November 2007

Neurology

Natasha Olby Vet. M.B. Ph.D. Diplomate ACVIM (Neurology)
Department of Clinical Sciences
North Carolina State University, College of Veterinary Medicine


The Neurological Examination and Lesion Localization in the Spinal Cord

A Review of the Diagnostic Approach and Treatment of Spinal Cord Diseases


Introduction
Most, if not all neurologists will admit a fascination for localizing neurological problems but understand that not everyone enjoys this process. However, it is extremely important that veterinarians are able to localize neurological problems in order to generate an accurate differential diagnosis list and perform the correct diagnostic tests. Nowadays it is common to hear the argument that the advent of advanced imaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT) negates the need for anything but a crude localization. In fact these imaging modalities increase the need for accurate localization because their sensitivity may reveal a number of abnormalities. It is important to interpret any imaging findings in the light of the clinical findings.

Definitions
It is important to use the correct terms when describing neurological signs in order to accurately convey the clinical picture. The following terms are pertinent to spinal cord disease.

Term Meaning
'Paresis (mono-, hemi-, para- and tetra-) Motor weakness of one limb, ipsilateral thoracic and pelvic limb, both pelvic limbs and all 4 limbs
'Plegia (mono-, hemi-, para- and tetra-) Complete absence of motor function
Ataxia, subclassified as:
  • Sensory
  • cerebellar
  • vestibular
Loss of coordination.
  • Due to dysfunction of conscious proprioceptive tracts in the spinal cord / brain stem
  • Due to cerebellar disease
  • Due to peripheral or central vestibular disease
Dysmetria/ hypermetria Gait deficit seen in cerebellar disease: the length of a movement is misgauged, often causing a goose stepping (hypermetric) gait. Can occur with spinal cord disease.
Hyper/hypo/areflexia Increased/decreased/absent reflexes
Hyperaesthesia Painful response to normal stimulus
Opisthotonus Posture dominated by increased extensor tone of the limbs and the neck
Kyphosis and lordosis Dorsal and ventral arching of the back
Scoliosis Lateral curvature of the back
Torticollis Neck twisted to one side.


The neurological examination
The neurological examination starts as soon as the veterinarian meets the patient: while taking a history it is important to keep one eye on the patient as they move around the room and are not the centre of interest. A useful rule of both the neurological examination and localization is to look for more than one line of evidence when deciding that something is abnormal. For example, if you think that an animal has proprioceptive deficits, check the nails of its toes for scuffing and watch it walk to see if it scuffs its toes on protraction and has any evidence of weakness or ataxia. An extremely good account of the neurological examination by Dr Alexander de Lahunta can be found in the on line book by Kyle Braund: Clinical Neurology in Small Animals: Localization, Diagnosis and Treatment at http://www.ivis.org/special_books/Braund/toc.asp
In brief, the neurological examination of the spinal patient involves working systematically through the following tests:
  1. Posture and involuntary movements at rest.
    The presence of a heat tilt, a head turn, wide based stance, body lean, inability to bear weight, kyphosis or lordosis, tremors and myoclonus can be detected at this point.
  2. Gait.
    The animals gait is observed walking in a straight line, turning in circles and walking up and down steps to detect sensory and motor deficits. If the animal is ataxic, it is useful to try to classify it as sensory (conscious proprioceptive deficits characterised by crossing the feet and scuffing the toes and due to compression of the long tracts), cerebellar (unconscious proprioceptive deficits characterised by movements of the wrong length causing dysmetria) or vestibular (characterised by a head tilt and body lean). Look for drifting to one side or circling.

    In general orthopaedic disease causes lameness: the animal still has motor function but bears less weight on the limb and may move the joints through a different range of motion. In contrast, neurological disease causes dragging of the limb with conscious proprioceptive deficits. However, the exception to this rule is the sign known as a "nerve root signature". Compression of a nerve root causes the animal to carry this limb in flexion and may cause lameness. A careful orthopaedic and neurological examination are necessary to localise such problems.
  3. Palpation and orthopaedic examination
    A careful orthopaedic examination should be performed in every neurologic patient. Orthopaedic disease can masquerade as neurologic disease, for example, animals with polyarthritis may be reluctant to bear weight at all. Muscle atrophy or hypertrophy should be identified as they can reflect dysfunction of the nerve supplying that muscle or primary muscle disease.
  4. Postural Reactions
    Postural reactions involve afferent and efferent pathways in the peripheral nerve, spinal cord, and brain. Therefore, while they are a sensitive indicator of neurologic dysfunction, postural reactions do not localize a lesion to one part of the nervous system. The main value of testing postural reactions is that they allow the detection of subtle deficiencies. Postural reaction deficits typically occur ipsilateral to peripheral nerve, spinal cord, and most brain stem lesions. If an animal has severe orthopaedic disease, its weight must be supported adequately while performing the postural reactions. The postural reactions include conscious proprioception, hopping, placing (tactile and visual), wheelbarrowing, extensor postural thrust, and hemiwalking. Videotapes of these tests will be shown.
  5. Spinal Reflexes
    A spinal reflex requires an intact sensory neurone, motor neurone, and varying number of interneurones within the spinal cord. Although reflexes are influenced by higher order neurones, they are not dependent on these supraspinal inputs for their presence. A reflex can be elicited even if the region of the spinal cord responsible for its presence is completely isolated from the brain. Several different spinal reflexes can be tested but the patellar and the withdrawal reflexes are the most reliable reflexes in the limbs, and the perineal and panniculus reflexes are also useful. It is often not possible to elicit the biceps and triceps reflexes in normal animals.

    Peripheral nerves and spinal cord segments involved in the spinal reflexes are summarised:

    Reflex Peripheral nerve Spinal cord segment
    Biceps Musculocutaneous C6-C8
    Triceps Radial C7-T2
    Extensor carpi radialis Radial C7-T2
    Withdrawal reflex: thoracic limb Ulnar, median and musculocutaneous C6-T2
    Patellar Femoral L4-L6
    Cranial tibial Common peroneal L6-S1
    Gastrocnemius Tibial L6-S1
    Withdrawal reflex: pelvic limb (hock flexion) Sciatic L6-S1
    Perineal Pudendal S1-3


    The most commonly encountered abnormal spinal reflex is the crossed-extensor reflex. Noxious peripheral stimuli applied to one limb result in stimulation of neurones contributing to muscles of the other three limbs. These so called long spinal reflexes coordinate movements of all four limbs and are suppressed by descending supraspinal input. Spinal injury removes this inhibitory influence and flexion of one pelvic limb is accompanied by extension of the opposite limb.

