Seizure and Epilepsy

Question 1

Epilepsy

Answer 1

The condition of recurrent unprovoked seizures

Question 2

Things that may provoke seizures in non-epileptic patients

Answer 2

Acute hypoglycemia, alcohol withdrawal, high fever, and medication or drug toxicity

These are all acute, reversible factors

Question 3

Things that may cause seizures, but do not technically “provoke” them

Answer 3

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.

Question 4

A patient with seizure(s) will generally present for evaluation in one of three scenarios:

Answer 4

1. After a first seizure or other spell
2. With a history of seizures (or other type of spell)
3. Actively seizing

Question 5

Whenever possible when trying to gather history on a suspected seizure, ___ should be obtained.

Answer 5

Whenever possible when trying to gather history on a suspected seizure, a clear description of the event by witnesses should be obtained.

Question 6

Seizures are broadly categorized as ___ or ___.

Answer 6

Seizures are broadly categorized as generalized seizures or focal seizures.

Question 7

Generalized seizures

Answer 7

• 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.

Question 8

Motor manifestations of seizures

Answer 8

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).

Question 9

Postictal state

Answer 9

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.

Question 10

Absence seizures

Answer 10

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.

Question 11

Focal (Partial) Seizures

Answer 11

• 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

Question 12

Post-ictal weakness / Todd’s paralysis

Answer 12

• 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.

Question 13

Aspects of history that suggest fall/loss of consciousness is more likely seizure than syncopy

Answer 13

• 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

Question 14

Seizures generally cause ___ while TIAs generally cause ___.

Answer 14

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).

Question 15

Distinguishing seizure from a migraine with aura

Answer 15

• 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.

Question 16

Distinguishing Seizures From Psychogenic Nonepileptic Spells (Pseudoseizures)

Answer 16

• 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

Question 17

Five categories of EEG findings

Answer 17

• 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)

Question 18

Sensitivity of a routine EEG in detecting epileptiform activity

Answer 18

• 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

Question 19

Notes on epileptiform activity on EEG

Answer 19

• A small proportion of the population may have EEG abnormalities of no clinical significance
• A number of medications can also cause EEG abnormalities

Question 20

The absence of epileptiform discharges ___ and their presence ___

Answer 20

The absence of epileptiform discharges does not “exclude” epilepsy and their presence does not “confirm” epilepsy

Question 21

Workup of a patient’s first seizure

Answer 21

• 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

Question 22

Epilepsy-protocol MRI

Answer 22

• 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.

Question 23

What is going on in this MRI?

Answer 23

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.

Question 24

When are antiepileptics useful?

Answer 24

• 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.
• 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.

Question 25

Counseling after first seizure

Answer 25

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.**

Question 26

Antiepileptics sometimes. . .

Answer 26

. . . **make epilepsy worse!!!!** It is important to know which diseases antiepileptics treat, and which they exacerbate. THESE ARE NOT BENIGN DRUGS.

Question 27

First-line therapy for idiopathic genetic generalized epilepsy syndromes

Answer 27

**Valproate** *with the exception* of **childhood absence epilepsy**, for which **ethosuximide** is first-line therapy.

Question 28

Valproate should be avoided in. . .

Answer 28

. . . **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.

Question 29

Carbamazepine is particularly effective for \_\_\_

Answer 29

Carbamazepine is particularly effective for **partial (focal) seizures** **BUT** may worsen **idiopathic genetic generalized epilepsy syndromes** such as **childhood absence epilepsy**

Question 30

Drug-drug interactions of antiepileptics

Answer 30

* 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.**

Question 31

Side effects of antiepileptics

Answer 31

* 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**

Question 32

The highest risks of Stevens-Johnson syndrome among antiepileptics are with. . .

Answer 32

. . . **phenytoin, phenobarbital, carbamazepine, and lamotrigine** The risk of Stephens-Johnson syndrome with **carbamazepine** is higher in **Asian**s with a particular **HLA type (HLA-B\*1502)**, so this should be screened for before starting carbamazepine in patients with Asian ancestry

Question 33

Risk of SJS may be reduced in antiepileptic treatment by. . .

