SeizuresAlison Smock, MDDepartment of NeurologyMedical University of South Carolina

What is a seizure?•Paroxysmal, hypersynchronous, abnormal

activity of neurons in the cerebral cortex

•Seizures are symptoms of an underlying process

•Manifestations of the seizure depend on the part of the brain affected

The way that I like to think about it diagnostically and prognostically…

Seizures

Provoked

Unprovoked• Medication non-

compliance• Metabolic derangements• Drug use/EtOH

withdrawal• Infection• Inflammatory state• Structural cause• Sleep deprivation

• Epilepsy• Secondary epilepsy

Mode of Onset Description

Focal Without impairment of consciousness or awareness:- With observable motor or autonomic components- Involving subjective sensory or psychic phenomena only, corresponding to the

concept of an aura

With impairment of consciousness or awareness

Evolving to a bilateral, convulsive seizure

Generalized Tonic-clonic (in any combination) Myoclonic Myoclonic-atonic Myoclonic-tonic

Non-convulsive

Absence Typical absence Atypical absence With special features (ie eyelid myoclonia) Myoclonic absence

ClonicTonicAtonic

Types of seizures

Continuum (Minneap Minn) 2013;19(3):571-597.

Semiology•Observable manifestations of a seizure

•Stereotyped

•Helps to classify the type of seizure/epilepsy a patient might have

Semiology – simple motor seizure •Simple, unnatural, rhythmic movements

that are due to stimulation of the primary and supplementary motor areas▫Myoclonic▫Tonic▫Clonic▫Tonic-clonic▫Versive

simple motor seizurefasciculation

Semiology – complex motor seizure•Complex motor movements that resemble

natural movements but that occur in an inappropriate setting▫Automatisms

•Complex partial seizures generally involve impaired awareness, so patients may appear to be doing purposeful things but are not responsive to external stimuli

Semiology – generalized•Primary generalized seizure

▫Tonic-clonic, tonic, clonic, myoclonic

•Secondary generalization▫Starts as a focal seizure and rapidly

spreads to involve both hemispheres

Semiology – non-convulsive•Non-convulsive or “subclinical” seizures

▫Highly varied spectrum of symptoms▫Mentation can range from alert, awake,

and following commands to obtundation▫Periods of abnormal mentation that cannot

be explained by metabolic/infectious abnormalities or structural lesions

▫Patient’s with recent status epilepticus

Standard work up for seizure•Take a good history

▫Semiology▫Medications▫Substance abuse▫Risk factors:

History of head trauma, stroke, brain tumor, intracerebral instrumentation

Febrile seizures as a child History of meningitis/encephalitis Family history Birth history

Semiology – taking a good history•If a patient’s chief complaint is “seizure” ask

them:▫How does your seizure start▫What do you do during your seizure▫Do you lose awareness▫Is there extremity jerking/shaking▫Is there tongue biting▫Is there bowel or bladder incontinence▫How long does it last▫Are you fatigued afterward

How long does it take for you to return to baseline

Agents reported to induce seizuresAnalgesics Fentanyl, mefenamic acid, meperidine, petazocine, propoxyphene, tramadol

Antibiotics Pencillins, penems, cephalosporine, isoniazid, lindane, metronidazole, nalidixic acid, pyrimethamine

Antidepressants Amitriptyline, bupropion, doxepin, maprotiline, mianserin, nomifensine, nortriptyline

Antineoplastic agents Busulfan, carmustine, chlorambucil, cytosine arabinoside, methotrexate, vincristine

Antipsychotics Chlorpromazine, haloperidol, perphenazine, prochlorperazine, thioridazine, trifluoperazine

Bronchial agents Aminophylline, theophylline

General anesthetics Enflurane, methohexital

Local anesthetics Bupivacaine, lidocaine, procaine

Sympathomimetics Ephedrine, phenylpropanolamine, terbutaline

Others Anticholinergics, antihistamines, aqueous iodinated contrast agents, atenolol, baclofen, cyclosporine, domperidone, ergonovine, flumazenil, folic acid, foscarnet, hyperbaric oxygen, insulin, lithium, oxytocin, tacrolimus

Medications – taking a good history

Substance abuse – taking a good history

•EtOH•Stimulants•Anxiolytics•Cocaine•PCP•Synthetic marijuana•Analgesics

Standard work up for seizure•Routine EEG•MRI brain with and without contrast•Basic lab work (and consideration of an

underlying systemic cause)•If associated symptoms (autonomic) it

would be prudent to get cardiology evaluation▫TTE▫Holter monitoring▫Orthostatic vital signs

If you are unsure if the patient seized...•Objective measures of a generalized

seizure (or multiple seizures)▫WBC▫Creatinine▫CO2▫CK▫Prolactin?

