Seizures and Epilepsy

Carl E. Stafstrom, MD, PhD Chief, Pediatric Neurology University of WisconsinMadison

OUTLINE
1. Definitions 2. Classification 3. How to diagnose? 4. Pathophysiology 5. Case examples

April 20, 2009

Definitions
Seizure (or epileptic seizure)
Abnormal firing of neurons causing neurologic dysfunction: awareness motor control sensory perception autonomic function

Definitions
Seizure (or epileptic seizure)
- Specific clinical manifestations of a seizure depend upon which parts of the brain affected Humunculus: L -> Arm -> Hand
QuickTime and a decompressor are needed to see this picture.

Definitions
Seizure (or epileptic seizure)
- A seizure is a single event - Tempo: usually sudden onset, secondsminutes - Status epilepticus (longer seizures) necessitates intervention

Definitions
Epilepsy (or epilepsy syndrome)
Recurrent seizures

Definitions
Epilepsy (or epilepsy syndrome)

Duration of epilepsy is variable from complete resolution to lifetime disorder

Definitions
Epilepsy (or epilepsy syndrome)
More than just seizures!

Cognitive, behavioral, mood changes Stigma, social factors Quality of life Drug side effects

Seizure Classification
clinical observations EEG findings

Focal (partial)
Begin in one part of the brain

Generalized
Begin in both hemispheres at once

A seizure begins either focally or generalized, and it matters for pathophysiology, treatment, prognosis

2. Can cross corpus collosum Focal seizure

Focal seizure with secondary generalization

Generalized seizure

Thalamus is commonly involved in generalized seizures

Focal seizures
Simple focal seizure Consciousness preserved aura Secondarily generalized seizure Consciousness impaired + bilateral cerebral involvement Simple: consciousness preserved or complex (consciousness impaired) Both can generalize to other hemisphere and rest of brain

Complex focal seizure Consciousness impaired automatisms

Generalized seizures - types

Generalized tonic-clonic (grand mal) Clonic (jerking) Tonic (tightening of muscles) Atonic (total loss of tone) Myoclonic (fast jerks) Absence (petit mal)

How do we diagnose epilepsy?

History
Signs/symptoms Localization (cortex; which lobe?) Tempo (acute onset; duration seconds-minutes) Patient specific factors
Age Etiology (genetic vs acquired) Concurrent medical conditions Family history Medication responsiveness Lab (EEG findings)

epilepsy syndrome

How do we diagnose epilepsy?

Electroencephalography (EEG) a map of the brains electrical activity

Signal through dura, CSF, skin, bone, hair = inexact

How do we diagnose epilepsy?

Neuroimaging (MRI, CT, PET)

L frontal lobe look like one single mass Child w/ cortical dysplasia

Cortical dysplasia abnormal neural circuits epileptic focus

How do we diagnose epilepsy?

Other tests
Metabolic testing Genetic testing Neuropsychology

How do we diagnose epilepsy?

Rule out seizure mimics These disorders share some features of epileptic seizures such as tempo, signs, symptoms, etc.: Syncope Movement disorders: Tics, tremor, choreoathetosis Hyperventilation/anxiety Migraine Episodic dyscontrol (rage) Daydreaming (absence seizure? Complex-partial?) Pseudoseizures (Somatization disorder)

Why does a seizure occur?

Imbalance of excitation and inhibition

What factors alter this balance?

Why does a seizure occur?

E
Increased Na channel activity Increased excitatory synapse function ( glutamate, network connectivity)

and/or

I
Decreased K channel activity Decreased inhibitory synapse function ( GABA)
Intracellular recordings of normal and epileptic neurons

Case examples
1. Focal epilepsy temporal lobe epilepsy 2. Generalized epilepsy absence epilepsy

These cases illustrate the etiology, pathophysiology, and clinical approach to a few common and representative types of epilepsy

Case 1: Focal sz

secondary generalization

A 16 y.o. girl presents with multiple seizures per week, beginning 3 years ago Seizures consist of brief stare head turn to left side fumble with hand tonic-clonic convulsion of all limbs for ~ 2 min, followed by sleep Hx:
Normal pregnancy and birth Prolonged (40 min) febrile sz at 2 y.o. (most febrile seizures are benign, some predispose) Moderate developmental delay, special ed

Video 1 will be here

R. Hippo - stare R. Motor cortex: head turn, arm jerk L. Motor cortex after crossing corpus collosum: arm jerk Generalized: all limbs affected

Case 1: Temporal lobe epilepsy

Neuronal injury early in life (here, a prolonged febrile sz), followed by several year latent period during which brain becomes epileptic Sz manifestations vary from aura to complex focal sz to GTC convulsion

Aura Self-described perception of abnormal feeling, odor, taste, etc. Represents a simple partial seizure

Case 1: Temporal lobe epilepsy

TLE tends to become refractory to medications; may respond to surgical resection of hippocampus Pathological basis is scarring (sclerosis) of hippocampus

normal hippocampus

sclerotic (scarred) hippocampus

HIPPO! ->

Hippocampal (medial temporal) sclerosis

Normal
CA3 dg dg

HS
CA3
(dentate gyrus)

Neuron death and gliosis/scarring

CA3

dg

CA3

dg

Case 2: Generalized seizure (absence type)

Healthy, normally developing 11 y.o. girl Episodes of staring and spaciness in class, up to 20 per day, 10 sec each Parents also noticed staring spells at home, described as like hitting the pause button on the VCR Seizures readily controlled with medication In clinic, episodes elicited by hyperventilation

Video 2 will be here

Little girl blowing on pin-wheel to induce seizure - a couple blinks w/ stopped blowing, didnt hear pink spaghetti and red something or another.

Case 2: Absence epilepsy

Staring/unresponsive spells in otherwise normal children EEG shows 3 Hz spike wave during seizure; abrupt onset and offset Pathophysiology is thalamo-cortical loop: abnormal calcium channels Genetic basis, no pathology Responds well to medication; children often outgrow Meds: valproic acid and other.

Absence seizure: 3 Hz generalized spike-wave

Normal

then 3 Hz. Spike-wave

1 2 3

THERAPEUTIC APPROACHES
1. Avoid triggers sleep deprivation, alcohol, flashing lights
Blowing on pinwheel induces hypocapnea and decreased blood flow to brain

2. Pharmacological (upcoming lecture) 3. Surgery (selected cases) 4. Other

Dietary (e.g., ketogenic diet) Brain stimulation (e.g., vagus nerve stimulator)

Summary
Seizures come in 2 basic flavors: focal and generalized Epilepsy consists of recurrent seizures Epilepsy is a disorder of neuronal excitability: excitation > inhibition Diverse clinical manifestations, ranging from staring to convulsion Management of a patient with epilepsy involves treating both the seizures and the associated cognitive, emotional, and social concerns