Neurologic syndromes: localizing a lesion (Proceedings)

When a veterinarian is presented with a patient with symptoms of difficulty walking, altered mentation, weakness, collapse or other movement disorders several potential causes must be considered. Disease processes involving the nervous, cardiovascular, endocrine and orthopedic systems may all produce symptoms very similar to one another. In addition, generalized systemic illness of other causes may debilitate patients severely enough that they can not or choose not to walk. Furthermore, in some patients such as geriatric animals the cause of immobility or altered mentation may be caused by disorders of more than one body system. Therefore, the most basic question that must be answered is whether a patient's symptoms are caused by neurologic disease or problems involving other body systems. Signalment, history and physical examination are the initial tools utilized to answer this question. Once neurologic symptoms have been identified it is necessary to localize the patient's symptoms within the nervous system. Once a neurologic lesion is localized a list of differential diagnoses can be formulated and a diagnostic and therapeutic plan developed.

The nervous system is made of component parts that work and interact with one another in a predictable manor. Because of this, abnormalities within any single area of the nervous system can be expected to produce a similar set of symptoms. These groups of symptoms and physical examination findings produce the neurologic syndromes that can be used to localize a patient's symptoms within the nervous system.

The most basic components of the nervous system are the central nervous system, which includes the brain and spinal cord and the peripheral nervous system made up of peripheral nerves, muscle (skeletal, smooth and cardiac), glands and the myoneural junction. The peripheral nervous system controlling motor movement to the body is also sometimes referred to as the neuromuscular system. In clinical veterinary neurology the central nervous system can be further divided into the forebrain, brainstem, and cerebellum within the skull as well as the cervical spinal cord (spinal cord segments C1-C5), the cervical enlargement (segments C6-T2), thoracolumbar spinal cord (segments T3-L3), and the lumbar enlargement and cauda equina (L4-Cd5). When all of a patient's symptoms can not be localized to one area of the nervous system a multifocal syndrome is present.

In order to utilize the syndrome approach to localizing lesions within the nervous system a basic understanding of neurophysiology is necessary. Lower motor neurons (LMN) originate in grey matter of all spinal cord segments and the nuclei of cranial nerves III-VII and IX-XII. The axons of the LMN form the peripheral and cranial nerves and connect the central nervous system to a muscle, gland or organ. The LMNs that innervate the thoracic limbs originate from the cervical enlargement (segments C6-T2) while the LMNs that innervate the pelvic limbs originate from the lumbar enlargement (segments L4-Cd5). Symptoms of LMN disease include reduced or absent reflexes, decreased muscle tone and early and rapid onset of muscle atrophy. Upper motor neurons (UMN) originate in the grey matter of the cerebrum, basal nuclei and brainstem. Axons of the UMN travel through the white matter tracts of the forebrain, brainstem and spinal cord. The UMNs inhibit the LMN and are responsible for initiating motor movement and maintaining tone to the extensor muscles of the limbs. Upper motor neuron symptoms include normal or exaggerated reflexes, increased muscle tone and late onset, milder muscle atrophy (disuse atrophy).

Forebrain (cerebral) syndrome

Patients with forebrain disease often have altered mentation or behavior changes but a normal or near normal gait. Loss of house training, failure to recognize the pet owner, personality changes and confusion within a known environment may be part of the history. Forebrain lesions that are unilateral or asymmetric may cause the pet to walk in circles or turn predominantly in one direction. The circles are usually wide and toward the side of the lesion. Often pets will head press into a corner or get stuck in closets or between furniture at home. Vision may be affected with cerebral disorders and animals may bump into objects when walking, such as door frames and legs to tables or chairs in an examination room. Altered vision from a forebrain disorder along with normal pupillary light and palpebral reflexes is cortical blindness. Despite a normal or near normal gait, postural reactions such as proprioceptive placing and hopping are often markedly altered in limbs contralateral to the lesion. Generalized or focal seizures may also occur in patients with cerebral disease. As symptoms of forebrain disease progress, often from increased intracranial pressure, patients may become stuporous, comatose and papilledema and altered respiration may develop. The diencephalon (thalamus, hypothalamus) is the caudal portion of the forebrain and in addition to the previously mentioned symptoms patients with disorders of the diencephalon may have altered temperature regulation, optic nerve (CN II) deficits and endocrinopathies such as hyperadrenocorticism, diabetes insipidus and hypothyroidism. Pituitary macroademomas are the primary cause of diencephalic symptoms.

