Case Report Rapport de cas Acute hind limb paralysis secondary to an extradural spinal cord Cryptococcus gattii lesion in a dog Lindsey Kurach, Chris Wojnarowicz, Tom Wilkinson, Colin Sereda Abstract — A 2-year-old, spayed female, German short-haired pointer was presented with a 1-day history of non-ambulatory paraplegia with absent deep pain perception. A computed tomography scan revealed an irregular eighth thoracic vertebral body and an extradural compressive lesion. Decompression was performed and abnormal tissues were submitted for analysis. Findings were consistent with a Cryptococcus gattii infection. Résumé — Paralysie aiguë du membre postérieur secondaire à une lésion de la moelle épinière extradurale due à Cryptococcus gattii chez un chien. Une chienne Pointer allemand à poil court stérilisée âgée de deux ans a été présentée avec une anamnèse de 1 journée de paraplégie avec l’absence de perception de 1a douleur profonde. Une lecture par tomodensitomètre a révélé un huitième corps vertébral thoracique irrégulier et une lésion compressive extradurale. La décompression a été effectuée et les tissus anormaux ont été soumis aux fins d’analyse. Les résultats étaient conformes à une infection à Cryptococcus gattii. (Traduit par Isabelle Vallières) Can Vet J 2013;54:463–466
A
2-year-old, spayed female, German short-haired pointer was presented to the Guardian Veterinary Centre (GVC) in November 2011 for evaluation of acute hind limb paralysis. Approximately 10 d earlier, the dog had appeared painful to the owners. Physical examination by the referring veterinarian revealed caudal thoracic spinal hyperesthesia without any neurological deficits. Medical management was initiated consisting of meloxicam (Metacam; Boehringer, Burlington, Ontario), 1.75 mg, PO, q24h; tramadol (compounded at Strathcona Pharmacy, Edmonton, Alberta), 50 mg, PO, q12h; and methylcarbamol (Robaxin; Pfizer, Kirkland, Quebec), 250 mg, PO, q8h, as well as instructions for strict activity restrictions. Clinically, the dog’s comfort improved; however, 1 d prior to presentation the dog developed ambulatory hind limb proprioceptive ataxia with delayed hind limb postural reactions. Results of a complete blood (cell) count (CBC) and serum chemistry panel were within normal limits. No spinal abnormalities were detected on survey thoracic and abdominal radiographs which were taken by the referring veterinarian and included
Michigan State University, College of Veterinary Medicine, East Lansing, Michigan, USA (Kurach); Prairie Diagnostic Services, University of Saskatchewan, Saskatoon, Saskatchewan (Wojnarowicz); Washington State University, College of Veterinary Medicine, Pullman, Washington, USA (Wilkinson); Guardian Veterinary Centre, Edmonton, Alberta (Sereda). Address all correspondence to Dr. Lindsey Kurach; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. CVJ / VOL 54 / MAY 2013
the thoracolumbar spine at the periphery of the films. Medical management was continued as described. The following day, clinical signs worsened to include non-ambulatory hind limb paralysis with questionable deep pain perception. The patient was referred to the GVC for further workup.
Case description On presentation to Guardian Veterinary Centre, the patient was anxious, alert, and responsive. The dog’s weight was 18.1 kg, and vital parameters were within normal limits. Neurological examination revealed normal mentation, cranial nerves, and proprioception in the forelimbs. The dog was non-ambulatory in the hind limbs, with absent conscious proprioception and no motor function. Spinal reflexes in the forelimbs were normal. In the hind limbs, the withdrawal and patellar reflexes were normal to slightly exaggerated. The perineal reflex was normal. The cutaneous trunci reflex was absent caudal to the ninth thoracic (T9) vertebral body bilaterally. No deep pain perception was present in either hind limb or in the perineal region. Spinal hyperesthesia was appreciated on palpation of the caudal thoracic spine. Neurological findings were consistent with a T3-L3 myelopathy. The dog was sedated with hydromorphone (Sandoz, Boucherville, Quebec), 0.1 mg/kg body weight (BW), IV and midazolam (Abbott Laboratories, Abbott Park, Illinois, USA), 0.1 mg/kg BW, IV. Anesthesia was induced using propofol (Rapinovet; Schering-Plough, Pointe Claire, Quebec), 4 mg/kg BW, IV and maintained on isoflurane (IsoFlo; Abbott, Saint-Laurent, Quebec) inhalant anesthetic at 2.5% in 2 L/min oxygen. Computed tomography (CT) of the spine revealed a lytic and irregular dorsal spinous process of the eighth thoracic (T8) vertebral body. A myelogram was performed using 463
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Figure 1. Computed tomography of the T8 vertebral body. A myelogram was performed and the computed tomography images demonstrated a severe extradural dorsal mass causing spinal cord ventral deviation and compression (thick black arrow). Note the osseous destruction of the vertebral body, which involved the dorsal spinous process (not shown) and lamina (thin black arrow).
