HYDROCEPHALUS IN DOGS AND CATS

Pathophysiology

The choroid plexuses of the paired lateral, third and fourth ventricles produce approximately 60 per cent of CSF.

The remaining 40 per cent is derived from the parenchymal capillaries, the pial-glial membrane covering the surface of the brain and the ependymal lining of the ventricles. The bulk of CSF flow occurs from the ventricular system to the subarachnoid space (^{Figure 1}). The CSF from the paired lateral ventricles escapes via the interventricular foramen into the ring-shaped third ventricle; from there it passes caudally through the mesencephalic aqueduct to the fourth ventricle.

Most of the CSF from the fourth ventricle escapes into the subarachnoid space through the lateral apertures, which are a pair of openings in the lateral wall of the fourth ventricle. Some CSF from the fourth ventricle may enter the central canal of the spinal cord. The CSF is removed by three main roots:

• absorption by the arachnoid villi, which are evaginations of the arachnoid into the venous sinuses of the dura mater;

• the venules of the subarachnoid space; and

• lymphatic vessels on the roots of cranial and spinal nerves.

Depending on whether the abnormal CSF accumulation is present within the ventricular system or the subarachnoid space, hydrocephalus may be classified as internal or external hydrocephalus, with the former being much more common. If there is a communication between the ventricular system and the subarachnoid space, the term “communicating hydrocephalus” is appropriate.

From the clinical and therapeutic point of view, it is very important to distinguish whether a hydrocephalus is going along with increased intracranial pressure and is, therefore, normo or hypertensive. Generally, hypertensive hydrocephalus can be due to obstruction of CSF flow, decreased resorption of CSF or increased CSF production (rarely seen with plexus tumours).

Obstructive hydrocephalus is the most common form in animals. It often occurs as an acquired disease, usually secondary to neoplastic and inflammatory diseases. However, it may also be seen as a congenital problem, due to stenosis of the mesencephalic aqueduct (connecting the third and fourth ventricle), which is frequently associated with fusion of the rostral colliculi (structure of the midbrain and/or mesencephalon associated with visual reflexes).

Less commonly, congenital stenosis of the lateral apertures (outflow of the fourth ventricle to the subarachnoid space) causes obstruction of CSF flow. Ventricular dilation occurs proximal to the obstructive site, with preservation of normal ventricular size distal to the block. Congenital hydrocephalus may be associated with other abnormalities, such as cerebellar hypoplasia, Dandy-Walker malformation (trias of vermis hypoplasia, cystic dilation of the fourth ventricle and hydrocephalus), Arnold-Chiari-like malformation and syringomyelia.

Decreased absorption of CSF is mostly due to inflammatory processes, but underdevelopment of the arachnoid villi may cause a congenital aresorptive hydrocephalus (this is rare). Infrequently, obstructive or aresorptive hydrocephalus may be seen secondary to intraventricular or subarachnoid haemorrhage.

If, on the other hand, CSF volume is increased to take up space where brain tissue has failed to develop, or was destroyed, a hydrocephalus ex vacuo will develop, which is normotensive. This compensatory hydrocephalus may be seen congenitally (extreme forms are called hydranencephaly, where the neocortex is a nearly transparent membrane and lateral ventricles are extensively dilated sacs filled with CSF) or subsequent to ischaemia, trauma or senile brain atrophy.

Clinical signs

Neurologic signs associated with hydrocephalus are variable. Forebrain signs tend to predominate and include seizures, depression, behavioural changes, head pressing, pacing, proprioceptive deficits or blindness. In severe cases, animals can be stuporous or comatose. Gait deficits, if present, may vary in severity depending on compromise of the brainstem and cerebellum.

Animals with congenital hydrocephalus are usually presented when they are young. They are often smaller than their littermates, and an enlarged, dome-shaped cranium and open fontanellae may be evident upon presentation. Bilateral ventrolateral strabismus (“sun-setting sign”) may occur and is believed to be primarily due to mechanical pressure on the eyes from orbital malformation.

