Module 14: CNS (Part 2)

Question 1

Define epilepsy:

Answer 1

Epilepsy is a neurological disorder that produces brief disturbances in the normal electrical activity in the brain

Question 2

What is epilepsy characterized by?

Answer 2

Epilepsy is characterized by sudden, brief seizures, the nature and intensity of which vary from person to person

Question 3

Define:

• Seizure
• Epileptic Seizure
• Non-epileptic seizure
• Epilepsy
• Status epilepticus

Answer 3

Seizure – A sudden alteration of behaviour that is caused by CNS dysfunction. Seizures are sudden and transient.

Epileptic Seizure – A seizure that is caused by primary CNS dysfunction. This is due to excess depolarization and hypersynchronization of neurons.

Non-Epileptic Seizure – A seizure-like episode that is not the result of abnormal electrical activity in the brain.

Epilepsy – A tendency for recurrent spontaneous epileptic seizures.

Status Epilepticus – A single unremitting epileptic seizure of duration longer than 30 minutes OR frequent seizures without recovery of awareness in between. Status epilepticus is an emergency.

Question 4

What are 3 types of epileptic seizures?

Answer 4

1) Focal/Partial Seizure
2) Generalized Seizure
3) Secondary Generalized Seizure

Question 5

What are focal/partial seizures?

Answer 5

They arise in one area of the brain

Question 6

Focal Partial Seizures: Simple Partial Seizures

• LOC?
• Symptoms?
• Example

Answer 6

• Involve no loss of consciousness.
• Symptoms depend on where the seizure activity is arising from.

Example Case:

• 45 year old man
• Clonic movements of his right arm
• Progression to right face then right leg
• No impairment of consciousness
• Lasting ~ 45 seconds
• MRI – L motor strip oligodendroglioma

Question 7

Focal Partial Seizures: Complex Partial Seizure

• LOC?
• Symptoms?
• Example

Answer 7

• A complex partial seizure involves loss of consciousness; Patients may appear to be awake, but are not aware of surroundings.
• Symptoms depend again on where the seizure activity is taking place.

Example Case:

• 37 year-old man with right temporal lobe epilepsy
• Whistling; bicycling movements in left leg.
• Rising epigastric sensation with nausea.
• Normal ictal speech.
• No memory of the events post-ictally (i.e. after seizure).
• Duration: 30 – 45 seconds.

Question 8

What is a generalized seizure?

- Types?

Answer 8

These seizures have a bilateral, diffuse onset, seeming to arise from all areas of the brain at once.

There are 5 different types of generalized seizures:

1. Absence seizures
2. Tonic/Clonic seizures
3. Myoclonic seizures
4. Tonic seizures
5. Atonic seizures

Question 9

Generalized Seizures: Absence Seizures

• Also called?
• LOC?
• Length?
• Common in?

Answer 9

• Also called “petit-mal” (an older name).
• Involve loss of consciousness, behavioural arrest and staring.
• Are usually brief but may occur in clusters and can recur multiple times in a day.
• Rarely associated with automatisms (unusual purposeless movements), usually minor if there are any.
• More common in childhood.

Question 10

Generalized Seizures: Tonic/Clonic

• Involves (3)
• Symptoms
• Used to be called?

Answer 10

Tonic clonic seizures involve:

• An abrupt loss of consciousness
• A tonic period (muscles become rigid), lasting ~ 1 minute
• A clonic period (involuntary muscle contractions), lasting and additional 2-3 minutes

Patients may become incontinent and have tongue biting.
- In the post-ictal phase patients may be drowsy, confused and frequently complain of headaches.

Used to be called “Grand-mal seizure”

Question 11

Generalized Seizures: Myoclonic Seizures

• Symptoms?
• LOC?
• Associated with?

Answer 11

• These seizures involve sudden, brief muscle contractions that can involve any muscle group.
• Usually there is no loss of consciousness.
• Sometimes they are associated with a later development of generalized tonic-clonic seizures.

Question 12

Generalized Seizures: Tonic seizures

- Involve (2)

Answer 12

• Often involve sudden muscle stiffening (rigidity).

- Often involve impaired consciousness.

Question 13

Generalized Seizures: Atonic Seizures

• Involve?
• Length?
• Known as?
• Potential for?

Answer 13

• Involve sudden loss of muscle tone
• Usually brief, around 15 seconds.
• Also known as “drop seizures”, as patients typically drop to the ground.
• Potential for falling injuries.

Question 14

What is a secondary generalized seizure?

Answer 14

• A seizure that begins in one area of the brain (like a focal seizure) and then spreads throughout the brain.
• The preliminary focal phase is sometimes referred to as an “aura”.

Question 15

How do you localize a focal seizure?

Answer 15

The location of a focal seizure can be determined by evaluating the patient’s symptoms and what we know about the various regions of the brain.

Question 16

Secondary Seizure:

- Frontal Lobe

Answer 16

• Simple repetitive motor movements involving a localized muscle group are associated with seizure activity in the contralateral (opposite side of the brain) primary motor cortex.
• Tonic posturing affecting the entire side of the body are associated with seizure activity in the contralateral Supplemental Motor Area (SMA) and other higher level motor structures.
• Very complex behavioural automatisms that involve bilateral movement such as swimming or bicycle riding movements are associated with seizure activity in higher areas of the frontal cortex. These behaviours often involve vocalizations, laughter and/or crying.

