Neurological emergencies (Proceedings)

Neurological emergencies are common in small animal practice. As with other body systems, infections, neoplasms, trauma, inflammatory processes, congenital and hereditary diseases all affect the central and peripheral nervous systems causing a range of mild to severe conditions. Advanced forms of imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI) in veterinary medicine are allowing improved diagnostic plans and management options. The assessment, stabilization and treatment of the neurology emergency, however, still relies on the ability of the emergency clinician to consider a complete history, perform a complete physical examination, and analyze test results readily available on an emergency basis. The following section provides an overview of common neurology emergencies: changes in mental alteration, seizures, paresis and paralysis, vestibular syndrome and traumatic brain injury. Basic knowledge of neurological disease processes in animals allows the emergency clinician to consider a variety of differential diagnoses quickly and efficiently. Conditions causing hypoxia such as pulmonary disease, airway obstruction and anemia, or hypovolemia can be manifested as mental alteration. Metabolic disorders such as hypoglycemia or electrolyte derangements can cause seizures. Cardiovascular and metabolic instability must be recognized and corrected prior to neurological evaluation. Once satisfied that other underlying causes of central nervous signs have been ruled out, the clinician can consider a primary neurological disorder.

1. Neurological abnormalities should be localized to help identify the underlying cause.

2. Recent advances in diagnostic imaging has dramatically advanced veterinary neurology.

3. Many neurological conditions respond well to therapy.

Seizures

Definition/overview

Seizures are the physical manifestation of an abnormal balance between excitatory and inhibitory tone in the central nervous system. Seizures are categorized as either generalized or partial. Generalized seizures include those that, in the past, have been referred to as convulsions, or grand mal seizures. Partial seizures are further classified as either simple partial or complex seizures. Partial seizures include seizure activity that is atypical. Both generalized and partial seizures represent a potentially life-threatening neurological emergency usually requiring treatment.

Etiology

The central nervous system relies on a balance of excitatory tone and inhibitory tone for normal function of neurons. Generally, excitatory tone is mediated by the neurotransmitter glutamate, and inhibitory tone is mediated by gaba aminobutyric acid (GABA). Depolarization of the cell membrane results with binding of glutamate to its receptors. Hyperpolarization of the cell membrane occurs when GABA binds to its receptors. Uncontrolled, perpetuated neuronal activity may derail normal mechanisms that act to prevent random excitation, resulting in seizures.

Pathophysiology and clinical signs

Seizures may occur with a wide variety of conditions. These conditions are grouped according to intracranial causes (structural epileptic seizures or SES), extracranial causes (reactive epileptic seizures or RES), and idiopathic epilepsy (primary epileptic seizures or PES). Although each of these categories should be considered with animals presenting with acute or recent onset of seizures, the age of the animal may suggest one group over another. Animals less than 1 year or older than 5 years of age are more commonly represented in the SES group. Recurrent SES typically occur within 2-4 weeks of the acute onset (first seizure). Dogs aged 1 to 5 years old are more likely to have PES, and recurrent seizures may not recur for greater than 4-6 weeks. Cats develop PES very uncommonly without a prior inciting cause (eg, trauma or inflammation).

Generalized seizures (commonly referred to as grand mal or convulsive seizures) are characterized by loss of consciousness and bilateral muscle activity. Generalized seizures may have increased tone (tone) and or muscle flexation (clonic). Loss of autonomic tone is common, so the animal may vomit, urinate or defecate. Generalized seizures are the most commonly recognized seizures in small animals.

Partial seizures (both simple and complex) are clinically manifested by unilateral, bizarre behavior. Partial seizures are commonly referred to as focal seizures. Dogs with simple seizures remain alert and responsive, where dogs with complex seizures may have some loss or alteration in consciousness. The seizure activity itself is stereotypical of the region of the brain that is involved, such as the temporal or frontal lobes. Commonly recognized partial seizures include biting at imaginary flies, tail chasing, circling, ear or whisker twitching, head turning, or pupil dilation/constriction.

The seizure or ictal state is can be followed by a post ictal phase, during which the animal may seem confused, tired, pant, pace, and have visual impairment. A pre ictal phase, if recognized, is commonly referred to as the aura. During the pre ictal phase, the animal may seem confused or seek the attention of the owner. A partial seizure that progresses to a generalized seizure, is also referred to as an aura.

A cluster of seizures is a series of isolated seizures lasting over minutes to days. Status epilepticus is prolonged single seizure lasting more than 3 minutes without recovery. Status epilepticus can be life threatening, resulting in brain anoxia and residual brain impairment or death.

