418 Seizures and Epilepsy Flashcards
Origin of the word “seizure”
“Sacire” which means “to take possession of”
What is seizure?
A seizure is a transient occurrence of signs or symptoms due to an abnormal excessive or synchronous neuronal activity in the brain
What is epilepsy?
Epilepsy describes a condition in which a person has a risk of recurrent seizures due to a chronic, underlying process (not a single or recurrent seizure that is due to correctable or avoidable circumstances).
Focal vs generalized seizure
Focal seizures
- originate within networks limited to one brain region
- usually associated with structural abnormalities of the brain
Generalized seizures
- arise within and rapidly engage networks distributed across both cerebral hemispheres
- may result from cellular, biochemical, or structural abnormalities that have a more widespread distribution
3 subtypes of Focal seizures
Focal seizures with intact awareness
Focal seizures with impaired awareness
Focal seizures that evolve into generalized seizures
Features of Focal seizures
1) Can have motor or nonmotor manifestations with or without impairment of awareness
2) The abnormal motor movements may begin in a very restricted region such as the fingers and gradually progress (over seconds to minutes) to include a larger portion of the extremity (“Jacksonian march”)
3) May experience a localized paresis (Todd’s paralysis) for minutes to many hours in the involved region following the seizure.
4) May continue for hours or days, in rare instances (“epilepsia partialis continua”)
Term used to denote the phenomenon in which there is gradual progression of a focal seizure from a small region to a larger portion of the extremity
Jacksonian march (described by Hughlings Jackson)
Term used to denote the localized paralysis for minutes to many hours in the involved region following a focal seizure
Todd’s paralysis
Term used to denote a focal seizure that continues for hours or days
Epilepsia partialis continua
Term used to denote subjective, “internal” events that are not directly observable by someone else but may actually be manifestations of a focal seizure
Auras
Illusion that objects are growing smaller
Micropsia
Illusion that objects are growing larger
Macropsia
Typical events in focal seizures with impaired awareness
Frequently begin with an aura that is stereotypic for the patient
Start of the ictal phase is often a motionless stare, which marks the onset of the period of impaired awareness, usually accompanied by automatisms
Confusion after the seizure
Transition to full recovery of consciousness may range from seconds up to an hour or longer. May have anterograde amnesia or transient neurological deficits
Usual variety of generalized seizure when it evolved from a focal seizure
Tonic-clonic variety
Region of the brain from which focal seizures that evolve into generalized seizures usually arise
Frontal lobe
Subtypes of Generalized onset seizures
Typical absence seizures
Atypical absence seizures
Generalized, tonic-clonic seizures
Atonic seizures
Myoclonic seizures
Epileptic spasms
Features of Typical absence seizures
Sudden, brief lapses of consciousness without loss of postural control
Usually lasts for only seconds
No postictal confusion
Usually accompanied by subtle, bilateral motor signs
Main seizure type in 15-20% of children with epilepsy
First clue is often unexplained “daydreaming” and a decline in school performance
EEG hallmark: Generalized, symmetric, 3-Hz spike-and-slow-wave discharges that begins and ends suddenly, superimposed on a normal EEG background
Hyperventilation tends to provoke these electrographic discharges
Features of Atypical absence seizures
Lapse of consciousness is usually of longer duration and less abrupt in onset and cessation
Accompanied by more obvious motor signs
EEG: Generalized, slow spike-and-slow-wave pattern with a frequency of <=2.5 per second
Associated with diffuse or multifocal structural abnormalities of the brain and therefore may accompany other signs of neurologic dysfunction such as mental retardation
Less responsive to anticonvulsants compared to typical absence seizures
Features of Generalized, Tonic-Clonic Seizures
Main seizure type in ~10% of all persons with epilepsy
Most common seizure type resulting from metabolic derangements
Usually begins abruptly without warning, but may sometimes have a prodrome
Phases:
1) Tonic phase 10-20s
2) Clonic phase (total ictal phase usually lasts no more than 1 min)
3) Postictal phase (bladder or bowel incontinence may occur)
Usually with postictal confusion
EEG:
1) Tonic phase - Progressive increase in generalized low-voltage fast activity, followed by generalized high-amplitude, polyspike discharges
2) Clonic phase - High-amplitude activity is typically interrupted by slow waves to create a spike-and-slow-wave pattern
3) Postictal phase - Diffuse suppression of all cerebral activity, then slowing that gradually recovers as the patient awakens
Features of Atonic seizures
Sudden loss of postural muscle tone lasting 1-2s
Consciousness is briefly impaired, but there is usually no postictal confusion
EEG: Brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves that correlate with the loss of muscle tone
Features of Myoclonic seizures
Myoclonus - sudden and brief muscle contraction that may involve one part of the body or the entire body
Most commonly seen in association with metabolic disorders, degenerative CNS disease, or anoxic brain injury
EEG: Bilaterally synchronous spike-and-slow-wave discharges immediately prior to the movement and muscle artifact associated with the myoclonus
Predominant feature of juvenile myoclonic epilepsy
Features of Epileptic Spams
Briefly sustained flexion or extension of predominantly proximal muscles, including truncal muscles
Occur predominantly in infants
EEG: Hypsarrhythmia (diffuse, giant slow waves with a chaotic background of irregular, multifocal spikes and sharp waves). During the clinical spasm, there is a marked suppression of the EEG background (the “electrodecremental response”)
EMG: Characteristic rhomboid pattern
Which type of generalized seizure is associated with a group of genetically determined epilepsies with onset usually in childhood (ages 4-10 years) or early adolescence and are the main seizure type in 15-20% of children with epilepsy?
