Cranial nerve disorders in dogs (Proceedings)

Generally, the underlying causes of neurological abnormalities of the head and face are similar whichever nerve (or nucleus) is affected, but, in addition, there are a few conditions that are specific to, or more commonly affect, certain nerves.

Table 1 Mechanism of Disease Specific Diseases of the Central Nervous System or Peripheral Nervous System affecting the Cranial Nerves Degenerative

CNS: progressive tetraparesis with laryngeal paralysis in              Rottweilers

PNS: Deafness – congenital, senile

Laryngeal paralysis – idiopathic in old dogs, breed related laryngeal paralysis -polyneuropathy complex

Congenital megoesophagus Anomalous

CNS: congenital hydrocephalus (strabismus)

Muscle: Persistent right aortic arch (megoesophagus) Metabolic/endocrine PNS: Hypothyroid neuropathy; diabetes mellitus [cats] Neoplastic

CNS:  – meningiomas, pituitary tumours, round cell tumors

PNS: -  nerve sheath tumours, round cell tumors, thyroid carcinomata Nutritional CNS: Thiamine deficiency Inflammatory

CNS: Infectious, inflammatory (GME)

PNS:  otitis media, myasthenia gravis, retrobulbar abscess

Muscle: myositis of extraocular muscles, masticatory myositis Idiopathic PNS: facial paralysis, trigeminal neuropathy, congenital megaesophagus Toxic

CNS: Tetanus, Metronidazole

PNS: Botulism, aminoglycoside antibiotics, cisplatin Traumatic

CNS: Head trauma

PNS: Skull fractures, iatrogenic damage to VII, VIII, X, XII, & sympathetic trunk Vascular CNS: brainstem hemorrhage, infarction

Neurodiagnostic investigation

A complete neurological examination is a prerequisite for investigating suspected neurological disease of the head and face. The neurological examination will help identify whether the cranial nerve dysfunction originates from a central nervous system or peripheral nervous system origin, which helps with determination of the differential diagnosis and the prognosis.

Neurologic Examination Results Indicative of Peripheral vs. Brainstem (central) Cranial Nerve Disease

Table 2 Neurologic Parameter Peripheral Cranial Disease Brainstem (central) Cranial Nerve Disease* Consciousness Normal Depression/stupor/coma Postural reactions Normal Frequently abnormal on ipsilateral side Segmental spinal reflexes May be abnormal if the underlying aetiology also causes a generalized peripheral neuropathy Intact Neck pain Absent May be a feature if the aetiology involves the nerve roots or meninges or causes and elevation of intracranial pressure Gait Commonly normal unless there is a concurrent generalized peripheral neuropathy Ipsilateral paresis Cranial nerves Frequently just one cranial nerve involved Multiple ipsilateral cranial nerves can be involved

* Central cranial nerve disease implies disease of the cranial nerve nuclei or the nerve roots as they leave the brainstem. Intracranial extra-axial disease affecting the cavernous sinus or retro-orbital areas can also cause signs, which can also be central in origin.

Several features of the investigation may require particular attention and are described below.

History

A thorough history is essential because certain neurological disorders of the head and face may produce signs that cannot be observed by the veterinarian during a consultation For instance, if an animal is reported to be vomiting, it is crucial to determine whether it is ‘true' vomiting or regurgitation. The owner of any animal in which generalised weakness or exercise intolerance is reported should be questioned about the animal's vocalisation, since dysphonia is commonly associated with laryngeal dysfunction.

Observations

Before conducting a ‘hands on' examination, several observations may aid in recognising or classifying disorders of the head and face. Firstly, as the animal walks around a room the position of the head and neck can be observed, looking in particular for a head tilt, or generalised tremors (which may also affect the head). Examination for symmetry provides important clues regarding the functioning of nerves innervating musculature of the head and face; this examination thus focuses on the relative sizes of the masticatory muscle mass, facial expression, palpebral fissures and pupils. The ability to close the jaw (dependent on the motor component of the trigeminal nerves) and maintain a normal tongue position (mediated by the hypoglossal nerves) is also apparent from simple observation.

Neurologic examination

Important functions for assessment of innervation of the head and face include the menace response, blink (or palpebral) reflex, vestibulo-ocular reflex and gag reflex. Several other tests may be of value for detecting neurological abnormalities of the head and face

·         Masticatory muscle tone is evaluated by opening the jaws

·         Tongue strength is evaluated by attempting to hold the tongue; normal animals can easily withdraw their tongues (since it is wet and slippery).