Categories of seizures

1. Generalized: loss of consciousness, tonic, clonic or myoclonic activity

2. Partial: unilateral, stereotypical or bizarre behavior

      a. simple partial: no loss of consciousness

      b. complex partial: altered mentation or loss of consciousness

Seizure classification

1. Structural epileptic seizures (SES) common causes

      a. congenital: hydrocephalus

      b. hereditary: lysosomal storage disease

      c. neoplasia: primary or metastatic

      d. infectious: viral (dog: rabies, canine distemper virus, cat: rabies, feline infectious peritonitis), bacterial, tick borne, fungal, protozoal, parasitic)

      e. inflammatory: pug dog encephalitis, granulomatous meningoencephalitis, necrotizing encephalitis of Maltese and Yorkshire Terriers

      f. trauma

      g. vascular or thromboembolic

2. Reactive epileptic seizures (RES) common causes

      a. hypoglycemia

      b. hyperammonemia

      c. toxin

      d. electrolyte derangement (hypernatremia, hyponatremia, hypocalcemia)

      e. hypertension

      f. polycythemia

      g. coagulopathy

3. Primary epileptic seizures (PES) (no known cause)

      a. common age: greater than 1 but less than 5 years of age

      b. common breeds: poodle, beagle, German Sheperd Dog, retrievers

Diagnosis

Diagnosis of seizures is usually made on the basis of physical examination and historical description of the event. The history that commonly accompanies seizure is a period of abnormal behavior that was preceded and then followed by normal behavior. The only other major differential to consider is syncope. The diagnosis of seizure is definitively made on the findings of an electroencephalogram (EEG). The availability of the EEG in practice, however, is limited. The electrocardiogram, in addition to assessment of cardiac function, should be performed to rule out syncope. If the ECG is unremarkable, and the history and physical examination is consistent with seizure, treatment can be administered based on index of suspicion.

Signalment and history are major components of diagnosis. All animals with acute onset or recurrent seizures should have minimum data base which includes complete blood count (CBC), serum chemistry analysis and urinalysis. Animals less than 1 year of age with acute or recurrent seizures should be considered for congenital and hereditary diseases. Animals greater than 5 years of age should be considered for neoplasia. Brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT), followed by analysis of cerebrospinal fluid (CSF) should be pursued. A CSF tap should almost always be performed following imaging. A preexisting brain lesion may cause increased intracranial pressure, and a sudden decrease in fluid pressure may allow brain herniation. Animals of all ages can be affected by inflammatory diseases, including infections due to viral, bacterial, tick borne disease, protozoal, fungal and parasitic diseases. Sterile inflammations are more common in specific breeds, including pug dog encephalitis, necrotizing encephalitis of Maltese and Yorkshire Terriers, or granulomatous meningoencephalitis (GME), but any breed and any age can be affected. Rabies should be considered in any animal with uncertain vaccination status, or a wound of unknown origin. Animals of all ages should also be considered for extracranial causes of seizure, including hypoglycemia, hyperammonemia, coagulopathy, toxin, hyperosmolality, electrolyte derangements or polycythemia. Hyperviscosity due to severe leukocytosis or hyperglobulinemia can cause seizure. Young animals at risk for portocaval shunts should be assessed for blood ammonia, bile acids. Young animals with portocaval shunts may present with urinary obstruction with ammonium biurate calculi. The presence of petechiae or ecchymoses should prompt assessment of platelets. Retinal examination should always be performed. Assessment of blood pressure should be obtained in all animals with recent onset of seizures. Assessment of the thorax and abdomen with survey radiography or ultrasonography for neoplasms should be obtained in older animals. A common cause of seizures in cats is hypoglycemia from insulin overdose. Any older cat (greater than 10 years of age) should be suspected of primary brain neoplasia, such as meningioma. Outdoor cats in summer and fall may suffer ischemic events from aberrantly migrating larvae. Pyrethrin exposure in cats and mycotoxin ingestion (compost or garbage) in dogs are common toxicities. Ethylene glycol ingestion should be considered in all animals with 1. potential exposure, 2. metabolic acidosis, hypocalcemia but no azotemia, or 3.acute renal failure and presence of calcium oxalate crystalluria. Hypocalcemic tetany should be considered in nursing animals.

Diagnostic plan

1. Minimum data base: CBC, serum chemistry analysis, urinalysis

2. Blood pressure measurement

3. Diagnostic imaging: brain MRI or CT, thoracic and abdominal radiography

4. CSF: analysis, culture, titers

5. Serum: titers

Differential diagnosis

Syncope from AV block or sick sinus syndrome may mimic a seizure. EKG analysis is warranted in any patient with a low heart rate or with signs that develop on exertion.

