CM- Epilepsy

Question 1

What is an epileptic seizure?

What is epilepsy?

Answer 1

It is a temporary, relatively sudden alteration of behavior and cognition due to hypersynchronous/excessive discharge from CEREBRAL neurons

Epilepsy is a disease of RECURRENT and multiple seizures

Question 2

What determines the probability that a neuron will be depolarizedand regenerate a neural signal?

Answer 2

1. One neuron generates an action potential that activates synaptic neurotransmitter release
2. Excitatory {EPSP} or inhibitory {IPSP} post-synaptic potentials are generated

Whether the neuron depolarizes or not depends on:

1. spatial and time summation of 1000s of separate EPSPs or IPSPs on a single neuron
2. intrinsic membrane properties

Question 3

What underlies the constant fluctuating patterns of voltage activity seen with the normal human EEG?

Answer 3

summation of EPSP and IPSP over the entire populations of cortical neurons

Question 4

What 3 factors determine the generation of the neuronal hyperexcitability and hypersyncrony [the epileptic focus]?

Answer 4

1. intrinsic properties of neuronal excitability
   - membrane properties [channel types/mutations]
2. exposure to inhibitory or excitatory neurotransmitters
   - balance can be upset with the loss of GABA input
3. manner by which the “epileptic” neuronal populations are interconnected
   - ex. post injury causing increased mossy fibers in the hippocampus

Question 5

If you see a spike and slow wave on scalp EEG, what does this mean?
What is the “spike” and what is the “slow wave”?
What would be seen on an intracellular recording?

Answer 5

Spike and slow wave correlate with abnormal, epileptogenic cortex in an interictal state [it shows the potential for epileptic seizure when the patient is currently NOT having a seizure]

Spike = paroxysmal depolarization shift [PDS]
Slow wave = after hyperpolarization

Question 6

What is the difference between provoked and unprovoked epileptic seizure?

Answer 6

Provoked = seizures that occur when a normal cortex is exposed to extreme [but mostly avoidable] conditions like:

• hypoglycemia
• hyponatremia
• acute infection
• alcohol withdraw
• drug intoxication

** provoked seizures are NOT considered or treated as epileptic disorders

Question 7

The operational and epidemiological definition of epilepsy is two or more ______________ epileptic seizures.

Answer 7

non-provoked

Question 8

When is the highest incidence of epilepsy?

Answer 8

Incidence is highest in early life and continues to fall throughout life

Question 9

What % of people will develop epilepsy within his/her lifetime?

What percent of the population will experience a SINGLE epileptic seizure at some point in a lifespan of 80 years?

Answer 9

Epilepsy = 1.5 to 3%

Single, epileptic seizure = 10%

Question 10

What is the cause of epilepsy in the vast majority of patients?

Answer 10

The vast majority have no specific cause identified!

[risks can range from brain traumatic injury to inherited epileptic syndromes]

Question 11

List 5 major risk factors for the development of epileptic seizures.

Answer 11

1. major head trauma [esp. military gun shot wounds]
2. encephalitis
3. Stroke
4. Alzheimer’s
5. moderate head injury

• MS, meningitis, mild head injury, antidepressants

Question 12

What are the 2 most common entities misdiagnosed as epilepsy?

Answer 12

1. Psychogenic attacks
   - fake seizures! differentiate from epileptic seizure by: biting the tip of the tongue, seizures lasting more than 2 minutes (easiest factor to distinguish), seizures having a gradual onset, a fluctuating course of disease severity, the eyes being closed during a seizure, and side to side head
   movements
2. convulsive syncope
   - bilateral decrease in blood flow to the brain causes loss of consciousness with convulsive movements

Question 13

What are the 3 phases a patient with epilepsy can be in?

Describe the transition between each stage.

Answer 13

1. Interictal = all events occuring between seizures when function [cognitive, behavioral, neurophys] is at baseline
   * baseline is probably still abnormal
2. ictal = the time when an epileptic seizure is occurring
3. post-ictal = 5 to 30 minutes when various functions are recovering from the seizure

Interictal –> ictal is abrupt and recognizable
ictal–> post and post–>inter are gradual and difficult to separate

Question 14

After a focal seizure, a patient may develop hemiparesis contralateral to the seizure origin. What is this called?