    The Schiff-Sherrington phenomenon is a characteristic posture adopted by dogs with thoracolumbar spinal cord injuries. In these paraplegic animals, the thoracic limbs have increased extensor tone but retain strength and voluntary motion. Ascending spinal cord tracts in the thoracolumbar spinal cord inhibit extensor muscles of the thoracic limbs. Functional transection of these pathways removes this inhibitory input causing the increase in extensor tone in the thoracic limbs.
  6. Sensation
    1. Pain sensation: There are two principal forms of pain sensation, superficial and deep pain. Superficial pain occurs due to stimulation of myelinated A-delta fibers, while deep pain is conveyed through nonmyelinated C fibers. Although in practice it is difficult to distinguish between these sensory modalities, superficial pain is elicited by pricking or pinching the skin. Deep pain is elicited by clamping the bone of a digit. Withdrawal of the limb alone does not mean that the animal has deep pain perception. The limb withdrawal is a spinal reflex; the animal must show evidence of conscious perception of the stimulus (such as turning around, crying out, pupillary dilation, etc.) Absence of deep pain is a grave prognostic sign because of the relative resilience of type C fibers and the fact that these pathways are diffuse and bilateral within the spinal cord. Severe spinal cord lesions may cause loss of pain sensation caudal to the site of the lesion.
    2. Hyperaesthesia: Hyperaesthesia is a painful response to an innocuous stimulus. This is generally elicited by palpating the paraspinal muscles or by flexing or extending the cervical spine. Compressive or inflammatory spinal lesions can stimulate sensory nerve endings in the meninges or nerve roots, resulting in pain.
Neurolocalization
  1. The significance of upper versus lower motor neurone signs
    Reflexes, whether testing spinal or cranial nerves, give invaluable specific details on the location of a problem if they are reduced or absent. In order for a reflex to be elicited, the sensory and motor nerves (including the cell body of the motor neurone that lies in the grey matter of the spinal cord or a nucleus in the brain, and the cell body of the sensory nerve that lies in a ganglion), the neuromuscular junction and any relevant interneurones must be intact. Thus, absence of a specific reflex isolates a lesion to these specific structures. Signs of lower motor neurone (LMN) dysfunction include flaccid paresis or paralysis, hypo- or areflexia, and rapid and severe muscle atrophy. Upper motor neurone (UMN) signs refer to spastic paresis or paralysis (normal or increased muscle tone), normal or hyperreflexia, and relatively slow muscle atrophy as a result of disuse. This increase in muscle tone and reflexes is a result of loss of the normal inhibitory tone exerted by the UMN (any neurone originating in the brain and projecting to the LMN) on the LMN. Detection of UMN paresis or paralysis indicates that the lesion is rostral to the nerves being tested.
  2. Recognition of syndromes
    Lesions in specific regions of the nervous system, no matter what their aetiology, will cause a consistent set of neurological deficits that can be recognized easily once the functions of these regions are understood. Common neurological syndromes are described below.
    1. Cervical spinal cord dysfunction: C1-5
      Diseases of the cervical spinal cord will produce UMN deficits in all 4 limbs. Typical signs include:
      • Normal mentation and cranial nerve examination.
      • Tetra- or ipsilateral hemiparesis/plegia.
      • Abnormal postural reactions ipsilateral to the lesion
      • Normal to hyper-reflexia in all 4 legs.
      • +/- neck pain
      • In severe lesions: hypoventilation.
    2. C6-T2 dysfunction
      These spinal cord segments contain the motor neurones that form the brachial plexus and innervate the thoracic limbs, provide the motor component of the panniculus reflex, and the sympathetic innervation to the head. Signs of dysfunction therefore include:
      • Normal mentation and cranial nerve examination.
      • Tetra- or ipsilateral hemiparesis/plegia.
      • Abnormal postural reactions ipsilateral to the lesion
      • Decreased or absent reflexes in the thoracic limbs and normal to hyper-reflexia in the pelvic limbs.
      • +/- complete absence of the panniculus reflex
      • +/- ipsilateral Horner's syndrome
      • +/- neck pain
      • In severe lesions: hypoventilation.
    3. T3-L3 dysfunction
      The thoracic limbs are spared and the pelvic limbs have UMN signs. With transverse myelopathies, the panniculus reflex may be absent caudal to the level of the lesion. Signs of dysfunction therefore include:
      • Normal mentation and cranial nerve examination.
      • Normal thoracic limbs. As a general rule, if a paraplegic animal is unable to wheelbarrow on its thoracic limbs, they are not normal, and the lesion is most likely cranial to T3.
      • Paraparesis/plegia.
      • Abnormal postural reactions in the pelvic limbs ipsilateral to the lesion
      • Normal to hyper-reflexia in the pelvic limbs.
      • UMN incontinence.
      • +/- absence of the panniculus reflex caudal to the level of the lesion
      • +/- back pain
      • In severe lesions, loss of deep pain perception to the pelvic limbs
    4. L4-S3 dysfunction
      The thoracic limbs are spared and the pelvic limbs have LMN signs. The motor neurones to the bladder and the anal sphincter are also impaired. Signs of dysfunction therefore include:
      • Normal mentation and cranial nerve examination.
      • Normal thoracic limbs.
      • Paraparesis/plegia. If the lesion is caudal to L6 the femoral nerve is spared and the animal should be able to stand and walk, even if its stance is plantigrade.
      • Abnormal postural reactions in the pelvic limbs ipsilateral to the lesion
      • Hypo- to areflexia in the pelvic limbs.
      • Paresis of the tail with decreased to absent tone.
      • LMN faecal and urinary incontinence with absence of the perineal reflex
      • +/- back pain
      • In severe lesions, loss of deep pain perception to the pelvic limbs
  3. Summarizing the signs
    Once the neurological examination is complete, an attempt should be made to fit the signs into one of the syndromes listed above using the flow chart on page 1. In general, signs should localize to one site unless there is a multifocal process occurring. When dealing with spinal lesions, we are referring to the spinal cord segments when we localize a lesion to for example, T3-L3. At the caudal end of the spine, the spinal cord segments do not overlie the respective vertebra. As a general rule, in the dog the spinal cord segments S1-3 lie over the 5th lumbar vertebra. Thus, if a lesion is localized to L7-S2 it is important to include the 3rd lumbar to the sacral vertebrae in radiographs.
Conclusion
If having difficulty in localizing the neurological signs in a patient, it is perfectly acceptable to perform repeat examinations at regular intervals: puzzling cases can become very obvious if re-evaluated 24 hours later. Once the signs have been localized to a specific area of the nervous system, the patient signalment, and history, and the progression of signs should be taken into account when developing a list of differential diagnoses.

Diagnostic Approach to Spinal Cord Disorders

Introduction
The spinal cord is protected from injury by the bones of the vertebrae and their associated soft tissues (i.e. the intervertebral discs and ligaments that allow the vertebral column to be mobile). Spinal cord disorders can result from disease of the spinal cord and meninges, the soft tissue structures of the vertebral column or the vertebrae. In order to diagnose spinal cord disorders it is therefore important to be able to evaluate all of these structures. A logical approach to diagnosing spinal cord disease is:
  1. Perform a careful neurological examination to localize the neurological signs. All subsequent findings will be correlated to the neurological signs and so this step is very important.
  2. Obtain a complete blood cell count (CBC), serum biochemistry panel and urinalysis.
  3. Take spinal radiographs under sedation. These can be used to identify abnormalities of the vertebrae, they are not useful for evaluating soft tissue structures. If no abnormality is identified, further diagnostics are needed under general anesthesia. These include:
    1. Cerebrospinal fluid (CSF) analysis: to diagnose inflammatory diseases and occasionally neoplastic diseases.
    2. Myelography: can be used to identify compression of the spinal cord.
    3. Computed tomography (CT) can be used to delineate vertebral lesions, to identify mineralized nuclear disc herniations (i.e. type I intervertebral disc disease) and to evaluate the lumbosacral region. CT will not identify spinal cord parenchymal lesions or type II disc herniations. It can be used in combination with myelography to assess the spinal cord further.
    4. Magnetic resonance imaging (MRI): this is the most sensitive test for evaluation of the spinal cord and will identify bone, soft tissue and intraparenchymal diseases. However, interpretation of spinal cord MRI is a specialized skill and it is easy to be misled because of the high sensitivity of this test.
The advantages and disadvantages of these imaging modalities are summarized below:

