Leigh syndrome

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Transverse section of an Alaskan Husky brain with bilaterally symmetrical areas of cavitation due to encephalomalacia in the thalamus[1]

Leigh syndrome (Alaskan Husky encephalopathy, subacute necrotizing encephalomyelopathy) is a rare hereditary and rapidly fatal neurological disease characterized by necrosis and cavitation of the brain.

This disease often affects multiple dogs from the same litter.

This disease has been reported in Alaskan Husky[2], Australian Cattle Dog[3] and Staffordshire Bull Terriers[4], and is caused by a mutation in the thiamine transporter 2 (SLC19A3) gene[1].

Clinical signs usually appear at 2 - 7 months of age with rapidly progressive central vestibular neurological signs such as ataxia, circling and seizures as well as behavioral abnormalities, blindness, facial hypalgesia and difficulties in prehension of food.

Blood tests frequently reveal elevated lactate levels and lactate:pyruvate ratio, suggesting a defect in the respiratory chain.

Imaging studies such as MRI should reveal bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum[5].

On postmortem examination, most lesions involve the thalamus, with widespread involvement microscopically in basal nuclei, midbrain, pons, and medulla[6]. These pathological changes appear similar to the striatonigral and cerebello-olivary degeneration observed in Kerry blue terriers. These dogs show clinical signs as early as 9 weeks, with lesions involving microcavition of the caudate nucleus and olivary nucleus, with degeneration in the cerebellar cortex, including severe loss of Purkinje cells, followed by degeneration in substantia nigra.

Histopathological findings in Leigh syndrome include neuronal loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration. Neuronal sparing in conjunction with apparently transient astrocytic vacuolation point to the possible pathogenetic role of astrocytes in the evolution of these lesions.

A differential diagnosis would include thiamine deficiency, Afghan hound hereditary myelopathy, neonatal encephalopathy, L-2-hydroxyglutaric aciduria, striatonigral and cerebello-olivary degeneration in Kerry blue terriers[7][8] and familial cerebellar abiotrophy in Bull Mastiffs[9].

There is no known treatment for this condition and most affected canine patients succumb to illness or require euthanasia.

References

  1. 1.0 1.1 Vernau KM et al (2013) Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy. PLoS One 8(3):e57195
  2. Brenner O et al (2000) Alaskan husky encephalopathy — a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome). Acta Neuropathol 100:50–62
  3. Brenner O et al (1997) Hereditary polioencephalomyelopathy of the Australian cattle dog. Acta Neuropathol 94(1):54-66
  4. Collins D et al (2012) Severe Subacute Necrotizing Encephalopathy (Leigh-like Syndrome) in American Staffordshire Bull Terrier Dogs. J Comp Pathol Nov 1
  5. Wakshlag JJ et al (1999) Subacute necrotising encephalopathy in an Alaskan husky. J Small Anim Pract 40(12):585-589
  6. Baiker K et al (2009) Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA. Acta Neuropathol 118(5):697-709
  7. Montgomery DL & Storts RW (1983) Hereditary striatonigral and cerebello-olivary degeneration of the Kerry blue terrier. Vet Pathol 20:143–159
  8. de Lahunta A & Averill DR (1976) Hereditary cerebellar cortical and extrapyramidal nuclear abiotrophy in Kerry blue terriers. J Am Vet Med Assoc 168:1119–1124
  9. Carmichael S et al (1983) Familial cerebellar ataxia with hydrocephalus in bull mastiffs. Vet Rec 112:354–358