0.4 mL/kg of iohexol (GE Healthcare, Missisauga, Ontario) administered intrathecally. A second CT scan revealed moderate extradural spinal cord compression at the T8 vertebral body (Figure 1). The radiographic and CT images were reviewed by a radiologist (TW). The osseous changes evident radiographically involved osseous destruction and proliferation of the spinous process of T8, essentially in its entirety, with no abnormalities of any neighboring bone. The myelogram images were indicative of a mass effect at the level of T8, with contrast evident cranial and caudal to this site but not at this site (VD view not available). The CT images revealed that the mass effect was created by severe extra-dural compression at the level of T8, originating dorsally, and compressing and deviating the cord ventrally (Figure 1). The radiographic diagnosis was moderate to severe extra-dural compression at the level of T8, with osseous destruction and proliferation of the T8 spinous process. Given the monostatic nature of the lesion, primary osseous neoplasia was considered the most likely differential, with an infectious cause being less likely. Surgical decompression was elected via a dorsal laminectomy. Cefazolin (Sandoz, Boucherville, Quebec), 22 mg/kg BW, IV q2h was administered perioperatively. The patient was positioned in sternal recumbancy and aseptically prepared over the mid thoracic spine. An 8-cm incision was made over the dorsal midline at the level of T7-T9. The epaxial muscles were reflected laterally from the dorsal spinous processes of T7-T9 to the level of the vertebral bodies. Rongeurs were used to remove the dorsal spinous processes of T7 (removed for improved visualization) and T8. The T8 dorsal spinous process and dorsal lamina were soft and irregular, with a grey/yellow discoloration. This was gently removed, revealing additional soft, irregular grey/yellow tissue directly over the dorsal and dorsolateral borders of the spinal canal. All of the resected tissues were collected and submitted to the Prairie Diagnostic Services (PDS) laboratory in Saskatoon, Saskatchewan, for histopathology and aerobic and anaerobic bacterial culture. Closure was routine. The patient recovered uneventfully from anesthesia, and was continued on oral metacam and tramadol as previously prescribed. Intermittent boluses of hydromorphone, 0.1 mg/kg BW, 464
IV were given q4 to 6h overnight as needed for discomfort. Cephalexin (Novolexin; Novopharm, Toronto, Ontario), 500 mg, PO, q12h was administered while histopathology and culture results were pending. Normosol-R intravenous fluids were administered overnight and discontinued the following day. Nursing care was initiated, which included bladder expression q6h and flipping the hind end q6h. Soft bedding was provided and changed as needed to minimize the risk of developing pressure sores. The following day, there was no change in the patient’s neurological status. Massage and passive range of motion exercises were initiated and performed 3 times daily. Two days following submission of the tissues, a moderate growth of a yeast was reported. The colonies became mucoid after further incubation at room temperature, suggesting a Cryptococcus species. The culture was sent to a mycology reference laboratory in Quebec for confirmation. Histopathology results revealed severe, diffuse pyogranulomatous fungal meningitis and osteomyelitis with intralesional yeast consistent with Cryptococcus sp. (Figure 2). Following this diagnosis, serum was submitted to PDS for Cryptococcus antigen titer. The patient was started on fluconazole (compounded at Strathcona Pharmacy, Edmonton, Alberta), 150 mg, PO, q12h, and cephalexin was discontinued. Follow-up questioning of the owners revealed that the patient had been to Vancouver Island during a vacation in July 2011. Final culture results revealed that the yeast was Cryptococcus gattii, a pathogen recently reported on the west coast of Canada, including Vancouver Island. A fungal serology titer (latex agglutination test) was performed at Cornell University Veterinary Diagnostics Lab. This was positive for Cryptococcus antigen at a dilution of 1:512. A full fundic examination was performed and no ocular lesions were noted. There were no respiratory signs or gastro intestinal signs reported by the owners at any time, and thoracic radiographs taken by the referring veterinarian at the time of initial presentation were normal. There was no other evidence of systemic Cryptococcus infection. The patient was discharged 9 d after initial presentation. Neurologically, the dog was still paralyzed in both hind limbs but had a return of pain perception. Extensor rigidity was noted in both hind limbs. Fluconazole therapy at 150 mg, PO, q12h, was prescribed for 6 mo, and tramadol 50 mg PO q8h was administered for an additional 3 d. The owners were given instructions for care of a paralyzed patient, including bladder expression and passive range of motion exercises in the hind limbs. At suture removal 14 d following surgery, the dog had improved neurologically and was demonstrating some early evidence of mild motor function in the hind limbs. The owners reported improvement in motor function at home over the next several weeks via follow-up telephone conversations. The patient began receiving bi-weekly rehabilitation therapy at a local veterinary clinic and was noted to be consistently improving. Approximately 2 mo following discharge, the dog was ambulatory in the pelvic limbs with hind limb proprioceptive ataxia. Conscious, voluntary bladder function was present. Spinal reflexes were within normal limits on all limbs. CVJ / VOL 54 / MAY 2013
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Figure 2. Histopathology of the extradural mass. A — The bone marrow cavity of the T8 dorsal lamina is dotted with numerous round Cryptococcus gattii organisms showing characteristic thick clear wall “soap bubble” morphology (arrows). The field is scattered with foamy macrophages and neutrophils (1003). B — Compressive extradural mass at T8. The meninges are heavily colonized with Cryptococcus gattii yeast (arrows) and saturated with a large number of foamy macrophages. The yeast in the center displays a typical narrow-base budding (1003).
