A 9-year-old neutered male domestic shorthair cat from Maricopa County in Arizona, weighing 4.6 kg (10.1 lbs) was presented to the Companion Animal Clinic at Midwestern University College of Veterinary Medicine (MWU-CVM) for evaluation of a 7-day history of progressive hind limb paraparesis. The cat lived inside the owner's residence and did not venture outside. Seven days before presentation to the MWU-CVM, the cat was evaluated by the primary care veterinarian for a 12-h history of right hind limb paresis. Physical examination revealed decreased patellar and withdrawal (flexor) reflexes of the right hind limb. The remainder of the examination was deemed unremarkable. The cat was administered dexamethasone (0.4 mg/kg subcutaneously once) and discharged with prednisolone (1.6 mg/kg PO q24h) for the purpose of empirically treating a presumed spinal cord disorder with suspected underlying spinal cord edema. The primary care veterinarian evaluated the cat 6 days later, at which time, the left hind limb had become moderately paretic and the right was unchanged. A complete blood count (CBC) and serum chemistry revealed no clinically relevant abnormalities.
Physical examination findings upon presentation to the MWU-CVM (day 1), included heart rate of 210 beats/minute, respiratory rate of 30 breaths/minute, and a normal temperature 100.5 F (38.1 C). Cardiothoracic auscultation did not reveal a murmur, arrhythmia, or abnormal lung sounds. There was no history of respiratory abnormalities (e.g., cough, dyspnea, tachypnea, cyanosis). Neurologic examination performed by a board-certified veterinary neurologist (JE) found ambulatory hind limb paraparesis and intact withdrawal reflexes. There was severely decreased voluntary ambulation on the right hind limb and moderate decrease in the left hind limb, with severe gluteal and hamstring muscle atrophy. Hind limb spinal reflexes were intact with increased patellar reflexes. The cutaneous trunci reflex was normal, and the cat vocalized on palpation of L1-L4. The remainder of the examination was unremarkable and neurolocalization supported a T3-L3 myelopathy. Primary differential diagnoses considered included spinal neoplasia (e.g., meningioma or lymphoma), intervertebral disc disease, a vascular event, infectious causes (feline infectious peritonitis, feline leukemia virus (FeLV), coccidioidomycosis, toxoplasmosis), or another inflammatory disorder. Three-view spinal and thoracic radiographs were procured and showed a diffuse miliary pattern (structured interstitial pattern) consisting of numerous small, ill-defined soft tissue nodules (~3 mm) within all lung lobes (Figure 1A). There was also a small broad-based soft tissue structure dorsal to the cranial sternum in the region of the sternal lymph node. The remaining thoracic structures were unremarkable. The lateral radiographs of the lumbar spine showed a widening of the vertebral canal associated with the L4 vertebral body, but there was no permeative/moth-eaten lysis to the bone. A commercial ELISA-based kit (SNAP Feline Triple Test, IDEXX, Westbrook, Minnesota) was negative for detection of antibodies for feline immunodeficiency virus and negative for FeLV and Dirofilaria immitis antigen. Tests for Toxoplasma gondii and Coccidioides spp. IgM and IgG serum antibody titers were submitted (Protatek Reference Laboratory, Mesa, Arizona). The cat was discharged with prednisolone (unchanged dosage) as the only medication.
The cat was presented again on day 4 for thoracic and spinal computed tomography (CT; CT Scanner, Syngo VC 40 16-slice, Siemens Healthcare, Germany). On examination, voluntary movement of the hind limbs was now absent. The previous paraparesis had progressed to paraplegia with decreased, but present deep pain sensation to both hind limbs. The diffuse miliary pulmonary pattern was confirmed with the CT scan (Figures 2B,C). There was also mild enlargement of the tracheobronchial lymph nodes, cranial mediastinal lymph nodes, and sternal lymph node (Figure 2A). In the pre-contrast series, there was an isoattenuating widening of the spinal cord silhouette dorsal to the vertebral body of L4 (Figure 3A). The focal widening had a diffuse, homogeneous enhancement with distinct borders. There was an expansile widening of the spinal canal dorsal to L4 associated with the strongly contrast-enhancing mass (Figures 3B,C).
