Status Epilepticus-clinical Features And Pa Tho Physiology

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Vol. 22, No. 7 July 2000

Refereed Peer Review

FOCAL POINT ★Status epilepticus (SE) is a medical emergency that requires prompt treatment for both the seizure activity and the resultant systemic abnormalities.

KEY FACTS ■ SE is defined by a period of at least 5 minutes of continuous seizure activity. ■ Several pathophysiologic changes, including hypertension, tachycardia, hypoglycemia, acidosis, and hyperthermia, occur during SE. ■ Although the precise mechanism underlying the pathophysiology of seizures is unknown, it is thought to be related to abnormal levels of excitation and inhibition within a group of neurons in which synchronous discharge cannot be suppressed. ■ Precipitating factors must be investigated to facilitate seizure control and thereby prevent irreversible cerebral damage.

Status Epilepticus: Clinical Features and Pathophysiology University of Georgia

Simon R. Platt, BVM&S, MRCVS John J. McDonnell, DVM, MS ABSTRACT: Status epilepticus (SE) has been defined as continuous seizure activity lasting at least 5 minutes or two or more discrete seizures between which there is incomplete recovery of consciousness. SE is a medical emergency that requires prompt treatment to avoid neurologic morbidity. The etiologies of SE are similar to those for individual generalized convulsive seizures. The pathophysiology of SE is also similar to that of an individual seizure event; however, loss of the inhibitory mechanisms responsible for the cessation of an isolated event is suspected. Systemic effects of continuous seizure activity can be damaging if not identified and treated promptly. This article discusses the clinical and physiologic features of SE as well as the pathophysiology of this disorder.

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tatus epilepticus (SE) is a common medical emergency that requires prompt treatment to avoid appreciable neurologic morbidity.1–5 Proper management involves prompt seizure control and treatment of the underlying etiology.3 Knowledge of the basic mechanisms of neuronal injury and systemic effects of SE provides the background required to determine the rapidity with which treatment should be initiated. These considerations should be balanced carefully against the side effects of aggressive pharmacologic agents to determine appropriate treatment. This article defines SE and addresses the clinical features, physiologic features, and pathophysiology of the condition. Companion articles will discuss systemic and pharmacologic management as well as therapy for refractory patients and potential at-home treatment.

DEFINITION Status epilepticus has been defined as a seizure that “persists for a sufficient length of time or is repeated often enough that recovery between attacks does not occur.”6 This definition has been modified to state that SE represents seizures that persist for 20 to 30 minutes, based on the duration necessary to cause injury to the central nervous system.3,4,6,7 This description is misleading, however, because SE is usually treated clinically well before this arbitrary time has elapsed.7 A more practical definition of SE is that it is a continuous series of two or more discrete seizures lasting at least 5 minutes between which there is incomplete recovery of consciousness.6–8

