What Is Your Diagnosis?

Danielle M. Zwueste1Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

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Jarrett Pacheco1Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

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Sally Sukut1Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada.

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History

A 13-month-old 21.6-kg (47.5-lb) castrated male Alaskan Husky mix was examined at the Western College of Veterinary Medicine because of seizures, blindness, and behavioral changes. The dog had had 4 generalized tonic-clonic seizures witnessed by the owner during the 7 days prior to the examination. The owners reported that 2 days after the first seizure, the dog seemed reluctant to descend stairs or jump, was ataxic, and bumped into objects. The dog had been adopted from the local humane society 10 months earlier, and there had been no previous health concerns. The dog did not have a history of travel, was up-to-date on vaccinations, and was fed a commercial puppy food. Information regarding potential littermates was not available.

On examination, the dog was obtunded and ambulatory, but ataxic and had moderate tetraparesis with a tendency to fall backward. Pupillary light reflexes were appropriate; however, the menace response was absent bilaterally, and the dog showed signs of blindness. In addition, the dog had signs of abnormally low facial sensation bilaterally, and postural reactions were delayed or absent in all limbs. No other abnormalities were noted on physical examination, CBC, serum biochemical analyses, or thoracic radiography. Because the dog's clinical signs were consistent with diffuse intracranial disease, the dog was hospitalized and underwent general anesthesia for MRI of the brain (Figure 1)

Figure 1—
Figure 1—

T2-weighted midsagittal (A) and transverse (B, C, and D) plane MRI images of the brain of a 13-month-old 21.6-kg (47.5-lb) castrated male Alaskan Husky mix examined because of a 7-day history of seizures, blindness, and behavioral changes. A—Cranial is to the left of the image. B, C, and D—Transverse plane images obtained at the level of the forebrain (B), midbrain (C), and occipital lobe and medulla (D) with the dog's left to the right of the images.

Citation: Journal of the American Veterinary Medical Association 255, 12; 10.2460/javma.255.12.1339

Determine whether additional imaging studies are required, or make your diagnosis from Figure 1—then turn the page —

Diagnostic Imaging Findings and Interpretation

Findings on T2-weighted MRI included multifocal, bilaterally symmetric lesions with hyperintense signal in the gray matter of the cerebrum, thalamus, and brainstem (Figure 2) The lesions in the thalamus were partially cavitated, characterized by central regions that had hyperintense signals on T2-weighted images, but suppressed signals on fluid-attenuated inversion recovery sequences (Figure 3) No mass effect was noted with these lesions, and results of gradient echo MRI (not shown) did not indicate hemorrhage. Following IV administration of gadobutrola (0.2 mL/kg [0.09 mL/lb]; 1.0 mmol of gadobutrol/mL), subtle and inconsistent contrast medium enhancement was noted in the noncavitated portions of the lesions (not shown). On the basis of the dog's clinical signs and the multifocal, bilaterally symmetric intracranial lesions detected with diagnostic imaging, the most likely differential diagnosis was Alaskan Husky encephalopathy (AHE).

Figure 2—
Figure 2—

Same MRI images as in Figure 1. There are bilaterally symmetric lesions with hyperintense signal identified in the thalamus (black arrow; A and C), red nucleus (short white arrow; A), medulla (long white arrow; A and D), caudate nucleus (white circle; B), claustrum (black circle; B), cingulate gyrus (asterisks; B and C), and base of sulci in the gray matter (box; C).

Citation: Journal of the American Veterinary Medical Association 255, 12; 10.2460/javma.255.12.1339

Figure 3—
Figure 3—

Transverse plane fluid-attenuated inversion recovery MRI image obtained at the level of the midbrain in the dog in Figures 1 and 2. The hyperintense signals of the AHE lesions appear more conspicuous on this than on the T2-weighted MRI images (Figures 1 and 2), and there is bilateral suppression of signal in the center of lesions in the thalamus (arrows), consistent with fluid accumulation secondary to cavitation. The dog's left is to the right of the image.