Imaging modality Advantages Disadvantages
Spinal radiographs
  • Readily available
  • Inexpensive
  • Non invasive
  • Doesn't require anesthesia
  • Useful for evaluating vertebrae
  • Does not evaluate soft tissues of vertebral column
Myelography
  • Available
  • Relatively inexpensive
  • Identifies compressive lesions
  • We have extensive experience at interpretation of myelograms
  • Can use to evaluate dynamic lesions
  • Invasive - may cause neurological deterioration and seizures
  • Does not evaluate spinal cord parenchyma
CT
  • Non invasive
  • Excellent bone detail
  • Sensitive test for mineralized disc herniations
  • Expense and availability
  • Does not evaluate spinal cord parenchyma
  • Does not identify soft tissue compressive lesions (e.g. type II disc herniations)
MRI
  • Extremely sensitive for all diseases
  • Non invasive
  • Expense and availability
  • Lack of experience at interpretation


Spinal radiographs
In order to obtain good quality spinal radiographs, it is usually necessary to sedate or anesthetize the patient. In some cases, sedation or anesthesia may be contra-indicated: for example a critically ill patient, or a patient with suspected unstable fractures or luxations in which the splinting effect of the spinal musculature plays a vital supportive role. As a general rule, any patient with suspected compressive spinal cord disease should be handled carefully when sedate, as there is less muscle tone and extension or flexion of the spine may exacerbate spinal cord compression or cause concussive injuries.

Lateral projections are usually obtained first. The animal should be supported with foam pads and sand bags to obtain good lateral views with no rotation. To obtain good images of the caudal cervical spine, the thoracic limbs may have to be pulled caudally so that the shoulder doesn't overly the area of interest. In some diseases it is always advisable to radiograph the entire spine, even in the face of focal signs, in view of the multifocal nature of the disease. These include discospondylitis, trauma and certain types of cancer (e.g. multiple myeloma). Multiple projections of the spine should be obtained to allow accurate interpretation (the divergent path of the X-ray beam prevents interpretation of the width of disc spaces at each end of the image.) Coned radiographs should be centered over certain problematic areas including the atlantoaxial junction, the caudal cervical spine, the thoracolumbar junction and the lumbosacral junction. Once it has been established that it is safe to turn the animal (in the case of trauma) from the lateral radiographs, the animal should be placed on its back and ventro-dorsal (VD) projections obtained. In cases that have potentially unstable fractures or luxations, a horizontal beam should be used to obtain this view to avoid moving the animal.

When interpreting spinal radiographs it is important to know the normal radiographic appearance. The normal dog or cat has 7 cervical, 13 thoracic, 7 lumbar and 3 fused sacral vertebrae. Much of the interpretation can be made from the lateral radiographs but ventro dorsal (VD) views are particularly important to evaluate the atlantoaxial and the lumbosacral junctions. VD views are also extremely important when evaluating cases with congenital malformations or fractures. Other parameters to evaluate include:
  • Width of the intervertebral disc space: each disc space should be compared with the disc spaces immediately cranial and caudal. A disc space is only considered to be narrowed if it is more narrow that both the cranial and caudal disc spaces.
  • Shape and opacity of the intervertebral foramen.
  • Integrity of the vertebral end plates: looking for lysis and proliferation indicative of infection.
  • Evidence of vertebral neoplasia in the form of lysis, sclerosis and distortion of bone outline.
  • Degenerative changes of the vertebrae (e.g. spondylosis deformans) or articular processes.
The radiographic characteristics of a variety of different disorders are given below.

Disorder Radiographic characteristics
Type I IVDD
  • Narrowed or wedged disc space
  • Dorsal displacement of mineralized nuclear disc material either within disc or into spinal canal
  • Opacification and change in shape of intervertebral foramen
  • Narrowing of articular facet space
  • Vacuum phenomenon (very rare)
Fracture/luxation
  • Lack of vertebral alignment in one or more planes
  • Change in shape of vertebral body
  • Fractures of dorsal spinous, articular and / or transverse processes.
Vertebral neoplasia
  • Lysis and/or sclerosis of the vertebra
  • Soft tissue mass around vertebral abnormality
  • May see widening/distortion of vertebral canal or intervertebral foramen.
Discospondylitis
  • Lysis and sclerosis of adjacent end plates
  • Disc space may be narrowed
Transitional vertebrae
  • Change in number of vertebrae
  • Absence of one transverse process or rib
Hemi and butterfly vertebrae
  • Short vertebral body
  • Butterfly appearance on VD view
Block vertebrae
  • Fusion of 2 vertebrae with no intervening disc space
Atlantoaxial subluxation
  • Absence or hypoplasia of dens
  • Lack of alignment of the atlas and axis
  • Increased space between the dorsal lamina of the atlas and the dorsal spinous process of the axis
Spinabifida
  • Double dorsal spinous process visible of VD view
Degenerative changes (may not be clinically significant)
  • Bridging spondylosis ventral and lateral to a disc space
  • Proliferative new bone formation around the articular facets
  • Mineralization of the nucleus.


Advanced imaging
Once it is clear that advanced imaging is necessary, it is sensible to refer the patient to a neurologist or neurosurgeon for those diagnostic tests to be performed. This is particularly important if surgery is likely to be necessary as it is common that individual surgeons like particular views in order to plan the surgery.

Conclusion
The two most important steps to take to diagnose a spinal disorder are localizing the neurological lesion accurately and taking good quality spinal radiographs. If a diagnosis is not established from the radiographs, advanced imaging modalities and CSF analysis are necessary. The invasive nature of myelography should not be underestimated, and it is preferable to perform an MRI or CT scan instead.


Background for Spinal Cord Diseases Case Presentations

Introduction
The spinal cord extends from the foramen magnum to the conus medullaris within the vertebral canal of the vertebral column. The vertebral column has the dual role of protecting the spinal cord from injury, and allowing movement of the spine. In order to facilitate movement, the vertebral column is composed of individual vertebrae that are linked by intervertebral discs and a complex system of ligaments and joints. This complicated anatomical arrangement predisposes the vertebral column to degenerative changes and makes it susceptible to traumatic injury. Therefore, unlike the brain, some of the most common spinal cord diseases are the result of disorders of the vertebral column itself.