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This definition of SE guides tic seizures were reported in TABLE I clinicians in treatment specif7% of the cases.12 Dogs with Classifications and Causes of Seizures ically intended to reduce reactive epileptic seizures are Responsible for Status Epilepticus in Dogs neurologic injury and is dis- Classifications and considered to have normal Percentage of Percentage of tinct from the definition of Causes of Seizures brain structure; the seizures 12,a 14,b Cases Cases cluster seizures. Cluster are caused by intoxication or 26.8 28.0 seizures are two or more Primary epilepsy by systemic, metabolic, or seizures occurring over a rela- Secondary epilepsy endocrine abnormalities. 13 35.1 32.0 tively brief period (i.e., min- Meningoencephalitis Chronic processes that result22.7 12.0 3.6 12.0 utes to 24 hours) between Neoplasia ed in SE included preexisting 8.8 8.0 which the patient regains Other epilepsy in which SE is (including trauma consciousness.9 caused by breakthrough and vascular disease) The essential element of seizures or the discontinuaSE is a failure of the mecha- Reactive seizures tion of antiepileptic drugs.7 6.7 12.0 nisms that terminate individ- Metabolic In almost 6% of the cases,12 5.2 4.0 1.5 8.0 ual seizures and produce a re- Intoxication low antiepileptic drug confractory period during which Other centration was determined to 31.4 28.0 another seizure cannot oc- Low antiepileptic be the cause of seizures. 5.7 Not evaluated cur.7 Thus, in SE seizures reWe have recently completed drug concentration cur before full recovery from Not determined a case-controlled cohort study 25.8 28.0 the pathophysiologic alterevaluating 50 dogs with genations in brain function in- aBased on 156 dogs admitted a total of 194 times for SE or eralized convulsive SE.14 Of 12 duced by the previous sei- bcluster seizures. the dogs studied, 28% were Based on 50 dogs admitted for SE only.14 zure.7 If recurrent convulsions diagnosed with primary are allowed to persist without epilepsy, 32% secondary treatment or with inadequate treatment, a progressive epilepsy, and 12% reactive epilepsy.14 A specific cause diminution of convulsive activity occurs such that the could not be determined in 28% of the cases (Table I). motor manifestations of SE become increasingly subtle. In the Bateman and Parent study,12 cerebrospinal fluid In this state, patients may exhibit profound stupor or (CSF) abnormalities were documented in 75 (73.5%) of coma, with convulsive activity consisting of only subtle the 102 dogs with either SE or cluster seizures. In our twitches of the extremities or trunk or nystagmoid movestudy, 12 (36%) of the 33 dogs with SE had abnormal ment of the eyes.7 CSF compared with 3 (12%) of the 25 dogs admitted Of adult human patients recently diagnosed with epfor non-SE seizures.14 6,10 ilepsy, 12% to 30% first presented in SE. ApproxiAn unbiased mortality rate of dogs with SE is unmately 100 to 150,000 cases of SE are reported in chilknown because many animals are euthanized before agdren and adults in the United States each year.7,11 The gressive diagnostics and treatment are undertaken. The prevalence of SE in veterinary medicine has not been overall mortality rate among human adults with SE determined; however, dogs with either SE or cluster ranges from 3% to 22%.2,10,15 These findings are diffiseizures have been estimated to be 0.44% of the total cult to interpret considering the variety of underlying hospital admissions.12 In addition, Podell and coworkproblems that can cause SE. These underlying factors ers reported fatal SE in 3 of 50 dogs (6%).13 may also explain why the mortality rate associated solely with SE has not been evaluated in animals. In the OUTCOMES AND CAUSES Bateman and Parent study,12 approximately 25% of 156 Emergent presentation of SE has recently been evaluatdogs with SE or cluster seizures died or were euthaed in veterinary medicine. In a study by Bateman and nized. No significant associations were observed beParent,12 156 dogs admitted to a veterinary hospital for tween the outcome of dogs with SE or cluster seizures SE or cluster seizures were retrospectively evaluated (Table and the breed, age at onset of seizure activity, type of I). A specific cause for the seizures could not be deterseizure activity at admission, or findings on CSF analymined in 25.8% of the cases. Approximately 27% were sis.12 However, a significant negative association was 12 diagnosed with primary (genetic or idiopathic) epilepsy. identified between the outcome and the diagnosis of Secondary or acquired epilepsy (having an identifiable granulomatous meningoencephalitis and the outcome structural cause within the brain)13 was identified as the and loss of control of the seizure activity at 6 hours afcause of seizures in 35% of the cases, and reactive epilepter admission.12 C L U S T E R S E I Z U R E S ■ R E A C T I V?E? ?E ?P I ■ L E P?T?I?C? S■E I Z? U ? ?R ?E S■ ■? ?C?E?R E B R O S P I N A L F L U I D A N A L Y S I S

