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Vol. 22, No. 7July 2000
Refereed Peer Review
FOCAL POINTKEY FACTS
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Status epilepticus (SE) is amedical emergency that requiresprompt treatment for both theseizure activity and the resultantsystemic abnormalities.
Status Epilepticus:Clinical Features andPathophysiology 
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 atleast 5 minutes or two or more discrete seizures between which there is incomplete recoveryof consciousness. SE is a medical emergency that requires prompt treatment to avoid neuro-logic morbidity.The etiologies of SE are similar to those for individual generalized convulsiveseizures. The pathophysiology of SE is also similar to that of an individual seizure event; how-ever, loss of the inhibitory mechanisms responsible for the cessation of an isolated event issuspected. Systemic effects of continuous seizure activity can be damaging if not identifiedand treated promptly. This article discusses the clinical and physiologic features of SE as wellas the pathophysiology of this disorder.
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tatus epilepticus (SE) is a common medical emergency that requires prompttreatment to avoid appreciable neurologic morbidity.
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Proper managementinvolves prompt seizure control and treatment of the underlying etiology.
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Knowledge of the basic mechanisms of neuronal injury and systemic effects of SEprovides the background required to determine the rapidity with which treatmentshould be initiated. These considerations should be balanced carefully against theside effects of aggressive pharmacologic agents to determine appropriate treat-ment. This article defines SE and addresses the clinical features, physiologic fea-tures, and pathophysiology of the condition. Companion articles will discuss sys-temic and pharmacologic management as well as therapy for refractory patientsand potential at-home treatment.
DEFINITION
Status epilepticus has been defined as a seizure that “persists for a sufficient lengthof time or is repeated often enough that recovery between attacks does not occur.”
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This definition has been modified to state that SE represents seizures that persist for20 to 30 minutes, based on the duration necessary to cause injury to the centralnervous system.
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This description is misleading, however, because SE is usually treated clinically well before this arbitrary time has elapsed.
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 A more practical defini-tion of SE is that it is a continuous series of two or more discrete seizures lasting atleast 5 minutes between which there is incomplete recovery of consciousness.
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SE is defined by a period of atleast 5 minutes of continuousseizure activity.
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Several pathophysiologicchanges, including hypertension,tachycardia, hypoglycemia,acidosis, and hyperthermia,occur during SE.
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Although the precise mechanismunderlying the pathophysiologyof seizures is unknown, it isthought to be related to abnormallevels of excitation and inhibitionwithin a group of neurons inwhich synchronous dischargecannot be suppressed.
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Precipitating factors must beinvestigated to facilitate seizurecontrol and thereby preventirreversible cerebral damage.
 
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This definition of SE guidesclinicians in treatment specif-ically intended to reduceneurologic injury and is dis-tinct from the definition of cluster seizures. Clusterseizures are two or moreseizures occurring over a rela-tively brief period (i.e., min-utes to 24 hours) between which the patient regainsconsciousness.
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The essential element of SE is a failure of the mecha-nisms that terminate individ-ual seizures and produce a re-fractory period during whichanother seizure cannot oc-cur.
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Thus, in SE seizures re-cur before full recovery fromthe pathophysiologic alter-ations in brain function in-duced by the previous sei-zure.
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If recurrent convulsionsare allowed to persist withouttreatment or with inadequate treatment, a progressivediminution of convulsive activity occurs such that themotor manifestations of SE become increasingly subtle.In this state, patients may exhibit profound stupor orcoma, with convulsive activity consisting of only subtletwitches of the extremities or trunk or nystagmoid move-ment of the eyes.
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Of adult human patients recently diagnosed with ep-ilepsy, 12% to 30% first presented in SE.
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 Approxi-mately 100 to 150,000 cases of SE are reported in chil-dren and adults in the United States each year.
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Theprevalence of SE in veterinary medicine has not beendetermined; however, dogs with either SE or clusterseizures have been estimated to be 0.44% of the totalhospital admissions.
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In addition, Podell and cowork-ers reported fatal SE in 3 of 50 dogs (6%).
