Forebrain Diseases of the Horse: Relevant Examination Techniques and Illustrative Video Segments

IN-DEPTH: NEUROLOGY

Robert J. MacKay, BVSc (Dist), PhD, Diplomate ACVIM

1. Introduction cortex for the awake state.2–4 This component of The forebrain comprises the diencephalon (thala- the formation, known as the ascending reticular ac- mus and hypothalamus) and the cerebral hemi- tivating system, is an ill-deﬁned meshwork of cells spheres. Both intrinsic and learned behaviors are concentrated in the midbrain and rostral brainstem forebrain-dependent, as are central perception of vi- that receives afferent input from all parts of the sion and touch. Forebrain injury thus may cause CNS and projects excitatory stimuli cortically.2 demented behavior, central blindness, and reduced Focal to extensive lesions in the midbrain, or, to a response to touch. Seizures usually arise in the lesser degree, anywhere else in the brainstem may forebrain. Careful evaluation of mentation, men- reduce the level of consciousness, whereas cerebral ace responses, and vision and reaction to touching injury must be diffuse to cause noticeable obtunda- the nasal septum, in conjunction with other parts of tion. The ascending reticular activating system the neurologic examination, should provide accurate also is involved in the initiation and maintenance of localization of forebrain lesions. Recognition of sleep. Abnormalities of production or action of hy- signs of forebrain dysfunction is an important step pothalamic arousal peptides (hypocretins/orexins)5 in the processes of diagnosis and treatment. or imbalances of brainstem neurotransmitters may result in narcolepsy/cataplexy sleep disorders. 2. Anatomy and Nomenclature The forebrain or prosencephalon includes the telen- Behavior (Limbic System, Temporal Lobes) cephalon (cerebrum) and diencephalon (thalamus 1 Normal behavior requires integration of signals and hypothalamus). from the entire CNS but principally involves the 3. Functions (Location) forebrain. Most important in controlling intrinsic behavior is the limbic system— a connected series of Level of Consciousness (Cerebrum, Brainstem, Especially structures in the cerebrum and diencephalon. A Front Half) minor component is also found in the midbrain. One of the critical functions of the reticular forma- Included are the amygdala, hippocampus, fornix, tion of the brainstem is activation of the cerebral cingulate gyrus, and septal area. A closely associ-

