range, < 5 cells/μL), and high RBC count (23 cells/μL; reference range, < 5 cells/μL). On microscopic examination of the CSF sample, occasional yeast organisms (2 to 10 μm in diameter) composed of a large capsule and narrow-based budding were detected; these organisms were consistent with Cryptococcus sp. Culture of the CSF sample was performed with organism typing to differentiate Cryptococcus neoformans from Cryptococcus gattii. Cryptococcal antigen testing yielded a positive result (1:6,613). Organism typing identified the yeast as C gattii.
Comments
Given the findings of the CSF analysis, cryptococcal antigen testing, and organism typing, a definitive diagnosis of C gattii infection was made for the cat of the present report. Cryptococcus gattii was first isolated from a human with leukemia in 1970, and at that time, it was described as a variant of C neoformans.1 Since the late 1990s, C gattii has emerged as a notable pathogen of both humans and other animals in the Pacific Northwestern United States and southwestern Canada.2 It had been thought that C gattii was geographically limited to tropical regions of the world; however, multiple reports2–7 have more recently indicated otherwise. Cryptococcus gattii has been isolated from maple, fir, and cedar trees as well as from air, freshwater, seawater, and the upper layer of soil of the British Columbia mainland and has also been isolated from the Gulf Islands and Washington State.3,4 In a recent study6 of cats and dogs with cryptococcosis in California, C gattii was most commonly isolated from cats for which fungal species identification had been performed. This organism appears to infect immunocompetent individuals, and the prognosis for infected animals that develop primary CNS signs is considerably worse than the prognosis for animals that are evaluated for other clinically relevant reasons and do not develop CNS signs.5
The cat of the present report was hospitalized for treatment with fluid therapy with a balanced electrolyte solution (1.5 × maintenance rate, IV), phenobarbital (3 mg/kg [1.36 mg/lb], PO, q 12 h), amphotericin B (1 mg/kg/d [0.45 mg/lb], IV, for 12 d; cumulative dose, 12 mg/kg [5.45 mg/lb]), and fluconazole (12.5 mg/kg [5.68 mg/lb], PO, q 12 h). Throughout the period of hospitalization, the cat's mentation and ability to ambulate improved considerably, to the point that it was able to urinate in a designated litter box. At the time of discharge from the hospital 14 days after admission, it was able to track objects with its eyes and had regained a menace response and pupillary light response. Nevertheless, the cat's ability to ambulate remained minimal (although present) and its appetite was lacking. The owner was instructed to continue administration of phenobarbital (3 mg/kg, PO, q 12 h) and fluconazole (12.5 mg/kg, PO, q 12 h). Although the cat continued to be receptive to oral syringe feedings following discharge from the hospital, an esophagostomy tube was placed by the referring veterinarian 10 days later because of its lack of appetite. Approximately 28 days following the placement of the feeding tube, the cat was noted to have an improved appetite and the feeding tube was removed. Twelve weeks following the initiation of treatment, the cat was eating unaided, playing with the other cats in the household, and jumping onto tall objects at the owner's home. The plan was to continue treatment with phenobarbital at a decreased dosage (2 mg/kg [0.91 mg/lb], PO q 12 h) and fluconazole (12.5 mg/kg, PO, q 12 h) indefinitely.
This feature is published in coordination with the American College of Veterinary Internal Medicine on behalf of the specialty of neurology. Contributors to this feature should contact Dr. Helen L. Simons (800-248-2862, ext 6692) for case submission forms. Submissions will be sent to Dr. Karen Kline, DVM, DACVIM, for her review, except when Dr. Kline is an author.
References
1. Vanbreuseghm R, Takashio M. An atypical strain of Cryptococcus neoformans (San Felice) Vuillemin 1894. II. Cryptococcus neoformans var. gattii var. nov. Ann Soc Belges Med Trop Parasitol Mycol 1970;50:695–702.
2. Dixit A, Carroll SF, Qureshi ST. Cryptococcus gattii: an emerging cause of fungal disease in North America. Interdiscip Perspect Infect Dis 2009;2009:1–13.
3. MacDougall L, Kidd SE, Galanis E, et al. Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis 2007;13:42–50.
4. Kidd SE, Chow Y, Mak S, et al. Characterization of environmental sources of the human and animal pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States. Appl Environ Microbiol 2007;73:1433–1443.
5. Duncan C, Stephen C, Campbell J. Clinical characteristics and predictors of mortality for Cryptococcus gattii infection in dogs and cats of southwestern British Columbia. Can Vet J 2006;47: 993–998.
6. Trivedi SR, Sykes JE, Cannon MS, et al. Clinical features and epidemiology of cryptococcosis in cats and dogs in California: 93 cases (1988–2010). J Am Vet Med Assoc 2011;239:357–369.
7. Lester SJ, Malik R, Bartlett KH, et al. Cryptococcosis: update and emergence of Cryptococcus gattii. Vet Clin Pathol 2011;40:4–17.
