Survival of a Suspected Case of Central Nervous System Cuterebrosis in a Dog: Clinical and Magnetic Resonance Imaging Findings

Introduction

Central nervous system (CNS) migration of Cuterebra spp. larvae in dogs is not well documented.^1–4 Confirmed case reports describe acute onset of CNS signs such as ataxia, paralysis, seizures, and depression.^1–4 Some animals, particularly cats, may be presented initially with coughing, sneezing, and other signs of upper respiratory tract infection.^5,6 The variability in clinical signs is based on the migratory tract of the larva. The first case report of CNS cuterebrosis was by Hatziolos.¹ A dog was examined for progressive ascending paralysis that led to coma and death within 7 days of the onset of clinical signs. Postmortem examination revealed a Cuterebra spp. larva in the mesencephalon between the oculomotor and trochlear nuclei, adjacent to the cerebral aqueduct. A mild focal inflammatory reaction was seen adjacent to the larva; a general, diffuse inflammatory reaction involved the cerebrum, medulla oblongata, and cerebellum; and spongy degeneration was noted along the parasitic migratory track. Another case report described a dog that became depressed and listless the day after routine vaccinations and deworming with pyrantel-pamoate.² Treatment consisted of diphenhydramine, dexamethasone, activated charcoal, atropine, and intravenous (IV) fluid therapy. The dog’s condition deteriorated, and death occurred 48 hours after the onset of clinical signs.² Postmortem examination revealed a Cuterebra spp. larva embedded in the meninges overlying the parietal lobes. A moderately severe meningoencephalomyelitis involving the meninges and outer cerebral cortex, as well as multiple perivascular foci throughout the cerebrum, were noted.² Less severe inflammatory changes were seen in the cerebellum and spinal cord.

Central nervous system migration of Cuterebra spp. larvae typically results in a fatal meningoencephalitis in both dogs and cats.^1–8 Although there are case reports of cats surviving infection with Cuterebra spp. larvae, there are no case reports of survival in dogs.^1–8 The purpose of this report is to illustrate a case of suspected intracerebral migration of a Cuterebra spp. larva in a dog that was successfully treated.

Case Report

A 3-year-old, spayed female rat terrier was referred to Auburn University Veterinary Teaching Hospital (AUVTH) with a 3-week history of progressive neurological signs. Clinical signs of stupor, disorientation, and tetraparesis started acutely. The dog was presented to the referring veterinarian 2 days after the onset of these signs. On initial presentation, the dog was ambulatory, circling to the left, and was blind in the right visual field. The dog was current on all routine vaccinations. A complete blood count (CBC) revealed a leukocytosis (29,000 cells/μL; reference range 6000 to 16,900 cells/μL) with a neutrophilia (17,100 cells/μL; reference range 3300 to 12,000 cells/μL) and lymphocytosis/monocytosis (11,900 cells/μL; reference range 1100 to 6300 cells/μL). A differential white blood cell count was not done. Prednisone^a (1 mg/kg per os [PO] q 12 hours for 5 days, then q 24 hours for 5 days, then 0.5 mg/kg q 24 hours), sucralfate^b (1 gm PO q 8 hours), and butorphanol^c (1 mg PO as needed for pain relief) were started by the referring veterinarian. One week after the initial evaluation, the dog’s condition progressed to tight circling to the left with severe ataxia, pruritus around the left eye, aggression, disorientation, depression, and intermittent vomiting.

The dog was presented to AUVTH 3 weeks after the initial evaluation for progression of neurological signs. At the time of admission, the owners brought an insect larva (approximately 8 × 3 × 3 mm) that the dog had expelled in vomitus 1 week earlier. Characteristics of the larva were typical of Cuterebra spp.⁹ The body of the larva was light tan, and numerous, stout, black spines were evenly distributed over the body segments. Posterior spiracles and anterior mouth hooks were present. Species identification was not performed.

Neurological examination showed depressed mentation, tight and frequent circling to the left, moderate ataxia, and falling to the right. A right-sided hemiparesis and proprioceptive deficits were also noted. Cranial nerve examination showed decreased pupillary light reflexes (direct and consensual) on the right, absent menace response on the right, and decreased right intranasal sensation. A multifocal CNS lesion was suspected. Differential diagnoses for a multifocal CNS disorder included infectious diseases (e.g., toxoplasmosis, canine distemper, or rickettsial, bacterial, and fungal infections), vascular diseases (e.g., thromboembolism, ischemia, hemorrhage), inflammatory diseases (e.g., granulomatous meningoencephalitis), and parasitism.