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Magnetic resonance (MR) breeds found in the overall imaging or computed tomoghospital population; all of the raphy (CT) yielded positive pugs and Boston terriers— findings in 19 (76%) of 25 with one exception—had secdogs with either SE or cluster ondary epilepsy, to which seizures.12 Of the 50 dogs evalthese breeds are considered uated for SE in our hospital, predisposed.12 Patients with SE usually CT was used in 28, 13 (46%) have clinically obvious seicases of which showed abnorzures, such as tonic, clonic, or mal findings.14 Although no evidence exists tonic–clonic movements of to indicate that early initiathe extremities.7 This activity is classified as generalized contion of appropriate treatment vulsive or grand mal seizures improves outcome in dogs and is usually accompanied by with seizures, such evidence does exist in human medicine Figure 1—The effects of status epilepticus (SE) on the marked impairment of conand remains an important ba- body. It is not always possible to obtain electroencephalo- sciousness.7,8 Typically, there is sic tenet of treatment.12 In ad- graphic evidence of seizure discharges. Electrocardio- gradual recovery of consciousdition to the above correla- graphic evidence of heart rhythm disturbances may be de- ness following each convultions, hospital visits during tected after SE occurs. Hyperthermic damage to muscles sion, but if the patient has not which partial motor SE was leading to rhabdomyolysis may cause renal failure. The recovered fully to baseline bedocumented had a significant detection of myoglobinuria and reduced urine production fore the next convulsion ocassociation with poor out- after SE is vital to outcome. curs, the patient is considered come for dogs.12 to be in generalized convulThe mean duration of hospitalization for dogs with sive or tonic–clonic SE. Nonconvulsive SE is well recogSE or cluster seizures is 51.6 ± 42.6 hours with a mean nized in humans (in whom patients are classified as havcost per hospital visit of $320 ± $175 (range, $45 to ing complex partial SE and absent SE).7 In veterinary 12 medicine, these types of SE have not been well docu$1131). These figures are biased by the year of the study and the types of seizures treated; however, they mented clinically or electroencephalographically. Howevare a good indication of the financial commitment that er, veterinary patients have been documented to have fomay be required to successfully treat a patient with SE. cal motor seizure activity without loss of consciousness. Focal motor activity is classified as a partial seizure indiCLINICAL FEATURES cating involvement of only a focal area of the brain.17 In Bateman and Parent’s study of 156 dogs admitted There is the possibility of this activity being prolonged to a veterinary hospital (between 1990 to 1995) with enough to be classified as partial motor SE or that it will SE or cluster seizures, the mean patient age was 4.2 ± be followed by generalized (tonic–clonic) SE.17 12 3.3 years (range, 1.9 to 13.9 years). In our study, the Human patients who have electroencephalographic mean age of the 50 dogs evaluated for SE at our hospievidence of SE with little or no visible motor activity tal over the course of 9 years (1990 to 1999) was 5.05 are still at risk for central nervous system injury and reyears (range, 0.15 to 15 years), with no statistical genquire immediate attention.10 Ongoing SE can produce 14 der prevalence ; however, the results of the Raw and neuronal death in experimental models of SE even Gaskell study indicate that there is a male sex predilecwhen metabolic factors are corrected and in paralyzed tion for primary epilepsy.16 In the Bateman and Parent animals that are ventilated.3,7 In our clinical experience, study, the sex distribution for severe seizures (i.e., SE we have found that nonconvulsive SE does occur in paand cluster seizures) was broken down as follows: tients with resultant poor outcomes if intervention is 23.7% were castrated, 35.3% were sexually intact not instituted. males, 26.3% were spayed, and 14.7% were sexually intact females.12 The English foxhound, pug, teacup pooPHYSIOLOGIC FEATURES dle, Boston terrier, and Lakeland terrier were signifiSeveral physiologic changes occur during the course cantly overrepresented in the Bateman and Parent of SE, including hypertension, tachycardia, hypostudy, but the authors urge cautious interpretation of glycemia, acidosis, and hyperthermia (Figure 1). The this finding.12 The English foxhound, Lakeland terrier, initial physiologic response is a massive release of and teacup poodle had low numbers of their respective epinephrine and norepinephrine into the circulation.4,7 P R I M A R Y E P I L E P S Y ■ T O N I C – C L O N?I C ? ?M ? O■V E?M?E?N? T■ S ■? ? F? O ? C■A L ?M ? ?O?T O R A C T I V I T Y ■ N E U R O N A L D E A T H