Brainstem syndrome

The brainstem is divided into the midbrain (rostral), pons (middle) and medulla (caudal) and contains the ascending reticular activating system which maintains consciousness by relaying sensory inputs from the body to the cerebral cortex. Thus, altered levels of arousal resulting in extreme dullness, stupor and coma may results from brainstem lesions. Motor inputs originating in the forebrain cross in the brainstem on the way to the lower motor neurons in the spinal cord. Unlike forebrain disorders, gait deficits are more apparent with brainstem disease and postural reaction deficits occur in limbs ipsilateral to the side of the lesion. Unilateral brainstem disease may produce ipsilateral hemiparesis whereas bilateral brainstem disease results in tetraparesis. The nuclei of cranial nerves III-XII are located in the brainstem with abnormalities resulting in an array of cranial nerve deficits.

Cerebellar syndrome

The cerebellum regulates (usually through inhibition) the rate and range of motor movements but is not responsible for initiating movement or limb strength. Patients with pure cerebellar symptoms have spastic, exaggerated, dysmetric movements of the limbs such as hypermetria (goose stepping) of the thoracic limbs. The range of limb movements may be exaggerated when testing postural reactions but the postural reactions should be intact. When standing patients with cerebellar symptoms often have a wide based stance and may sway slightly from side to side. Intention tremors of the head may be present and are most noticeable when patients are sniffing, eating or drinking. Symptoms of central vestibular disease may be present if the flocculonodular and fastigial nuclei of the cerebellum are damaged. An ipsilateral menace deficit and contralateral mydriasis may also occur with cerebellar disease. Because of the close proximity and relationship between the cerebellum and brainstem, lesions within the cerebellum often compress the brainstem which results in the development of hemi or tetraparesis. Mentation is normal in patients with cerebellar disease, unless the brainstem is also involved.

Vestibular syndrome

The vestibular system can be divided into its peripheral and central components. The peripheral vestibular system consists of the vestibular receptors in the petrous temporal bone and the vestibular component of CN VIII (vestibulocochlear nerve). The nuclei of CN VIII in the brainstem and cerebellum are the central components of the vestibular system. It is important to try to distinguish between peripheral and central vestibular disease because treatment and prognosis are often quite different. Many symptoms of vestibular disease such as head tilt, rolling, circling, ataxia, leaning or drifting to the side when walking, horizontal/rotary nystagmus and ventral strabismus are present in both central and peripheral vestibular disease. Symptoms of brainstem involvement such as proprioceptive placing deficits, ipsilateral hemiparesis, altered levels of consciousness, cranial nerve deficits (other than CN VII), and vertical nystagmus or nystagmus that changes direction in different body positions are symptoms seen only with central vestibular disease. A patient's circling and head tilt is typically toward and the fast phase of nystagmus is way from the side of the lesion causing vestibular symptoms. Paradoxic vestibular symptoms are an exception to this rule and may occur with lesions involving the cerebellar peduncles. In paradoxic vestibular syndrome hemiparesis and postural reaction deficits remain ipsilateral to lesion and are the most reliable examination finding for localizing the side of lesion in patients with central vestibular symptoms.

Horner's syndrome (miosis, ptosis, enophthalmos and third eyelid elevation) is most often associated with peripheral vestibular disease and indicates involvement of the ipsilateral sympathetic innervation to the eye. Ipsilateral facial nerve paralysis also occurs most frequently in conjunction with peripheral vestibular symptoms caused by disease within the tympanic bullae. Bilateral peripheral vestibular symptoms sometime occur and result in wide swaying of the head, a crouched wide based gait and absence of nystagmus.

Cervical syndrome (C1-C5)

Disorders affecting spinal cord segments C1-C5 produce symptoms ranging from cervical pain without gait abnormalities to tetraplegia and respiratory paralysis. Symptoms of cervical pain include neck guarding, fasciculation of cervical musculature and vocalization or resistance to cervical flexion and extension. Reflexes are normal or exaggerated and increased extensor tone may be present in all limbs. Symmetric tetraparesis, asymmetric tetraparesis and hemiparesis may occur along with bilateral or unilateral postural reaction deficits. Tetraplegia may also occur and indicates severe spinal cord impairment, although complete loss of sensation to the limbs is uncommon without accompanying respiratory compromise. Scoliosis and torticollis may occur with central spinal cord lesions from C1-C5 with disorders such as Syringo hydromyelia. Root signature may also be seen, but this finding is more common with lesions involving spinal cord segments C6-T2. Mentation and cranial nerve examination is normal, except that Horner's syndrome may rarely occur with lesions in this area.