Typical absence seizures
Most common seizure type resulting from metabolic derangements
Generalized, tonic-clonic seizures
Type of seizure that occur predominantly in infants
Epileptic spasms
EEG: Generalized, symmetric, 3-Hz spike-and-slow-wave discharges that begins and ends suddenly, superimposed on a normal EEG background
Typical absence seizure
EEG: Generalized, slow spike-and-slow-wave pattern with a frequency of <=2.5 per second
Atypical absence seizure
EEG: Different phases with spiking then slowing
Generalized, tonic-clonic seizure
EEG: Brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves
Atonic seizure
EEG: Bilaterally synchronous spike-and-slow-wave discharges and muscle artifact
Myoclonic seizure
EEG: Hypsarrhythmia with electrodecremental response
Epileptic seizure
Term used to denote the marked suppression of the EEG background during a clinical spasm
Electrodecremental response
Term used to denote diffuse, giant slow waves with a chaotic background of irregular, multifocal spikes and sharp waves
Hypsarrhythmia
Type of seizure that shows a characteristic rhomboid pattern on EMG
Epileptic spasm
3 important epilepsy syndromes
1) Juvenile myoclonic epilepsy
2) Lennox-Gastaut syndrome
3) Mesial temporal lobe epilepsy syndrome (MTLE)
Epilepsy syndrome in which the seizures are most frequent in the morning after awakening and can be provoked by sleep deprivation
Juvenile myoclonic epilepsy
Triad of Lennox-Gastaut syndrome
1) Multiple seizure types
2) EEG: Slow (<3 Hz) spike-and-wave discharges and a variety of other abnormalities
3) Impaired cognitive function in most but not all cases
Most common epilepsy syndrome associated with focal seizures with impairment of consciousness
Mesial temporal lobe epilepsy syndrome (MTLE)
Characteristic MRI finding in mesial temporal lobe epilepsy syndrome (MTLE)
Hippocampal sclerosis
Term used to denote the process in which a brain injury results in a long-lasting pathologic change in the CNS that transforms a presumably normal neural network into one that is abnormally hyperexcitable
Epileptogenesis
Term used to denote the specific changes that result in a lowered seizure threshold
Epileptogenic factors
Seizures that are due to inborn errors of metabolism usually occurs how many days after birth?
2-3 days after birth (once regular feeding begins)
Most common seizures arising in late infancy and early childhood
Febrile seizures
What are febrile seizures?
Seizures associated with fevers but without evidence of CNS infection or other defined causes
Peak incidence of febrile seizures
18 to 24 months
Simple febrile seizures differ from complex febrile seizures in that…
Single, isolated event, brief, and symmetric in appearance
Not associated with an increase in the risk of developing epilepsy
Complex febrile seizures differ from simple febrile seizures in that…
Repeated seizure activity, duration >15 mins, or by focal features
Have a 2-5% risk of developing epilepsy
Recurrence of febrile seizure is much more likely when the febrile seizure occurs in what year of life?
In the first year of life
TRUE OR FALSE: The likelihood of developing epilepsy is strongly correlated with the severity of the injury.
TRUE
Definition of Mild head injury
A concussion with amnesia or loss of consciousness <30 mins
Condition that may account for ~50% of new cases of epilepsy in patients >65 years
Cerebrovascular disease
Acute seizures are seen more often with which type of stroke? Embolic, hemorrhagic, or thrombotic?
Embolic
TRUE OR FALSE: There is variety of antiepileptic drugs that is effective for the prevention of seizure after CNS injury.
FALSE. There are currently no drugs known to prevent the formation of a seizure focus following CNS injury.
