Diseases Associated With Clinical Signs Originating From Cranial Nerves

Diseases Associated With Clinical Signs Originating From Cranial Nerves

C H A P T E R

83

 

CAROLINE HAHN

T

he nerves emanating from the brainstem (the midbrain, pons, medulla, and cerebellum), whether they are sensory or motor, autonomic or somatic, are called cranial nerves. The brainstem and cranial nerves coordinate and control unconscious sensory, proprioceptive, and motor functions. Disorders of these structures are characterized by one to all of a set of distinctive abnormal neurologic signs. Twelve pairs of cranial nerves innervate the head and extend into the body, and each nerve may carry motor, sensory, or both types of nerve fibers, and may mediate somatic, autonomic, or both types of functions (Table 83-1). Knowledge of the location and action of individual cranial nerves is critical for interpretation of the neurologic examination (see the sixth edition of Current Therapy in Equine Medicine, Chapter 130). Cranial nerves and their central nervous system (CNS) components are numbered sequentially from rostral to caudal on the basis of site of attachment to the brain: cranial nerve I (CN I; olfactory) and CN II (optic) attach to the forebrain; CNs III (oculomotor) and IV (trochlear) are associated with the midbrain (rostral brainstem); CNs V (trigeminal), VI (abducens), VII (facial), VIII (ves­ tibulocochlear), IX (glossopharyngeal), X (vagus), XI (spinal accessory), and XII (hypoglossal) are associated with the mid and caudal portions of the brainstem. All but the optic and olfactory nerves have a peripheral portion that is ensheathed or myelinated by Schwann cells. Cranial nerves I and II are not peripheral “nerves” at all, but are actually extensions of the CNS; early anatomists assumed that these two structures were peripheral nerves, and the nomenclature has persisted. Cranial nerve nuclei can have two names, depending on whether their function is somatic or autonomic (parasympathetic). For example, the oculomotor nucleus of CN III supplies some of the extraocular muscles, whereas the parasympathetic nucleus of CN III innervates smooth muscle of the eye and orbit. Some nuclei contain neurons of multiple cranial nerves, yet all those neurons have a similar function. For example, the nucleus ambiguus, comprising neurons associated with CN IX, X, and XI, innervates the striated muscle of the larynx and pharynx. An understanding of the relative position of the peripheral portion of the cranial nerves (Figure 83-1), as well as the location of their nuclei (Figure 83-2), is important in establishing whether a particular combination of cranial nerve signs could be caused by a single lesion or has to involve a multifocal disease process. A lesion affecting a particular cranial nerve could be affecting the peripheral nerve or its soma in the brainstem, and a thorough neurologic examination and ancillary tests may be required to establish the exact location—brainstem lesions can be expected to additionally affect other cranial nerves as well as upper motor neuron and proprioceptive tracts and, if the ascending reticular activating system is additionally affected, abnormalities in levels of

arousal. Neurons of CNs III to XII are arranged in nuclei in the brainstem.

DISORDERS COMMONLY AFFECTING THE BRAINSTEM AND CRANIAL NERVES Guttural Pouch Infection

The guttural pouch is principally found in members of order Perissodactyla (“odd toed” nonruminant ungulates: horses, tapirs, rhinoceros). The medial compartment contains CNs IX, X, XI, and XII as well as the internal carotid artery, a portion of the sympathetic trunk, and the cranial cervical ganglion. The dorsal part of the lateral compartment lies close to cranial nerve VII, and the external carotid artery and maxillary vein are also in close proximity. Primary guttural pouch disease commonly involves empyema (often caused by Streptococcus equi subsp equi infection) or mycosis (frequently Aspergillus fumigatus [see Chapter 57]). The infection affects the guttural pouch mucosa and the nervous and vascular structures within it. The mucosa at this site is subject to mycotic infection that causes signs of cranial nerve dysfunction, usually unilaterally; clinical signs most often consist of unilateral nasal discharge, dysphagia, and epistaxis.

Otitis Media-Interna Infections of the middle and inner ear are not commonly diagnosed in horses, but it may be that advanced imaging would disclose further cases (Figure 83-3). The neurologic significance of lesions in the petrous temporal bone is that CN VII passes along the edge of the middle ear (which is contained in the petrous temporal bone), separated from it by only a thin layer of mucosa. CN VIII is the only cranial nerve that does not leave the skull, and it provides the peripheral sensory receptors for balance and audition. Infections can extend from one ear compartment to another, and patients will show varying degrees of CN VII or CN VIII dysfunction. Unlike small animals and humans, postganglionic sympathetic fibers from the cranial cervical ganglion do not appear to pass through the middle ear in horses, and Horner’s syndrome is not a feature of otitis media (see Chapter 86). Myringotomy and middle ear flushing are difficult in equids because of the anatomy of the horizontal ear canal, but treatment with penicillin or trimethoprim sulfa is a reasonable intervention.

