Vestibular syndrome

The vestibular apparatus is the most important apparatus for maintaining the body’s equilibrium, a function which it achieves by integrating information from the visual system with that from the general proprioceptive system. The vestibular apparatus plays a fundamental role in maintaining proper posture and co-ordinating eye movements as a function of the position and movements of the head.

Dysfunction of the vestibular apparatus produces a complex of symptoms, referred to as the vestibular syndrome, which is characterized by varying degrees of loss of equilibrium that results in problems of postural instability, lack of co-ordination in gait and alteration of eye movements. The term “vestibular syndrome” is, therefore, used to define a set of symptoms of vestibular origin manifested by the animal, regardless of the cause. Most disorders of the vestibular system produce unilateral signs (asymmetrical); however, diseases that affect the vestibular system bilaterally are encountered occasionally.

FUNCTIONAL ANATOMY OF THE VESTIBULAR APPARATUS

The vestibular apparatus has traditionally been divided into two parts: one peripheral and one central. The peripheral part is made up of structures located in the inner ear (the vestibule and the semicircular canals) and of the vestibular part of the VIII_^th  pair of cranial nerves. The central part is located in the brainstem, where the four vestibular nuclei are located, and in the cerebellum, where the flocculonodular lobe and fastigial nucleus are found. When assessing an animal with vestibular syndrome, clinicians must always remember this anatomical distinction because the aetiology, treatment and, in particular, the prognosis differ considerably depending on whether the vestibular syndrome is peripheral or central.

CLINICAL PRESENTATION

The possible findings of a neurological examination in a patient with vestibular syndrome are presented below, following the order of the examination itself. The clinical differentiation between peripheral vestibular syndrome and central vestibular syndrome will be discussed after defining the common signs.

Postural changes: head tilting, falling, leaning
One of the most characteristic signs of a unilateral vestibular dysfunction is a “head tilt”, which is the result of reduced activity of the antigravity muscles which affects only one side of the neck (Fig. 1).This abnormal head posture is characterized by rotation of the midline plane of the head: the result is that one ear is lower than the other. A head tilt should not be confused with a “head turn”, in which the midline plane of the head is perpendicular to the ground, but the nose is turned to one side. Except in the case of a paradoxical vestibular syndrome, which will be discussed later, the inclination of the head is always on the side of the lesion. For this reason, when identifying a vestibular problem, it must always be specified whether the lesion is on the right or on the left.

A correct posture is characterized by the normal distribution of body weight on all four limbs; in the course of vestibular dysfunction several changes may occur in body posture, ranging from a broad-based stance, in the pursuit of greater stability, to “falling”, when the subject is unable to maintain its balance and falls to the ground. The most severe postural change in the course of vestibular  syndrome is “rolling” (video), in which the animal rolls on itself because of an exaggerated alteration in the tone of the antigravity muscles on the affected side compared to the normal side. Falling and rolling generally occur on the same side as the vestibular lesion.

Pathophysiology of the signs
A lesion of the left vestibular system results in a suspension of neural inputs from the left side, while the right vestibular system continues to send the inputs originating from the right side normally. This imbalance between the two streams of information causes stimulation of the right vestibulospinal tracts, which react by increasing the tone of the antigravity muscles on the right side. This produces rotation of the head and body and bending to the left, i.e. towards the side of the lesion. By rotating the head, the body adapts to the different and abnormal perception of equilibrium caused by the vestibular lesion, thus allowing the normal part of the vestibular system to prevail over the damaged part. Falling towards the affected side, as well as the asymmetry of the ataxia with deviation and sagging on the same side as the lesion, can be easily explained by the loss of action of the vestibulospinal tract on the affected side with an ipsilateral loss of extensor tone and lack of inhibition of the contralateral extensor tone.

Gait changes

In patients with vestibular system dysfunction, especially the more acute and severe forms, it may be difficult to examine the gait because the subject may be unable to maintain the quadruped  stance. When it is possible to evaluate the gait, the most prominent deficit is ataxia, defined as uncoordinated gait. The vestibular lesions cause an ataxia characterized by a broad-based stance and oscillations of the head and trunk when walking. This type of ataxia, called vestibular ataxia, is generally lateralised, unless the vestibular lesions are bilateral. The severity of the ataxia can be highly variable and is not related to the severity of the disease. In the unilateral forms, the animal has a tendency to divert the direction of its walking towards the affected side, an alteration referred to in clinical practice as “leaning” or “drifting”; in other cases there may be circular movements  (“circling”). In severe cases, vestibular ataxia may be accompanied by the abovementioned falls and rolling on the affected side because the patient with a vestibular lesion usually shows hypertonicity of the extensor muscles of the contralateral limbs and decreased muscle tone in the muscles ipsilateral to the lesion, thus preventing maintenance of the quadruped stance. Unless other regions of the central nervous system (CNS) are involved, an animal with vestibular syndrome does not lose awareness of the spatial position of its limbs (general proprioception) (video). Sight helps to compensate for the vestibular deficit, so removing visual input during the neurological examination may increase the severity of the clinical signs.

