Seizures
Alison Smock, MD
Department of Neurology
Medical 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
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Provoked
Unprovoked
Medication non-compliance
Metabolic derangements
Drug use/EtOH withdrawal
Infection
Inflammatory state
Structural cause
Sleep deprivation
• Epilepsy
• Secondary epilepsy
Types of seizures
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
Clonic
Tonic
Atonic
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
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Myoclonic
Tonic
Clonic
Tonic-clonic
Versive
simple motor seizure
fasciculation
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
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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:
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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
Medications – taking a good history
Agents reported to induce
seizures
Analgesics
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
Substance abuse – taking a good history
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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)
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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
Neurocrit Care. 2012 Aug;17(1):3-23
Continuum (Minneap Minn) 2013;19(3):571-597.
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 GCSE
Neurocrit 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 impairment
Neurocrit 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):631–7
Neurocrit 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-Syndromefollowing-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:
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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:
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Lamotrigine
Carbamazepine
Phenobarbital
Ethosuximide
Levetiracetam
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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
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Phenytoin
Valproate
Carbamazepine
Phenobarbital
• 2-4 days (send out)
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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
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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:
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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