Status Epilepticus• 5 minutes or more of:

▫Continuous clinical or electrographic seizure activity, or

▫Recurrent seizure activity without recovery between seizures

• Most clinical and electrographic seizures last <5’ and seizures that last longer often do not stop spontaneously

• Animal data suggest that permanent neuronal injury and pharmacoresistance may occur before the traditional definition of 30’ of continuous seizure activity has passed

Continuum (Minneap Minn) 2013;19(3):571-597.

Neurocrit Care. 2012 Aug;17(1):3-23

Status Epilepticus•Convulsive status epilepticus

Convulsions that are associated with rhythmic jerking of the extremities

Clinical characteristics of GCSE: GTC movements Mental status impairment May have focal neurological deficits in the

postictal period Focal motor status/EPC is not included in this

definition

Neurocrit Care. 2012 Aug;17(1):3-23

Non Convulsive Status Epilepticus•Seizure activity seen on EEG without

clinical findings associated with GCSE•Two distinct phenotypes:

▫The “wandering confused” patient presenting to the ED with a relatively good prognosis or chronic epileptic syndromes or,

▫The acutely ill patient with severely impaired mental status, with or without subtle motor movements Frequently follows uncontrolled GCSENeurocrit Care. 2012 Aug;17(1):3-23

Non Convulsive Status Epilepticus•Semiological spectrum of non-convulsive

seizures is highly variable▫Negative symptoms: anorexia,

aphasia/mutism, amnesia, catatonia, coma, confusion, lethargy, staring

▫Positive symptoms include agitation/aggression, automatism, blinking, crying, delirium, delusions, echolalia, facial twitching, laughter, nausea/vomiting, nystagmus/eye deviation, perseveration, psychosis Neurocrit Care. 2012 Aug;17(1):3-23

What’s the prognosis?•GCSE

▫Mortality At hospital discharge: 9-21% At 30 days: 19-27% At 90 days: 19%

▫Morbidity Severe neurological or cognitive sequelae:

11-16% Deterioration in functional status: 23-26% At 90 days after SE, 39% will have marked

functional impairmentNeurocrit Care. 2012 Aug;17(1):3-23

What’s the prognosis?• NCSE

▫Mortality At hospital discharge: 18-52% At 30 days: 65% Factors associated with poor outcome

Underlying etiology, severe MS impairment, longer seizure duration

For patients diagnosed within 30’ of seizure onset, mortality was 36% compared with 75% for those diagnosed >24 hours after onset

Patients with NCSE treated and resolved within 10h had 10% mortality vs 85% mortality if seizures continued >20h

Neurocrit Care. 2012 Aug;17(1):3-23

Acute treatment of SE•1. ABCs

•2. Emergent initial therapy▫Benzodiazepines

IV >IM/PR/Nasal Lorazepam IV Midazolam IM/nasal Diazepam PR

Acute treatment of SE•Benzodiazepines

▫Dosing: optimal ranges have not been defined Lorazepam 0.1mg/kg IV up to 4mg/dose

May repeat dosing in 5-10 minutes Midazolam 0.2mg/kg IM up to 10mg (max) Diazepam 0.15mg/kg IV up to 10mg/dose

May repeat dosing in 5 minutes

▫Concern for respiratory depression and hypotension?

N Engl J Med. 2001;345(9):631–7Neurocrit Care. 2012 Aug;17(1):3-23

Acute treatment of SE

•3. Urgent Control Therapy▫Treatment with an AED following

administration of short acting benzos is required in all patients who present with SE Exceptions?

Neurocrit Care. 2012 Aug;17(1):3-23

Acute treatment of SE•Two potential goals of urgent control

therapy▫For patients who respond to emergent

initial therapy and have complete resolution of SE, the goal is rapid attainment of therapeutic levels of an AED and continued dosing for maintenance therapy

▫For patient who fail emergent initial therapy, the goal of urgent control is to stop SE Neurocrit Care. 2012 Aug;17(1):3-23

Acute treatment of SE•Which AED to choose?