However, congenital hydrocephalus’ clinical progression rate is highly variable, and some animals might not develop overt signs of encephalopathy until adulthood. Older animals with acquired hydrocephalus often have clinical signs reflecting the location of the underlying cause (such as neoplasia) of the hydrocephalus, especially in earlier stages of their disease.

Fundic examination may display a swollen optic disc (papilloedema) in cases of hypertensive hydrocephalus, as the optic nerve is surrounded by meninges, which contain CSF.

Breed disposition

The phenomenon of excessive accumulation of CSF in the brain ventricles occurs most commonly in the toy and brachycephalic dog breeds, and less commonly in the cat. Congenital hydrocephalus may be autosomal, and recessively inherited in the Siamese cat. Breeds such as the Maltese, Yorkshire terrier, English bulldog, chihuahua, Lhasa apso, Pomeranian, toy poodle, cairn terrier, Boston terrier, pug and Pekingese were determined to be at a greater risk for hydrocephalus compared to other breeds.

However, the normal ventricular size strongly varies among breeds. For example, Yorkshire terriers and English bulldogs have larger ventricles than German shepherd dogs or beagles when compared to the brain volume. In addition, the ventricular size can vary between healthy individuals of one breed. Therefore, in the absence of clinical signs, the term ventriculomegaly often seems much more appropriate, as hydrocephalus always implies ongoing pathology. Likewise, physiological ventricular asymmetry can be observed in individuals, and frequently reflects an incidental finding.

Diagnosis

Congenital hydrocephalus may be suspected, based on physical examination and signalment. Electroencephalography has been used historically and displays an unspecific slow wave and high amplitude activity, which may be superimposed by a high frequency.

Radiographs of the skull are usually not helpful for definite diagnosis, but doming of the calvarium, persistent fontanellae and thinning of the cortical bone (displaying a typical ground-glass appearance) may be seen. Pneumo or contrastventriculography, where air or radiologic contrast medium is injected in the ventricles, has been used in the past to demonstrate ventriculomegaly.

These invasive methods have been supplanted by ultrasound and advanced imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound through the open fontanellae or the temporal window in young animals allows assessment of ventricular dimensions. Doppler ultrasound via the foramen magnum can be used to measure the basilar artery resistance index as an indicator of intracranial pressure.

CT is very useful in defining the ventricular size, as CSF is hypodense compared to brain parenchyma. Therefore, the ventricular system can be readily identified, based on its relative blackness to brain parenchyma. MRI is the most sensitive advanced imaging modality in assessing soft-tissue structures, and, therefore, provides valuable information, not only on the presence and extent of hydrocephalus, but also on the surrounding brain parenchyma. The terms hyper and hypointense are always used in comparison to the brain’s grey matter.

Typically, CSF is hyperintense (bright) in T2-weighted images (^{Figure 2a}) and suppresses, with fluid attenuation inversion recovery (FLAIR) sequences appearing dark. FLAIR sequences help to distinguish CSF and CSF-like fluids from other forms of fluid, such as oedema, which will remain hyperintense. In T1-weighted images, CSF is hypointense , appearing dark (^{Figure 2b}).

From the therapeutic point of view, it is important to note whether hydrocephalus is normo or hypertensive. On both MRI and CT images, a hypertensive (internal) hydrocephalus may give the subjective impression of somewhat “turgid” ventricles, but the FLAIR sequence on MR images will help to objectify this impression, as periventricular “interstitial” oedema will be apparent (^{Figure 3a}, ^3b and ^3c). If the intracranial pressure is markedly increased, cervical spinal cord oedema may be an additional feature (^{Figure 3d}). Severely increased intracranial pressure may also lead to transtentorial and/or foramen magnum herniation.

CSF analysis should be considered if there is suspicion of an underlying inflammatory CNS disease. However, the risk of a spinal tap via both cisterna magna or lumbar puncture is very high if the hydrocephalus is hypertensive. If the decision is taken to obtain CSF, despite the suspicion of increased intracranial pressure, mannitol (0.2- 1g/kg IV over 15 to 20 minutes) should be given prior to performing this. If there is evidence of cervical spinal cord swelling due to oedema, a lumbar puncture should be performed.

