Toxoplasma gondii spinal granuloma in a cat

Abstract

Case summary

A 7-year-old female spayed domestic shorthair cat was presented with a history of progressive pelvic limb ataxia. A CT scan of the thoracic spine identified an extradural, left lateralised and compressive soft tissue mass at the level of T9. A decompressive hemilaminectomy at the level of T8–T10 and tissue sampling of the mass were performed. Histopathological examination revealed a parasite granuloma caused by Toxoplasma gondii infection. Postoperatively, the cat improved consistently, but mild left pelvic limb lameness remained. At 5 weeks, a recheck CT scan showed a small, enhancing soft tissue lesion in the left epidural space at T9, causing a mild left lateral compression of the spinal cord. After 9 months, the cat acutely deteriorated neurologically and was euthanased without postmortem examination.

Relevance and novel information

To our knowledge, this is the first report of a T gondii spinal granuloma in a cat. Such a granuloma should be considered as a differential in cats with evidence of an extradural soft tissue mass.

Introduction

In cats, the most common causes for pelvic limb ataxia are inflammatory/infectious or neoplastic spinal diseases. Less common causes are trauma, congenital, vascular and degenerative or metabolic/alimentary diseases.^{1 –3}

Toxoplasmosis is a common feline parasite disease causing central nervous deficits and is considered to be one of the most important parasite diseases of the central nervous system in cats.^{4 –8} This report describes a case of a histopathologically and PCR-confirmed spinal Toxoplasma gondii granuloma in a cat.

Case description

A 7-year-old, female spayed domestic shorthair cat was referred to our veterinary hospital with a history of progressive pelvic limb ataxia. The cat had been regularly vaccinated and dewormed. At the time of presentation, the cat was in a good body condition and had no reported pre-existing illnesses. Trauma could not be excluded, as the cat had access to the outdoors, but no obvious injuries had been observed.

Before presenting to our hospital, the cat had been examined by a local veterinarian. Radiographs of the spine, haematology and biochemistry were unremarkable at the time. Treatment with meloxicam (Metacam suspension 0.5 mg/ml; Boehringer Ingelheim) 0.1 mg/kg q24h PO for several weeks did not lead to an improvement of the clinical signs.

A general physical examination at our hospital revealed no abnormalities. The neurological examination showed moderate pelvic limb ataxia. Proprioception and spinal reflexes were normal. Palpation of the spine at the thoracolumbar junction was painful. No cranial nerve deficits or behavioural abnormalities were present. For further investigations, a CT scan (GE Healthcare) of the spine was performed under general anaesthesia. The cat received butorphanol (Butorgesic 10 mg/ml; CP-Pharma) 0.2 mg/kg, dexmedetomidine (Dexdomitor 5 mg/10 ml, Zoetis) 2 g/kg, midazolam (Midazolam-ratiopharm 5 mg/ml; Ratiopharm) 0.1 mg/kg and Alfaxalon (Alfaxan 10 mg/ml; Jura) 2 mg/kg. During the CT scan, the cat received oxygen and isoflurane to maintain the anaesthesia.

During CT, an extradural, left lateralised, well-demarcated, oval-shaped and moderately enhancing soft-tissue attenuating mass was identified at the level of T9 (Figure 1). The mass occupied approximately two-thirds of the vertebral canal, resulting in severe compression of the spinal cord. The maximum width, height and length of the extradural mass was 4.5 × 3.5 × 9.3 mm. No osseous response of the vertebral body of T9 could be demonstrated.

Figure 1

(a) CT image in soft-tissue window: sagittal reconstruction of the spine from the sixth to 12th thoracic vertebra. There is a moderately enhancing soft-tissue attenuating mass in the spinal canal over the body of T9 (arrow). (b) CT image in soft-tissue window: transverse image at the midbody level of the ninth thoracic vertebra. The moderately enhancing soft-tissue attenuating mass is causing severe compression of the spinal cord (arrow)

A neoplastic or inflammatory mass was considered as the main differential diagnosis. Surgical exploration was initially declined and the cat was continued on medical treatment with meloxicam (Metacam suspension 0.5 mg/ml; Boehringer Ingelheim) 0.1 mg/kg q24h PO. However, due to the progression of neurological signs, the owner consented to surgery 5 days later. Preoperatively, the general examination was still unremarkable; however, the progression of ataxia without lateralisation was evident on the neurological examination.