Alterations of the postural and proprioceptive responses and spinal reflexes

It may sometimes be difficult to examine a patient with vestibular syndrome, especially with regards to assessing postural and proprioceptive responses, because the loss of balance may be such as to render the animal unable to respond adequately to specific tests (hopping test, hemiwalking, wheelbarrowing, etc.). The only test considered vital for assessing the integrity of proprioceptive function is the proprioceptive positioning test (also called dorsiflexion of the foot). In this test the animal must be able to maintain the quadruped stance in such a way that weight bearing is distributed as evenly as possible on the ground through all fours limbs. This test is highly significant for evaluating conscious proprioception since it is the key item in the neurological examination, revealing the site of the lesion in the central vestibular structures if the response is deficient. (Video) Spinal reflexes may be difficult to assess, given that the animal may be reluctant to lie on the side of the lesion or continuously rolls to the side of the lesion. Spinal reflexes should be normal unless there are concomitant disorders of the peripheral nerves of the limbs; in this case the reflexes will be depressed or absent. Spinal reflexes on the opposite side of the vestibular lesion may be slightly increased for the reasons explained above.

Changes in the cranial nerves
Examination of the cranial nerves can reveal alterations that are common to both the peripheral vestibular syndrome and the central vestibular syndrome, in particular pathological nystagmus and vestibular strabismus. Functions of the vestibular system in the co-ordination of eye movements.

Pathological nystagmus

Nystagmus consists of involuntary rhythmic oscillatory movements of the eyes.It is defined as pathological if observed when the head is maintained in a static position (also called spontaneous nystagmus),or if it is evoked when the head is made to assume unusual positions (positional nystagmus). The presence of pathological nystagmus, whether spontaneous or positional, is always pathological and usually indicates vestibular dysfunction. The direction of movement of the nystagmus varies; the fast component is generally in the direction opposite to the affected side, while the slow phase is directed towards the affected side. If the patient is not examined in the early days after the onset of the lesion, the spontaneous nystagmus may not be obvious because of compensation by the body. Considering that spontaneous nystagmus tends to resolve in a few days, the clinician should always try to induce positional nystagmus through extension of the head and placing the patient in lateral recumbency, right and left, and in a dorsal position. In some patients suffering from a severe vestibular disorder, synchronous contraction of the eyelid is observed, caused by the action of the levator palpebrae muscle which is stimulated, like the extraocular muscles, by the oculomotor nerve (video). Pathological nystagmus linked to a dysfunction of the vestibular apparatus should not be confused with pendular nystagmus.

Strabismus

Positional or vestibular strabismus can be found in many animals with a unilateral vestibular disorder and consists of a ventral or ventrolateral shift of the eye ipsilateral to the lesion. It is often impossible to notice it during the first assessment of the animal's posture. It can, however, be demonstrated by using one hand to hold the animal's neck steady, and the other to lift the muzzle. It should be remembered that if this procedure is accomplished without altering the position of the head with respect to the sagittal plane, i.e., without cancelling the head tilt, the new pathological state of equilibrium, achieved by the animal with a vestibular lesion, does not change and it might, therefore, be difficult to evoke the strabismus. The examiner’s hand that guides the muzzle must, therefore, first turn the head of the animal until the two ears return to the same horizontal plane, and then raise the animal's muzzle (video).

Signs of the vestibular syndrome
In the course of vestibular syndrome, other neural structures located in the proximity of the peripheral and central vestibular structures may be involved. It is, therefore, possible to detect other signs that are not directly vestibular which, as we shall see, can help to localise the lesion.

Vomiting
Vomiting can occur with any type of vestibular dysfunction, but it is more common in dogs with acute peripheral vestibular disorders. This occurs because of the existence of vestibular connections to the vomiting centre, in the reticular formation of the brainstem. According to some authors vestibular symptoms are only occasionally accompanied by vomiting, while in one study 42.4% of patients with idiopathic vestibular syndrome had a history of vomiting.

Horner's syndrome

The closeness of sympathetic pathways to the peripheral part of the vestibular system accounts for the fact that lesions of the temporal region can cause signs of both vestibular dysfunction and deficient sympathetic innervation (Fig. 2).The term Horner's syndrome refers to the set of ocular signs associated with the loss of sympathetic innervation. The clinical signs include: miosis (constriction of the affected pupil); enophthalmos, due to loss of orbital smooth muscle tone (which normally protracts the eyeball) and retraction of the eyeball in the orbit; protrusion of the third eyelid which in dogs occurs passively as a result of enophthalmos while in cats it is also caused by dysfunction of the third eyelid retractor muscle; ptosis of the upper eyelid and decreased tone of the lower eyelid, due to the loss of smooth muscle tone of Müller’s muscle.

