Seizures & Epilepsy Flashcards
Seizure
Definition
Transient event that includes symptoms and/or signs of abnormal excessive hypersynchronous activity in the brain.
A seizure is a symptom and one must search for underlying cause, acute or chronic
Epilepsy
Definition
A disease of the brain defined by any of the following conditions:
≥ Two unprovoked (or reflex) seizures occurring > 24 h apart
OR
One unprovoked (or reflex) seizure and a 60% likelihoood of a recurrent sz
Provoked Seizures
Seizures can be provoked by many causes including:
- Acute head trauma
- CNS infection
- Hypoxia/Ischemia
-
Acute metabolic causes
- Hypo/Hypernatremia
- Hypomagnesemia
- Uremia
- Hepatic failure
-
Toxins
- Drugs (tricyclics, neuroleptics, etc.)
- Alcohol withdrawal
- Recreational drug
Epilepsy
Etiologies
Causes of epilepsy include the following:
- Genetic
-
Structural processes
- Past parenchymal injury
- Tumors
- Cortical malformations
- Vascular malformations
- Cerebrovascular disease
- Hippocampal sclerosis
- Unknown
Seizures and Epilepsy
Pathophysiology
- Glutamate ⇒ major excitatory neurotransmitter
- GABA ⇒ major inhibitory neurotransmitter in the brain.
- Seizures result from an imbalance between excitation and inhibition, with either too little inhibition or too much excitation
- Epilepsy is caused by the bursting behavior of an epileptic neuronal aggregate
- Abnormal neurons display prolonged depolarization with repetitive sodium dependent action potentials which is called a paroxysmal depolarization shift.
- At the time of a seizure, this discharge spreads into the neighboring areas with propagation to the other areas of the brain

Seizure Triggers
Causes of decreased threshold to have a seizure:
- Stress, emotion
- Sleep/sleep deprivation
- Fever/illness
- Medications, metabolic disturbance
- Hyperventilation (absence seizures)
-
Reflex seizures – 4-7% prevalence in epilepsy
- Visual stimuli: strobe lights, visual patterns
- Musicogenic: specific songs, genres of music, tones
- Reading, eating, calculating
Epilepsy
Epidemiology
- Cumulative epilepsy incidence: 4.4% (~1 in 23 people) by age 85
- Adults: ~75% epilepsy with focal seizures
- Children: ~55% epilepsy with focal seizures
- Mortality long-term is twice that of general population overall
- Up to 1%/year for patients with uncontrolled seizures
Epilepsy
Morbidity
Morbidity is significant and can be due to all of the following:
- Traumatic injuries
- Underemployment
- Antiepileptic drug side effects
- Cognitive dysfunction
- Neuropsychiatric comorbidities higher prevalence over non-epilepsy population:
- ADHD, depression, anxiety, sleep disorders, migraine
Simple
Partial Seizures
Partial: seizures starting in one area of the brain
Simple (no loss of consciousness or memory)
- Sensory: visual, olfactory, gustatory, vertiginous
- Motor: focal motor without march, focal motor with march (Jacksonian), postural
- Sensory-Motor
-
Psychic (abnormal thoughts or perceptions): Dysphasic, dysmnesic, cognitive, illusions, structured hallucination
- Dysmnesic = inability to learn simple new skills in spite of an ability to perform complex skills learnt before the onset of the disorder
- Autonomic (heat, nausea, flushing, etc.): epigastric sensation, pallor, sweating, flushing, piloerection, pupillary dilation

Complex
Partial Seizures
Partial: seizures starting in one area of the brain
Complex: consciousness or memory impaired
- With or without aura (warning)
- With or without automatisms

Secondarily Generalized Seizures
- Begins focally, with or without focal neurological symptoms
- Becomes generalized
- Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases
- Typical duration 1-3 minutes
- Postictal confusion, somnolence, with or without transient focal deficit

Generalized Seizures
Seizures starting in both sides of the brain at the same time
- Absence
- Myoclonic
- Clonic
- Tonic
- Tonic-Clonic
- Atonic

Unclassifiable Seizures
- Complex Partial Seizures
- Impaired consciousness
- Clinical manifestations vary with site of origin and degree of spread
- Presence and nature of aura
- Automatisms
- Other motor activity
- Duration typically < 2 minutes

