Seizure and Epilepsy Flashcards
Epilepsy
The condition of recurrent unprovoked seizures
Things that may provoke seizures in non-epileptic patients
Acute hypoglycemia, alcohol withdrawal, high fever, and medication or drug toxicity
These are all acute, reversible factors
Things that may cause seizures, but do not technically “provoke” them
Brain tumors, prior stroke, prior head trauma, prior CNS infection, and cortical malformations
These entities are neither acute nor reversible, and so recurrent seizures due to any of these causes are considered unprovoked. Therefore, patients with recurrent seizures due to brain tumors, prior trauma, prior stroke, prior neurosurgery, prior CNS infection, or any other irreversible underlying seizure focus are considered to have epilepsy and should be treated as such.
A patient with seizure(s) will generally present for evaluation in one of three scenarios:
- After a first seizure or other spell
- With a history of seizures (or other type of spell)
- Actively seizing
Whenever possible when trying to gather history on a suspected seizure, ___ should be obtained.
Whenever possible when trying to gather history on a suspected seizure, a clear description of the event by witnesses should be obtained.
Seizures are broadly categorized as ___ or ___.
Seizures are broadly categorized as generalized seizures or focal seizures.
Generalized seizures
- Characterized by impaired consciousness and bilateral motor manifestations if motor manifestations are present
- Self-injury, bladder/bowel incontinence, and altered level of consciousness commonly occur with generalized tonic-clonic seizures.
- A postictal state is common after a generalized seizure
- If a patient is found comatose or confused without clear cause and recovers without specific intervention, unwitnessed seizure with a subsequent postictal state should be considered in the differential diagnosis.
- Some generalized seizures produce altered consciousness without motor features, such as absence seizures.
Motor manifestations of seizures
Motor manifestations can be:
- tonic (stiffening of involved body parts),
- clonic (rhythmic movements),
- tonic-clonic (mix of tonic and clonic),
- myoclonic (brief jerks),
- atonic (loss of postural tone causing drop attacks).
Postictal state
Characterized by altered consciousness, which can range from confusion to coma depending on the severity and length of preceding seizure activity
In a patient with altered level of consciousness following seizure(s), continued nonconvulsive seizures may be occurring and must be distinguished from a postictal state. EEG is essential to making this distinction, as there may be barely visible motor activity or no motor activity at all.
Absence seizures
Absence seizures are characterized by brief periods of altered awareness in which patients are unable to communicate or engage with the environment, but have no motor features.
Absence seizures are more common in children.
Focal (Partial) Seizures
- Focal seizures can occur with impairment of consciousness (complex partial seizures) or with consciousness preserved (simple partial seizures)
- The clinical manifestations depend on the origin of seizure activity within the brain and can include focal motor symptoms (tonic-clonic movements, posturing, head and/or eye deviation), focal sensory symptoms (paresthesias that tend to spread over seconds), visual, auditory, or olfactory hallucinations, and/or psychic phenomena such as déjà vu (a sense of already having experienced a new place or event), jamais vu (a sense of never having been in a familiar place or situation), or a sense of fear.
- A seizure may begin with focal manifestations and secondarily generalize
Post-ictal weakness / Todd’s paralysis
- May occur in the limb(s) affected by seizure activity
- If a seizure is unwitnessed and a patient is found with focal postictal weakness, the patient may be initially thought to have had a stroke. Therefore, seizure with subsequent postictal paralysis should be considered in the differential diagnosis of acute stroke and transient ischemic attack (TIA) and vice versa.
Aspects of history that suggest fall/loss of consciousness is more likely seizure than syncopy
- Tonic clonic activity pre-, during, or post-fall
- Tongue biting
- Fecal or urinary incontinence
- Prolonged unconsciousness before awakening
- Prolonged confusion or weakness post-fall
- Preceding aura (foul odor, sense of déjà vu)
- No memory of just before the fall
Seizures generally cause ___ while TIAs generally cause ___.
Seizures generally cause “positive” symptoms (i.e., abnormal movements, paresthesias, visual phenomena) while TIAs generally cause “negative” symptoms (i.e., weakness, loss of sensation, visual field deficits).
Distinguishing seizure from a migraine with aura
- Positive symptoms of migraine auras tend to evolve/spread over minutes, whereas those of seizures generally evolve/spread over seconds.
