In this article, I help you correctly interpret the findings of a neurologic evaluation in order to answer the most important question when dealing with a neurologic problem: Where is the lesion?
As the previous article showed, performing a good neurologic examination can be challenging and needs to be done in a relaxed environment with enough time allowed for a thorough evaluation. Interpreting the findings can be difficult as well. In this article, I help you correctly interpret the findings of a neurologic evaluation in order to answer the most important question when dealing with a neurologic problem: Where is the lesion? Once a lesion's location is determined, a proper list of differential diagnoses can be compiled based on the onset and progression of the clinical signs and the patient's signalment. Appropriate diagnostic procedures can then be recommended.
The central nervous system encompasses the cerebral cortex and thalamus, midbrain, pons, medulla oblongata, cerebellum, and spinal cord. The peripheral nervous system includes the sensory, autonomic, and neuromuscular system. The neuromuscular system is also called the lower motor neuron system and is composed of the nerve roots (including the cauda equina), peripheral nerves, neuromuscular junction, and muscles.
Together, these structures are responsible for personality, behavior (instinctual and learned), vision, and most reactions. Signs of thalamocortical involvement include a change in personality or behavior, cortical blindness, compulsive behavior (pacing, circling), mental confusion, and abnormal reactions (not reflexes, see "Skills Laboratory, Part 1: Performing a neurologic examination") on the neurologic examination. Seizures are also a common clinical sign.1-3 During the neurologic examination, clues of thalamocortical involvement will be obtained from evaluating the mental status and everything that is a conscious reaction (menace reaction, reaction to a nasal sensation, conscious proprioception). The signs and deficits are contralateral to the lesion except for circling, which is usually toward the side of the lesion.4 In cats, the most common presenting complaint of a brain tumor is a change in behavior.5 Although a change in behavior suggests cerebrocortical or thalamic involvement, it can also occur because of a change in the pet's environment, stress, training, or other factors.
Together, these structures are also responsible for mental status, primarily alertness, through the large and diffuse reticular formation. These areas also contain the nuclei from the third to 12th cranial nerves, the nuclei of most of the upper motor neurons responsible for motor function, and the ascending sensory and proprioceptive tracts traveling through to the thalamus and cerebrum. Signs of involvement of these areas include a change in mental status (mental depression, stupor, coma), ipsilateral cranial nerve dysfunction, and motor (upper motor neuron paresis) and proprioceptive deficits (ipsilateral to the lesion). Because the reticular formation is so large and diffuse, a brainstem lesion will virtually always cause at least some mental alteration. To identify this mental alteration, it is important to consider your own assessment but also any changes reported by the owner (e.g. suddenly seems older, is not as excited as it used to be, is not greeting the owner at the door anymore). If there is no alteration in the mental status, the lesion is unlikely to be in the brainstem.
Keep in mind that a cranial nerve deficit does not always indicate a brainstem disease. Cranial nerve deficits can be seen with a cranial neuropathy (e.g. trigeminal neuritis, idiopathic facial paralysis) or a neuromuscular problem (e.g. pharyngeal paresis associated with myasthenia gravis). Also, although proprioceptive ataxia and upper motor neuron tetraparesis can be signs of brainstem disease, they are more often signs of a cervical spinal cord problem. The same is true for a vestibular syndrome, which can be secondary to a brainstem disease or a peripheral vestibular system involvement (inner ear or vestibulocochlear nerve) as well as a cerebellar disease. This is one example of why it is so important to do a complete neurologic examination before attempting to localize the lesion.
The cerebellum is responsible for fine coordination and movement adjustment and for vestibular functions. It also plays a role in the ipsilateral menace reaction and pupillary size. Cerebellar diseases can lead to a lack of menace reaction with normal vision. Anisocoria may also be seen. Signs of cerebellar involvement may include vestibular dysfunction (head tilt, loss of balance), intention tremors, dysmetria (mostly hypermetria), and opisthotonos if the damage is severe. Opisthotonos is an abnormal posture characterized by marked hyperextension of the neck. The hypermetria may be seen when you evaluate the gait (e.g. excessive flexion of the limbs, bouncing gait) or the postural reaction (e.g. excessive movement of the tested limb during placing or hopping). Intention tremors are present on initiation of movement. They are usually best identified when the patient moves its head to try to eat or smell something. Strength is not affected by cerebellar disease since there are no upper or lower motor neuron nuclei in the cerebellum. When the caudal cerebellar peduncles (at the cerebellomedullary junction) or the flocculonodular lobe of the cerebellum is affected, signs of a paradoxical vestibular disease can be seen.4,6 With paradoxical vestibular disease, the head is tilted away from the lesion and other localizing signs indicative of cerebellar (e.g. hypermetria) or brainstem (e.g. conscious proprioception deficit) involvement are present. It is important to recognize a paradoxical vestibular disease as it allows for accurate lesion localization. A neoplastic process, a granuloma, and a vascular problem are the primary rule-outs.