The owners’ perception of outcome was considered excellent. Serum Cryptococcus antigen titers were obtained 3 mo following the initial surgery, and were unchanged at 512. Fluconazole therapy was continued at the previously prescribed dose, and Cryptococcus antigen titers at 5 mo following initial surgery was 256. Molecular typing was consistent with Cryptococcus gattii serotype VGIIA. At the time of manuscript submission, the dog was still receiving fluconazole therapy as previously prescribed and clinically had very mild paraparesis.
Discussion Cryptococcus is an environmental fungus that has the potential to be pathogenic to humans and animals. Traditionally, Cryptococcus gatti was thought to be limited to the tropics and subtropics (1). Since 1999, however, C. gattii infections have emerged in multiple species in southwestern British Columbia (2). By March 2002, there were 45 animal cases and 50 human cases confirmed by cytological, histopathological, or culture methods (2). Infection by Cryptococcus typically occurs when dessicated yeast cells or basidiospores found in the environment are inhaled (1). These can then cause infection directly within the lungs, or they can spread to other parts of the body. The most common clinical signs in dogs with infection from the Pacific northwest (including southwestern British Columbia), in descending order, include respiratory signs, central nervous system (CNS) signs, generalized illness, subcutaneous tissue lesions, ocular lesions, and gastrointestinal signs (3,4). Typical CNS signs include ataxia, neck pain, and seizures secondary to direct invasion by the fungus. Evidence of CNS signs is typically associated with a poorer prognosis (3). In our patient, clinical signs were not only attributed to direct CNS invasion (meningeal invasion on histopathology), but also to extradural compression caused by infection of the surrounding tissues as seen on the CT scan. To the authors’ knowledge, there has only been 1 other report of extradural spinal cord compression caused by cryptococcosis CVJ / VOL 54 / MAY 2013
in a dog, which occurred in Louisiana (5). In that case, a cervical intervertebral disc was infected and subsequently extruded into the spinal canal, resulting in acute non-ambulatory tetraparesis. The patient was successfully treated with surgical decompression and fluconazole therapy. Similar to our patient, there was no evidence of involvement of other organ systems. Molecular typing of the C. gattii strain isolated from our patient was consistent with VGIIa. In Canada, this strain has been found on the British Columbia mainland and Vancouver Island (6). It has also been found in the USA in Washington, North Carolina, California, and Oregon (6,7). Our patient had never travelled in the USA, and had been to Vancouver Island approximately 5 mo prior to developing clinical signs. In addition, on Vancouver Island, the risk factors for infection with C. gattii include high activity level outdoors and living near a site of commercial environmental disturbance (8). Our patient spent time outdoors hiking through the natural terrain. It is therefore reasonable to conclude that this patient most likely contracted Cryptococcus infection while on Vancouver Island, as the natural climate in central Alberta does not support growth of this fungus and there is no other travel history to areas that support Cryptococcus growth. In humans, immunosuppression is a risk factor for cryptococcosis infection in British Columbia (9). Immunosuppression has not been identified as a predisposing feature in animal cases (2,8). The dog in this case report had no evidence of immunosuppression, and had not been on any immunosuppressive therapies. Fluconazole therapy was initiated in our patient following the histopathological diagnosis. Fluconazole has been very effective as a sole antifungal agent in cats in some studies (10). Current recommendations for treatment in dogs with cryptococcosis include long-term azole maintenance therapy to enhance survival and prevent relapse in patients with central nervous system infections (11). Serology can be useful in monitoring clearance of infection with treatment. One study recommends that antifungal therapy should be continued until the serology 465
