World Small Animal Veterinary Association World Congress Proceedings, 2005 (2025)

Seizures are a common problem in veterinary medicine. Their treatment can be made complicated by multiple factors in the decision making process. These factors include the signalment of the patient, the likely or confirmed aetiology of the seizures, how long the patient has been seizuring, how severe the seizures are, the drugs that are available to veterinary patients, the cost of the diagnosis and treatment options and the wishes of the owners.

Chronic seizure therapy is generally indicated for seizures that last more than 5 minutes, cluster seizures (for which there is no detectable inter-ictal period), or seizures that occur more frequently than once per month. Control of canine epilepsy is only possible in up to 70-80 % of cases on monotherapy. This therapy may improve if combination therapy is used. This treatment must be for initiated for the life of the animal. The most common anti-epileptic drugs (AEDs) used in veterinary medicine are phenobarbitone, primidone, diazepam, and potassium bromide. Other drugs found to be less useful include phenytoin and valproic acid. More recently, several human drugs, such as gabapentin, have been evaluated for seizure therapy in veterinary patients.

Phenobarbitone (PB)

Phenobarbitone is the drug used most commonly by veterinarians, as the drug of first choice for seizure control in dogs due to its low cost and approximately 80% success rate in controlling seizures in epileptic dogs.(3) This drug has been well documented to occasionally have fatal hepatotoxic effects in dogs as well as cause neutropenia. A good slow induction dosage of PB is 2-4 mg/kg/day divided BID or TID. If indicated, the dosage may be slowly increased to as much as 18-20 mg/kg divided BID or TID. Serum PB concentrations should be monitored to assess therapy. A PB serum concentration of 15-45 ug/ml should be achieved immediately prior to each subsequent dosage of medication. It will take 7 to 18 days to achieve a steady state serum concentration with sustained maintenance doses. If dosages of 4 mg/kg/day or higher are used to initiate PB therapy, some dogs will appear depressed, drowsy or ataxic for about one month. This effect then generally resolves, and much higher doses can be given without sedation occurring. Some dogs will be polyuric, polydipsic and polyphagic while receiving PB, especially at higher doses. The serum alkaline phosphatase (AP) and the serum alanine transaminase (ALT) will increase in many dogs maintained on the drug. At least once/year, a PB serum concentration, serum chemistry profile, and haematology should be done on any animal receiving PB maintenance therapy. Any dramatic change in results from one year to the next may signal potential toxicity. This is the drug of choice in cats with multiple seizure episodes. The dose advised is 1.5 to 2.5 mg/kg PO every 12 hours. Due to the formulation of this drug, it is often best to start with 7.5 mg twice daily, which can be increased in 7.5 mg increments as necessary. Polyphagia with weight gain is documented as a frequent side-effect of PB administration in cats. Hepatotoxicity has not been documented in cats on this drug, but cutaneous hypersensitivities and bone marrow suppression have.

Potassium bromide (KBr)

Potassium bromide is becoming the drug of first choice for the management of epilepsy in dogs since it is the only anticonvulsant known that has no hepatic toxicity and all the adverse effects of KBr are completely reversible once the drug is discontinued. KBr controls approximately 80% of the epileptic dogs it is used to treat and is often effective in dogs that fail PB therapy. When high dose KBr and low dose PB are used together, approximately 95% of epileptic dogs can be controlled.

The maintenance dosage of is 20-100 mg/kg/day (which can be divided BID to avoid GI upsets) to achieve serum concentration of 1-5 mg/ml measured just before the next dose is administered. It requires 2 to 3 weeks of therapy before bromide serum concentration will enter therapeutic range and close to 4 months before steady state values are approximated. If seizure control is needed more rapidly than this, a total oral loading dose of 400 to 600 mg/kg of potassium bromide can be given prior to instituting the maintenance dosage schedule divided qid over 4-5 days. By dividing the loading dose, excessive sedation may be avoided in case the dog is especially sensitive to the sedative effects of bromide. The loading dosage should be mixed well with food to avoid the induction of vomiting. Be sure to stress to owners that it is important to keep the salt content of the diet consistent to prevent marked serum concentration fluctuations of bromide.

The most common adverse effect of bromide therapy is polyphagia, and it is recognized in about 25% of the dogs on therapy necessitating changing to a low calorie diet such as canine R/D or W/D to prevent excessive weight gain. Polydipsia and polyuria are less common with KBr therapy than with PB therapy, but these adverse effects are sometimes recognized. Personality changes that can occur are; irritability leading to snapping at people or other animals, seeking constant attention from the owner, aimless pacing behavior, and most commonly, depressed mental level as a result of sedation. Clinical signs of bromide toxicity are sedation, incoordination, and in dogs, pelvic limb weakness and/or stiffness is observed, easily misdiagnosed as pelvic limb stiffness due to osteoarthritis, since specific neurologic deficits are absent. Bromide toxicity can be seen in dogs that have renal insufficiency because the halide ion is excreted by the kidneys. There has been an association made between the use of bromide in cats and the onset of a reversible respiratory disease.

Primidone

Primidone is metabolized in the liver to phenylethylmalonic acid (PEMA) and PB. Phenobarbital levels should be monitored in dogs on primidone as they correlate better with anticonvulsant efficacy than primidone levels. The same side-effects that phenobarbital create are seen with the use of primidone. The target therapeutic ranges are also the same. Primidone is advised for use in those patients who have proven refractory to phenobarbital although its efficacy has not been proven. Otherwise there is no evident advantage of primidone over the use of PB as a first choice AED. The conversion rate of primidone to PB is close to 4:1. Therefore the use of 250 mg of primidone equals the use of 60mg of PB. Conversion from primidone to PB should take place slowly (1/4 of the dose each month). In the dog, the use of this drug has resulted in progressive hepatic injury, which seems to be more common than that seen with PB.

Phenytoin

This drug has anticonvulsant properties but is not a sedative. However, it has not been shown to be an effective AED in the dog due to a failure in attaining therapeutic concentrations owing to its short half-life and poor absorption from the canine GI tract. The short half-life means that there has to be a high dosing frequency.

The use of phenytoin in combination with PB or primidone may lead to increased concentrations of epoxide metabolites, which could result in cholestatic hepatic injury. There are now slow-release preparations of phenytoin which need to be evaluated and may have some value in canine seizure control.

Diazepam

Tolerance to the anticonvulsant effects of diazepam develops in 1-2 weeks in the dog. It therefore has limited use in dogs. After prolonged treatment, abrupt withdrawal of diazepam can elicit seizure or signs of withdrawal (shakes, anorexia, weight loss). The half-life of diazepam in cats is nearly 20 hours, which is up-to 6 times longer than in dogs. The dose is 0.25 to 0.5 mg/kg PO every 8 to 12 hours, incrementing 1 to 2 mg at a time to avoid the CNS side-effects such as sedation. Unfortunately, the documentation of hepatotoxicosis as an adverse effect of the use of this drug in cats makes its use less frequent than phenobarbital. Acute hepatic necrosis has been seen as early as 5 days after initiation of the recommended doses of oral diazepam. Therefore, the evaluation of liver enzymes 5-7 days after the initiation of diazepam in cats is recommended.

Chorazepate

Tolerance seems to develop to this drug at a slower rate than with diazepam. Its use in dogs in conjunction with PB will increase the concentrations of PB. Start at 1mg/kg q12hrs orally and measure both PB and chlorazepate at 2 and 4 weeks. It has been useful for short-term breakthrough seizure control.

Gabapentin (Neurontin)

Gabapentin is a recent addition to the human anti-convulsant market, which has primarily been used as an adjunctive drug for humans with uncontrolled partial seizures with and without secondary generalization. Gabapentin is well absorbed from the duodenum in dogs with maximum blood levels reached in 1 hour after oral administration. The elimination half-life of gabapentin in dogs is 3-4 hours in dogs, meaning that it may be difficult to attain steady state levels in dogs even with tid dosing. The dose at present estimated to be necessary to achieve some effect in dogs is 30 to 60 mg/kg divided tid to qid. It may be that its use in dogs demands higher doses making its expense prohibitive.In dogs, gabapentin is metabolised in the liver, therefore liver function needs to be closely evaluated when dogs are on this treatment; it is excreted nearly 100% through the kidneys, with 60% being the unchanged parent drug. The author has used this drug with no deleterious effects, in addition to PB and KBr. In a study of 11 dogs, 45% demonstrated improved seizure control with success based upon a 50% reduction in seizure frequency. However, many dogs still exhibited multiple days on which there was cluster seizure activity. Forty-five percent (5/11) of the dogs in this study also demonstrated sedation and ataxia after the addition of this medication. The therapeutic range documented is 4-16 mg/L, however long term efficacy and toxicity trials with this drug have not been done in the dog.

Levetiracetam

Levetiracetam was approved in November 1999 as a human add-on therapy for the treatment of partial onset seizures, with or without generalisation, in adults. Studies show that levetiracetam displays potent protection in a broad range of animal models of chronic epilepsy. Levetiracetam is water-soluble, is not metabolized by the liver, is excreted by the kidneys and is free of significant drug-drug interactions. The dose range documented for dogs is estimated to be 5-25 mg/kg q 8-12hrs PO. Levetiracetam has been documented as the most well tolerated anti-epileptic drug in humans,with adverse reactions equal to that of placebo. Overall, this drug is proven to be a highly effective adjunctive therapy in humans to control seizures refractory to treatment. The author presently has 10 dogs on this medication in addition to PB and KBr with initial promising effects in 5 of them.

Zonisamide

Zonisamide has an estimated elimination half-life of 15 hours in dogs, and has been administered twice daily (2-4 mg/kg) in 12 refractory idiopathic epileptic dogs with 58% of dogs responding favourably, experiencing a mean reduction in seizures of 81.3%. Five of the twelve (42%) dogs actually had an increased seizure frequency and 50% of the dogs exhibited side-effects which included sedation, ataxia and vomiting.

Severe head trauma is associated with high mortality in human beings and animals.Although there is no standard of care for head trauma in human medicine, a series of guidelines have been developed centered around maintaining adequate cerebral perfusion (The Brain Trauma Foundation 2000). The appropriate therapy for head trauma patients remains controversial in veterinary medicine due to a lack of objective information on the treatment of dogs and cats with head injuries. Treatment of affected animals must be immediate if the animal is to recover to a level that is both functional and acceptable to the owner. Many dogs and cats can recover from severe brain injuries if systemic and neurological abnormalities that can be treated are identified early enough.

Primary Patient Assessment

As with all types of acute injury, the "ABCs" (airway, breathing, cardiovascular status) of emergency care are extremely important.

Initial physical assessment of the severely brain-injured patient focuses on imminently life threatening abnormalities. It is important not to focus initially on the patient's neurological status as many patients will be in a state of hypovolaemic shock following a head injury, which can exacerbate a depressed mentation. Hypovolemia and hypoxemia need to be recognised and addressed immediately. In addition, a minimum essential data-base includes a PCV, total protein level, a blood urea level, glucose and electrolyte levels as well as a urine specific gravity. Respiratory system dysfunction can be common after head injury. The most dramatic respiratory abnormality seen following head injury can be neurogenic pulmonary oedema (NPO). Neurogenic pulmonary oedema is usually self-limiting if the patient survives, and will resolve in a matter of hours to days, but can cause severe dyspnoea, tachypnea and hypoxemia. Hypoxemia exacerbates the development of secondary tissue damage. There is no clinical localising value to specific breathing patterns and these patterns may vary over time.

Secondary Patient Assessment

Once normovolemia and appropriate oxygenation and ventilation are established (see below), the patient should be thoroughly assessed for traumatic injuries. These include skull, vertebral and long bone fractures as well as splenic torsions and ruptured bladder and ureters. The neurological examination, cranial imaging and ICP measurement can then be considered.

Neurological Assessment

Neurological assessment should be repeated every 30 to 60 minutes in severely head injured patients to assess the patient for deterioration or to monitor the efficacy of any therapies administered. This requires an objective mechanism to 'score' the patient so that treatment decisions could be made logically.

The Modified Glasgow Coma Scoring System

In humans, traumatic brain injury is graded as mild, moderate or severe on the basis of an objective scoring system, the Glasgow coma scale (GCS). A modification of the GCS has been proposed for use in veterinary medicine (Table 1.). The scoring system enables grading of the initial neurological status and serial monitoring of the patient. Such a system can facilitate assessment of prognosis, which is crucial information for both the veterinarian and owner. The modified scoring system incorporates 3 categories of the examination (i.e., level of consciousness, motor activity, brainstem reflexes),which are assigned a score from 1 to 6 providing a total score of 3 to 18, with the best prognosis being the higher score.

Diagnostic Imaging

Imaging of the patient's head is often indicated, especially in those animals that fail to respond to aggressive medical therapy or deteriorate after initially responding to such therapy. Skull radiographs are unlikely to reveal clinically useful information about brain injury but may occasionally reveal evidence of calvarial fractures.

Computed tomography (CT) is the preferred modality for imaging the head in cases of severe head injury. Even patients with 'mild' head trauma can exhibit abnormalities on the CT scan and so the initial decision to image the patients head should not be based on the neurological examination alone. CT image acquisition time is faster and often less expensive than MRI and CT also demonstrates acute haemorrhage and bone detail better than MR. However, MR imaging has been shown to provide key information relevant to the prognosis based upon its ability to detect subtle parenchymal damage not evident on CT imaging.

