Provide a concise study guide for medical students preparing for an exam on seizures.

Seizure Study Guide for Medical Students

Definitions and Classification

A seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain 1. Understanding this fundamental definition is critical for distinguishing true seizures from seizure mimics like syncope, rigors, or psychogenic nonepileptic seizures 1.

ILAE 2017 Classification System

The International League Against Epilepsy revised seizure classification in 2017, creating an operational framework essential for diagnosis, treatment, and prognosis 1. Seizures are classified into three main categories: focal onset, generalized onset, or unknown onset 1.

Focal Seizures

• Arise within networks of a single cerebral hemisphere and may remain localized or spread 1
• Further characterized by:
  • Motor onset vs. nonmotor onset symptoms 1
  • Awareness level: aware vs. impaired awareness 1
• May be associated with structural lesions including tumors, infection, infarction, traumatic brain injury, vascular malformations, or developmental abnormalities 1

Generalized Seizures

• Rapidly affect both hemispheres and both sides of the body, even when caused by a focal lesion 1
• Subdivided into:
  • Tonic-clonic 1
  • Other motor types 1
  • Nonmotor (absence) 1

Epilepsy Definition

Epilepsy is defined by the ILAE as having:

1. At least two unprovoked seizures occurring more than 24 hours apart, OR 1
2. One unprovoked seizure with probability of further seizures similar to the general recurrence risk after two unprovoked seizures over the next 10 years, OR 1
3. Diagnosis of an epilepsy syndrome 1

Provoked vs. Unprovoked Seizures

Provoked (Acute Symptomatic) Seizures

Occur at the time of or within 7 days of an acute neurologic, systemic, metabolic, or toxic insult 1. Common causes include:

• Hyponatremia or other electrolyte abnormalities 1
• Withdrawal syndromes 1
• Toxic ingestions 1
• Encephalitis 1
• CNS mass lesions 1

Unprovoked Seizures

Occur without acute precipitating factors 1. Include:

• Idiopathic seizures 1
• Remote symptomatic seizures (from CNS or systemic insult >7 days in the past) 1
• Seizures attributed to history of stroke, traumatic brain injury, or other past events 1

Epidemiology

• Active epilepsy affects 1.2% of the United States population (approximately 3.4 million people) 1
• Approximately 50 million people worldwide have epilepsy 1
• About 10% of the population experiences at least one epileptic seizure during their lifetime 1
• In children, approximately 470,000 or 0.6% of those <17 years suffer from epilepsy, with 50,000 new cases diagnosed annually 1

Age-Specific Considerations

Neonatal Seizures (0-29 days)

• Incidence: 3 per 1,000 live births per year 1
• Higher in preterm infants: 57-132 per 1,000 live births 1
• An underlying cause can be identified in about 95% of neonatal seizures 1

Most common etiologies:

• Hypoxic ischemic injury (46%-65%) - by far the most common cause in both term and preterm infants 1
• Intracranial hemorrhage and perinatal ischemic stroke (10%-12%) 1
• Approximately 90% of infants with hypoxic ischemic encephalopathy experience seizure onset within 2 days after birth 1
• Seizures occurring beyond the seventh day of life are more likely related to infection, genetic disorders, or malformations of cortical development 1

Initial Imaging Approach

New-Onset Seizure (Unrelated to Trauma)

Noncontrast CT head has a central role in the emergent situation 1. This is the initial imaging modality for acute presentations to identify:

• Structural abnormalities 1
• Hemorrhage 1
• Mass lesions 1

Neonatal Seizures Imaging

• Ultrasound may be useful as initial imaging, particularly if the infant is unstable or unable to have MRI 1
• CT is helpful in identifying structural anomalies 1
• MRI provides superior detail for developmental abnormalities and cortical malformations 1

Status Epilepticus Management

Definition and Importance

Status epilepticus is the most common neurologic emergency in children 1. In adults, it represents a life-threatening condition requiring immediate intervention.

Second-Line Agent Selection

For patients with generalized convulsive status epilepticus who continue to have seizures despite receiving optimal dosing of benzodiazepine, emergency physicians should treat with a second-line agent 1.

Fosphenytoin, levetiracetam, or valproate may be used with similar efficacy 1. Key safety considerations:

• Life-threatening hypotension frequency:

  • Levetiracetam: 0.7% 1
  • Fosphenytoin: 3.2% 1
  • Valproate: 1.6% 1

• Cardiac arrhythmias: only seen in 0.7% of levetiracetam group 1

• Endotracheal intubation rates:

  • Levetiracetam: 20% 1
  • Fosphenytoin: 26.4% 1

Advanced Imaging Considerations

PET Imaging

FDG-PET is beneficial for localization of epileptogenic foci 1. Additional specialized tracers include:

• 11C-flumazenil for evaluating GABA (inhibitory neurotransmitter important in epileptic activity regulation) 1
• 11C-carfentanil for opioid receptors (anticonvulsant effect) 1
• 18F-MPPF for serotonin (anticonvulsant effect) 1
• 18F-fallypride for dopamine receptors 1
• Alpha-[11C]methyl-L-tryptophan useful in tuberous sclerosis, temporal lobe epilepsy, and cortical dysplasia 1

Diffusion Tensor Imaging

Utilized to assess disruption in white matter tracts following trauma, though its use remains investigational 1.

Common Pitfalls to Avoid

Seizure Mimics

Many clinical conditions resemble convulsive seizures but are not true seizures 1:

• Brief stiffening or rhythmic jerks accompanying syncope or concussion 1
• Rigors 1
• Psychogenic nonepileptic seizures 1
• Even after thorough ED evaluation, correct categorization may be difficult 1

Trauma-Related Seizures

Seizures related to trauma are subdivided into immediate and late seizures 1:

• Immediate seizures: secondary to the force of injury itself 1
• Late seizures: occurring later (>7 days post-injury) 1

Medication Management Errors

Do not prescribe benzodiazepines or antiseizure medications for patients with functional seizures without co-occurring epilepsy or another indication 2. Clinicians should taper off antiseizure medications for patients with functional seizures without another indication 2.

Key Clinical Pearls

• The basic mechanism of epileptic seizures has not been fully elucidated; classification is operational, not based on fundamental mechanisms 1
• Correct identification of seizures and epilepsy is essential because etiologic diagnosis, appropriate treatment, and accurate prognostication all depend on it 1
• Approximately 10%-25% of individuals with late-onset unexplained epilepsy (onset after age 55) develop dementia within 3-4 years following their first seizure 3