Treatment

Emergency treatment depends of the cause of seizure. Rapid assessment of the clinical signs, history, signalment and available test results including blood glucose, hematocrit, electrolytes and blood pressure is essential. Animals presenting with ongoing seizure should be treated. Intravenous access should be established and maintained for continued antiepileptic medication administration. Animals with PES and occasional isolated seizures once every 4-6 months may be untreated, but any animal presenting with clusters of seizures or status epilepticus should be started on long term antiepileptic therapy. Intravenous antiepileptic medications that quickly cross the blood brain barrier are the foundation of emergency seizure control. These include the benzodiazepines, such as diazepam (Valium) at 0.2 mg/kg IV bolus. This dose can be repeated up to 4 times. Pentobarbital is a fast-acting barbituate that causes anesthesia, although its antiepileptic control is controversial. Phenobarbital is the standard antiepileptic treatment, and can be administered according to a loading dose protocol. Phenobarbital is not as quick acting as diazepam or pentobarbital, however, and should be used in place of these options for the emergency control of ongoing seizure only when diazepam is unavailable. Propofol has been used as both an IV bolus or administered as a constant rate infusion (CRI). An appealing advantage of propofol and pentobarbital CRIs is that with discontinuation of the medications the animal can be more quickly recovered. The animal that has been administered a phenobarbital loading dose may require longer to recover. Antiepileptic management producing profound sedation should be accompanied with close monitoring including continuous ECG and pulse oximetry. Particularly when the cause of seizure has not yet been determined, the sedated neurologic animal should be managed with adequate IV fluid therapy and maintenance of a patent airway, sometimes requiring intubation and manual ventilation. Aspiration pneumonia is a common complication of prolonged seizures requiring anesthesia for epileptic control.

Identified causes of seizures should be addressed. Animals with suspected intracranial lesions should be administered IV mannitol (0.25-2 grams/kg slowly over 20 minutes, and can be repeated once if signs progress). Animals should be assessed to be cardiovascularly stable prior to mannitol administration. If a brain tumor or hydrocephalus is considered likely, rapidly acting corticosteroid therapy should also be given (prednisolone sodium succinate (Soludelta Cortef) 20 mg/kg IV slowly over 20 minutes). Hypoglycemia should be treated with dextrose infusions, hypocalcemia should be treated with calcium supplementation, polycythemia should be treated with phlebotomy. Hepatic encephalopathy should be cautiously treated with oral medications to reduce blood ammonia only if the animal is awake and appropriate to prevent aspiration. Rapidly progressive encephalopathy due to hyperammonemia should be treated with IV mannitol and enemas with lactulose or betadine. Traumatic brain injury should be treated with supportive therapies including fluid resuscitation, with the treatment objective being maintenance of systemic mean arterial blood pressure and adequate oxygenation. Rarely, an animal may require surgical intervention for brain injury that results from depressed skull fractures or subdural hematoma. Hypertension at levels greater than 200 mmHg systolic should be treated with oral antihypertensive agents such as amlodipine, enalapril, or prasozin, or intravenous agents including hydralazine or nitroprusside. Cats with pyrethrin exposure usually respond to IV boluses of diazepam, methylcarbamol or propofol. Dogs with mycotoxin ingestion usually respond to IV therapies including fluids and diazepam boluses. Ethylene glycol toxicity is best treated with dialysis to remove toxin and metabolites of the toxin. Administration of fomepazole or ethanol and aggressive IV diuresis may help prevent progression to acute renal failure. However, once renal failure occurs, prognosis for recovery is poor. Animals with undetermined vaccination status should be considered for rabies, and appropriate measures observed to prevent unvaccinated personnel from potential exposure.

For control of repeated seizure or status epilepticus

a. obtain venous access

b. diazepam (0.2 mg/kg IV bolus up to 4 doses)

c. propofol (4 mg/kg IV bolus or constant rate infusion)

d. supportive management (IV fluids, supplemental oxygen)

Identify and treat any underlying cause

a. hypoglycemia

b. electrolyte disorders

c. toxin

d. polycythemia

e. encephalopathy

f. hypertension

Presumptive intracranial mass lesion

a. Mannitol (0.5-2 gram/kg IV bolus)

b. Corticosteroids

Long term antiepileptic treatment

a. Phenobarbital (2.2 mg/kg bid)

b. Potassium bromide (25-50 mg/kg sid)

Prognosis

Prognosis relies on the underlying cause for the seizure. Animals with PES typically have excellent long term prognosis with seizure control. Animals with RES usually have good prognosis for seizure control once the underlying cause has been identified and corrected. Animals with SES have a fair to guarded prognosis, depending on whether the underlying brain disease can be treated.