Facial palsy (cranial nerve VII)

The motor partof the facial nerve innervates the superficial muscles of the face and head and determines facial expression. This nerve also supplies preganglionic parasympathetic fibres to the lachrymal and salivary glands. Dysfunction of the facial nerve may be due to alterations of the peripheral part of the nerve caused by otitis media/interna, trauma, hypothyroidism, cancer of the middle/inner ear and polyneuropathies. In a study of 83 dogs with vestibular syndrome, more than half of the animals with otitis media-interna also had facial involvement. The affected patients may show a clear lowering of the ear, lip and lower eyelid on the affected side. This asymmetry of the face (Fig. 3) is also characterized by a deviation of the atonic nose toward the healthy side. The pet's owner may report that the patient has excessive salivation or that food falls from the mouth on the side of the lesion. The eyelid and corneal reflexes and response to threat are reduced or absent because of the inability to close the eyelids.

A dry neurogenic keratoconjunctivitis and dryness of the nasal mucosa may be signs of palsy of the facial nerve due to damage to the parasympathetic innervation of the lachrymal glands. Corneal ulceration is a frequent complication and is the result of the inability to close the eyelids and a decreased production of tears. In addition to the presence of recurrent corneal ulceration, a mucous discharge from the eye and chronic keratitis are often detected. If the palsy of the face becomes chronic, contractions and fibrosis of the denervated muscles lead to deviation of the nose toward the affected side and elevation of the ear. Hemifacial spasm can be found in the early stages of middle ear pathologies as a result of inflammation of the facial nerve (video).

Signs associated with lesions of the brain stem
Central vestibular syndrome, because of the concomitant involvement of structures adjacent to the vestibular nuclei, is also characterized by the presence of clinical signs that indicate dysfunction of brain stem structures. The brain stem is the site of the nuclei of cranial nerves III to XII, but it is also crossed by proprioceptive and sensory fibres ascending to the cerebral and cerebellar cortices, as well as  by descending fibres of the upper motor neuron system. Moreover, it is the site of the major centres that regulate vegetative functions. Lesions in this area can cause depression, stupor or coma in animals. Disorders that cause central vestibular syndrome may, therefore, be associated with depression of mental state.

Lesions causing a central vestibular syndrome may also be accompanied by dysfunction of the cranial nerves that originate, as already stated, at this level. The clinical signs that suggest involvement of the cranial nerves include: ipsilateral facial hypoalgesia (cranial nerve V = trigeminal nerve), atrophy of the masticatory muscles (mandibular branch of the trigeminal nerve); decreased tone of the jaw (cranial nerve V = trigeminal nerve), facial palsy (cranial nerve VII = facial nerve), weakness of the tongue (cranial nerve XII = hypoglossal nerve) and loss of the swallowing reflex (cranial nerves IX and X = glossopharyngeal and vagus nerves). Motor dysfunction such as ataxia of the four limbs and quadriparesis/hemiparesis may be present in central vestibular syndrome because the descending motor pathways and the ascending proprioceptive  bundles, running in the brain stem, are often compromised by the same injury that damages the vestibular nuclei.

Site of the lesion
Determining whether the lesion is in central or peripheral vestibular structures is of fundamental importance not only for planning the protocol of associated investigations, but especially for the prognostic implications which, in the case of peripheral forms, are generally favourable, while the prognosis in the case of central involvement is usually much worse. The direction of head tilt and vestibular ataxia, as well as the fast phase of nystagmus, make it possible to determine whether there is a right or left vestibular problem.

The presence of other neurological deficits must be determined in order to locate the lesion in the central or peripheral nervous system correctly. This is not always easy to achieve because often the subject’s disorientation, inability to stand and altered balance can be so severe as to make the neurological examination difficult and to simulate central symptoms that are actually absent.

Among the “pure” vestibular signs, nystagmus can provide precise information about the location of the lesion. In peripheral vestibular disorders, nystagmus is usually horizontal or rotational and the fast phase is directed from the opposite side of the lesion. In central vestibular disorders, the most frequent response is that of vertical or multidirectional nystagmus. Clinical experience does, however, question the validity of this rule. The lesion is located in central nervous system structures when there are signs indicating involvement of the brain stem.

The mental state of an animal may be different in peripheral or central vestibular disease: if the lesion is located at the periphery, the animal is conscious but may appear disoriented or even hyperexcited. In lesions of the central nervous system, however, the involvement of the reticular substance activating the brain stem, which is essential for maintaining the state of consciousness, can lead to manifestations of various degrees of depression, stupor and coma, signs observed in a recent study in 45% of patients with central vestibular syndrome. When examining gait, a unilateral dysmetria indicates an ipsilateral dysfunction of the brain stem or cerebellum. The most significant aspect of a central disturbance is the possible presence of paresis due to dysfunction of the upper motor neuron system and, most importantly, the presence of conscious proprioceptive deficits which usually involve in particular the limbs ipsilateral to the lesion. Therefore, the finding of paresis and/or proprioception deficits in an animal with vestibular ataxia is one of the most significant indicators that the lesion is located in the brain stem (See video "proprioceptive deficit").