Results of a CBC, biochemical panel, and urinalysis were normal. Serum titers for Ehrlichia canis, Rickettsia rickettsii, and Toxoplasma gondii were negative. Results of serum canine distemper virus titers were consistent with exposure but not active infection (immunoglobulin G [IgG] 1:1250 and immunoglobulin M [IgM] <1:10; reference ranges, IgG >1:150 protective and IgM <1:10 negative for active infection). Thoracic radiographs and an electrocardiogram were normal.

Magnetic resonance imaging (MRI)^d and cisternal collection of cerebrospinal fluid (CSF) were performed under general anesthesia. The dog was premedicated with butorphanol^e (0.4 mg/kg intramuscularly [IM]) and induced with midazolam^f (0.2 mg/kg IV) and thiopental^g (11 mg/kg IV). General anesthesia was maintained with isoflurane^h in oxygen. Cerebrospinal fluid was collected from the cerebellomedullary cistern and was analyzed immediately. Analysis showed elevated red blood cells (3890 cells/μL; reference range 0 cells/μL), white blood cells (30 cells/μL; reference range <5 cells/μL), and total protein (35 mg/dL; reference range <25 mg/dL). Cytology revealed 15% neutrophils, 15% small lymphocytes, and 70% large macrophages—many of which were large and highly vacuolated. These small vacuoles often contained acidophilic or basophilic proteinaceous material [Figures 1, 2]. Cytological results were consistent with a mild inflammatory process.

On the transverse T1-weighted (Repetition time [TR] 670, Echo time [TE] 16) and T2-weighted (TR 2500, TE 80) spin-echo MRIs, there was a lesion involving the gray and white matter of the left cerebral hemisphere. This lesion extended from the left temporal lobe gray matter adjacent to the thalamus and the lateral ventricle through the internal capsule into the parietal lobe gray matter. The left lateral ventricle was mildly dilated. The lesion was hypointense to surrounding gray matter on T1-weighted images, hyperintense to surrounding gray matter on T2-weighted images, and enhanced with administration of gadoteridolⁱ (0.3 mL/kg IV) [Figures 3, 4, 5]. Contrast enhancement on the T1-weighted images was indicative of breakdown of the blood-brain barrier or an increased vascular supply to the area, compatible with neoplasia, inflammation, edema, or pera-cute hemorrhage. No mass was seen. The lesion location and enhancement with contrast were consistent with a parasitic (Cuterebra spp.) migratory tract, as described previously.^5,10

The dog remained hospitalized for 4 weeks for observation. Prednisone^a was continued for its anti-inflammatory effects (0.5 mg/kg PO q 24 hours) and was tapered to every-other-day administration at discharge. Omeprazole^j (0.5 mg/kg PO q 24 hours) was started as a gastrointestinal protectant because of the potential effects of corticosteroid therapy. The dog’s neurological deficits improved substantially over the 4-week period. Consecutive neurological examinations showed persistent, right-sided hemiparesis and blindness; however, the circling to the left and ataxia decreased to the extent that the dog was able to walk nearly normally. Left-sided circling became less frequent and tended to occur in wider circles. One month after discharge, the owners reported continued improvement in the dog, with only mild persistent weakness of the right side.

Discussion

Visceral larva migrans involving the CNS is uncommon. Cuterebra spp. larvae attach to the host’s hair and then enter a natural orifice or burrow into the skin and subcutaneous tissue, where they continue to develop.⁹ Developing larvae may migrate a considerable distance through tissues and can enter the CNS.⁹ Entry into the CNS may occur through the ethmoid foramina or other skull foramina, hematogenously via large vessels, or by direct penetration through the middle ear into meninges and venous sinuses.^{1,5,7,8,11,12}

In the case reported here, it was speculated that the Cuterebra spp. larva gained entrance into the CNS via the nares and cribriform plate. Because the presence of the larva in the vomitus of this dog suggested an exit site associated with the oral cavity, it was theorized that the larva exited through the cribriform plate and then entered the nasopharynx and the oral cavity. Ingestion of a host animal (e.g., rabbit or squirrel) infected with a larva was also a possibility. Ultimately, entrance and exit sites for the larva were not confirmed. Migration of the larva through the CNS may have been responsible for the changes in neurological signs over the initial 3-week period.

