A 9-year-old 17.5-kg (38.5-lb) neutered male crossbred dog was referred for evaluation of nonambulatory tetraparesis and signs of cervical pain of a few hours' duration. The dog had had 3 episodes of ataxia and signs of cervical pain during the preceding month; 1 episode occurred after the dog was bitten by another dog and resolved following oral administration of a single dose of an NSAID. During the referral examination, the dog had nonambulatory tetraparesis with delayed postural reactions in all 4 limbs; clinical signs were more pronounced on the right side. The withdrawal reflex of the right forelimb was mildly decreased. Signs of pain were elicited when the dog's neck was flexed to either side. With the exception of the neurologic examination findings, results of a complete physical examination were unremarkable.
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 |
|---|---|
| Nonambulatory tetraparesis with delayed postural reactions in all 4 limbs | Focal or diffuse lesion within the CI-T2 spinal cord segments, brainstem, or peripheral nervous system (peripheral nerves or neuromuscular junction), or myopathy |
| Decreased right forelimb withdrawal reflex | Focal or diffuse lesion within the CI-T2 spinal cord segments or peripheral nervous system (peripheral nerves or neuromuscular junction), or myopathy |
| Increased muscle tone in all 4 limbs | Focal or diffuse lesion within the CI-C5 spinal cord segments or cerebellum, peripheral nervous system hyperexcitability, or myopathy |
| Signs of cervical pain | Focal or diffuse lesion within the CI-T2 spinal cord segments or orthopedic or muscular conditions |
Likely location of 1 lesion
A lesion within the CI-C5 spinal cord segments was suspected.
Etiologic diagnosis—Diagnoses to consider for acute painful C1-C5 myelopathy in a dog include intervertebral disk disease (compressive extrusion or acute noncompressive nucleus pulposus extrusion), inflammatory or infectious meningomyelitis, vertebral fracture or luxation, neoplasia, diskospondylitis, and empyema or paravertebral abscesses. Other myelopathies secondary to a subarachnoid diverticulum or a vascular accident are less likely because they are not associated with signs of pain. The diagnostic plan included clinicopathologic analyses (to help rule out inflammatory or infectious diseases), thoracic radiography (to rule out the presence of metastasis or primary neoplasms), and plain survey radiography and CTa myelography of the cervical portion of the vertebral column (to identify a primary focus of infection, fracture, luxation, or neoplasm). Magnetic resonance imaging was also indicated but was not available at that time. Collection and analysis of a CSF sample was planned to rule out meningeal inflammation. Subsequent diagnostic procedures, such as biopsy of any abnormal tissue, would be guided by the imaging findings.
Diagnostic test findings—Results of a CBC, serum biochemical profile, and urinalysis were within reference ranges. Thoracic and cervical radiography did not reveal any abnormalities. Computed tomographic myelography (slice width, 0.625 mm; helical pitch, 1; image production interval, 0.625 mm; 120 kV; and automatic interval, 80 to 200 mAs) revealed extradural symmetric dorsal and lateral spinal cord compression at the level of the occipitoatlantoaxial (OAA) joint (Figure 1) consistent with capsular hypertrophy, OAA joint arthritis, hematoma, empyema, neoplasia, or ganglioneuritis. A small C2-C3 disk protrusion was also identified but was not considered relevant on the basis of the dog's neurologic signs. A CSF sample was obtained from the cerebellomedullary cistern; both the CSF total cell count and the protein concentration were within reference ranges. The dog was hospitalized (day 1), and treatment with methadoneb (0.3 mg/kg [0.14 mg/lb], SC, q 4 h) and carprofenc (2 mg/kg [0.91 mg/lb], IV, q 12 h) was initiated. Twenty-four hours later, the dog was able to ambulate with moderate ataxia and its signs of cervical pain had resolved. On day 3, the dog was discharged from the hospital and the owner was instructed to continue treatment with carprofenc (2 mg/kg, PO, q 12 h for 5 days) and administer tramadold (4 mg/kg [1.82 mg/lb], PO, q 8 h for 7 days). On day 9, the dog was almost neurologically normal but was returned 3 days later (day 12) because of nonambulatory tetraparesis. Cervical CTa following IV administration of contrast mediume was performed and revealed mild contrast enhancement of the previously identified compressive lesion. Cervical CT myelography was repeated and the findings were the same as those of the previous myelography. At that time, differential diagnoses included OAA articular capsule hypertrophy secondary to arthritis or neoplasia. An exploratory OAA arthrotomy was performed. A