When the lesion affects the central vestibular component, there may be signs of cerebellar dysfunction which are mainly recognizable as vestibular-cerebellar ataxia. Other neurological signs relevant to the location are the cranial nerve deficits, previously mentioned, which are usually evidence of an involvement of brain stem structures. It should, however, be borne in mind that isolated involvement of cranial nerve VII is a common occurrence in peripheral vestibular diseases due to middle and inner ear problems and does not, therefore, necessarily imply a central lesion. Similarly, the presence of Horner's syndrome is more frequently associated with lesions of the middle ear.

Table 1. Clinical findings associated with central and peripheral vestibular lesions (modified from Muñana, 2004).

Paradoxical vestibular syndrome

In the case of unilateral lesions of the peripheral vestibular system, the head and body are always inclined towards the side of the lesion. With some exceptions, the same occurs when there are lesions to the central components of this system. These exceptions should be referred to as paradoxical symptoms. Some unilateral lesions of the central vestibular pathways, especially with involvement of the medulla oblongata and the caudal cerebellar peduncle, produce inclination of the head towards the side opposite to that of the lesion. Likewise, the drifting or circling that may be seen during the neurological examination are usually contralateral to the lesion. Not all authors agree in defining the deviation of direction as contralateral to the lesion. In an effort to go beyond the opinions of the various authors, who do not always agree on the definition of paradoxical vestibular syndrome, it may be advisable to base the definition on a head tilt contralateral to the lesion and proprioceptive deficits ipsilateral to the lesion. Lesions that produce a paradoxical vestibular syndrome are usually destructive space-occupying lesions such as tumours or inflammatory lesions. These lesions often affect the general proprioceptive system afferent to the cerebellum, producing, as mentioned previously, deficits in postural responses on the same side as the lesion. This finding is, therefore, more reliable for the purpose of locating the site of the lesion.

Bilateral vestibular syndrome

Bilateral peripheral vestibular syndrome is characterized by symmetrical ataxia, loss of equilibrium on both sides and conservation of strength. There is no postural asymmetry. The patient often crouches on the ground with its legs spaced far apart from each other; the patient might crawl in this position, sometimes staggering and falling sideways. Head tilt and pathological nystagmus are not present and normal vestibular and post-rotational nystagmus cannot be induced. Often there is a rocking motion of the head from side to side, characteristic of bilateral vestibular dysfunction. The animal may also be deaf if the disease involves the auditory receptors.

DIFFERENTIAL CLINICAL DIAGNOSES

The list of differential diagnoses in an animal with vestibular syndrome varies considerably depending on the location, peripheral or central, of the vestibular lesion. For the sake of clarity, the main causes of peripheral and central vestibular syndromes are discussed below, separately. The disorders are indicated with the letters of the acronym VITAMIN D (V: Vascular; I: Inflammation/Infection, T: Traumatic, A: Abnormal/congenital, M: Metabolic/toxic I: Idiopathic, N: Neoplastic, D: Degenerative).

Peripheral vestibular syndrome
Inflammatory and infectious diseases - the most common cause of peripheral vestibular inflammatory disease is the spread of a middle ear infection (otitis media) into the structures of the inner ear (otitis interna). The vestibular signs that accompany otitis media/interna occur when the inflammation of the middle ear directly or indirectly affects the function of the membranous labyrinth. It is important to remember in these cases that some inflammatory diseases can mimic malignancies in the auditory canal. These conditions are of primary importance in cats while they are only occasionally reported in dogs. They include inflammatory polyps which may also extend through the auditory tubes to the nasopharynx to the point of causing signs of respiratory distress.

Trauma - a head injury can damage the peripheral vestibular structures and lead to the onset of acute unilateral vestibular signs in animals of any age. At physical examination palpation of the region of the tympanic bulla may be painful and bleeding can be seen, with or without rupture of the tympanic membrane, during the otoscopic evaluation.

Congenital abnormalities - congenital vestibular disorders, characterized by varying degrees of peripheral vestibular dysfunction, are generally found in purebreds in the period ranging from birth to the third month of age. The animal has no history of trauma, otitis externa, pharyngitis, systemic diseases or antibiotic therapy. All investigations are normal. In many of these cases, the prognosis is good because the deficits are usually compensated and subjects can become acceptable pets. Deafness may accompany congenital vestibular disorders. Because of the strong family relations of all the affected litters, several studies have suggested a hereditary condition. Other possible causes include congenital or developmental malformations.

Metabolic diseases - metabolic diseases do not usually produce vestibular symptoms. The only exception is hypothyroidism. The pathogenesis of peripheral nerve disorders associated with hypothyroidism is not completely understood, although the symptoms reported are considered the result of a deficit of energy metabolism that leads to an axonal transport dysfunction. Several substances may become toxic to the vestibular apparatus. It has long been known that prolonged treatment with high doses of aminoglycoside antibiotics (especially streptomycin, dihydrostreptomycin, neomycin, kanamycin, and gentamicin) causes degeneration of the labyrinthine receptors of the vestibular or acoustic systems, or both.