Answer 33

. . . **slowly uptitrating the drug rather than giving the full dose all at once.**

Question 34

Among antiepileptics, ___ both have mood-stabilizing properties, whereas ___ can cause irritability and depression

Answer 34

Among antiepileptics, **valproate and lamotrigine** both have mood-stabilizing properties, whereas **levetiracetam** can cause irritability and depression

Question 35

At each follow-up visit, a patient on AEDs should be assessed for . . .

Answer 35

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).**

Question 36

Antiepileptics must always be. . .

Answer 36

. . . **slowly up-titrated and down-titrated, not abruptly started and stopped.**

Question 37

Carbamazepine autoinduction

Answer 37

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.**

Question 38

Refractory epilepsy

Answer 38

* 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

Question 39

Tapering off antiepileptics in seizure-free patients

Answer 39

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.​**

Question 40

Status epilepticus

Answer 40

defined as **5 or more minutes** of **continuous seizures,** or repeated seizures **without return to consciousness between them.**

Question 41

Aspects of managing status epilepticus

Answer 41

1. **Management of the “ABCs” (airway, breathing, circulation):** Continuous oxygen saturation monitoring and cardiovascular monitoring are essential and intubation/mechanical ventilation may be necessary. 2. **Treatment of seizures in status epilepticus**: Use the status epilepticus treatment algorithm 3. **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.

Question 42

Status epilepticus treatment algorithm

Answer 42

1. Serial doses of **benzodiazepines** along with **glucose** and **thiamine** 2. If not under control, **phenytoin load** is given (some practitioners use valproate, phenobarbital, or levetiracetam instead) 3. If not under control, an **additional partial load** of the antiepileptic loaded in the prior step 4. If not under control, **patient is intubated** and **24-hour coma is induced** with **pentobarbitol, midazolam, or propofol.****Continuous EEG**monitoring is generally initiated at this point to guide success of therapy. A**daily 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 5. **Sedatives are weaned** to see if patient will seize again. If so, **additional AEDs and/or sedative agents** can be added 6. 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).

Question 43

Why do we give glucose and thiamine to patients in status epilepticus?

Answer 43

**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

Question 44

Nonconvulsive status epilepticus

Answer 44

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.

Question 45

\_\_\_ should be considered in patients who fail to recover consciousness after one or more seizures

Answer 45

**NCSE** should be considered in patients who fail to recover consciousness after one or more seizures

Question 46

Diagnostic criteria for epilepsy

Answer 46

* An epilepsy syndrome * OR, 1 seizure with \>60% risk of another * OR, 2 seizures \>24 hr apart

Question 47

\_\_\_% of people will develop epilepsy at some point in their lifetime.

Answer 47

**3%** of people will develop epilepsy at some point in their lifetime.

Question 48

\_\_% of people will have a seizure in their lifetime

Answer 48

**10%** of people will have a seizure in their lifetime

Question 49

#1 cause of epilepsy worldwide

Answer 49

**Infection** * **Neurocysticercosis** (Taenia solium, aka pork tapeworm) * **HIV** * **TB** * **ToRCHeS** infections

Question 50

Childhood Absence epilepsy syndrome

Answer 50

* During childhood, ages ~4-8 * 3 Hz spike wave pattern on EEG (shown) * Normal neurologic exam * Treated w/ ethosuxamide with good prognosis

Question 51

West epilepsy syndrome

Answer 51

* Begins in infancy * EEG has hypsarrhythmia (shown) * Intellectual dysfunction on exam * Treated w/ ACTH, variable prognosis

Question 52

Juvenile Myoclonic epilepsy syndrome

Answer 52

* Begins in late teens * Fast, spike wave discharges (shown) * Neuro exam normal * Treated w/ broad-spectrum antiepileptics, prognosis requires lifelong antiepileptic therapy

Question 53

Mesial temporal sclerosis

Answer 53

Very common finding on MRI that can produce focal elilepsy

Question 54

Convulsive syncopy

Answer 54

Phenomenon where syncopy **can produce convulsions.** However, people still regain consciousness rapidly. Important to know that this does exist and can be very difficult to differentiate from a seizure. Even more confusing, syncopy can sometimes trigger a true seizure.