biopsy specimen of the articular capsule was obtained and an impression smear was examined microscopically. The impression smear of the articular capsule had evidence of a granulomatous inflammatory reaction with numerous amastigotes consistent with Leishmania spp inside the macrophages and free in the inflammatory infiltrate. Histologic examination of the biopsy sections of the articular capsule confirmed the cytologic findings including the presence of Leishmania-like organisms. Leishmania DNA was detected in the CSF sample by use of a PCR assay. A blood sample from the dog was obtained; by use of an ELISA, anti-Leishmania antibodies (titer, 1:80; reference range, < 1:80) were detected in the serum. On the basis of the diagnostic findings, a diagnosis of compressive myelopathy attributable to Leishmania-induced OAA joint arthritis and capsular hypertrophy was made.
A transverse CT myelogram (bone window) obtained at the level of the occipitoatlantoaxial joint in a dog that was evaluated because of nonambulatory tetraparesis and signs of cervical pain of a few hours' duration and 3 episodes of ataxia and signs of cervical pain during the preceding month. Notice the extradural symmetric circumferential spinal cord compression.
Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.789
A transverse CT myelogram (bone window) obtained at the level of the occipitoatlantoaxial joint in a dog that was evaluated because of nonambulatory tetraparesis and signs of cervical pain of a few hours' duration and 3 episodes of ataxia and signs of cervical pain during the preceding month. Notice the extradural symmetric circumferential spinal cord compression.
Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.789
A transverse CT myelogram (bone window) obtained at the level of the occipitoatlantoaxial joint in a dog that was evaluated because of nonambulatory tetraparesis and signs of cervical pain of a few hours' duration and 3 episodes of ataxia and signs of cervical pain during the preceding month. Notice the extradural symmetric circumferential spinal cord compression.
Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.789
Comments
Leishmaniasis is a zoonotic systemic disease caused by diphasic protozoan parasites of the genus Leishmania that affects people and other animals, with domestic dogs being the main reservoir host.f Etiopathogenesis and clinical forms of canine leishmaniasis are widely reported.1 After introduction into the host's skin through the bite of a sand fly, the Leishmania parasites are phagocytized by macrophages. Within those cells, the organisms replicate as round, nonmotile amastigotes1; eventually, replication leads to lysis of the macrophages.1 The released amastigotes are then taken up by additional macrophages, with resultant spread of infection throughout the internal organs.1 Lesions are caused by the host's inflammatory and degenerative reactions to the parasite in the affected organs and by the formation of immune complex deposits in some tissues.1 In cases of canine visceral leishmaniasis, Leishmania infantum has the ability to cross the blood brain barrier and penetrate the CNS without necessarily resulting in neurologic signs, even though histopathologic alterations in the CNS are apparent.2,3
Numerous clinical syndromes have been associated with canine leishmaniasis, including intra-cranial, spinal cord, or peripheral nervous system signs,1,4–16,f and lead to various pathological findings. The reported findings related to nervous system dysfunction include vasculitis affecting spinal cord vessels and choroid plexuses of the brain,1,4,6,8,f myositis,1,5,9 intramedullary spinal cord granuloma,15 extradural granuloma,10 granulomatous radiculoneuritis,8 meningomyelitis,1,8 multiple presumed ischemic brain infarctions (MRI findings),7 meningoencephalitis,1,8,12 granulomatous meningitis,14 serum hyperviscosity,11 brain hemorrhagic stroke,1 and ischemic myelopathy.1 However, only a few reports have shown the presence of small inflammatory infiltrates directly linked to the observation of amastigotes in nervous tissue2,3,8 or in the lesion.10
During Leishmania infection, articular involvement can also occur; of 80 dogs with untreated leishmaniasis, 30 (37.5%) were reluctant to walk or had an abnormal gait (or both).17 This atypical pathological change may develop as a result of an inflammatory reaction to either the organisms or the immune complexes in the synovium18; however, only on rare occasions have Leishmania amastigotes been observed in synovial fluid samples.19–21 Leishmania-induced arthritis in dogs has been reported previously,18–24 but no cases have involved the OAA joint and caused capsular hypertrophy, leading to compressive myelopathy, as occurred for the dog of the present report.