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titers decline to , 1 (12). Alternatively, therapy may be discontinued after a 32-fold or greater reduction in titer (12). Periodic evaluations of antigen titer can be performed once every 1 to 2 mo to guide when treatment may be discontinued. Without histopathology, it is impossible to determine when clearance has occurred. Relapse of infection has been documented in 1 dog up to 30 mo following complete resolution of clinical signs (13); however, in that case the antigen titer was never less than 1:32 (13). To date, there has not been a case report of recurrence in a dog if the antigen titer had returned to , 1. It seems reasonable, therefore, that fluconazole therapy could be stopped once the antigen titer declines to , 1. In our patient, the Cryptococcus antigen titer did not decrease 3 mo following fluconazole therapy, despite clinical improvement. It is possible that antigen titers may have increased initially once treatment was started, as antigen was released from the tissues. The titer may then have subsequently decreased to the level observed 3 mo later. Surgical decompression likely played the most important and significant role in clinical improvement. Recent in vitro studies have revealed that fluconazole may be less effective than ketoconazole and amphotericin B, thus additional antifungal therapies may be considered (6,14). However, additional therapies must be weighed against the potential negative side effects as well as additional cost to the client. At 5 mo following diagnosis, the titer had decreased to 256. Additional antifungal therapies, therefore, were not initiated and the patient was continued on fluconazole therapy. One limitation to our case is that a CSF sample was not submitted at the time of the initial diagnostic workup. A tumor was initially suspected; therefore, only tissue samples for histopathology were obtained, which we thought would be more likely to provide a diagnosis. Because of this, a baseline CSF Cryptococcus antigen titer was not obtained. An initial CSF titer may be used for future comparisons. However, obtaining a CSF sample is somewhat invasive, is not without inherent risks, and requires a financial commitment by the owner. In a patient that is clinically improving, it can be challenging to convince clients such tests are necessary. Continued monitoring has been elected, but if improvements are not seen, additional treatments may be initiated. Dogs that are presented for acute hind limb paralysis with absent deep pain perception secondary to thoracolumbar disc disease are typically given a guarded prognosis (approximately 50%) for return of function (15–17). Prognosis for our patient at the time of diagnosis was difficult to predict because of the unusual cause. However, it was reasonable to assume that if the clinical signs were related primarily to an extradural spinal cord compression that could be removed, prognosis should be similar to decompression following an intervertebral disc extrusion. At the time of submission of this manuscript, the patient was ambulatory with mild proprioceptive ataxia in the hind limbs. In addition, full urinary and fecal continence returned. This was considered a successful outcome, as a good return to normal activity and function was obtained. Neurological improvement is expected to continue over the next several months (17).
466
In conclusion, this case report describes Cryptococcus gattii infection causing extradural spinal cord compression in a dog. Treatment consisting of decompressive surgery and fluconazole therapy was successful in returning the dog to a functional level. Although some neurological deficits remain, the patient’s outcome is considered good to excellent. This is the first report of extradural spinal cord compression from C. gattii infection in Canada.