Cervical spinal radiographs are also advised at the time of any skull imaging to rule out concurrent spinal lesions. As for spinal trauma, thoracic radiographs will help to evaluate for evidence of thoracic and cardiac trauma.

Intracranial Pressure Monitoring

Medical and surgical decisions based on ICP measurements rather than on gross neurologic findings have decreased morbidity and mortality in human head trauma victims. ICP monitoring is a standard procedure for human head trauma management but has only recently been investigated in dogs and cats. Unfortunately, the extremely high cost of the fibreoptic system is likely to limit its use in veterinary medicine, however other systems may become available to enable ICP monitoring to become an integral part of head trauma management in dogs and cats.

Urinary Tract Assessment

Urinary output should be monitored and if it is elevated (>2-3 mL/kg/hour) for at least 2 consecutive hours, the patient should be considered for possible central diabetes insipidus (DI), which may suggest severe damage to the hypothalamic area. Diagnosis is based upon the presence of high serum sodium as well as low urine sodium and low urine osmolality. However, polyuria due to fluid overload, hyperglycaemia, and therapeutic osmotic diuresis must be ruled out in the diagnosis of central DI. Oliguria (in the absence of hypovolemia), may indicate the syndrome of inappropriate antidiuretic hormone secretion, if it is accompanied by hyponatraemia and increased urine sodium; however hypotension, pain and even stress can cause a similar situation. The most important consideration in head injury is maintenance of cerebral perfusion by treatment of hypotension and elevated ICP. As well as ensuring adequate cerebral perfusion, head injury management is aimed at measures to prevent and limit the development of secondary nervous system damage, as in the case of spinal cord trauma.

A. MEDICAL THERAPY

1. Minimising increases in ICP

Simple precautions can be taken in positioning the animal with its head elevated at a 30^° angle from the horizontal to maximize arterial supply to and venous drainage from the brain. It is also important to ensure that there is no constrictive collar obstructing the jugular veins as this immediately elevates ICP.

2. Fluid therapy

The basic goal of fluid management of head trauma cases is to maintain a normovolaemic to slightly hypervolaemic state. There is no support for attempting to dehydrate the patient in an attempt to reduce cerebral oedema and this is now recognized to be deleterious to cerebral metabolism. In contrast immediate restoration of blood volume is imperative to ensure normotension and adequate CPP.

Initial resuscitation usually involves intravenous administration of hypertonic saline and or synthetic colloids. Use of these solutions allows rapid restoration of blood volume and pressure while limiting volume of fluid administered. In contrast, crystalloids will extravasate into the interstitium within an hour of administration and thus larger volumes are required for restoration of blood volume. As a result this could lead to exacerbation of oedema in head trauma patient. Hypertonic saline administration (4-5 ml/kg over 3-5 minutes) draws fluid from the interstitial and intracellular spaces into the intravascular space which improves blood pressure and cerebral blood pressure and flow, with a subsequent decrease in intracranial pressure. However, this should be avoided in presence of systemic dehydration or hypernatraemia and it should be noted that the effects of this fluid only last up to an hour. Colloid solutions, such as Dextran-70 or Hetastarch should be administered after hypertonic saline is used, to maintain the intravascular volume. Hypertonic solutions act to dehydrate the tissues, thus it is essential that crystalloid solutions are also administered after administration of HSS to ensure dehydration does not occur. The sole use of colloids will not prevent dehydration; in addition, the co-administration of hypertonic solutions and colloids are more effective at restoring blood volume than either alone.

3. Osmotic diuretics

Osmotic diuretics such as mannitol are very useful in the treatment of intracranial hypertension. Mannitol has an immediate plasma expanding effect that reduces blood viscosity, and increases cerebral blood flow and oxygen delivery. This results in vasoconstriction within a few minutes causing an almost immediate decrease in ICP. The better known osmotic effect of mannitol reverses the blood-brain osmotic gradient, thereby reducing extracellular fluid volume in both normal and damaged brain.

Mannitol should be administered as a bolus over a 15 -minute period, rather than as an infusion in order to obtain the plasma expanding effect; its effect on decreasing brain oedema takes approximately 15-30 minutes to establish and lasts between 2 and 5 hours. Administering doses of 0.25 g/kg appear equally effective in lowering ICP as doses as large as 1.0 g/kg, but may last a shorter time. Repeated administration of mannitol can cause an accompanying diuresis, which may result in volume contraction, intracellular dehydration and the concomitant risk of hypotension and ischaemia. It is therefore recommended that mannitol use is reserved for the critical patient (Glasgow coma score of < 8) or the deteriorating patient. There has been no clinical evidence to prove the theory that mannitol is contraindicated in the presence of intracranial haemorrhage. There is evidence that the combination of mannitol with frusemide (0.7 mg/kg) may lower ICP in a synergistic fashion, especially if frusemide is given first.

4. Arterial blood pressure support

Presence of arterial hypotension despite fluid resuscitation (see above) may require administration of vaso-active agents such as dopamine (2-10 µg/kg/min). Conversely, arterial hypertensive episodes ("Cushing's response") may be managed with calcium channel blockers such as amlodipine (0.625 to 1.25 mg/cat every 24 hours; 0.5 to 1.0 mg/kg in dogs every 24 hours). However, the author recommends treating the increased ICP aggressively before using drugs to assist blood pressure regulation.

5. Oxygenation and ventilation

Hyperoxygenation is recommended for most acutely brain-injured animals. Partial pressure of oxygen in the arterial blood (PaO₂) should be maintained as close to normal as possible (at or above 80 mm Hg). Supplemental oxygen should be administered initially via face-mask as oxygen cages are usually ineffective as constant monitoring of the patient does not allow for a closed system. As soon as possible, nasal oxygen catheters or transtracheal oxygen catheters should be used to supply a 40% inspired oxygen concentration with flow rates of 100 ml / kg / min and 50 ml / kg / min respectively. If the patient is in a coma, immediate intubation and ventilation may be needed if blood gas evaluations indicate. A tracheostomy tube may be warranted in some patients for assisted ventilation.

Hyperventilation has traditionally been known as a means of lowering abnormally high ICP through a hypocapnic cerebral vasoconstrictive effect. However, hyperventilation is a double-edged sword. Besides reducing the ICP, it induces potentially detrimental reductions in the cerebral circulations if the pCO₂ level is less than 30-35 mmHG. The major difficulty with hyperventilation is our present inability to monitor the presence and effects of ischaemia on the brain. It is important that animals do not hypoventilate, and such animals should be ventilated to maintain a PaCO₂ of 30-40mmHg. Aggressive hyperventilation can be used for short periods in deteriorating or critical animals.

6. Seizure prophylaxis

Although the role of prophylactic anticonvulsants in preventing post-traumatic epileptic disorders remains unclear, seizure activity greatly exacerbates intracranial hypertension in the head injury patient. For this reason, it is recommended to treat all seizure activity in these patients aggressively. As most cases need to be treated parenterally, phenobarbitone (2 mg/kg IM q 6-8hrs) is recommended. This can be continued for 3-6 months after the trauma and can then be slowly tapered off if there have been no further seizures. Phenobarbitone will have the additional benefit of reducing cerebral metabolic demands and therefore acts as a cerebral protectant.

7. Corticosteroids

Corticosteroids, known to be beneficial in brain oedema attributed to a tumour, have been studied extensively in head injury. Clinical trials in people have not shown a beneficial effect of corticosteroids, including MPSS, in the treatment of head injury. In addition, they have been associated with increased risks of infection, are immunosuppressive, cause hyperglycemia and other significant effects on metabolism.

8. Nutritional support

Nutritional support is essential in the management of the head injured patient. Such support has been shown to improve the neurological recovery as well as shorten the time to recovery. On a short-term basis, a nasogastric tube can be used to deliver peptide rich compounds; caution should be used when placing and maintaining these tubes as they may cause sneezing, which may elevate intracranial pressure. For medium to long-term management, pharyngostomy or oesophagostomy tubes should be used. If there is brain stem damage, a gastrostomy tube should be inserted, in case of poor oesophageal function. Care should be taken to avoid hyperglycaemia, which may promote cerebral acidosis in brain-damaged individuals. For details on the above procedures and on diet selection, the reader is directed to more comprehensive descriptions.

B. SURGICAL THERAPY

A description of the surgical techniques for intracranial surgery can be found elsewhere. Although it is rare that surgery is indicated in head injury cases, there are several specific abnormalities that can be associated with an episode of head trauma that may warrant the consideration of surgical treatment:

1. Acute Extra-axial Haematomas

Generous craniotomies are generally indicated once these abnormalities have been diagnosed with imaging. If the haematoma is due to a fracture across a venous sinus, there may be profuse bleeding associated with surgical intervention. The need for blood transfusions should be expected. Haematoma removal also risks the chance of bleeding from previously compressed vessels.

2. Calvarial Fractures

A skull fracture per se may or may not have significant implications for patient management. Skull fractures are typically differentiated based upon:

Pattern--depressed, comminuted, linear.

Location

Type--open, closed

A fracture is generally classed as depressed if the inner table of the bone is driven in, to a depth equivalent to the width of the skull. All but the most contaminated, comminuted and cosmetically deforming depressed fractures can be managed without operative intervention.

3. Acute Intraparenchymal Haematoma

In contrast to acute extra-axial haematomas, acute intraparenchymal clots may be conservatively managed, unless subacute enlargement of initially small intraparenchymal clots is identified with repeat MR scanning.

4. Haemorrhagic Parenchymal Contusions

Most haemorrhagic contusions do not require surgical management. The main indication for surgery with these types of lesions is limited to cerebellar contusions with compression of the 4^th ventricle and brain stem; surgery aims to reduce the potential for further compression and herniation, which can develop over the initial 24-48 hours.

5. Intracranial Hypertension (ICH)

Benefit can be found when decompressive procedures are carried out before irreversible bilateral papillary dilation has developed. Conversely, "prophylactic" decompressive surgery seems inappropriate before non-surgical management of elevated ICH has been carefully maximized.

Table 1. Modified Glasgow Coma Scale

Lumbosacral pain in dogs has multiple aetiologies. Pathological abnormalities of the lumbosacral region have been termed cauda equina syndrome, lumbosacral stenosis, degenerative lumbosacral stenosis, lumbosacral spondylopathy, spondylolisthesis, lumbosacral malformation-malarticulation, and lumbosacral disease. Lumbosacral disease is a collective term for a variety of pathological conditions that may include malformation, growth abnormalities, degeneration, compression, inflammation, infection, displacement and reduced vascular circulation. These conditions may involve the last lumbar vertebra, the sacrum, the lumbosacral disc, the soft tissue structures around the lumbosacral joint or the cauda equina and associated nerve roots. The most common cause of lumbosacral disease is degenerative lumbosacral stenosis. Lumbosacral instability, including dorsal dislocation of L7, has also been reported. Morphometric studies suggest that multilevel congenital or developmental stenosis of the lumbosacral canal may contribute to acquired lumbosacral stenosis in large-breed dogs. Other causes of acquired stenosis include discospondylitis, neoplasia, and traumatic fracture/luxation of L7-S1, sacrum, or the sacrococcygeal junction. Also, lumbosacral osteochondrosis, a developmental disturbance of the end plate of either the sacrum or L7 vertebra, with subsequent separation of an osteochondral flap, has been reported as a cause of lumbosacral stenosis in mature dogs

Diagnosis of this condition can be difficult especially when considering there may be a need to identify a surgically correctable lesion with a high degree of confidence.

Clinical Signs of Lumbosacral Disease

Lesions involving spinal cord segments L4-5 through S1-3 (+ coccygeal segments) or lumbosacral nerve roots that form the cauda equina (including femoral, obturator, sciatic, pudendal, pelvic, and coccygeal nerves) will result in a lumbosacral syndrome. The lumbosacral syndrome reflects various degrees of involvement of the pelvic limbs, bladder, anal sphincter, and tail. Clinical signs will range from flaccid weakness to paralysis of pelvic limbs and tail. Owners often note that affected dogs have difficulty rising or climbing stairs, and show signs of pain or stiffness during extensive physical activity. Clinical signs may include pain (the most commonly reported sign) during direct palpation (especially downward pressure) of the lumbosacral area or during lumbosacral hyperextension, unilateral or bilateral pelvic limb paresis or lameness, proprioceptive deficits, tail paresis, hypotonia of anal sphincter with faecal incontinence, and urinary incontinence. Patellar and withdrawal reflexes (as well as gastrocnemius and cranial tibial reflexes) may be depressed or absent in pelvic limbs, as may be perineal (anal) and bulbocavernosus (in male dogs) reflexes. Tone in pelvic limb muscles may be reduced or absent. After 1 to 2 weeks of clinical signs, segmental muscle atrophy due to denervation will be observed. "Segmental" refers to the particular spinal cord segment involved in the lesion (e.g., segmental atrophy may develop in the iliopsoas, quadriceps, and sartorius muscles following an injury to the L4-6 spinal cord segments). Pain perception in pelvic limbs, tail, and perineum may be reduced or absent. Pelvic limb postural reactions such as hopping and placing may be depressed. Thoracic limb function is unaffected. Normal micturition requires synchronized contraction of the urethral smooth muscle and relaxation of the urethral skeletal muscle. Urethral smooth muscle is supplied by pelvic (parasympathetic) and hypogastric (sympathetic) nerves; pelvic and hypogastric nerves form the pelvic plexus. The pudendal nerve innervates the urethral skeletal muscle. Lesions involving the pelvic nerves, sacral cord segments, or pathways to and from the brainstem will abolish the micturition reflex. Consequently, the bladder will distend with urine and eventually overflow. Lesions of the sacral segments will also result in loss of innervation to the skeletal muscle of the urethra. As a result of minimal urethral resistance, manual expression of the bladder is easy in such cases. Thus, animals with sacral cord lesions may suffer from continual overflow incontinence. The anal sphincter may be flaccid and dilated, resulting in faecal incontinence. Since the external anal sphincter is innervated by the pudendal nerve, which also originates in the sacral segments, the perineal (anal) reflex provides a good assessment of sacral spinal cord function.