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ciated morbidity and mortaliThis increase in circulating Trans-membrane voltage-gated sodium–potassium channel ty. It is clear that seizures are catecholamines results in inlinked, at the lowest level, to creased systemic, pulmonary, membrane potentials, ionic and left atrial blood pressure; fluxes, and the generation of heart rate; plasma glucose action potentials. 27 In neuconcentration,7,18,19 and cardiac 20 rons, action potentials result arrhythmias. Based on experfrom changes in the memimental animal studies, it has brane permeability to sodibeen suggested that the hyperum, chloride, calcium, and glycemia may exacerbate SEpotassium. These ions enter induced neuronal damage.21 the cell by voltage-gated Therefore, glucose administration during SE should be Figure 2—A voltage-gated sodium–potassium channel as- channels (Figure 2). In the resting state, the excautious unless true hypo- sists in the creation of an action potential when the sudglycemia can be established. den influx of sodium ions (Na+) alters the relative concen- tracellular sodium concentration is much higher than the Respiratory function is fre- trations of sodium and potassium (K+) in the cytosol. intracellular concentration quently impaired in early and the sodium channels are SE.22 Pulmonary edema is a minimally permeable. A sodicommon finding in experium-potassium-ATPase pump mental SE and has also been maintains the high extracellureported on postmortem exlar sodium and intracellular aminations following clinical potassium concentrations. episodes of SE.23 Membrane depolarization is Acidosis, which is caused caused by a sudden increase by a combination of respirain the membrane permeabilitory failure and the release of ty to sodium, consequently systemic lactate during genergenerating an action potenalized convulsive activity,7 is tial.27 Immediately after the frequently reported in SE. action potential generation, Some degree of acidosis can be found even in paralyzed Figure 3—Release of a neurotransmitter from the axonal sodium channels close and terminal following the propagation of an action potential. and artificially ventilated ani- The synaptic vesicles contain neurotransmitter substance potassium channels open to mals.7 In late SE (usually after that is released into the synaptic cleft and binds to the allow the rapid efflux of potassium from the intracel30 minutes of seizure activi- postsynaptic receptors. lular space. 27 As the action ty), many physiologic parampotential reaches the axon tereters return to baseline values minal, voltage-dependent calcium channels allow entry or even drop below baseline.7 After an initial period of of calcium ion into the terminal, causing the release of hypertension, blood pressure begins to decrease after 15 a neurotransmitter (Figure 3).27 The generation of the to 30 minutes of experimental SE and may be marked18,24,25 action potentials may be critical in the initiation and ly low after 2 hours of continuous seizure activity. propagation of the seizure discharge. The theory that Plasma glucose levels may begin to decrease to hypomany normal cerebral neurons exhibit intrinsic burstglycemic levels.18,24,25 Renal failure may develop as a reing activity in which populations of cells fire in a rhythsult of rhabdomyolysis with resultant myoglobinuria.26 mic and repetitive manner is already well accepted.27 PATHOPHYSIOLOGY Seizures are likely if the balance between excitation or Seizures are the clinical manifestation of rapid, excesinhibition surrounding these cell populations is abnorsive neuronal discharges in the brain.4 However, the mal.27 The synchronous firing of populations of neuprecise electrophysiologic and molecular mechanisms rons is ultimately responsible for a seizure event.27 that underlie the pathophysiology of seizures and SE Several neurotransmitters have been implicated in the are poorly understood. A firm understanding of the generation of seizures. γ-Aminobutyric acid (GABA) is pathophysiologic causes and effects of SE will enable a critical neuromodulator in the brain.27 GABA mediveterinarians to make informed treatment decisions for ates synaptic inhibition in the hippocampus by generatanimals that present in SE, perhaps decreasing the assoing inhibitory postsynaptic potentials, which counterG L U C O S E A D M I N I S T R A T I O N ■? ?A?C?I D■O S?I?S? ?■ ■A C?T?I?O?N ■P O?T?E?N?T I A L S ■ S O D I U M C H A N N E L S