A repeat CT scan before surgery showed an increase in size of the extradural mass at T9, measuring 4.9 (W) × 3.7 (H) × 11 (L) mm, resulting in more severe spinal cord compression. The general anaesthesia was induced with midazolam (Midazolam-ratiopharm 5 mg/ml, Ratiopharm) 0.1 mg/kg and alfaxalon (Alfaxan 10 mg/ml; Jurox) 4 mg/kg. Maintenance of the anaesthesia was achieved with oxygen and isoflurane. Perioperatively, the cat received a continuous infusion with isotonic crystalloid solution (Ringer’s lactate Hartman B Braun; Braun Melsungen) 5 ml/kg/h and fentanyl (Fentadon 50 µg/ml; Dechra) 5 µg/kg/h.

A left-sided decompressive hemilaminectomy was performed at the level of T8–T10. Intraoperatively, the mass was located at the level of T9 and appeared as a left-sided homogeneous non-bone-invasive extradural mass, resulting in severe spinal cord compression. The mass had no obvious capsule, and due to a very friable consistency, it could only be removed piecemeal. The mass was debulked as much as possible but could not be removed in its entirety. Tissue samples were preserved in formaldehyde and sent for histopathological examination (Fachpraxis für Tierpathologie München).

The cat recovered uneventfully from the general anaesthesia and remained hospitalised postoperatively. Therapy was started with amoxicillin–clavulanic acid (Synulox RTU 140/35 mg/ml; Zoetis) 20 mg/kg q24h SC, maropitant (Prevomax 10 mg/ml; Dechra) 1 mg/kg q24h IV, buprenorphine (Buprenovet Multidose 0.3 mg/ml; Bayer) 20 µg/kg q8h IV, metamizole sodium (Metapyrin 500 mg/kg; Serumwerk Bernburg) 50 mg/kg SC, prednisolone (prednisolone 5 mg, CP-Pharma) 0.8 mg/kg q24h PO and continuous infusion with isotonic crystalloid infusion solution (Ringer’s lactate according to Hartman B Braun; Braun Melsungen) 3 ml/kg/h was continued.

A histopathological examination revealed an eosinophilic supporting framework interspersed with multiple lymphocytes, plasma cells, and some granulocytes and macrophages. In addition, interspersed smaller vessel incisions, as well as isolated necrosis, could be found. Furthermore, individual globular structures or cystic formations with granular contents (most likely bradyzoites) could be identified (Figure 2). Histopathologically, a diagnosis of high-grade mixed-cell, chronic purulent and necrotising, partially granulomatous inflammation due to toxoplasmosis was made. Subsequently, a blood test and antibody determination by immunofluorescence (IDEXX Laboratories) confirmed, with IgM-IFT being negative and IgG-IFT being strongly positive with values of >1:1024. A subsequent PCR investigation of the granuloma tissue (SYNLAP.vet) was also positive for T gondii.

Figure 2

Representative histopathological image of the resected mass located in the spinal canal. Note the cystic formation with granular content in the middle, being identified as bradyzoites (arrow)

Based on the histopathological and laboratory results, therapy was changed to clindamycin (Cleorobe 75 mg; Zoetis or Zodon 25 mg/ml; Ceva Tiergesundheit) 22 mg/kg q12h PO for 6 weeks. Prednisolone was discontinued after 5 days and after a washout period of 48 h, and meloxicam (Metacam suspension 0.5 mg/ml; Boehringer Ingelheim) 0.1 mg/kg q24h PO was administered for a total of 2 weeks.

A recheck examination was performed 5 weeks after discharge at our hospital. According to the owner, the cat’s neurological function improved initially but then remained stagnated. At the recheck, mild pelvic limb ataxia was detectable, proprioception and spinal reflexes showed no deficits in all four limbs. However, because of persisting pelvic limb ataxia and concern for residual compression by or recurrence of the granuloma, a follow-up CT scan was performed under general anaesthesia using the same drug regime and inhalation as before. The follow-up CT scan showed a small, enhancing soft-tissue lesion in the left epidural space at T9, measuring 0.8 (W) × 3.4 (H) × 7 (L) mm, resulting in mild left lateral compression of the spinal cord. Contrast enhancement of the soft tissues could also be demonstrated in the region of the left hemilaminectomy and left lateral side along the spinous process of T9 (surgical approach).

Subsequent telephone updates by the owner revealed that the cat’s gait gradually improved further, but a mild gait abnormality remained. Nine months after surgery, the cat’s neurological condition acutely deteriorated and it was euthanased at the owners’ request without further clinical assessment. The owners refused a pathological examination.

