CM II Week 5 (Seizures/Epilepsy)

At the level of the neuron...

glutamate vs GABA

Glutamate: Excitatory NT ... excess glutamate. Seizure: too much excitation (glutamate) without enough inhibition

GABA: Inhibitory NT

Seizure

signs or symptoms caused by electrical hyper synchronization of neuronal networks in the cerebral cortex

Epilepsy

an enduring predisposition to generate epileptic seizures. Neurobiological, cognitive, psychological, and social consequences are present

Clinical definition of Epilepsy (what criteria you must meet to categorize as epilepsy)

1. At least TWO unprovoked seizures > 24 hrs apart (excludes clustered seizure pts.)

2. One unprovoked seizure and high risk of recurrence (over next 10 years)

3. Previous Diagnosis of epilepsy syndrome (ex. juvenile myoclonic seizures)

What clinical variables determine high risk of seizure recurrence in patients?

1. Prior Brain Insult (stroke, seizure, meningitis)

2. Epileptiform EEG

3. Abnormal CT/ MRI (cortical dysfunction)

4. Nocturnal seizure (wake up w/ seizure)

Epidemiology of seizure disorders

affects 8-10% of population

Epilepsy 0.5% of population

Seizures make up 1% of ED visits

What age groups are more susceptible to seizures and epilepsy

Very young (<20)

Very Old (>70)

Acute symptomatic seizure

"provoked seizure" occurring with systemic insult or acute brain insult

insults include metabolic derangements, drug/alcohol withdrawal, and acute neurologic disorders such as stroke, encephalitis, or acute head injury

25-30% of first seizures are...

acute symptomatic/provoked seizures

What is the recurrence rate of provoked seizures?

Less than 20%

Unprovoked seizure

a seizure of unknown etiology as well as one that occurs in relation to a preexisting brain lesion or progressive nervous system disorder

What type of seizure is spontaneous?

Unprovoked

seizures occur spontaneously and expected to recur in the absence of treatment

Has no obvious cause so will need to obtain hx, epilepsy risk factor, imaging

List acute neurologic illnesses that may cause seizures

Stroke

Intracranial hemorrhage

Subarachnoid hemorrhage

Subdural Hemorrhage

Anoxic brain injury

Example of reversible factor that could cause seizure

Metabolic causes: hyper/hypoglycemia, hyponatremia, hypocalcemia

Provoking factors can cause epilepsy in?

Provoking factors can cause epilepsy in any patient. Some factors are reversible (metabolic causes). Over time patent should improve from insult with low chance of recurrence

Triggers for Seizures

Seizure Triggers causes seizures in those with epilepsy due to lowering their seizure threshold

Sleep Deprivation

Bright lights

Alcohol intoxication AND WITHDRAWAL

ASM (anti-seizure) noncompliance

provoking factors for seizures

strong enough to cause a seizure in ANYONE without epilepsy

Can provoked seizures be considered epilepsy?

NO

Can an unprovoked seizure cause future epilepsy?

YES if there is a >60% chance of recurrence

Causes of childhood epilepsy are typically...

genetic

metabolic (reversible)

congenital

structural

Adult epilepsy are more likely caused by...

acquired vascular, degenerative, or neoplastic (cancer) causes

Triggered seizures are

seizures in those with diagnosed epilepsy that have a lower seizure threshold

Structural Causes of Epilepsy Include

Vascular: Vascular malformation, stroke

Neoplastic: primary and mets

Trauma

Infectious - meningitis, encephalitis

Autoimmune encephalitis

Degenerative - Alzheimer's

Mesial Temporal Sclerosis

Congenital: Focal Cortical Dysplasia and tuberous sclerosis

Genetic causes of epilepsy

known or presumed genetic defect

multiple gene abnormalities w/ seizure susceptibility

Ex: childhood absence epilepsy, juvenile myoclonic epilepsy

Metabolic causes of Epilepsy

glucose transporter deficiency

creatine deficiency

mitochondrial cytopathies

Immune causes of Epilepsy

CNS inflammation

Rasmussen and NMDA encephalitis

Infectious causes of epilepsy

HIV

TB

Malaria

Unknown causes of epilepsy

~30-50% of patients have an unknown cause of epilepsy

Causes of Acute Symptomatic Seizures and Epilepsy in older adults

Most common cause of provoked seizures in older adults

Acute hemorrhagic and ischemic stroke

Most common cause of unprovoked seizures/ epilepsy in adults

Cerebrovascular disease (prior stroke, vascular malformation)

