A 12-year-old 5.4-kg (11.88-lb) spayed female Miniature Dachshund was referred for evaluation of a left head tilt and vestibular ataxia. The dog had become progressively ataxic over the preceding 3 days. Initially, the dog was presented to the primary veterinarian, who performed a CBC and serum biochemical panel; there were no important hematologic findings, and moderately high alanine transaminase activity (237 U/L; reference range, 10 to 125 U/L) and mild hyperglobulinemia (4.6 g/dL; reference range, 2.5 to 4.5 g/dL) were identified. The dog was given maropitant citrate (1 mg/kg [0.45 mg/lb], SC, once) just prior to referral. At the referral hospital, physical examination of the dog revealed mild dental tartar but no other abnormalities. Neurologic examination findings included right-sided vestibular signs. The dog paced in circles to the left; the menace and nasocortical stimulation responses on the right side were absent. Shortly after being admitted to the hospital, the dog developed generalized seizures.
Neurologic examination
Etiologic diagnosis
The primary differential diagnoses for the dog of the present report included neoplasia (intra- or extra-axial), infectious disease (bacterial, fungal, protozoal, or tick-borne infection), and inflammatory disease (meningoencephalitis). Plans for diagnostic investigation included 3-view thoracic radiography (to evaluate for evidence of neoplasia, infection, or any cardiac or pulmonary disease that could affect the dog's anesthetic risk level), abdominal radiography (to evaluate for any evidence of neoplasia or organomegaly), and MRIa of the brain (to assess for structural brain abnormalities, evidence of increased intracranial pressure, or evidence of inflammation). Depending on the results of the MRI scan, analysis of a CSF sample, and infectious disease testing of CSF and serum samples to further rule out inflammatory and infectious diseases were also considered. Abdominal ultrasonography was discussed with the owner; however, because this procedure could not be completed prior to the MRI scan, it was not pursued.
Diagnostic test findings
Three-view abdominal radiography revealed mild hepatomegaly and splenomegaly. These findings suggested an endocrine, regenerative, infectious, or inflammatory cause of the hepatomegaly and lymphoid hyperplasia or extra-medullary hematopoiesis as the cause of the splenomegaly. Radiographically, there was mild rounding of the caudal and cranial cardiac waists and rounding of the cardiac silhouette in the region of the right atrium. These findings were consistent with probable left atrial enlargement and mitral valve insufficiency.
The dog was anesthetized, and MRI of the brain was performed with a 3.0-T magnet. Multiplanar images of the brain to the level of the C3 vertebra were acquired including sagittal and transverse T1-weighted images; dorsal, sagittal, and transverse T2-weighted images; transverse T2*-gradient recall echo images; transverse diffusion-weighted and T2-weighted FLAIR images; and diffusion-weighted images before and after IV administration of a paramagnetic contrast agent (0.22 mL/kg [0.1 mL/lb]; total dose, 344.4 mg of gadodiamide).
The MRI scan revealed a large lesion within the left aspect of the thalamus and dorsal aspect of the left frontal and parietal lobes. The lesion was hyperintense on T2-weighted and T2-weighted FLAIR images and hypointense on T1-weighted images with central noncontrast enhancing and peripheral contrast enhancing material (Figure 1). This lesion measured approximately 1.4 × 1.8 × 1.5 cm and followed a somewhat curvilinear, well-defined tract extending in a ventroaxial to dorsoabaxial direction. No regions of susceptibility artifact were noted on transverse T2*-gradient recall echo images, and no restricted diffusion was noted on diffusion-weighted images. There was a slight rightward midline shift of the thalamus as a result of this lesion, and the intrathalamic adhesion was mildly displaced rostrally. There was crowding of the cerebellum within the cerebellar fossa. The caudal aspect of the cerebellum approached the foramen magnum, but no transforaminal herniation was evident. The ventricular system appeared normal with no evidence of dilation. The meninges appeared normal with no evidence of abnormal contrast enhancement or thickening. Air-filled tympanic bullae were observed. No lymphadenopathy was detected. The musculature of the head was symmetric and normal in appearance. There were no notable osseous abnormalities. Owing to the severity of the MRI findings, analysis of a CSF sample was not performed.
Transverse T2-weighted (A), transverse T2-weighted FLAIR (B), and dorsal T2-weighted (C) images of the brain of a dog that was referred for evaluation of a left head tilt and vestibular ataxia. The transverse images were obtained at the level of the thalamus. On the transverse T2-weighted and T2-weighted FLAIR images (A and B, respectively), notice the curvilinear hyperintense lesions (asterisks) in the left thalamus and frontal lobe. The hyperintense (bright) material surrounding this curvilinear tract on the T2 images (A and C), which is hypointense (dark) on the T2-weighted FLAIR image (B), is consistent with perilesional edema.