In some animals with lumbosacral disc extrusion, one pelvic limb may be held in partial flexion or a repetitive "stamping" motion may be observed. These animals frequently show considerable pain on manipulation of the limb and lumbosacral spine. This combination of signs is termed "root signature" and is believed to be associated with nerve root compression or entrapment by a fragment of extruded disk material. The occurrence of exercise-induced pain in some affected dogs, termed neurogenic intermittent claudication, may be related to dilatation of radicular vessels and subsequent compression of adjacent nerve roots in a stenotic region, e.g., intervertebral foramen or lateral recess of the caudal L7 vertebral foramen narrowed by a degenerative process.

Survey radiography

On plain films, indirect evidence of degenerative lumbosacral stenosis includes spondylosis deformans, disk space narrowing, and end-plate sclerosis. None of these abnormalities are specific however, and they occur in clinically normal dogs. There may be evidence of lumbosacral fracture/luxation, osseous neoplasia, intradiscal osteomyelitis associated with discospondylitis, or congenital lumbosacral stenosis. However, the greatest limitation of survey radiography is the inability to assess compression of neural tissue. Survey radiographs need to be performed with the animal deeply sedated or under general anaesthesia, properly positioned and preferably with an empty colon.

In one study, over 30% of German Shepherds with clinical signs of cauda equina compression had radiographic abnormalities compatible with osteochondrosis of the sacral end plate. In another study, transitional vertebrae were found in nearly 40% of German Shepherds with degenerative lumbosacral stenosis and in 11% without.

In dogs with lumbosacral osteochondrosis, a radiolucent defect occurs in the dorsal aspect of the affected end-plate along with one or more bone fragments in the vertebral canal and lipping, angling, and sclerosis of the dorsal part of the end-plates. Stress radiography, such as dynamic flexion/extension studies, may accentuate the lumbosacral instability. One study evaluated the LS angle and degree of subluxation of the sacrum in relation to L7 as seen on survey radiographs in 52 normal dogs and 32 normal dogs with LS spondylosis (of which 24 had neurological deficits). The conclusion was that such measurements were not helpful in the diagnosis of this disease.

Contrast-Enhanced radiography

Epidurography and discography may provide useful information. In one study, combined survey radiography and discography-epidurography were correctly positive in 16 of 18 dogs (89%). Alone, epidurography has been reported to be diagnostic in 78%-93% of dogs confirmed surgically. It is easier to perform than myelography and has less morbidity. The disadvantage is that filling of the epidural space may be incomplete because this space is poorly defined, contains fat and has multiple lateral openings. Flexed and extended views of the LS joint during epidurography may accentuate a compressive lesion. Concomitant filling of the vertebral venous sinuses or the paravertebral venous system may occur in normal dogs but is more common in those with LS disease.

Myelography has limited value in the evaluation of the cauda equina because the dural sac is elevated from the vertebral canal floor and often ends before the lumbosacral junction; It has been reported that 85% of normal dogs and 80% of dogs with degenerative lumbosacral stenosis had a dural sac that ended at the level of the sacrum and that myelography with the LS joint in neutral, flexed and extended positions was successful in the diagnosis of LS disease. In another study, 77% of 30 dogs had a dural sac that ended within the sacrum. Myelography allows evaluation of the spinal cord cranial to the LS region and thus may help to rule out other diseases.

Myelography performed at the cerebellomedullary cistern produces less local artifact than does lumbar injection; lumbar myelography can be non-diagnostic when there is epidural leakage.

Computed Tomography

Computed tomography and MRI are probably the diagnostic procedures of choice although findings of similar CT changes (but not vertebral subluxation) in the lumbosacral spine of older dogs without clinical disease may complicate diagnosis. Dorsal and sagittal images can be reformatted from the transverse ones. CT is accurate and allows evaluation of structures that cannot be visualised completely with conventional radiography such as the lateral recesses, intervertebral foramen and articular processes. It provides bone detail superior to that seen with MRI and soft tissue contrast superior to that of conventional radiography. It allows visualisation of individual nerve roots because of the contrast provided by the epidural fat. Disadvantages of CT are the use of ionising radiation and the cost and limited availability of this procedure.

In a study evaluating canine lumbosacral stenosis using intravenous contrast- enhanced CT, the positive predictive values for compressive soft tissues involving the dorsal canal, ventral canal and lateral recesses were 83%, 100%, and 81% respectively. A gas-filled lumbosacral disk space (vacuum disk phenomenon) along with smaller gas bubbles in between the degenerated L5-L6 dorsal articular facets (vacuum facet phenomenon) has also been revealed by CT in a 7 year old Rottweiler with cauda equina syndrome. A diagnostic role for CT densitometry awaits further studies.

MRI

MRI can clearly reveal soft tissue, such as cauda equina, epidural fat, and intervertebral disk, at the lumbosacral region without use of contrast medium. MRI is also considered to give better information about the condition of the intervertebral disc (e.g., the hydration status of the nucleus pulposus) in dogs with degenerative lumbar spine diseases, than radiography OR CT. However, no correlation was found between severity of the clinical signs and the severity of cauda equina compression as assessed by MRI in one study. In humans, it has been proposed that MR imaging can lead to overdiagnosis of disc disease because many people without back pain have disc bulges or protrusions on MR imaging. As MR imaging is used more frequently now in veterinary medicine, inconsistency between disc abnormalities and clinical signs must be considered, and the diagnosis should always be based upon clinical acumen in addition to the imaging.

Electrophysiology

Electromyographic (EMG) studies can demonstrate fibrillation potentials in lumbosacral paraspinal muscles, pelvic limbs, coccygeal muscles, and anal sphincter; as such this procedure can help confirm neurological disease as well as mapping out denervation. One study found that EMG was accurate in predicting the presence or absence of cauda equina compression in all cases. Another study found that some dogs with LS disease (particularly those presented with only pain) had normal findings on EMG, however. Dogs with mild disease can have a largely neurapraxic lesion that does not produce denervation.

Exploratory Surgery

In those cases where results of ancillary aids are equivocal, exploratory surgery may be the only means available for definitive diagnosis and treatment. Grossly, marked compression and indentation of nerve roots may be seen, associated with stenotic lesions, bone fragments, disc material, inflammatory lesions, neoplasia, etc.

References

References are available upon request.

Important part of the anatomical diagnosis it is supported in the neurological exam of the patient one, thus also, the diagnostic differential and the definitive diagnosis of any neurological affection can be better evaluated if we take into account the anatomy of the nervous system and we achieve to correlate its functions. Afterwards we will try to see to the nervous system since the anatomic-functional point of view and with some anatomic-pathologic relation examples.

Basically the nervous system functions in form of a reflex arch, with two main ways or systems called system afferent and system efferent. These mechanisms include so much the autonomous nervous system as the nervous system volunteer (sensitive and motor).

The system afferent sensitive is that that contributes information of temperature, touch, proprioceptive positioning, and pain. It forms part of the nervous system peripheral consisting of a neuron unipolar that grasp information of the body through its receptors and carry it to the spinal marrow and to the cerebral stem (to the central nervous system). To medullar level, these neurons before entering to the marrow present its body neuronal to level of the dorsal roots and enter way the dorsal shafts to the spinal cord.

In the gray substance of the spinal cord, these neurons can do synapses directly with the body neuronal of a neuron multipolar whose function is that of producing an motor effect upon leaving its axon of the marrow way the shafts and ventral roots, peripheral nerve and to do synapses in the muscle effectors in which reflected arch is called. For which to this neuron it is called neuron effectors or lower motor neuron (LMN). However, the neuron sensitive can also do synapses with neurons intermediate or internuncials, which inside its functions is that of doing synapses with the body neuronal of a neuron multipolar that will ascend via the ascending tracts to the high centers of the cerebellum, brain and cerebral stem. Here the information is processed and later, in the high motor centers (located mainly in the cerebral bark) arises a neuron whose axon way descends the tracts descendents until doing synapses with the neuron effectors or LMN, functioning like initiator of the voluntary movement besides serving like modulator inhibitory or calming effect upon the LMN. To this neuron by having its body neuronal in the high centers is called it upper motor neuron (UMN).

The spinal reflex are obtained stimulating neuro receptors located in the fascias of the tendons or ligaments of the members, so much thoracic as pelvic, as well as of coetaneous and to be developed is necessary that patents be found the components of the reflected arch; receptor, way afferent, segment medullar, way efferent, organ defector. Any wound the some of its components will produce that the effect be seen diminished or absent and to this it is called sign of neuron motor lowers. By another side, if the damage is located for ahead of the segment medullar where enters the neuron sensitive (each reflection enters in a segment medullar specific), including in the high cerebral centers, the reflection will be performed but freed of the action modulator inhibitory of the UMN so that the effect will be of normal to increased in which sign is called of upper motor neuron. For example, for the patellar reflex, is stimulated upon striking the ligament of the rotula, the receptor neuron that perceives the stimulus through its receptor, as well as the effectors that stimulates to the quadriceps femoral enter and come out of the spinal marrow through the spaces inter vertebrates L4-L5 and L5-L6, so any wound that involve said segment medullar or the remainder of the reflected arch will produce decrease or the extension of the articulation of the knee (sign of lower motor neuron). By another side, if the spinal cord is affected by ahead of L4 or ascending ways or descendents located in the brain, the extension of the articulation of the knee will be seen of normal to increased (sign of upper motor neuron).

All the spinal reflections of the member thoracic arise of the medullar segment C6-T2, and all the spinal reflections of the pelvic legs as well as the anal and the micturition arise of the segment medullar L4-S3.

Before continuing with this chapter, is necessary to remember some terms necessary for the comprehension of the neurologic theme.

Nuclei: neuronal bodies inside the central nervous system

Ganglion: neuronal bodies out of the central nervous system

Tract: joint of axons inside the central nervous system

Nerve: joint of axons out of the central nervous system

To evaluate the brain and the cerebral functions we will divide this in three portions; brain, cerebellum, and cerebral stem.

The brain or forebrain is composed by the telencephalon and diencephalon, in this area found the cerebral cortex. Its have four lobes (frontal, parietal, temporal, and occipital) conforming the cerebral hemispheres besides the thalamus and the hypothalamus. The cerebellum is a great dorsal extension of the metencephalon. The brain stem is composed of the mesencephalon, the metencephalon, and of the myelencephalon.

Still and when the diencephalon is technically the most rostral aspect of the brain stem, this have functional and dysfunctional but similar to the brain that the remainder of the brain stem (since the medium brain to the medulla oblongata), so that we can say that the "forebrain" includes the telencephalon and the diencephalon.

Skilled responses and motor functions volunteers are processed in the frontal lobule. The frontal cortex is the terminal point of the system reticular activator (SRA) maintaining the conscious, alert and awake individual of its environment, besides participating in functions of gait and posture. Its main tract is the corticospinal, thus, the lobule frontal is mainly effector. The parietal lobe process the sensorial information such as touch, pain, and the proprioception. The thalamus may process more of the sensory information in the animals than in humans, the animals do not seem to depend on the parietal lobe for processing many sensations. The occipital lobe is necessary for an adequate vision and process of the visual information. The temporal lobe processes auditory information and aids in the localization of sound. Animals do not appear to depend on the temporal lobe for the complete ability to hear, since the information additive can also be processed in the cerebral stem. The temporal lobe is also responsible for some complex behavior. Parts of the temporal and frontal lobe cortex are included in the limbic system.

The limbic system is the responsible for many of the emotions and for the innate survival behavior such as protective, maternal, aggressiveness and sexual reactions. Parts of the hypothalamus are also included in the limbic system.

The diencephalon is the part more rostral of the cerebral stem and includes to the hypothalamus and to the thalamus.

The hypothalamus modulates the autonomic nervous system. Many of the neurons motor high sympathetic and parasympathetic are originated in this place. Appetite, thirst, regulation of the temperature, balance electrolytic, sleeps and behavior responses are some hypothalamic functions. The gland pituitary is found united by a stem of the surface ventral of the hypothalamus. The gland pituitary controls many of the functions endocrines of the body. The thalamus is a complex of many nuclei with intricate functions. The nuclei ventral, abundant and medial constitute the real system nociceptive and proprioceptive of the cerebral cortex. Many of the process of sensory information occurs in the thalamus of the animals, more than in the lobule parietal. Part of the system reticular ascending (RAS) is projected since the medium brain through the thalamus and diffusing to the cerebral bark, and is the responsible for maintaining alert to the cerebral bark and to maintain awake to the animal. Another part of the system reticular ascending projects through the subthalamus the cerebral cortex. Still and when there is many structures located here, the diencephalon can have large wounds with relatively few clinical signs.