Ancillary diagnostic tests

·         Hearing can be tested crudely by observing responses to noise; however, a more sophisticated and objective test is the brainstem auditory evoked response (BAER).

·         Schirmer tear test can be used to detect deficits in tear production.

·         Pharmacological testing with adrenergic agonists can be used to investigate Horner's syndrome.

·         Measurement of antibodies to the acetylcholine receptor can be used to substantiate the diagnosis of immune-mediated myasthenia gravis.

·         Measurement of antibodies to type 2M muscle fibres can be used as an aid to diagnosis of masticatory muscle myositis.

·         MRI or CT scanning to detect CNS lesions, especially tumors

·         Cisternal CSF analysis to detect inflammatory disease of the CNS or nerve roots.

·         Electrodiagnostics (EMG, NCV) to objectively diagnose generalised peripheral neuropathies, or to assess specific cranial nerve function such as that of the facial and trigeminal nerves.

·         Measurement of antibodies  against various infectious agents, including Toxoplasma, Neospora, Rickettsia, Leishmaniasis.

Specific neurological syndromes of the head and face

Laryngeal paresis / paralysis

Inspiratory stridor and dysphonia are the classical clinical signs associated with laryngeal paresis or paralysis, although severe inspiratory dyspnoea, cyanosis and collapse can occasionally be identified. These signs may be sufficiently mild that animals will only present for treatment following particular periods of respiratory stress, such as prolonged exercise or extreme hot weather, at which time they may present in a hyperthermic crisis. Affected animals may also cough, especially when drinking water, and can develop clinical signs related to the secondary development of aspiration pneumonia (after they have inhaled food). 

Congenital laryngeal paralysis  is considered to account for up-to 30% of the cases seen in clinical practice and has been proven or suspected in several breeds including Bouvier des Flandres, Siberian Huskies, Husky crosses, Dalmatians and Bull Terriers (see manual appendix); it may be accompanied by a generalised peripheral neuropathy, when it has been termed laryngeal paralysis peripheral neuropathy complex (LPPC). In Bouviers and Huskies there is evidence of degeneration of neuronal cell bodies within the nucleus ambiguus in the medulla oblongata with subsequent Wallerian-like degernation of the laryngeal nerves; whereas in Dalmatians and Rottweilers it occurs as part of a generalised ‘dying back' axonal degeneration.

The onset of clinical signs in these dogs can be as early as 4 to 6 months of age, at which time the condition can be unilateral or bilateral. Electromyographic examination can reveal variable bilateral denervation of the laryngeal abductor muscles usually correlating with laryngoscopic examination. Surgery is necessary to relieve airway obstruction, but will only be a short-term measure in those breeds with concurrent progressive tetraparesis. As the disease is inherited as an autosomal dominant trait in Bouviers, selective breeding should be employed.

Most commonly, laryngeal paralysis occurs as an acquired disease in middle-aged and older large breed dogs, notably Labradors. Although laryngeal paralysis in mature animals is often considered ‘idiopathic' there is some evidence that it commonly occurs as one, particularly prominent, component of a generalised polyneuropathy. Since the recurrent laryngeal nerve is especially long, it has been proposed that it will be more susceptible than other peripheral nerves to axonal ‘dying back' diseases, in which transport of vital substances to the tip of the axon is compromised. Therefore it is important to consider investigation for systemic disease that can cause polyneuropathies.

Acquired laryngeal paralysis occasionally occurs as a consequence of trauma to the vagus nerve during cervical surgery, lead and organophosphate toxicity, retropharyngeal infection and neoplasia in the vicinity of the recurrent laryngeal nerve; the most commonly incriminated tumour type is thyroid carcinoma. Laryngeal paresis / paralysis can occasionally be seen to be due to brainstem disease; in these cases there are usually other cranial nerves involved and there is often a profound alteration of the dog's consciousness.

Diagnosis

Laryngeal paralysis is usually diagnosed simply by examination of the movement of the vocal folds, either directly through the mouth when the animal is lightly anaesthetised, or by ultrasonography during consciousness. In equivocal cases, EMG examination is helpful, not only in objectively defining denervation of the larynx, but also in detecting more generalised disease both of cranial structures (especially the pharynx) and throughout the entire body. Palpation, ultrasonography and biopsy readily diagnose thyroid tumours.

