Where is the lesion--localizing disease in the nervous system (Proceedings)

The overall aim when approaching neurological problems is essentially the same as with any clinical problem.  Initially it is necessary to identify the nature of the problem, its extent and severity.  Following this, it is necessary to determine the possible differential diagnoses in order to formulate an effective diagnostic approach.  In this way an accurate diagnosis can be made and an appropriate treatment regime formulated whilst additionally offering prognostic information to the owner of the animal.

Primarily the aim is to address two main questions:

·         Where is the lesion?

·         What is the nature of the lesion?

Anatomical localisation of the lesion is generally necessary with neurological cases in order to make a definitive diagnosis.  This relates to the fact that the clinical signs observed in neurological cases reflect the location of the lesion and the function of the section of the nervous system involved far more than the underlying aetiology of the lesion.  Hence the approach should generally be to determine the lesion site, primarily employing the neurological examination in order to do this, and then to compile a differential diagnosis list weighted according to the anatomical location. 

Comprehensive knowledge of the anatomy and the physiology of the nervous system is very useful in clinical neurology; however, the majority of neurologic problems in clinical practice can be diagnosed and managed through knowledge of several principles of nervous system organisation.

Functional Arrangement of the Nervous System

Simplistically, the nervous system can be broken down into motor and sensory systems. The motor system consists of both upper and lower motor neurons, whilst the sensory system consists primarily of proprioception and pain sensation neurons.

A.      The Motor System

·         Lower Motor Neuron

The lower motor neuron (LMN) connects the central nervous system (CNS) to an effector organ such as muscle and is the final common pathway responsible for movement.   Lower motor neurons are located in all spinal cord segments in the intermediate and ventral horns of the gray matter, and in cranial nerve nuclei III-VII and IX-XII in the brainstem. In other words, LMNs can be thought of as the main components of peripheral spinal and cranial nerves. Frequently, the identification of LMN signs can help to specifically localise a lesion within the nervous system because the loss of reflex function highlights specific neuroanatomic dysfunction.

·         Upper Motor Neuron

Upper motor neuron (UMN) is a collective term for motor systems in the CNS that control LMNs . The UMNs are responsible for (a) the initiation and maintenance of movement as well as (b) the maintenance of tone in the weight bearing extensor muscles of the limbs. The UMNs originate in the intracranial structures of the brain and brainstem. Signs of UMN dysfunction are listed in Table 1. However, because disease at many different levels of the nervous system may produce signs of UMN dysfunction, these signs are rarely helpful in localising a disease to particular place. Additional more specific signs need to be considered in this situation in contrast to the situation with LMN signs.

B.       The Sensory System

·         Pain sensation

Sensory neurons are located in the ganglia of dorsal roots along the spinal cord, and in the ganglia of some cranial nerves. One spinal nerve innervates an area of skin called a dermatome, which are arranged in a roughly segmental fashion. Alterations in the sensation of a dermatome can be used to localise a lesion to a spinal nerve or a dorsal root. The area of skin innervated by the sensory neurons of an appendicular nerve also allow specific localisation of lesions. Superficial pain pathways are located primarily in the dorsolateral portion of the spinal cord and project to the contralateral cerebral cortex for conscious recognition of pain. The deep pain pathway, responsible for the perception of severe pain from bones and joints, is a bilateral multisynaptic system, which also projects to the cerebral cortex.

Lesions of the sensory neurons produce characteristic signs, which include (a) anaesthesia – complete loss of pain sensation, (b) hypaesthesia – partial loss of pain sensation, (c) hyperaesthesia – increased pain sensation, and (d) loss of reflexes. Increased or decreased pain sensation can be assessed by pinching the skin, which can help map out sensory nerve damage accurately. Lesions of the deep pain pathways within the spinal cord cause loss of deep pain sensation; this is poor prognostic indicator as it indicates severe, potential total damage to the spinal cord pathways with limited potential for complete resolution.

·         Proprioception

Proprioceptive pathways are located in the dorsal and dorsolateral portions of the spinal cord. They project to the cerebral cortex and the cerebellum. Signs of damage to these pathways cause proprioceptive deficits and ataxia. They may often be accompanied by weakness (motor dysfunction) due to concurrent damage to the neighbouring motor pathways. 

Localisation of Disease within the Central Nervous System

A.      Spinal Cord

The examination of the motor system should enable localisation of spinal disease to one of five segments of the spinal cord. It is essential to note that the divisions of the spinal cord listed below refer to spinal cord segments, which do not correspond exactly with vertebrae of the same number. Motor dysfunction can also occur with brainstem disease but there will be an association with cranial nerve dysfunction in this situation; this is considered separately below.

The most common signs of spinal cord dysfunction are ataxia or incoordination, weakness caudal to the lesion and spinal pain. Ataxia can also be a feature of vestibular and cerebellar diseases (see below). The presence of focal spinal pain is localising and suggests a compressive lesion such as disc extrusion or neoplasia (extradural or intradural-extramedullary lesions). Non-painful spinal diseases are usually lesions that affect the spinal cord parenchyma only (intramedullary lesions), such as degenerative and vascular disorders. The degree of weakness of the patient often parallels the severity of the lesion. Proprioceptive deficits are an early indicator of compressive spinal cord lesions. In severe cases, superficial and deep pain perception are absent caudal to the lesion. In all cases of focal spinal cord disease, whatever the location, there are no mentation changes or signs of cranial nerve dysfunction.