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348 2011 ր Vol. 57 ր AAEP PROCEEDINGS IN-DEPTH: NEUROLOGY ated region, which is important in primate behavior, Perception of Pain/Touch (Parietal Cortex, Cranial Nerve V) is the temporal lobe of the cerebrum. It is thought Pain/touch sensation is transmitted from the body to that behavior based on conditioning and experience the brain in multisynaptic spinothalamic tracts. (i.e., learning) is controlled by the temporal lobes. Signals initiated by stimulation of pain receptors on Structural, metabolic, or psychological disturbances one side of the body pass through spinothalamic affecting these areas may result in behavioral ab- tracts on both sides of the spinal cord. Axons in normalities (i.e., dementia). Dementia can be de- these tracts course rostrally to terminate in the thal- fined as changes in normal habits, personality, amus. From there, cell bodies project axons to the attitude, reaction to the environment, or loss of sensory (somesthetic) cortex for conscious percep- learned skills. Some of the signs that may be seen tion of pain or other sensory modalities. It is include disorientation in a familiar environment, thought that the somesthetic cortex is located prin- failure to recognize a handler or object, loss of the cipally in the parietal lobe of the cerebrum. The ability to be led, frequent yawning, head-pressing, pathways for pain perception in the head pass irritability, unprovoked kicking or biting, compul- through the maxillary, ophthalmic, and mandibular branches of the trigeminal nerve. The central com- sive walking or circling, and dramatic changes in ponent of this pathway is predominantly contralat- eating or drinking habits. eral. Unilateral lesions of the sensory parts of the Almost any disturbance of the forebrain poten- forebrain (thalamus, internal capsule, sensory cor- tially can cause dementia. Encephalitis, head tex) thus cause contralateral facial hypalgesia. trauma, space-occupying lesion, malformation, in- Because the central components of vision and facial farct, and metabolic disorders all are likely to cause pain/touch perception are close anatomically, it is changes in behavior. It is likely that structural or common to find unilateral facial hypalgesia and metabolic forebrain disease is the cause of dementia blindness (on the same side) in the same horse. if other neurologic abnormalities are found by neurologic examination or imaging studies. In the ab- Smell (Olfactory Bulbs, Cranial Nerve I) sence of such supportive findings, abnormal Olfactory nerves pass through the cribriform plate behavior such as self-mutilation6 - may have a psy and into the olfactory bulbs of the cerebrum. The chological basis. sense of smell is relayed through the thalamus to centers in the unconscious (limbic system) and con- Seizures scious cerebrum. Seizures are sudden, transient attacks of abnormal motor and/or behavioral activity attributable to par- Vision (Thalamus, Occipital Cortex, Cranial Nerve II) oxysmal depolarization of part to all of the brain. In horses, 80% to 90% of optic nerve fibers from one Depolarization occurs either simultaneously eye cross at the optic chiasm and 80% of fibers in the throughout the brain or originates from a hyperirri- optic tracts synapse at the lateral geniculate nucleus table focus in the forebrain. Seizures originating in the thalamus. The remainder course to the mid- from a focus probably will initially have asymmetric brain to function in the pupillary light reflex. Neu- clinical signs, and there may be additional signs of rons in the lateral geniculate nucleus project via the forebrain disease between seizures that are revealed internal capsule to the visual cortex in the occipital by neurologic examination. Seizures frequently lobe of the cerebrum. This area is caudal in the originate in the frontal (motor) cortex and involve cerebrum, immediately rostral to the tentorium cer- muscle fasciculations and tremors around the head ebelli and caudal to the parietal cortex. The path- or abnormal movements of the jaws and tongue way from the eye to the contralateral visual cortex (“chewing gum fits”). Convulsions characteristic of via the optic nerve, optic tract, lateral geniculate neonatal encephalopathy often are of this type. nucleus, and internal capsule must be intact for In their most severe (generalized) form, seizures normal vision. Lesions in the pathway caudal to manifest as sudden recumbency, with a brief phase the optic chiasm result in blindness predominantly of extensor tonus, followed by clonic (“galloping”) in the opposite eye and lesions rostral to the chiasm affect vision in the ipsilateral eye. Damage to the movements of the legs, loss of consciousness, and a cortex should not affect the pupillary reflex path- variety of signs of autonomic discharge (e.g., sweat- way. Visual perception is evaluated by obstacle ing, urination, defecation, pupillary dilation). Mild tests (with and without blindfolding of one eye) and motor seizures are often accompanied by behavioral by the menace response. The menace response re- signs such as obtundation, compulsive walking, hy- quires the central visual pathway just described perresponsiveness to stimuli, or other signs of de- plus normal facial nerve function. Integrity of the mentia. Seizure foci in the forebrain may occur at cerebellar cortex is also needed, although it is not sites of previous or current trauma or inflammation. known if the pathway that mediates this response Syndromes of more than multiple seizure episodes actually passes through the cerebellum. It is im- without interictal evidence of brain disease often are portant to note that the menace response does not described as epilepsy. develop in foals until they are 1 to 2 weeks old.