The objectives of treatment for Leishmania infection are typically to induce a general reduction of the parasite load, treat organ damage caused by the parasite, restore efficient immune responses, stabilize any drug-induced clinical improvement, and treat clinical relapses.25 The recommended treatment protocol for a sick dog (at stage C [ie, a dog with clinically evident leishmaniasis] as outlined in the guidelines for diagnosis and clinical classification of leishmaniasis26) includes the combination of meglumine antimoniate administered at a dosage of 100 mg/kg (45.5 mg/lb), SC, once a day for 4 weeks and allopurinol administered at a dosage of 10 mg/kg (4.5 mg/lb), PO, every 12 hours for at least 6 months.26
A canine host's immune response has an important role in the development, outcome, and response to treatment of Leishmania infection.26 All known drugs used to treat Leishmania infection in dogs can lead to temporary or permanent remission of clinical signs, but none effectively eliminate the infection.26 In most dogs with stage C leishmaniasis, correct application of the aforementioned meglumine antimoniate-allopurinol treatment protocol should result in a clinical cure that is stable for > 1 year.26
For the dog of the present report, treatment with meglumine antimoniate and allopurinol, as described, achieved complete resolution of the clinical signs; the dog remained neurologically normal for 26.5 months thereafter. This case has highlighted the fact that in endemic areas, Leishmania-induced arthritis should be included in the differential diagnoses for compressive myelopathy of the OAA joint in dogs with ambulatory problems and signs of cervical pain, even in the absence of systemic or clinicopathologic evidence of the disease.
Footnotes
Helical 16-slice unit, Brivo, General Electric Healthcare, Madrid, Spain.
Metasedin, Esteve Laboratories, Barcelona, Spain.
Rimadyl injectable solution, Zoetis, Madrid, Spain.
Tramadol Normon, Normon, Valencia, Spain.
Iohexol (0.3 mL/kg [0.14 mL/lb], intrathecal or 400 mg/kg [181.8 mg/lb], IV), General Electric Healthcare, Madrid, Spain.
Sánchez D, Navalón I, Font A, et al. Central nervous system involvement induced by Leishmania infantum in a dog (abstr), in Proceedings. 20th Annu ESVN& ECVN Symp 2007; 511.
References
1. Giannuzzi AP, Ricciardi M, De Simone A, et al. Neurological manifestations in dogs naturally infected by Leishmania infantum: descriptions of 10 cases and a review of the literature. J Small Anim Pract 2017;58:125–138.
2. Lopes Macau W, Cortez de Sá J, de Carvalho da Silva AP, et al. Main lesions in the central nervous system of dogs due to Leishmania infantum infection. BMC Vet Res 2017;13:255.
3. da Costa Oliveira V, Cardoso Boechat V, Velho Mendes AA Jr, et al. Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: parasite load, viability, co-infections and histological alterations. PLoS One 2017;12:e0175588.
4. Font A, Mascort J, Altimira J, et al. Acute paraplegia associated with vasculitis in a dog with leishmaniasis. J Small Anim Pract 2004;45:199–201.
5. Paciello O, Oliva G, Gradoni L, et al. Canine inflammatory myopathy associated with Leishmania infantum infection. Neuromuscul Disord 2009;19:124–130.