Hansen type I intervertebral disc disease

Etiology and pathogenesis
  • This is a very common condition encountered primarily, but not exclusively in chondrodystrophoid dogs.
    • Dachshunds account for nearly 50% of cases
    • Other breeds such as the Pekingese, beagle, Shih Tzu, bassett hound and cocker spaniel are commonly affected
    • Large breed dogs such as the Labrador retriever, German shepherd dog, and Shar pei can also be affected
    • Cats suffer acute disc herniations rarely.
  • Chondroid degeneration of the intervertebral disc occurs with age.
  • The disc dehydrates and the nucleus pulposus is invaded by hyaline cartilage and becomes mineralized.
  • The degenerate disc loses its shock absorbing capacity, and the annulus fibrosus develops fissures and weakens.
  • Mineralized nuclear material acutely extrudes through the annulus to lie within the vertebral canal, causing both spinal cord compression and concussion.
  • The peak age for acute disc herniations is between 3 and 6 years
  • The most common sites of acute disc herniations in the cervical spine are C2/3 - C4/5, and in the thoracolumbar spine are T11/12 to L1/2. They can occur from C2/3 to C7/T1 and from T9/10 to L7/S1.
Clinical findings
  • Signs reflect the location of the disc herniation
  • In the thoracolumbar spine, signs progress from spinal pain, to ataxia and paraparesis, paraplegia and then loss of deep pain perception. Most affected dogs have UMN signs, and there is a panniculus cut off just caudal to the lesion. 10-15% of dogs have LMN signs reflecting a L3-L7 lesion.
  • In the cervical spine, the most common sign is severe neck pain, which is often associated with a nerve root signature (thoracic limb lameness and holding the thoracic limb in flexion). With more severe injuries the animal may be tetraparetic or tetraplegic.
  • The degree of dysfunction for thoracolumbar disc herniations is graded as follows:
    • Grade 1 - pain only
    • Grade 2 - conscious proprioceptive deficit, ataxia, paraparesis
    • Grade 3 - paraplegia
    • Grade 4 - paraplegia with urinary retention and overflow
    • Grade 5 - as for grade 4 and loss of deep pain perception
  • The degree of dysfunction for cervical disc herniations is assessed as pain only, tetraparesis, tetraplegia and tetraplegia with hypoventilation:
Diagnosis
  • The diagnosis is suspected from characteristic clinical signs in a dog of typical signalment for the disease.
  • Survey radiographs may be suggestive but are only accurate in identifying the exact location in only 50-60% of disc herniations.
  • Computed tomography (CT) identifies mineralized disc material safely, sensitively and quickly. However, if the disc material is not mineralized, it will not be visible on these images.
  • Alternative imaging modalities include myelography and MRI.
Treatment

Conservative treatment for both TL and cervical discs
  • Dogs should be strictly cage confined in a crate for a minimum of 2 weeks, taken out to urinate and defecate 3 - 4 times a day and at that time, passive range of motion exercises done on both legs. After 2 weeks, the amount of controlled exercise the dog can do when it is taken out can be slowly increased, with the dog on a leash and walking only.
  • If grade 4 or 5, methylprednisolone sodium succinate (MPSS) can be given (see spinal cord trauma for doses). This should only be used if the dog is seen within 8 hours of injury and has not been treated with NSAIDs or corticosteroids. The benefits in dogs are unknown and in people are small; side effects are potentially life threatening.
  • Pain can be managed with:
    • NSAIDs such as carprofen or etogesic (if MPSS has not been used).
    • Muscle relaxants e.g. diazepam or methacarbamol (helpful with neck pain). - Opiates such as torbugesic (can be given orally) or fentanyl.
    • Anti-inflammatory doses of corticosteroids (0.25 - 0.5mg/kg/day of prednisone) can be used in dogs with neck pain, but are not necessary for back pain, and should never use without cage confinement.
  • Regularly evaluate the dog for any deterioration in neurologic status, or lack of improvement over 2 weeks, both of which indicate treatment failure.
  • If improvement is seen after 2 weeks, this should be followed by a further 2 weeks rest, and a gradual increase in exercise between the fifth through eighth week.
Surgical treatment - Hemilaminectomy and fenestration for TL discs, ventral slot and fenestration for cervical discs
  • Surgery is the treatment of choice for any non-ambulatory dog
  • Ventral slot is treatment of choice for dogs with severe persistent neck pain.
  • Should be performed as soon as possible after the onset of neurological signs, especially in dogs with Grade 5 deficits where prognosis declines rapidly if surgery is not performed within 48 hours.
  • Specifically recommended for:
    • Paraplegic dogs (grade 4)
    • Paraplegic dogs with loss of deep pain perception (grade 5) for less than 48h
    • Deterioration or lack of response with non surgical therapy
    • Recurrence after previous treatment
  • Concurrent fenestration of discs T11/12 to L2/3 and C2/3 to C5/6 reduces the risk of a recurrence
  • Approximately 10% of dogs with grade 5 injuries will develop ascending myelomalacia: this disease is fatal.

Treatment Advantages Disadvantages
Conservative management
  • Inexpensive
  • No aesthesia/surgical risk
  • Can be done at home
  • Effective if mild signs
  • High chance of recurrence
  • Slower recovery
  • Extent of recovery may be limited
  • Not as effective as surgery in severe injuries
Surgical management
  • Effective
  • Decrease chance of recurrence
  • Cost
  • Surgical skill required
  • Risk of anesthesia and surgery


Prognosis for thoracolumbar disc herniations: expressed as % dogs recover

Neurological grade Conservative Hemilaminectomy
1 100 100
2 75-85 100
3 75-85 90-100
4 50 80-100
5 <10 50-60


Prognosis for cervical disc herniations
There are fewer numbers available for outcome of cervical disc herniations. In general, all dogs that have motor function should recover with surgery, although they may not be responsive to conservative management. Dogs that are tetraplegic with respiratory compromise (hypoventilation) have a guarded prognosis unless mechanical ventilation can be provided.