First priorities when a patient presents shortly after a seizure
Vital signs, respiratory, and cardiovascular support, and treatment of seizures if they resume
What diagnostic study is mandatory in all patients infected with HIV, even in the absence of symptoms or signs suggesting infection?
Lumbar puncture
Predominant rhythm on EEG in normal awake adults lying quietly with the eyes closed
8- to 13-Hz alpha rhythm intermixed with a variable amount of generalized faster (beta) activity (>13 Hz)
What rhythm on EEG is attenuated when an awake adult opens his eyes?
Alpha rhythm
Predominant rhythm on EEG during light sleep
Theta (4-7 Hz) and delta (<4 Hz)
A lumbar puncture is mandatory in all patients infected with _____.
HIV
TRUE OR FALSE: A patient with a possible seizure disorder should undergo an EEG 7 days after the seizure.
FALSE. All patients who have a possible seizure disorder should be evaluated with an EEG as soon as possible.
TRUE OR FALSE: The EEG is always abnormal during generalized tonic-clonic seizures.
TRUE
TRUE OR FALSE: The absence of electrographic seizure activity excludes a seizure disorder.
FALSE. Focal seizures may originate from a region of the cortex that cannot be reached during generalized tonic-clonic seizures.
TRUE OR FALSE: The initial routine interictal EEG may be normal in up to 60% of individuals with known epilepsy.
TRUE
What is the only potential exception in the rule that almost all patients with new-onset seizures should have a brain imaging study to determine whether these in a underlying structural abnormality?
Children who have an unambiguous history and examination suggestive of a benign, generalized seizure disorder such as absence epilepsy
Imaging that is superior to other modalities for the detection of cerebral lesions associated with epilepsy
MRI
Features that distinguish generalized tonic-clonic seizure from syncope
Page 3060, Table 418-7
Seizure or Syncope?
Immediate precipitating factors: Usually none
Seizure
Seizure or Syncope?
Premonitory symptoms: Tiredness, nausea, diaphoresis, tunneling of vision
Syncope
Seizure or Syncope?
Posture at onset: Usually erect
Syncope
Seizure or Syncope?
Transition to unconsciousness: Often immediate
Seizure
Seizure or Syncope?
Duration of unconsciousness: Seconds
Syncope
Seizure or Syncope?
Duration of unconsciousness: Minutes
Seizure
Seizure or Syncope?
Duration of tonic or clonic movements: Never >15 s
Syncope
Seizure or Syncope?
Facial appearance during event: Pallor
Syncope
Seizure or Syncope?
Disorientation and sleepiness after event: <5 min
Syncope
Seizure or Syncope?
Aching of muscles after event: Often
Seizure
Seizure or Syncope?
Biting of tongue: Sometimes
Seizure
Seizure or Syncope?
incontinence: Sometimes
Both
Seizure or Syncope?
Headache: Sometimes
Seizure
What are psychogenic seizures?
Nonepileptic behaviors that resemble seizures, often part of a conversion reaction precipitated by underlying psychological distress
Measurement of serum _____ may help to distinguish between epileptic and psychogenic seizures.
Prolactin
(Most generalized seizures and some focal seizures are accompanied by rises in serum prolactin during the immediate 30-min postictal period, whereas psychogenic seizures are not.)
An almost universal precipitating factor for seizures
Sleep deprivation
Mainstay of treatment for most patients with epilepsy
Antiepileptic drug therapy
Most generalized seizures and some focal seizures are accompanied by rises in the serum level of this substance
Prolactin
Overall goal of antiepileptic drug therapy
To completely prevent seizures without causing any untoward side effects, preferably with a single medication and a dosing schedule that is easy for the patient to follow
TRUE OR FALSE: Antiepileptic drug therapy should be started in a patient with history of a single seizure.
FALSE. Antiepileptic drug therapy should be started in any patient with recurrent seizures of unknown etiology or a known cause that cannot be reversed. Whether to initiate therapy in a patient with a single seizure is controversial.
