Download LESSON 4.6 WORKBOOK What causes epilepsy?

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LESSON 4.6 WORKBOOK
What causes epilepsy?
DEFINITIONS OF TERMS
Generalized seizures –
seizures that involve the entire
brain.
Partial seizures – seizures that
do not involve the entire brain.
Positive symptom – symptom
in which one acquires an
abnormal behavior.
Negative symptom – symptom
in which one loses a normal
behavior.
For a complete list of defined
terms, see the Glossary.
So far in this unit we’ve seen how the activity of circuits
regulate behaviors, as well as how the activity of circuits can
be regulated by feedback inhibition and feed-forward inhibition. In this lesson, we’ll turn our attention to a disorder in
which the control of circuit activity is abnormal – epilepsy.
When neuronal activity is unregulated
All complex behaviors rely on precisely ordered communication between neurons in circuits. What happens to the circuit when the ordered communication between neurons breaks down? The result is called
a seizure – one of the most dramatic examples of disordered electrical behavior in the mammalian brain.
Epilepsy is the chronic neurological condition that results from unprovoked seizures. It affects approximately 50 in every 1000 people in developed countries. In the US, about 3% of all people living to the age
of 80 will be diagnosed with epilepsy. Three to four times that number will have epilepsy in developing
countries – why the discrepancy? No one knows.
How seizures are classified
Not all seizures are the same, and they must be sorted out according to their clinical features before any
treatment program can begin. Seizures can include both ‘positive’ and ‘negative’ motor or sensory symptoms. A positive symptom involves acquiring an abnormal behavior – like jerking an arm for instance.
A negative symptom involves losing a normal behavior – like briefly losing sight for instance. What
symptoms appear depends on the effected region of the brain and the extent to which the normal brain
tissue is involved.
Seizures can be classified clinically into two categories: partial seizures and generalized seizures. This
simple classification is very useful because the effectiveness of the treatment depends on the category of
seizure being treated.
Wo r k b o o k
Lesson 4.6
What is a seizure? What is epilepsy?
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What are the two main types of symptoms
associated with seizures? And what determines what types of symptoms will appear
with a seizure?
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What are the two main types of seizures?
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LESSON READING
Partial Seizures
DEFINITIONS OF TERMS
Complex partial seizures –
partial seizure in which patient
loses consciousness.
Seizure focus – specific area of
the brain where partial seizures
begin.
Simple partial seizures –
partial seizure without the loss of
consciousness
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 4.6
Partial seizures originate in a small group of
neurons that are called
the seizure focus. The
seizure focus can be
any small group of excitatory neurons that are
damaged in some way –
for example because of
a blood clot, a tumor, or
a scar. The symptoms of
a partial seizure depend
on where the seizure
focus is located (Figure
30).
Somatosensory What is the seizure focus?
Motor in limbs Visual Motor in face and head Auditory Figure 30: The symptoms of seizure depend on where the seizure focus
is located. Symptoms may include visual, auditory, somatosensory and
motor abnormalities depending on where the abnormal electrical activity
is located.
If the activity in the focus is intense, the inhibitory neurons surrounding the area can’t keep up with the
excitation. The excitatory electrical activity then begins to spread to other brain regions (Figure 31). This
spread follows the normal connections in the affected circuit. The cortex is heavily interconnected. Therefore seizure foci in the cortex are more likely to spread within that hemisphere of the cortex, then to the
other hemisphere, and finally to the thalamus, which can redirect the seizure throughout the entire brain.
Partial seizures are further classified into two categories: simple and complex. Simple partial seizures
often cause changes in consciousness,
but do not cause loss of consciousness.
A. B. Simple partial seizures involve localized
symptoms, such as jerking of the arm. The
simple partial seizure becomes a complex
partial seizure if it progresses so that the
patient loses consciousness.
People who experience partial seizures
often describe symptoms that precede the
actual seizure called auras. Common auras include a sense of fear, a rising feeling
in the abdomen, or a specific odor.
Figure 31: Secondary spread of the seizure. (A)
Seizure activity may spread within the same lobe of the
cortex, to the opposite lobe via the corpus callosum or
throughout the entire brain via the thalamus. (B) Once
the thalamus is involved, the seizure is likely to spread
widely throughout the brain. This is known as secondary
spread.
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What causes the abnormal activity in a seizure focus to spread?
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What is the difference between simple and
complex partial seizures?
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LESSON READING
What is a generalized seizure? How is it different from a partial seizure?
Generalized seizures
In contrast to partial seizures that originate in the cortex, generalized seizures involve connections to the
cortex from subcortical structures like the thalamus, and connections from the cortex to subcortical structures like the thalamus (Figure 32). Generalized seizures begin without an aura or a seizure focus and involve both hemispheres of the brain from the onset. They can be divided into non-convulsive or convulsive.
DEFINITIONS OF TERMS
Absence seizure – seizure
in which patients have a
transient loss or impairment of
consciousness.
Convulsive seizure – seizure
involving uncontrollable jerking
of the body.
Grand mal seizure – (also
known as tonic-clonic seizure)
type of generalize seizure that
affects the entire brain.