Acknowledgments The authors thank Dr. Karen Bartlett and Dr. Musangu Ngeleka for helping facilitate and perform phenotyping. We also thank Dr. Kim Robinson for helping with rehabilitation and follow-up assessments of the patient. CVJ
References 1. Sorrell TC. Cryptococcus neoformans variety gattii. Med Mycol 2011;39: 155–168. 2. Stephen C, Lester S, Black W, Fyfe M, Raverty S. Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia. Can Vet J 2002;43:792–794. 3. 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. 4. Malik R, Dill-Macky E, Martin P, Wigney DI, Muir DB, Love DN. Cryptococcosis in dogs: A retrospective study of 20 consecutive cases. J Med Vet Mycol 1995;33:291–297. 5. Kerwin SC, McCarthy RJ, VanSteenhouse JL, Partington BP, Taboada J. Cervical spinal cord compression caused by cryptococcosis in a dog: Successful treatment with surgery and fluconazole. J Am Anim Hosp Assoc 1998;34:523–526. 6. Lester SJ, Malik R, Bartlett KH, Duncan CG. Cryptococcosis: Update and emergence of Cryptococcus gattii. Vet Clin Path 2011;40:4–17. 7. 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. 8. Duncan CG, Stephen C, Campbell J. Evaluation of risk factors for Crytococcus gattii infection in dogs and cats. J Am Vet Med Assoc 2006; 228:377–382. 9. Bartlett KH, Cheng PY, Duncan C, et al. A decade of experience: Cryptococcus gattii in British Columbia. Mycopathologia 2012;173: 311–319. 10. Malik R, Wigney DI, Muir DB, Gregory DJ, Love DN. Cryptococcosis in cats: Clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole. J Med Vet Mycol 1992;30:133–144. 11. Lavely J, Lipsitz D. Fungal infections of the central nervous system in the dog and cat. Clin Tech Small Anim Pract 2005;20:212–219. 12. Malik R, McPetrie R, Wigney DI, Craig AJ, Love DN. A latex cryptococcal antigen agglutination test for diagnosis and monitoring of therapy for cryptococcosis. Aust Vet J 1996;74:358–364. 13. Panciera DL, Bevier D. Management of cryptococcosis and toxic epidermal necrolysis in a dog. J Am Vet Med Assoc 1987;191:1125–1127. 14. Lester SL, Kowalewich NJ, Bartlett KH, Krockenberger MB, Fairfax TM, Malik R. Clinicopathologic features of an unusual outbreak of cryptococcosis in dogs, cats, ferrets and a bird: 38 cases (January to July 2003). J Am Vet Med Assoc 2004;225:1716–1722. 15. Scott HW, McKee WM. Laminectomy for 34 dogs with thoracolumbar intervertebral disc disease and loss of deep pain perception. J Small Anim Pract 1999;40:417–422. 16. Laitinen OM, Puerto DA. Surgical decompression in dogs with thoracolumbar intervertbral disc disease and loss of deep pain perception: A retrospective study of 46 cases. Acta Vet Scand 2005;46:79–85. 17. Ruddle TL, Allen DA, Schertel ER, et al. Outcome and prognostic factors in non-ambulatory Hansen Type I intervertebral disc extrusions: 308 cases. Vet Comp Orthop Tramatol 2006;19:29–34.
CVJ / VOL 54 / MAY 2013
A
2-year-old, spayed female, German short-haired pointer was presented to the Guardian Veterinary Centre (GVC) in November 2011 for evaluation of acute hind limb paralysis. Approximately 10 d earlier, the dog had appeared painful to the owners. Physical examination by the referring veterinarian revealed caudal thoracic spinal hyperesthesia without any neurological deficits. Medical management was initiated consisting of meloxicam (Metacam; Boehringer, Burlington, Ontario), 1.75 mg, PO, q24h; tramadol (compounded at Strathcona Pharmacy, Edmonton, Alberta), 50 mg, PO, q12h; and methylcarbamol (Robaxin; Pfizer, Kirkland, Quebec), 250 mg, PO, q8h, as well as instructions for strict activity restrictions. Clinically, the dog’s comfort improved; however, 1 d prior to presentation the dog developed ambulatory hind limb proprioceptive ataxia with delayed hind limb postural reactions. Results of a complete blood (cell) count (CBC) and serum chemistry panel were within normal limits. No spinal abnormalities were detected on survey thoracic and abdominal radiographs which were taken by the referring veterinarian and included
Michigan State University, College of Veterinary Medicine, East Lansing, Michigan, USA (Kurach); Prairie Diagnostic Services, University of Saskatchewan, Saskatoon, Saskatchewan (Wojnarowicz); Washington State University, College of Veterinary Medicine, Pullman, Washington, USA (Wilkinson); Guardian Veterinary Centre, Edmonton, Alberta (Sereda). Address all correspondence to Dr. Lindsey Kurach; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. CVJ / VOL 54 / MAY 2013
the thoracolumbar spine at the periphery of the films. Medical management was continued as described. The following day, clinical signs worsened to include non-ambulatory hind limb paralysis with questionable deep pain perception. The patient was referred to the GVC for further workup.