Epileptic Myoclonus
- Brief, shock-like jerk of a muscle or group of muscles, usually < 50 ms
- Differentiate from benign, nonepileptic myoclonus (e.g., while falling asleep)
- EEG: Generalized 4-6 Hz polyspike-wave discharges

Typical Absence Seizures
- Brief staring spells (“petit mal”) with impairment of awareness
- 3-20 seconds
- Sudden-onset and sudden-resolution
- Often provoked by hyperventilation
- Onset typically between 4-14 years of age
- Often resolve by 18 years of age
- Normal development and intelligence
- EEG: Generalized 3 Hz spike-wave discharges

Atypical Absence Seizures
- Brief staring spells with variably reduced responsiveness
- 5-30 seconds
- Gradual (seconds) onset and resolution
- Generally not provoked by hyperventilation
- Onset typically after 6 years of age
- Often in children with global cognitive impairment
- EEG: Generalized slow spike-wave complexes (<2.5 Hz)
- Patients often also have Atonic and Tonic seizures

Tonic Seizures and Atonic Seizures
-
Tonic seizures
- Symmetric, tonic muscle contraction of extremities with tonic flexion of waist and neck
- Duration: 2-20 seconds
- EEG – Sudden attenuation with generalized, low-voltage fast activity (most common) or generalized polyspike-wave
-
Atonic seizures
- Sudden loss of postural tone
- When severe often results in falls
- When milder produces head nods or jaw drops
- Consciousness usually impaired
- Duration: usually seconds, rarely more than 1 minute
- EEG – sudden diffuse attenuation or generalized polyspike-wave

2017 ILAE Classification of Seizures

Focal Seizures
Originate within networks limited to one hemisphere
May be localized or could be widely distributed

Generalized Seizures
Originate at some point within and rapidly engage bilaterally distributed networks
Can include cortical and subcortical structures but not necessarily the entire cortex

Seizures of Unknown Origin
- Can be motor or non-motor
- Most important use is for tonic-clonic seizures for which the beginning was obscured
- Epileptic spasms and behavior arrest are other possible seizure types of unknown onset
- Epileptic spasms may require detailed video-EEG monitoring to clarify the nature of onset
- Important because a focal onset may correspond to a treatable focal pathology
- An unknown-onset behavior arrest seizure could represent a focal impaired awareness behavior arrest seizure or an absence seizure
- A seizure might be unclassified due to inadequate information or inability to place the seizure in other categories
- If an event is not clearly a seizure, then it should not be called an unclassified seizure; rather, this classification is reserved for unusual events likely to be seizures, but not otherwise characterized
Aware vs Impaired Awareness
- During a focal aware seizure, consciousness will be intact
- Implies the ability of the person having the seizure to later verify retained awareness
- Awareness specifically refers to awareness during a seizure, and not to awareness of whether a seizure has occurred
- Awareness may be impaired without being fully absent
- If awareness of the event is impaired for any portion of the seizure, then seizure classified as a focal seizure with impaired awareness
Absence Seizures
vs
Focal Impaired Aware Seizure