▫VA Cooperative Trial in 1998 Many of the new AEDs were not available at

the time of this trial▫Preferred top tier agents are:

IV fosphenytoin/phenytoin IV valproate sodium (best choice for patients

with PGE) IV phenobarbital IV levetiracetam Continuous midazolam infusion

Neurocrit Care. 2012 Aug;17(1):3-23

http://www.bjs.co.uk/details/media/1043941/Purple-Glove-Syndrome-following-intravenous-phenytoin.html

Phenytoin• Check a free level ~8 hours after IV load

▫ PTN is protein bound▫ Unbound PTN is active PTN▫ Decreased protein binding contributes to higher levels of

biologically active medication• Keep on continuous telemetry• Enzyme inducer – decreases AED levels of:

▫ VPA▫ Lamotrigine▫ Topiramate▫ Oxcarbazepine▫ Zonisamide▫ Benzodiazepines▫ Levetiracetam

Valproate• Check a total level ~8 hours after IV load

▫VPA is protein bound▫Unbound VPA is active VPA▫We don’t have the ability to measure free VPA at

MUSC• Monitor platelets • Can be given as a gtt for refractory seizures• Enzyme inhibitor –increases AED levels of:

▫Lamotrigine▫Carbamazepine▫Phenobarbital▫Ethosuximide

Levetiracetam•Bioavailability is 100%•Oral absorption is rapid and almost

complete•Renally excreted•Little to no drug-drug interactions•Behavioral symptoms (5-13% of adults)•Can cause leukopenia and neutropenia

When should you check AED levels?•If you are trying to achieve a therapeutic

level after SE•If the patient displays symptoms

consistent with toxicity•If there are no other reasons that you can

find for a patient to have breakthrough seizures (and is supposed to be taking an AED)

AED levels at MUSC•< 24 hours

▫Phenytoin▫Valproate▫Carbamazepine▫Phenobarbital

•2-4 days (send out)▫Levetiracetam▫Oxcarbazepine▫Zonisamide▫Lamotrigine▫Lacosamide▫Topiramate

EtOH withdrawal seizures•GABA – major inhibitory neurotransmitter

in the brain▫Highly specific binding sites for ethanol are

found on the GABA receptor complex▫Chronic ethanol use induces insensitivity to

GABA such that more inhibitor is required to maintain a constant inhibitory tone

▫As alcohol tolerance develops, the individual retains arousal at concentrations which would normally produce lethargy or coma

EtOH withdrawal seizures•Generalized tonic-clonic•Usually occur within 12-48 hours after the

last drink, but may occur more quickly after abstinence

•Predominantly occur in patients with long history of chronic alcoholism

•Usually singular or occur as a brief flurry over a short period

•Recurrent or prolonged seizures or SE should prompt an investigation into other etiologies

EtOH withdrawal seizures•Treatment is typically benzodiazepines •Several studies have demonstrated that

phenytoin is ineffective in this clinical context

•If a patient has epilepsy but is also an alcoholic, leave their AEDs as they are and proceed with AWS protocol

•Gabapentin taper is a great tool▫400mg TID x 3d 400mg BID x 3d 400mg

Qday x 3d off Alcohol Clin Exp Res. 2009 September; 33(9): 1582–1588.

Non-epileptic events•Convulsive syncope•Cardiac arrhythmias•Parasomnias•Movement disorders•Conversion disorder•Malingering

Convulsive syncope

•Paroxysmal event of loss of consciousness and postural tone caused by cerebral hypoperfusion with spontaneous recovery

•Patients are generally orthostatic by vital signs or their history

Psychogenic NEEs•Hints that this might be a non-epileptic

event:▫Eyes are closed▫Head crosses midline▫Asynchronous movements of extremities▫Events are only ever witnessed▫Multiple types of spells▫Duration of event▫Rapid return to baseline▫Do not occur during sleep▫Lack of autonomic symptoms▫No response to AEDs

Psychogenic NEEs•Diagnosis

▫EEG▫Psychiatric history▫Referral for psychiatric evaluation