Case description On presentation to Guardian Veterinary Centre, the patient was anxious, alert, and responsive. The dog’s weight was 18.1 kg, and vital parameters were within normal limits. Neurological examination revealed normal mentation, cranial nerves, and proprioception in the forelimbs. The dog was non-ambulatory in the hind limbs, with absent conscious proprioception and no motor function. Spinal reflexes in the forelimbs were normal. In the hind limbs, the withdrawal and patellar reflexes were normal to slightly exaggerated. The perineal reflex was normal. The cutaneous trunci reflex was absent caudal to the ninth thoracic (T9) vertebral body bilaterally. No deep pain perception was present in either hind limb or in the perineal region. Spinal hyperesthesia was appreciated on palpation of the caudal thoracic spine. Neurological findings were consistent with a T3-L3 myelopathy. The dog was sedated with hydromorphone (Sandoz, Boucherville, Quebec), 0.1 mg/kg body weight (BW), IV and midazolam (Abbott Laboratories, Abbott Park, Illinois, USA), 0.1 mg/kg BW, IV. Anesthesia was induced using propofol (Rapinovet; Schering-Plough, Pointe Claire, Quebec), 4 mg/kg BW, IV and maintained on isoflurane (IsoFlo; Abbott, Saint-Laurent, Quebec) inhalant anesthetic at 2.5% in 2 L/min oxygen. Computed tomography (CT) of the spine revealed a lytic and irregular dorsal spinous process of the eighth thoracic (T8) vertebral body. A myelogram was performed using 463
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Figure 1. Computed tomography of the T8 vertebral body. A myelogram was performed and the computed tomography images demonstrated a severe extradural dorsal mass causing spinal cord ventral deviation and compression (thick black arrow). Note the osseous destruction of the vertebral body, which involved the dorsal spinous process (not shown) and lamina (thin black arrow).
0.4 mL/kg of iohexol (GE Healthcare, Missisauga, Ontario) administered intrathecally. A second CT scan revealed moderate extradural spinal cord compression at the T8 vertebral body (Figure 1). The radiographic and CT images were reviewed by a radiologist (TW). The osseous changes evident radiographically involved osseous destruction and proliferation of the spinous process of T8, essentially in its entirety, with no abnormalities of any neighboring bone. The myelogram images were indicative of a mass effect at the level of T8, with contrast evident cranial and caudal to this site but not at this site (VD view not available). The CT images revealed that the mass effect was created by severe extra-dural compression at the level of T8, originating dorsally, and compressing and deviating the cord ventrally (Figure 1). The radiographic diagnosis was moderate to severe extra-dural compression at the level of T8, with osseous destruction and proliferation of the T8 spinous process. Given the monostatic nature of the lesion, primary osseous neoplasia was considered the most likely differential, with an infectious cause being less likely. Surgical decompression was elected via a dorsal laminectomy. Cefazolin (Sandoz, Boucherville, Quebec), 22 mg/kg BW, IV q2h was administered perioperatively. The patient was positioned in sternal recumbancy and aseptically prepared over the mid thoracic spine. An 8-cm incision was made over the dorsal midline at the level of T7-T9. The epaxial muscles were reflected laterally from the dorsal spinous processes of T7-T9 to the level of the vertebral bodies. Rongeurs were used to remove the dorsal spinous processes of T7 (removed for improved visualization) and T8. The T8 dorsal spinous process and dorsal lamina were soft and irregular, with a grey/yellow discoloration. This was gently removed, revealing additional soft, irregular grey/yellow tissue directly over the dorsal and dorsolateral borders of the spinal canal. All of the resected tissues were collected and submitted to the Prairie Diagnostic Services (PDS) laboratory in Saskatoon, Saskatchewan, for histopathology and aerobic and anaerobic bacterial culture. Closure was routine. The patient recovered uneventfully from anesthesia, and was continued on oral metacam and tramadol as previously prescribed. Intermittent boluses of hydromorphone, 0.1 mg/kg BW, 464
IV were given q4 to 6h overnight as needed for discomfort. Cephalexin (Novolexin; Novopharm, Toronto, Ontario), 500 mg, PO, q12h was administered while histopathology and culture results were pending. Normosol-R intravenous fluids were administered overnight and discontinued the following day. Nursing care was initiated, which included bladder expression q6h and flipping the hind end q6h. Soft bedding was provided and changed as needed to minimize the risk of developing pressure sores. The following day, there was no change in the patient’s neurological status. Massage and passive range of motion exercises were initiated and performed 3 times daily. Two days following submission of the tissues, a moderate growth of a yeast was reported. The colonies became mucoid after further incubation at room temperature, suggesting a Cryptococcus species. The culture was sent to a mycology reference laboratory in Quebec for confirmation. Histopathology results revealed severe, diffuse pyogranulomatous fungal meningitis and osteomyelitis with intralesional yeast consistent with Cryptococcus sp. (Figure 2). Following this diagnosis, serum was submitted to PDS for Cryptococcus antigen titer. The patient was started on fluconazole (compounded at Strathcona Pharmacy, Edmonton, Alberta), 