Paralysis and paresis

Definition/overview

Paralysis denotes a loss of voluntary motor function due to spinal cord or peripheral nerve disease. Paresis represents retention of voluntary motor despite measurable conscious proprioceptive deficits. Paresis, like paralysis, is caused by defects in the spinal cord, or in the motor nerves as they exit the spinal cord. Plegia describes the loss of voluntary motor function in a single limb. Plegia and paresis are diagnoses based on findings from a complete physical examination. Weakness, lethargy and lameness should be ruled out, and a neurologic examination performed prior to the diagnosis of paralysis or paresis.

Etiology

Injury to the spinal cord can arise as the result of an external force causing compression and subsequent edema, or from a intradural, parenchymal lesion. Intervertebral disk disease can occur chronically or acutely, and is a common cause extradural spinal cord compression. Tumors and inflammatory lesions are a less common cause of cord compression, in addition to traumatic fractures or luxations. Tumors can also occur in the intradural, extramedullary or intramedullary space. Other intraparenchymal lesions include inflammatory lesions, embolic and vascular accidents.

The optimal approach to the plegic or paretic animal includes the acquisition of a complete history and physical examination. Potential trauma should be considered with any acute onset of signs. Arterial pulses should be assessed, along with limb temperature and nail base color, in all animals to rule out vascular disease. Cardiovascular and pulmonary status should be determined and any derangements corrected prior to performing a neurologic examination. The neurologic examination should be performed prior to the administration of sedation or analgesia. Once the animal has been determined to be cardiovascularly stable, a thorough neurologic examination should be obtained, including mentation, cranial nerve reflexes, and examination of the cervical, thoracic, lumbar and sacal spinal reflexes. Localization of the lesion based on examination is essential for continued diagnostic testing, and may help in determination of prognosis. History, in addition to examination, is essential in establishing differentials diagnoses. A chronic, progressive history is more suggestive of a compressive lesion. Compressive lesions are more likely to cause bilateral signs, such as pelvic limb paraparesis or paralysis. Acute onset of signs can also be caused by a compressive lesion, however embolic or vascular accident, and trauma should be considered, as well. Signalment should be considered. Chondrodystrophic breeds, for example, may more commonly present with intervertebral disk disease. Young dogs should be considered for congenital problems, including occipital-atlanto or atlanto-axial instabilities and defects of the dens. Young great danes or middle-aged Doberman pinchers should be suspected of cervical vertebral instability ("wobbler" disease). Pelvic trauma or aortic thromboembolism should be considered in cats, as spinal cord disease is uncommon in this species. The cat can be rarely affected by spinal cord tumors including lymphosarcoma, spinal trauma and infectious disease including feline infectious peritonitis , fungal disease and toxoplasmosis. Rabies should be considered in any animal with unkown vaccination status, and particularly if a wound of unknown origin is identified.

Intradural causes of spinal cord disease or injury should be suspected in animals with acute onset of signs and lack of discomfort. Vascular accidents should be considered in any young animal. Inherited or acquired coagulopathy can present with acute spinal cord hemorrhage. Spontaneous hemorrhage can also occur with severe thrombocytopenias, or neoplastic metastases. Embolism of disk material, known as fibrocartilagenous embolism (FCE) is a common cause of acute plegia or paresis. In rare cases, the embolism may cause concurrent vascular injury and leakage of blood into the extradural space, resulting in compression. Acute traumatic disk extrusions can occur with trauma, such as hit by car accidents.

Peripheral nerve disease or neuromuscular disease can result from inflammatory or neoplastic lesions, or trauma. A common cause of a traumatic neuropathy is the brachial plexus avulsion injury. Generalized lower moter neuron disease should be considered with diffuse loss of tone and spinal reflexes. Gas distension of the esophagus, bark change, loss of cranial nerve reflexes and laryngeal/pharyngeal weakness may be present. A variety of disorders including myasthenia gravis, polyradiculoneuritis ('coonhound paralysis"),botulism, organophosphate toxicity, thyroid dysfunction and adrenocortical deficiency should be considered.

Common causes of paralysis or paresis in small animals

1. intervertebral disk disease

2. neoplasia

3. vascular or embolic events (FCE)

4. inflammatory or infectious

5. trauma

6. peripheral neuropathy (myelinopathy, axonopathy, radiculoneuritis)

7. neuromuscular disease

Clinical features

A neurologic examiniation will provide important information for localization of a lesion.