AAEP PROCEEDINGS ր Vol. 57 ր 2011 349 IN-DEPTH: NEUROLOGY Upper Motor Neuron System: Voluntary Movement maintaining normal alertness. Botulism is a dis- (Cerebrum, Brainstem) ease of this type. A stuporous horse stands in one The upper motor neuron (UMN) system is responsi- place with the head held low and responds only to ble for the initiation of voluntary movement and strong stimuli. Stuporous horses that are recum- regulation of posture through support against grav- bent are defined as semi-comatose, whereas recum- ity. The latter is effected in part by modulation of bent horses that do not respond to any stimulus are the anti-gravity myotactic reflexes of the limbs. comatose. Some horses with reduced alertness ap- The component of the UMN system originating in pear irritable and anxious, walk compulsively, or the hypothalamus is responsible for the control of otherwise interact abnormally with handlers. An muscular activity associated with visceral functions obtunded horse showing such behavior may be (respiratory, cardiovascular, urinary). Direct corti- termed delirious. It is very unlikely that a horse cal influence over motor activity in the horse via the with narcolepsy will have a sleep attack while being pyramidal system is largely limited to fine control of examined; thus, assessment of possible narcolepsy the muzzle and lips. The much more important usually rests on description by the owner or video extrapyramidal system is a multisynaptic pathway recordings of an attack. Occasionally, neonatal from the brain to the lower motor neurons of the foals will collapse during examination and briefly spinal cord and brainstem. The frontal and pari- appear comatose. These typically are benign epi- etal lobes of the cerebrum, basal nuclei, diencepha- sodes of cataplexy and probably are an exaggerated lon, midbrain, and hindbrain all contribute to the version of the collapse response by which a normal UMN system. UMN, particularly those originating foal can be cast into recumbency. in the midbrain, generally are inhibitory to myotac- Obtundation reflects damage in the brainstem, tic reflexes. Damage to the neurons or axons of especially in the midbrain and rostrally or diffusely these tracts in the caudal midbrain, hindbrain, or in the cerebrum. Dementia is a sign of forebrain spinal cord increases extensor tonus and may result dysfunction. Limb ataxia/weakness and signs of in limb spasticity (“stiffness”). With UMN injury, cranial nerve dysfunction are common in horses there also is limb weakness, hyperactive extensor with obtundation secondary to brainstem disease. reflexes, and crossed extensor reflexes, all in the ipsilateral limbs. Movement disorders are charac- Behavior teristic of UMN disease in the rostral brainstem. Abnormalities of behavior can be termed dementia. Abnormal involuntary movements include dystonia Behavior is assessed from history and general ob- (writhing movements of the muscles of the head and servation in the course of the examination. Typical spine), ballism (violent flailing of a limb), chorea abnormal behaviors resulting from CNS disease in- (repetitive jerky movements of different muscle clude self-mutilation, head-pressing, compulsive groups), and myoclonus (repetitive movements of a walking (often in a circle), yawning, aggression (in- single muscle group). Nigropallidal encephaloma- cluding unprovoked biting or kicking), timidity, loss lacia is a disease of this type in horses that is caused of affinity of a foal for its dam, and loss of learned by the chronic consumption of yellowstar thistle or behaviors and skills. Inability or refusal of a Russian knapweed plants.7 There is dystonia and trained horse to follow when being led is a form of rigidity of the muscles of the head resulting in lip dementia that may be obvious during neurologic retraction, tongue protrusion, and inability to pre- examination. Compulsive turning of the head and hend food. More generalized extrapyramidal syn- neck in one direction, blindness, and seizures are dromes in horses reportedly are associated with other signs of forebrain dysfunction that may be reactions to fluphenazine (an antipsychotic sedative seen in demented horses. drug) and metaclopramide (a prokinetic agent). Orientation and Coordination of the Head 4. Clinical Examination of Forebrain Function Evaluate the orientation of the head from directly in Note that all parts of the CNS contributing to a front. Any head “tilt” is described from the pa- particular neurologic function are covered in this tient’s perspective; thus, if the poll is rotated to the section. For example, both vestibular and fore- horse’s left (i.e., clockwise from the examiner’s point brain influences on head position are discussed.2,3,8 of view), the abnormality is described as a left head tilt. Repeatedly straighten and release the horse’s Alertness neck and head and observe whether or not the head Assess level of consciousness or alertness on a con- returns to one side. Asymmetric disease of the ves- tinuous scale from normal (i.e., bright and alert) to tibular system causes the head to tilt and turn, comatose. Progressive levels of obtundation are whereas asymmetric cerebral disease may cause the termed lethargy, stupor, semi-coma, and coma. head and neck to turn without tilting. Carefully With lethargy, there is a somewhat blank facial ex- blindfold the horse and observe the effect on head pression with slight drooping of the ears and eyelids, position. Blindfolding removes visual input to sluggish responsiveness to stimuli, and reduced vol- head position and exacerbates abnormalities caused untary activity. It should be noted that some con- by either vestibular or cerebral disease. Observe ditions cause horses to lose facial expression while the head and neck from the side. Persistent hori-