150 mg, PO, q12h, and cephalexin was discontinued. Follow-up questioning of the owners revealed that the patient had been to Vancouver Island during a vacation in July 2011. Final culture results revealed that the yeast was Cryptococcus gattii, a pathogen recently reported on the west coast of Canada, including Vancouver Island. A fungal serology titer (latex agglutination test) was performed at Cornell University Veterinary Diagnostics Lab. This was positive for Cryptococcus antigen at a dilution of 1:512. A full fundic examination was performed and no ocular lesions were noted. There were no respiratory signs or gastro intestinal signs reported by the owners at any time, and thoracic radiographs taken by the referring veterinarian at the time of initial presentation were normal. There was no other evidence of systemic Cryptococcus infection. The patient was discharged 9 d after initial presentation. Neurologically, the dog was still paralyzed in both hind limbs but had a return of pain perception. Extensor rigidity was noted in both hind limbs. Fluconazole therapy at 150 mg, PO, q12h, was prescribed for 6 mo, and tramadol 50 mg PO q8h was administered for an additional 3 d. The owners were given instructions for care of a paralyzed patient, including bladder expression and passive range of motion exercises in the hind limbs. At suture removal 14 d following surgery, the dog had improved neurologically and was demonstrating some early evidence of mild motor function in the hind limbs. The owners reported improvement in motor function at home over the next several weeks via follow-up telephone conversations. The patient began receiving bi-weekly rehabilitation therapy at a local veterinary clinic and was noted to be consistently improving. Approximately 2 mo following discharge, the dog was ambulatory in the pelvic limbs with hind limb proprioceptive ataxia. Conscious, voluntary bladder function was present. Spinal reflexes were within normal limits on all limbs. CVJ / VOL 54 / MAY 2013
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Figure 2. Histopathology of the extradural mass. A — The bone marrow cavity of the T8 dorsal lamina is dotted with numerous round Cryptococcus gattii organisms showing characteristic thick clear wall “soap bubble” morphology (arrows). The field is scattered with foamy macrophages and neutrophils (1003). B — Compressive extradural mass at T8. The meninges are heavily colonized with Cryptococcus gattii yeast (arrows) and saturated with a large number of foamy macrophages. The yeast in the center displays a typical narrow-base budding (1003).
The owners’ perception of outcome was considered excellent. Serum Cryptococcus antigen titers were obtained 3 mo following the initial surgery, and were unchanged at 512. Fluconazole therapy was continued at the previously prescribed dose, and Cryptococcus antigen titers at 5 mo following initial surgery was 256. Molecular typing was consistent with Cryptococcus gattii serotype VGIIA. At the time of manuscript submission, the dog was still receiving fluconazole therapy as previously prescribed and clinically had very mild paraparesis.
Discussion Cryptococcus is an environmental fungus that has the potential to be pathogenic to humans and animals. Traditionally, Cryptococcus gatti was thought to be limited to the tropics and subtropics (1). Since 1999, however, C. gattii infections have emerged in multiple species in southwestern British Columbia (2). By March 2002, there were 45 animal cases and 50 human cases confirmed by cytological, histopathological, or culture methods (2). Infection by Cryptococcus typically occurs when dessicated yeast cells or basidiospores found in the environment are inhaled (1). These can then cause infection directly within the lungs, or they can spread to other parts of the body. The most common clinical signs in dogs with infection from the Pacific northwest (including southwestern British Columbia), in descending order, include respiratory signs, central nervous system (CNS) signs, generalized illness, subcutaneous tissue lesions, ocular lesions, and gastrointestinal signs (3,4). Typical CNS signs include ataxia, neck pain, and seizures secondary to direct invasion by the fungus. Evidence of CNS signs is typically associated with a poorer prognosis (3). In our patient, clinical signs were not only attributed to direct CNS invasion (meningeal invasion on histopathology), but also to extradural compression caused by infection of the surrounding tissues as seen on the CT scan. To the authors’ knowledge, there has only been 1 other report of extradural spinal cord compression caused by cryptococcosis CVJ / VOL 54 / MAY 2013
in a dog, which occurred in Louisiana (5). In that case, a cervical intervertebral disc was infected and subsequently extruded into the spinal canal, resulting in acute non-ambulatory tetraparesis. The patient was successfully treated with surgical decompression and fluconazole therapy. Similar to our patient, there was no evidence of involvement of other organ systems. Molecular typing of the C. gattii strain isolated from our patient was consistent with VGIIa. In Canada, this strain has been found on the British Columbia mainland and Vancouver Island (6). It has also been found in the USA in Washington, North Carolina, California, and Oregon (6,7). Our patient had never travelled in the USA, and had been to Vancouver Island approximately 5 mo prior to developing clinical signs. In addition, on Vancouver Island, the risk factors for