Brain: cerebellum – congenital disorders

• Several syndromes are recognized:
  • Cerebellar abiotrophies Cerebellar hereditary ataxia.
  • Dandy Walker syndrome Dandy-Walker like syndrome.
  • Hypomyelination/dysmyelination.
  • Neuroaxonal dystrophy Neuroaxonal dystrophy.
  • Leucoencephalomyelopathy Leukoencephalomyelopathy.
  • Congenital malformations of the cerebellum.
  • Cerebellar hypoplasia/aplasia.
• Seen from 6 weeks old.
• Signs: non-progressive cerebellar signs.
• Diagnosis: rule out other causes of similar signs, eg inflammatory and degenerative diseases.
• Treatment: none.
• Prognosis: guarded.

• Cerebellar signs from 6 weeks of age:
  • Truncal ataxia Ataxia with preservation of strength.
  • Generalized tremor.
  • Intention tremor of head,
  • Nystagmus.
  • Hypermetria.
  • Broad-based stance.

• Neonates.

• Cerebellar abiotrophies:
• • Kerry blue Terrier Kerry Blue Terrier.
  • Gordon Setter Gordon Setter.
  • Rough-coated Collie Collie - Rough.
  • Border Collie Border Collie.
  • Bull Mastiff Bullmastiff , and rarely in
  • Samoyeds Samoyed , Airedales Airedale Terrier , Finnish Harriers , Labrador Retrievers Retriever: Labrador , Golden Retrievers Retriever: Golden , Beagles Beagle , Cocker Spaniels English Cocker Spaniel , Bernese Mountain dog Bernese Mountain Dog , Brittany spaniels Brittany , Finnish Hound Finnish Lapphund , Italian Spinone Spinone Italiano , Cairn Terriers Cairn Terrier and Great Danes Great Dane.
  • In Gordon setters, a late onset cerebellar degeneration has been described (Steinberg and others 1983).
• Hypomyelination/dysmyelination:
• • Chow Chow Chow Chow.
  • Springer Spaniel English Springer Spaniel.
  • Samoyed Samoyed.
  • Weimaraner Weimaraner and
  • Bernese Mountain dogs Bernese Mountain Dog.
• Neuroaxonal Dystrophy:
• • Rottweilers Rottweiler.
  • Collies Border Collie Collie - Rough Collie - Smooth.
  • Chihuahuas Chihuahua - Long Coat Chihuahua - Smooth Coat.
  • Collie Sheepdog Collie - Rough.
  • Bull Mastiff Mastiff.
  • Papillons Papillon.
  • German Shepherd dogs German Shepherd Dog.
  • Jack Russell terriers Jack Russell Terrier (American).
  • Boxers Boxer.
• Leucoencephalomyelopathy:
• • Rottweilers Rottweiler.
• Cerebellar hypoplasia:
• • Chow Chows Chow Chow.
  • Airedales Airedale Terrier.
  • Boston terrier Boston Terrier.
  • Irish Setters Irish Red and White Setter and
  • Wire-haired Fox Terriers Fox Terrier - Wire.
• Cerebellar aplasia:
• • Siberian Huskies Siberian Husky.

• To breeder if litter unfit for sale.

• Cerebellar abiotrophies: also called cerebellar cortical degeneration - it is a process by which cells develop normally but later degenerate because of an intrinsic cellular defect necessary for continued life of the neuron. Many of these diseases may result from underlying abnormalities of cellular metabolism or function. Known to be inherited in Old English Sheepdog, Gordon setter, Finnish Hound, Italian Spinone, Beagle and Brittany Spaniel.
• Dandy Walker syndrome: is a congenital problem assumed to be associated with abnormal embryogenesis (primarily parenchymal midline developmental field defect of unknown origin). Represent partial or complete absence of the vermis of the cerebellum. Associated with these vermal defects is cyst-like dilation of the fourth ventricle. In addition many of these patients have dilated third and lateral ventricles (hydrocephalus), stenosis of the aqueduct, and absence of the corpus callosum.
• Hypomyelination/dysmyelination: disease is inherited in an X-linked manner is Springer Spaniels.
• Lysosomal storage diseases Storage disease progressive loss of neurone function → cerebellum degeneration.
• Hypomyelination has been associated within uterocanine herpes virus infections Canine herpesvirus disease.