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other neurons, it may propabalance excitatory inputs from gate to other areas of the other brain regions.27 There brain. It is hypothesized that a are two primary GABA receppopulation of cortical neurons tor subtypes—GABA A and within an epileptic focus unGABAB. GABAA is believed to dergoes paroxysmal synchrobe more intimately involved nous depolarization termed in the neurochemistry of paroxysmal depolarizing shift seizures.27 After GABA binds (Figure 5).29 This results in an to GABAA, there is an influx abnormal burst of action poof chloride ions through the tentials that continue in synchloride channel, which rechronous volleys without apsults in hyperpolarization and propriate inhibition.27 Although hence inhibition (Figure 4). A elevated extracellular potassilarge body of evidence curum levels may induce seizures, rently suggests that disruption the appearance of seizures is of GABAergic function may also dependent on intact be central to the molecular is synaptic inputs from the hippathophysiology of seizures.27 Figure 4—The γ-aminobutyric acid (GABA) receptor – During a seizure, an extra- responsible for an influx of chloride ions (Cl ) into the pocampus, which appears to neuron after binding with a benzodiazepine (BZD), facilitate the transition from cellular elevation of potassi- GABA, or a barbiturate (BBT) such as phenobarbital. normal to ictal cell firing.27 um and a decrease in calcium The basic pathophysiology are responsible for enhancing of SE involves a failure of mechanisms that usually stop neuronal excitability and facilitating seizure spread.4,28 an isolated seizure.7 This failure can arise from abnorIf there is synchronization of the seizure discharge with mal excessive excitation or ineffective recruitment of inhibition.7 It is likely that numerous mechanisms are involved depending on the underlying cause. Recent experimental work has suggested that the failure of in• Easy Reference Index hibition may be caused by a shift in the functional Emergency Medicine • 364 Pages properties of the GABA receptor that occurs as seizures in Small Animal Practice • Color and become prolonged.7,10 Repetitive neuronal firing imposBlack-and-White es a massive metabolic demand, which is exacerbated Photographs ✶ Cardiac Emergencies by glutamate-mediated excitotoxicity and decreased ✶ Trauma GABA inhibitory neurotransmission.7,10 This has be✶ Shock Emergency come known as the excitotoxic theory of neuronal Medicine ✶ Seizure-related damage.7 Disorders Many molecular signals are triggered by SE, activat✶ Toxicology ing receptors in neuronal membranes.7 Activation of ✶ Thermal Emergencies the N-methyl-D-aspartate (NMDA) receptor has been and much more known to play a key role in neuronal signaling and de! $ f f o layed neuronal death.28 It has been shown that NMDA 10% in Small A nimal Prac receptors become activated during continuous neuronal tice 0 stimulation; in several animal models, NMDA receptor 0 $ The antagonists have been shown to block or delay seizure COMPENDIUM COLLECTION activity. However, little is known about the receptor’s precise role.7 Excess concentrations of the excitatory amino-acid glutamate causes NMDA receptors to open cation channels to calcium (Figure 6). Large concentrations of calcium enter the neuron and then induce a Email: [email protected] cascade of intracellular neurochemical events that can to order your copy or request a catalog of the kill the cell.7 Other possible neurotoxic substances reVLS BOOKS complete line of VLS books, journals, and videos. leased during SE include aspartate, free fatty acids, arachidonic acid, and free radicals.28

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Brain injury during prolonged seizure events may also be related to a mismatch between substrate supply and demand.3,28 Compensatory factors may be unable to meet the considerable metabolic demand placed on the brain during seizures.3 SE lasting longer than 30 minutes can cause brain damage, especially in the limbic structures.10,28 In several animal models of SE, histopathologic evidence of neuronal damage was identified following prolonged seizure activity within CA1 and CA3 sectors of the hippocampus; layers 3, 5, and 6 of the neocortex; Purkinje cells within the cerebellum; the thalamus; and the amygdala. 27 Animal models of SE have also demonstrated the deleterious role that hyperthermia, hypoxia, and hypotension play in creating further neuronal damage.10 However, observation of neuronal changes in well-ventilated animals in which adequate glucose levels have been maintained suggests that ongoing seizure activity itself substantially contributes to neuronal damage.10 In human studies, it has been suggested that SE may diminish neurocognitive abilities.27

UNDERLYING CAUSAL FACTORS When treating animals with SE, the precipitating factors must be recognized and treated in order to facilitate seizure control and ensure that the underlying cause is ministered to before irreversible cerebral damage results. Many cases of SE occur in patients with known chronic seizure disorders,30 although the true incidence of this has not been

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Figure 5—The spread of an ictal discharge through the cerebrum depends on the synchronization of individual neuronal electrical disturbances known as paroxysmal depolarizing shifts (PDS). A generalized convulsive seizure is the physical manifestation of the recruitment and synchronization of neuronal PDS throughout both cerebral hemispheres.

Figure 6—The glutamate receptor and its role in the pas-

sage of calcium into the cell body. Excessive passage of calcium into the cell because of excessive concentrations of glutamate can be responsible for cell destruction. (AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazole; NMDA = N-methyl-D-aspartate)