Some substances can cause ototoxicity when used topically: the best known are iodophor compounds and chlorhexidine. Because of their ototoxic potential, topical ear preparations should never be used if the tympanic membrane cannot be viewed or when it has lesions. If the vestibular disorders occur shortly after the local administration of potentially ototoxic substances, the auditory canal should be washed immediately with saline solution.

Idiopathic diseases - in older subjects, the most common cause of peripheral vestibular disease is idiopathic benign vestibular disease. This disease is rarely seen before 5 years of age, which is why it is sometimes called idiopathic geriatric vestibular syndrome.

Neoplastic diseases - tumours that can produce a peripheral vestibular syndrome may originate from the tympanic bulla or the bony labyrinth (osteosarcoma, fibrosarcoma and chondrosarcoma), or from soft tissues (squamous cell carcinomas, adenocarcinomas of the ceruminous glands and lymphomas). Even tumours of the vestibulocochlear nerve, such as neurofibrosarcomas, may result in vestibular disorders, but unlike in humans, these are extremely rare in small animals.

Table 2. Adapted from Rossmeisl: Vestibular disease in dogs and cats. Vet Clin North Am Small Anim Pract 2010:40:81-100.

Central vestibular syndrome
Vascular diseases - vascular diseases include ischaemic or haemorrhagic phenomena, characterized clinically by an acute or hyperacute onset of focal cerebral dysfunction, often asymmetrical and non-progressive. The clinical signs vary greatly depending on the affected area. When central vestibular structures in the brain stem or cerebellum are involved, there are the typical signs of central vestibular disease, which may be accompanied or not by deficits of the cranial nerves, and changes in mental state, proprioception and autonomic activity. The diagnosis is made based on information obtained from magnetic resonance imaging of the brain structures. The prognosis depends on the extent and location of the lesion.

Inflammatory and infectious diseases - inflammatory lesions of the brain and meninges constitute an important group of disorders with variable clinical signs that reflect the neuroanatomical location of the lesion. In cases in which the vestibular structures of the brain stem and cerebellum are involved, the symptoms of central vestibular syndrome are observed. Encephalitis and meningo-encephalitis can affect animals of any age, but are less frequent in elderly pets. Most infectious-inflammatory diseases of the central nervous system are characterized by the onset of acute or subacute symptoms, which tend to be progressive. Neurological signs are variable, but often indicate that there is multifocal disease. Indeed, in addition to the central vestibular signs, the affected subject may have quadriplegia, neck pain, cerebellar ataxia, cranial nerve deficits, blindness, and personality changes. There may or may not be signs of systemic infection. Most cases of encephalitis and meningo-encephalitis in pets do not have an infectious aetiology and are probably immune-mediated. The aetiological diagnosis of this group of diseases, defined meningo-encephalitis of unknown aetiology, is made based on the histological findings of a biopsy or anatomopathological examination. Infectious diseases of the central nervous system are less common in pets and include viral, bacterial, fungal and protozoan aetiologies. Nuclear magnetic resonance imaging has contributed significantly to the diagnosis of this category of disease.

Head injury - head injury can be caused by several different events, including road traffic accidents, bites or kicks, as well as injuries caused intentionally such as gunshot wounds. Animals showing central vestibular signs after a head injury usually also have neurological deficits associated with damage to nearby structures in the brain stem. Possible clinical signs are those associated with injury to the nuclei of cranial nerves V, VI, VII, IX and X, cardiac arrhythmias, ataxic breathing, changes in the level of consciousness and abnormal motor responses. The degree of the vestibular disturbance depends on the level of interference of the symptoms related to CNS lesions which, if severe, could mask the vestibular disease. Pathological nystagmus may be the only obvious sign of a vestibular disorder in semi-comatose and quadriplegic patients.

Given the importance of the brain stem in maintaining the body's vital functions, central vestibular lesions associated with trauma to this structure always have an extremely poor, if not dismal, prognosis.

Congenital diseases - numerous congenital malformations of the central nervous system have been described in dogs and cats. Some of these malformations are extremely rare, whereas others have a more significant incidence and clinical relevance. Congenital diseases in which the presence of vestibular signs has been described are hydrocephalus, arachnoid cysts, Chiari-type malformations and the Dandy-Walker syndrome.

Metabolic diseases - some intoxications may cause central vestibular diseases, associated to a greater or lesser degree with other neurological signs. The most important are metronidazole poisoning and thiamine deficiency. Central vestibular signs of acute onset (from 3 to 14 days) were observed in dogs after the administration of metronidazole at doses above 60 mg/kg/day. Even doses below 30 mg/kg/day have been considered to cause intoxication because there seems to be a considerable variation in the susceptibility of dogs to the side effects of this drug. Initially, the animal shows signs such as anorexia and vomiting, which then quickly progress to the point of reaching a set of vestibular signs, which can be either symmetrical or asymmetrical, with generalised ataxia and vertical positional nystagmus. Head tilt and seizures are less frequently present.