Discussion

According to the study by Marioni-Henry,^1,2 the prevalence for infectious spinal diseases in cats is 32%. Another study of MRI examinations due to suspected spinal disease in cats revealed a prevalence of 14% for inflammatory/infectious diseases. ⁷ T gondii infection is considered to be the second most frequently diagnosed parasite disease of the central nervous system in cats, representing 6% of central nervous disorders.^2,4,5,8 However, to the authors’ knowledge, this is the first reported case of a spinal T gondii granuloma in a cat.

Infection with T gondii can occur in all mammals. Cats are the only definitive hosts, whereas other warm-blooded animals are considered intermediate hosts. Infection can occur diaplancentary and lactogenic or by oral ingestion of oocysts or other developmental stages; for example, through infected intermediate hosts, water, plants or soil. The most common route of entry of the parasite is thought to be through ingesting infected intermediate hosts.^{6,9 –11}

Toxoplasmosis is a common worldwide parasite disease, and depending on geographic location, a very high proportion of felids, especially older male cats, are seropositive. ¹² Globally, a seroprevalence of antibodies to T gondii among cats is thought to be approximately 35%. ¹³ Symptomatic cats present with dyspnoea, polypnea, abdominal discomfort, fever, anorexia, lethargy, vomiting, dermatitis, paresis or icterus. Intraocular inflammation due to multifocal iridochoroiditis was also evident in one or both eyes in 81.1%.^14,15 In addition, gastrointestinal, cardiac, muscular, cutaneous and pulmonary diseases have been described.^16–24 On the other hand, neurological signs, such as in the presented case, are rare with toxoplasmosis. In a study of 100 histologically proven infected cats, only 7% showed neurological signs, even though T gondii were detected in 80% of 55 examined brains. ¹⁴ The symptomatology in neurologically manifested toxoplasmosis appears highly variable. Anisocoria, torticollis, changes of behaviour, paresis secondary to segmental non-suppurative myelitis, distal polyneuropathy and seizures due to intracranial granulomas caused by T gondii have been reported in cats.^{25 –30}

Extradural spinal granulomas have not been reported due to T gondii, but due to a variety of other infectious organisms, such as Cryptococcoma, Coccidi-oides immitis, Histoplasma capsulatum and Mycobacterium microti.^{27,30 –34} To determine the aetiology of the extradural soft-tissue mass in this cat, a decompressive hemilaminectomy and tissue sampling were performed. Although the mass occupied approximately two-thirds of the vertebral canal, the cat showed only mild neurological signs, similar to some of the already reported extradural spinal granulomas due to parasite disease.^31,32 In relation to the severe spinal cord compression, more severe neurological deficits could have been suspected. This leads to the assumption that the compression has developed over a longer period, so that the nerve tissue could adapt slowly. Once toxoplasmosis was confirmed, recommended antibiotic treatment with clindamycin was started. ³⁵ The influence of viral diseases and clinical toxoplasmosis is controversial. There is evidence that an infection with feline leukaemia virus (FeLV) or feline immunodeficiency virus (FIV) can trigger an acute generalised toxoplasmosis, but in the general population, this could not be identified.^{36 –39} The presented cat was not tested, because it was regularly vaccinated against FeLV and FIV. Retrospectively, however, it would have been of interest if there was a concurrent infectious disease with impact on the immune system. Moreover, especially referring to cats and the fact that neurological disorders are often of infectious origin, a complete analysis of cerebrospinal fluid (CSF) should be done generally. ⁴⁰ MRI is considered the diagnostic tool of choice for disorders of the central nervous system. ⁴¹ In contrast, CT is currently superior to MRI for imaging bony structures. Since spinal tumours are often associated with osseous lesions and MRI was not available at our hospital, a CT scan was performed in the case described. ⁴²

Unfortunately, the cat showed significant neurological deterioration 9 months postoperatively and it was euthanased without further diagnostics. Based on the evidence of recurrence of an extradural soft-tissue mass on the 5-week postoperative CT scan, it is likely that clinically significant regrowth of the mass occurred. Retrospectively, a repeated determination of antibodies at the time of the second CT scan could have been of interest. More sensitive would have been an analysis of CSF or fine-needle aspiration of the previous granuloma location. ³⁵ Revision surgery or repeated treatment with clindamycin alone or with a second anti-T gondii drug could have been considered for a possible longer survival time, free of clinical signs.

Conclusions

An extradural granuloma caused by T gondii can be the cause for gait abnormalities in cats due to spinal cord compression. A hemilaminectomy and mass debulking can lead to temporary improvement of clinical signs.