evaluated in veterinary medicine. Other disease processes commonly associated with SE are tumors, central nervous system infections, trauma, metabolic disorders (e.g., electrolyte disturbances), and vascular events. On initial presentation of the patient, it is prudent to examine the skull and spine for evidence of recent trauma. This should be done by gentle palpation, with particular attention in the assessment of crepitance, pain, and asymmetry. Standard laboratory blood tests, including evaluations for glucose, sodium, and calcium level abnormalities; renal and hepatic dysfunction; and serum acetylcholinesterase levels should be performed.3,31 It should be noted that liver enzymes may be increased shortly after seizure activity because of the effects of hypoxia and hypotension. 4 If hypoglycemia is the potential cause of SE or if blood glucose determination is unavailable, 500 mg/kg body weight of 50% dextrose (preferably diluted to 25%) should be administered intravenously over 15 minutes.3,7 Hyperglycemia can be detrimental to the brain in the hypoxic environment created by SE. To counteract this potential, intramuscular administration of thiamine (vitamin B1) at 25 to 50 mg per animal should precede glucose administration.3,7 Thiamine is essential as a coenzyme in glucose utilization by the brain.8 If intravenous therapy is difficult to perform, oral administration of Karo® syrup can be a useful substitute.

BRAIN DAMAGE ■ HIPPOCAMPUS ■ HYPOGLYCEMIA ■ SEIZURE STABILIZATION

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If the patient has been on phenobarbital or other anticonvulsants prior to SE, serum levels should be obtained. If encephalitis is suspected, a CSF analysis should be considered as soon as seizure stabilization occurs. The use of glucocorticoids can reduce cerebral edema formation and modulate the inflammatory response in the brain after a hypoxic event.32 However, corticosteroids have been shown to potentiate neuronal damage when ischemia is present and inhibit neuronal repair.32 The administration of glucocorticoids in SE should be aimed at interrupting the development of cerebral edema–induced brain swelling, which may elevate intracranial pressure. The use of high doses of methylprednisolone has not been evaluated in patients with SE but has been associated with improved outcome and survival when administered shortly after brain injury causing cerebral edema in experimental animals.32 Patients with new-onset seizures should be considered for brain imaging procedures such as MR imaging or CT. However, a normal CT scan does not exclude the possibility of cerebral pathology.7 In humans, reversible lesions documented in MR images following seizures have been characterized as having increased signal intensity on T2-weighted images, little or no mass effect, and partial or complete resolution without specific therapy.33 Recently, three dogs with lesions in the piriform/temporal lobe region secondary to seizure activity were described.33 All of the lesions had varying hyperintensity on T2-weighted images and hypointensity on T1-weighted images, and all partially or completely resolved after variable periods (10 days to 18 weeks) without seizure activity.33 The increased signal intensity on T2-weighted images represents an increase in relative water content of the brain tissue. Cytotoxic and vasogenic edema may both be responsible for this signal intensity seen following seizure activity.33 A team approach to patients in SE will be beneficial to accomplishing emergency stabilization, therapeutic intervention, and diagnostic investigation simultaneously. Concurrently, a medical history should be obtained from the owners or retrieved from available medical records.

SUMMARY Status epilepticus is a common medical emergency and should be treated immediately in an attempt to prevent permanent cerebral damage. The effects of SE on the heart, kidneys, muscles, and lungs can be equally devastating. Attention must be directed to each body system during and after the seizures. The etiology of this abnormality is not always immediately evident; furthermore, it is not always treatable. Although this is important to remember when devising a treatment pro-

tocol, it should not prevent the rapid institution of patient stabilization. ACKNOWLEDGMENT

The authors thank Ms. Allison Wright, Department of Educational Resources, University of Georgia, Athens, for providing the artistic content.