West Nile Virus Encephalitis caused by West Nile virus (and perhaps by Murray Valley virus, another member of the Japanese B antigenic group) apparently does not have the cortical involvement characteristic of other forms of encephalomyelitis (see Chapter 35). By contrast, symmetrical or asymmetrical signs of brainstem and particularly caudal spinal cord involvement—including muzzle fasciculations (nuclei

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TABLE 83-1 Clinical Signs and Cranial Nerve Testing

Function

Innervation

Clinical Testing

Dysfunction

Vision

II, IIa, VIIe

Pupil size

IIa, IIIe, parasympathetic, sympathetic

Menace response Pupillary light reflex—IIa and IIIe (parasympathetic) Pupillary light reflex Pharmacologic testing

Eyeball position

VIIIa IIIe, IVe, VIe Va—all three branches

Blindness, dilated pupil (although this can also be related to CN III dysfunction) Anisocoria, mydriasis (↓ CN II or parasympathetic innervation) Miosis (↓ sympathetic innervation) (cerebellar lesions and primary ophthalmic lesions can also affect pupil size) Strabismus—static (LMN), dynamic (vestibular) Facial hypoalgesia

Facial sensation

Eyeball position in different head positions Vestibulo-ocular reflex VIIIa and IIIe, IVe, VIe Tactile stimulation Va—different regions of the face: nasal septum, ventral eyelid, dorsal eyelid Palpebral reflex—Va and VIIe (dorsal and ventral eyelids) Auriculopalpebral reflex Va and VIIe (stimulate just in front of the external ear canal; sensation to the inside of the pinna is principally provided by CN VII) Jaw tone Assess the bulk of the masticatory (temporalis and masseter muscles) Facial symmetry Palpebral reflex Va and VIIe Movement and position of muzzle, external nares, eyelids, ears Head position Eyeball position (also involves III, IV, VI) Vestibulo-ocular reflex (VIIIa and IIIe, IVe, VIe) Gait and movement Swallowing

Mastication

Ve—mandibular

Facial expression and movement

VIIe

Vestibular function

VIIIa

Pharyngeal function Laryngeal function

IX and X, a and e X and XI, a and e

Phonation Respiration

Tongue

XIIe

Observation—LMN signs, usage Withdrawal from tactile stimulus

Muscle atrophy Dropped jaw, if bilateral dysfunction Facial paresis/paralysis

Head tilt, circling, rolling Spontaneous nystagmus Strabismus Deranged body posture and ataxia Dysphagia Salivation (ptyalism) Dysphonia Respiratory stridor—laryngeal obstruction, aspiration Atrophy, paresis/paralysis— unilateral or bilateral

a, Afferent; e, efferent, LMN, lower motor neuron.

of CN VII); paresis of the lip, muzzle (CN VII), and tongue (CN XII); depressed mentation; and limb ataxia or paresis— are typical.

Recent evidence indicates that most equine herpesvirus type 1 (EHV-1) myeloencephalitis cases are caused by a strain of the virus with a single nucleotide polymorphism that results in a higher degree of viremia and the ability of the virus to preferentially infect CD4 lymphocytes, allowing transfer to endothelia while remaining relatively uninhibited by virus neutralizing antibodies (see Chapter 90). As the name implies, myelitis is more common than encephalitis; nevertheless, some horses do develop signs of brain lesions, including stupor and diffuse face, jaw, tongue, and pharyngeal paresis, and rarely, vestibular signs.

blamed on the fact that the horse is an aberrant intermediate host for this protozoan. A single case report, however, intriguingly demonstrated schizonts in the brain and spinal cord and mature sarcocysts in the tongue and skeletal muscle of a horse, which suggests that horses do have the potential to act as true intermediate hosts. Either way, the ability of the organism to target very specific neurons or tracts is remarkable. Less than 5% of horses with equine protozoal myeloencephalitis have obvious clinical evidence of brain disease, but in those cases, signs of asymmetric brainstem involvement predominate and typically involve various degrees of vestibular disease, facial nerve paralysis, and atrophy of the muscles of mastication and the tongue. Dysphagia and respiratory stridor may also predominate. See Chapter 85 for a detailed discussion of diagnostic modalities and treatment strategies.