Citation: Journal of the American Veterinary Medical Association 255, 12; 10.2460/javma.255.12.1339

Treatment and Outcome

Cerebrospinal fluid was collected with a cisternal puncture technique, and results of cytologic evaluation were unremarkable. A blood sample was submitted to an external laboratoryb to test for the AHE genetic mutation, and while the results were pending, treatment with phenobarbital (3.0 mg/kg [1.4 mg/lb], IV, q 12 h) and thiamine (47.0 mg/kg [21.4 mg/lb], SC, q 24 h) was initiated. After 3 days of treatment, the dog showed signs of improved mentation and facial sensation, reduced ataxia, and bilaterally returned menace responses.

The dog was discharged for continued treatment at home with thiamine (5.0 mg/kg [2.3 mg/lb], PO, q 12 h) and biotin (5.0 mg/kg, PO, q 24 h), both of which the owners were to purchase from their local vitamin store. The results of the genetic testing were received and indicated that the dog was homozygous for the genetic mutation that causes AHE.

Comments

Alaskan Husky encephalopathy is a heritable neurodegenerative disorder that is caused by a mutation in the SLC19A3 gene, which codes for the CNS thiamine transporter protein, THTR2.1 Abnormal transporter structure and function results in failure of thiamine transport across CNS cell membranes and severe metabolic disturbances.1 Affected animals are typically < 24 months of age and display acute onset of neurologic signs, such as seizures, inappropriate mentation, dysphagia, absent menace response, central blindness, hypermetria, postural reaction deficits, reduced facial sensation, ataxia, and tetraparesis.1,2 Magnetic resonance imaging is a critical tool in clinically diagnosing AHE, particularly while results of genetic testing are pending. As in the dog of the present report, AHE lesions are multifocal and bilaterally symmetric, have hyperintense signals on T2-weighted MRI images, and affect the caudate nucleus, putamen, claustrum, thalamus, bases of cortical sulci, and brainstem.1,3 Contrast medium enhancement is not a substantial feature of AHE lesions.

Seizures were a prominent component of the history of the dog in the present report, and lesions suspected to be related to gliosis and cytotoxic and vasogenic edema have been identified with MRI as a consequence of seizure activity.4,5 However, those lesions on T2-weighted MRI images have ill-defined areas of hyperintense signals in the parietal, temporal, and frontal lobes and in the thalamus.4,5 In addition, loss of distinction between white and gray matter and heterogenous contrast medium enhancement may occur.4,5 Because the MRI findings in the dog of the present report differed from those reported as consequences of seizure activity, peri-ictal encephalopathy was an unlikely diagnosis in the dog of the present report.

There are other causes of bilaterally symmetric intracranial lesions of animals, and most pertain to metabolism, nutrition, or toxicoses. Findings on MRI, particularly lesion distribution, are useful in differentiating those other causes from AHE. For example, in a dog with fulminant hepatic encephalopathy, bilateral lesions that appear hyperintense on T2-weighted images and fluid-attenuated inversion recovery sequences have been identified in the thalamic nuclei.5 Unlike with AHE, however, the CNS lesions with fulminant hepatic encephalopathy typically have restricted diffusion on diffusion-weighted images and concurrent diffuse cortical hyperintense signals noted.5 In addition, myelinolysis, such as that secondary to severe osmotic disturbances, can lead to MRI findings of lesions within the pons, basal nuclei, cerebellum, and cerebral cortex.5 However, regions affected by myelinolysis that are not typically affected with AHE include the hippocampus, corpus collosum, and white matter.5 Further, thiamine deficiency secondary to an improperly balanced or incorrectly processed or preserved diet can also produce symmetric lesions that have hyperintense signals on MRI images; however, involvement of lateral geniculate nuclei and caudal colliculi in thiamine deficiency help differentiate it from AHE.5 Thus, when patient history and signalment are combined with MRI findings, clinicians should be able to distinguish AHE from other potential underlying causes of intracranial disease.