·         Spinal Segments Cervical 1-Cervical 5

Lesions affecting the spinal cord segments C1-C5 can cause weakness or paralysis in all four limbs (tetraparesis / tetraplegia) or in the limbs on just one side (hemiparesis). Lesions in the centre of the spinal cord in this region can cause weakness in the thoracic limbs with minimal deficits in the pelvic limbs (central cord syndrome). Segmental spinal reflexes are not affected by lesions in this region of the spinal cord and therefore remain intact. Severe lesions can cause respiratory weakness or apnoea.

·         Spinal Segments Cervical 6 – Thoracic 2

Lesions affecting spinal cord segments C6-T2 can result in the same pattern of motor dysfunction in the thoracic and pelvic limbs as that seen with C1-C5 lesions, with the addition of weak or absent spinal reflexes in the thoracic limbs. Segmental spinal reflexes are intact in the pelvic limbs. With mild extradural lesions, the pelvic limbs can be more severely affected than the thoracic limbs.

·         Spinal Segments Thoracic 3 – Lumbar 3

Lesions affecting the T3 through L3 spinal segments may cause varying degrees of ataxia and weakness in the pelvic limbs with normal motor function in the thoracic limbs. The segmental spinal reflexes in all limbs remain intact with lesions in this region. Acute lesions in this region may cause a Schiff-Sherrington posture but this does not have prognostic significance. The cutaneous trunci reflex (panniculus) may be absent two vertebral levels caudal to the site of the lesion.

·         Spinal Segments Lumbar 4 – Sacral 2

Lesions affecting the L4 through the second sacral spinal segments cause weakness in the pelvic limbs with limited ataxia and reduced spinal reflexes (patella reflex /femoral nerve L4-L5; flexor withdrawal reflex / sciatic nerve L6-S2).

·         Spinal Segments Sacral 1 – Sacral 3

Lesions affecting the sacral spinal segments can cause mild pelvic limb weakness with reduced or absent flexor withdrawal reflexes but may predominantly cause urinary and faecal incontinence with reduced or absent perineal or anal reflex, in addition to reduced motor function in the tail.

B.       Brain Stem

The brain stem includes the midbrain, pons and medulla oblongata with cranial nerves III through XII. Severe brain stem lesions can cause severe depression, stupor or coma, but the animal's personality and behaviour is appropriate unless there is concurrent cerebral disease. Tetraparesis or tetraplegia with decerebrate rigidity, conscious proprioception deficits and intact spinal reflexes are often seen with brain stem disease. Ipsilateral cranial nerve deficits are possible in isolation or in conjunction with central motor and sensory dysfunction, depending on whether the cranial nerve is affected after it has exited the brainstem or before respectively. In addition to the above signs, there is the potential for cardiac and respiratory abnormalities, including apnoea and cardiac arrest.

C.       Vestibular System

The function of the vestibular system is to send messages to the brain about the gravitational forces acting on the head and any movement that the head experiences. The brain can then determine the position of the head in space and can coordinate subsequent movements of the eyes and limbs.

·         Peripheral component

The peripheral component of the vestibular system is located in the inner ear and is made up of a membranous labyrinth and the vestibular portion of cranial nerve VIII. This system is intricately associated with the auditory system and is enclosed in the petrous temporal bone close to cranial nerve VII and the sympathetic supply to the eye and face.

·         Central component

The central component of the vestibular system consists of vestibular nuclei in the caudal brainstem (medulla oblongata) and the flocculonodular lobe of the cerebellum.  These nuclei are connected to the nuclei of cranial nerves III, IV, and VI to control the movement of the eyes so that the eyes move in a coordinated fashion with the head. The vestibular nuclei are also connected via the vestibulospinal tract to the extensor muscles of the neck and the limbs; they are responsible for extensor tone in the ipsilateral limbs and cause contralateral extensor inhibition

.

Clinical Signs of Vestibular Disease

Damage to either the peripheral or the central components of the vestibular system will cause vestibular dysfunction. It is most common to see unilateral lesions and therefore asymmetric signs but bilateral lesions are possible. The signs exhibited by the patient depend upon the portion of the vestibular system affected. Indeed, it is important to use these differences in lesion localization, as peripheral and central vestibular diseases have several different differentials to be considered as well as different prognoses.

·         Head Tilt – this is the most common sign of unilateral vestibular disease and occurs because of the loss of muscle tone on one side of the neck. The head tilt is towards the side of the lesion in peripheral disease whereas it can be to any side if there is a central lesion. Often, there is no head tilt if there is bilateral disease and instead there are wide excursions of the head and neck from side to side.

·         Ataxia & Dysequilibrium – the loss of general balance that is experienced by the animal with vestibular disease is manifested by a base-wide stance and swaying of the head and trunk. This can progress to rolling, leaning or falling to one side with unilateral lesions. Peripheral vestibular disease occurs without any deficits in conscious proprioception or strength, whereas a central lesion may cause these abnormalities.