Equine Protozoal Myeloencephalitis

Botulism and Tetanus

The predilection of Sarcocystis neurona for infecting the nervous system of horses remains unexplained but has been

The clostridial neurotoxins responsible for tetanus and botulism are proteins capable of neurospecific binding,

Equine Herpesviral Myeloencephalopathy



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membrane translocation, and proteolysis in specific components of the neuroexocytosis apparatus. Tetanus neurotoxin binds to the presynaptic membrane of the neuromuscular junction, becomes internalized, and is transported retroaxonally to the spinal cord. The spastic paralysis induced by the toxin is caused by blockade of neurotransmitter release from spinal inhibitory interneurons. In contrast, the botulinum neurotoxins induce a flaccid paralysis by inhibiting acetylcholine release at the neuromuscular junction. Paralysis or spasm of the muscles innervated by cranial nerves that are involved in swallowing, breathing, facial expression, and mastication develops and can be life threatening.

Olfactory bulb

I

Olfactory peduncle II

Optic chiasm

III

Optic tract

IV V VI VII VIII IX X XI XII

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Polyneuritis Equi Polyneuritis equi is a relentlessly progressive immunemediated attack against nerve roots that most commonly affects the caudal equina, but asymmetrical cranial nerve involvement may be evident. Facial paralysis and vestibular signs may be the most common manifestation of cranial nerve involvement and may precede cauda equina signs (see the fifth edition of Current Therapy in Equine Medicine, Chapter 14.6).

Temporohyoid Osteoarthropathy Temporohyoid osteoarthropathy is a neurologic disorder of adult horses characterized by acute onset of cranial nerve dysfunction (most often unilateral) secondary to bony proliferation of the temporohyoid joint and proximal stylohyoid bone that ultimately leads to fusion of the temporohyoid joint. Fusion of the joint predisposes horses to fracture along the base of the skull or the shaft of the stylohyoid bone, and this may occur secondary to normal tongue and laryngeal movement if the joint has fused. Associated fracture of the petrous temporal bone damages the inner and middle ear and can lead to damage of CN VII, CN VIII, or both, with resulting facial nerve paresis and peripheral vestibular signs. The etiology of the osteoarthritis may in some cases be from extension of otitis media or interna, but recent evidence suggests it is more likely to be caused by age- or trauma-related degeneration. The prevalence of the disease in horses with vestibular signs is currently unclear. Diagnosis rests on detecting enlargement of the proximal aspect of the stylohyoid bone by use of endoscopy (Figure 83-4) or advanced imaging techniques. Surgery involving the removal of the ceratohyoid bone may be useful, but the prognosis for return to full athletic function is fair to guarded in horses with vestibular signs.

Lead Poisoning Figure 83-1  Ventral aspect of the brain depicting the site of origin of the cranial nerves. (From Thomson CE, Hahn C: Veterinary Neuroanatomy: A Clinical Approach, Saunders, Ltd., 2012.)

Lead poisoning in livestock has historically been caused by contact with lead-based paint, linoleum, caulking compounds, batteries, old machinery oil, and lead-acid accumulator batteries. Horses are unique in rarely, if ever, showing

Cervical spinal cord

Thoracic spinal cord

Cochlear nucleus (VIII) Vestibular nuclei (VIII) Trigeminal sensory nuclear complex (V, VII, IX, X) Nucleus of the solitary tract VII, IX, X Sensory Sulcus limitans Autonomic Motor Parasympathetic nucleus of III III IV

VII

Parasympathetic nucleus of X

VI V

Nucleus ambiguus (IX, X, XI) XII Salivatory nuclei (VII, IX)

Figure 83-2  The relative position of autonomic and somatic motor nuclei (and columns) in the brain. (From Thomson CE, Hahn C: Veterinary Neuroanatomy: A Clinical Approach, Saunders, Ltd., 2012.)

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Otitis media

Figure 83-3  T2-weighted magnetic resonance image of a 6-month-old Thoroughbred with unilateral facial nerve paralysis and ipsilateral otitis media.

Figure 83-4  Swelling of the stylohyoid bone at the temporohyoid joint in the guttural pouch (arrows). (From Auer JA, Stick JA. Equine Surgery. 4th ed. St Louis: Elsevier, 2012.)

any cerebral signs other than somnolence associated with weight loss when affected by lead poisoning, but they do develop very selective signs of cranial neuropathy. This particularly involves laryngeal and pharyngeal paralysis, resulting in roaring and dysphagia, and is most probably the result of peripheral axonopathy. Other motor nerves can be involved, resulting in pharyngeal, esophageal, facial, and anal paralysis. Horses with bilateral laryngeal paralysis can become frantic in attempts to breathe and may become uncontrollable—usually as a terminal event unless a tracheotomy is performed. No gross neuropathologic findings are found except laryngeal muscle atrophy in chronically affected horses.

