Epilepsy CBL Primer

Question 1

Define epilepsy

Answer 1

“an occasional, an excessive and a disorderly discharge of nervous tissue “induced by any process involving the cerebral cortex that pathologically increases the likelihood of depolarization and synchronized firing of groups of neurons. Epilepsy is the habitual unprovoked recurrence of seizures, because of an electrically irritable brain. About ½% of the population has epilepsy.

Question 2

Describe the pathophysiology of epilepsy

Answer 2

All neurons in the nervous system are capable of excessive firing when damaged - However, the threshold for this abnormality varies considerably in different areas. -The cerebral cortex is the only area from which epileptiform activity arises with any frequency. -Even still, not all areas of the cerebral cortex have the same tendency to epileptic activity: –>most of the neocortex is relatively resistant, –>the temporal lobes and frontal lobes (particularly the limbic areas) are highly susceptible.

Question 3

What are the possible etiologies of epilepsy??

Answer 3

There are many potential underlying causes such as: - metabolic disorders of nerve cells - virtually any disorder that damages cortical tissue including: –> trauma –> hemorrhage –> ischemia –> anoxia –> infection –> hyperthermia –> the presence of scar tissue relating to prior injury.

Question 4

What is the prevalence of seizures?

Answer 4

~9% of the population will have seizure at some point, but that does not constitute epilepsy. Any acute brain injury, trauma, anoxia, high fever etc. can cause an acute seizure. Most do not recur.

Question 5

What is the prevalence of epilepsy?

Answer 5

About ½% of the population has epilepsy. Epilepsy is the habitual unprovoked recurrence of seizures, because of electrically irritable brain.

Question 6

Provide a basic description of seizures at the neuronal level.

Answer 6

–>Excitatory synapses generate EPSPs by depolarization making action potentials more likely. –>Inhibitory synapses generate IPSPs by hyperpolarization, making action potentials less likely. –>If excitation substantially exceeds inhibition, repetitive action potentials result in seizures.

Question 7

What is the role of glutamate in seizures

Answer 7

Glutamate binding to its receptors opens Na+ and Ca++ channels that depolarize the cell, making neuronal firing and seizures more likely.

Question 8

What is the mechanism of action of topiramate?

Answer 8

Anti-epileptic drug glutamate receptor antagonists

Question 9

What is the mechanism of action of lamotrigine?

Answer 9

Anti-epileptic drug block release of glutamate

Question 10

What is the role of GABA in seizures?

Answer 10

GABA binding to its receptor opens a chloride channel that hyperpolarizes the cell. This makes neuronal firing and seizures less likely.

Question 11

What is the mechanism of action of benzodiazepenes?

Answer 11

Some anti-epileptic drugs, particularly benzodiazepines and barbiturates, are agonists at GABA receptors

–> both work on GABA, A receptor

Question 12

What are the causes of epilepsy based on age of onset?

Answer 12

Intrauterine & Perinatal Injury: Birth- 3 yrs

Metabolic Defect:presents in childhood

–> Birth - 5 yrs

Congenital Malformation: presents in childhood

–>Birth - 9 yrs

Genetic Epilepsy: present in later childhood through adolescence(basically school ages)

4 years- ~19 yrs

Postnatal Trauma: Some conditions can affect any age, including trauma or infections (such as encephalitis)

–> After birth+

Brain Tumor: brain tumors and strokes are usually a cause of epilepsy in adulthood

–> 15yrs +

Vascular Disease:

Question 14

Some syndromes are quite characteristic in age of onset?

–> What is the age of onset for petit mal epilepsy?

Answer 14

petit mal epilepsy in early school age children

Question 15

Some syndromes are quite characteristic in age of onset.

What is the characteristic age on onset for temporal lobe epilepsy?

Answer 15

Temporal lobe epilepsy develops in late adolescence or early adulthood –>(often in patients with a history of prolonged, severe febrile seizures as a young child), or juvenile myoclonic epilepsy (JME) in adolescence.

Question 16

How are seizures classified?

Answer 16

The International Classification of Epileptic Seizures

Clinical observations + EEG Findings —>

1. Partial seizure: focal or localization related
2. Generalized seizure: bilateral initially or widespread cerebral involvement

Question 17

Characterize generalized epilepsies.

–> Include pathophysiology

Answer 17

Generalized epilepsies are associated with diffuse electrographic changes in the brain. Seizures may be …

–> convulsive (grand mal)

–> staring spells (absence aka petit mal)

–> tonic (stiffening)

–> atonic (loss of muscle tone).

Generalized seizures involve abnormal electrical activity in all of the cerebral cortex simultaneously.

PATHOPHYSIOLOGY

–>It is presumed that the triggers and signals for these seizures are arising outside of the cortex (reticular formation of the upper brain stem or thalamus).

–>some signal recruits all of the cerebral cortex to depolarize synchronously and, therefore, results in sudden loss of consciousness and massive synchronous motor activity.

Question 18

Characterize focal epilepsies.

Answer 18

Focal epilepsies are associated with focal seizure onsets arising usually from focal structural lesions or focal electrical abnormalities.

Question 19

What is the clinical presentation for a generalized seizure?

Answer 19

TONIC CLONIC SEIZURE

This is manifested initially by tonic contraction of all muscles of the body. –>The individual assumes a rigid extended posture due to extensor muscles overpowering the flexors.

–>Respiration is arrested and air is expelled from the lungs through a closed glottis (resulting in a guttural “cry”). This is followed in seconds (up to one minute) by synchronous intermittent contraction and relaxation (clonic activity) of the limbs and trunk, and then complete relaxation as the electrical seizure dies.

–>The clonic phase and the postictal phase probably result from massive activation of inhibitory neurons in the brain. Usually the seizure ends within several minutes but rarely may continue for hours or days as “status epilepticus”.

–>Autonomic motor overflow frequently occurs simultaneously, manifested clinically by emptying of the bladder and, less often, the bowel.

–>The pupils are large during the ictal phase and blood pressure and pulse are erratic (usually elevated).

–>A variable postseizure (postictal) period of depressed consciousness and confusion ensues. The length of this period probably depends on the length of the seizure and to some degree the general health of the brain. For example, it is likely to be much longer in the elderly and in those with a background of diffuse brain dysfunction.

Question 20

Describe the clinical presentation of a “Grand Mal Sz”

Answer 20

LOSS CONSCIOUSNESS

ICTUS

–> Fall

–> Muscular rigidity (tonic)

–> Repiration inhibited (cyanosis)

–> Rhythmic jerking (clonic)

–> 1-5 min

–> Tongue- biting/ injury common

–> Bladder/ bowel incontinence

POSTICTAL CONFUSION

Question 21

What is the prognosis for epilepsy with generalized convulsive seizures?

Answer 21

•Epilepsy with generalized convulsive seizures, but no other brain problems, is usually an idiopathic or genetic disorder with good prognosis. It usually begins in childhood or adolescence.

Question 22

What is Todd’s paralysis?

Answer 22

“After the focal seizure, the area of cortex that is most involved can have postictal depression of function lasting from minutes to hours.

–>This can result in paralysis (“Todd paralysis”) if the motor cortex is involved. Patients can have the appearance of focal deficit during this period and it may be difficult to distinguish from a patient with stroke. The history of seizure and the gradual recovery of function is critical to this differentiation.