Cytologic interpretation of samples obtained via fine needle aspiration of the lung and sternal lymph node revealed pyogranulomatous inflammation with Coccidioides spp. spherules and endospores (Figures 4A,B). Cisternal cerebral spinal fluid (CSF) was examined cytologically and revealed a nucleated cell count of 1 cell/muL (normal, <8 cells/muL), a red blood cell count of 2,470 cells/muL (reference, 0 cells/muL), and a total protein of 22.5 mg/dL (reference, <25 mg/dL). A total of 12 nucleated cells were present on the cytospin preparation and consisted solely of non-degenerative neutrophils. There were no infectious agents or evidence of neoplasia observed. The small amount of red blood cells in the CSF sample likely represented a slight blood contamination from the collection process and was not considered significant. Based upon the cytologic results from the lung lobe and sternal node, a suspected diagnosis of a spinal Coccidioides spp. granuloma was made. Magnetic resonance imaging (MRI) of the thoracolumbar spinal cord with emergent surgical decompression at a veterinary referral hospital with MRI capabilities was recommended, but the owner declined and elected to have an exploratory spinal cord decompressive procedure performed at the MWU-CVM. The cat was discharged with the following medications: fluconazole (10.9 mg/kg PO q12h) and prednisolone (unchanged dosage).
Scheduling conflicts resulted in the cat being presented for surgery 3 days later (day 7). Immediate surgical decompression is generally recommended for paraplegic patients or those with acute rapid deterioration of myelopathic signs as delay in surgical intervention could result in a poor prognosis. The neurological examination at presentation for surgery was unchanged from the previous evaluation. A right hemilaminectomy/spinal exploratory surgery at mid-body of L4 was performed (Supplemental Figure 1). No extradural lesion was present upon opening the window, but the spinal cord was focally swollen and discolored over the midbody of L4 (Supplemental Figure 1A). A durectomy was performed over the exposed spinal cord and revealed a swollen and discolored spinal cord segment (Supplemental Figure 1B). A myelotomy was performed that revealed an intra-medullary mass (Supplemental Figure 1C). The mass was approximately 0.75 cm, round, semi-firm, and was removed en bloc (Supplemental Figure 1D). The spinal cord ventral to the mass was bruised and substantially compressed, leaving an indent that gradually re-expanded as the mass was removed (Supplemental Figure 1D). The overall dark purple coloring of the spinal cord gradually improved (Supplemental Figure 1E). A small amount of dark coloration and hemorrhage remained at the center of the residual indentation. It was undetermined if the remaining indentation was due to compression from the mass or a focal area of myelomalacia. The excised mass was submitted for histopathology. The cat was hospitalized overnight with an indwelling urinary catheter. Treatments included: fentanyl (3 mug/kg IV CRI), Lactated Ringers solution (12 mL/h), dexamethasone (0.22 mg/kg IV q24h), cefazolin (22 mg/kg IV q8h), fluconazole (10.9 mg/kg PO q12h), and 7.2% NaCl (5 mL/kg IV q6h). Hypertonic saline was administered because it accelerates the reduction of spinal cord edema and stabilizes neuronal function in cases of acute, severe spinal cord injury.
The day after surgery (day 8), the urinary catheter was removed. Minimal voluntary movement was noted in the right hind limb with good voluntary movement in the contralateral limb. Postural reactions were decreased in both hind limbs, but were improved compared to before surgery when they were absent. The following day (day 9), the cat was able to use the left hind limb to stand and ambulate, but there was still minimal movement in the right hind limb though, there was improvement in muscle tone. There was normal tactile placing and proprioception in the left hind limb with absent postural reactions in the right. Histopathology of the excised mass showed that normal spinal cord architecture was obscured by mixed inflammation dominated by epithelioid macrophages, few multinucleated giant cells, neutrophils, and fewer, often perivascular, lymphocytes and plasma cells. Admixed within the inflammatory cells were frequent hyperemic reactive vessels and numerous circular spherules that measured up to 33 mum in diameter with a thin 1 mum refractile capsule that surrounded combinations of central basophilic stippling, vacuolation, and packed with 2-3 mum diameter endospores (consistent with Coccidioides spp.). Occasionally, the spherules were degenerate with externally released endospores. At the periphery of sections, residual neuroparenchyma contained gemistocytic astrocytes, acute hemorrhage, degeneration, and malacia (Figures 4C,D). Serologic test results for Toxoplasma gondii (IgM and IgG negative) and Coccidioides spp. (IgM negative, IgG 1:4) also returned. The cat was discharged (2 days after surgery) on day 10, at which time, there had been considerable improvement. The cat was mobile using the left hind limb, which demonstrated moderate paresis. The right hind limb had good extensor tone, but still was without voluntary movement. The medications prescribed at discharge included fluconazole (unchanged dosage) and prednisolone (gradually weaned and discontinued 14 days later).