If there is herniation of the cerebellum through the foramen magnum, a cisterna magna puncture is definitively contraindicated, and lumbar puncture should only be considered after the administration of mannitol.

Therapy

The treatment of hydrocephalus must be dictated by the underlying cause. If meningoencephalitis or neoplasia have been diagnosed, this should be specifically addressed as well. With hypertensive hydrocephalus, the main aim of medical treatment is to decrease CSF volume and production through diuretics and glucocorticoids. For the former, it is essential to ensure electrolytes and the hydration status of the patient are appropriate. If the hydrocephalus is compensatory, this treatment form has no expected benefit.

A primary mechanism of glucocorticoids is reduction of CSF production. Initially, dexamethasone may be given slowly IV at a dosage of 0.2mg/kg. Because of the higher incidence of side effects with dexamethasone, prednisolone is the treatment of choice in the long term. Dosages of 0.5mg/kg to 1mg/kg daily (sid or divided in bid) PO are recommended, which should be gradually reduced at weekly intervals to the lowest dosage possible.

Mannitol, an osmotic diuretic, is used in cases of rapidly decompensating hydrocephalus. Dosages of 0.2g/kg to 1g/kg should be administered IV as a bolus over 15 to 20 minutes. If required, this can be repeated two to four times over the next 24 to 48 hours. It is important, however, to maintain the animal on IV fluids (isotonic saline supplemented with potassium as required) to avoid dehydration.

Besides its well – known osmotic effect, which reverses the blood-brain osmotic gradient and thereby reduces extracellular fluid volume, mannitol has an immediate plasma-expanding effect. It reduces blood viscosity and increases cerebral blood flow and oxygen delivery.

This results in vasoconstriction and a subsequent decrease in intracranial pressure within a few minutes.

Frusemide is a loop diuretic that decreases CSF production by inhibiting the sodium-potassium pump. It can initially be given IV and continued orally at a dosage of 0.5mg/kg to 2(4)mg/kg PO q12h-24h, and then tapered off to the lowest dose possible.

Alternatively, acetozolamide, a diuretic that reduces CSF production by inhibiting carbonic anhydrase, can be given alternatively – a dose of 10mg/kg PO quaterly, every six to eight hours is recommended. Acetozolamide’s side effects include weakness, vomiting and panting. Care to avoid potassium depletion must be taken, particularly when combined with glucocorticoids. In case of seizures, anticonvulsant drugs such as phenobarbitone (3mg/kg bid PO), potassium bromide (30mg/kg to 40mg/kg sid PO), levetiracetam (10mg/kg to 20mg/kg tid PO) or gabapentin (10mg/kg to 20mg/ kg tid PO) might be necessary alone, or in combination.

Medical management may only result in temporary palliation of clinical signs. If no satisfactory results are achieved within two to three weeks, or unacceptable side effects develop, surgery should be considered. The goal of surgical treatment for hypertensive hydrocephalus is to continually divert (“shunt”) excessive CSF from the ventricles of the brain into another cavity, such as the peritoneum or the right atrium of the heart. It is imperative that the surgeon has experience with the shuntplacing technique.

Ventriculoperitoneal shunting (^{Figure 4a} and ^4b) is the most common type of shunting, as it is less invasive, and the peritoneal cavity has a high absorptive capacity. The shunt system consists of a ventricular catheter (or two ventricular catheters if the septum pellucidum separating the lateral ventricles is present), a one-way pressure cut-off valve, and a distal (long) catheter to be placed in the peritoneal cavity. Contraindications for shunting are evidence of CSF infection or peritoneal inflammation.

It is also important to resolve other systemic infections before ventriculoperitoneal shunting. Complications of shunt placement mainly include shunt infection or obstruction, as well as under or over-shunting.

The latter can potentially lead to the collapse of cerebral hemispheres and subsequent subdural haemorrhage, a complication to which animals with a thin cortex are particularly predisposed.

The success rate for ventriculoperitoneal shunting in dogs varies from 50 per cent to 90 per cent, depending on the severity of the underlying disease process.