REFERENCES 1. Maytal J, Shinnar S, Moshe SL, et al: Low morbidity and mortality of status epilepticus in children. Pediatr 83(3): 323–331, 1989. 2. Harrison AM, Lugo RA, Schunk JE: Treatment of convulsive status epilepticus with propofol: Case report. Pediatr Emerg Care 13(6):420–422, 1997. 3. Cascino GD: Generalized convulsive status epilepticus. Mayo Clin Proc 71:787–792, 1996. 4. Boothe DM: Anticonvulsant therapy in small animals. Vet Clin North Am Small Anim Pract 28(2):411–448, 1998. 5. Singhi S: Refractory status epilepticus in children: Role of continuous diazepam infusion. J Child Neurol 13(1):23–26, 1998. 6. Lowenstein DH, Alldredge BK: Status epilepticus. N Engl J Med 338(14):970–976, 1998. 7. Treiman DM: Generalized convulsive status epilepticus, in Engel J, Pedley TA (eds): Epilepsy: A Comprehensive Textbook. Philadelphia, Lippincott-Raven Publishers, 1997, pp 669–680. 8. Podell M: Seizures in dogs. Vet Clin North Am Small Anim Pract 26 (4):779–809, 1996. 9. Braund KG: Clinical Syndromes in Veterinary Neurology. St. Louis, Mosby, 1994, pp 234–251. 10. Hauser WA: Status epilepticus: Epidemiologic considerations. Neurology 40(Suppl 2):9–13, 1990. 11. Morton LD, Rizkallah E, Pellock JM: New drug therapy for acute seizure management. Semin Pediatr Neurol 4(4): 51–63, 1997. 12. Bateman SW, Parent JM: Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases (1990–1995). JAVMA 215(10):1463–1468, 1999. 13. Podell M, Fenner WR, Powers JD: Seizure classification in dogs from a non-referral-based population. JAVMA 206(11): 1721–1728, 1995. 14. Platt SR, McDonnell JJ: Status epilepticus in the dog: A case-controlled cohort study. J. Small Anim Pract, submitted for publication, July 2000. 15. Walker LA, Slovis CM: Lidocaine in the treatment of status epilepticus. Acad Emerg Med 4(9):918–922, 1997. 16. Raw M, Gaskell CJ: A review of one hundred cases of presumed canine epilepsy. J Small Anim Pract 26:645–652, 1985. 17. Sorjonen DC: Psychomotor seizures in dogs, in Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI: Small Animal Practice. Philadelphia, WB Saunders Co, 1992, pp 992–995. 18. Benowitz NL, Simon RP, Copeland JR: Status epilepticus: Divergence of sympathetic activity and cardiovascular response. Ann Neurol 19(2):197–199, 1986.

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19. Plum F, Posner JB, Troy B: Cerebral metabolic and circulatory responses to induced convulsions in animals. Arch Neurol 18(1):1–13, 1968. 20. Lathers CM, Schraeder PL: Autonomic dysfunction in epilepsy: Characterization of autonomic cardiac neural discharges associated with pentylenetetrazol-induced epileptogenic activity. Epilepsia 23(6):633–647, 1982. 21. Pulsinelli WA, Levy DE, Sigsbee B, et al: Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med 74(4): 540–544, 1983. 22. Paydarfar D, Eldridge FL, Scott SC, et al: Respiratory responses to focal and generalized seizures in cats. Am J Physiol 260(5):R934–R940, 1991. 23. Kiessling M, Hossman KA, Kleihues P: Pulmonary edema during bicuculline-induced seizures in rats. Exp Neurol 74(2):430–438, 1981. 24. Horton RW, Meldrum BS, Pedley TA: Regional cerebral blood flow in the rat during prolonged seizure activity. Brain Res 192(2):399–412, 1980. 25. Meldrum BS, Horton RS, Bloom SR, et al: Endocrine factors and glucose metabolism during seizures in baboons. Epilepsia 20(5):527–534, 1979. 26. Singhal PC, Chugh KS, Gulati DR: Myoglobinuria and renal failure after status epilepticus. Neurology 28(2):200–201, 1978.

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27. Cruz J: Neurologic and Neurosurgical Emergencies. Philadelphia, WB Saunders Co, 1998, pp 51–88. 28. Ropper AH: Neurological and Neurosurgical Intensive Care. New York, Raven Press, 1993, pp 383–410. 29. Russo ME: Pathophysiology of epilepsy. Cornell Vet 71(2): 221–247, 1981. 30. Wilmore LJ: The first seizure and status epilepticus. Neurology 51(Suppl 4):34–38, 1998. 31. Walsh GO, Delgado-Escueta AV: Status epilepticus. Neurol Clin 11(4):835–853, 1993. 32. Johnson JA, Murtaugh RJ: Craniocerebral trauma, in Bonagura JD (ed): Kirk’s Current Veterinary Therapy XIII: Small Animal Practice. Philadelphia, WB Saunders Co, 2000, pp 178–186. 33. Mellema LM, Koblik PD, Kortz GD, et al: Reversible magnetic resonance imaging abnormalities in dogs following seizures. Vet Radiol Ultrasound 40(6):588–595, 1999.

About the Authors Drs. Platt and McDonnell are affiliated with the Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens. Both are Diplomates of the American College of Veterinary Internal Medicine (Neurology).