Test to evaulate a patient with possible encephalopathy

EEG

Scalp EEGs

can miss focal epilepsies

Buzz Words for Epileptiform waves

Spike and Sharp waves w/ lateralized epileptiform discharges

Reasons to admit someone to an epilepsy monitoring unit

1. Based on your diff diagnosis

2. Seizure classification

3. Medication Titration & Surgical Evaluation

true or false: in epilepsy monitoring unit, pts are stimulated with potential seizure triggers to attempt to provoke another seizure

TRUE!

Try to induce seizures in epilepsy monitoring unit by:

•Sleep deprivation

•Photic stimuli

•Alcohol intoxication/withdrawal

•ASM noncompliance

Natural History of Seizure Disorders

•Up to 70% of individuals with epilepsy can achieve seizure freedom

•Others will have drug resistant epilepsy that will be difficult to manage

•In children, epilepsy syndromes such as absence seizures often resolve by adolescence

•Other epilepsy syndromes typically genetic or developmental have worse outcomes and associated with frequent seizures and encephalopathy

What are the stages of a seizure?

1. Prodromal/ Trigger

2. Aura

3. Ictus

4. Post Ictus

Prodromal/Trigger stage of seizure

only with provoked seizures:

•Sleep deprivation

•Photic stimuli

•Alcohol intoxication/withdrawal

•ASM noncompliance

Aura of a seizure

Period of altered sensation before the onset of a seizure

- Often aware of strange smells, auditory, motor activity, or sights prior to seizure

- Aura - déjà vu and detachment from reality

- Auras are focal seizures that affect enough of the brain to cause symptoms, but not enough to interfere with consciousness (sense of doom)

Ictal phase

full seizure - impairment, tonic, clonic

Stereotypical

Rhythmic

Brief

(Depends on brain region)

Post-ictal phase

The final phase of a generalized seizure, during which the patient becomes extremely fatigued and disoriented

fractures, incontinence, tongue biting, often characterized by somnolence, confusion, and headache

Todd's paralysis/ paresis

focal weakness in a portion of the body following a seizure, typically left or right side

How are seizures classfied?

Focal or generalized

Generalized seizures involve

both hemispheres of the brain

focal seizures involve

one part of the brain

Focal Seizure with Retained Awareness

Simple partial seizure; patient is aware of and able to recall event and able to answer questions about it

characteristics of Focal with Retained Awareness Seizure (simple partial)

•Auras are focal aware sensory seizures

•Paraesthesias, tingling, gustatory, olfactory, visual and auditory sensations

•Behavioral arrest, speech arrest, déjà vu, fear/feeling of doom

•Epigastric pain, sweating, tachycardia

•Can have automatisms and unilateral motor features

List examples of sensory signs of Aura

Sensory Effects: Paresthesia, tingling, olfactory, gustatory, visual & auditory sensations

List examples of autonomic signs of Auras

Epigastric Pain

Sweating

Tachycardia

Focal Impaired Awareness Seizure (FIAS)

Focal Impaired Awareness (complex partial): impaired responsiveness with environment, confusion, unable to recall events

characteristics of Focal Impaired Awareness Seizure (FIAS)

•Appears awake but not responding normally to instructions or questions

•Automatisms: repetitive behaviors such as facial grimacing, gesturing, chewing, lip smacking, or repeating words

•Seizures typically last less than three minutes

•Can be postictal: characterized by somnolence, confusion, and headache for up to several hours

Focal Motor Seizure

The clinical manifestations of seizures vary based on?

The clinical manifestations of seizures vary based on the location of the seizure in the brain and the amount of cortex that is involved

Focal Motor Seizure - motor sx

•can have unilateral tonic, clonic, myoclonic events

•Jacksonian March

Jacksonian March Seizure

progressive neuroanatomic spread

focal seizures may propagate diffusely to cause?