Treatment and prognosis

Treatment of laryngeal paralysis requires surgical lateralisation of the arytenoid cartilage regardless of the underlying cause as it is usually a permanent defect. Nevertheless, surgical lateralisation of the arytenoids should not be undertaken lightly in cases in which deglutition is compromised, since it will dramatically increase the risk of food inhalation. Some thyroid tumours can be excised surgically but others are extremely locally invasive, implying that other anti-cancer treatment modalities should be considered.

Megaesophagus

Clinical signs

The characteristic sign of megaesophagus is regurgitation, usually involving both food and fluid; during initial investigation it is of course critical to differentiate regurgitation from true vomiting. Because of regurgitation there may be several other associated clinical signs such as weight loss (or failure to gain weight) and coughing because of inhalation / aspiration pneumonia.

Pathogenesis

There are both congenital and acquired forms of megoesophagus. The underlying cause of congenital megaesophagus is unknown, but recent studies have suggested that afferent function may be aberrant rather than denervation or muscle anomalies. Congenital megoesophagus can also arise as a secondary consequence of a persistent right aortic arch or as one aspect of congenital myasthenia gravis (although not all affected breeds develop megoesophagus). Acquired megoesophagus can result from a wide range of lesions including both brainstem and systemic disease, most notably myasthenia gravis, in which there is immune-mediated destruction of the acetylcholine receptor.

Diagnosis

Megoesophagus is readily diagnosed by radiography, especially if food mixed with barium mixed is given shortly before. Determining the cause for megoesophagus relies on detecting and investigating other signs of systemic or brainstem disease. For instance, routine blood analysis of haematology and blood chemistry can suggest hypoadrenocorticism, myositis or systemic lupus erythematosus and hypothyroidism and myasthenia gravis can be detected by specialist blood tests. 

If neurological examination detects generalised peripheral nerve diseases, botulism or generalised peripheral neuropathies may be considered, whereas if nearby cranial nerves show deficits then brainstem disease may be suspected and diagnosed using advanced imaging techniques or CSF analysis. In cats, the possibility of dysautonomia should be considered (dogs do not develop megoesophagus with dysautonomia because they have striated muscle throughout the length of the oesophagus). If all of these conditions can be ruled out then idiopathic disease must be assumed.

Treatment and prognosis

For many acquired cases of megoesophagus treatment of the underlying disease is possible – most often by immunosuppressive therapy using corticosteroids or other drugs. In congenital myasthenia gravis, although the disease can be treated using anticholinesterases it can be difficult to achieve the correct dose to restore satisfactory swallowing function. Similarly, unless persistent aortic arches are surgically treated early the megoesophagus will not resolve adequately.

No matter what the cause, postural feeding (i.e. feeding the animal with the head directly above the stomach) and feeding a diet that is of a gelatine-like consistency is highly recommended to aid passage of food from mouth to stomach and avoid inhalation.

The prognosis for animals affected with megoesophagus is guarded because of the very high incidence of inhalation pneumonia, which is life-threatening; many animals succumb within a few weeks to months of starting therapy. It has been suggested that since spontaneous remission can occur in myasthenia gravis it may be preferable to avoid immunosuppressive therapy because it may promote respiratory tract infection.

Table 3 Causes of Megaesophagus Distinguishing Diagnostic Features Myasthenia gravis

+/- exercise intolerance

+ve Ach receptor antibody titre

Congenital megaesophagus

No other neurologic deficits

Certain breeds predisposed: Botulism Generalized LMN signs Polymyositis

Generalized weakness, increased CK

Myositis on muscle biopsy Addison's disease Generalized weakness, electrolyte abnormalities, negative ACTH, stimulation test Persistent right aortic arch Radiographic appearance Oesophagitis

History of vomiting

Endoscopic evidence

Brain stem disease Other signs of brain stem disease Systemic lupus erythematosus

Myositis on muscle biopsy

Mult-system immune-mediated disease

+ve ANA (disputed value) Dysautonomia [cats]

Multiple signs of dysautonomia

(dilated pupils, constipation etc)

Masticatory myositis

This is an immune-mediated disorder in which antibody directed inflammation is targeted at the muscles of mastication, which include the masseters, temporalis and pterygoid muscles. Atrophy of the masticatory muscles can occur unilaterally or bilaterally; bilateral disease is not associated with failure to close the mouth, but some individuals will exhibit limited mouth opening (trismus). Differentials for such a presentation include all the causes of generalised myopathies as well as diseases of the trigeminal nerve (CN V) or its nucleus in the pons of the brainstem.The absence of other detectable neurological deficits confirms that brainstem involvement is improbable in most cases. Bilateral atrophy can be caused by many systemic diseases, most notably cachexia (e.g. in association with cancer) and prolonged influence of exogenous or endogenous corticosteroids (e.g. hyperadrenocorticism).