Thiamine (vitamin B1) deficiency is linked to malabsorption phenomena or an incorrect diet, the latter being more sporadic in dogs and more frequent in cats. Thiamine deficiency is associated with diets based exclusively on fish, because such diets contain high levels of thiaminase, an enzyme naturally present in many fish species, which degrades thiamine. Even commercial diets, although balanced, may have vitamin deficiencies due to improper heat treatment (over 100°C) of the product during the manufacturing process. Various pathogenic mechanisms have been proposed, but is not yet clear how a thiamine deficiency can lead to a selective dysfunction of nerve cells and their subsequent death; currently the most credited theory is that an energy deficit causes necrosis. The initial clinical signs are anorexia and lethargy, followed a few days later by the development of neurological signs, which commonly occur together with vestibular symptoms, concomitant seizures and mydriasis. Given that the origin of this disease is metabolic, the vestibular syndrome in this case is bilateral and symmetrical. The diagnosis is based on the detection of neurological signs in animals fed a thiamine-deficient diet. The blood-biochemistry findings which can be observed during thiamine deficiency are increased levels of lactate and pyruvate and a decrease in erythrocyte transketolase, although tests to measure these are rarely performed. Just as in other metabolic diseases, magnetic resonance imaging can detect bilateral symmetrical abnormalities in the brain (hyperintense lesions on T2-weighted images). Treatment involves supplementation with vitamin B1, which can be administered intravenously, intramuscularly or subcutaneously, at a dose of 5-50 mg/day in dogs and at a dose of 1-20 mg/day in cats. If not treated in the early stages of the disease, the prognosis is poor or even dismal.

Neoplastic diseases - all tumours involving intracranial nerve structures can potentially trigger the onset of central vestibular syndrome, as these can produce direct and indirect damage to vestibular structures. The direct damage is caused by the development of neoplastic lesions within the brain stem or cerebellum, while tumours in other structures of the neurocranium, such as the forebrain, may also exert compression and cause indirect effects on vestibular structures. Intracranial tumours typically develop in middle-aged or elderly dogs, most commonly in subjects over the age of 5 years, with the average age being 9 years. However, even young animals can develop tumours, such as medulloblastoma. Signs may develop gradually and progressively or acutely, depending on the neuroanatomical location of the lesion, its aggressiveness and the type and severity of the associated lesions (peritumoural oedema, acquired hydrocephalus, bleeding).

Diagnostic imaging is the investigation that provides the most information about tumours in the brain parenchyma: magnetic resonance imaging, in particular, which is better than computed tomography, can provide greater detail of the nerve tissue. The alterations that can be detected vary depending on the type of cancer, but in spite of the special features of resonance, the recurrent aspects are the presence of a space-occupying lesion, which may be within the nervous parenchyma (intra-axial) or outside it (extra-axial). The lesion may have clear or undefined margins, can sometimes cause displacement of the surrounding structures, may or may not be surrounded by oedema and has a variable capacity to take up contrast medium. There are several therapeutic options for intracranial neoplasms, which differ depending on the biological behaviour and site of the neoplasms. Chemotherapy, radiotherapy and surgery should, therefore, be considered on a case by case basis.

Degenerative diseases – the degenerative diseases that cause central vestibular syndrome include a group of pathologies with a hereditary component. Signs usually present in the first weeks of life. These diseases are characterized by the fact that they involve a broad area of the CNS and that they worsen gradually. They are commonly referred to as storage diseases since specific enzyme deficiencies in cells lead to alterations in the metabolism of substrates such as lipids, glycoproteins, glycogen and mucopolysaccharides which accumulate in the cellular compartment and alter normal cellular functions to the point of causing cell death. The storage diseases are invariably progressive and untreatable. They often lead to the death of the animal due to the development of the disease itself or because they induce clinical states that are increasingly incompatible with a decent life for the animal.

DIAGNOSTIC PROTOCOL

Given the variety of causes of vestibular syndrome, the diagnostic protocol is not univocal and  differs depending on the site (central or peripheral) and the clinician’s diagnostic suspicions. The investigations that may be needed in subjects with vestibular syndrome are reported below. It should be noted, however, that the usefulness of these tests is different for each patient.

Otoscopic examination - when there is suspicion of a peripheral vestibular syndrome, a careful examination of the ear structures should always be carried out to verify the presence or absence of lesions.

Blood-biochemistry and urine tests – a full blood count, complete biochemical profile and urinalysis are always recommended in patients with neurological or neuromuscular disorders, in order to have a minimal database. Although these tests are useful in the overall assessment of the patient, they do not often contribute to the aetiological diagnosis of the vestibular syndrome. Sometimes a neutrophil leucocytosis is found in the course of severe infections of the ear, whereas leucopenia may suggest a viral infection such as distemper. These tests must be done in any case, because the patient should be given general anaesthesia in order to perform investigations such as the removal of cerebrospinal fluid, electrodiagnostics and conventional and advanced imaging techniques.

Patients with hypothyroidism may have a mild form of normocytic, normochromic, non-regenerative anaemia, while blood-biochemistry tests may reveal high cholesterol values. These laboratory results, associated with the clinical findings, suggest the need for more detailed diagnostic tests of thyroid function; assays of the thyroid hormones, TSH, T4 and free T4, are, therefore, advisable.