The cerebellum is situated over the fourth one ventricle in the union of the bridge and the marrow oblong. The cerebellum modulate and coordinates all the motor activity of the head, neck, trunk and extremities. The cerebellum also controls the muscular tone in the animals. The cerebellum is part of the system vestibular and maintains the equilibrium in the animal. These functions elaborates them not by direct action upon the motoneurons but by indirect influence through the tracts descendents, mainly acting like a comparator of the movements desired and the movements carried out.

The olfactory nerve or nerve cranial I (NC I) is a sensitive nerve, responsible for the olfaction and is located rostral to the hypothalamus. The optic nerve (NC II) is also a sensitive nerve and together with the optic chiasm are necessary for the vision.

The mesencephalon or medium brain contains great part of the system reticular ascending, passes through the tegmentum (lower half) of the midbrain through the thalamus and subthalamus to the cortex. When the animal does not receive or processes these impulses, tends to be slept. Wounds in the cerebral cortex, diencephalon and medium brain can produce state of comma. The mesencephalon or midbrain contains the NC III and IV. The nerve oculomotor common (NC III) contains a motor effector component, innerves the ocular muscles medial rectus, dorsal rectus, ventral rectus, inferior oblique and the muscle upper eyelid, as well as the pupil constrict through a parasympathetic way. The trochlear nerve or pathetic (NC IV) effector, innerves the muscle superior oblique dorsal of the eye. Processes pathologic in the abundant portion of the medium brain are capable to produce ataxia or paralysis.

The metencephalon contains the pons and the cerebellum. The nerve trigeminal (NC V) is a mixed nerve, its portion afferent is sensitive for the head (touch, temperature, proprioception and pain) and contributes motor effector activity of the masticators muscles. Some vital centers associates with the respiration are also located in the pons.

The cerebellum is situated over the fourth one ventricle in the union of the pons and the medulla oblongata. The cerebellum coordinates all the motor activity of the head, neck, trunk and extremities. The cerebellum also controls the muscular tone in the animals. The flocculonodular lobe of the cerebelo is part of the vestibular system and maintains the equilibrium in the animal.

In the myelencephalon or medulla oblongata is located the NC VI to the XII. The nerve abducent (NC VI) nerve motor effectors innervate to the lateral rectus and retractor muscles of the ocular globe. The facial nerve (NC VII) is mixed, its motor portion produces movement of the lips, ears and close the eyelids. The facial nerve, presents sympathetic fibers that innerves the nasopalatines tear glands and the mandibular and sublingual salivary glands, besides, its sensitive portion obtains information of the flavor of the two third cranial portions of the tongue. The nerve vestibule cochlear (NC VIII) sensitive specialized, in its portion vestibular maintains the equilibrium of the animal, while the portion cochlear is necessary to hear. The nerve glossopharyngeal (NC IX) presents effectors functions and innerves muscles of the larynx and the pharynx (phonation together with the vague one), as well as sympathetic fibers for the glands salivates zygomatic and parotid. The nerve glossopharyngeal also contributes sensation of the caudal portion of the tongue and the pharynx, as well as the sense of the flavor of the part caudal of the tongue. The vagus nerve (NC X) innerves the thoracic and abdominal glands, cardiac muscle and smooth muscle to the colon. Besides innerves the skeletal muscle of the larynx, pharynx (phonation), and the soft palate. Besides, the vagus nerve transmits information sensorial since the pharynx, larynx, thoracic and abdominal viscera. The spinal accessory (NC XI) effector nerve, innerves the trapezius, brachiocephalic, and sternocleidomastoid muscles. The hypoglossal (NC XII) nerve effector innerves the skeletal muscle of the tongue, give its mobility. Finally, vital centers for the control of the respiration, blood pressure, and cardiac rhythm are located through the central nucleus of the medulla oblongata.

References

1.Cheryl L. Chrysman. Problems in Small Animal Neurology. Ed. Read & Febiger 1991

2.Michael D. Lorenz; Joe N. Korngay. Handbook of Veterinary Neurology 4a Ed. Saunders 2004

3.Curtis W. Dewey. Canine and Feline Neurology to practical guide. Ed. Iowa State Press 2003

4.Fernando Pelllegrino; Adriana Suraniti; Luis Garibaldi. Neurología for the Practical Clinic. Ed. INTER-MEDICAL 2003

5.Vicente Aige Gil. Neurología Veterinaria in the Dog and the Cat. Ed. Pulso 1998

The neurological examination is the basic and most important tool of clinical neurology.

The neurological examination allows:

to determine if the nervous system is affected by a disease process

to localize the lesion within the nervous system (neuroanatomic diagnosis)

to assess the severity of dysfunction

to construct a list of differential etiological diagnoses (along with the information provided by the signalment, the history and the general physical examination)

These information are necessary to establish which diagnostic procedures are required (CBC, chemistry profile, serology, urinalysis, CSF analysis, survey radiographs, myelography, CT, MRI, electrodiagnostics, muscle/nerve biopsy, etc).

I would like to emphasize that performing the neuroanatomic diagnosis should always precede consideration of the differential etiological diagnoses and therefore of the diagnostic work-up.

Taking a thorough medical history and performing a detailed general physical examination are prerequisites to the neurological examination. This should be performed in a systematic manner and each result has to be recorded in a standard form so that no part of the examination is omitted. In certain cases, it might be necessary to modify the examination according to the chief complaint, the condition and cooperative attitude of the patient. For instance, in an animal presented with acute spinal trauma any manipulation that might exacerbate a possible vertebral instability (such as performing hopping and wheel-barrowing) should be avoided until an unstable vertebral injury has been ruled out. In addition, in order to perform and interpret correctly each test, it is of paramount importance to achieve and maintain patient cooperation throughout the examination. Therefore any disagreeable or painful procedures, such as palpating a painful area, should be performed only at the end of the examination.

The neurologic examination includes assessment of mental status and behaviour, posture, gait, postural reactions, cranial nerve function, muscle tone and mass, spinal reflexes, and pain perception.

Mental status and behaviour

The level of consciousness is influenced by the functional relationship between the ascending reticular activating system within the brain stem and the cerebral cortex. An animal with normal mental status is bright, alert and appropriately responsive to the surrounding environment. Depression or obtundation occurs in animals that are awake but relatively unresponsive to normal environmental stimuli. Depression is not a specific sign of brain disease and may be seen in association with systemic illness. Stupor is present in an animal that sleeps except when aroused by strong stimuli. Coma is a state of unconsciousness from which an animal cannot be aroused even with noxious stimuli. Stupor and coma are commonly caused by a brain stem lesion that produces a partial or complete, respectively, disconnection of the reticular formation and the cerebral cortex. Stupor and coma Stupor and coma can also take place with severe diffuse forebrain disease. Delirium occurs when an animal is overactive and responds inappropriately to stimuli; it indicates forebrain dysfunction.

Behavioural changes such as loss of learned habits (for instance house training), aggression, head pressing, inability to recognize the owner suggest a forebrain disorder involving the limbic system.

Hemi-neglect syndrome, also known as hemi-inattention syndrome, refers to an abnormal phenomenon in which an animal with a structural forebrain disease ignores sensory input from one half of his/her environment (e.g., eats only from one side of the bowl, turns to the opposite direction when called from the ignored side). Since most sensory stimuli are interpreted primarily in the cerebral hemisphere contralateral to the side of the stimulus, the side that the patient ignores is contralateral to the side of the lesion.

Posture

Normal posture is maintained by coordinated motor responses to sensory inputs from receptors in the limbs and the body, the visual system, and the vestibular system to the CNS. Posture abnormalities include:

Wide-based stance in animals with vestibular or cerebellar disease, or with a lesion involving proprioceptive pathways between the spinal cord and the cerebral cortex. This stance may also be seen with generalised peripheral nerve disease.

Knuckling on one or more paws while standing indicates a conscious proprioceptive deficit.

Head tilt (one ear lower than the other) indicates unilateral vestibular dysfunction. The head is usually tilted toward the side of the lesion. Cerebellar lesions involving the flocculonodular lobe, the fastigial nucleus, or the caudal cerebellar peduncle can also produce a head tilt.

Head turn (the ears are level, the nose is turned to one side) and Pleurothotonus (the head, neck and trunk are twisted to one side) may occur with cerebral lesions and usually are toward the side of the lesion.

Head and neck ventroflexion may be observed with certain myopathies (e.g., hypokalemic myopathy in cats) or junctionopathies (e.g., myasthenia gravis in cats).

Kyphosis is often present in association with painful diseases of the thoracolumbar spine (e.g., intervertebral disc extrusion). Lordosis or scoliosis may occur in animals with vertebral column malformations (e.g., hemivertebrae).

The head and neck may be held in a fixed position when cervical pain is present.

Shiff-Sherrington posture is characterised by thoracic limb extension (best appreciated with the animal in lateral recumbency) and pelvic limb paralysis. It results from an acute severe lesion of the thoracolumbar spinal cord which interrupts the ascending inhibitory impulses from the border cells of the lumbar gray matter to the extensor muscle α-motor neurons in the cervical intumescence.

Decerebrate rigidity is due to a rostral brain stem lesion and is characterised by extension of all four limbs and sometimes opisthotonus. Affected animals are recumbent and typically have decreased consciousness (often stupor or coma).

Decerebellate rigidity is characterized by opisthotonus, thoracic limb extension, flexion of the hips (pelvic limbs flexed forward), and normal consciousness. It is due to an acute cerebellar lesion mostly involving the rostral lobe which is especially inhibitory to the stretch reflex mechanism of antigravity muscles. If the cerebellar rostral lobe lesion involves the ventral lobules, the pelvic limbs may be rigidly extended away from the body.

Gait

The ability to stand and move requires intact proprioceptive and motor systems. Gait assessment should be performed by observing the patient walking (straight, in circles, up and down stairs) on non-slippery surface. The observer should look at the animal from the side, front and rear. The examiner must be knowledgeable of gait differences among dog breeds. Patients that are recumbent and have no disease that could be exacerbated by movement (e.g., spinal fracture/luxation) should be encouraged/helped to get up and walk if they can, or at least to show any voluntary motor activity.

Gait abnormalities include ataxia, circling, paresis, and lameness. Ataxia is an inability to perform normal coordinated motor activity that is not caused by weakness, musculoskeletal problems, or abnormal movements. Ataxia can be classified as sensory, cerebellar and vestibular.

Sensory or proprioceptive ataxia is caused by lesions of the general proprioceptive pathways in the peripheral nerve, dorsal root, spinal cord, brain stem and forebrain. It is characterized by a loss of the sense of limb and body position. The animal has a swinging motion of the affected limbs and scuffing of the toes while walking. It is important to remember that since proprioceptive and motor pathways are intimately associated, sensory ataxia is often compounded by weakness.

Cerebellar ataxia is caused by cerebellar disease or selective dysfunction of the spinocerebellar tracts. It is characterized by inability to regulate the rate and range of movements with subsequent dysmetria, especially hypermetria.

Vestibular ataxia is associated with unilateral vestibular dysfunction and is characterized by leaning, drifting, falling, rolling to one side. This type of ataxia is often accompanied by other vestibular signs such as head tilt, circling, strabismus and spontaneous nystagmus.

Circling may occur with unilateral vestibular diseases and with asymmetrical or focal forebrain disorders. The presence of other neurological deficits typical of each syndrome (vestibular versus forebrain) will help to localize the lesion.

Paresis is a partial loss of voluntary movement. Plegia or paralysis is a complete loss of voluntary movement. These two terms are combined with the following prefixes to designate the limb involved: mono (of one limb), para (of both pelvic limbs), hemi (of both limbs on one side of the body), tetra (of all four limbs). There are two types of paresis: upper motor neuron (UMN) and lower motor neuron (LMN), causing a spastic or flaccid paresis, respectively.

Lameness is usually caused by orthopaedic disorders, but it can occur also with neurological diseases affecting a nerve root (e.g., attenuation by a lateralised intervertebral disc extrusion causing the so called "root signature") or a spinal nerve (e.g., nerve sheath tumor).

Abnormal involuntary movements include

Tremors are involuntary rhythmic movements of a body part (or of the entire body) produced by alternating contractions of antagonistic groups of muscles. Tremors may be associated with several conditions such as cerebellar disorders (intention tremors), hypomyelination of the CNS, "shaker dog disease", toxin exposure (e.g., hexachlorophene), hypocalcemia.

Myoclonus is a repetitive rhythmic contraction of a particular group of muscles (e.g., limb flexors, masticatory muscles) and may persist during sleep. It can be associated with encephalomyelitis, especially canine distemper.

Myotonia is a delayed relaxation of muscle following voluntary contraction. It occurs in certain congenital or acquired muscle disorders.