Most commonly, however, it occurs as a consequence of masticatory myositis because of destruction of muscle fibres and scarring, which can occur rapidly. The acute phase of this disease can cause muscle swelling and pain, but not all cases appear to exhibit these signs. Exophthalmos and fever can occasionally be seen. Palpation of the muscles or attempts to open the jaws can cause a painful response. Unilateral atrophy is occasionally encountered and although many animals live for many years without developing other signs it is now recognised that nerve sheath tumours can be responsible.

There is no gender predisposition documented for masticatory myositis and the only breed noted to have a predisposition is the German Shepard. Most dogs are large breeds and are often young adults. Cats are infrequently affected by this condition.

Diagnosis

Detection of significant levels of anti-Type 2M muscle fibre antibodies will confirm masticatory myositis, although by the time animals reach the chronic phase the antibody response may well have subsided. Serum creatine kinase levels may also be elevated. Muscle biopsy can confirm the presence of inflammatory infiltrate, myofibre necrosis and phagocytosis and specifically identify antibody localisation to the Type 2M myofibers. Electromyography will often identify spontaneous abnormalities and should always be performed to evaluate the rest of the patient's musculature in cases where a more generalised myopathy is suspected.

Treatment and prognosis

Treatment of the underlying cause is possible in cases of masticatory myositis by immunosuppressive doses of corticosteroids, but some cases of masticatory muscle atrophy are too far advanced for this therapy to be effective. The recommended dose of prednisolone is 1-2 mg/kg per os q 12hr for 3-4 weeks after which the dosage is tapered slowly to achieve the lowest every other day dosage that will achieve the clinical signs. Most dogs treated aggressively in the early stages will show a good response to this therapy but relapses are possible. Some cases will require the addition of a further immunosuppressive medication such as azathioprine as with idiopathic polymyositis.

With an early response the prognosis may be favourable. In those cases with chronic loss of muscle mass and trismus, permanent dysphagia may be a feature of the condition. Feeding regimens should be discussed with the owner as even in the early stages of a responsive condition, feeding tubes may be necessary if only to reduce the potential for aspiration pneumoinia subsequent to the dysphagia. Additional therapy advisable includes vigorous physiotherapy of the jaw muscles; this can be done by encouraging the dog to chew rawhide or play with tennis balls.

An uncommon variant of masticatory myositis may be extraocular myositis, where the inflammatory disease is restricted only to the extraocular muscles. Young Golden retrievers may be predisposed. Dogs have been reported to present with acute bilateral exophthalmos. Creatine kinase levels, EMG and muscle biopsy are recommended diagnostic techniques. Treatment and prognosis is suggested to be as for masticatory myositis.

Idiopathic trigeminal nerve palsy

Clinical signs

Motor deficits caused by trigeminal nerve palsy are recognised in the syndrome of ‘dropped jaw', in which the patient (almost always a dog) cannot close the mouth or prehend food properly. Other cranial nerves are not affected but there can be a variable degree of sensory loss (sensory trigeminal distribution) and some animals display Horner's syndrome.

Pathogenesis

The cause is thought to be an idiopathic neuritis, although older texts suggested an unsubstantiated link with dogs carrying heavy loads in their mouths. It is important to recognise that the condition must be bilateral to produce the clinical signs and therefore must affect the peripheral nerves and not the brainstem.

Treatment and prognosis

Treatment is simply supportive – helping the animal to eat by offering boluses of soft food and assisting with drinking or the placement of a temporary feeding tube. It has been suggested that holding the mouth shut with a muzzle may aid recovery. Most animals recover rapidly – so that they can eat unassisted within three weeks.

Facial paralysis

Facial nerve dysfunction may be due to disease of the peripheral facial nerve (CN VII) due to otitis media-interna, trauma, hypothyroidism, neoplasia of the middle/inner ear or polyneuropathies. Disease of the facial nerve nucleus in the medulla of the brainstem can be due to any of the diseases affecting the CNS. The most common cause of peripheral facial nerve paralysis has been reported to be idiopathic (75% of dogs and 25% of cats with facial paralysis).

