Seizures

A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Diagnosis is clinical, relying on history and physical exam, but also may use EEG and other tools. Management includes both abortive and preventive medications but may not be required in self-limited cases with no etiology found during workup.

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Overview

Definition

Seizures are episodes of neurologic dysfunction caused by abnormal excitatory activities of neurons characterized by a sudden change in senses, perception, motor activity, or behavior.

  • Seizure occurrences with motor activity are referred to as convulsions. 
  • Unprovoked seizures are those with an unknown etiology or those that result from a preexisting nervous system disorder.
  • Epilepsy is a disorder consisting of recurrent, unprovoked seizures.
  • Status epilepticus is recurrent seizure activity lasting > 5 minutes or without return to baseline mental status between seizures.

Epidemiology

  • Occur very commonly
  • Lifetime prevalence: 8%–10%
  • Roughly 1%–2% of ED visits are due to seizures. 
  • 25% of these ED visits are 1st-time episodes. 
  • Risk of recurrent seizure after 1st episode is roughly 40%.

Seizure phases

  • Aura:
    • Initial warning/trigger prior to seizure episode 
    • Individual may realize a seizure is about to happen. 
  • Ictal:
    • Initial onset of the seizure episode as well as the episode itself
    • Actual seizure symptomatology is manifested in this phase.
  • Postictal: 
    • Period after the seizure episode during which the individual is disoriented
    • May last up to 2 hours
Timeline of seizure phases

Time line of seizure phases

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Pathophysiology

Step 1: short in the circuit

  • Also known as paroxysmal depolarization shift 
  • All seizures arise from cell bodies and the gray matter of neurons. 
  • Astrocytes may inappropriately secrete glutamate, the excitatory neurotransmitter, causing neurons to become hyperexcitable.
Seizure step 1 - short in the circuit

Step 1: short in the circuit describing the 1st step of the pathophysiology of seizures
AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
NMDA: N-methyl-D-aspartate

Image by Lecturio.

Step 2: driving of normal neighbors

  • Repeated paroxysmal depolarizations of a large enough group of neurons will ↑ the extracellular K+ concentration → depolarization of surrounding neurons
  • As more K+ builds up in the extracellular space, less K+ diffuses out during the hyperpolarized state and the cell remains “partially depolarized” → ↑ hyperexcited neuronal activity leads to ↑ extracellular K+ concentration, which depolarizes surrounding neurons.
  • ↑ Extracellular K+ may also flow down its concentration gradient and aid in depolarization.
  • Normal, surrounding neurons are co-opted into the seizure activity. 
Step 2 of the pathophysiology of seizures, driving of normal neighbors

Step 2 of the pathophysiology of seizures, driving of normal neighbors:
The diagram shows a membrane potential and steps that allow excess K+ to polarize surrounding cells.

Image by Lecturio.

Step 3: failure of inhibition

  • Failure arises as a result of repeated paroxysmal depolarization shifts, which causes:
    • ↓ Afterhyperpolarization
    • ↓ Surround inhibition
    • ↑ Glutamate stimulation
    • ↑ Intracellular Ca2+
    • Recurrent excitatory feedback circuit 
  • Goal of management is to restore inhibition of seizure activity.
Step 3 failure of inhibition in pathophysiology of seizures

Step 3: failure of inhibition in pathophysiology of seizures

Image by Lecturio.

Clinical Presentation

Focal seizures

  • With retained awareness:
    • Depends on the location of the seizure activity 
    • May present with various sensory, autonomic, motor, or psychic symptoms 
  • With altered awareness: 
    • Most common type in adults with epilepsy 
    • May engage in automatisms (repetitive, unconscious behaviors):
      • Facial grimacing
      • Lip smacking
      • Chewing
  • Secondary generalized: start as focal seizures then progress to generalized type
Table: Types of focal or partial seizures
SimpleComplexSecondary generalized
  • Retained consciousness
  • Abnormal smell or taste
  • Staring spells without consciousness
  • Retained muscle tone
  • Loss of consciousness preceded by aura
  • Postictal confusion
  • Complex ictal automatisms
  • Initial aura
  • Convulsive +/– Jacksonian march
  • Postictal confusion +/– Todd’s paralysis

Generalized seizures

  • Absence:
    • Also called petit mal
    • Typically occur in childhood
    • Lasts for short periods (5–10 seconds) 
    • Present with loss of awareness or behavioral arrest
  • Myoclonic: short, sudden, focal muscle contractions 
  • Tonic: focal stiffening of the muscles
  • Clonic: shaking/jerking of the muscles usually in arms, neck, and face
  • Tonic-clonic:
    • Combination of tonic and clonic 
    • Most often convulsive
  • Atonic:
    • Loss of tone or stiffness of the muscles
    • Opposite of tonic seizures 
    • Drop attacks are most common among children
    • Often related to falls
Table: Types of generalized seizures
AbsenceFirst-degree generalized brief staring spells, often confused with daydreaming, with 3-Hz spike-and-wave EEG
MyoclonicTypically focal myoclonic jerks with brief loss of consciousness but no convulsions and little postictal confusion
TonicFocal, isolated rigidity
Generalized tonic-clonicMost often convulsive (but may be nonconvulsive) with first-degree generalization without aura
AtonicDrop attacks are most common in children.
Types of seizures and classifications

Types of seizures and classifications

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Diagnosis

Initial evaluation and stabilization centers around screening for hypoglycemia, hypoxia, and hemodynamic instability.