- Migraine does not lead to alterations in level of consciousness, although it can cause mild confusion in some patients
- A headache is a common (but not universal) accompaniment to migraine with aura, but a headache can also be a component of a seizure aura or postictal state.
Distinguishing Seizures From Psychogenic Nonepileptic Spells (Pseudoseizures)
- Psychogenic nonepileptic spells (also called pseudoseizures) are generally a manifestation of an underlying psychiatric condition (e.g., conversion disorder)
- Clinical features suggestive of psychogenic nonepileptic spells rather than epileptic seizures include:
- prolonged bilateral movements with preservation of consciousness
- forced eye closure during episodes (eyes are generally open during seizures)
- episodes provoked by stress or other emotional circumstances
- continued events in spite of multiple antiepileptic medications (though this can also occur in refractory epilepsy)
- Remember, patients with epilepsy can have both seizures and nonepileptic spells, and patients with underlying psychiatric conditions can have seizures
Five categories of EEG findings
- Normal variants not associated with epilepsy but of unclear significance (e.g., small sharp spikes, wicket spikes)
- Findings associated with focal or global cerebral pathology but not necessarily with epilepsy (e.g., focal or generalized slowing, triphasic waves, frontal intermittent rhythmic delta activity [FIRDA])
- Findings indicating cortical irritability and risk of seizures (e.g., spike-wave discharges, periodic lateralized epileptiform discharges [PLEDs], generalized periodic discharges [GPEDs]).
- Seizures
-
Artifact, which can be due to:
- Patient factors (e.g., blinking, movements)
- Technical factors (e.g., electrocardiographic [ECG] artifact, interference from electrical hospital equipment, issues with EEG leads)
Sensitivity of a routine EEG in detecting epileptiform activity
- Only 50%
- BUT, can be improved by:
- performing the EEG in the sleep-deprived state
- performing EEG within 24 hours of a seizure event
- repeating EEG on multiple occasions
Notes on epileptiform activity on EEG
- A small proportion of the population may have EEG abnormalities of no clinical significance
- A number of medications can also cause EEG abnormalities
The absence of epileptiform discharges ___ and their presence ___
The absence of epileptiform discharges does not “exclude” epilepsy and their presence does not “confirm” epilepsy
Workup of a patient’s first seizure
- Medication/drug history
- Labs (electrolytes, tox screen)
- Neuroimaging (preferably MRI w/ contrast, possibly also arterial/venous imaging)
- Lumbar puncture if CNS disease suspected from clinical picture
Epilepsy-protocol MRI
- Includes coronal views of the hippocampi to look for asymmetries in size or signal characteristics on T2/FLAIR that may suggest an underlying focus for temporal lobe epilepsy (mesial temporal sclerosis)
- Seizures can produce transient MRI abnormalities, most commonly diffusion restriction (on DWI/ADC sequences) and/or T2/FLAIR hyperintensity in the cortex, splenium, and/or thalamus
- Diffusion restriction on MRI can also be caused by acute stroke
- The pattern of diffusion restriction due to seizure can be distinguished from stroke in that it is often limited to the cortex and can span multiple vascular territories.
What is going on in this MRI?
Mesial temporal sclerosis
A: Coronal T1-weighted image showing asymmetric hippocampi (smaller left hippocampus). B: Coronal FLAIR image showing increased signal in the left hippocampus.
When are antiepileptics useful?
- If a clear acute, reversible etiology of a patient’s seizure is identified and the patient has returned to normal with treatment of this underlying provoking condition, antiepileptic drug treatment is not necessarily indicated.
- EEG is not particularly helpful in this scenario
- If a structural lesion is also found, anti-epileptics may be used prophylactically
- If there were multiple and/or difficult-to-control seizures due to an underlying acute reversible provoking factor, a short course of antiepileptics may be maintained and later tapered.
- If there is a structural lesion identified in a patient with a first seizure, long-term antiepileptic treatment is generally indicated.
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After an unprovoked seizure, medium-risk or high-risk patients should be treated immediately with long-term antiepileptic therapy
- For low-risk patients, it is a joint decision between patient and clinician, but data is unclear on benefits.
Counseling after first seizure
Patients with active epilepsy or who have just had a first seizure should be counseled not to drive, operate heavy machinery, work at heights or near fire, bathe/swim alone, or participate in any other activity during which a seizure could lead to significant injury or death
Laws vary from state to state with respect to the seizure-free period necessary before driving, so local regulations should be consulted.