infection with C. gattii include high activity level outdoors and living near a site of commercial environmental disturbance (8). Our patient spent time outdoors hiking through the natural terrain. It is therefore reasonable to conclude that this patient most likely contracted Cryptococcus infection while on Vancouver Island, as the natural climate in central Alberta does not support growth of this fungus and there is no other travel history to areas that support Cryptococcus growth. In humans, immunosuppression is a risk factor for cryptococcosis infection in British Columbia (9). Immunosuppression has not been identified as a predisposing feature in animal cases (2,8). The dog in this case report had no evidence of immunosuppression, and had not been on any immunosuppressive therapies. Fluconazole therapy was initiated in our patient following the histopathological diagnosis. Fluconazole has been very effective as a sole antifungal agent in cats in some studies (10). Current recommendations for treatment in dogs with cryptococcosis include long-term azole maintenance therapy to enhance survival and prevent relapse in patients with central nervous system infections (11). Serology can be useful in monitoring clearance of infection with treatment. One study recommends that antifungal therapy should be continued until the serology 465
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titers decline to , 1 (12). Alternatively, therapy may be discontinued after a 32-fold or greater reduction in titer (12). Periodic evaluations of antigen titer can be performed once every 1 to 2 mo to guide when treatment may be discontinued. Without histopathology, it is impossible to determine when clearance has occurred. Relapse of infection has been documented in 1 dog up to 30 mo following complete resolution of clinical signs (13); however, in that case the antigen titer was never less than 1:32 (13). To date, there has not been a case report of recurrence in a dog if the antigen titer had returned to , 1. It seems reasonable, therefore, that fluconazole therapy could be stopped once the antigen titer declines to , 1. In our patient, the Cryptococcus antigen titer did not decrease 3 mo following fluconazole therapy, despite clinical improvement. It is possible that antigen titers may have increased initially once treatment was started, as antigen was released from the tissues. The titer may then have subsequently decreased to the level observed 3 mo later. Surgical decompression likely played the most important and significant role in clinical improvement. Recent in vitro studies have revealed that fluconazole may be less effective than ketoconazole and amphotericin B, thus additional antifungal therapies may be considered (6,14). However, additional therapies must be weighed against the potential negative side effects as well as additional cost to the client. At 5 mo following diagnosis, the titer had decreased to 256. Additional antifungal therapies, therefore, were not initiated and the patient was continued on fluconazole therapy. One limitation to our case is that a CSF sample was not submitted at the time of the initial diagnostic workup. A tumor was initially suspected; therefore, only tissue samples for histopathology were obtained, which we thought would be more likely to provide a diagnosis. Because of this, a baseline CSF Cryptococcus antigen titer was not obtained. An initial CSF titer may be used for future comparisons. However, obtaining a CSF sample is somewhat invasive, is not without inherent risks, and requires a financial commitment by the owner. In a patient that is clinically improving, it can be challenging to convince clients such tests are necessary. Continued monitoring has been elected, but if improvements are not seen, additional treatments may be initiated. Dogs that are presented for acute hind limb paralysis with absent deep pain perception secondary to thoracolumbar disc disease are typically given a guarded prognosis (approximately 50%) for return of function (15–17). Prognosis for our patient at the time of diagnosis was difficult to predict because of the unusual cause. However, it was reasonable to assume that if the clinical signs were related primarily to an extradural spinal cord compression that could be removed, prognosis should be similar to decompression following an intervertebral disc extrusion. At the time of submission of this manuscript, the patient was ambulatory with mild proprioceptive ataxia in the hind limbs. In addition, full urinary and fecal continence returned. This was considered a successful outcome, as a good return to normal activity and function was obtained. Neurological improvement is expected to continue over the next several months (17).
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In conclusion, this case report describes Cryptococcus gattii infection causing extradural spinal cord compression in a dog. Treatment consisting of decompressive surgery and fluconazole therapy was successful in returning the dog to a functional level. Although some neurological deficits remain, the patient’s outcome is considered good to excellent. This is the first report of extradural spinal cord compression from C. gattii infection in Canada.
Acknowledgments The authors thank Dr. Karen Bartlett and Dr. Musangu Ngeleka for helping facilitate and perform phenotyping. We also thank Dr. Kim Robinson for helping with rehabilitation and follow-up assessments of the patient. CVJ
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