History

  • Interview witnesses whenever possible (without a witness, the diagnosis is often more difficult)
  • Identify onset and progression of symptoms.
  • Find potential triggers for seizures (e.g., noncompliance with antiepileptic medications). 
  • Questions that can determine type of seizure:
    • Was there a warning or aura before the spell?
    • What happened during the spell?
    • Does the individual remember the spell?
    • Was the individual postictal? 
    • How long did it take to get back to baseline condition?
    • How long did the spell last?
    • How frequently have the spells occurred?
    • Are there any associated precipitants?

Physical exam

  • Type of seizure activity
  • Changes in level of arousal
  • Focal deficits
  • Pupillary changes
  • Physical findings are often normal after resolution of postictal period.
  • Examine seizure-related trauma secondary to a fall.
  • Tongue biting has high specificity in ruling out psychogenic nonepileptic seizures and syncope.
  • Urinary or bowel incontinence can occur.
  • Todd’s paralysis: The seizure is followed by a brief period of temporary paralysis.

Laboratory evaluation

  • CBC
  • Basic metabolic panel 
  • Calcium and magnesium levels 
  • Pregnancy test for women of childbearing age 
  • Urine toxicology 
  • Prolactin levels obtained shortly after a seizure can differentiate epileptic from nonepileptic seizures.
  • Serum levels of anticonvulsant agents for determining:
    • Baseline levels
    • Potential toxicities
    • Lack of efficacy
    • Noncompliance

Neuroimaging

  • Routine neuroimaging is not indicated in someone with previous seizure history.
  • Imaging with brain CT or MRI recommended for:
    • New focal neurologic findings
    • Seizure activity without known etiology 
  • Noncontrast CT in the emergency setting to screen for immediate threats (structural causes, strokes, bleeding, etc.)
  • Brain MRI is most useful for new-onset seizure.

Electroencephalography (EEG)

  • Test that uses electrodes to monitor the electrical sensitivity of the brain and thereby detect any disorders
  • Indicated for those who do not return to baseline consciousness in the emergent setting
  • Included as part of workup for new-onset seizures
  • More specific in adults than in children
  • Video-EEG monitoring is the standard test for classifying:
    • Type of seizure or syndrome
    • Diagnosis of pseudoseizures (psychiatric-related)
  • Exam:
    • Electrodes are placed on the scalp and connected to a computer.
    • The computer outputs lines of brain electrical activity.
  • In EEGs, can use:
    • Surface electrodes: placed on the surface of the skin/scalp (most common)
    • Cortical electrodes: placed on the surface of the brain at the time of surgery
    • Depth electrodes: inserted deep into the brain to detect deeper foci of seizures
  • Abnormalities on an EEG may include:
    • Epileptiform discharges
    • Focal slowing
    • Diffuse background slowing
    • Intermittent diffuse slowing

Other testing

  • CSF examination by lumbar puncture:
    • Obtunded individuals
    • When meningitis or encephalitis is suspected
    • If concern exists for subarachnoid hemorrhage
  • ECG is indicated for individuals with hypoxic seizure presenting as cardiogenic syncope.
  • Consider metabolic, cardiogenic, and psychiatric causes of seizure-like episodes.
Table: Different types of seizure-like episodes and appropriate work up to be initiated
SpellSeizureSyncopePNES
Laboratories
  • CBC
  • CMP
  • Urinalysis
  • UDS
  • Blood sugar
  • Lactic acid
  • CBC
  • Prolactin
  • Serum anticonvulsant levels
  • Orthostatic blood pressure
  • Cardiac monitoring
  • Variable
  • UDS
Imaging
  • +/- CT brain
  • CTA brain for stroke or SAH concern
  • CT brain without contrast
  • +/- MRI brain
  • ECG
  • Chest X-ray
None needed
Other testing
  • Vital signs
  • ECG
  • +/- LP
  • EEG
  • +/- video EEG
  • Echo
  • +/- TEE
  • Psychiatric eval
  • Video EEG
PNES = psychogenic nonepileptic seizures
EEG = electroencelopahography
UDS = urine drug screen, ECG = electrocardiogram
MRI = magnetic resonance imaging
TEE = transthoracic echocardiogram
CT = computerized tomography
LP = lumbar puncture
CTA = CT angiography
SAH = subarachnoid hemorrhage
Echo = echocardiogram

Comparison of seizure-like episodes

Table: Distinguishing features among common disorders included in the differential diagnosis of seizure
SeizureSyncopeTransient ischemic attack
AuraYes or noneNone, nausea and vomiting, dizzinessNone
PostureNoneErectNone
OnsetAcuteAcute/variableAcute
Duration1–2 minutesSeconds to minutesMinutes to hours
MovementsVariable/tonic-clonicLost-tone myoclonusDeficits
IncontinenceVariableVery rareNone
EEGEpileptiformGeneral slowFocal slowing or generalized slowing with posterior circulation event
TraumaVariableVariableUsually none
OffsetSlow/confusedRapid/alertAlert

Management

Isolated or 1st-time seizures

  • Stabilize individual and then initiate evaluation in the ED and monitor for life-threatening causes of seizure.
  • Many seizures resolve on their own without intervention. 
  • Abortive therapy with benzodiazepines or anticonvulsant medications are not indicated in the initial stabilization of individuals with isolated seizures.
  • Admission is not needed, and close outpatient follow-up can be arranged.