Postural reactions assess the same neurologic pathways that are involved in gait, that is, the proprioceptive and motor systems. The main value of postural reaction testing is to detect subtle deficits that may not be obvious during the analysis of locomotion (e.g., in animals with forebrain disease). Postural reactions are sensitive indicators of neurologic dysfunction, but, by themselves, do not provide a specific localization of the lesion within the nervous system. Postural reaction deficits typically occur ipsilateral to peripheral nerve, spinal cord, medulla oblongata and pontine lesions, and contralateral to forebrain and midbrain lesions. Postural reaction tests include the paw placement response (proprioceptive positioning), tactile and visual placing, hopping, hemiwalking, wheelbarrowing, and extensor postural thrust. The occurrence of deficits during two or more of these tests in any limb indicates a significant deficit.

Cranial nerve function

The cranial nerve examination should be performed when the patient is in the most cooperative attitude. Space precludes a detailed description of the functional neuroanatomy of each cranial nerve, consequently the procedure for cranial nerve examination will be briefly described indicating in parenthesis the specific cranial nerve/s being evaluated. The head is observed for any evidence of a head tilt (vestibular VIII), facial asymmetry related to weakness/ spasm of the muscles of facial expression (VII) or to atrophy of the masticatory muscles (motor V). To elicit the menace response (II-VII) one eye of the patient is covered and the opposite eye is menaced with a threatening gesture of the hand, being careful to avoid mechanical stimulation of the vibrissae; the normal response is a blink (VII) and some degree of head withdrawal. The menace response is a learned response and may not occur until 10 to 12 weeks of age in puppies and kittens. The palpebral and corneal reflexes are elicited by touching the medial/lateral canthus of the eye and the cornea (sensory V), respectively; the normal response is a blink (VII) and a retraction of the globe (VI). Facial sensation (sensory V) is assessed over the distribution of the three branches: ophthalmic, maxillary, and mandibular of the trigeminal nerve (V). If a sensory deficit is suspected, the most sensitive area to test with a blunt object is the mucosa of the nasal septum inside each nostril, the normal animal will immediately withdraw the head. The temporalis and masseter muscles are palpated to detect any swelling, atrophy, or asymmetry (motor V). The eyes are observed for evidence of strabismus or spontaneous nystagmus (III, IV, VI, vestibular VIII). By moving the head from side to side and up and down the vestibulo-ocular reflex (physiological nystagmus) can be elicited (III, IV, VI, vestibular VIII). The size and symmetry of the pupils (II, parasympathetic III, sympathetic innervation) and their response to light (II-parasympathetic III) are assessed. By opening the mouth we can evaluate jaw tone (motor V), position, movements and symmetry of the tongue (XII), and elicit the gag reflex (IX, X).

Muscle tone and mass

Muscle tone is maintained by the muscle stretch reflex (muscle stretch receptor- Ia afferent neurons--spinal cord--lower motor neuron--muscle). Decreased muscle tone can result from injury to this reflex arc or intrinsic disease of the muscle itself. Increased muscle tone can result from a lesion of the upper motor neurons that originate in the brain and have an inhibitory influence on the lower motor neurons. Muscle mass and tone are evaluated with the animal standing (try to have the patient bearing the same amount of weight on the two limbs that are being compared) and in lateral recumbency. Abnormalities include atrophy (early and severe with LMN diseases, chronic and mild with UMN disorders), hypo/atonia (LMN signs), and spasticity (UMN sign). Generalized or localized muscle hypertrophy may be associated with myotonic myopathies or with muscular dystrophies.

Spinal reflexes

Examination of the spinal reflexes tests the integrity of the sensory and motor components of the spinal reflex arch and the influence of descending UMN pathways on this reflex. Spinal reflexes include muscle stretch reflexes (such as extensor carpi radialis and patellar reflexes), thoracic and pelvic limb flexor reflexes, perineal and cutaneous trunci reflexes. Accurate evaluation of spinal cord reflexes, and particularly muscle stretch reflexes, requires a relaxed patient, a muscle placed in optimum position and the application of an adequate stimulus. Spinal reflexes are decreased to absent with LMN disorders and normal to increased with UMN disease. It is important to evaluate muscle tone and spinal reflexes along with the gait abnormality. For instance, in dogs with myasthenia gravis we might observe severe neuromuscular paresis with normal muscle tone and reflexes.

Pain perception (nociception)

Perception of a noxious stimulus should be assessed with the animal relaxed in a quiet environment. It is important to remember that pain is the subjective response of the patient to a noxious stimulus and varies between individuals.

Superficial pain sensation is assessed by grasping and lifting a small fold of skin at the test site with a blunt haemostat. The force of pinch is gradually increased until a response is elicited.

Deep pain sensation is tested by pinching the digits with the fingers or a haemostat. Always apply the minimum stimulus that allows eliciting a response. Normal responses to superficial or deep pain testing include:

A reflex flexion of the limb or a skin twitch indicating that peripheral nerves, nerve roots (motor and sensory) and spinal cord segments are intact.

A behavioural response, (such as turning the head towards the stimulus, crying or biting), which indicates that peripheral nerves, nerve roots, spinal cord segments and the ascending pain pathways in the spinal cord and brain stem to the forebrain are intact.

The pain pathways that carry superficial and deep pain sensation are different. The latter ones are more resistant to damage than other pathways including those responsible for proprioception, motor function, and superficial pain. Therefore testing deep pain perception is necessary only if superficial pain is absent. In patients with severe spinal cord injuries, the presence or absence of deep pain perception is important in assessing prognosis for recovery. It is very important NOT to confuse reflex flexion of the limb with conscious perception of the noxious stimulus (look for a behavioural response!). Altered states of consciousness (e.g., following trauma and shock) and certain drugs such as analgesics and sedatives may alter results of pain sensation testing.

Superficial pain assessment is particularly useful to map the distribution of a sensory loss in cases of peripheral nerve and brachial plexus injuries. Thorough knowledge of dermatomes and autonomous zones is required.

Finally the spine is palpated in order to detect any areas of hyperalgesia.

The abnormalities recorded during the neurological examination form the "building blocks" of the neurological syndromes. These include: cerebral, diencephalic, midbrain, cerebellar, vestibular, pontomedullary, cervical, cervicothoracic, thoracolumbar, lumbosacral, neuropathic and multifocal syndromes. The neurological syndrome approach helps performing correct lesion localization within the nervous system.

For further information on functional neuroanatomy, correct execution and interpretation of each test of the neurological examination and for a detailed description of the clinical signs that characterize each neurological syndrome I recommend reading the references listed below (n° 2 is available also in Spanish).

References

1.Braund KG: Clinical Syndromes in Veterinary Neurology, 2^nd ed, Mosby, St Louis, 1994

2.Braund KG: Clinical Neurology in Small Animals. International Veterinary Information Service, IVIS (www.ivis.org), Ithaca, New York, 2003

3.Braund KG, Sharp NJ: Neurological examination and localization. In: Slatter D: Textbook of Small Animal Surgery, WB Saunders, Philadelphia, 2003

4.Chrisman CL, Mariani C, Platt S, Clemmons R: Neurology for the Small Animal Practitioner, Teton New Media, Jackson, WY, 2002

5.De Lahunta A: Veterinary neuroanatomy and clinical neurology, 2nd ed, WB Saunders, Philadelphia, 1983

6.Dewey CW: A practical guide to canine and feline neurology. Blackwell, Iowa State Press, 2003

7.Lorenz MD, Kornegay JN: Handbook of Veterinary Neurology, 4^th ed, WB Saunders, Philadelphia, 2004

8.Platt SR, Olby NJ: BSAVA Manual of Canine and Feline Neurology, 3^rd ed, BSAVA Publications, 2004

9.Thomas WB: Initial assessment of patients with neurologic dysfunction. In: Thomas WB: Common neurologic problems. The Veterinary Clinics of North America, Small Animal Practice, WB Saunders, Philadelphia, 2000

10.Wheeler SJ: BSAVA Manual of Small Animal Neurology, 2^nd ed, BSAVA Publications, 1995

Among primary thyroid dysfunction, hypothyroidism is a common endocrine disorder found in dogs; hyperthyroidism is more common in cats. Neuro-muscular signs associated with thyroid dysfunction have been recognized for years although central neurological signs have been described more recently.

Thyroid function testing is usually performed by serum thyroxin concentration measurement. The more accurate diagnosis of hypothyroidism is based on low-resting free T4 concentration (100% predictive value). Basal T4 has a 95% positive predictive value, the 5% lacking are due to the presence of T4 antibodies. If the value is intermediary, a final diagnosis cannot be made. The TSH stimulation test improves the diagnosis in 70% of these cases; an inadequate response to TSH stimulation is in favor of hypothyroidism. Anaphylactic reactions with bovine or porcine TSH may be lethal. Recombinant TSH is expensive. A high TSH seric measurement may improve the final diagnosis. 20% of false negative and 30% of false positive are expected. Alone, this test is diagnostic in 37% of the cases. TRH stimulation is so weak that it helps to rule out hypothyroidism only if T4 normalizes. T3, reverse T3, TSH post TRH stimulation are useless.

Collateral biochemical changes may be found: hypercholesterolemia is in favor although a third of the cases may have normal values.¹

In the literature, hypothyroidism is often named as an etiology for numerous diseases. Most of theses studies were single or few clinical cases carried out before than modern more sensitive T4 and TSH assays were available. Since, this idea has been carried out in the literature without verification until recently, mainly by Dr A Jaggy.^2-5

Hypothyroidism

Primary hypothyroidism is characterized by lethargy, weight gain, symmetrical alopecia, bradycardia, and generalized weakness. In human medicine, hypothyroidism as been associated with the clinical feature of myopathy (prevalence of 20 to 80%), mono-neuropathy, and sensory-motor axonal polyneuropathy (prevalence of 10 to 70%). Sensory symptoms predominate initially. Among clinical signs encountered in hypothyroid dogs, cranial, laryngeal and appendicular neuropathies have been described. Signs of encephalopathy have been less observed although hypothyroidism is incriminated in case of peripheral vestibular syndrome. In people, hearing loss has also been described. The patho-physiology behind the neurological signs in acquired hypothyroidism is poorly understood. The decreased ATPase activity in these patients drives to ATP deprivation responsible for the alteration of the axonal transport, leading to axonal degeneration and clinical neuropathy.

Generalized weakness: Large and giant breeds of dogs presenting with generalized weakness have Lower Motor Neurons signs (flaccid paresis or paralysis: hypotonia, hyporeflexia and muscle atrophy). Clinical signs usually progress from weakness to non ambulatory tetraplegia within 4 to 6 weeks, which is characteristic of a polyneuropathy. The diagnosis of polyneuropathy is based on electromyographic (fibrillation potentials, positive sharp waves, complex repetitive discharges), electroneurographic (decrease nerve conduction velocity, conduction blocs), and histo-pathological (neurogenic muscle atrophy, wallerian type degeneration and demyelinisation) findings. The myopathic electrodiagnostic changes (polyphasic or giant motor unit action potentials as an evidence of reinnervation activity) do not correlate with muscle weakness in human hypothyroid patients.⁶

Cranial nerve involvement: Hypothyroidism has been recognized as a cause of peripheral vestibular syndrome. These dogs are presented with head tilt, asymmetrical ataxia (hypertonia on the side opposite to the head tilt, and hypotonia on the same side) and nystagmus without postural reaction deficit. The history (no exposure to ototoxic drugs, no history of trauma) and the normal findings of complementary diagnostic procedures (otoscopic examination, Brainstem Auditory Evoked Response, radiographs, computerized tomography or magnetic resonance imaging (bullae, petrous bone, and brain stem) and cerebrospinal fluid analysis) rule out middle or internal ear structural causes. The Brainstem Auditory Evoked Response may show decreased amplitude and latency, consistent with a degenerative neuropathy. Mild EMG or ENG finding consistent with a diffuse polyneuropathy without clinical expression may also be found concomitantly. Facial paralysis has been associated with hypothyroidism in dog.⁷

Megaoesophagus: Megaoesophagus is a common finding in myasthenia gravis, neuropathy of congenital or metabolic origin, hypoadrenocorticism, LE, However, a large number of cases have an idiopathic etiology. Some of those have a concomitant hypothyroid status and their megaoesophagus may be reversed by thyroid supplementation.

Laryngeal paralysis: Acquired laryngeal paralysis is a middle-aged to old large or giant dog condition. The recurrent nerve degenerative changes may or may not be included in a more generalized polyneuropathy. In some of them, concomitant hypothyroidism has also been reported and clinical signs reversed by thyroid supplementation.

Central hemispheric signs: Hyperlipoproteinemia and the lipidic form of arteriosclerosis, named atherosclerosis, have been described in primary hypothyroid dogs. Involvement of cerebral arteries may induce hypoxia and spontaneous vascular accidents inducing seizures or other supra-tentorial neurological expression (circling, head pressing, hemi-negligence syndrome). Hypothyroidism is more prevalent in dogs with atherosclerosis compared to dogs without atherosclerosis on postmortem examination.⁸ In a retrospective study, dogs with atherosclerosis were over 51 times more likely to have concurrent hypothyroidism than dogs without atherosclerosis. Hypothyroidism has also been diagnosed in non-structural epileptic dogs. Thyroid supplementation may resolve the problem and anti-epileptic drugs may be discontinue.