Wobbler syndrome

Etiology and pathogenesis
  • The term "wobbler" is loosely applied to dogs with degenerative changes in their cervical spine that result in compression of the spinal cord.
  • There are many names given to this syndrome including cervical stenotic myelopathy, caudal cervical spondylomyelopathy, and cervical malformation/malarticulation, reflecting its many different components.
  • It is thought of as a disease of large and giant breed dogs, with Doberman Pinschers the most commonly affected large breed, and Great Danes over-represented in the giant breeds.
  • There is also a population of small and toy breed dogs such as Yorkshire terriers, Pugs and Miniature Pinschers that have very similar changes in their cervical spine.
  • The pathological changes that are present include
    • vertebral malformation,
    • hypertrophy of the dorsal annulus with type II disc herniation,
    • hypertrophy of the dorsal longitudinal ligament and the ligamentum flavum,
    • degenerative joint disease of the articular facets
    • synovial cysts can also develop at the articular facets in association with the syndrome.
  • All of these changes cause compression of the cervical spinal cord that is typically worsened by extension of the neck.
Doberman Pinschers
  • The syndrome in Dobermans has been called disc-associated wobbler syndrome as compression of the caudal cervical spinal cord results from hypertrophy and protrusion of the dorsal annulus, and hypertrophy of the dorsal longitudinal and flaval ligaments.
  • This occurs in association with tipping of the vertebral body, stenosis of the cranial orifice of the neural canal and ventral spondylosis.
  • Signs usually occur in dogs greater than six years of age.
Great Danes
  • Giant breed dogs typically present when less than three years of age
  • Cord compression most commonly results from degenerative changes and malformation of the articular facets and their associated soft tissues.
General points
  • Heritability, nutrition and growth rate, body conformation and trauma have all been proposed as causes of wobbler syndrome but no single cause has been identified and etiology probably varies between breeds.
  • The proliferative and progressive nature of the degenerative processes that occur suggest that instability of the cervical spine plays a central role in the syndrome.
Clinical findings
  • Progressive tetraparesis and ataxia. Sudden deterioration can occur.
  • Neck pain may be present, particularly in caudal cervical lesions. It is less common in giant breed dogs.
  • Signs may localize to C1-5 or C6-T2. In dogs with C6-T2 signs, there is often a short choppy gait in the thoracic limbs, and atrophy of the supraspinatous and infraspinatous muscles.
Diagnosis
  • Diagnosis is suggested by the clinical findings.
  • Survey radiographs may show degenerative changes but are NOT diagnostic for this disease.
  • Myelography (in combination with CT) or MRI are used to identify the sites of spinal cord compression.
Treatment
  • Conservative management consists of controlled exercise, low dose of anti-inflammatory drugs and physical therapy.
  • It is appropriate if mild signs are present
  • There is little information on the efficacy of this approach and if signs progress in spite of treatment, surgery should be considered.
  • Surgical management of wobbler syndrome is typically undertaken in dogs with moderate to severe neurological deficits.
  • The aim of surgery is to decompress the spinal cord and, in many cases, to stabilize the affected vertebrae.
  • Traditional workup with myelography +/- computed tomographic scanning enables the surgeon to identify and describe the lesion(s), and to determine whether the lesion is dynamic (distraction results in decompression of the spinal cord) or static.
  • Static lesions causing ventral compression of the spinal cord are typically treated with a ventral slot.
  • Dynamic ventral and dorsal lesions are treated by distraction and fusion of the vertebrae.
  • Dorsolateral spinal cord compression or multilevel lesions are typically treated by a dorsal laminectomy.
  • We have recently treated dorsolateral compression by fusion with good success.
  • No matter which surgical technique is used, most current studies report short-term success rates of 80-90%.
  • Long-term success rates are not as good and are difficult to compare between studies on different surgical techniques due to differences in follow-up.
Degenerative lumbosacral disease

Etiology and pathogenesis
  • Degenerative lumbosacral (LS) disease is the term used to describe compression of the nerve roots of the cauda equina at the level of the LS junction as a result of degenerative changes.
  • Common changes present include disc protrusion, new bone formation around the LS foraminae, hypertrophy of the synovial membranes of the articular facets with degenerative joint disease of the facets, and instability.
  • Any or all of these processes can be present.
Clinical findings
  • Classic signs displayed by dogs with LS disease in the early phases include difficulty rising or jumping up onto things, a stiff stilted pelvic limb gait that can be associated with lameness and therefore be confused with orthopedic disease, and LS pain (this is probably the most reliable sign of LS disease).
  • As the disease progresses the owners note that tail carriage changes (you usually need to ask owners about this specifically), pelvic limb CP deficits and ataxia may develop along with muscle atrophy and eventually fecal and urinary incontinence.
  • As neurological signs may not be evident early in the course of the disease, LS disease is probably much more common in older large breed dogs than realized.
Diagnosis
  • Clinical signs are suggestive of the disease
  • Survey radiographs of the area usually show degenerative changes such as spondylosis but cannot be used to definitively diagnose the condition
  • Diagnosis is made by computed tomographic (CT) or magnetic resonance (MR) imaging of the LS region,
  • Epidurography can be used but has largely been replaced by CT and MRI
  • Imaging findings must be supported by clinical evidence of disease, as some animals can appear to have severe compression of nerve roots on images but have no associated signs.
Treatment
  • Treatment is surgical or conservative although little is known about the success of conservative management.
  • Conservative management includes pain control with anti-inflammatory drugs and muscle relaxants, and controlled exercise on flat surfaces.
  • Surgical decompression and sometimes stabilization is achieved by performing a dorsal laminectomy and fenestrating the LS disc.
  • Surgical outcomes are good in dogs with pain and mild neurological deficits but the prognosis is worse if incontinence is present.
Atlantoaxial (AA) subluxation

Etiology and pathogenesis
  • May be congenital or acquired secondary to trauma.
  • Most common congenital cause is absence or hypoplasia of the odontoid process (dens), which is seen in younger toy or miniature breed dogs.
Clinical findings in congenital cases
  • Onset of signs usually occurs in the first year of life but may occur in much older dogs.
  • Clinical signs vary from cervical pain to tetraplegia with hypoventilation and death.
  • Many dogs do not appear to be painful.
  • Signs may be acute in onset, slowly progressive or wax and wane.
Diagnosis
  • Diagnosis is established from survey radiographs.
  • We usually perform them with the animal awake to lessen the likelihood of further movement of the axis.
  • Lateral views will show lack of alignment of the axis and atlas, and an increased space between the dorsal lamina of the atlas and the dorsal spinous process of the axis.
  • Hypoplasia or aplasia of the dens is seen on VD radiographs.
  • If the lateral views look normal, but the VD views show absence of the dens, careful flexion under fluoroscopy can be performed to determine whether the junction is unstable.
Treatment
  • Conservative therapy involves placing an external splint for 6 weeks to immobilize the AA junction to allow healing of the soft tissues around the junction.
  • This often improves dogs in the short term but may not provide a long term solution.
  • It is not appropriate in dogs with severe compression and neurological signs.
  • Surgical stabilization provides a more definitive long term solution but is associated with a high mortality rate in the perioperative period.
Vertebral and spinal neoplasia

Etiology and pathogenesis
  • Approximately 50% of spinal tumors in dogs are extradural sarcomas (e.g. osteosarcoma, fibrosarcoma, hemangiosarcoma, lymphosarcoma)
  • Intradural-extramedullary tumors (nerve root tumors, meningiomas) account for 35% of canine spinal tumors
  • The remaining 15% of spinal tumors in dogs are intramedullary. (lymphosarcoma, gliomas, nephroblastomas)
  • The most common spinal tumor in cats is extradural lymphosarcoma.
Clinical findings
  • Tumors cause chronic progressive neurologic deficits related to their location, but clinical course can vary considerably.
  • There is usually focal spinal pain in all but intramedullary tumors.
Diagnosis
  • Survey radiographs identify tumors that affect the vertebrae.
  • Myelography or MRI is necessary if no boney changes are seen.
Treatment
  • Treatment options include surgical debulking, radiation or palliation with corticosteroids.
  • Meningiomas are treated most effectively by surgical removal followed by radiation: survivals of up to 30 months may be achieved.
  • Sarcomas carry a poor prognosis even with radiation and surgery. Palliative radiation can really decrease pain, and anti-inflammatory doses of a corticosteroid may reduce peritumoral edema and improve neurological signs transiently.


A Review of the Diagnostic Approach and Treatment of Brain Diseases

The Neurological Examination and Lesion Localization in the Brain

Definitions
It is important to use the correct terms when describing neurological signs.