Acknowledgments

There was no funding provided for this report, and none of the authors have financial interests in the manufacturers of any products or equipment used.

Footnotes

a.

Gadovist, Bayer HealthCare LLC, Whippany, NJ.

b.

Veterinary Genetics Laboratory, University of California-Davis, Davis, Calif.

References

  • 1. Vernau KM, Runstadler JA, Brown EA, et al. Genome-wide association analysis identifies a mutation in thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy. PLoS One 2013;8:e57195.

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  • 2. Brenner O, Wakshlag JJ, Summers BA, et al. Alaskan Husky encephalopathy—a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome). Acta Neuropathol 2000;100:5062.

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  • 3. Wakshlag JJ, de Lahunta A, Robinson T, et al. Subacute necrotising encephalopathy in an Alaskan Husky. J Small Anim Pract 1999;40:585589.

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  • 4. Mellema LM, Koblik PD, Kortz GD, et al. Reversible magnetic resonance imaging abnormalities in dogs following seizures. Vet Radiol Ultrasound 1999;40:588595.

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  • 5. Wisner ER, Zwingenberger AL. Metabolic, toxic, and degenerative disorders. In: Wisner ER, Zwingenberger AL, eds. Atlas of small animal CT and MRI. Ames, Iowa: Wiley Blackwell, 2015;184196.

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Contributor Notes

Dr. Zwueste's present address is Vancouver Animal Emergency and Referral Centre, 2303 Alberta St, Vancouver, BC V5Y 4A7, Canada.

Address correspondence to Dr. Zwueste (dmz5l4@mail.usask.ca).
  • View in gallery
    Figure 1—

    T2-weighted midsagittal (A) and transverse (B, C, and D) plane MRI images of the brain of a 13-month-old 21.6-kg (47.5-lb) castrated male Alaskan Husky mix examined because of a 7-day history of seizures, blindness, and behavioral changes. A—Cranial is to the left of the image. B, C, and D—Transverse plane images obtained at the level of the forebrain (B), midbrain (C), and occipital lobe and medulla (D) with the dog's left to the right of the images.

  • View in gallery
    Figure 2—

    Same MRI images as in Figure 1. There are bilaterally symmetric lesions with hyperintense signal identified in the thalamus (black arrow; A and C), red nucleus (short white arrow; A), medulla (long white arrow; A and D), caudate nucleus (white circle; B), claustrum (black circle; B), cingulate gyrus (asterisks; B and C), and base of sulci in the gray matter (box; C).

  • View in gallery
    Figure 3—

    Transverse plane fluid-attenuated inversion recovery MRI image obtained at the level of the midbrain in the dog in Figures 1 and 2. The hyperintense signals of the AHE lesions appear more conspicuous on this than on the T2-weighted MRI images (Figures 1 and 2), and there is bilateral suppression of signal in the center of lesions in the thalamus (arrows), consistent with fluid accumulation secondary to cavitation. The dog's left is to the right of the image.

  • 1. Vernau KM, Runstadler JA, Brown EA, et al. Genome-wide association analysis identifies a mutation in thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy. PLoS One 2013;8:e57195.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Brenner O, Wakshlag JJ, Summers BA, et al. Alaskan Husky encephalopathy—a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome). Acta Neuropathol 2000;100:5062.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Wakshlag JJ, de Lahunta A, Robinson T, et al. Subacute necrotising encephalopathy in an Alaskan Husky. J Small Anim Pract 1999;40:585589.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Mellema LM, Koblik PD, Kortz GD, et al. Reversible magnetic resonance imaging abnormalities in dogs following seizures. Vet Radiol Ultrasound 1999;40:588595.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Wisner ER, Zwingenberger AL. Metabolic, toxic, and degenerative disorders. In: Wisner ER, Zwingenberger AL, eds. Atlas of small animal CT and MRI. Ames, Iowa: Wiley Blackwell, 2015;184196.

    • Search Google Scholar
    • Export Citation

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