The best understood non-convulsive generalized seizure is the absence seizure (formerly called petit
mal). These seizures begin abruptly, usually last less than 10 seconds and are characterized by repeated
loss of attention or consciousness without any physical symptoms. Absence seizures can happen many
times a day and are most common in children. In this case the issue is not a defective area in the brain
but a sudden generalized cortical hyper-excitability. This hyper-excitability then synchronizes with the excitatory input from the thalamus to the cortex, which causes a massive depolarization. In response, the
inhibitory neurons in the thalamus try to control the output. The resulting prolonged hyperpolarization
causes the neurons to take a long time to repolarize, but once they do, the synchronized depolarization
can happen again. Interestingly, the EEG in absence seizures is very similar to the EEG in the deep stages
of sleep known as ‘sleep spindles’.
The most common convulsive generalized seizure is the tonic-clonic or grand mal seizure. These seizures also begin abruptly, often with a grunt or a cry as the thorax and diaphragm contract suddenly. The
patient may fall to the ground with a clenched jaw, lose bladder or bowel control, and become blue in the
face (cyanotic). This tonic phase typically lasts 30 seconds before evolving into jerking of the extremities
lasting 1 - 2 min. This active phase is followed by an ictal phase during which the patient is sleepy and may
complain of headache and muscle soreness.
What is an absence seizure?
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What is a grand mal seizure?
Non-convulsive seizure –
seizure without jerking.
Thalamus For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 4.6
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Figure 32: Generalized seizures involve connections
both to and from the cortex via the thalamus and
other subcortical structures. Since the thalamus is
involved, the seizure activity immediately spreads to
the entire brain.
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LESSON READING
You can imagine that it is often difficult to distinguish a generalized seizure from a complex partial seizure
with a brief aura. The distinction isn’t academic – it’s vital to choosing the proper treatment as well as
pinpointing the underlying cause.
Electrical activity and seizures
As you can imagine, the most accurate way
to pinpoint the region that initiates a seizure
would be to impale the brain with electrodes and then measure where activity is
defective. This is obviously not feasible in
human patients. So, the EEG is called into
service. The EEG provides a non-invasive
way of examining brain activity.
EEG recordings made during partial seizures show abnormal neuronal firing beginning first in a single region. This abnormal
activity then may spread to other regions,
but initially only one region is affected (Figure 33).
How do doctors diagnose the origin of a seizure?
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What would an EEG trace look like during a
partial seizure?
Figure 33: EEG of partial seizure. Seizure activity shows
up initially on only some the EEG leads, indicating that
initially only one area is involved, but may recruit others if
the seizure spreads.
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What would an EEG trace look like during a
generalized seizure?
Conversely, EEG recordings made during generalized seizures show abnormal
neuronal firing beginning simultaneous
throughout many, if not all, brain regions
(Figure 33).
Wo r k b o o k
Lesson 4.6
Figure 33: EEG of generalized seizure. Seizure activity
shows up simultaneously on all the leads of the EGG,
indicating that the entire cortex is involved.
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LESSON READING
Treatments
Seizure disorders are treated with anticonvulsant drugs, many of which work
by increasing the effectiveness of inhibitory synapses. Most patients respond well
enough to drugs that they can lead a normal life. In a few instances, drugs provide
little or no help. Sometimes, seizure foci
remain so irritable that despite drug treatment, brain surgery is required (Figure
34). In these cases, the surgeon removes
the seizure foci and some of the region of
the brain surrounding the focus. Most patients recover well from surgery, with their
seizures eliminated or greatly reduced in
frequency.
Wo r k b o o k
Lesson 4.6
Figure 34: Most patients with epilepsy respond well to
anticonvulsant medications which increase the effectiveness of inhibitory synapses. In some cases surgery
is required to remove a seizure focus. Surgery often
means removing a considerable amount of brain tissue,
but it can be extremely effective.
Figure 35: Vagus nerve stimulation (VNS). VNS
is a treatment option for patients who do not
respond well to medications and are not considered good candidates for surgery. VNS involves
the implantation of a pacemaker like device that
provides electrical stimulation to the brain via the
vagus nerve.
For those patients who do not respond to anticonvulsant medications, and who are not
considered good candidates for surgery (because their seizures are produced throughout
the brain), vagus nerve stimulation (VNS) is
another treatment option (Figure 35). VNS involves the implantation of a pacemaker device
that generates pulses of electricity to stimulate
the vagus nerve. While it is not exactly known
how VNS works, it is thought that by stimulating
the vagus nerve, electrical energy is discharged
upward into a wide area of the brain, disrupting the abnormal activity that causes seizures.
Another theory suggests that stimulating the
vagus nerve causes the release of inhibitory
neurotransmitters that decrease seizure activity.
What treatments are available for epilepsy?
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STUDENT RESPONSES
If a friend of yours was diagnosed with epilepsy, what questions would you ask to find out whether it caused partial or general
seizures?
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Remember to identify your
sources
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How would you tell the difference between a partial seizure that has spread or a generalized seizure?
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