Elements of Consciousness
- Awareness of ongoing activities
- Memory for time during the event
- Responsiveness to verbal or nonverbal stimuli
- Sense of self as being distinct from others
Common Seizure Symptoms
- Cognitive – aphasia; attention impairment; déjà vu; memory impairment, neglect; responsiveness impairment
- Emotional or affective – agitation; anger; anxiety, crying; fear, laughing; paranoia
- Autonomic – bradycardia or tachycardia; flushing; hyper or hypoventilation; GI symptoms (nausea or vomiting); piloerection; erection
- Automatisms – aggression; eye-blinking; head-nodding; pelvic thrusting; vocalization/speech; undressing; walking.
- Motor – dysarthria; dystonic; incoordination; “Jacksonian; paralysis; paresis
- Sensory – auditory; gustatory; hot-cold sensations; olfactory; somatosensory; vestibular; visual
- Laterality – left; right; or bilateral
Epilepsies and Epileptic Syndromes
1989 ILAE Classification
-
Localization related (Partial, Focal, Local) Epilepsies and Syndromes
- Idiopathic (with age related onset)
- Symptomatic
- Cryptogenic
-
Generalized Epilepsies and Syndromes
- Idiopathic
- Cryptogenic or Symptomatic
- Symptomatic
- Epilepsies and syndromes undetermined as to whether they are focal or generalized
- Special syndromes
Epilepsy Syndromes
Overview
Grouping of patients that share similar:
- Seizure type(s)
- Age of onset
- Natural history/Prognosis
- EEG patterns
- Genetics
- Response to treatment
Epilepsies and Epileptic Syndromes
Revision of Classification
-
Abandoned terms
- “Localization-related epilepsy syndromes”
- “Generalized epilepsy syndromes”
- Instead syndromes were arranged by age of onset
-
Term changes:
- Idiopathic → Genetic
- Genetic means the epilepsy is the direct result of a known or presumed genetic defect(s) in which seizures are the core sx of the disorder
- Symptomatic → Structural/metabolic
- Cryptogenic → Unknown cause
- Idiopathic → Genetic
Electroclinical Syndromes / Epilepsies
-
Electroclinical syndromes arranged by age at onset:
- Neonatal
- Infantile
- Childhood
- Adolescence
- Adult
- Distinctive constellations
- Epilepsies due to structural/metabolic causes
- Epilepsies of unknown cause
- Conditions with epileptic seizures that are traditionally not dx as a form of epilepsy
Epilepsy Syndromes by Age
For reference. Dot not memorize.
-
Neonatal
- Benign familial neonatal epilepsy
- Early Myoclonic Encephalopathy
- Ohtahara syndrome
-
Infantile
- Epilepsy of Infancy with migrating focal seizures
- West syndrome
- Myoclonic epilepsy in infancy (MEI)
- Benign infantile epilepsy
- Benign familial infantile epilepsy
- Dravet Syndrome
- Myoclonic encephalopathy in nonprogressive disorders
-
Childhood
- Febrile seizures plus (FS+) (can also start in infancy)
- Panayiotopoulos syndrome
- Epilepsy with myoclonic atonic (previously astatic) seizures
- Benign epilepsy with centrotemporal spikes (BECTS)
- Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
- Late onset childhood occipital epilepsy (Gastaut type)
- Epilepsy with myoclonic absences
- Lennox-Gastaut Syndrome
- Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)
- Landau-Kleffner syndrome (LKS)
- Childhood Absence Epilepsy
-
Adolescence - Adult
- Juvenile absence epilepsy (JAE)
- Juvenile myoclonic epilepsy (JME)
- Epilepsy with GTC seizures alone
- Progressive myoclonus epilepsy (PME)
- Autosomal dominant epilepsy with auditory features (ADEAF)
- Other familial temporal lobe epilepsies
-
Less specific-age relationship
- Familial focal epilepsy with variable foci (childhood to adulthood)
- Reflex epilepsies
Distinctive Constellations
- Clinically distinctive constellations on the basis of specific lesions or other causes
- May have implications for clinical treatment, particularly surgery
- Age at presentation is not a defining feature
-
Some specific distinctive constellations include:
- Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS)
- Rasmussen syndrome
- Gelastic seizures with hypothalamic hamartoma
- Hemiconvulsion-hemiplegia-epilepsy
Structural-Metabolic
Epilepsies
- Cortical malformations
- Neurocutaneous syndromes
- Neoplasms
- Infections
- Trauma
- Vascular malformations
- Perinatal insults
- Stroke
Epileptic Seizures Conditions
(Not dx as a form of epilepsy)
- Benign neonatal seizures
- Febrile seizures
Electroencephalogram
(EEG)
A recording of the electrical activity of the brain
-
1st EEG: ~40% likelihood of identifying epileptiform abnormalities in a pt w/ a single unprovoked seizure
- ↑ with repeated EEG, activation procedures, and extended EEG monitoring
- Activation procedures: capturing sleep, hyperventilation, and photic stimulation
- Epileptiform discharges in isolation are NOT diagnostic of epilepsy
- Epileptiform abnormalities on EEG after the first unprovoked seizure raise 2-year recurrence risk to 58% and fulfill current dx criteria for epilepsy
- Routine EEG may be helpful in guiding initial treatment (focal vs. generalized)
- Extended video-EEG monitoring beneficial for seizure diagnosis, classification, and localization
Seizure
Differential Diagnoses
-
Non-epileptic, physiologic events
- Syncope
- Hyperventilation / Panic
- Migraine / Migraine Equivalents
- Paroxysmal Movement Disorders
- Sleep Disorders
- Metabolic Disorders
- Transient Ischemic Attacks
- Non-epileptic, psychogenic events
Non-epileptic Events
vs
Epileptic Seizures