The recommended seizure-free period for driving (6–12 months in most U.S. states) can be used as a rough guide for avoidance of other potentially risky activities.
Antiepileptics sometimes. . .
. . . make epilepsy worse!!!!
It is important to know which diseases antiepileptics treat, and which they exacerbate. THESE ARE NOT BENIGN DRUGS.
First-line therapy for idiopathic genetic generalized epilepsy syndromes
Valproate
with the exception of childhood absence epilepsy, for which ethosuximide is first-line therapy.
Valproate should be avoided in. . .
. . . women of child-bearing age, due to its teratogenicity.
Same goes for topiramate.
It should also be avoided in children <2 years of age, due to hepatotoxicity in this population.
Carbamazepine is particularly effective for ___
Carbamazepine is particularly effective for partial (focal) seizures
BUT may worsen idiopathic genetic generalized epilepsy syndromes such as childhood absence epilepsy
Drug-drug interactions of antiepileptics
- The older AEDs phenobarbital, phenytoin, carbamazepine, and valproate have the most drug–drug interactions
- Phenobarbital, phenytoin, and carbamazepine are enzyme inducers, lowering the levels of other medications, AND decreasing the effectiveness of oral contraceptives
- Valproate is an enzyme-inhibitor, increasing the levels of other medications.
Side effects of antiepileptics
- Nearly all AEDs can cause dizziness, double vision, sedation, and/or behavioral changes. Worse w/ older agents, less so with newer ones.
- Life-threatening toxicities include hepatic toxicity, agranulocytosis, aplastic anemia, and Stevens-Johnson syndrome
- Initiation of most AEDs requires evaluation with baseline CBC and hepatic and renal function tests. Tests are then followed serially to monitor for toxicities
- Carbamazepine and oxcarbazepine can cause hyponatremia, so serum sodium is also monitored for these
- Lacosamide can cause PR interval prolongation, and so a baseline ECG should be obtained with serial monitoring
- Topiramate and zonisamide can increase the risk of nephrolithtiasis
- Topiramate and valproate are teratogenic
The highest risks of Stevens-Johnson syndrome among antiepileptics are with. . .
. . . phenytoin, phenobarbital, carbamazepine, and lamotrigine
The risk of Stephens-Johnson syndrome with carbamazepine is higher in Asians with a particular HLA type (HLA-B*1502), so this should be screened for before starting carbamazepine in patients with Asian ancestry
Risk of SJS may be reduced in antiepileptic treatment by. . .
. . . slowly uptitrating the drug rather than giving the full dose all at once.
Among antiepileptics, ___ both have mood-stabilizing properties, whereas ___ can cause irritability and depression
Among antiepileptics, valproate and lamotrigine both have mood-stabilizing properties, whereas levetiracetam can cause irritability and depression
At each follow-up visit, a patient on AEDs should be assessed for . . .
At each follow-up visit, a patient on AEDs should be assessed for whether seizure frequency has improved and whether there are side effects of the AED(s).
Antiepileptics must always be. . .
. . . slowly up-titrated and down-titrated, not abruptly started and stopped.
Carbamazepine autoinduction
Unique effect to carbamazepine
Carbamazepine induces its own metabolism, and so as a result, the initial effectiveness may decrease around 6 weeks to 2 months after initiating the medication, requiring a dose increase.
Refractory epilepsy
- If a patient is not controlled after adequate trials of two well-tolerated AEDs (individually or together), the patient is considered to have refractory (drug-resistant) epilepsy.
- Such patients should be considered for vagal nerve stimulator, epilepsy surgery, and/or the ketogenic diet
- If surgical resection of the epileptic focus is under consideration and MRI or nuclear medicine study does not reveal the causative lesion, intracranial EEG can be used to more precisely localize the epileptogenic lesion
Tapering off antiepileptics in seizure-free patients
In patients who have been seizure free for 2 years, the question often emerges as to whether AEDs can be titrated off.
A gradual taper can be attempted, explaining to the patient that there is about a 40% risk of seizure recurrence, and that that risk is greatest during the period of off-titration. Therefore, during this period, the patient should not drive, should not swim or bathe unaccompanied, and should not work at heights.