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OUTCOMES AND CAUSES
Emergent presentation of SE has recently been evaluat-ed in veterinary medicine. In a study by Bateman andParent,
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156 dogs admitted to a veterinary hospital forSE or cluster seizures were retrospectively evaluated (TableI). A specific cause for the seizures could not be deter-mined in 25.8% of the cases. Approximately 27% werediagnosed with primary (genetic or idiopathic) epilepsy.
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Secondary or acquired epilepsy (having an identifiablestructural cause within the brain)
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 was identified as thecause of seizures in 35% of the cases, and reactive epilep-tic seizures were reported in7% of the cases.
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Dogs withreactive epileptic seizures areconsidered to have normalbrain structure; the seizuresare caused by intoxication orby systemic, metabolic, orendocrine abnormalities.
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Chronic processes that result-ed in SE included preexistingepilepsy in which SE iscaused by breakthroughseizures or the discontinua-tion of antiepileptic drugs.
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In almost 6% of the cases,
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low antiepileptic drug con-centration was determined tobe the cause of seizures. We have recently completeda case-controlled cohort study evaluating 50 dogs with gen-eralized convulsive SE.
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Of the dogs studied, 28% werediagnosed with primary epilepsy, 32% secondary epilepsy, and 12% reactive epilepsy.
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 A specific causecould not be determined in 28% of the cases (Table I).In the Bateman and Parent study,
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cerebrospinal fluid(CSF) abnormalities were documented in 75 (73.5%) of the 102 dogs with either SE or cluster seizures. In ourstudy, 12 (36%) of the 33 dogs with SE had abnormalCSF compared with 3 (12%) of the 25 dogs admittedfor non-SE seizures.
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 An unbiased mortality rate of dogs with SE is un-known because many animals are euthanized before ag-gressive diagnostics and treatment are undertaken. Theoverall mortality rate among human adults with SEranges from 3% to 22%.
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These findings are diffi-cult to interpret considering the variety of underlyingproblems that can cause SE. These underlying factorsmay also explain why the mortality rate associated sole-ly with SE has not been evaluated in animals. In theBateman and Parent study,
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approximately 25% of 156dogs with SE or cluster seizures died or were eutha-nized. No significant associations were observed be-tween the outcome of dogs with SE or cluster seizuresand the breed, age at onset of seizure activity, type of seizure activity at admission, or findings on CSF analy-sis.
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However, a significant negative association wasidentified between the outcome and the diagnosis of granulomatous meningoencephalitis and the outcomeand loss of control of the seizure activity at 6 hours af-ter admission.
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Compendium 
July 2000Small Animal/Exotics
 
CLUSTER SEIZURES
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REACTIVE EPILEPTIC SEIZURES
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CEREBROSPINAL FLUID ANALYSIS
TABLE IClassifications and Causes of SeizuresResponsible for Status Epilepticus in Dogs
Classifications andPercentage ofPercentage of  Causes of SeizuresCase
12,a 
Cases 
14,b 
Primary epilepsy 
26.828.0
Secondary epilepsy 
35.132.0Meningoencephalitis22.712.0Neoplasia3.612.0Other8.88.0(including traumaand vascular disease)
Reactive seizures
6.712.0Metabolic5.24.0Intoxication1.58.0
Other
31.428.0Low antiepileptic5.7Not evaluateddrug concentrationNot determined25.828.0
Based on 156 dogs admitted a total of 194 times for SE orcluster seizures.
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Based on 50 dogs admitted for SE only.
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Magnetic resonance (MR)imaging or computed tomog-raphy (CT) yielded positivefindings in 19 (76%) of 25dogs with either SE or clusterseizures.
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Of the 50 dogs eval-uated for SE in our hospital,CT was used in 28, 13 (46%)cases of which showed abnor-mal findings.
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 Although no evidence existsto indicate that early initia-tion of appropriate treatmentimproves outcome in dogs with seizures, such evidencedoes exist in human medicineand remains an important ba-sic tenet of treatment.