Answer 14

Todd’s paralysis

Question 15

If after a seizure, language is disrupted and there is post-ictal aphasia, where is the seizure localized?

Answer 15

dominant hemisphere [left]

Question 16

When you are classifying seizures according to various behavioral and electrophysiologic characteristics, what are the 3 categories?

Answer 16

1. Partial - beginning w/in one hemisphere
2. generalized- simultaneously affecting both hemispheres
3. unclassified

Question 17

What are the 3 types of partial seizures?

Answer 17

1. simple
2. complex
3. secondary generalized

Question 18

A person who presents experiencing strange odors [olfactory], flashing lights [visual], tingling [somatosensory], deja vu [psychic], fear or sadness [affective], nausea or rising from the pit of stomach [autonomic] or jerking of a limb [motor] but with NO amnesia/loss of consciousness, experienced what kind of seizure?

Answer 18

Simple partial

Question 19

Describe the features of a simple partial seizure.

Answer 19

• starts in one hemisphere of the brain
• subjective or objective alteration of cognition or behavior
• NO altered consciousness [as defined by absence of amnesia]
• odor, lights, fear or sadness, rising from pit of stomach, deja vu, jerking of a limb, tingling, “jacksonian march”
• “aura”

Question 20

What is the jacksonian march?

Answer 20

A simple partial seizure that spreads along the cortex causing successive activation of contiguously represented body parts [hands to face to legs]

Question 21

When a patient subjectively experiences a simple partial seizure, this is referred to as an aura. What does this allow neurologist to do?
What patients with simple partial seizures will not experience an aura?

Answer 21

“Aura” - helps neurologists localize the onset or early stages of epileptic seizure

Aura will not be experience if the seizure is in an area of the brain that does not elicit a noticeable function [like the frontal cortex]

Question 22

How do you test for preservation of consciousness during a seizure?

Answer 22

if the patient is conscious, the patient will have the ability to remember a word or phrase given during the time of seizure

Question 23

What does the EEG show on a simple partial seizure?

Answer 23

It can be normal OR abnormal

Question 24

Describe what occurs during a complex partial seizure.

Answer 24

Complex partial involve impaired consciousness and imply the spread of epileptic activity to a bilateral memory system [hippocampus]

The patient will be:

1. unresponsive
2. automatisms- repetitive movements with no purpose [chewing lip, picking at clothes]
3. anmestic about the event

Question 25

Why is there a greater threat for injury in a complex partial seizure than in a simple partial seizure?

Answer 25

In complex partial seizures, the epileptic spread is so fast, that it precludes any activated cortical symptoms from reaching awareness.

Question 26

How do simple partial and complex partial seizures differ in terms of consciousness?

