Cerebellar Purkinje cell degeneration

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Purkinje cell atrophy in an American Staffordshire Terrier showing marked atrophy of the cerebellum at gross examination[1]

Cerebellar Purkinje cell degeneration is a rare autosomal-recessive genetic disease of dogs affecting only the Purkinje cells of the cerebellum.

The disease, which is a form of canine cerebellar abiotrophy[2], is caused by a missense mutation in the SEL1L gene, a component of the endoplasmic reticulum–associated protein degradation gene machinery.

This is a breed-specific disease reported in the Lagotto Romagnolo, Scottish Terrier, Old English Sheepdog, American Staffordshire Terrier[3], Bavarian Mountain Dog[4] and Finnish Hound[5].

Affected pups (often around 3 months of age) usually present with early-onset progressive cerebellar ataxia characterized by an inability to walk and slowed growth, intention tremors, jerky limb movements and difficulty crawling, suckling and maintaining the body in a specific position. Puppies with this disability, however, seem to be aware of their surroundings and respond when stimulated[6].

Cerebellar Purkinje cell degeneration can occur in different forms. In the neonatal form, clinical signs of dysfunction start at birth or a few days later. In the postnatal form, reported in the Old English Sheepdog[7], the symptoms start a few weeks to months after birth and slowly progresses over time.

A syndrome of cerebellar Purkinje's cell degeneration and coat color dilution has been diagnosed in a family of Rhodesian Ridgeback dogs[8]. Epilepsy was reported in several litters of Lagotto Romagnolo dogs which was associated with loss of Purkinje cells[9].

Many affected dogs remain with mild incoordination their entire lives, and live out a normal life span. Other animals progress to the point where they can not walk without assistance.

Histological examination of brain tissues usually shows a cerebellum-restricted neurodegeneration with marked loss of Purkinje cells in the cerebellar cortex with secondary changes in other cortical layers.

A differential diagnosis would include hydrocephalus, Chiari malformations, arachnoid cysts[10], cerebellar hypoplasia, Dandy-Walker syndrome, cerebellar abiotrophy[11], neuroaxonal dystrophy[12] and intrauterine canine parvovirus infection[13], and these should be considered in any differential diagnosis.

There is no effective treatment for this condition and many pups have to be euthanized due to rapidly worsening symptoms.

References

  1. Sisó S et al (2006) Neurodegenerative diseases in domestic animals: a comparative review. Vet J 171(1):20-38
  2. de Lahunta A (1990) Abiotrophy in domestic animals: A review. Can J Vet Res 54:65–76
  3. Hanzlícek D et al (2003) Cerebellar cortical abiotrophy in American Staffordshire terriers: clinical and pathological description of 3 cases. Schweiz Arch Tierheilkd 145(8):369-375
  4. Flegel T et al (2007) Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs. J Small Anim Pract 48(8):462-465
  5. Kyöstilä K et al (2012) A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet 8(6):e1002759
  6. LIDA
  7. Steinberg HS et al (2000) Cerebellar degeneration in Old English Sheepdogs. J Am Vet Med Assoc 217(8):1162-1165
  8. Chieffo C et al (1994) Cerebellar Purkinje's cell degeneration and coat color dilution in a family of Rhodesian Ridgeback dogs. J Vet Intern Med 8(2):112-116
  9. Jokinen TS et al (2007) Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Intern Med 21(3):464-471
  10. Thomas WB (1999) Nonneoplastic disorders of the brain. Clin Tech Small Anim Pract 14(3):125-147
  11. van der Merwe LL & Lane E (2001) Diagnosis of cerebellar cortical degeneration in a Scottish terrier using magnetic resonance imaging. J Small Anim Pract 42(8):409-412
  12. Fyfe JC et al (2010) Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia. J Comp Neurol 518(18):3771-3784
  13. Schatzberg SJ et al (2003) Polymerase chain reaction (PCR) amplification of parvoviral DNA from the brains of dogs and cats with cerebellar hypoplasia. J Vet Intern Med 17:538–544