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In ad-dition to the above correla-tions, hospital visits during which partial motor SE wasdocumented had a significantassociation with poor out-come for dogs.
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The mean duration of hospitalization for dogs withSE or cluster seizures is 51.6 ±42.6 hours with a meancost per hospital visit of $320 ±$175 (range, $45 to$1131).
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These figures are biased by the year of thestudy and the types of seizures treated; however, they are a good indication of the financial commitment thatmay be required to successfully treat a patient with SE.
CLINICAL FEATURES
In Bateman and Parent’s study of 156 dogs admittedto a veterinary hospital (between 1990 to 1995) withSE or cluster seizures, the mean patient age was 4.2 ±3.3 years (range, 1.9 to 13.9 years).
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In our study, themean age of the 50 dogs evaluated for SE at our hospi-tal over the course of 9 years (1990 to 1999) was 5.05years (range, 0.15 to 15 years), with no statistical gen-der prevalence
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; however, the results of the Raw andGaskell study indicate that there is a male sex predilec-tion for primary epilepsy.
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In the Bateman and Parentstudy, the sex distribution for severe seizures (i.e., SEand cluster seizures) was broken down as follows:23.7% were castrated, 35.3% were sexually intactmales, 26.3% were spayed, and 14.7% were sexually in-tact females.
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The English foxhound, pug, teacup poo-dle, Boston terrier, and Lakeland terrier were signifi-cantly overrepresented in the Bateman and Parentstudy, but the authors urge cautious interpretation of this finding.
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The English foxhound, Lakeland terrier,and teacup poodle had low numbers of their respectivebreeds found in the overallhospital population; all of thepugs and Boston terriers— with one exception—had sec-ondary epilepsy, to whichthese breeds are consideredpredisposed.
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Patients with SE usually have clinically obvious sei-zures, such as tonic, clonic, ortonic–clonic movements of the extremities.
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This activity is classified as generalized con-vulsiveor grand mal seizuresand is usually accompanied by marked impairment of con-sciousness.
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Typically, there isgradual recovery of conscious-ness following each convul-sion, but if the patient has notrecovered fully to baseline be-fore the next convulsion oc-curs, the patient is consideredto be in generalized convul-sive or tonic–clonic SE. Nonconvulsive SE is well recog-nized in humans (in whom patients are classified as hav-ing complex partial SE and absent SE).
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In veterinary medicine, these types of SE have not been well docu-mented clinically or electroencephalographically. Howev-er, veterinary patients have been documented to have fo-cal motor seizure activity without loss of consciousness.Focal motor activity is classified as a partial seizure indi-cating involvement of only a focal area of the brain.
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There is the possibility of this activity being prolongedenough to be classified as partial motor SE or that it willbe followed by generalized (tonic–clonic) SE.
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Human patients who have electroencephalographicevidence of SE with little or no visible motor activity are still at risk for central nervous system injury and re-quire immediate attention.
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Ongoing SE can produceneuronal death in experimental models of SE even when metabolic factors are corrected and in paralyzedanimals that are ventilated.
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In our clinical experience, we have found that nonconvulsive SE does occur in pa-tients with resultant poor outcomes if intervention isnot instituted.
PHYSIOLOGIC FEATURES
Several physiologic changes occur during the courseof SE, including hypertension, tachycardia, hypo-glycemia, acidosis, and hyperthermia (Figure 1). Theinitial physiologic response is a massive release of epinephrine and norepinephrine into the circulation.
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Small Animal/Exotics
Compendium 
July 2000
 
PRIMARY EPILEPSY
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TONIC–CLONIC MOVEMENTS
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FOCAL MOTOR ACTIVITY
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NEURONAL DEATH
Figure 1—
The effects of status epilepticus (SE) on thebody. It is not always possible to obtain electroencephalo-graphic evidence of seizure discharges. Electrocardio-graphic evidence of heart rhythm disturbances may be de-tected after SE occurs. Hyperthermic damage to musclesleading to rhabdomyolysis may cause renal failure. Thedetection of myoglobinuria and reduced urine productionafter SE is vital to outcome.
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