·         Nystagmus – this is rhythmic movement of the eyes with a fast and a slow phase. The direction of the nystagmus is often described as the direction of the fast phase but can be horizontal, rotational or vertical in its direction. In normal animals, a physiologic nystagmus should be induced by rotation of the head, with the direction being in the plane of the head movement and the fast phase being towards the side of rotation (this may also be termed the occulocephalic reflex). This may be altered or absent in animals with vestibular disease. Nystagmus can be spontaneous which means that it occurs when the head is stationary in a normal position. With unilateral peripheral lesions, the fast phase is away from the side of the disease and the direction can be horizontal or rotational. With central lesions, the fast phase is usually away from the side of the disease but the direction can be vertical as well as horizontal or rotatory. If the nystagmus is detected only when the head is placed in an unusual position, this is called positional nystagmus and can occur with both peripheral and central lesions but may be more common with the latter. Animals with bilateral disease usually do not have spontaneous or positional nystagmus.

·         Strabismus – Vestibular disease may cause one eye to be deviated ventrally or ventrolaterally when the neck is extended – positional strabismus. The ventrally deviated eye is usually on the side of the lesion. Occasionally, a constant ventral strabismus is present with vestibular disease.

·         Cranial Nerve Abnormalities - Peripheral vestibular lesions may be accompanied by ipsilateral facial nerve paresis and, or Horner's syndrome due to the anatomical proximity of these two nerve supplies. It is possible that multiple cranial nerve defects be present with central vestibular disease.

D.      Cerebellum

Cerebellar disease is one of the most readily recognizable syndromes in veterinary practice. The cerebellum coordinates movements. It controls the rate and range of movements but not the initiation of the movement itself. Cerebellar disease results in an inability to regulate the rate, range, and force of a movement (i.e., dysmetria). Clinical signs include an exaggerated limb response when a movement is initiated, such as "goose-stepping" (hypermetria) when walking. Limb movements are typically spastic and clumsy. Initiation of movement is delayed and often accompanied by tremors (i.e., intention tremors). Tremors are especially noticeable involving the head. Intention tremors disappear at rest. Fine, pendular, or oscillatory eye movements also may be present. A bilateral menace deficit may be noted, although vision is not affected. If the lesion involves only one side of the cerebellum, the menace deficit will be ipsilateral.

Infrequently observed signs associated with specific areas of the cerebellum include opisthotonus (e.g., when a lesion involves the rostral lobe of the cerebellum), and vestibular signs (e.g., when a lesion occurs in the flocculonodular lobe or fastigial nuclear area of the cerebellum).

E.       Thalamus and Hypothalamus (Diencephalon)

The hypothalamus is intimately involved in autonomic visceral body functions, including appetite, sexual activity, sleep-wake cycle, body temperature, blood pressure regulation, heart rate, and emotions. It also regulates much of the body's endocrine activity. Animals with the hypothalamic syndrome may show signs of altered mental status (e.g., disorientation, lethargy, or coma); and / or behaviour changes (e.g., aggression, hyperexcitability, pacing, wandering, hiding, tight circling, head pressing, and trembling). Gait is usually normal. Abnormal temperature regulation may be manifested as hyperthermia, hypothermia, or poikilothermia. Abnormalities in appetite are seen as polyphagia and obesity, or anorexia and cachexia. Vision is frequently impaired if the lesion extends to involve the optic chiasm, in which case pupils may be dilated and weakly or non-responsive to light stimulation. Endocrine disturbances most often include diabetes insipidus or hyperadrenocorticism (clinical signs include polydypsia, polyuria, polyphagia, alopecia, pendulous abdomen, and muscular weakness).

Pure thalamic lesions are infrequently reported in dogs and cats; however, signs might include postural reaction deficits (contralateral), mild ataxia, visual deficits (contralateral), hypalgesia (contralateral and especially involving the head), an "adversive" syndrome (propulsive circling and head/eye deviation toward the side of the lesion) with rostral thalamic lesions, and possible disturbances in consciousness (depression, semicoma) or seizures.

Cerebrum

Diseases of the cerebrum usually cause alterations in behaviour and / or mental status, seizures, blindness with normal pupillary reactivity, and contralateral proprioception deficits. Many animals will present with just one of these signs representing a lesion in a focal area of the brain.

Behavioural changes include those seen with lesions of the thalamus and hypothalamus in addition to circling (usually to the side of the lesion), compulsive pacing, head pressing, standing in corners, and getting trapped under furniture. Circling however, can also be seen with lesions of the brain stem, so is not a definitively localising sign. With cerebral disease, the animal's gait is reasonably normal in most cases although with severe lesions, there may be a moderate ataxia. Depression, stupor or coma represent decreasing levels of consciousness seen with disease of the cerebrum. These signs can also be seen with brain stem disease, so the clinician should attempt to discern whether there is an inappropriate mentation (dementia) in addition to the altered consciousness, which would confirm the cerebral origin of the disease.