Cervicothoracic syndrome (Cervical enlargement C6-T2)

Animals with disorders of the cervical enlargement may have tetraparesis/plegia, hemiparesis/plegia or monoparesis as well as cervical pain. In some patients the thoracic limbs are weaker than the pelvic limbs because of disruption in the reflex arc to the thoracic limbs and resultant decrease in muscle tone. Disorders of the cervical enlargement may also produce a "two engine" gait, characterized by a shortened quick stride in the thoracic limbs and slower ataxic pelvic limb movements. Segmental spinal cord reflexes may be hyporeflexic and muscle tone diminished to the thoracic limbs, however, thoracic limb reflexes may also be normal depending on the degree of disruption to the reflex arc. Mild hemiparesis may occur with extradural spinal cord compression but marked asymmetric hemiparesis/plegia is most often caused by intramedullary spinal cord damage. When nerve root compression only is present intermittent flexion of the limb to the body (root signature sign) may occur. With severe impairment of the nerve roots a monoparesis/plegia may be evident. Atrophy of the thoracic limb muscles may be prominent with C6-T2 spinal cord disorders and may develop early in the course of weakness. With lesions involving the C8-T2 spinal cord segments the efferent arm of the cutaneous trunci (panniculus) reflex may be absent or decreased.

Thoracolumbar syndrome (T3-L3)

The majority of spinal cord disorders encountered in small animal practice occur in spinal cord segments T3-L3. Patients may have a normal gait with back pain or develop proprioceptive placing and other postural reaction deficits to the rear limbs. As symptoms progress posterior paresis or paraplegia may develop. Pelvic limb muscle tone and reflexes are normal or exaggerated, as are reflexes to the anus and perineum. The cutaneous trunci reflex may be absent one to two vertebral bodies caudal to the area of spinal cord injury. Thoracic limb postural reactions, muscle tone, reflexes and sensation is normal with lesions involving spinal cord segments T3-L3, however, the length of stride to the front limbs may shorten with lesions affecting the cranial and middle thoracic spinal cord segments. Careful palpation of the vertebral column often identifies an area of hyperesthesia and is useful for further localizing a lesion within the thoracolumbar segment.

Lumbosacral syndrome and cauda equina (Lumbar enlargement L4-CD5)

Symptoms of L4-Cd5 affect the rear limbs, tail, anal sphincter and urinary bladder. Thoracic limbs, cranial nerves and mentation are normal. The gait of patients with lumbosacral syndrome ranges from normal to paraplegia. The more cranial the lesion is within the lumbar enlargement the more severe the paresis and postural reactions deficits will be. Tail tone may be diminished resulting in a change in the carriage of the tail. In breeds with long tails that do not normally carry the tail high the tail may swing side to side when a patient walks. Anal tone may be flaccid and the anal and perineal reflexes diminished or absent. Urinary and fecal incontinence with little to no changes in the gait may be caused by lesions involving only the sacral and caudal spinal cord segments. Muscle atrophy to the rear limbs is more prominent and develops more quickly with lesions of the lumbar enlargement than more cranial segments of the spinal cord. Disorders that compress the lumbosacral nerve roots may produce rear limb root signature. This is especially common with lesions at the L5-L6 and L6-L7 disc spaces.

Neuromuscular syndrome

Patients with neuromuscular symptoms have generalized or focal weakness without ataxia. Some patients prefer to walk or lie down and are reluctant to stand still. When standing tremors to the limbs many indicate weakness. Fatigue with exercise is common and results in a decreased length of stride as exercise progresses which produces a short, choppy gait. At times a patient may appear lame as they try to rapidly take weight off the limb because of weakness. If forced to continue walking patients may also develop weakness of the muscles of the trunk and may have difficulty holding up the head. Continued walking often results in collapse. Patients often regain strength after a short period of rest only to fatigue again with exercise. If neuromuscular weakness is severe enough patients may not be able to stand without assistance. Despite exercise fatigue or marked weakness, proprioceptive placing is often normal or only mildly delayed. This disparity between weakness and proprioceptive placing is an important indicator of neuromuscular weakness. Segmental spinal cord reflexes are usually absent or hyporeflexic. At times reflexes appear normal initially but fatigue with repeated testing. This is especially true for the palpebral reflex in disorders such as myasthenia gravis. Vertebral and spinal pain is absent unless inflammation of the nerve roots is present but pain may be present in the muscle with certain Myopathies. Muscle atrophy occurs early and can progress quickly. Cranial nerves may also be affected in some neuromuscular disorders. With severe weakness voice changes and respiratory depression can occur. Other findings suggestive of neuromuscular disease include megaesophagus and respiratory stridor.

Multifocal syndrome

Whenever possible, all of a patient's neurologic symptoms should try to be explained by a single lesion within one of the previously discussed neuroanatomical sections. At times, however, a patient clearly has symptoms of more than one neurological syndrome and is said to have multifocal symptoms. Infectious, neurotoxic and metabolic diseases are some of the most common causes of multifocal disorders.