Citation: Journal of the American Veterinary Medical Association 258, 10; 10.2460/javma.258.10.1075
The differential diagnoses for the mass included neoplasia, parasitic meningoencephalitis (including infection with Cuterebra spp, Dirofilaria spp, or Toxascaris spp), or meningoencephalitis from another cause (bacterial or fungal infection or immune-mediated disease). Given the severity of the dog's clinical signs and the MRI findings, serologic infectious disease testing was not performed. The owner elected euthanasia of the dog by IV injection of propofol followed by IV injection of euthanasia solution. A necropsy was performed. Affecting the left thalamus and adjacent white matter tracts and extending to the meninges, there were locally extensive areas of rarefaction and neuropil necrosis with infiltration by moderate numbers macrophages and an abundant amount of phagocytized myelin (gitter cells). Adjacent vessels were reactive with plump endothelial cells. Adjacent to the areas of necrosis were perivascular cuffs of macrophages, lymphocytes, and plasma cells in variable numbers. There were occasional areas in which small vessel walls were expanded by homogeneous eosinophilic material (fibrinoid necrosis). Within areas of necrosis, multiple neurons were shrunken, angular, and hypereosinophilic (neuronal necrosis). Perivascular spaces were moderately expanded by clear space (edema). These findings were consistent with a diagnosis of necrotizing meningoencephalitis (NME).
Comments
Necrotizing meningoencephalitis is a fatal, non-infectious inflammatory disease of the CNS of dogs.1 This disease was first reported as affecting Pugs but has since been described for other breeds such as Maltese, Chihuahua, Yorkshire Terrier, Pekingese, West Highland White Terrier, Boston Terrier, Japanese Spitz, and Miniature Pinscher and for 1 Staffordshire Bull Terrier mix.2,3 To the authors' knowledge, a case of NME in a Miniature Dachshund has not been previously reported. A genetic predisposition for NME has been confirmed in Pugs.4 However, the cause of this disease is unknown for all other breeds, although it is suspected to be an autoimmune disease of multifactorial pathogenesis.4
Necrotizing meningoencephalitis generally affects dogs between 6 months and 7 years of age, with a mean age of 29 months.3 Clinical signs of NME vary depending on the region of the brain affected; however, cerebrothalamic areas are often affected and result in seizures. Other common clinical signs include abnormal mentation, visual deficits, vestibulocerebellar dysfunction, and death.5 Antemortem indication of NME is based on signalment, neurologic signs, and results of cross-sectional imaging of the CNS, analysis of a CSF sample, and infectious disease testing of samples of CSF and serum.3 Nevertheless, NME requires a histopathologic diagnosis. The antemortem diagnosis is classified as meningoencephalitis of unknown origin along with other similar diseases, such as granulomatous meningoencephalitis and necrotizing leukoencephalitis; these diseases are then further differentiated on the basis of postmortem histopathologic findings.6
The lesions of NME include nonsuppurative inflammation dominated by plasma cells, lymphocytes, and histiocytes. Inflammation commonly involves the leptomeninges, cerebral cortex, corona radiata, and subcortical white matter. This leads to a loss of demarcation between the white and gray matter. The hallmark characteristic of this disease is the extensive necrosis from neuronal death and gliosis leading to gross vacuolization of the parenchyma.1,5
Treatment is aimed at controlling the clinical signs and promoting immunosuppression. Immunosuppression is generally achieved with administration of glucocorticoids (generally prednisone) and a secondary immunosuppressant. There are many secondary immunosuppressive drugs used for the treatment of NME, such as cytarabine, procarbazine, cyclosporine, lomustine, leflunomide, mycophenolate mofetil, and azathioprine.3 There is no consensus regarding which treatment or secondary immunosuppressant is the most effective, although cytarabine and cyclosporine appear to be most consistently used.
Among dogs with NME, the reported mean survival time is 10 months for dogs treated with prednisone and cyclosporine and 2 months for dogs treated with prednisone alone.7 Another study8 found that Pugs have a mean survival time of 93 days, with those receiving treatment living significantly longer (mean survival time, 101 days) than those not receiving treatment (mean survival time, 7.4 days). For the dog of the present report, no treatment was initiated owing to the severity of the disease.8
The case described in the present report had classic features of NME, namely the dog's progressive history, MRI findings, and classic histopathologic findings. However, the breed and age of this dog were considered extremely unusual among cases of NME. Thus, the authors recommend inclusion of NME in the differential diagnosis list for any Miniature Dachshund with progressive multifocal intracranial signs.
Acknowledgments
The authors declare no financial or other conflicts of interest.
Footnotes
Signa HDxt 3.0T MRI, General Electric, Milwaukee, Wis.
References
- 1. ↑
Cooper JJ, Schatzberg SJ, Vernau KM, et al. Necrotizing meningoencephalitis in atypical dog breeds: a case series and literature review. J Vet Intern Med 2014;28:198–203.
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Barber RM, Porter BF, Li Q, et al. Broadly reactive polymerase chain reaction for pathogen detection in canine granulomatous meningoencephalomyelitis and necrotizing meningoencephalitis. J Vet Intern Med 2012;26:962–968.
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Coates JR, Jeffery ND. Perspectives on meningoencephalomyelitis of unknown origin. Vet Clin North Am Small Anim Pract 2014;44:1157–1185.
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Hoon-Hanks LL, McGrath S, Tyler KL, et al. Metagenomic investigation of idiopathic meningoencephalomyelitis in dogs. J Vet Intern Med 2018;32:324–330.
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Jung D-I, Kang B-T, Park C, et al. A Comparison of combination therapy (cyclosporine plus prednisolone) with sole prednisolone therapy in 7 dogs with necrotizing meningoencephalitis. J Vet Med Sci 2007;69:1303–1306.
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Levine JM, Fosgate GT, Porter B, et al. Epidemiology of necrotizing meningoencephalitis in pug dogs. J Vet Intern Med 2008;22:961–968.