Term Meaning
'Paresis (mono-, hemi-, para- and tetra-) Motor weakness of one limb, ipsilateral thoracic and pelvic limb, both pelvic limbs and all 4 limbs
'Plegia (mono-, hemi-, para- and tetra-) Complete absence of motor function
Ataxia. (subclassified as sensory, cerebellar and vestibular) Loss of coordination.
Dysmetria/ hypermetria Gait deficit seen in cerebellar disease: the length of a movement is misgauged, often causing a goose stepping (hypermetric) gait
Depression Decreased responses to normal stimuli
Stupor Only roused by strong/painful stimuli
Coma Cannot be roused
Dementia Inappropriate response to stimuli
Hyper/hypo/areflexia Increased/descreased/absent reflexes


As for spinal cord disease, an accurate history should be taken and a careful evaluation of the general physical health of the animal completed. The neurological examination should include
  1. Assessment of Mental Status and behavior.
    Remember that the owner does know the normal behavior of their pet and so be careful to listen to their observations.
  2. Posture and involuntary movements at rest.
    The presence of a heat tilt, a head turn, wide based stance, body lean, inability to bear weight, kyphosis or lordosis, tremors and myoclonus can be detected at this point.
  3. Gait.
    The animals gait is observed walking in a straight line, turning in circles and walking up and down steps if appropriate to detect sensory and motor deficits. If the animal is ataxic, it is useful to try to classify it as sensory (conscious proprioceptive deficits characterized by crossing the feet and scuffing the toes and due to compression of the long tracts), cerebellar (unconscious proprioceptive deficits characterized by movements of the wrong length causing dysmetria) or vestibular (characterized by a head tilt and body lean). Look for drifting to one side or circling.
  4. Postural Reactions.
    Postural reactions involve afferent and efferent pathways in the peripheral nerve, spinal cord, and brain. Therefore, while they are a sensitive indicator of neurologic dysfunction, postural reactions do not localize a lesion to one part of the nervous system. The main value of testing postural reactions is that they allow the detection of subtle deficiencies. Postural reaction deficits typically occur ipsilateral to peripheral nerve, spinal cord, and most brain stem lesions; cerebrocortical and thalamic lesions result in contralateral deficits. If an animal has severe orthopaedic disease, its weight must be supported adequately while performing the postural reactions. The postural reactions include conscious proprioception, hopping, placing (tactile and visual), wheelbarrowing, extensor postural thrust, and hemiwalking.
  5. Cranial Nerve Function.
    Cranial nerves I to XII can be evaluated by the tests listed in the table below. Testing each nerve allows the testing of different segments of the brain.

Cranial nerve, site of origination Function Signs of dysfunction Specific test
I Olfactory Telenphalon Olfaction Few apparent; loss of appetite in cats No good test: behavioral response to strong odours
II Optic Diencephalon Vision Blindness Menace response, obstacle course, PLR
III Oculomotor Mesencephalon Extraocular muscles & pupil constriction Ventrolateral strabismus and mydriasis PLR, physiologic nystagmus
IV Trochlear Mesencephalon Extraocular muscles Extremely rare as isolated deficit. Strabismus Physiologic nystagmus
V Trigeminal Metencephalon Sensory to face (ophthalmic, maxillary & mandibular branches), motor to masticatory muscles (mandibular) Facial hypalgesia or analgesia. Neurogenic KCS, atrophy of muscles of mastication, dropped jaw if bilateral involvement Palpebral and corneal reflex
Stimulation of nasal mucosa
Jaw tone and strength.
VI Abducent Myelencephalon Extraocular muscles Extremely rare as isolated deficit. Strabismus Corneal reflex: look for retraction of eyeball.
VII Facial Myelencephalon Motor to muscles of facial expression, taste and PS to lachrimal and salivary glands Drooping of one side of face, accumulation of food in affected cheek, KCS, widening of affected palpebral fissure Menace response and palpebral reflex.
Schirmer tear test
Nostril movements
VIII Vestibulocochlear Myelencephalon Balance and hearing Unresponsive to owner
Roused from sleep by touch only (Hearing)
Head tilt, nystagmus, ataxia, circling 		Hearing: brainstem auditory evoked response
Balance: characteristic signs. Can elicit nystagmus by placing the animal on its back.
IX Glossopharyngeal Myelencephalon Taste, PS to salivary glands and motor to the pharyngeal muscles Coughing after drinking, progressing to obvious difficulty swallowing, presence of excess saliva in pharynx Gag reflex
Observation of eating and drinking.
X Vagus Myelencephalon Motor to oesophagus and larynx, PS to contents of thoracic cavity and cranial abdomen. Inspiratory dyspnoea (stridor), regurgitation due to megaoesophagus, effects on heart and GI tract are rare (except in dysautonomia) Auscultation and observation of larynx.
Thoracic radiograph to identify megaoesohpagus.
Oculocardiac reflex.
XI Accessory spinal Myelencephalon Motor to the trapezius & parts of the sternocephalicus & brachiocephalicus. Very rare to note any signs. Theoretically atrophy of the innervated muscles None
XII Hypoglossal Myelencephalon Motor to the tongue Difficulty prehending food, tongue hanging out of the mouth, drooling Visual inspection of the tongue.


Neurolocalization

1. Forebrain dysfunction
The forebrain consists of the cerebrum and limbic system (the telencephalon) and the hypothalamus and thalamus (the diencephalon).

The telencephalon
Integration of sensory information (visual, auditory, tactile etc) from the contralateral side of the body occurs in the cerebrum and results in a behavioral response, thus both behavior and perception originate in the forebrain. Forebrain dysfunction can therefore result in loss of sensory information about the contralateral side of the body (hemi-neglect syndrome). A relatively unimportant motor tract, the corticospinal tract, projects from the cortex to flexor muscles, but the motor cortex can be removed with only minor effect on postural reactions and no effect on gait. A summary of signs that can be present includes:
  • Abnormal mentation
  • Behavioral changes often manifested as loss of learned behaviour
  • Circling towards the side of the lesion
  • Contralateral menace deficits with intact pupillary light reflex
  • Contralateral facial hypalgesia
  • Compulsive pacing, head pressing, circling
  • Normal gait but contralateral postural reaction deficits
  • Normal spinal reflexes
  • Seizures
The diencephalon
The thalamus is a mass of grey matter in which most if not all tracts projecting to and from the cerebrum synapse. The close connections with the cerebrum result in many of the same signs as seen with telencephalic lesions. A thalamic pain syndrome in which animals exhibit generalised pain has been described with thalamic lesions. The hypothalamus plays an important role in maintaining homeostasis by regulating thirst, appetite and temperature, and by its projection to the pituitary. The sympathetic nervous system also originates here. The optic nerve originates in the diencephalon and the chiasm lies just in front of the pituitary. Signs that can be present with diencephalic lesions in addition to the signs listed above include:
  • Abnormal thirst and appetite
  • Signs of endocrine disorders (e.g. PUPD, hair loss)
  • Menace deficit with fixed dilated pupil
  • Abnormal temperature regulation
2. The brainstem dysfunction
The brainstem includes the midbrain (mesencephalon), pons (metencephalon) and medulla (myelencephalon). Most of the cranial nerves originate from nuclei within the brainstem (see cranial nerve exam table) and so testing of the cranial nerves can help to localize lesions. The vestibular nuclei in the medulla seem particularly prone to dysfunction producing easily detectable signs of vestibular disease (see vestibular syndrome). The important motor tracts all originate in and project through the brainstem. These include the rubrospinal tact originating from the red nucleus in the midbrain and important in producing flexion (and hence movement), the vestibulospinal tracts originating in the medulla and projecting to extensors (so maintaining posture) and the reticulospinal tracts (originating in the pons and medulla and also important in extensor tone). These tracts, along with the sensory tracts projecting from the spinal cord, are often referred to collectively as the "long tracts". Compression of the long tracts results in ipsilateral hemiparesis, and postural reaction deficits. The brainstem also contains the reticular activating system (RAS), projecting from the medulla, through the pons and midbrain to the thalamus, responsible for maintaining consciousness. Finally, the vasomotor center and centers that regulate respiration also reside in the pons and medulla. Brain stem dysfunction therefore causes:
  • Cranial nerve deficits reflective of the site of the lesion
  • Ipsilateral hemiparesis or tetraparesis
  • Ipsilateral postural reaction deficits
  • Normal to increased spinal reflexes
  • Changes in consciousness
  • Changes in respiratory pattern
  • Changes in heart rate, rhythm and blood pressure
In general cranial nerve deficits and paresis are present initially, and as signs become more severe, changes in conscious ness occur. Changes In heart rate and rhythm and respiratory patterns tend only to occur in stuperous/comatose animals.

