From Head Trauma to Toxicity, Cerebellar Disease Diagnosis

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FROM HEAD TRAUMA TO TOXICITY, CEREBELLAR DISEASE DIAGNOSIS

Author : Dan Forster

Categories : Vets

Date : December 8, 2008

DAN FORSTER examines the clinical pointers indicating a disease that not only affects movement, but also eating, and describes the possible differential diagnoses behind the dysfunction.

ANIMALS with cerebellar disease will often present with classic signs of ataxia and dysmetria. However, the aetiology of the cerebellar damage is not always straightforward.

This article reviews some of the causes of cerebellar dysfunction that may be encountered in general practice.

The cerebellum occupies 10 per cent of the brain parenchyma in dogs and cats, and lies behind the cerebrum. It is connected to the brainstem by three paired cerebellar peduncles on each side, which act as a conduit for both afferent and efferent information related to cerebellar function. It is divided into functional units by a series of transverse fissures.

The small flocculonodular node is important for balance, and the caudal lobe is associated with the feedback regulation of motor function. The more rostral lobe receives proprioceptive information.

At a cellular level, the inner portion of the cerebellum is the medullary substance that contains the deep nuclei. The outer portion is the cerebellar cortex and is composed of three layers; the molecular cell layer, the Purkinje cell layer and the granule cell layer (Figure 1). The Purkinje cells are large and very active, metabolically, which makes them highly susceptible to ischaemic and toxic damage.

1 / 15 An understanding of the microscopic anatomy is useful when considering how different cerebellar diseases manifest themselves clinically.

The major function of the cerebellum is to coordinate voluntary, postural and reflex movements. The cerebellum is also thought to influence conscious thought processes, such as judging the timing of events and solving spatial and perceptual reasoning problems.

Coupled with the vestibular system, the cerebellum also places a vital role in assisting equilibrium maintenance. Coordination and motor control in neonates is dictated by the degree of cerebellar development at birth.

Clinical signs

• Ataxia

Cerebellar ataxia is due to a failure of motor coordination, although musculature strength is preserved. Swaying of the body (truncal ataxia – Figure 2) may be present, and animals will often stand with a broad-based stance.

• Dysmetria (Figure 3)

With dysmetria, limbs either overstep (hypermetria) or understep (hypometria). Hypermetria is more usually seen and changes are more evident in thoracic limbs.

These changes reflect the animal’s inability to regulate the rate, range and force of movement. Dysmetria of the head is manifested as an intentional tremor that may be seen at rest (although, strictly, this is a tremor that appears after initiation of a movement), but is most easily appreciated when the animal concentrates on a task, such as when the animal attempts to eat. Poor balance complicates the process of eating further, as animals often cannot stand steady for long enough (Figure 4).

• Vestibular signs

Disequilibrium may occur due to involvement of the flocculonodular lobe. Signs reflect those seen in vestibular disease and may include loss of balance, falling to one side, head tilt etc.

• Other signs

Various other symptoms may be seen in association with specific diseases that affect more than just the cerebellum. Occasionally, with cerebellar pathology alone, there may be:

– delayed postural reactions, with usually normal proprioceptive positioning;

2 / 15 – menace reaction deficits (ipsilateral to side of lesion), but with normal facial nerve function and vision; and

– increased muscle tone and normal to hyperreflective reflexes.

Assessment is often complicated by neurological damage elsewhere, and this should be taken into consideration during the neurological examination.

Diagnosis

In some instances the diagnosis is straightforward, such as a young kitten with ataxia, dysmetria and poor balance control – these factors scream cerebellar hypoplasia. However, this is not always the case, particularly if other systems are affected, and further investigation is often necessary.

Physical examination (particularly neurological exam) aids the clinician in localising the lesion. Full bloods are, as ever, necessary and usually coupled with urinalysis and survey radiographs. Other forms of imaging can be useful, where available. MRI is preferable to CT for examining the brain since beam-hardening artefacts can obscure areas of the brain with CT scans.

CSF analysis may aid the diagnosis and might be used in combination with serology tests for FIP, distemper, toxoplasmosis etc. Histopathology of the cerebellum is very useful, but rarely performed – except at postmortem.

Differential diagnoses

• Trauma

Trauma is thought to be uncommon due to the isolated nature of the cerebellum, although cats present more often than dogs.

Severe trauma can cause acute decerebellation, which occurs when the entirety of the organ is affected. There will usually be opisthotonus (hyperextension of neck and tail), plus rigidity of all four limbs. Animals may present in this fashion and often look like they are in rigor mortis – although they are still alive (Figure 5).

Treatment should focus on managing any associated shock and maintaining good cerebral blood flow. Oxygenation is also important, and blood pressure plus intracranial pressure should be monitored.

• Cerebellar abiotrophy

Abiotrophy may be defined as spontaneous, premature neuronal death. These diseases refer to

3 / 15 degeneration of normal neuronal cell populations within the cerebellar cortex after birth and are thought to be due to inherited defects of cellular metabolism.

Autosomal recessive modes of inheritance have been suggested for most of the abiotrophies. The cerebellar Purkinje cells seem to be targeted (Figure 1). Affected animals usually have progressive cerebellar neurological signs. This differs to the static nature of signs seen in cats with hypoplasia. The rate of progression differs between breeds, however.

