Epilepsy Emergencies (Epilepsy 2016)

Educational Objectives

The goal of this lecture is to improve diagnosis and treatment of epilepsy. After hearing and assimilating this lecture, the clinician will be better able to:

1. Recognize and manage nonconvulsive status epilepticus.

Summary

Definition: Status epilepticus historically defined as continuous seizure activity lasting 30 minutes (duration connoting neuronal injury); this definition impractical because clinical intervention earlier than 30 minutes desirable; operational definition — seizure lasting more than 5 minutes despite intervention.

Pathophysiology: Status epilepticus associated with mismatch between excitation and inhibition; after 3 to 5 minutes of seizing, inhibitory mechanisms in brain typically suppress electrical activity; when these mechanisms fail, patient in status epilepticus with continuous seizures or acute repetitive seizures that merge into continuous seizures; seizure activity self-facilitated through downregulation of inhibitory γ–aminobutyric acid receptors and upregulation of excitatory glutamate receptors; process may be amplified in other areas of brain; most frequent amplifier mesial temporal lobe; input traverses perforant pathway and enters parahippocampal and dentate gyri, then travels back to hippocampus; long-term consequences of status epilepticus include loss of memory and atrophy of brain; on MRI, restricted diffusion sometimes observed in mesial temporal region.

Classification: Convulsive and nonconvulsive status epilepticus exist on continuum; generalized convulsive status epilepticus — associated with faster rate of damage in brain; should be treated emergently; nonconvulsive — may persist longer and be unrecognized; patient may demonstrate only subtle twitch of eyes or face; although damage to brain probably accumulates more slowly, nonconvulsive seizures should be treated aggressively because of possibility of delayed diagnosis; continuum — seizures may initially have generalized motor features but evolve to nonconvulsive status epilepticus (ie, motor features disappear as electromechanical dissociation develops); 37% of patients treated for convulsive status epilepticus continue to have electrographic seizures; neurologist must consider this possibility and use video-EEG monitoring to detect nonconvulsive status epilepticus.

Neuronal damage: Pathophysiology — greater capacity for damage to brain with convulsive status epilepticus as yet unexplained; long-term nonconvulsive status epilepticus often one component of acute symptomatic etiology (eg, left temporal stroke, tumor, hemorrhage); in such cases, seizures may be generated by areas of brain with preexisting damage; however, patients with absence epilepsy (with typical 3-Hz spike-and-wave pattern) have less damage than patients with convulsive status epilepticus, so some unknown factor responsible for damage; metabolic requirements — during convulsive status epilepticus, need for oxygen and glucose rises rapidly; after 20 to 30 minutes, supply cannot meet metabolic demands and lactic acid levels spike; metabolic failure probably responsible for most damage caused by convulsive status epilepticus; in patients in nonconvulsive status epilepticus, electrical activity from surrounding areas (rather than pure metabolic failure) causes damage.

Mechanism of electromechanical dissociation: May present with subtle movements in patients unable to make larger movements because of “energy failure”; however, nonconvulsive status epilepticus that originates in non-eloquent area, or in region that produces altered mental status, may mask clinical signs.

Diagnostic clues to nonconvulsive status epilepticus: Mental status — most important predictor; among patients evaluated for possible nonconvulsive status epilepticus, seizures detected in 6% of awake patients, 20% of lethargic patients, 25% of stuporous patients, and one-third of comatose patients; primary neurologic injury — high-risk conditions include hemorrhagic stroke (subdural, subarachnoid, or intracerebral), tumor, and infection of CNS; experienced clinician may notice changes in mental status beyond those expected for patients with these conditions alone; when mental status inconsistent with clinical condition, continuous EEG monitoring indicated.

Management: Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) — showed that time to treatment more however, because nonconvulsive seizures associated with delay in diagnosis, response to first medication seen in only 15%; Veterans Administration Cooperative Trial — randomized controlled trial confirmed efficacy of IV lorazepam for status epilepticus in dose of 0.1 mg/kg; dosage and administration — in clinical practice, inadequate dose of lorazepam often given because of concerns about respiratory suppression (although 2 mg/kg to 4 mg/kg often prescribed, typical patient needs 8 mg).

Other options for acute treatment: Midazolam autoinjector used in prehospital setting; similar results might be obtained with rectal diazepam or buccal or intranasal midazolam; in hospital, IM midazolam may be used when no IV access obtained; otherwise, IV lorazepam given, followed by antiepileptic medications; antiepileptic drugs — in Veterans Administration Cooperative Trial, fosphenytoin 20 mg/kg showed lowest efficacy (43%) among medications studied; ongoing Established Status Epilepticus Trial comparing fosphenytoin with other medications; other choices include IV levetiracetam, IV valproate, IV lacosamide, and IV phenobarbital; efficacy of phenobarbital 60%, but drug profoundly sedating; third-line agents (anesthetics) preferred over phenobarbital.

Urgency of treatment: Administration of series of medications may require several hours; however, status epilepticus most likely to respond when treated early; goal to complete first- and second-line treatments within 1 hour; third-line agents — third-line therapy for resistant status epilepticus includes constant infusions of first-line agents; typical first choice midazolam has minimal effects on blood pressure in critically ill patients; propofol accessible and has short half-life, but high doses over long period may produce propofol infusion syndrome with heart failure and rhabdomyolysis; pentobarbital effective but has long half-life, so propofol or midazolam typically tried first.

Readings

Hantus S. Epilepsy emergencies. Continuum (Minneap Minn) 2016;22(1).

Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 1998 Sep 17;339(12):792-8.

Disclosures

For this program, the following was disclosed: Dr. Hantus reports nothing to disclose. Unlabeled Use of Products/Investigational Use Disclosure: Dr. Hantus reports nothing to disclose. To view disclosures of planning committee members with relevant financial relationships, visit: audiodigest.org/continuumaudio/committee. All other members of the planning committee report nothing to disclose.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

CA050201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.