New-onset Seizure
Evaluation
- Detailed history of seizure characteristics, epilepsy/seizure risk factors, and possible signs of past seizures
-
Should be part of evaluation
-
EEG - with recording of sleep, photic stimulation, and hyperventilation
- Sleep deprivation increases the dx yield
- Brain imaging - MRI best, but CT if no MRI
-
EEG - with recording of sleep, photic stimulation, and hyperventilation
-
Possibly helpful but not enough evidence to support
- Bloodwork (glucose, electrolytes, CBC)
- Lumbar puncture
- Toxicology
Recurrent Seizure
Risk
-
40% after first unprovoked seizure
- If both EEG and MRI are normal, risk is about 25%
- Risk of recurrence is 60% after 2nd unprovoked seizure or 1st unprovoked seizure with epileptiform abnormalities on EEG
- Usually don’t treat after a single unprovoked seizure unless there are specific EEG findings
Anti-Seizure Medication (ASM)
Guidelines
- Diagnose seizure types and epileptic syndrome
- Safest, most specific drug for seizure type
- Start low, go slow (depending on severity)
- Use small dose increments in therapeutic zone
- Newer medications not more effective, but may have more favorable side effect profiles
New-Onset Focal Epilepsy
Initial therapy
- Oxcarbazepine / Carbamazepine/ Phenytoin
- Levetiracetam
- Lamotrigine
- Topiramate

New-Onset Generalized Epilepsy
Initial therapy
- Valproate (not in a young woman due to teratogenicity)
- Levetiracetam
- Lamotrigine
- Topiramate / Zonisamide

Anti-Seizure Meds
Memorable Side Effects
- Oxcarbazepine/Carbamazepine – Hyponatremia
- Topiramate/Zonisamide – cognitive dysfunction (word finding difficulties), nephrolithiasis, hypohydrosis
- Lamotrigine, Carbamazepine, Phenytoin, Phenobarbital, Zonisamide – Stevens-Johnson Syndrome
- Phenytoin – gingival hyperplasia, cerebellar atrophy, peripheral neuropathy
- Levetiracetam – Depression, Anger/Agitation
- Felbamate–Hepatic Failure, Aplastic Anemia
- Valproate- weight gain, tremor, hepatic failure, pancreatitis

Status Epilepticus (SE)
Definition
Neurologic emergency
Current definition – defined by two time points
-
T1 - time beyond which seizures are likely to be prolonged
- Tonic-Clonic seizure ⇒ 5 min
- Focal SE with impaired consciousness ⇒ 10 min
- Absence SE ⇒ 10-15 min
-
T2 - time beyond which seizures lead to long-term consequences
- Tonic-Clonic seizure ⇒ 30 min
- Focal SE with impaired consciousness ⇒ > 60 min
- Absence SE ⇒ unknown
Status Epilepticus (SE)
Subtypes
-
Convulsive status epilepticus
- Repetitive tonic-clonic movements occur
- Post-ictal state
-
Epilepsia partialis continua
- Focal neurological deficits and/or motor dysfunction occur
- AMS is not present
-
Nonconvulsive status epilepticus
- Continuous or fluctuating mental status changes
- Possible subtle twitching of face/limbs
- Unresponsiveness
- Possible automatisms
- No definitive criteria for nonconvulsive status epilepticus exists
- Continuous or fluctuating mental status changes

Convulsive Status Epilepticus
Therapy
- ABCs: ensure airway and O2, maintain blood pressure, monitor cardiac function
- Obtain baseline blood studies and establish IV access
- Give glucose IV (if low or unable to measure)
-
Administer anticonvulsant drugs
- Lorazepam 0.1mg/Kg
- Fosphenytoin 20 mg/Kg
- If no response, general anesthesia
- Propofol, midazolam, pentobarbital
- Obtain additional clinically indicated diagnostic studies once status is controlled
Refractory Epilepsy
Failure of two anti-seizure medications at therapeutic doses
Not failed due to side effects

Epilepsy
Other Therapeutic Approaches
- Resective surgery
- Ketogenic diet
- Neurostimulation
- RNS (Responsive nerve stimulation)
- VNS (Vagus nerve stimulation)
- DBS (Deep brain stimulation)