Answer 26

``` Simple = conscious Complex = not conscious ```

Question 27

What happens to someone after they have a complex partial seizure that helps you differentiate it from syncope?

Answer 27

Post-ictal period is marked by confusion and disorientation ["post-ictal confusion] -the patient may also have unilateral weakness [Todds] or trouble speaking [post-icteral aphasia]

Question 28

What does the EEG show for a complex partial seizure?

Answer 28

rhythmic sharp discharges beginning in one area and becoming more diffuse

Question 29

What is a secondary generalized seizure? | Which type of seizures can progress to it?

Answer 29

Simple and complex partial can directly spread to become secondarily generalized Both hemispheres, subcortical region and brainstem are involved

Question 30

What are the 2 phases of a secondary generalized seizure? How does the seizure begin? What happens during the seizure? How long does it last?

Answer 30

1. Tonic phase - started by and ictal cry [due to forced vocalization by contracting diaphragm and intercostals] - limbs extend and become rigid - jaw closure may cause tongue or cheek to become bitten - bladder empties 2. Clonic phase - limbs and facial muscles contract rhythmically The entire seizure from cry to clonic jerk lasts less than 2 min

Question 31

What are the 6 types of generalized seizures? Describe what occurs in each. Which is the most dangerous?

Answer 31

1. absence [typical/classic or atypical] - less than 30 second staring spell w/ or w/o automatisms. ALWAYS with amnesia. Despite amnesia, there is no post-ictal confusion [the patient might not even know they have it] 2. tonic -sudden increase in body tone that lasts less than 1min 3. clonic - repetitive muscle jerk of all limbs w/o clear tonic phase 4. tonic-clonic = just like secondary generalized 5. myoclonic - sudden rapid muscle jerk involving arms and trunk bilaterally and synchronous 6. atonic- sudden loss of muscle tone which can cause rapid collapse. **MOST DANGEROUS

Question 32

A teacher complains that a boy is zoning out during class. He has 30sec staring spells were he chews his lip. Onset of these spells will be abrupt. After the boy refocuses, he acts as if nothing had happened. What is the likely type of seizure and what would the EEG show for classic? atypical?

Answer 32

Absence seizure Classic --> 3Hz spike-slow wave discharges Atypical --> 1-2 Hz spike-slow wave discharges

Question 33

What is an epileptic syndrome? | What does it allow us to do?

Answer 33

Epileptic syndromes constitute an array of shared characteristics such as: - age of onset - associated cognitive and physical manifestations - stereotyped EEG pattern - type of seizure experienced This allows us to: 1. assist with prognosis 2. identify common etiology 3. predict the most effective treatment

Question 34

What is the most important characteristic of epileptic syndrome?

Answer 34

similar clinical and EEG seizures

Question 35

What are the 4 classifications of epileptic syndromes?

Answer 35

1. localization-related syndromes - idiopathic - symptomatic - cryptogenic 2. generalized syndromes - idiopathic - symptomatic - cryptogenic 3. Undetermined if focal or generalized 4. special syndromes

Question 36

When defining epileptic syndromes, what can "focal" and "generalized" be further subdivided into?

Answer 36

1. idiopathic - implies genetic etiology in which the only abnormalities is INTRINSIC NEURONAL hyperexcitability [channelopathy] 2. Symptomatic- distinct, acquired brain injury - ex. cortical hamartoma, Tuberous sclerosis 3. Cryptogenic- thought to be an acquired injury, but no specific lesion can be identified

Question 37

What is the prime example for focal, idiopathic epilepsy? How does it present? What is seen on MRI, neuro exam, and EEG? How does the frequency of seizures change w/ age?

Answer 37

Benign Rolandic Epilepsy - children have focal motor or secondarily generalized seizures - normal intelligence, MRI and neuro exam - EEG shows epileptiform discharge from central-temporal region These tend to remit spontaneously in adolescence

Question 38

What is a prime example of focal, cryptogenic epilepsy? How does it present? What is seen on the MRI, neuro exam, and EEG? What is treatment ?

Answer 38

Mesial Temporal Lobe Epilepsy - history of febrile seizures - normal neuro exam - cognitive dysfunction localized to one temporal lobe - EEG shows focal, temporal epileptiform discharges - MRI shows unilateral hippocampal atrophy This is an intractable, drug resistant epilespy. Treatment is surgical

Question 39

What is the prime example of generalized, idiopathic epilepsy? What are the 3 ways it can present? What is seen on MRI and neuro exam? How does seizure frequency change w/ age?

Answer 39

Juvenile Myoclonic Epilepsy 1. absence 2. myoclonic 3. tonic/clonic - normal neuro exam, MRI and intelligence - seizures are well-controlled but persist throughout life

Question 40

What is an example of generalized epilepsy that can be symptomatic or cryptogenic? What are the presentations? What does neuro exam, MRI and EEG show?