• Failure of normal cerebellar development.

• Degeneration of cerebellar neurones after the differentiation process is complete → inadequate function to control movement.
• Dandy Walker syndrome: there is a malformation resulting in a cyst-like abnormality in the cerebellum. The lateral and third ventricles are commonly dilated concurrently.
• Hypomyelination/dysmyelination: disorders of myelin synthesis and maintenance. In most cases the underlying derangement directly or indirectly affects the oligodendrocyte numbers or function.
• Neuroaxonal dystrophy: underlying pathogenesis is unknown. The cell bodies in the grey matter are affected (axonal spheroids) throughout the nervous system except the cerebral cortex. The most severe lesions are in the spinocerebellar tracts and the Purkinje cells.

• From 6 weeks of age (when puppies become more active).

• Incoordination.
• Tremors.

• Age.

• Ataxia.
• Generalized tremor.

• Because of its unique function, clinical signs of cerebellar disease are often characteristic and include:
• Ataxia and dysmetria.
• Intention tremor of head/eyes.
• Vestibular signs.
• Menace deficits with normal vision and normal CN VII function.
• Decerebellate rigidity.
• Anisocoria.
• Increased frequency of urination.
• Unilateral lesions of the cerebellum result in ipsilateral clinical signs.
• Cerebellar abiotrophies: clinical signs are of a progressive cerebellar disease.
• Hypomyelination/dysmyelination: clinical signs consist of generalized tremor which may appear to be cerebellar in origin. This tremor usually worsens with excitement.
• Neuroaxonal dystrophy: characterized by cerebellar signs (ataxia, hypermetria, loss of menace, head tremor) beginning at 1 to 2 years (ataxia) and progressing over the next 2-4 years (menace deficits, intention tremor). Conscious proprioception remains intact.
• Leucoencephalomyelopathy: progressive ataxia and weakness. No head signs are seen. Clinical signs suggest a pure spinal cord problem.
• Congenital malformations of the cerebellum, eg cerebellar hypoplasia/aplasia: clinical signs of a diffuse cerebellar disease.

• Poor coordination.
• Generalized tremor.
• Ataxia and dysmetria are commonly, but not exclusively, seen with disease of the cerebellum.
• The animal's strength is normal with pure cerebellar disease, however, movements may be somewhat delayed or compensations may be exaggerated.
• If the head is extended and dropped, it may descend further ventrally than normal (rebound phenomenon).
• Intention tremor may involve the whole body but is usually most obvious in the head. The head usually moves in an up and down ("Yes") direction at a frequency of 2-4 Hz. This type of tremor is exaggerated by goal-oriented movement such as eating. This is most likely a dysmetria of head movement.
• Involvement of the flocculonodular lobe or fastigial area may result in a vestibular disturbance characterized by lack of balance, nystagmus, head tilt (usually contralateral to the lesion) and a broad-based stance.
• The nystagmus may only be seen when the head is flexed to one side (positional nystagmus), with the fast phase directed toward the side in which the head is tilted.
• A pendulous eye movement (eyes oscillate from side to side) may also be seen with cerebellar disease.
• A menace deficit with normal vision and normal CN VII function can be seen ipsilateral to a unilateral cerebellar lesion as cerebellar influence is needed for performance of this response.
• With unilateral lesions of the fastigial or interposital nuclei, a pupillary dilation which is slowly responsive to light may be seen.
• The pupillary dilation occurs in the eye ipsilateral to an interposital nuclear lesion and contralateral to a fastigial nuclear lesion.

• Occasionally, animals with cerebellar disease may have abnormal posture.
• The rostral cerebellar lobe is inhibitory to stretch in the antigravity muscles, and lesions here may result in opisthotonus with the thoracic limbs extended (decerebellate posture).
• The pelvic limbs are usually flexed forward under the body by the hypertonia of the iliopsoas muscles that flex the coxofemoral joints.
• Mentation remains normal.
• If the lesion also involves the ventral lobules, the pelvic limbs may be in rigid extension.
• Reflexes are usually exaggerated.
• Occasionally, the third eyelid may protrude and the palpebral fissure may be enlarged.