The spinal cord is divided into four segments for function and lesion localization: C1-C5 (or C1-C8 white matter), C6-T2, T3-L3, and L4-S3. Remember that these spinal cord segments are not necessarily in the corresponding vertebrae since the spinal cord ends around the sixth or seventh lumbar vertebra in most dogs (L7-S1 in cats and small dogs). The spinal cord carries the descending tracts (upper motor neuron) from the brainstem nuclei and other higher centers to the lower motor neuron nuclei located in the ventral horn of the gray matter. It also carries the ascending sensory tracts (e.g. proprioception, nociception) from the body and limbs toward the superior center. In spinal cord disease, the lesion's location defines the type of clinical signs, whereas the lesion's extent defines the severity.
Clinical signs seen with spinal cord disease vary depending on the segment affected. They usually progress in a specific order, based on the size of the nerve fiber and its location in the spinal cord. The larger myelinated, peripherally located proprioceptive and motor tracts will usually be affected first, causing proprioceptive ataxia and ambulatory paresis followed by a nonambulatory paresis. With a more severe involvement, paralysis will occur along with incontinence, then loss of superficial pain, and finally loss of deep pain perception. The latter is an indication of a severe cord lesion associated with a guarded to poor prognosis. As a reminder, when evaluating for deep pain perception, it is extremely important to look for a reaction from the patient (e.g. it cries or turns its head) and not to conclude that deep pain perception is present because of limb flexion (spinal reflex only). Lesions involving the spinal cord only should not cause a change in mental status or a cranial nerve deficit.
Involvement of the C1-C5 segment causes proprioceptive ataxia and upper motor neuron tetraparesis. Tetraplegia is unlikely with this location since it would also cause paralysis of the respiratory muscles (the diaphragm by the phrenic nerve and intercostal muscles).
A C6-T2 involvement will cause proprioceptive ataxia and upper motor neuron paraparesis along with lower motor neuron paresis in the thoracic limbs because of gray matter involvement of the cervicothoracic intumescence. This results in a characteristic "two-engine gait" with short, stiff steps in the forelimbs and slower, large, ataxic and spastic steps in the hindlimbs. A C6-T2 lesion can also cause an ipsilateral Horner syndrome because of involvement of the sympathetic fibers coming from T1-T3, the loss of the ipsilateral cutaneous trunci reflex, or both, since the innervation of the cutaneous trunci muscle (lateral thoracic nerve) comes from the spinal segments C8-T1. If only the white matter is affected, signs similar to a C1-C5 involvement will be seen.
Signs of T3-L3 involvement are usually well recognized, consisting of proprioceptive ataxia and upper motor neuron paraparesis or paraplegia with normal function in the thoracic limbs.
With L4-S3 involvement, lower motor neuron paraparesis or paraplegia and proprioceptive ataxia occur. The ataxia might be difficult to appreciate at this level.
As a rule, the prognosis for spinal cord disease depends mainly on the lesion's location (gray vs. white matter), severity, etiology (treatable or not), and chronicity.7 Although the prognosis depends partly on the lesion's severity, the same type of lesion in two different spinal cord segments does not necessarily carry the same prognosis. For example, since L5 is the most important segment for the femoral nerve, a lesion affecting the gray matter at L5 will cause a femoral deficit. This would result in a loss of patellar reflex and, most important, an inability to support weight in that pelvic limb.
The neuromuscular system transmits information from the nuclei of the lower motor neuron to the effector muscle, resulting in a muscle contraction. The main clinical sign of neuromuscular system involvement is weakness (lower motor neuron paresis). As a general rule, lesions of the neuromuscular system will not cause ataxia, although a marked gait abnormality might be noticed. For example, in a dog with a bilateral sciatic paresis, the gait may be characterized by reduced hock flexion during protraction that is sometimes associated with excessive hip flexion (from the femoral nerve as a compensation). Because of the reduced hock flexion and possibly a loss of proprioception (the afferent pathway being mainly the sciatic nerve for the pelvic limb), the dog may also drag its toes (i.e. exhibit paresis). Despite the fact that the pet drags its toes, incoordination (i.e. ataxia) isn't present, and the gait is regularly abnormal because the same movement always occurs and you can predict where the animal will place its feet on the floor. Neuromuscular system involvement can be focal (e.g. unilateral facial paralysis) or diffuse (e.g. generalized weakness associated with botulism). Keep in mind that the cauda equina is part of the peripheral nervous system since it consists of spinal nerves and not spinal cord segments.