Serology tests - these can be performed when infectious diseases such as distemper, toxoplasmosis and neosporosis are suspected. The serological test in the cases of suspected distemper is aimed at detecting the presence of antibodies to the virus: the results of this test should be interpreted with great caution, as there can be false negative or false positive results. In acute forms it can be useful to perform polymerase chain reaction analysis on the buffy coat or, if pleocytosis is present, on the cerebrospinal fluid since this method, unlike serology, can detect the presence of the virus directly.

Radiology - radiology is useful for screening the tympanic bullae; in addition the external auditory canal can be evaluated for the presence of chronic changes, such as mineralisation and stenosis. General anaesthesia is required to be able to position the animal correctly for radiographic studies of the tympanic bullae. In fact, the position of the head is fundamental for obtaining adequate views when evaluating these structures, since tissue overlap in the skull has a significant influence on the image. Five traditional X-ray projections are described: dorso-ventral, latero-lateral, open-mouth rostrocaudal (with varying inclinations depending on the shape of the occipital crest) and oblique-lateral with an inclination of 20° to both the right and the left.

The radiographic signs associated with middle ear pathologies include opacity of the soft tissue of the bulla,  sclerosis of the wall of the tympanic bulla or of the petrous portion of the temporal bone, which may be accompanied by bone proliferation, as well as signs of otitis externa. If the process is sufficiently severe, lysis of the bulla may also be observed. The sensitivity of radiology in the diagnosis of otitis media is still very modest and, since it requires general anaesthesia, has no significant advantages over advanced diagnostic imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI).

Computed tomography and magnetic resonance imaging - these are the two advanced imaging techniques commonly used in clinics for small animals. These techniques produce sections of the cranial structures in different planes of space in order to provide more information than that given by conventional radiology, in terms of both the study of the tympanic bulla and the study of the central vestibular structures located in the brain stem.

When comparing these two methodologies, it should be noted that MRI has greater sensitivity than CT in the visualisation of soft tissues and the caudal fossa: this superiority in the definition of nervous tissue makes it the “gold standard” for diagnostic imaging of the central nervous system. CT provides better image definition for hard tissues, but given the presence of the beam hardening artefact produced in the caudal fossa, where central vestibular structures are located, this diagnostic technique has objective limits in the diagnosis of central vestibular syndrome.

Patients with peripheral inflammatory diseases, such as otitis media/interna, may have pathological material within the tympanic bulla, a thickening of the tympanic bulla in the presence of chronic disease and involvement of the inner ear (this is best evaluated by MRI). Polyps have the same characteristics as soft tissue and such abnormal growths may be found in the auditory canal and the nasopharynx; the same applies to cancers involving auricular structures.

Central vestibular disorders caused by vascular pathologies have highly diversified MRI pictures, particularly with regards to haemorrhagic phenomena; the MRI characteristics of bleeding differ depending on the time elapsed since the vascular event and, therefore, require special imaging sequences for better characterization. For further information refer to the section "vascular diseases".

Inflammatory diseases produce typical MRI lesions: focal or multifocal, intra-axial, hyperintense in T2-weighted images, hypo- or iso-intense in T1-weighted images, hyperintense in FLAIR and with variable contrast enhancement. The lesions may have a characteristic topography depending on the particular type of meningo-encephalitis of unknown aetiology being studied.

In animals with a head injury it may be possible to detect  fractures of the cranial vault (best demonstrated by CT), bleeding and/or compression of the brain parenchyma.

Congenital pathologies, such as hydrocephalus, Chiari-type syndrome and the Dandy-Walker syndrome are indicators of possible alterations of the ventricular system, which are sometimes, but not always,  accompanied by disturbances in the flow of cerebrospinal fluid.

As previously mentioned, neoplastic diseases produce variable pictures, depending on the type of cancer being examined. They are usually space-occupying lesions and may be intra- or extra-axial, with either poorly defined or sharp margins. Adjacent structures may be displaced to a greater or lesser degree with respect to the normal anatomy (mass effect), and the contrast enhancement varies depending on the type of vascularisation of the tumour. For a description of the typical findings of individual cancers, please refer to the specific files.

TREATMENT

As previously stated, in the context of clinical neurology, signs are determined by the location of the lesion, rather than by its aetiology, and the treatment of vestibular syndrome is aimed at resolving the underlying cause. Therefore, an overview of the different options available to clinicians is given below, but the reader should refer to the specific files for further information.

Subjects with otitis media/interna will require prolonged antibiotic treatment, whereas surgical removal should be considered for polyps or malignancies involving peripheral structures. A hypothyroid subject should be treated with  levothyroxine supplementation, while the management of head injury may involve intensive care treatment, depending on the patient's condition.

Cerebrovascular accidents, if they are limited and do not progress, have a favourable prognosis because the animal is able to recover autonomously if the damage is not massive. Physiotherapy is recommended in severe cases.