3. Vestibular syndromes
The vestibular system controls balance, helps to maintain posture against gravity, and controls eye movements relative to head movements. Lesions of the vestibular system can occur peripherally affecting the inner ear, or the vestibulocochlear nerve as it passes through the middle ear, or centrally within the brainstem. Paradoxical vestibular syndrome refers to vestibular signs due to cerebellar dysfunction. In general signs of vestibular disease include:
  • Head tilt to the side of the lesion
  • Ataxia with a body lean and increased extensor tone contralateral to the lesion
  • Circling to the side of the lesion
  • Falling and rolling to the side of the lesion
  • Nausea
  • Spontaneous nystagmus
  • Loss of physiologic nystagmus
  • Ventral strabismus in the eye ipsilateral to the lesion (usually evident when the head is elevated)
Central and peripheral disease can be distinguished by looking for other signs of brainstem disease (i.e. hemiparesis with postural reaction deficits, changes in consciousness, multiple cranial nerve deficits), and at the direction of nystagmus: vertical nystagmus is unique to central vestibular disease, while rotary and horizontal nystagmus can occur with either central or peripheral disease. Disease in the middle ear can affect the sympathetic supply to the head and the facial nerve and so concurrent ipsilateral facial paresis, vestibular signs and Horner's syndrome are strongly suggestive of a middle ear disease. If animals are severely affected it may not be possible to assess postural reactions accurately and repeat examinations are vital. It is also important to note that extra-axial diseases can affect the cranial nerves as they exit the brain prior to producing brain stem compression and obvious signs of central vestibular disease. In paradoxical vestibular syndrome, there are signs of central vestibular disease, however, postural reaction deficits should appear to be cerebellar (i.e. dysmetria and slow initiation of movements) and the head tilt is to the contralateral side. Other signs of cerebellar dysfunction may be present (see below).

4. Cerebellar Dysfunction
The cerebellum modulates the range, rate and force of movements producing the smooth sophisticated movements to which we are accustomed. The cerebellum is also intimately associated with the vestibular system and appears to influence the menace response. Cerebellar lesions can therefore produce a variety of signs including:
  • Normal mentation
  • Dysmetric movements with normal strength
  • Wide based stance
  • Abnormal postural reactions characterized by delayed responses and dysmetric movements, but normal conscious proprioception
  • Truncal sway (a form of dysmetria of the trunk)
  • Intention tremor
  • Menace deficit with normal vision.
  • Paradoxical vestibular signs (see above)
  • Rarely: anisocoria
  • Severe lesions may cause extension of the thoracic limbs with opisthotonus and flexion of the pelvic limbs.

Diagnostic Approach to Brain Disorders
Introduction
The brain is protected from injury by the skull but although there are some disorders that are caused by the skull (e.g. some cancers, Chiari malformations, skull fractures), most of the disorders we see in small animal medicine relate to the brain. In order to definitively diagnose brain diseases advanced imaging of the brain is usually necessary; skull radiographs tend not to be useful. However, because systemic diseases and inappropriate blood supply can cause brain dysfunction, blood work and measurement of blood pressure are an important part of the diagnostic workup. It is also important to appreciate that the retina is in direct communication with the brain and therefore and fundic examination to look for evidence of hypertension or inflammatory disease should be performed.

The first step in diagnosing a brain disorder is to take a good history and complete a physical and neurological examination. The owner can often provide the best assessment of the animal's behavior and level of consciousness and should be questioned carefully about this. If they report seizures, a careful seizure history should be taken. When performing the neurological examination, it is important to differentiate between focal, diffuse and mutlifocal signs. Focal signs are caused by disease such as brain tumors, whereas metabolic diseases cause diffuse cerebral signs. Encephalitis is more likely to cause multifocal signs. Having localized the neurological signs, and identified any other health problems, the work up is relatively straight forward:
  1. Complete blood work and urinalysis
  2. Blood pressure measurement and fundic examination
  3. Bile acid tolerance test: important if liver disease is suspected and in any animal with seizures.
  4. Imaging of the brain with CT or MRI, US is useful in toy breeds with suspected hydrocephalus.
  5. CSF analysis if the brain imaging is not diagnostic. The CSF sample is typically obtained after imaging in order to avoid sampling animals that have large intracranial masses that could herniate during the procedure.
  6. +/- lead level, endocrine testing, titers for infectious diseases.
  7. Take thoracic radiographs under sedation prior to advanced imaging in older animals to rule out metastatic neoplasia.
    The advantages and disadvantages of CT and MRI are summarized below:

Imaging modality Advantages Disadvantages
CT
  • Non invasive
  • Excellent bone detail
  • Tends to identify treatable lesions
  • Expense and availability
  • Expense and availability
  • Does not identify non hemorrhagic strokes, metabolic disorders, some brain tumors.
  • Artifact makes evaluation of brainstem difficult
MRI
  • Extremely sensitive for all diseases
  • Non invasive
  • Expense and availability


Cerebrospinal fluid (CSF) analysis
CSF is taken under general anesthesia from the cerebellomedullary and/or lumbar cistern. It is relatively straightforward to obtain a diagnostic CSF sample from the cerebellomedullary cistern. However, the CSF obtained at this site is more reflective of intracranial disease processes than spinal cord diseases (because of the direction of flow of CSF). In contrast, although a lumbar sample is desirable to evaluate spinal cord disease, it is technically more difficult to obtain a sample without blood contamination from the lumbar cistern (usually the sample is taken from the L5/6 interspace). We therefore take a sample from both sites. A CSF sample should always be obtained before performing myelography.