Suspect involvement of the neuromuscular system in patients with weakness and paresis without ataxia, in patients with cranial nerve deficits without a change in mental status, and in patients with generalized weakness.
After obtaining a patient's history and performing physical and neurologic examinations, create a list of neurologic abnormalities. With this list in mind, determine which part of the nervous system is affected (e.g. spinal cord segment T3-L3, diffuse lower motor neuron). This is the neuroanatomical diagnosis. If possible, all the clinical signs should be explained with a single anatomical location. For example, a dog with seizures and a conscious proprioception deficit in the left thoracic and pelvic limbs most likely has a lesion in the right thalamocortical region rather than both a cortical and a spinal cord lesion. When the clinical signs cannot be explained with a single neuroanatomical location, multifocal involvement is likely. Once you've determined the neuroanatomical diagnosis, you can compile an accurate list of differential diagnoses, taking into consideration the patient's signalment and the history (onset, progression) (Table 1).
Table 1. Examples of Common Differential Diagnoses by Neuroanatomical Localization
When identifying differential diagnoses, you should understand the diseases' pathophysiology in relation to their presentation and progression (Tables 2 & 3). For example, a young animal that presents with an insidious and progressive problem is more likely to have a degenerative disease than a traumatic problem. Also, a 5-year-old cocker spaniel with a two-week history of back pain followed by an acute onset of upper motor neuron paraplegia (T3-L3 lesion) is more likely to have a disk problem than a fibrocartilaginous embolism, since a fibrocartilaginous embolism is unlikely to occur in a chondrodystrophic animal, is usually not painful, and should be acute (i.e. not preceded by two weeks of pain).
Table 2. An Acronym for Categorizing Neurologic Diseases
Some clinical presentations are classic and worth mentioning. Metronidazole toxicosis causes a severe central vestibular ataxia, possibly associated with some depression, hypermetria, and conscious proprioception deficits.8-10 A history of metronidazole administration at a high dosage (usually > 50 mg/kg/day) or long-term administration should lead to an easy diagnosis. Treatment is mainly supportive, although administering diazepam appears to hasten recovery.10
Table 3. Categories of Neurologic Diseases by Presentation and Progression
A shaker syndrome is reported most frequently in small-breed dogs with white coats (e.g. Maltese, West Highland white terriers), although dogs with other coat colors can be affected. The disease has been called white shaker syndrome, and affected dogs present with generalized but fine whole-body tremors.4,11,12 The tremors are usually exaggerated by excitement, handling, and movement and are usually absent during sleep. Some dogs will also have a pathological nystagmus, although it is more common to see an oscillation of the ocular globes; seizures have also been reported. The cause is unknown, but the lesions consist of a mild, nonsuppurative encephalitis mainly affecting the cerebellum.4 The condition responds favorably to corticosteroid administration, and the prognosis is good.
A masticatory muscle myositis can be seen in dogs.13 In the acute form, the masticatory muscles (masseter and temporalis muscles) are swollen, firm, and quite painful. The patient may also be febrile. The chronic form is characterized by marked muscle atrophy and fibrosis of the masticatory muscles. This can lead to trismus with a complete inability to open the mouth, even when the patient is anesthetized. The disease is secondary to an immune-mediated reaction against specific fibers (2M) of the masticatory muscles. The disease is diagnosed based on positive type 2M antibody assay results or a temporalis of masseter muscle biopsy. Immunosuppressive doses of corticosteroids is the treatment of choice and should be instituted as soon as possible to prevent extensive fibrosis.
Once you've developed a list of differential diagnoses, decide which diagnostic procedures are most pertinent, especially since many of these procedures are expensive and can be invasive.