The cat was presented for planned evaluations on days 20 and 35. The surgical incision was unremarkable on day 20. Neurologic findings at both examinations were similar; the cat was ambulatory in the hind limbs with a mild to moderate hind limb ataxia and right hind limb paresis. Postural reactions to the left hind limb were nearly normal but delayed to the right hind limb. Spinal reflexes to the left hind limb were normal, but the withdrawal reflex to the right hind limb was mildly decreased. The cutaneous trunci reflex was normal and the cat was only mildly reactive on spinal palpation over the surgery site (Supplemental Video 1).
A serum chemistry, CBC, Coccidioides spp. antibody titers (Protatek Reference Laboratory) and thoracic radiographs were performed on day 35. The Coccidioides spp. IgM remained negative and there was a one-fold reduction in IgG titer (1:2). Thoracic radiographs revealed an improvement to the miliary pulmonary pattern with static sternal lymphadenomegaly (Figure 1B). The CBC and serum chemistry were unremarkable. Medications at the time of discharge included fluconazole (unchanged dosage) and gabapentin (3.0 mg/kg PO q12h, as needed for pain).
On day 140, the cat was presented for a planned evaluation and the owner reported the cat had become fully ambulatory and recently started to climb a "cat tree" in the home. Neurologic examination revealed mild ataxia in the right hind limb with slight toe-dragging. The postural reactions in the right hind limb were still decreased (Supplemental Video 2). Serum chemistry, CBC, Coccidioides spp. antibody titers, urinalysis, and thoracic radiographs were performed. The Coccidioides spp. titers remained similar (IgM negative, IgG 1:4) (Antech Diagnostics, Irvine, California) and the CBC, chemistry, and urinalysis were unremarkable. Thoracic radiographs revealed improvement of the miliary pattern with fewer pulmonary nodules and the remaining soft tissue nodules were less distinct. The sternal lymphadenomegaly was still identifiable and similar to the previous study (Figure 1C). Fluconazole was continued unchanged and gabapentin was discontinued 30 days later.
The cat was presented for an additional recheck evaluation on day 310. The owner reported that since the last examination, the cat ambulated normally, was able to jump to the second tier of the "cat tree", and run, but occasionally limped on the right hind limb. Neurologic examination revealed continued mild improvement with ambulation to both hind limbs with mild paresis of the right hind limb that occasionally "knuckled" while walking. Postural reactions on the right hind limb were slightly delayed but normal in the remaining three limbs (Supplemental Video 3). Serum chemistry, CBC, Coccidioides spp. antibody titers (Antech Diagnostics), urinalysis, and thoracic radiographs were performed. The Coccidioides spp. titers were negative and the CBC and urinalysis were unremarkable. There was a mild increase in serum alanine transaminase activity (ALT; 196 IU/L, reference interval chemistry, 10-100 IU/L); all other measured chemistry analytes were unremarkable. Fluconazole was decreased (12 mg/kg PO q24h) and then discontinued approximately 4 months later (day 452). Thoracic radiographs at this time showed resolution of the pulmonary nodules (Figure 1D). A recheck assessment performed on day 463 revealed persistent proprioceptive ataxia and decreased postural reactions of the right hind limb (Supplemental Video 4). Coccidioides spp. antibody titers (Protatek Reference Laboratory) were similar (IgM negative; IgG 1:2). No medications were prescribed at discharge.
The last in-hospital recheck examination took place on day 739 (2 years). The owner reported that although there was some decrease in function of the right hind limb, it did not hinder normal activity. There were no systemic signs of illness that could be associated with Coccidioides spp infection (e.g., altered appetite and lethargy). On examination, the cat was ambulatory with a moderate shuffling gait associated with the right hind limb, with occasional knuckling. Postural reactions and spinal reflexes to the right hind limb were delayed to absent. Evaluation of the left hind limb was unremarkable (Supplemental Video 5). The functional deterioration of the right hind limb was within the spectrum of reasonable expectation 2 years after a severe spinal cord injury. Coccidioides spp. antibody titers (Protatek Reference Laboratory) were repeated and were unchanged from previous results (IgM negative; IgG 1:2). Given there were no significant clinical changes, other than what might be expected over time, no specific treatment was recommended.
Computed tomography of the thorax in a cat with a compressive Coccidioides spp. spinal granuloma before surgery or administration of fluconazole. Dorsal plane reconstruction with bone window display. There were numerous, irregular, small soft tissue nodules (white chevrons) within all lung lobes.