• The cerebellum normally has an inhibitory influence on urination. Rarely, a cerebellar lesion will result in frequent urination due to loss of this inhibitory input.

Histopathology

• Hypomyelination.
• Enlarged lysosomes.

• Purkinje cells may also be destroyed.

• Abnormal cerebellar development.

• The cerebellum may appear small to non-existant.
• The normal gyral and sulcal pattern may be lost.

• Depending upon the disease process, there will be a deficiency or absence of cellular component of the cerebellum.
• This most often includes the Purkinje and granular cell layers.

• With storage diseases, the neurons or supporting cells are usually enlarged and distended with abnormal accumulations of cellular products.

• Inclusion bodies may be seen in some cells if a viral etiology has been present.

• Storage diseases Storage disease.
• Spinal tract disease (sensory ataxia).

• Other cerebellar diseases:
  • Inflammatory.
  • Degenerative.
  • Toxic.
  • Traumatic.
  • Vascular.
  • Idiopathic.
  • Metabolic.
  • Degenerative.
• Vestibular disease Vestibulocochlear neuritides.

• None available.

• Monitor development (or lack of it) in growing puppy.

• Often progressive.
• Guarded in most cases.
• Animals with hypomyelination improve with time and may lead an adequate life.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Van der Merwe L L, Lane E (2001) Diagnosis of cerebellar cortical degeneration in a Scottish terrier using magnetic resonance imaging. JSAP 42, 409-412 PubMed.
• Tago Y et al (1993) Granule cell type cerebellar hypoplasia in a beagle dog. Lab Anim 27 (2), 151-155 PubMed.
• Schmid V, Lang J & Wolf M (1992) Dandy-Walker-like syndrome in four dogs - Cisternography as a diagnostic aid. JAAHA 28 (4), 355-360 VetMedResource.
• Kornegay J N (1986) Cerebellar vermian hypoplasia in dogs. Vet Pathol 23 (4), 374-379 PubMed.
• Harari J et al (1983) Cerebellar agenesis in two canine littermates. JAVMA 182 (6), 622-623 PubMed.
• Steinberg, H S, Troncoso, J C, Cork, L C & Price, D L (1981) Clinical features of inherited cerebellar degeneration in Gordon Setters. JAVMA 179 (9), 886-890 PubMed.
• deLahunta A (1980) Comparative cerebellar disease in domestic animals. Comp Cont Educ 2, 8-19.
• Holliday T A (1980) Clinical signs of acute and chronic experimental lesions of the cerebellum. Vet Sci Comm 3 (4), 259-78 VetMedResource.
• Pearson H (1979) Changing attitudes to congenital and inherited diseases. Vet Rec 105 (14), 318-23 PubMed.

Other sources of information

• Bagley R S, Platt S R (2013) Tremors, involuntary movements and paroxysmal disorders. In: Platt S E & Olby N (eds). BSAVA Manual of Canine and Feline Neurology. BSAVA, pp 233-251.
• De Lahunta A, Glass E (2009) Veterinary Neuroanatomy and Clinical Neurology. 3rd edn. St. Louis, Saunders Elsevier, p 360-370.
• Braund K G (1987) Degenerative and developmental diseases. In:Veterinary Neurology. Eds. J E Oliver Jr, B F Hoerlein & I B Mayhew. W B Saunders, Philadelphia. pp 186.
• Chrisman C L (1986) Neuroaxonal dystrophy and Leukoencephalomyelopathy of Rottweiler dogs. In:Current Veterinary Therapy. 9th edn. Ed R W Kirk. W B Saunders, Philadelphia. pp 805-806.
• deLahunta A (1983) In: Veterinary Neuroanatomy and Clinical Neurology. 2nd edn. W B Saunders, Philadelphia. pp 189.