In previous reports, aberrant Cuterebra spp. larva migration has resulted in severe meningoencephalitis and death of affected dogs.^1–4 Histopathological lesions and CSF analysis have shown suppurative inflammation consistent with meningoencephalitis.^2,3 Other reported histopathological lesions included the presence of a parasitic migratory tract characterized by spongy degeneration, cerebral infarction, and hemorrhage; necrosis; astrogliosis; and focal granulomatous encephalitis surrounding the larva.^1–8,11 Damage to the CNS from parasitic migration appeared to be a two-fold process: mechanical damage from the presence of the parasite and secondary inflammation. Both processes have probably contributed to the high mortality rate in dogs; however, the inflammatory response may be particularly harmful, especially with death of the parasite.^1–4

Central nervous system infection with a Cuterebra spp. larva was not confirmed by necropsy in the dog reported here, but it was compatible with results of CSF analysis. Cerebrospinal fluid analysis was characterized by a mild increase in total protein and leukocytes, with macrophages predominating. These macrophages had acidophilic and basophilic vacuoles that may have represented necrotic debris. Nonsuppurative inflammation characterized by a predominance of macrophages and mildly elevated total protein has been described previously in feline cerebral cuterebrosis.^5,6 Other reports have shown elevated eosinophils and suppurative inflammation within the CSF.^3,5 Mild increases in CSF protein (<100 mg/dL) and leukocytes (<100 cells/μL), primarily mononuclear cells, are typical of parenchymal damage or necrosis seen with neoplasia, viral disease, and degenerative diseases.¹³ In this case, these changes were thought to be indicative of necrosis associated with parasite migration.

Results of both CSF analysis and MRI led to the diagnosis of aberrant Cuterebra spp. larva migration in this dog. There are few descriptions in the veterinary literature of neuroimaging findings in cerebral cuterebrosis. Computed tomography (CT) may show a mottled appearance to the brain, focal or multifocal areas of decreased attenuation, minimal mass effect, and tract-like lesions.^5,10 With MRI, lesions may appear hypointense on T1-weighted images and hyperintense on T2-weighted images.¹⁰ Lesions are often contrast enhancing on both CT and MRI.^5,10

Descriptions are limited regarding MRI findings in human visceral larval migrans syndrome involving the CNS. Neurotoxocariasis may be characterized by a granulomatous process. Typical MRI changes include multiple contrast-enhancing subcortical, cortical, or white matter lesions that are hypointense on T1-weighted images and hyperintense on T2-weighted images.^14–16 A hemorrhagic tract with scattered, deep intracerebral hemorrhage and diffuse, white matter lesions has been described in cerebral gnathostomiasis.¹⁷

In this dog, the MRI findings were supportive of larval migrans within the left cerebral hemisphere. Lesion hypointensity on T1-weighted images and hyperintensity on T2-weighted images with contrast enhancement, as described in this case, are not specific for parasitic CNS infection. These characteristics may be seen with other infectious and inflammatory diseases of the CNS and may reflect the limited way the brain responds to inflammation.¹⁰ However, the tract-like lesion seen in this case was characteristic for migrating parasitism and was unlikely to develop with other inflammatory or infectious diseases or vascular lesions.^{1,5,6,8,10,11,17}

A recent report described treatment for cerebral cuterebrosis.⁵ It is, however, unclear whether it is more harmful to allow continued migration of the larva within the CNS or to kill the parasite and induce damage from the inflammatory reaction. Cats with cerebral cuterebrosis have benefited from the use of antiparasiticals combined with anti-inflammatory drugs.⁵ Glass et al. gave diphenhydramine^k (4 mg/kg IM) 1 to 2 hours before ivermectin^l (400 μg/kg subcutaneously) and dexamethasone^m (0.1 mg/kg IV).⁵ The antihistamine and corticosteroids were given to prevent anaphylactic or allergic reactions associated with larval death from the ivermectin. Enrofloxacinⁿ (5 mg/kg PO q 12 hours) was also used in these cats to prevent bacterial infection associated with migration of the larvae. This treatment protocol was not used in the current case. Not only did the dog’s clinical signs stabilize, but it was also believed that the Cuterebra spp. larva was no longer present in the CNS based on MRI. An anti-inflammatory dose of prednisone was given and tapered over 1 month. The dog’s condition improved over time, but it was unknown whether this improvement was from the natural course of the disease or a result of corticosteroid therapy. Ultimately, the anti-inflammatory dose of prednisone alone may not have been useful if the larva was still present and migrating within the CNS.

Conclusion

Possible intracerebral migration of a Cuterebra spp. larva was diagnosed in a dog with acute onset of multifocal CNS signs. Diagnosis was based on discovery of a Cuterebra spp. larva within the dog’s vomitus and compatible findings on MRI and CSF analysis. Clinical signs improved slowly over time with the use of anti-inflammatory doses of prednisone.