Answer 40

Lennox- Gastaut syndrome "catastrophic epilepsy" - multiple seizure types [mostly absence, tonic] - mental retardation, abnormal MRI, characterisctic EEG

Question 41

What are the 2 focal epileptic syndromes?

Answer 41

1. Benign Rolandic Epilepsy | 2. Mesial Temporal Lobe Epilepsy

Question 42

What are the 3 generalized epileptic syndromes?

Answer 42

1. Juvenile Myoclonic epilepsy 2. Lennox-Gastaut syndrome 3. benign familial neonatal convulsions

Question 43

What are the 2 genetic epileptic syndromes? | What is the inheritence pattern and what is the mutation?

Answer 43

1. Autosomal Dominant nocturnal frontal lobe epilepsy - mutation in the nicotinic Ach receptor - presents in first 2 decades with clusters of nocturnal seizures 2. benign familial neonatal convulsions - K+ channel mutation where abnormal repolarization leads to neuronal excitability

Question 44

What are the 2 goals for epilepsy treatment? | What are the 3 steps the physician must go through before deciding on treatment?

Answer 44

1. seizure-freedom 2. minimal or no side effects that detract from quality of life Physicians must 1. determine the patient actually has epilepsy [not psychogenic or syncope 2. define the epileptic seizure 3. define the epileptic syndrome

Question 45

What 4 things are included on the workup for a patient with epilepsy?

Answer 45

1. detailed history from patient and witness who has seen the seizures 2. general and neuro exam 3. MRI 4. EEG

Question 46

What is an EEG? What does it measure? | What neurons are involved?

Answer 46

EEG is a voltage over time graph that records over multiple site over the human scalp. Voltage is generated by synchronously activated populations of cortical neurons [particularly large pyramidal neurons. Thousands of EPSP and IPSP achieve spatial and temporal summation to generate sufficient voltage to be recorded

Question 47

What is typical surface voltage over the human scalp?

Answer 47

20 to 200 microvolts [can get up to 1000 in certain pathological situations]

Question 48

What is the technique for setting up the EEG? Describe the electrodes? What techniques are used to minimize common signal, focus on significant frequencies for humans, and connect the electrodes to each other?

Answer 48

Multiple metal electrodes are applied to the human scalp with conductive paste in the "international 10-20" system 1. Letters = location on the brain [F, P, C, T] 2. Evens on the right, odds on the left Electrodes are paired to minimize common signal. Filters are used to focus on 0.5-40 Hz Montage connects electrodes in "anterior-posterior-bilateral"

Question 49

What are the 4 EEG frequency bands? What frequencies correlate with each?

Answer 49

1. Beta [>13] 2. alpha [8-13] 3. theta [4-7.5] 4. delta [ below 3.5]

Question 50

In maximal wakefulness, what waveform is usually seen in the posterior head regions? Anterior regions? During sleep, what waveform predominates? What area of the brain does it come from?

Answer 50

Wakefulness 1. posterior = alpha rhythm 2. anterior beta activity [little or NO theta or delta] Sleep: delta activity with brief 14 Hz [beta] bursts from "sleep spindles" in central region of the brain

Question 51

What are the 2 possible patterns seen on an abnormal interictal EEG?

Answer 51

1. generalized increase in slow frequency | 2. focal pattern of slowing [structural lesion]

Question 52

What is epileptiform discharge? What are the 2 types? What does it look like on EEG?

Answer 52

discharges seen on EEG during an interrictal state that have an >90% correlation with clinical epilepsy - focal = one hemisphere or part of hemisphere - generalized = both hemispheres simultaneously It is a spike and slow wave on EEG

Question 53

What are the 4 patterns of focal epileptiform discharges? What determines what you will see? What are the eleptiform discharges reflections of? What area of cortex must be epileptic to provide enough neuronal synchronization to show voltage recordable on the human scalp?

Answer 53

1. spike [less than 70ms] 2, sharps [between 70 and 200 ms] 3. spike and slow wave 4. polyspike and slow wave Differences in epileptic tissue size, geometry and other factors determine the pattern Eleptiform discharges are reflections of paroxysmal depolarization shifts and after hyperpolarizations 6cm-sq of cortex is the amount necessary to get enough neuronal stimulation to be recordable on the scalp

Question 54

What are the 2 patterns of generalized epileptiform discharges seen on EEG? In what leads will you see them?

Answer 54

1. spike and slow wave 2. polyspike and slow wave They occur in both hemispheres simultaneously and show predominance on the anterior hemispheres

Question 55

Because epileptic seizures are relatively rare events, it is difficult to get an ictal EEG outpatient. If a patient has difficult to treat epilepsy, they are admitted for continuous EEG monitoring. What 2 features on EEG allow you to recognize a seizure?