The concentration of protein and the cell count and cytology are determined from the CSF sample. It is important to evaluate the CSF in as short a time as possible, because the cells rapidly deteriorate. Typical CSF changes are listed below:

Disease process Protein concentration Cell count Cytology
Normal CSF
Cisternal
Lumbar 		25mg/dl
45mg/dl 		0-5cells/ul
0-3cells/ul 		Mononuclear cells
Infectious/inflammatory Increased Increased + to +++ Depends on disease
Vascular Increased +++ Normal to increased + Neutrophilic pleocytosis +/- erythrophagia
Neoplasia Increased + to ++ Normal or increased (meningiomas or lymphoma) May see lymphoblasts if lymphoma
Chronic compression Increased + to ++ Normal or mild increase Normal or mixed pleocytosis
Acute injury (trauma, IVDD) Increased + to ++ Normal to moderate increase Normal or mixed pleocytosis



Background Notes for Brain Disease Case Discussions
Brain tumors

Etiology and pathogenesis
  • Meningiomas are the most common brain tumors in dogs and cats. They arise from the arachnoid mater and compress the brain as they grow.
  • Choroid plexus papillomas and gliomas account for most of the remaining tumors.
  • More unusual brain tumors include olfactory nerve ensheathing tumors, medulloblastomas, microgiomatosis, granular cell tumors, suprasellar germ cell tumors, neuroblastomas, lymphoma and metastatic tumors.
Clinical signs
  • Brain tumors usually affect older dogs and cats, but can occur at young ages, particularly in breeds such as the boxer and in cats infected with feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV).
  • Signs reflect the location of the tumor. Tumors arise in the forebrain more often than in the brainstem and cerebellum.
  • Seizures is the most common presenting sign.
Diagnosis
  • Diagnosis is by imaging the brain with MRI or CT.
  • Biopsy provides a definitive diagnosis of tumor type and grade.
Treatment
  • Treatment options include surgical removal, radiation, chemotherapy and symptomatic treatment.
  • Surgical removal is a good option for meningiomas in the forebrain and can even be curative in cats. Surgical removal followed by radiation is the treatment of choice for meningiomas in dogs and can achieve median survivals of over 1 - 2 years (depending on the study you read). [Note: median survival reflects the point at which 50% of the animals are alive].
  • Radiation involves administering multiple doses of radiation over 3- 4 weeks. At NCSU we administer 16 doses of 3 Gy over 3 weeks. This is the treatment of choice for intra-axial tumors such as gliomas and if all tumors are considered together, median survivals of just under a year are reported.
  • Chemotherapy involves administration of CCNU (lomustine) as this penetrates the CNS parenchyma well. It is indicated for gliomas although we know little about efficacy. At NCSU we administer CCNU at a dose rate of 70mg/m2 every 3 weeks while monitoring hepatic and bone marrow function. Irreversible hepatic and bone marrow dysfunction can occur and so the drug should be discontinued once there are persistent changes in blood work.
  • Symptomatic therapy includes administration of anti-epilepetic drugs if there are seizures (this should be done no matter what therapy is chosen) and prednisone at anti-inflammatory doses to target peritumoral edema. It is important to understand that these therapies do not target the tumor and are purely palliative.
  • Further information on brain tumors is available at http://www.cvm.ncsu.edu/docs/brain_tumor.html
Granulomatous meningoencephalitis

Etiology and pathogenesis
  • This is an inflammatory disorder of unknown origin.
  • An autoimmune cause is suspected and treatment is by immunosuppression.
Clinical signs
  • This disease can affect any dog, but is most common in young adult small breed dogs. Females are over-represented.
  • Three different forms are recognized:
    • Ocular form, causing optic neuritis and blindness
    • Focal form: the animal presents with focal CNS signs and a single lesion is seen on imaging studies.
    • Diffuse form: the clinical signs reflect multifocal involvement.
    Diagnosis
    • Diagnosis is by demonstration of inflammatory CSF (typically a mononuclear pleocytosis) and ruling out infectious causes.
    • Focal or multifocal edema and contrast enhancing lesions may be present on CT or MRI images of the brain.
    Treatment
    • Once infectious causes have been rules out, the animal is immunosuppressed usually with 1-2mg/kg of prednisone q12h for 2 weeks. If the animal responds, the prednisone is then tapered monthly.
    • If the animal still fails to respond, or the signs recur other immunomodulatory drugs can be added in. At North Carolina we use CCNU (50-60mg/m2 q4 weeks) or cyclosporine. Cytarabine and procarbazine have also been advocated. All of these drugs require careful monitoring.
    • Prognosis is extremely variable. Prognosis as reported in the literature is poor. However, as the definitive diagnosis is only established post mortem, all published cases have by definition already died. In practice, neurologists see a large number of cases of encephalitis that respond well to immunosuppression.
    Necrotizing encephalitis

    Etiology and pathogenesis
    • This group of diseases was first recognized in the pug (pug dog encephalitis).
    • Similar diseases have now been recognized in other breeds such as the Maltese terrier and the Yorkshire terrier.
    • The etiology is unknown.
    • Histologically there is necrosis associated with a mononuclear infiltrate of the cortex in particular the subcortical white matter.
    Clinical signs
    • This disease typically affects young adult dogs.
    • Dogs present with signs of cerebral disease including seizures, circling and behavioral changes.
    • Signs are usually progressive.
    Diagnosis
    • Imaging the brain with MRI or CT often shows the areas of necrosis.
    • CSF is usually mildly inflammatory characterized by mononuclear pleocytosis.
    • Infectious causes of encephalitis should be ruled out.
    Treatment
    • There is no specific treatment and prognosis is poor.
    • Seizures can be treated with anti epileptic drugs.
    • Corticosteroids are not beneficial.
    Chiari malformations

    Etiology and pathogenesis
    • This is a congenital malformation that is known to be inherited in Cavalier King Charles spaniels.
    • The occipital bone is hypoplastic decreasing the volume of the caudal fossa.
    • As a result, the cerebellum starts to herniated through the foramen magnum, and CSF flow through the foramen magnum becomes turbulent.
    • The turbulent CSF flow causes CSF accumulation within the cervical spinal cord (syringohydromyelia).
    Clinical findings
    • Onset of signs can occur at any time, but signs are usually evident within the first 2 years of age.
    • The most prominent sign is scratching at the neck or flank due to the syringohydromyelia. This may be induced by touching the area involved, or by exercise and excitement. The underlying skin is normal. With progression, weakness or dysmetria may appear.
    Diagnosis
    • The diagnosis should be strongly suspected from the clinical picture
    • Definitive diagnosis can only be made by performing an MRI of the brain.
    Treatment
    • Surgical decompression of the caudal fossa can be attempted and has mixed results.
    • Anti-inflammatory doses of prednisone help some dogs.
    • Gabapentin (used to target the parasthesia) can also be tried.
    • Some people advocate the use of furosemide. All of the above treatments have mixed results.
    Cerebellar infarcts

    Etiology and pathogenesis
    • This syndrome is being recognized with increasing regularity in dogs with the advent of MRI.
    • There is infarction of one of the cerebellar arteries
    • In some cases there is no predisposing cause, but many patients are hypertensive or have some other underlying disorder (e.g. renal disease).
    Clinical findings
    • Peracute onset of cerebellar signs, with concomitant paradoxical vestibular signs.
    • Sign may progress over the first 12 hours, but should start to improve within 24 - 48 hours.
    Diagnosis
    • This syndrome should be suspected in any case with peracute onset of focal signs.
    • MRI will identify the area of infarction.
    • A full evaluation of the animal should be completed to identify any underlying cause.
    Treatment
    • Underlying causes, including hypertension, should be treated.
    • The animal should be supported using the same principles as discussed in the brain trauma lecture.
    • Prognosis is guarded if the signs are very severe. However, this is often a self limiting disease and animals with less severe signs show a rapid and dramatic recovery.


    • © 2007 - Natasha Olby Vet. M.B. Ph.D. Diplomate ACVIM - All rights reserved