Diagnosis may not be straightforward. Horses usually have a normal hemogram, although nucleated erythrocytes are occasionally detected. Blood lead concentrations may or may not be high, but a concentration greater than 0.6 ppm (0.6 mg/L) is probably diagnostic of lead poisoning; however, monitoring of urinary lead excretion following disodium Ca-ethylenediaminetetraacetic acid (EDTA) chelation treatment is more helpful. Estimation of very high total and relative lead intake from analysis of forage and feedstuff provides strong evidence for toxicosis. Analysis of lead concentration in various tissues obtained at necropsy may be useful in evaluating excessive accumulation and may reflect the level or duration of exposure and severity of poisoning. Concentrations of lead in the blood at 0.35 ppm, liver at 10 ppm, or kidney cortex at 10 ppm are consistent with a diagnosis of lead poisoning. Removal from access to lead may be all that is required to halt an outbreak, and slow reversal of mild signs can occur. Lead chelation also may be achieved with meso-2,3dimercaptosuccinic acid administered orally at 25 mg/kg, every 24 hours for 4 days, and may be more effective than use of EDTA. The laryngeal paralysis seen in horses carries a poor prognosis.

Hypoxic-Ischemic Encephalomyelopathy Hypoxic-ischemic brain injury results from a reduction in cerebral blood flow and oxygenation during the antepartum, peripartum, or postnatal period. Hypoxia can develop during labor because of compression of the umbilical cord, insufficient uteroplacental circulation, cord prolapse, uterine rupture, shoulder dystocia, or vaginal breech delivery. Reduction in cerebral blood flow and oxygen delivery initiates a cascade of deleterious biochemical events, causing a switch to energy-inefficient anaerobic metabolism and leading to depletion of high-energy phosphate reserves, lactate accumulation, and an inability to maintain cellular homeostasis. This results in failure of critical transcellular ion pumps, which causes cytotoxic edema and calcium accumulation. The increase in calcium stimulates the release of, and also inhibits the reuptake of, excitatory amino acids such as glutamate. In the immature brain, glutamate is an important trophic factor that mediates normal brain development and plasticity and contributes to increased vulnerability to excitotoxic cell death in the immature brain. The term neonatal encephalopathy has been used to encompass all neonatal foals with neurologic abnormalities, and hypoxic-ischemic encephalomyelopathy is a specific type of neonatal encephalopathy. The predominant cortical signs of hypoxic-ischemic encephalomyelopathy are described in Chapter 177. In some foals, severe depression reflects brainstem damage, and asymmetric signs of ischemic damage to specific brainstem nuclei may be seen, including head tilt, circling, and pharyngeal paresis. These signs generally improve slowly and incompletely.

Recurrent Laryngeal Neuropathy Potentially the most common cranial nerve abnormality, and certainly the most important obstructive upper airway disorder of horses, is recurrent laryngeal neuropathy (see Chapter 52). The disease causes airway obstruction and reduced exercise performance in 2.6% to 8.3% of horses, is unilateral and left sided, and affects taller horses. The etiology of this distal axonopathy remains unknown, but recent clinical studies have unequivocally revealed that recurrent laryngeal neuropathy is a progressive disorder in many horses. In addition, it is now understood that this disease only affects the



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recurrent laryngeal nerves and can be classified as an inherited multiple mononeuropathy distinct from other human or canine neuropathies.

Suggested Readings Borges AS, Watanabe MJ. Guttural pouch diseases causing neurologic dysfunction in the horse. Vet Clin North Am Equine Pract 2011;27:545-572. Dickey EJ, Long SN, Hunt RW. Hypoxic ischemic encephalopathy: what can we learn from humans? J Vet Intern Med 2011;25:1231-1240.

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Hilton H, Puchalski SM, Aleman M. The computed tomographic appearance of equine temporohyoid osteoarthropathy. Vet Radiol Ultrasound 2009;50: 151-156. Mayhew IG. Large Animal Neurology. 2nd ed. Ames, IA; Blackwell, 2008. Walter J, Seeh C, Fey K, Bleul U, Osterrieder N. Clinical observations and management of a severe equine herpesvirus type 1 outbreak with abortion and encephalomyelitis. Acta Vet Scand 2013;55:19.