A minimum database should include a complete blood count, a serum chemistry profile, and urinalysis. A thoracic radiographic examination is also helpful to identify any concomitant problem that may indicate a more diffuse or systemic involvement (e.g. megaesophagus, metastasis, lesions compatible with fungal disease). Then, based on the differential diagnoses, more specific diagnostic procedures can be considered. In cases of multifocal central nervous system disease, an inflammatory cause is the first consideration. In these cases, a funduscopic evaluation can reveal lesions of chorioretinitis or anterior uveitis suggestive of an infectious disease. Measuring titers for specific diseases (fungal, rickettsial, protozoal) is noninvasive and can provide a definitive diagnosis. Cerebrospinal fluid analysis is the next logical step and can be regarded as the "blood test" of the central nervous system. Bacterial culture or titer testing can also be performed on a cerebrospinal fluid sample.
In cases of diffuse disease of the central nervous system, multiple blood glucose, electrolyte, bile acid, and thyroid hormone evaluations and blood pressure monitoring are warranted. Specific tests can also be performed for suspected intoxication (e.g. blood lead concentration, ethylene glycol evaluation, cholinesterase activity).
For spinal cord disease, obtain survey radiographs since they may show a malformation (hemivertebrae, atlantoaxial instability), evidence of trauma (luxation, fracture), signs of an infectious process (chronic diskospondylitis, osteomyelitis), or a tumor. If the survey radiographs are unremarkable, further imaging of the spine is usually necessary (myelogram, computed tomography, magnetic resonance imaging). In cases of diffuse neuromuscular diseases, a metabolic or endocrine problem should be ruled out (see above). Then, depending on the differential diagnoses, creatine kinase activity measurement, a thyroid profile, or tests to detect acetylcholine receptor antibodies or antibodies against the type 2M fibers could be performed. If a polyneuropathy or a polymyopathy is suspected, muscle and nerve biopsies are recommended. Electrodiagnostic testing can also be performed but usually requires referral to a neurologist.
Cases of focal brain disease usually require advanced imaging of the brain, such as computed tomography or magnetic resonance imaging. But a proper minimum database is always recommended before these advanced procedures.
A complete neurologic examination should lead to accurate lesion localization. Once you've localized a lesion, you can compile a proper list of differential diagnoses and propose a list of diagnostic procedures to the client. Also, a proper list of differential diagnoses will allow you to discuss the treatments and prognoses of the diverse possible conditions with the client. Although referral to a neurologist may sometimes be warranted, many diagnostic procedures and treatments can be performed by primary care veterinarians.
Veronique Sammut, DVM, MS, DACVIM (neurology)
California Animal Hospital
1736 S. Sepulveda Blvd.
Los Angeles, CA 90025
1. Bagley RS, Gavin PR. Seizures as a complication of brain tumors in dogs. Clin Tech Small Anim Pract 1998;13:179-184.
2. Bagley RS, Gavin PR, Moore MP, et al. Clinical signs associated with brain tumors in dogs: 97 cases (1992-1997). J Am Vet Med Assoc 1999;215:818-819.
3. Platt SR, Haag M. Canine status epilepticus: A retrospective study of 50 cases. J Small Anim Pract 2002;43:151-153.
4. de Lahunta A. Veterinary neuroanatomy and clinical neurology. 2nd ed. Philadelphia, Pa: WB Saunders, 1983.
5. Dewey CW, Coates JR, Bahr A, et al. Primary brain tumors in dogs and cats. Compend Cont Educ Vet Pract 2000;22:756-762.
6. Holliday T. Clinical signs of acute and chronic experimental lesions of the cerebellum. Vet Res Commun 1980;3:259-278.
7. Sharp NJH, Wheeler S. Small animal spinal disorders. In: Diagnosis and surgery. 2nd ed. St. Louis, Mo: Mosby, 2005;31-32.
8. Wright KH, Tyler JW. Recognizing metronidazole toxicosis in dogs. Vet Med 2003;98:410-418.
9. Caylor KB, Cassimatis MK. Metronidazole neurotoxicosis in dogs. J Am Anim Hosp Assoc 2001;37:258-262.
10. Evans J, Levesque D, Knowles K, et al. Diazepam as a treatment for metronidazole toxicosis in dogs: A retrospective study of 21 cases. J Vet Intern Med 2003;17:304-310.
11. Bagley RS. Differential diagnosis of animals with peripheral nervous system disease, in Proceedings. Atlantic Coast Vet Conf, 2002.
12. Yamaya Y, Iwakami E, Goto M, et al. A case of shaker dog disease in a miniature dachshund. J Vet Med Sci 2004;66:1159-1160.
13. Podell M. Inflammatory myopathies. Vet Clin North Am Small Anim Pract 2002;32:147-167.