6. Pumarola M, Brevik L, Badiola J, et al. Canine leishmaniasis associated with systemic vasculitis in two dogs. J Comp Pathol 1991;105:279–286.
7. José-López R, De la Fuente C, Añor S. Presumed brain infarctions in two dogs with systemic leishmaniasis. J Small Anim Pract 2012;53:554–557.
8. Márquez M, Pedregosa JR, López J, et al. Leishmania amastigotes in the central nervous system of a naturally infected dog. J Vet Diagn Invest 2013;25:142–146.
9. Vamvakidis CD, Koutinas AF, Kanakoudis G, et al. Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum). Vet Rec 2000;146:698–703.
10. Cauduro A, Favole P, Lorenzo V, et al. Paraparesis caused by vertebral canal leishmaniotic granuloma in a dog. J Vet Intern Med 2011;25:398–399.
11. Proverbio D, Spada E, Perego R, et al. Seizures as a consequence of hyperviscosity syndrome in two dogs naturally infected with Leishmania infantum. J Am Anim Hosp Assoc 2016;52:119–123.
12. Ikeda FA, Laurenti MD, Corbett CE, et al. Histological and immunohistochemical study of the central nervous system of dogs naturally infected by Leishmania (Leishmania) chagasi. Braz J Vet Res Anim Sci 2007;44:5–11.
13. Toplu N, Aydogan A. An immunohistochemical study in cases with usual and unusual clinicopathological findings of canine visceral leishmaniosis. Parasitol Res 2011;109:1051–1057.
14. Viñuelas J, García-Alonso M, Ferrando L, et al. Meningeal leishmaniosis induced by Leishmania infantum in naturally infected dogs. Vet Parasitol 2001;101:23–27.
15. José-López R, De la Fuente C, Pumarola M, et al. Intramedullary spinal cord mass presumptively associated with leishmaniasis in a dog. J Am Vet Med Assoc 2014;244:200–204.
16. Cardinot CB, Silva JES, Yamatogi RS, et al. Detection of Ehrlichia canis, Babesia vogeli and Toxoplasma gondii DNA in the brain of dogs naturally infected with Leishmania infantum. J Parasitol 2016;102:275–279.
17. Slappendel RJ. Canine leishmaniasis. A review based on 95 cases in The Netherlands. Vet Q 1988;10:1–16.
18. McConkey SE, López A, Shaw D, et al. Leishmanial polyarthritis in a dog. Can Vet J 2002;43:607–609.
19. Santos M, Marcos R, Assunção M, et al. Polyarthritis associated with visceral leishmaniasis in a juvenile dog. Vet Parasitol 2006;141:340–344.
20. Agut A, Corzo N, Murciano J, et al. Clinical and radiographic study of bone and joint lesions in 26 dogs with leishmaniasis. Vet Rec 2003;153:648–652.
21. Spreng D. Leishmanial polyarthritis in 2 dogs. J Small Anim Pract 1993;34:559–563.
22. Blavier A, Keroack S, Denerolle P, et al. Atypical forms of canine leishmaniosis. Vet J 2001;162:108–120.
23. Buracco P, Abate O, Guglielmino R, et al. Osteomyelitis and arthrosynovitis associated with Leishmania donovani infection in a dog. J Small Anim Pract 1997;38:29–30.
24. Wolschrijn CHPM, Hazewinkel H, Wolvekamp WTC. Destructive polyarthritis in a dog with visceral leishmaniasis. J Small Anim Pract 1996;37:601–603.
25. Oliva G, Roura X, Crotti A, et al. Guidelines for treatment of leishmaniasis in dogs. J Am Vet Med Assoc 2010;236:1192–1198.
26. Paltrinieri S, Solano-Gallego L, Fondati A, et al. Guidelines for diagnosis and clinical classification of leishmaniasis in dogs. J Am Vet Med Assoc 2010;236:1184–1191.