Answer 55

1. Rhythmicity - sharp waves or spike and slow wave 2. Evolution - steadily changing of seizure over time in terms of: - morphology - frequency - distribution

Question 56

What 2 situations would get a patient admitted to the Epilepsy Monitoring Unit? What occurs there?

Answer 56

1. prior tests were not diagnostic 2. patient does not respond to epilepsy drugs In EMU, the patient has their epilepsy medications held in order to capture one or more seizures and receives 24 hours of: - video - can help decide if it is non-epileptic AND based on behavior can help localize if it IS epileptic - EEG

Question 57

What neuroimaging is used in epilepsy?

Answer 57

1. MRI - reduces need for invasive intracranial electrodes [pro] - lesions sometimes don't correlate with site of seizure onset [con] 2. Ictal and interictal SPECT scans help localization because: - seizing cortex will have hyperperfusion - interictal SPECT shows hypoperfusion 3. FDG-PET shows hypometabolism where the seizure originates

Question 58

What are the 3 "experimental" neuroimaging techniques?

Answer 58

1. functional MRI - localization of the seizure onset - limited by unpredictability of seizures so often is restricted to correlating specific function w/ anatomic territory 2. magnetic resonance spectroscopy - evaluates focal epilepsy by measuring relative levels of N-acetyl aspartate and choline or creatine to assess regions of NEURONAL LOSS 3. magnetoencephalography - measures small electric fields generated by cortical electrical fields

Question 59

When is neuropsychologic testing performed for epilepsy? | Why is it given?

Answer 59

It is performed when a patient is a candidate for surgery. The cortex giving rise to seizures is likely to show a functional deficit. These tests can assess them. ex. right temporal --> language deficit ex. mesial temporal --> memory/visuospatial deficit

Question 60

What is the Wada test? | What are the 2 reasons it is used as a pre-op tool?

Answer 60

Wada test involves: 1. cerebral angiogram and injecting Na-amobarbital [rapid anesthetic] in one hemisphere at a time 2. while one hemisphere is anesthetized, assess the language and memory from the other hemisphere 3. patients will show worse memory performance when their "good" aka non-epileptic hemisphere is knocked out It is a good pre-op tool b/c 1. ensures that the non-operated hemisphere can sustain normal/near normal memory 2. identify hemisphere with language dominance

Question 61

What are the 5 types of treatment for epilepsy?

Answer 61

1. behavioral modification 2. medications 3. vagal nerve stimulation 4. resective/ disconnective surgery 5. ketogenic diet

Question 62

How does behavioral modification work for stress?

Answer 62

- emotional stress - anxiety - certain drugs - sleep deprivation Are all triggers for seizures Modifying these things can help prevent seizures

Question 63

What are the 3 principle mechanisms of action of anti-epileptic drugs?

Answer 63

1. increase inhibitory GABA neurotransmission 2. decrease excitatory glutamate neurotransmission 3. inhibit activity-dependent, voltage-activated Na channels * AEDs are specific for certain types of seizures

Question 64

Phenytoin and valproic acid both rely on what mechanism for AED? What types of seizures are they very effective on? What types of seizures do they have no effect on?

Answer 64

It inhibits Na channels ``` Phenytoin is Very effective for: 1. primary generalized tonic-clonic 2. secondarily generalized tonic-clonic 3. partial seizures ``` No effect on: 1. absence 2. myoclonic Valproic acid is very effective on all types

Question 65

What is the vagal nerve stimulator? | What is the proposed mechanism for why it works?

Answer 65

device delivers recurrent electrical pulses to the left vagal nerve. the mechanism is not clear, but it has been shown to reduce seizure freq. It may make a net inhibitory influence over diverse and widespread parts of the brain via the nucleus tractus solitarius

Question 66

What is the most successful and common epilepsy surgery?

Answer 66

Anteromesial temporal lobe resection for mesial temporal lobe epilepsy. Resect a few cm of anterior and lateral temporal neocortex with most/all of the hippocampus

Question 67

What surgical technique is used when seizures arise from cortex that provides critical function [language or motor functions] aka the eloquent cortex?

Answer 67

Multiple sub-pial transections technique - surgeon makes cuts in the cortex to sever intracortical connections without disturbing axonal projections carrying vital info - you are "disconnecting" the epileptogenic region

Question 68

What surgical technique would be used for "catastrophic" childhood epilepsy [Rasmussen's encephalitis]?

Answer 68

the entire hemisphere can be removed or surgically isolated

Question 69

What is the ketogenic diet? | What patient population is this treatment restricted to?

Answer 69

High fat diet with the elimination of carbs This diet is used by children with SEVERE forms of epilepsy