Risk factors associated with recurrent seizures
1) Abnormal neurologic examination
2) Seizures presenting as status epilepticus
3) Postictal Todd’s paralysis
4) Strong family history of seizures
5) Abnormal EEG
First-Line Drugs for Generalized-onset tonic-clonic seizures
Lamotrigine
Valproic acid
(4 syllables for GTC)
First-Line Drugs for Focal seizures
Lamotrigine Carbamazepine Oxcarbazepine Phenytoin Levetiracetam
First-Line Drugs for Typical absence seizures
Lamotrigine
Valproic acid
Ethosuximide
(Absence of LaVE)
First-Line Drugs for Atypical absence, Myoclonic, and Atonic seizures
Valproic acid
Lamotrigine
Topiramate
Drug that is considered first-line for almost all types of seizures (based on the table)
Lamotrigine
Mutation in the SLC2A1 gene, which encodes the glucose type 1 transporter (GLUT-1) and is a cause of GLUT-1 deficiency, should immediately prompt treatment with _____
Ketogenic diet
Mutations of the ALDH7A1 gene, which encodes antiquitin, can cause alterations that can reversed by treatment with _____
Pyridoxine
Asian individuals carrying the human leukocyte antigen allele, _____, are at particularly high risk of developing serious skin reactions from carbamazepine, phenytoin, oxcarbazepine, and lamotrigine.
HLA-B*1502
Antiepileptic drug that can precipitate Stevens-Johnson syndrome
Lamotrigine
Antiepileptic drug that causes the following cosmetic effects: hirsutism, coarsening of facial features, gingival hypertrophy
Phenytoin
Antiepileptic drug with the advantage of having no known drug-drug interactions
Levetiracetam
Antiepileptic drug that can cause an irreversible, fatal hepatic failure appearing as an idiosyncratic rather than dose-related side effect
Valproic acid
Considered the best initial choice for the treatment of primary generalized, tonic-clonic seizures
Lamotrigine
Valproic acid
Levetiracetam
(LVL for GTC)
Antiepileptic drug that is teratogenic and may effect fertility
Valproic acid
What should be periodically monitored during treatment with ethosuximide?
Blood cell counts (rarely causes bone marrow suppression)
TRUE OR FALSE: Monotherapy should be the goal whenever possible.
TRUE
Patient profile that yields the greatest chance of remaining seizure free after drug withdrawal
1) Complete medical control of seizures for 1-5 years
2) Single seizure type, with generalized seizures having a better prognosis than focal seizures
3) Normal neurologic examination, including intelligence
4) No family history of epilepsy
5) Normal EEG
Most seizure recurrences occur in the first _____ after discontinuing therapy, and patients should be advised to avoid potentially dangerous situations.
3 months
If there is a response to a third drug, which of the first 2 drugs should be gradually withdrawn?
The less effective or less well tolerated of the first 2 drugs
Most common surgical procedure for patients with temporal lobe epilepsy
Temporal lobectomy or Amygdalohippocampectomy
What is status epilepticus?
Continuous seizures or repetitive, discrete seizures with impaired consciousness in the interictal period. Duration is traditionally specified as 15-30 min.
A more practical definition is a situation in which the duration of seizures prompts the acute use of anticonvulsant therapy. For GCSE, this is typically when seizures last beyond 5 mins.
TRUE OR FALSE: Generalized convulsive status epilepticus (GCSE) is an emergency and must be treated immediately.
TRUE
What should be done when a patient with status epilepticus stops having overt seizures, yet remains comatose?
a. Stop treatment
b. Brain imaging
c. EEG
d. Check for serum prolactin
EEG (may be the only method of establishing diagnosis because after 30-45 mins of uninterrupted seizures, the signs may become increasingly subtle)
First drug given in impending and early status epilepticus
IV benzodiazepine
Typical duration of seizure that prompts the acute use of anticonvulsant therapy
5 mins
TRUE OR FALSE: Postictal psychosis usually resolves spontaneously.
TRUE
Most of the increased mortality in epilepsy is due to _____.
The underlying etiology of epilepsy (i.e. tumors or strokes)
Syndrome that usually affects young people with convulsive seizures and tends to occur at night and causes death
Sudden unexpected death in epilepsy (SUDEP)
Seizure frequency during pregnancy will remain unchanged in __% of women, increase in __%, and decrease in __%.
Seizure frequency during pregnancy will remain unchanged in ~50% of women, increase in ~30%, and decrease in ~20%.
Most common fetal malformations due to antiepileptic treatment were defects in _____.
Cardiovascular and musculoskeletal system
The newer antiepileptic drugs are safer in pregnancy except for
Topiramate
Valproic acid
What supplement should be given to pregnant women undergoing antiepileptic treatment to prevent fetal malformation?
Folate (1-4mg/d)
What should be given to women and infants to prevent neonatal hemorrhage caused by the transient and reversible deficiency of vitamin K-dependent clotting factors due to enzyme-inducing antiepileptic drugs?
The mother should be treated with oral vitamin K in the last 2 weeks of pregnancy
The infant should receive intramuscular vitamin K at birth
Ratio of drug concentration in breast milk relative to serum with regards to valproic acid and levetiracetam
~5% valproic acid
~300% levetiracetam