The onset of signs is variable from breed to breed. For example, Kerry blue terriers may show signs at six to eight weeks of age, whereas Gordon setters may be a few years old before the onset of clinical signs. Cerebellar abiotrophy has been mainly reported in dogs, with a few sporadic feline cases reported.

• Neuroaxonal dystrophy

This has been reported in both cats and dogs, and characterised histologically by swellings at axonal ends – “spheroids”. The condition is thought to be due to a defect in axonal transport, leading to an accumulation of transport products at the distal axon. The disease is genetically transmitted in cats (Siamese and domestic shorthairs) and also thought to be hereditary in dogs. A similar pattern is seen histologically following the accumulation of metabolic by-products in lysosomal storage diseases. Symptoms are typical of cerebellar syndrome and usually present within the first few months of life.

• Dandy-Walker syndrome

This rare congenital malformation is well-recognised in human medicine. The disease features specific cerebellar abnormali ties, including cerebellar vermian hypoplasia, hydrocephalus and the presence of a fluid-filled cyst in the posterior fossa. The condition has been reported in one kitten and several breeds of dog; typical cerebellar signs were noted.

• Feline cerebellar hypoplasia

This is seen sporadically in kittens and, less commonly, in dogs. A feline panleukopaenia virus infection in utero is considered the main cause of this condition in cats, and canine herpesvirus in dogs, although toxins and genetic defects have also been reported. The cytopathic effect of the virus on rapidly dividing cerebellar cells of the external germinal layer, coupled with the virus’ direct effect on Purkinje cells, is sufficient to cause a hypoplasia of the granule cell layer. Signs are usually observed when kittens or pups start to walk. Animals show typical signs of dysmetria and poor balance (Figure 6). Some kittens are reported to improve, which is probably due to compensation using conscious proprioception and vision.

• Cerebellar toxicity

4 / 15 Metronidazole has been reported to cause signs of acute cerebellar dysfunction, which may occur from as early as seven days after the start of therapy, although toxicity is usually associated with higher doses and/or longer durations of medication. Signs will slowly resolve once therapy is stopped.

• Infectious and inflammatory cerebellar disease

Other areas of the CNS, with or without other organ systems, will often be affected, depending on the disease. Each condition cannot be discussed in detail, but a summary for infectious conditions that can affect the cerebellum is provided here:

• canine distemper (early and late onset, cerebellar peduncles are typically affected in association with other areas of brain tissue);

• feline panleukopaenia virus;

• mycotic disease (diffuse or multifocal meningoencephalitis can cause damage throughout the CNS. Any mycotic organism may cause disease, with Cryptococcus and Blastomyces most commonly reported);

• parasite migration (rare);

• canine herpesvirus;

• toxoplasma and neospora (protozoa typically present as multifocal disease, and infectious foci can also form granulomas);

• ricketssial disease (vasculitis caused by Rocky Mountain spotted fever – or ehrlichiosis – an cause meningoencephalitis in dogs. Cerebellovestibular signs are common, in association with other CNS symptoms);

• algal disease (Prototheca species) is a rare cause of CNS disease and immunosuppressed animals are most at risk. Pyogranulomatous lesions may be seen in the brains of affected animals; and

• feline infectious peritonitis (the dry form can cause inflammation of the ependyma, choroid plexus or meninges that surround the brain stem and cerebellar and/or medullary junction).

MRI, CSF analysis, serology, PCR tests and biopsy are all useful diagnostic tools.

• Granulomatous meningoencephalitis (GME)

5 / 15 This can occur as a disseminated disease or a focal mass lesion. Typically seen in small terriers, the specific aetiology is unknown. CSF can help diagnose this condition, and there is often a mononuclear plaeocytosis with raised protein. Reports suggest that lesions in the region of the cerebellomedullary angle are most common. MRI may indicate inflammatory changes or a mass lesion, and corticosteroids remain the treatment mainstay.

• Cerebellar neoplasia

Both primary and secondary tumours can affect animals, and lymphomas, meningiomas and astrocytomas frequently affect the cerebellum.

Meningiomas are the most common brain tumours in dogs and cats. Feline meningiomas are benign growths that tend not to invade surrounding tissue. Their encapsulated nature makes them more amenable to surgery than canine meningiomas, which are aggressive and invasive.

Medulloblastomas are less common, but can also affect the cerebellum. They are highly metastatic, and often invade the fourth ventricle, causing obstructive hydrocephalus. Choroid plexus tumours can impinge on the cerebellum, and they develop in the fourth ventricle. Treatment and/or prognosis depends on the specific tumour type, but it is usually guarded.

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Figure 1. Cellular arrangement of the cerebellar cortex.

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Figure 2. Cerebellar ataxia is due to failure of motor coordination, although strength of musculature is preserved. Truncal ataxia (swaying of the body) may be present, and animals will often stand

8 / 15 with a broad-based stance.

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Figure 3. With dysmetria, limbs either overstep (hypermetria) or understep (hypometria). Changes are more evident in thoracic limbs and reflect the animal’s inability to regulate the rate, range and force of movement.

Figure 4 (top). Cerebellar damage can make eating more difficult for patients.

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Figure 5 (right). Severe trauma can cause acute decerebellation; this patient has suffered a head trauma.

Figure 6 (above). Feline panleukopaenia virus characteristics are usually observed when kittens start to walk. Animals show signs of dysmetria and poor balance.

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