Sterile inflammatory diseases require immunosuppressive therapy. Several protocols have been proposed and include chemotherapy drugs used in cancer patients in addition to corticosteroids at immunosuppressive doses. In the case of infectious diseases, the ones caused by protozoa, Toxoplasma and Neospora can be treated effectively with clindamycin in combination with sulphonamides; in cases of infectious diseases of viral aetiology, distemper and feline infectious peritonitis, treatment is palliative and the prognosis is extremely poor.

There are several options, mentioned only briefly here, for the treatment of intracranial neoplasms. From a medical point of view, intracranial tumours can be treated with chemotherapy or radiotherapy; direct surgical intervention is also an option, especially in cases of extra-axial neoplasms. The success of these therapies is strongly linked to the type and location of the tumour. Not all tumours can be managed surgically and, by the same token, it is not possible to radiate all regions of the central nervous system equally. As regards chemotherapy, one of the major problems is obtaining sufficient concentrations of the chemotherapeutic drug at the tumour mass, given the presence of the blood-brain barrier. The prognosis does, therefore, vary widely, with survival ranging from several months to several years, depending on all these variables. The central vestibular structures are located in the brain stem and cerebellum: this severely limits the surgical options because of the difficulty of accessing the area. Radiation therapy is not considered an option given the close proximity of the body’s vital centres, which would be difficult to protect from radiation.

Suggested readings

1. Bernardini M., (2010): Neurologia del cane e del gatto. Manuali pratici di veterinaria, Poletto Editore.
2. Bortolami, Callegari, Beghelli (2006): Anatomia e Fisiologia degli Animali Domestici. Edagricole.
3. De Lahunta A., (2008): Vestibular system – special proprioception. Veterinary neuroanatomy and clinical neurology. Philadelphia: W.B. Saunders.
4. Dewey C.W., (2009): A practical guide to Canine and Feline Neurology. Blackwell Publishing.
5. Garosi L., Dennis R., Penderis J., Lamb C.R., Targett M.P., Cappello R., Delauche A.J., (2001): Results of magnetic resonance imaging in dogs with vestibular disorders: 85 cases (1996-1999). Journal of American Animal Hospital Association, 218 (3): 385-91.
6. Garosi L., Dennis R., Schwartz T., (2003): Review of diagnostic imaging of ear diseases in the dog and cat. Veterinary Radiology and Ultrasound, 44: 137-46.
7. Garosi L, Dawson A, Couturier J, Matiasek L, de Stefani A, Davies E, Jeffery N, Smith P., (2010): Necrotizing cerebellitis and cerebellar atrophy caused by Neospora caninum infection: magnetic resonance imaging and clinicopathologic findings in seven dogs. Journal of Veterinary Internal Medicine. 2010; 24(3):571-78.
8. Higgins M.A., Rossmeisl J.H., Panciera D.L., (2005): Hypothyroid –associated central vestibular disease in 10 dogs: 1999-2005. Journal of Veterinary Internal Medicine, 20:1363-69.
9. Jones J.C., (2004): Neuroimaging. In: International Veterinary Information Service (www.ivis.org). Ithaca, New York, USA.
10. King A.S. (1994): Special Sensis. Phisiological and clinical anatomy of the domestic animals. Oxford University Press pag. 106-109.
11. Lamb C.R., Garosi L.S., (2000): Images in medicine: Two little ducks went on swimming one day. Veterinary Radiology and Ultrasound, 41: 292.
12. Le Couter R.A., (2006): Vestibular diseases of cats and dogs. In: NAVC Proceedings 2006, North America Veterinary Conference (Eds). Publisher: NAVC (www.tnavc.org). Internet Publisher: International Veterinary Information Service, Ithaca NY (www.ivis.org).
13. Owen M.C., Lamb C.R., Targett M.P., (2004): Material in the middle ear of dogs having magnetic resonance imaging for investigation of neurologic sings. Veterinary Radiology and Ultrasound, 45: 149-55.
14. Platt SR E Olby NJ., (2004): BSAVA Manual of Canine and Feline Neurology. BSVA 3rd edition, pag. 1-23.
15. Rossmeisl J.H., (2010): Vestibular Disease in Dogs and Cats. Veterinary Clinics of North America: Small Animal Practice, 40(1):81-100.
16. Sturges B.K., Dickinson P.J., Kortz G.D., Berry W.L., Vernau KM, Wisner E.R., Le Couter R.A., (2006): Clinical sings, Magnetic Resonance Imaging features, and outcome after surgical and medical treatment of otogenic intracranial infections in 11 cats and 4 dogs. Journal of Veterinary Internal Medicine, 20: 648-56.
17. Summers B.A., Cummings J.F., De Lahunta A., (1995): Veterinary Neuropathology. St. Louis, Mosby, pag. 237-49.
18. Thomas W.B., (2000): Vestibular disfunction. Veterinary Clinics of North America: Small Animal Practice, 30: 227-249.
19. Troxel M.T., Drobatz K.J., Vite C.H., (2005): Sings of neurologic dysfunction in dogs with central versus peripheral vestibular disease. Journal of American Veterinary Medical Association, 227: 570-74.