Introduction

• Cause: rare disease of pet rabbits but experimental models common. Congenital or acquired lesions and most frequently affecting dwarf breeds.
• Signs: growth retardation, paresis, blindness, seizures and early neonatal death.
• Diagnosis: predisposed breed with compatible clinical signs, ultrasound, computed tomography, MRI, serology.
• Treatment: anticonvulsants, corticosteroids, supportive care for concurrent disease.
• Prognosis: fair to poor – congenital cases often die before adulthood.

Pathogenesis

Etiology

• May be present at birth without an obvious cause (congenital) but inherited gene defects are reported in dwarf breeds.
• May occur secondary to several causes:
  • Inflammatory or infectious diseases of the brain or meninges causing increased CSF production.
  • Hemorrhage into the ventricles following head trauma and hypertension.
  • Obstructed or impaired ventricular drainage (intraventricular or extraventricular lesions), due to neoplasia affecting the ventricles and choroid plexus or inflammatory conditions.
• Diffuse ventricular dilation is suggestive of congenital lesions or obstruction at the foramen magnum or lateral apertures.
• Focal ventricular dilation is suggestive of focal obstruction or loss of local parenchymal tissue.

Predisposing factors

General

• Inflammation of the brain or meninges.

Specific

• Hemorrhage into the ventricles:
  • Recent history of head or neck trauma.
  • Bleeding disorders, eg ingestion of rat poison.
• Congenital disease:
  • Brachycephalic breeds carrying the dwarf gene Brachycephalic syndrome. The dwarf allele has been shown to be responsible for the craniofacial changes noted in dwarf breeds:
    • 25% heritability estimate.  
    • Simple autosomal recessive inheritance with incomplete penetration. 
    • Associated with a deletion mutation in the coding sequence.  
    • Homozygous dw/dw is usually lethal:
      • ‘Peanut’ deformity with tiny ears, swollen head and markedly reduced birth weights to littermates. 
      • Death often within a few days following birth due to neurological and gastrointestinal dysfunction.  
      • A small number may survive to adulthood but have reduced longevity.
• Many crossbreed rabbits also have dwarf ancestry.

Pathophysiology

• Ventricles are present in the normal brain as areas devoid of parenchymal tissue and filled with cerebrospinal fluid (CSF):
  • The lateral ventricles sit ventral to the cerebral hemispheres and open rostrally into the olfactory ventricles and caudally into the third ventricle via the foramen of Monro.
  • The third ventricle connects to the fourth ventricle by the aqueduct of Sylvius.
  • The fourth ventricle drains into the spinal cord via the central canal.
  • Ventricles are lined with specialized ependymal cells which contain microvilli and act as a partial barrier between the CSF and parenchyma.
• Any abnormal dilation of these structures is termed ‘hydrocephalus’ and may result from impaired drainage or elevated secretion of CSF.
• Most often caused by impaired drainage of the CSF with normal levels of production (obstructive):
  • CSF accumulates at the level of the obstruction (non-communicating hydrocephalus).
  • In some cases, small volumes of CSF may drain but is insufficient to prevent pathological changes.
  • Obstruction can occur due to tumors, inflammation, granulomas, hemorrhage or congenital abnormalities of the ependymal cell layer.
• May develop due to increased production of CSF which overwhelms the drainage system capacity, eg infection and inflammation.
• Hydrocephalus is uncommon in pet rabbits, but many experimental models of this disorder are well-studied.

Specific causes of hydrocephalus

Neoplasia

• Choroid plexus tumors, ependymomas and pituitary tumors have been associated with hydrocephalus in many species, including dogs, cats and rats.
• Possible but not reported in rabbits.

Infectious disease

• Infectious agents may damage the ependymal layer and facilitate penetration by neurotoxic components that damage the parenchyma and cause impeded drainage:
  • Ongoing inflammation causes swelling and localized damage which may cause additional obstruction or drainage impairment.
  • Ependymal cells may be destroyed and replaced by astrocytes or microgliacytes with longer term consequences for function.
• Infectious agents include bacteria, viruses and protozoa: Toxoplasma gondii Toxoplasma gondii has been associated with neonatal hydrocephalus in rabbits.

Congenital

• The cause of congenital hydrocephalus is not always obvious, but it is thought to be caused by disturbances to the ependymal cells during fetal development:
  • Failure of ventricles to communicate will lead to obstructed drainage.
  • Impaired drainage may occur due to changes to the structure and function of the ependymal cell border lining the ventricles, eg loss of microvilli.
• An underlying genetic cause is reported in dwarf breeds but appears uncommon:
  • In one litter the condition was due to abnormal CSF movement within the aqueduct due to ectopic ependymal cells.
  • Increased intracranial pressure resulted in herniation of the right ventricle through the dorsal cranium (meningoencephalocele).
• May develop following injury or infection to the placenta during gestation with impeded oxygen and nutrient supply.

Vitamin A Vitamin A

• A reported cause of congenital hydrocephalus in rabbits.
• Can occur with both hypervitaminosis A Hypervitaminosis A and hypovitaminosis A Hypovitaminosis A.
• Both conditions can impede the maturation of nervous tissue as well as prevent correct division of the brain and spinal cord segments during the process of neurulation which may be associated with hydrocephalus.

Trauma

• Swelling and inflammation may damage the ependymal layer and facilitate penetration by neurotoxic components that damage the parenchyma and cause impeded drainage:
  • Hemorrhage into the ventricles may interfere with the normal drainage process and thrombi may cause a direct obstruction to outflow.
  • Ongoing inflammation causes swelling and localized damage which may cause additional obstruction or drainage impairment.
  • Ependymal cells may be destroyed and replaced by astrocytes or microgliacytes with longer term consequences for function.

Timecourse

• Congenital disease is apparent from birth and the effects are lifelong. Affected rabbits often have reduced longevity compared to unaffected siblings.
• Acquired disease incubation and duration depends upon inciting cause:
  • Effective and early intervention may significantly reduce the duration of morbidity. An accurate diagnosis will aid targeted treatment.
  • Long-term effects of brain lesions may persist for prolonged periods and may be lifelong.

Epidemiology

• Dwarf breeds and dwarf cross rabbits predisposed to congenital hydrocephalus.

Diagnosis

Treatment

Prevention

Outcomes