Antiepileptic medications

  • Starting treatment after a single unprovoked seizure remains controversial.
  • Goal of treatment:
    • Seizure-free status 
    • No adverse effects
  • Causes of unprovoked seizure with higher chance of recurrences include:
    • Preexisting brain lesion
    • Presentation with status epilepticus
    • Presence of epileptic discharges on EEG 
    • Family history of epilepsy 
  • Antiepileptic drugs are sorted by mechanisms of action.
Mechanism of action of anticonvulsants

Mechanisms of action of anticonvulsants
VGCC: voltage-gated calcium channels

Image by Lecturio.

Status epilepticus

  • Rapid stabilization and history and physical screening 
  • Abortive therapy: 
    • Hallmark is IV benzodiazepines 
    • Agents:
      • Lorazepam
      • Diazepam
      • Midazolam
  • Definitive treatments:
    • Indicated to prevent recurrence of seizures 
    • Equal efficacy among:
      • Levetiracetam
      • Fosphenytoin
      • Valproate 
  • Refractory cases:
    • > 60 minutes of seizure activity 
    • Airway protection by intubation and sedation
    • Continuous EEG monitoring
    • Supplement with:
      • Phenobarbital
      • Fosphenytoin
  • Surgical treatments: 
    • Indicated in refractory status epilepticus or refractory epilepsy 
    • Examples of procedures include:
      • Resection of specific seizure nidus
      • Vagus nerve stimulation
      • Brain stimulation and deep brain stimulation

Seizure preventive measures

  • Psychoeducation of individuals to avoid common triggers:
    • Sleep deprivation
    • Alcohol
    • Certain drug types:
      • Opioid
      • Stimulants
      • Some anticancer drugs
      • Some antibiotics
      • Some immunosuppressants
  • In certain countries or states, abstinence from operating motor vehicles may be required.

Differential Diagnosis

  • Syncope: brief loss of consciousness and muscle tone with spontaneous recovery. Syncope has numerous causes but is usually a result of decreased blood flow to the brain. Those with syncopal events do not have the postictal confusion or prolonged duration of unconsciousness that are prevalent in those with seizure events. Management of syncope includes identifying and treating the secondary cause. 
  • Migraine: headache disorder characterized by headaches that may be associated with increased sensitivity to light and sound as well as nausea. The clinical features of seizures depend on the location of the seizure focus and may not necessarily present with the severe headaches that are the hallmark of migraines. Management strategies of migraines include controlling acute episodes as well as prophylactic treatments.
  • Psychogenic nonepileptic seizure (PNES): resembles epileptic seizures but there is no defined cortical EEG activity, which would be diagnostic in epileptic seizures. Subtle physical exam findings differentiate PNES from true seizures, including closed eyes in a convulsing individual with PNES. Management includes potential admission to the epilepsy observation unit with video-EEG monitoring.  
  • Hypoglycemia: emergency condition defined as a serum glucose level ≤ 70 mg/dL. Hypoglycemia may present with a variety of nonspecific symptoms, including adrenergic symptoms and neuroglycopenic symptoms such as seizures. Diagnosis is based on serum glucose measurement and clinical presentation. Management is with oral glucose, IV dextrose, or IM glucagon and frequent serum glucose checks.
  • Narcolepsy: neurologic sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. Diagnostic criteria are identified using sleep studies that show a decrease in REM latency. Management includes good sleep hygiene. Medications that act as CNS stimulants and antidepressants are used to target the cataplexy. 

References

  1. Schachter, S. (2021) Evaluation and management of the first seizure in adults. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/evaluation-and-management-of-the-first-seizure-in-adults 
  2. Drislane, F. (2021) Convulsive status epilepticus in adults: treatment and prognosis. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/convulsive-status-epilepticus-in-adults-treatment-and-prognosis 
  3. Berg A. T. (2008). Risk of recurrence after a first unprovoked seizure. Epilepsia 49(Suppl 1):13–18. 
  4. Oliva, M., Pattison, C., Carino, J., Roten, A., Matkovic, Z., O’Brien, T. J. (2008). The diagnostic value of oral lacerations and incontinence during convulsive “seizures.” Epilepsia 49:962–967.
  5. Kapur, J., Elm, J., Chamberlain, J. M., et al. (2019). Randomized trial of three anticonvulsant medications for status epilepticus. New England Journal of Medicine 381:2103–2113.

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