Focal seizures may propagate diffusely to cause bilateral tonic-clonic seizures (previously referred to as secondarily generalized seizures)

Temporal Lobe Epilepsy

most common form of focal epilepsy

almost 2/3 of cases of intractable epilepsy managed surgically

etiology of temporal lobe epilepsy

Mesial temporal sclerosis is common etiology

Temporal Lobe Epilepsy associated with what sx

Associated with aura including anxiety, déjà vu, olfactory, gustatory/auditory, hypokinetic, staring, aphasia, amnesia

Temporal Lobe Epilepsy

Can have seizure freedom after?

can have seizure freedom after temporal lobectomy surgery

Occipital Lobe Seizures sx

flashing lights, elementary visual hallucinations

prominent blinking/eyelid fluttering

Parietal Lobe Seizures sx

may cause distortion of spatial perception; sensory and language changes

Frontal lobe Seizures sx

•may cause sudden speech difficulties and hyperkinetic movement, nocturnal

•Hypermotor and bizarre movements (proximal limbs, tonic), bicycling kicking, pelvic thrusting

•Gaze deviation and aphasia

•it may occur during sleep and lack post-ictal phase

Treatment of Focal seizures

Antiseizure medications for focal seizures:

• Lamotrigine, Levetiracetam, carbamazepine, oxcarbazepine, Valproic acid, phenytoin

Epilepsy surgery: temporal lobectomy etc

Generalized Seizures involve? determine onset with?

Involve seizure onset in both hemispheres

May need an EEG to determine onset in some cases

generalized seizures: in kids? generally?

Can have automatisms

Absence seizures in children

What is the most common generalized seizure type

tonic clonic (grand mal)

Treatment of generalized seizures

Lamotrigine, Levetiracetam, Valproic acid, topiramate, zonisamaide

Types of Motor Seizures

Tonic

Clonic

Atonic

Myoclonic

Tonic Seizure physical signs

rigidity and sudden stiffness of trunk and limbs

Muscle extension

Fall backwards

Clonic Seizures physical signs

jerking

sustained muscle contraction w/ alternation of relaxation

Atonic seizure signs

drop attacks

loss of tone

fall forward

Myoclonic seizure signs

Brief muscle contractions can occur singly or in clusters

Arms are affected

Consciousness is NOT impaired

What are absence seizures

Petit mal seizures. Brief lapse of consciousness.

When are absence seizures most commonly seen (AGE)

seen in childhood 4-10, usually stop by 20

BUZZ WORDS associated with Absense Seizures (signs & symptoms)

Staring, rhythmic eye blinking, automatisms

•Person not always aware of interruption in consciousness

•Break off in mid sentence

KIDS!

EEG signs of absence seizure

bursts of 3 Hz synchronous & symmetrical spike-waves

Treatment of Absence Seizures (Petit Mal)

Ethosuximide (Zarotonin)

Valproic acid (Depakene)

Generalized Tonic Clonic Seizures (Grand Mal)

epidemiology

•Mostly seen in ages 10-25 (associated with genetic generalized epilepsy)

•New onset of generalized epilepsy is uncommon in adults: often is a focal to bilateral tonic clonic seizure that generalizes

•Frequency ranging from daily to once every few months or years

•The prognosis for remission can vary, with some individuals experiencing only a single seizure, while others may go into status needing multiple ASMs

•Three risk factors for seizure recurrence: are the number of seizures, underlying neurological disorder, and an abnormal electroencephalogram

Phases of grand mal seizure (in order)

1. Tonic phase (20 sec -1 minute)

2. Clonic phase (30 to 90 seconds)

3. Post-ictal

What occurs during the tonic phase of grand mal seizure

muscle rigidity and stiffness

•Sudden LOC followed by respiratory arrest

•Involuntary crying out from contraction of respiratory muscles

•Extension of muscles

•Associated cyanosis

What occurs during the clonic phase of grand mal seizure

Brief, violent, generalized flexor contractions alternating with progressively longer muscle relaxation

•Possible cheek or tongue biting

•Foamy salivation

•Possible loss of bowel or bladder control

What occurs during post-ictal phase of grand mal seizure

can be in deep sleep, confusion & somnolence, muscle soreness

Treatment of Grand Mal (Tonic/ Clonic) Seizure

Lamotrigine (Lamictal)

Levetiracetam (Keppra)

Topiramate (Topamax)

Valproate (Depakene)

Atypical Absence

•More changes in tone that regular absence

•More gradual start and prolonged episodes

•May be associated with developmental delay

•Slower spike-wave patterns

•About 12 to 13 percent of children develop generalized tonic clonic, however should be reevaluated if patient has absence seizures

Status Epilepticus

Convulsive Status is? timeline?