350 2011 ր Vol. 57 ր AAEP PROCEEDINGS IN-DEPTH: NEUROLOGY zontal or low position of the head may indicate neu- tundation, and abnormal behaviors may also be rologic or muscular weakness of the neck, whereas seen. Peripheral lesions of the trigeminal nerve extended head position may be found in horses with may involve motor fibers and result in weakness and upper cervical vertebral problems or guttural pouch atrophy of masticatory muscles. disease. Offer feed or a treat to the horse and observe the way in which the horse moves its head in Menace Response response. Horses with cerebellar disease often make jerky or bobbing movements of the head as Test menace responses while standing in front of the they move toward the offered feed. horse. To do this, use the palm of the hand to make Head tilt suggests involvement of the vestibular a threatening gesture toward the eye. Test from labyrinth, nerve, or root peripherally, or the vestib- both temporal and nasal directions on each side. ular nuclei and connections in the medulla oblon- Stimulate the horse just before each menace gesture gata or cerebellum centrally. The first 2 cervical by tapping the skin below the eye. For safety rea- nerves have connections to the vestibular nuclei, sons, always hold the noseband of the halter with and injury to the sensory components of these one hand while the other is used for testing. A nerves (or dorsal roots, spinal ganglia, or central normal menace response is blinking of the eye, connections) may cause signs suggestive of vestibu- sometimes accompanied by evasive movement of the lar disease. If the head is turned without tilting, head and neck. Compare carefully the intensity of involvement of the cerebrum is likely. Coarse or the menace responses elicited from each side. In fine head bobbing, especially intentional, indicates this regard, menace should be considered a quanti- diffuse cerebellar dysfunction. tative response. Unlike simple reflexes, which are Because of the close association of cranial nerves assessed as present or absent, a menace response VII and VIII, facial paralysis is often seen in horses can be considered abnormal if it is less vigorous than with vestibular disease. With peripheral vestibu- that elicited from the opposite (normal) side. The lar disease, there often is spontaneous horizontal or menace response can be interrupted anywhere in its arc-shaped nystagmus with the fast phase directed pathway from the eye via the optic nerve to the away from the side of the lesion. In horses with contralateral optic tract, diencephalon, internal cap- involvement of the central components of the vestib- sule, and visual cortex. From the visual cortex, the ular system, there may be horizontal or vertical menace response pathway continues through the nystagmus. Damage to adjacent structures in the ipsilateral motor cortex to the facial nucleus and hindbrain may additionally cause obtundation, nerve on the side being tested and receives essential other signs of cranial nerve dysfunction such as dys- phagia and masseter atrophy, and weakness/ataxia input from the cerebellum. If there is no other sign of the limbs on the side of the lesion. Horses with of cerebellar involvement, and facial nerve function cerebellar cortical disease may lack menace re- and pupillary light reflexes are intact, the lesion is sponses despite having normal vision. contralateral, central to the optic chiasm, and probably in the forebrain. In normal neonates and in Facial Sensation older horses with diffuse cerebellar cortical disease, While standing in front of the horse, place the palm there is no menace response but the horse can see. of the right hand on the muzzle, work the thumb In these settings, vigorous threatening gestures to- into the right nostril and touch the nasal septum on ward the eye may cause evasive movements of the that side. In mirror-image fashion, use the left head without blinking of the eye. There may be thumb to stimulate the left side of the septum. other signs of asymmetric cerebral disease such as The normal response to this noxious stimulus is compulsive walking in circles, dementia, head and vigorous movement of the head away from the side neck turn, obtundation, seizures, and facial hypal- of the stimulus. Compare the intensity of re- gesia on the side opposite the lesion (i.e., the same sponses on each side. If there is obvious asymme- side as the defective menace). If the site of the try of response, test cutaneous sensation at multiple lesion causing a menace deficit is the optic nerve or locations over the face by pinching the skin with fundus of the eye, the pupillary light reflex on the hemostats. The pathway for perception of this same side should also be abnormal. Head-bobbing, stimulus is input through the sensory division of the dysmetria, and ataxia are expected in horses with trigeminal nerve to the pons and thence to the som- defective menace responses resulting from cerebel- esthetic area of the contralateral cortex. If flick lar dysfunction. If eyelid paralysis is preventing reflexes are normal, a reduced or absent response to the menace response, the palpebral (eyelid flick) re- a noxious stimulus suggests involvement of the con- flex should also be abnormal and there may be ad- tralateral forebrain, probably at the level of the pa- ditional signs of facial paralysis. rietal cortex. In contrast, hypalgesia and hyporeflexia of flick reflexes of part to all of one side of the head indicates involvement of the trigeminal References nerve or branches. With hemifacial hypalgesia 1. Sisson S, Grossman JD. The anatomy of the domestic ani- caused by forebrain disease, cortical blindness, ob- mals. 3rd ed. Philadelphia: Saunders, 1941;784–856.

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