Treatment: Because of the difficulties encountered to obtain a final diagnosis of hypothyroidism, a therapeutic diagnosis may often confirm the hypothesis of a neurological dysfunction related to hypothyroidism. A T4 supplementation is preferred to a T3/T4 mixed supplementation. The risk of thyrotoxicosis is null with the first one. 33% of hypothyroid human patients have residual symptoms after 1 year of therapy. The patho-physiological changes found in hypothyroid muscle (type II fibers atrophy, increased numbers of internal nuclei, core-like structures in type I fibers) may explain this. Hypothyroidism induces less a myopathy than a muscle dysfunction.

Hyperthyroidism

Hyperthyroidism has been associated with the clinical features of neuromuscular and central nervous system dysfunction similar to signs described in human beings. Weakness is a common feature in cats with hyperthyroidism. The most common clinical expressions are neck ventro-flexion, decrease ability to jump, fatigue after physical activity. Restlessness, hyper-excitability, irritability and aggression are behavior signs that can develop in hyperthyroid cats. Focal or generalized seizures are rarely reported.

These neurological manifestations are associated with more systemic signs, i.e., increased appetite, weight loss, polydipsia, vomiting and diarrhea associated with high liver enzyme activity and hypertrophic cardio-myopathy. There are no specific pathological changes in muscles of hyperthyroid patients. Paraclinical evidence of myopathy is lacking. It is more a functional muscle disorder than a myopathy. The muscle weakness has a good and rapid recovery once the treatment is instituted. Most of the central nervous system signs resolve also with correction of hyperthyroidism.

Conclusion

The physio-pathological relation of megaoesophagus, laryngeal paralysis, ocular abnormalities, and other neuropathies with hypothyroidism remains to be scientifically established. Confirmation of the relation between neurological signs and hypothyroidism will depend on the type of neurological presentation, clinico-pathological results including T4 and if possible TSH level or TSH stimulation test, electrodiagnostic findings, histo-pathological findings and response to unique T4 supplementation.

References

1.Nelson RW, Ihle SL, Feldman EC, et al. Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness. J Am Vet Med Assoc 1991;198:1401-1407.

2.Bichsel P, Jacobs G, Oliver JE. Neurologic manifestations associated with hypothyroidism in four dogs. JAVMA 1988;193:1745-1747.

3.Panciera DL. Conditions associated with canine hypothyroidism. Vet Clin North Am Small Anim Pract 2001;31:935-950.

4.Jaggy A. Neurologic manifestation of hypothyroidism in dogs. In: ACVIM FORUM, WASHINGTON 1990;1037-1040.

5.Jaggy A, Oliver JE, Ferguson DC, et al. Neurological manifestations of hypothyroidism: a retrospective study of 29 dogs. JVIM 1994;8:328-336.

6.Tyler JW, Jennings DP. What is your neurologic diagnosis? Peripheral neuropathy or myopathy secondary to hypothyroidism. J Am Vet Med Assoc 1998;212:25-27.

7.McKeown HM. Hypothyroidism in a boxer dog. Can Vet J 2002;43:553-555.

8.Hess RS, Kass PH, Van Winkle TJ. Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs. J Vet Intern Med 2003;17:489-494.

Traumatic peripheral nerve and nerve root injuries are common in companion animals and may be caused by motor vehicle accidents, fractures (humeral, pelvic, proximal femoral), fracture/luxations (sacroiliac, sacrocaudal), bite wounds, gunshot wounds, and iatrogenic lesions (misplaced intramuscular injections, surgical "misadventures"). The nerve injury may result from compression, crushing, stretching, laceration or complete transection.^{(3, 8, 16, 17)} Clinical signs associated with peripheral nerve injury include: pain, proprioceptive deficits, lower motor neuron type motor dysfunction (paresis/plegia, muscle hypotonia, hypo/areflexia, neurogenic muscle atrophy), and hypo/anaesthesia. Peripheral nerve injuries have been classified based on the degree of functional and structural integrity of the nerve trunk:^{(4, 18, 19)}

1.Neurapraxia--refers to a transient interruption in nerve function (impulse conduction) due to ischemia and/or mild paranodal demyelination. There is no structural damage to the axons and their supportive connective tissue. Neurapraxia is the mildest form of nerve injury and it is commonly caused by blunt trauma or compression. The degree of proprioceptive and motor dysfunction can be variable, nociception is usually preserved. Neurogenic muscle atrophy is unlikely to occur. Recovery is usually spontaneous, complete and occurs within one to two weeks once the compression and edema resolve. Local demyelination may take 4 to 6 weeks to resolve.

2.Axonotmesis--few to several axons and surrounding myelin are disrupted (structural damage), but the Schwann cells, their basal lamina and the endoneurium remain intact. Wallerian degeneration occurs. Distally to the point of injury the axons and their myelin sheaths degenerate and undergo phagocytosis. Degenerative changes also occur in the axons proximal to the injury site but usually involve only one to three nodes of Ranvier. Axonotmesis may result from severe stretching or crush injury of the nerve. The degree of proprioceptive, motor and nociceptive deficit is proportional to the number of axons that are damaged. In general, significant neurological dysfunction and neurogenic muscle atrophy are expected. Axonal regrowth occurs spontaneously (1 mm/day) along the connective tissue scaffold, but the time until return to function depends on the extent of injury and the distance from the denervated end-organs.

3.Neurotmesis--is the most severe type of injury and is characterised by complete severance of the nerve trunk (axons, Schwann cells, supportive connective tissue). It is associated with complete proprioceptive, motor and nociceptive dysfunction (i.e., no deep pain perception). Neurogenic muscle atrophy is severe. As in axonotmesis the distal segment undergoes Wallerian degeneration, but the proximal axons will not regrow to their end-organ since there is no guiding scaffold (Schwann cell basal lamina and the endoneurium have been disrupted). Scar tissue tends to interfere with sprouting axons and may result in neuroma formation. Consequently, surgical intervention is necessary to assist regenerating axons to reach and reinnervate their appropriate end-organs.

The neurological examination, especially if repeated overtime, may help distinguishing between neurapraxia and axonotmesis or neurotmesis, however it might be difficult or even impossible to differentiate severe axonotmesis from neurotmesis on the basis of clinical assessment. Our ability to estimate clinically the severity of a nerve injury is mostly based on the relationship between the diameter of a nerve fibre and its susceptibility to compression. Large myelinated fibres, (supplying mainly proprioceptive function) are the most sensitive to injury. The slightly smaller myelinated fibres controlling motor function are the next most susceptible. Small non-myelinated fibres supplying nociception are the most resistant to compression. Therefore, with increasing compression of a nerve, proprioceptive function will be impaired at first, followed by motor function and finally by nociception. The presence of deep pain sensation in the dermatome of a certain nerve implies a much better prognosis than its absence.⁽¹⁷⁾ A thorough knowledge of the dermatomes and autonomous zones of the principal nerves of the limbs is essential to perform an accurate assessment of sensory function.^{(1, 7, 8, 13)} It is important to remember that with brachial plexus nerve root avulsion there may be inconsistency in the pattern of sensory versus motor deficits as the ventral nerve roots appear more susceptible to damage than the dorsal nerve roots. Clinical signs associated with dysfunction of most commonly affected spinal peripheral nerves have been thoroughly described.^{(3, 7, 13, 17)}

The diagnostic investigation for patients with peripheral nerve injury will include:

A minimum data base consisting of complete blood count, serum biochemistry profile and urinalysis to assess general health condition prior to anaesthesia for electrodiagnostics and/ or diagnostic imaging. In certain cases it might be indicated to perform also thoracic radiographs, abdominal ultrasound and a coagulation profile.

Electrodiagnostic tests are useful in assessing nerve integrity, functionality, severity of damage, distribution of nerve injury and in monitoring reinnervation.

Immediately after a brachial plexus or a peripheral nerve injury electromyography (EMG) can be used in the awaken animal to determine if some axons are still functional in the injured nerve and therefore if the muscle is still innervated by that nerve. By eliciting a withdrawal reflex (stimulating an area that the animal can definitely feel) and simultaneously recording EMG activity from a flexor muscle, motor unit action potentials will be recorded if any muscle function remains. For example, the presence of motor unit activity in the biceps brachii muscle of a dog or a cat with brachial plexus injury implies that some functional axons must have survived through the musculocutaneous nerve.^{(6, 17)} However, the absence of compound muscle action potentials does not indicate the severity or permanency of the nerve damage because transient conduction block due to edema may also prevent conduction down a nerve.⁽⁶⁾ Five to 10 days after peripheral motor nerve injury (that is the time required for the degeneration of the distal axonal segment), denervated muscle fibres exhibit spontaneous depolarizations that can be recorded by EMG (in the anaesthetized animal) in the form of fibrillation potentials and positive sharp waves.⁽¹⁴⁾ If EMG studies are repeated over time they may help monitoring disease progression. The presence of giant motor unit potentials on EMG indicates reinnervation.

Motor nerve conduction velocity (MNCV) and the recorded amplitudes of muscle evoked action potentials provide an accurate evaluation of the severity of the damage to the LMN. F-wave studies allow assessment of ventral nerve root function and may be useful in cases of proximal motor nerve injuries such as brachial plexus avulsion.

Sensory function can be assessed by means of sensory nerve conduction velocity (SNCV) study and cord dorsum potential (CDP). For example, in a dog with sensory dysfunction following brachial plexus injury, the absence of the CDP with a normal SNCV indicates a complete nerve root injury above the dorsal root ganglion.⁽⁶⁾

Intraoperative nerve action potential are used in human medicine in order to identify functional regeneration of an injured nerve and accurately trace the length of regenerating axons and the length of nonviable nerve.⁽⁹⁾ These information are extremely helpful to decide whether and exactly where segmental nerve resection and reanastomosis should be performed.

Survey radiographs are indicated when the nerve injury is likely to be associated with fractures (i.e., humeral, femoral, pelvic, sacrocaudal) or with intramedullary pinning. Ultrasound may be helpful in assessing nerve anatomy and further characterise traumatic nerve lesions in companion animals.⁽¹⁰⁾ We have successfully used ultrasound to visualise sciatic nerve entrapment following penetrating wound in the caudal thigh of dogs previously attacked by a boar. A recent study in human medicine has shown that ultrasound can be a useful diagnostic aid in the determination of the precise localisation of the injured site along the involved peripheral nerve, the type of injury and the diagnosis of neuroma.⁽⁵⁾

Computerized tomographic (CT)--myelography is indicated in the diagnosis of brachial plexus nerve root avulsion since it allows visualization of meningeal diverticula and abnormalities of the spinalnerve roots. In a recentprospective study of 40 human patients suffering severebrachial plexus injuries, CT-myelography was found tobe 85% accurate in predicting the intraoperative findings.⁽¹¹⁾

MRI provides fine anatomic detail of soft tissue and can be used to visualise nerve structures. In veterinary medicine MRI has been successfully used in the diagnosis of peripheral nerve sheath tumors and will certainly have a role in the diagnosis of peripheral nerve injuries. In human medicine, it has been demonstrated that conventional MRI can detect signal changes in injured nerves and in denervated muscles.⁽¹¹⁾ In addition, in human medicine, the use of custom designed phase array coils has led to the development of MR neurography (MRN). MRN produces images with higher resolution improving the ability to visualize both normal and abnormal peripheral nerves in various regions of the body.⁽¹¹⁾ These advanced diagnostic imaging techniques may have an important role in the assessment of peripheral nerve and brachial plexus injuries in companion animals in the near future.

Treatment of peripheral nerve injury depends on the cause, the severity and the site of the lesion. In general, anti-inflammatories and analgesics are indicated to relieve inflammation and pain. Physical therapy should be started in the early stages following nerve injury in order to maintain range of motion and minimise muscle atrophy. If the nerve injury produces monoparesis and knuckling such as with radial or sciatic nerve lesions, the paw should be protected by means of commercially available boots, splints or special bandages.

When the primary cause of nerve injury can be identified (trauma by fractured/dislocated bone, excessively long femoral intramedullary pin, entrapment by inflammatory/fibrous tissue) it should be addressed surgically as soon as possible (fracture repair, intramedullary pin removal/shortening, neurolysis).