Animals with altered mentation, tendencies to pace or circle, cranial nerve deficits or recent onset of seizures may have paresis. Unless comatose or severely obtunded, paralysis would be an unlikely finding in an animal with intracranial disease. Extensor tone and ability to withdrawl should be assessed with each limb. A high cervical (C1-C4) lesion should produce convincing, increased tone and reflexia to all limbs. A low cervical-high thoracic (C5-T2) lesion should result in weak withdrawl (flaccid) of the thoracic limbs, but strong withdrawl of the pelvic limbs. A thoracolumbar (T3-L3) lesion should identify increased tone and reflexia of the pelvic limbs, and unaffected thoracic limbs. With Schiff-Sherington signs, however, the thoracic limbs will demonstrate excessive extensor tone. Lower lumbar (L4-L6) lesions will produce weak extensor tone and reflexia of the pelvic limbs. Lumbo-sacral (L-S) disease may produce weak tail and anal tone. Bladder tone may be increased with pelvic limb paralysis or tetraplegia. Weak bladder tone is common with flaccid paralysis. A lack of tone diffusely in all limbs suggests peripheral nerve (lower motor neuron) disease, or neuromuscular disease. Urine leakage from an "overflow" bladder can be difficult to differentiate from urinary incontinence. An overflow bladder, present with upper motor neuron signs to the pelvic limbs, is hard to express. Normal anal tone and tail tone are likely to accompany an upper neuron bladder.

Diagnosis

Accurate diagnosis of paralysis or paresis relies on history and physical examination. Minimum data base including CBC, serum chemistry and urinalysis may provide important information suggesting the presence of underlying diseases such as infection or neoplasia. Evaluation of clotting by assessing platelet count, PT and PTT, and buccal mucosal bleeding time may identify clotting factor deficiency or bleeding disorders. Survey spinal radiography should be obtained in any animal with known or potential trauma. Survey thoracic radiography in addition to spinal radiographs should be assessed for lytic or metastatic lesions. Imaging of the spinal cord with contrast myelography, computed tomography (CT) or magnetic imaging resonance (MRI) is the standard for diagnosis.for spinal cord disease. Contrast myelography is useful in providing definitive localization of compressive lesions. Some intradural lesions can be identified, as well. Imaging with CT and MRI may provide improved imaging of both intraparenchymal and extraparenchymal lesions. Further information may be gained with analysis of cerebrospinal fluid. Injection of contrast for imaging should be performed only following fluid inspection for suspected infection. Animals with suspected nontraumatic peripheral nerve disease, polyneuropathy or neuromuscular disease should be tested for hypothyroidism and hypoadrenocortism, and a neurologic consultation obtained with electrodiagnostic muscle and nerve testing. If myasthenia gravis is suspected, an edrophonium (Tensilon) response test should be performed. Thoracic imaging with survey radiography or CT should be performed to rule out thymoma. Histopathology of peripheral nerve and muscle may be required for definitive diagnosis.

Treatment

Cardiovascular and pulmonary compromise should be stabilized prior to assessement of or therapies for paralysis or paresis. Animals with high cervical lesions and lower motor neuron diseases may be hypoventilatory and require immediate intubation and manual ventilation. Once stabilized, treatment should be aimed at the most highly suspected cause for the animal's signs. A surgeon should be consulted for animals suspected of spinal trauma or compressive spinal cord lesions. Prognosis for return of function relies in part on the ability of the animal to display deep pain of the affected limbs, and in part on the length of time the animal has been affected. Generally, paralysis due to spinal cord compression is best treated with surgical decompression. Use of anti-inflammatory agents including nonsteroidal anti-inflammatory medications or corticosteroids is recommended but is controversial. Protocols for the use of intravenous high dose methylprednisolone sodium succinate (Solumedrol, 30 mg/kg over 20 minutes at time 0, followed by 15 mg/kg over 10 minutes at 2 and 4 hours) and prednisolone sodium succinate (Soludelta Cortef, 20 mg/kg over 10-20 minutes) are well-described, and have been indicated for the perioperative period. Caution is advised with the use of dexamethasone, which may cause colonic ulceration and perforation. Animals diagnosed with lower motor neuron disease may require long term care including intravenous fluid therapies and mechanical ventilation. If thymoma is present, thymectomy is recommended following stabilization of the animal. If megaesophagus is present, vigilant measures to prevent aspiration pneumonia are advised. Clotting factor deficiencies should be corrected with blood product transfusions and vitamin K1 if applicable. Animals with severe thrombocytopenias should be assessed for immune-mediated disease and treated with immunosuppressive therapies including corticosteroids and azathioprine if present. The emergency clinician should work closely with the neurologist and surgeon for continued management and diagnostic plans.