If a patient has a seizure during the taper, lifelong AED therapy is generally warranted.
Status epilepticus
defined as 5 or more minutes of continuous seizures, or repeated seizures without return to consciousness between them.
Aspects of managing status epilepticus
- Management of the “ABCs” (airway, breathing, circulation): Continuous oxygen saturation monitoring and cardiovascular monitoring are essential and intubation/mechanical ventilation may be necessary.
- Treatment of seizures in status epilepticus: Use the status epilepticus treatment algorithm
- Search for an underlying cause: Evaluation for hypoglycemia, electrolyte abnormalities, drug intoxication or withdrawal, structural lesion, or an infectious or inflammatory etiology in parallel with treatment. Glucose and thiamine are generally given immediately to patients in status epilepticus.
Status epilepticus treatment algorithm
- Serial doses of benzodiazepines along with glucose and thiamine
- If not under control, phenytoin load is given (some practitioners use valproate, phenobarbital, or levetiracetam instead)
- If not under control, an additional partial load of the antiepileptic loaded in the prior step
- If not under control, patient is intubated and 24-hour coma is induced with pentobarbitol, midazolam, or propofol.Continuous EEGmonitoring is generally initiated at this point to guide success of therapy. Adaily maintenance AED is also initiated.
- This step is generally only taken for generalized convulsive seizures but not for focal motor status epilepticus; use of these measures in nonconvulsive status epilepticus is debated
- Sedatives are weaned to see if patient will seize again. If so, additional AEDs and/or sedative agents can be added
- If still not under control, extreme measures may include ketamine, hypothermia, ketogenic diet, immunotherapy (if there is concern for an autoimmune etiology), electroconvulsive therapy, and/or surgical intervention (if a seizure focus can be identified).
Why do we give glucose and thiamine to patients in status epilepticus?
Hypoglycemia is a common cause of seizures, and adding glucose will quickly resolve the seizure. And, even if hypoglycemia isn’t the cause, giving glucose is a very cheap and low-risk thing to do.
Thiamine is given with glucose so as to prevent development of Wernicke’s encephalopathy in potentially at-risk patients
Nonconvulsive status epilepticus
Status epilepticus seizure activity without frank convulsions.
Subtle motor signs (e.g., eye deviation or nystagmus, eyelid or facial twitching, extremity twitching) may be present, but some patients may only have alterations in level of consciousness ranging from confusion to coma
The diagnosis is made definitively by EEG. Continuous EEG for at least 24 hours is generally required to evaluate for NCSE, since seizures may be intermittent. If EEG is ambiguous, a benzodiazepine trial can be undertaken to see if there is both electrographic and clinical improvement.
___ should be considered in patients who fail to recover consciousness after one or more seizures
NCSE should be considered in patients who fail to recover consciousness after one or more seizures
Diagnostic criteria for epilepsy
- An epilepsy syndrome
- OR, 1 seizure with >60% risk of another
- OR, 2 seizures >24 hr apart
___% of people will develop epilepsy at some point in their lifetime.
3% of people will develop epilepsy at some point in their lifetime.
Childhood Absence epilepsy syndrome
- During childhood, ages ~4-8
- 3 Hz spike wave pattern on EEG (shown)
- Normal neurologic exam
- Treated w/ ethosuxamide with good prognosis
West epilepsy syndrome
- Begins in infancy
- EEG has hypsarrhythmia (shown)
- Intellectual dysfunction on exam
- Treated w/ ACTH, variable prognosis
Juvenile Myoclonic epilepsy syndrome
- Begins in late teens
- Fast, spike wave discharges (shown)
- Neuro exam normal
- Treated w/ broad-spectrum antiepileptics, prognosis requires lifelong antiepileptic therapy
Mesial temporal sclerosis
Very common finding on MRI that can produce focal elilepsy
Tuberous sclerosis
- Genetic disease
- Patient will typically be < 2 years old, have ash leaf spots (visible w/ Wood’s lamp) and angiofibromas on skin, afebrile or complex febrile seizures
- On brain imaging, cortical tubers
- Diagnose w/ CT or MRI of brain
- Treatment of supporting
- Risk of development of benign tumors anywhere in body
Syndrome of trigeminal neuralgia
Unilateral, burning/electric pain coming from the trigeminal nerve, which starts near the top of the ear and splits in three, toward the eye, cheek and jaw.