If the nerve has been severed sharply (e.g., by a piece of glass or a knife), and the wound is not contaminated, immediate nerve repair is recommended. Special microsurgical instrumentation and magnification (ocular loupes or operating microscope) are required to perform a meticulous neurorrhaphy. The surgical repair must be accomplished with the least possible trauma to minimise inflammation and fibrosis. The sutures have to be positioned with no longitudinal and circumferential tension at the repair site. Excessive scar formation at the suture line will markedly decrease the progression of regenerating axons. An essential part of neurorrhaphy is accurate anatomical alignment of the nerve fascicles. Failure to match the fascicles in the two segments prevents regenerating axons from reaching their appropriate end-organs. The surgical techniques (epineural, perineural, nerve grafts) to perform nerve repair have been described.^{(15, 16)}

When the nerve lesion is caused by stretch and/or compressive forces associated with a closed traumatic injury, it is not possible to determine immediately whether the lesion is neurapraxic, axonometric or neurotmetic. Therefore medical management (analgesics, anti-inflammatories) and frequent re-evaluation (neurological examination, electrodiagnostics, and if indicated also diagnostic imaging) are advised. It is interesting to note that these guidelines are quite similar to the ones used in human medicine even though patient cooperation during clinical and electrodiagnostic assessment is much higher than in veterinary medicine and more sophisticated facilities are usually available. Hence, we can state that frequently the greatest diagnostic aid in patients with closed traumatic nerve injuries is the passage of time. Unfortunately, while awaiting for a possible improvement some complications may occur, these include: muscle atrophy and joint contracture (that can be prevented/ addressed with physiotherapy), abrasion of the dorsal surface of the paw (preventable with adequate foot protection), and paraesthesias with self mutilation. This latter complication results from abnormal sensation in an affected area due to pathological changes in the peripheral and/or central nervous system and may be difficult to control pharmacologically.⁽²⁰⁾

In those instances where limb dysfunction is profound and nerve damage is chronic (no improvement after 3 to 6 months post-injury), severe and irreversible, treatment options are quite limited. Muscle-tendon transfer alone or in association with carpal/tarsal arthrodesis may be indicated as a salvage procedure in selected cases.^{(2, 12)} When these techniques have failed or are not indicated and delayed nerve repair is not an option, limb amputation may be the only possibility.

Future developments in the treatment of peripheral nerve injury include the use of neurotrophic and neurotropic factors to stimulate axonal survival and regeneration (trophic effect) and to direct growing axons to their proper target organ (tropic effect).

REFERENCES

1.Bailey CS, Kitchell RL: Cutaneous sensory testing in the dog. J Vet Intern Med 1987, 1, 128- 135

2.Bennett D, Vaughan LC: The use of muscle relocation techniques in the treatment of peripheral nerve injuries in dogs and cats. J Small Anim Pract 1976, 17, 99-108

3.Braund KG: Neuropathic disorders, Traumatic neuropathy. In: Braund KG: Clinical Neurology in Small Animal. International Veterinary Information Service, IVIS (www.ivis.org), Ithaca, New York, 2003

4.Burnett MG, Zager EL: Pathophysiology of peripheral nerve injury: a brief review. Neurosurg focus 2004, 16: 5, 1-7

5.Cockluk C, Aydin K, Senel A: Presurgical ultrasound-associated neuroexamination in the surgical repair of peripheral nerve injury. Minim Invasive Neurosurg 2004, 47: 3, 169-172

6.Cuddon PA, Murray M, Kraus K: Electrodiagnosis. In: Slatter D: Textbook of Small Animal Surgery, Philadelphia, WB Saunders, 2003, 1218-1226

7.De Lahunta A: Veterinary neuroanatomy and clinical neurology. 2^nd ed, Philadelphia, WB Saunders, 1983, 53-74

8.Dewey CW: A practical guide to canine and feline neurology. Blackwell, Iowa State Press, 2003, 397-401

9.Ehni BL: Treatment of traumatic peripheral nerve injury. American family physician, March 1991

10.Fisher A, Reese S: Sonographic examination of the ischiadic nerve in the dog. Proceedings ESVN/ECVN Annual Meeting 2003.

11.Grant GA, Goodkin R, Kliot M: Evaluation and surgical management of peripheral nerve problems. Neurosurgery 1999, 44: 4, 825-840

12.Lesser AS: Tendon Transfer for Treatment of Sciatic Paralysis. In: Bojorab MJ: Current Techniques in Small Animal Surgery, Ed. Lea & Febiger, 1990, 59-62

13.Oliver JE, Lorenz MD, Kornegay JN: Handbook of Veterinary Neurology. 3^rd edition, WB Saunders, 1997, 115-122

14.Poncelet L: Electrophysiology. In: Platt SR, Olby NJ: BSAVA Manual of Canine and Feline Neurology, 3^rd ed, BSAVA, 2004

15.Raffe MR: Principles of peripheral nerve repair. In: Newton CD, Nunamaker DM: Textbook of Small Animal Orthopedics, International Veterinary Information Service, IVIS (www.ivis.org), Ithaca, New York, USA.

16.Rodkey WG, Sharp NJ: Surgery of the peripheral nervous system. In: Slatter D: Textbook of Small Animal Surgery, Philadelphia, WB Saunders, 2003, 1218-1226

17.Sharp NJ: Neurological deficits in one limb. In: Wheeler SJ: BSAVA Manual of Small Animal Neurology, 2^nd ed, 1995, 159-178

18.Seddon HJ: Three types of nerve injury. Brain 1943, 66: 237-288

19.Sunderland S: The anatomy and physiology of nerve injury. Muscle Nerve 1990, 13:771-784

20.Yaksh TL, Chaplan SR. Physiology and pharmacology of neuropathic pain. Anesthesiology Clinics of North America 1997, 15, 2: 335-352

1. Spinal Cord Tumors

Although spinal cord tumors are uncommon causes of spinal disease in dogs and cats, they are significant once the more common problems such as disc disease and trauma have been eliminated. Older animals are usually affected although certain tumor types occur in young animals, e.g., lymphoma in cats.

Clinical signs produced by tumors of the spine are the same as those seen for any spinal disorder. Animals with spinal tumors often have initial onset of nonspecific discomfort, followed by progressive neurological deficits and evidence op spinal pain. Marked muscle atrophy is often present caudal to the lesion. Sudden deterioration in neurological status or sudden increase in spinal pain is possible, e.g., with pathological fracture of a tumorous vertebral body. In case of extradural or intradural spinal cord tumors, the tumor mass may grow slowly which gives unaffected spinal parenchyma time to compensate. Therefore clinical signs may become apparent when considerable tumor mass has already filled up the spinal canal, especially in case of cervical localization. Tumors involving the brachial plexus or lumbosacral plexus may present first as progressive unilateral lameness, and later with spinal cord dysfunction when the vertebral canal is invaded (see under nerve sheath tumors).

Diagnosis of spinal cord tumors relies on electromyography, radiography, scintigraphy, myelography, and advanced imaging techniques such as (spiral) computed tomography (CT) and/or magnetic resonance imaging (MRI). Electromyography may be helpful in the confirmation of neurological disease and to determine the neurological localization for further imaging. The value of survey radiographs of the spine lies in the identification of primary tumors involving bony structures of the spine (osteosarcoma, chondrosarcoma) or metastasizing tumors to vertebral bodies. Radiographs also rule out discospondylitis. In most cases of spinal neoplasia radiographs result in negative findings necessitating further imaging with myelography. Evaluation of the myelogram provides information about the location of the tumor and also its position in the vertebral canal relative to the dura mater and the spinal cord. It is important to take lateral and ventrodorsal views to allow correct evaluation of the myelogram. A cerebrospinal fluid (CSF) sample should be kept when a myelogram is performed; occasionally neoplastic cells may be identified in the CSF. In case the tumor is within reach, a needle aspiration biopsy may be attempted. However, in most cases of spinal neoplasia the tumor is out of range of needle aspiration because of its localization in the vertebral canal. Radiographs of the thorax are recommended in all cases with suspicion of spinal cord neoplasia. Bone scintigraphy may be helpful in the localization of vertebral bone tumors or metastasizing lesions to the spine.

CT and especially MRI, when available, are the imaging tools of choice for spinal cord neoplasia. CT and MRI allow for direct assessment of the spinal cord itself instead of indirect visualization of extradural or intradural space-occupying lesions in case of myelography. CT and MRI also allow for differentiation between normal spinal cord parenchyma and the neoplastic tissue. Based on the CT and MR images, planning of microneurosurgical procedures is possible, using the best approach with wide surgical exposure and allowing for precise dissection between unaffected spinal cord parenchyma and spinal cord neoplasia.

Based on the myelogram, CT, and/or MRI findings spinal cord tumors are classified in extradural tumors, intradural-extramedullary tumors and intramedullary tumors (Figure 1).

Figure 1. Extradural (1), intradural-extramedullary (2), and intradural-intramedullary localization of a spinal cord neoplasia.

Extradural tumors

Extradural tumors are the most prevalent type in dogs, accounting for 50% of the cases. They encompass the tumors that lie outside the dura mater, i.e., vertebral body neoplasia (osteosarcomas, fibrosarcoma, chondrosarcoma, myeloma) and metastasized extradural tumors (carcinoma, sarcoma, melanoma). In cats, the most common extradural tumor is lymphoma that may also affect the spinal cord itself (intradural localization).

Intradural-extramedullary tumors

These tumors lie within the dura mater but outside the spinal cord parenchyma. The most common are meningiomas and nerve sheath tumors (neurofibroma, neurofibrosarcoma, schwannoma; see below). Meningiomas are far less common in the spinal cord than in the brain. Nerve sheath tumors make up the majority of neoplasm in this location. When they occur in the cervical (C1-C5) and thoracolumbar spine (T3-L3) spine, signs of spinal cord compression and dysfunction are seen. Since these tumors usually lead to lower motor neuron dysfunction, electromyography is very useful to identify the nerve roots involved.

Intramedullary tumors

Intramedullary tumors (glioma, astrocytoma, ependymoma or metastasizing tumors, e.g., lymphosarcoma) occur within the spinal cord parenchyma and are the least common types.

Surgical intervention in primary spinal cord neoplasia may be considered 1) to collect tissue for histopathological diagnosis or 2) to improve spinal cord function by tumor removal and decompression. Surgical treatment is considered appropriate in extradural tumors and intradural-extramedullary tumors. In case of intramedullary tumors there is usually not a sharp border between neoplastic tissue and normal spinal cord parenchyma and surgical resection is considered palliative. Surgical approaches must be tailored to the location of the tumor and, ideally, are planned using the information available by CT and MRI. Generally, wide exposure of the tumor and spinal cord is desirable. Dorsal laminectomy is recommended in most patients with a spinal cord neoplasia in the cervical or thoracolumbar area. The 'ventral slot' approach in the cervical area is not useful since access to the spinal cord and nerve roots is limited. Also, the venous sinuses hamper an undisturbed, dry surgical field. In the thoracolumbar area dorsal laminectomy will lead to instability, therefore following tumor removal the vertebral stability must be restored using internal fixation techniques such as Lubra plates or spinal plates. The intradural localization of meningiomas necessitates a durotomy and often also a partial durectomy. The use of surgical magnification (loupes or operating microscope) makes identification of tumor margins easier. Often the neurosurgeon has to weigh the advantages of complete tumor removal including a margin against potential damage to the spinal cord leading to worsening of neurological deficits. Therefore spinal cord neoplasia removal of tumor tissue may not be complete and other therapies (chemotherapy and radiation) should be considered as follow up treatment. Methylprednisolone is administered pre-operatively (2-5 mg/kg) to minimize the effects of spinal cord manipulation.

2. Nerve Sheath Tumors (NST)

Nerve sheath tumors (NSTs) have a low incidence in dogs and most commonly involve the peripheral nerves of the brachial plexus. NSTs are benign or malignant mesenchymal tumors and they originate from periaxonal Schwann cells (schwannoma) and fibroblasts (neurofibroma/neurofibrosarcoma). Due to its mesenchymal origin the terminology for NSTs is diverse and a wide range of names has been used in the literature, e.g., neurinoma, schwannoma, neurofibroma, neuro(fibro)sarcoma, neurilemmoma, neurogenic sarcoma, and neurofibromatosis. Currently the most widely used name is nerve sheath tumor. On histological examination NSTs exhibit Antoni A or Antoni B patterns; the former (Antoni A) comprises compact spindle cells arranged in interlacing fascicles and palisades (whorls), whereas the latter (Antoni B) is less cellular, consisting of spindle cells arranged loosely and supported by edematous matrix. NSTs may occur in every large or small nerve in the body but will only receive attention from the orthopedic surgeon or the neurosurgeon when the spinal cord, cauda equina or main peripheral nerves of limbs are involved. Although most NSTs grow outside the dura mater (extradural) they may extend along the pathways of the nerve roots into the intervertebral foramen. Once inside the spinal canal they may develop an intradural-extramedullary component or even an intradural-intramedullary component (Figure 1). Clinical signs include severe, unexplained, and intractable pain, thoracic or pelvic limb lameness, monoparesis, ataxia and proprioceptive deficits. Early diagnosis and an aggressive surgical protocol maximize the possibility for complete tumor resection sparing the limb. NSTs have a high rate of recurrence, and the overall prognosis is considered poor.

At the Utrecht University eight dogs with a nerve sheath tumor were seen in which the diagnosis of NST was confirmed by imaging or histological examination of the surgical specimen. The dogs (German Shepherd, English Cocker Spaniel, Bouvier, Irish Terrier, Labrador Retriever and 3 Golden Retrievers) ranged in age from 14 months to 10 years and were referred for limb lameness, monoparesis, severe muscle atrophy, and (periodic) severe limb or axillary pain unresponsive to medical treatment. Pain was eventually localized in the upper cervical area (1 dog), in the lower cervical area and axillary region (4 dogs), in the lower back region (1 dog), and in the distal limb (2 dogs). Electromyography was performed in 4 dogs and showed denervation potentials of the muscles of the affected limb. In all dogs radiography was not diagnostic or inconclusive.