Idiopathic facial paralysis

Idiopathic facial nerve paralysis or palsy may be unilateral or bilateral, but usually occurs in the absence of other neurological deficits (sometimes affected animals also develop idiopathic vestibular syndrome). Exposure keratitis occurs commonly subsequent to the improper lubrication of the cornea. Clinical signs are usually maximal in 7 days and recovery can take 3-6 weeks if at all. Since unilateral facial nerve palsy can also develop in association with CNS diseases it is essential to consider the possibility of CNS lesions as a cause – typically these will be associated with abnormalities of the postural reactions.

In early reports on idiopathic facial nerve palsy, biopsies revealed marked depletion of large diameter myelinated axons.

Diagnosis

All possible causes of facial paresis/paralysis should be excluded before this specific diagnosis can be made. A thorough investigation for ear disease should take place in addition to blood tests for hypothyroidism and electromyography to rule out polyneuropathies.

Treatment and prognosis

There is no effective treatment for the underlying disease but it important to ensure that the cornea is adequately lubricated (either by endogenous production, or eye drops). The prognosis for idiopathic facial palsy varies – many animals make a gradual recovery (weeks to months) but some will be left with permanent deficits, which may progress to produce muscle contracture and deform the facial expression permanently.  This can be mistakenly interpreted as an uncommon syndrome in dogs and cats of hemifacial spasm.

Hemi-facial spasm

Clinical signs of this syndrome include blepharospasm, elevation of the ear, deviation of the nose to the affected side and wrinkling or displacement of the upper lip. The signs may precede facial paralysis but the spasm must be differentiated from contraction secondary to denervation atrophy and fibrosis. Hemi-facial spasm may be due to lesions of the middle-inner ear or the brainstem and should be investigated thoroughly. Control of hemifacial spasm depends on identifying and treating the underlying cause, if possible.  

Multiple cranial nerve problems

Various combinations of unilateral or bilateral cranial nerve deficits are sometimes detected; almost any combination of signs is possible, depending on the underlying cause (see below). In some instances there will be concomitant depression in limb postural reactions and some animals may exhibit stupor.

Pathogenesis

It is important to recognise the significance of bilateral cranial nerve disorders and postural reaction deficits: bilateral cranial nerve deficits suggest that the lesion is not in the CNS (a lesion in the brainstem large enough to cause bilateral deficits would likely be fatal), and postural reaction deficits in combination with cranial nerve deficits suggest that the lesion is in the CNS. 

Generalised peripheral neuropathies can cause any combination of cranial nerve deficits, therefore it is of the utmost importance to examine all peripheral nerve reflexes in any animal in which there is a cranial nerve disorder. Occasionally, the most prominent signs are confined to the cranial nerves, for instance there are uncommon idiopathic diseases that can affect multiple cranial nerves – most notably: i) feline dysautonomia, in which pupillary dilatation and megaoesophagus are characteristic signs and ii) polyganglioneuritis, which has been reported as a cause of multiple somatic cranial nerve deficits.

Brain tumours may occasionally cause multiple cranial nerve signs, especially if they develop within the caudal part of the brainstem; in most instances these signs would be accompanied by depression in limb postural reactions. A more confusing presentation is that associated with skull-base tumours (i.e. cavernous sinus syndrome) in which there may be multiple cranial nerve deficits, often bilaterally, but without evidence of brainstem involvement. Such animals are often also very depressed because of elevated intracranial pressure. 

Miscellaneous

·         Iatrogenic cranial nerve lesions

·         Several cranial nerves and associated structures are susceptible to injury during surgical procedures around the head and neck:

·         The facial nerve is vulnerable because of its superficial location on the side of the face. Surgery around the deep portions of the external auditory canal and the middle ear, or parotid duct transposition, is a common cause of facial nerve palsy. Clinical signs due to neurapraxia usually improve in 2 weeks or less. Axonotmesis requires regrowth of the axon from the site of injury at an approximate rate of 1 inch per month.

·         The sympathetic trunk is vulnerable to injury during bulla osteotomy (especially in cats) and any deep neck surgery that involves prolonged retraction of the soft tissues including the sympathetic trunk where it is contained within a common sheath alongside the vagus. Occasional dogs appear to develop Horner's syndrome after vigorous restraint using choke chains.

·         The recurrent laryngeal nerve may be injured during approaches to, or around, the trachea – especially extraluminal stenting procedures for tracheal collapse.

·         The hypoglossal nerve is susceptible to injury during mandibular surgery – especially hemimandibulectomy. Bilateral injury can lead to dramatic drooping of the tongue from the mouth.

·         The peripheral vestibular system can be damaged by over-vigorous curettage during bulla osteotomy.