Convulsive Status is a medical emergency!

≥5 minutes of continuous seizures, or

≥2 discrete seizures between which there is incomplete recovery of consciousness

Long-term consequences of Status Epilepticus

Long-term consequences (after 30 mins): neuronal death, neuronal injury, and alteration of neuronal networks

Etiology of Status Epilepticus

•Most cases of status epilepticus in adults are due to an acute underlying structural brain lesion or a toxic or metabolic disturbance

•Patient with known epilepsy or low ASM levels

Clinical Manifestation of Status Epilepticus? If no return to baseline?

tonic and/or clonic motor activity and loss of consciousness

•If no return to baseline, obtain EEG

•it may show continuous spike and wave activity indicative of generalized seizure activity.

Nonconvulsive status epilepticus (NCSE

• challenging diagnosis. It typically manifests as an altered mental status with confusion, psychosis, lethargy, or coma

•a condition of ongoing or intermittent seizure activity without convulsions, without recovery of consciousness between attacks, and lasting more than 10 minutes. Diagnosis is made in EEG

Management of status epilepticus

IV access = lorazepam (ativan)

no IV access = midazolam

ensure patent airway

second line management of status epilepticus

Second line: Load ASM

1. Levetiracetam (Keppra)

2. Depakote/Depacon (valproic acid)

3. Fosphenytoin

more seizure management

intubation

midazolam

continuous EEG

notify ICU

>60 minutes of seizure

Non contrast head CT

Add propofol or pentobarb with EEG

History for seizure activity (general)

Prodrome or Aura?

Seizure activity

•Convulsions, tongue biting, awareness

•Was there a Witnesses or video recording

•Timing: age of onset, awake vs sleep

•Duration: should not be longer than 5 minutes

Postictal: state of confusion, can last mins to hours. Aphasia, hemianopsia, or numbness. Todd paralysis or postictal paresis.

Postictal - Todd paralysis or postictal paresis

postictal paresis is weakness of a hand, arm, or leg that appears following a focal motor seizure involving the one side of the body

history - triggers?

•strong emotions, intense exercise, loud music, and flashing lights, fever, the menstrual period, lack of sleep, pregnancy, and stress.

•Can have no triggers as well

Epilepsy Risk Factors (SH/PMH/FHx)

•CNS structural changes: neoplasm or malformation, Birth complications, premature, Family history, febrile seizures, autism, developmental delays

•SH: Drug and alcohol use

•PMH: Neurologic hx, immunosuppression, cancer, past epileptic events

•FHx: A positive family history of seizures is a risk factor for epilepsy. In particular, absence seizures and myoclonic seizures may be inherited

Physical Exam for seizures

•Look for signs of injury: tongue bite or injury

•Post ictal confusion

•Todd's Ictal paralyses

•Hyperreflexia

•Can have a normal exam

Differential Dx for transient neurologic event

•TIA: Rapid loss of neurologic function due to interrupted blood flow; typically "negative” symptoms (eg, weakness, numbness, aphasia, visual loss)

•Panic Attack: Palpitations, dyspnea, chest pain, lightheadedness, sense of impending doom; 

•Migraine Aura: Positive and/or negative neurologic symptoms, most often visual and sensory, evolving > 5 min

•Psychogenic nonepileptic seizure: seizure like activity w/o EEG correlate, eyes closed, no post ictal

•Generalized: cardiac problem causing lack of blood to brain?

•Syncope: Transient loss of consciousness, loss of postural tone; has prodrome of lightheadedness, temperature, sweating, palpitations, pallor; myoclonic jerks or tonic posturing may occur, no post ictal confusion

•Narcolepsy