Computed tomography was performed in 5 dogs, magnetic resonance imaging in 2 dogs, and ultrasonography in 2 dogs. CT revealed a brachial plexus tumor at C6-C7-T1 in 3 dogs, an intradural-extramedullary tumor component of a NST at C6 in 1 dog, and lumbosacral disc disease together with a right spinal nerve root S1 tumor in 1 dog. MRI revealed an intradural-extramedullary tumor component of a left paravertebral NST at C1-C2 in an Irish Terrier. Ultrasonographic examination revealed an elongated tumor along the trajectory of the tibial nerve at the medioplantar aspect of the talocrural joint in an English Cocker Spaniel. Ultrasonographic examination and MRI revealed an elongated tumor along the trajectory of the median nerve at the mediopalmar aspect of the carpus in a Labrador Retriever.

The Irish Terrier with a NST at level C1-C2 and two dogs with a brachial plexus tumor were euthanized at the request of the owner. Five dogs underwent surgical exploration and tumor resection sparing the limb. Histopathological examination of surgical specimens revealed a schwannoma (spinal cord, brachial plexus), a low-malignant neurofibrosarcoma (S1 nerve root, median nerve) and a myxosarcoma (tibial nerve). Follow up examination showed a recurrence in 3 dogs at 2 to 5 months after surgery. Two dogs (C6 spinal cord NST and S1 nerve root NST) were euthanized at the time of recurrence. The Labrador Retriever with a median NST was successfully re-operated. Two dogs with a brachial plexus NST and a tibial NST went into full remission. The dogs that underwent resection of NSTs of median nerve and tibial nerve at distal limb showed no significant neurological deficits following surgery due to overlapping innervation of other peripheral limb nerves.

References

1.Wheeler SJ, SharpNJH. Small Animal Spinal Disorders. Diagnosis and Surgery. Mosby-Wolfe, London, 1994.

2.Jeffery ND. Handbook of Small Animal Spinal Surgery. WB Saunders, Philadelphia, 1995.

3.Bradley RL, Withrow SJ, Snyder SP. Nerve sheath tumors in the dog. JAAHA 1982;18:915-921.

4.Targett MP, Dyce J, Houlton JEF. Tumours involving the nerve sheaths of the forelimb in dogs. J Small Anim Pract 1993;34:221-225.

The nervous system is divided in two parts: 1. central (brain and spinal cord) and 2. peripheral (nerve, neuromuscular junction and muscle). Inflammation of the nervous system is a frequent cause of neurological manifestations in dogs, less common in cats. The confirmation of an inflammatory origin is usually made during the work-up by cerebrospinal fluid (CSF) analysis for brain, spinal cord or nerve roots involvement. The diagnosis is more difficult for peripheral involvement. A battery of complementary tests must be run once an inflammation is suspected to precise its origin. The treatment is often based on the use of steroids.

When to suspect a nervous system inflammation

Inflammation of the nervous system induces clinical signs that are not characteristic enough to tell with certainty that the patient has neurological signs secondary to such an origin. As always in neurology, the clinical signs are expressed according to the localization rather than the cause of a lesion. The signalment of the patient (breed, age, sex, habitat), the acuteness of occurring signs and a "multifocal" neuro-localization needed to explain these signs, are more in favor of an inflammatory origin. However, very focal signs and a chronic course of the disease cannot rule out an inflammatory origin. Ataxia and paresis may occur with central or peripheral localization. In case of encephalitis however, the patient will express fore brain signs: 1. seizures, disorientation, hemi-inattention syndrome in case of hemispheric involvement; 2. cranial nerve deficits from II to XII and especially vestibular signs in case of brain stem involvement. In case of myelitis, the patient will shows an upper motor or lower motor neuron presentation according to, respectively, a C1-C5/T3-L3 or a C6-T2/L4-S3 involvement. In case of peripheral nervous system involvement (polyneuritis), the paresis/paralysis is associated with hypo or atonia and hypo or areflexia. With neuro-muscular junction immune related inflammation (myasthenia gravis), clinical expression is mainly characterized by generalized weakness although more focal forms exist (oesophagus, ocular muscle). With polymyositis, weakness, reluctancy to move and muscle pain are the main clinical signs. However, there is a fair number of cases where the inflammation of the nervous system is mild enough or superficial enough (meningitis); in such cases, the clinical signs will be subtle and not specific for obvious neurological involvement. The owner is complaining that its pet is "not doing right", usually anorexic, febrile, reluctant to move, or show diffuse poorly localized pain.

How to confirm neuro-muscular system inflammation?

Cerebrospinal fluid collection should be conducted early on in front of patients showing the latest non specific signs or more obvious signs of encephalitis or myelitis. The tap should be performed at the site the closest to the neuro-localization, i.e., lumbar in case of general ataxia/paresis, cisternal in case of cerebral involvement. In front of a non-localized patients, a cisternal tap is preferred: the risk of blood contamination is lower at this site and the amount collected is usually higher. As soon as the first drops are coming out from the needle hub, a drop is put on the protein stamp of a urinary stick. In case of proteinorachia, it will, within seconds, turn positive (normal is less than 0,25 g per liter. If so, 1 to 2 ml of CSF is then collected for further testing. Immediately, the cell count is performed with a Malassez cell allowing for definitive confirmation of the inflammation of the central nervous system (normal is less than 5 nucleated cells per micro liter). False negatives exist if the immune system of the patient is depressed or if high dose of steroids have been given the days prior to CSF collection. CSF should be collected also in front of a rapid generalized lower motor neuron presentation without cranial nerve involvement; coon-hound paralysis or idiopathic polyradiculo-neuritis shows an albumino-cytologic dissociation, i.e., an increased protein content without pleocytosis.

Nerve biopsy and identification of an inflammatory infiltration is the only way to diagnose neuritis.

Anti-acethyl choline receptor measurement is the most sensitive test to diagnose an immune response directed against the posts synaptic neuro-muscular junction (myasthenia gravis).

Creatine phosphokinase measurement is increased in case of polymyositis. The presence of anti 2M muscle antibodies is diagnostic for masticatory muscle myositis.

What other tests must be run once nervous system inflammation has been confirmed?

Pleocytosis and proteinorachia mean that the central nervous system is responding to an aggression. The origin of the inflammation may be secondary to compression (disc hernia, spondylosis, trauma, neoplasia,) or primary. Because of the non specific changes in secondary inflammation, imaging of the brain or cord may be necessary when the patient history and signalment are not consistent with the most common primary inflammation of the central nervous system, i.e., breed specific meningo-encephalitis (Yorkshire, pug, boxer, Burmese mountain dog, beagle), granulomatous meningo-encephalitis, juvenile suppurative aseptic meningitis, or meningo-encephalo-myelitis of infectious origin. For example, an adult cat with subacute paraparesis may have a dry form of Feline Infectious Peritonitis or an extradural spinal cord lymphoma. A myelography will be necessary after a CSF collection to rule out the second possibility if the protein level or the differential cell count do not favor one or the other of the two hypothesis.

When images are not needed, complementary tests should be requested (biochemistry, serology, PCR, cytology, etc.) to narrow the differential diagnosis.

1.By sedimentation or cyto-centrifugation, the cell type population is carefully identified: lymphoblastic cells will be indicative of lymphoma (other type of neoplastic cell is rarely found); thousands of poly-nucleated cell without bacteria are indicative of juvenile suppurative non septic meningitis; fungal or leishmania organisms are diagnostic for central nervous system infestation. However, in numerous conditions, a mixed pleocytosis, especially after a few days of steroid treatment, are not characteristic of any peculiar final diagnosis. Immune encephalitis or myelitis may show any type of differential count.

2.Intrathecal IgG synthesis can be confirmed by comparing the amount of immunoglobulin in the CSF with the one in serum using albumin as a reference protein. IgG-Index helps to distinguish inflammatory/infectious diseases from other disorders except Distemper in young dogs.

3.IgA can be measured by ELISA. A combined elevation of CSF and serum IgA levels is highly indicative for aseptic suppurative meningitis. Single elevation of IgA in the CSF is rather indicative of primary (infectious or non infectious) or secondary (neoplasia) immune reaction. Other proteins, such as myelin basic protein, S-100 protein and C-reactive protein are not useful in clinical practice; too many disorders are accompanied by an elevation of these proteins.

4.Specific antibodies can be found in the CSF. Pair titers, IgG and IgM titers, Albumin ratio and Immunoglobulin index are run to bypass the possibility of CSF contamination due to blood brain barrier disruption. Canine distemper virus detection can also be performed by indirect immunofluorescent antibody examination.

5.Blood cell count may show a leucocytosis; however it is far from being systematic even with severe meningitis. Eosinophilia may be noted with parasitic origin.

6.Antigen detection is the best test to prove the etiology of an infectious disease. Bacterial or fungal organisms (Cryptococcus) may be seen by microscopic evaluation or culture. Polymerase chain reaction (PCR) is becoming a strong sensitive and specific test to confirm or rule out infectious origin. Distemper, Parvovirus, Coronavirus, Feline Immunodeficiency Virus, Feline Leukemia Virus, Toxoplasmosis, Neosporosis, Ehrlichiosis, and other infectious agent are now diagnosed by PCR. Serum and CSF should be tested.

7.Flow cytometry may be requested on mononuclear pleocytosis to confirm monoclonal population.

Recently, an association between central nervous system inflammation and polyarthritis has been recognized. Join tap should be performed with CSF collection to confirm a potential multifocal immune connectivitis also associated with renal involvement (detected by proteinuria and confirmed by protein/creatinine ratio).

Biopsy may be performed in case of muscle, nerve or even focal brain inflammatory suspicion although it is rarely helpful for a final etiological diagnosis.

How to treat inflammation of the neuro-muscular system?

Encephalitis and myelitis of infectious cause are usually difficult to treat. There is no treatment against Distemper, Feline Infectious Peritonitis or FeLV/FIV central nervous system involvement. Interferon is probably the only new drug to try, although antibiotic and steroids may increase the chance of recovery. Toxoplasmosis and Neosporosis should be treated with Clindamycin 10-20 mg/Kg BID. Non infectious encephalitis and myelitis are usually extremely steroid responsive. Immunosuppressive dosage is recommended initially and progressively tapered. An immediate association with other immunomodulating drugs should be proposed systematically to prolong the time of remission on the patient on whom drugs cannot be completely discontinued. Prednisolone, 1 mg/Kg BID initially, tapered to 0,5 mg/Kg every other day within a month, plus either azathioprine, 2 mk/Kg SID progressively tapered, either cytosine arabinosine 100 mg/m2 BID, two days in a row, every 3 weeks are the protocol of choice for the author. Check for neutropenia should be regularly performed the first months.

There is no treatment for the polyradiculo-neuritis; steroids do not shorter the recovery time that can last for a few days to a few months, usually with a return of motor function in the opposite way of occurrence, rear limbs last.

Steroids are used when a non-infectious polyneuritis or polymyositis has been confirmed by histopathology.

Conclusion

The incidence of inflammatory central nervous system disease and especially non-infectious form is high especially in small breeds of dogs, especially young adult females and in juvenile dogs of large breeds. The majority of peripheral nervous system inflammatory cases are also immune mediated. This explain why steroids is a common drug used in Neurology although it should be used when a tentative diagnosis has been made, not because the clinician expect some blind improvement of its use ... The infectious meningo-encephalo-myelitis, neuritis or myositis have often a poor prognosis.

References

1.Aubrey A. Steroid-responsive meningitis-arteritis in dogs with noninfectious, non erosive, idiopathioc, immune-mediated polyarthritis. J Vet Int Med 2002;16:269-273.

2.Radaelli ST, Platt SR. Bacterial meningoencephalomyelitis in dogs: a retrospective study of 23 cases (1990-1999). J Vet Intern Med 2002;16:159-163.

3.Tipold A. Diagnosis of inflammatory and infectious diseases of the central nervous system in dogs: a retrospective study. JVIM 1995;9:304-314.

4.Ducote JM, Johnson KE, Dewey CW, et al. Computed tomography of necrotizing meningoencephalitis in 3 Yorkshire Terriers. Vet Radiol Ultrasound 1999;40:617-621.

5.Kuwamura M, Adachi T, Yamate J, et al. Necrotising encephalitis in the Yorkshire terrier: a case report and literature review. J Small Anim Pract 2002;43:459-463.

6.Nuhsbaum MT, Powell CC, Gionfriddo JR, et al. Treatment of granulomatous meningoencephalomyelitis in a dog. Vet Ophthalmol 2002;5:29-33.

7.Schatzberg SJ. Polymerase chain reaction (PCR) amplification of parvoviral DNA from the brains of dogs and cats with cerebellar hypoplasia. J Vet Int Med 2003;15:538-544.

8.Suzuki M, Uchida K, Morozumi M, et al. A comparative pathological study on canine necrotizing meningoencephalitis and granulomatous meningoencephalomyelitis. J Vet Med Sci 2003;65:1233-1239.

9.Podell M. Inflammatory myopathies. Vet Clin North Am Small Anim Pract 2002;32:147-167.

10.Evans J, Levesque D, Shelton GD. Canine inflammatory myopathies: a clinicopathologic review of 200 cases. J Vet Intern Med 2004;18:679-691.

11.Shelton GD. Myasthenia gravis and disorders of neuromuscular transmission. Vet Clin North Am Small Anim Pract 2002;32:189-206, vii.