Question 17

Secondary Seizure:

- Temporal Lobe

Answer 17

• Emotions such as anger, fear, euphoria and psychic symptoms such as déjà vu, jamais vu or amnesia are associated with seizure activity in the temporal lobe.
• Auditory (hearing) hallucinations of buzzing or voices talking, and olfactory (smell) and gustatory (taste) hallucinations are associated with the temporal lobe.
• More complex sensory phenomena, involving visual distortions, paresthesias (i.e. numbness) and autonomic disturbances can also be associated with temporal lobe seizures.

Question 18

Secondary Seizures:

- Parietal Lobe

Answer 18

• Localized paresthesias, such as numbness and “pins and needles”, are associated with seizure activity in the contralateral somatosensory cortex.
• More complex and widespread paresthesias are associated with seizure activity in the somatosensory association cortex.
• Seizure activity in the higher order sensory association areas in the parietal lobe can be associated with complex multi-sensory hallucinations and illusions. Can be hard to distinguish from temporal lobe seizure activity, which is more common.

Question 19

Secondary Seizures:

- Occipital Lobe

Answer 19

• Visual hallucinations, such as flashing or a repeated pattern in the environment, are associated with seizure activity in the occipital lobe. The hallucinations are less likely to be of organized objects such as people or faces.
• Seizure activity in the occipital lobe can also produce temporary blindness or decreased vision, as well as the sensation of eye movement. Patients may have reflex nystagmus (involuntary eye movement).
• Simple partial seizures in the occipital lobe can be mistaken for migraine headaches, as many of the symptoms are similar to common migraine auras.

Question 20

What is the etiology of epilepsy (3)?

Answer 20

1. Symptomatic epilepsy - Epilepsy arising from an identified physical cause, such as a brain tumor, stroke, infection, or other injury.
2. Idiopathic Epilepsy - Epilepsy that does not have an identifiable cause; there is often a family history of seizures, and genetics likely play a role.
3. Cryptogenic epilepsy - Epilepsy that is likely to have an underlying cause that has not been identified.

Question 21

What is the seizure threshold?

- Factors

Answer 21

The seizure threshold can be thought of as the balance between excitable and inhibitory forces in the brain.

• Everybody has a seizure threshold and the seizure threshold affects how susceptible a patient is to having a seizure.
• Keep in mind that seizures are mediated by changes in electrical activity, so the ability to reach threshold and fire an action potential is important in the generation of a seizure.

Some factors that may affect the seizure threshold are: stroke, head injury, drug/alcohol withdrawal, infection, tumour, severe fever, visual stimuli (flashing lights).

Question 22

What are the 4 types of mechanisms involved in anti-epileptic drugs?

Answer 22

1. Blocking sodium channels.
2. Blocking voltage-dependent calcium channels.
3. Glutamate antagonists
4. Potentiating the actions of GABA.

Question 23

Define depression:

Answer 23

• Occasional feelings of depression are normal, as are grief and sadness following any form of loss.
• When these symptoms are prolonged and interfere with everyday life, depression may be diagnosed.

Question 24

Diagnosis of depression:

Answer 24

For a diagnosis of depression, at least five of the following symptoms must occur for at least two weeks:

• Depressed mood most of the day, nearly everyday.
• Loss of interest or pleasure in all or almost all activities.
• Significant weight loss (without dieting) or weight gain.
• Insomnia or hypersomnia.
• Psychomotor agitation or retardation.
• Fatigue and energy loss.
• Feelings of worthlessness or excessive guilt.
• Decreased ability to think, concentrate, or excessive indecisiveness.
• Recurrent thoughts of death or suicidal ideations.

Question 25

Types of depression (2)?

Answer 25

Depression can be classified into two major types: exogenous or endogenous.
- Exogenous depression is triggered by external stimuli, whereas endogenous depression may or may not be related to external events.

Question 26

How is exogenous depression classified (2)?

Answer 26

Pathological grief – Prolonged grieving coupled with excessive guilt. Psychotherapy is usually more effective in terms of treatment than drugs.

Adjustment disorder– Prolonged depression following failure or rejection (i.e. losing your job, failing out of school). Common symptoms include hypersomnia (excess sleep) and hyperphagia (overeating). Psychotherapy is often more effective than drug therapy.

Question 27

How is endogenous depression classified (7)?

Answer 27

Major depression – Common symptoms include loss of interest and lack of response to positive stimuli. Symptoms are usually worse in the morning. Insomnia and weight loss are also typical.

Severe depression – Similar symptoms to major depression with the addition of severe suicidal ideation and psychoses.

Atypical depression - Similar symptoms to major depression but patients have the atypical symptoms of hypersomnia and hyperphagia. Often patients with atypical depression are obese.

Dysthymia - The patient’s mood is regularly low but symptoms are not as severe as major depression. Symptoms are usually more noticeable to family members/close friends than they are to the patient. Usually responds better to psychotherapy than to drugs.

Seasonal Affective Disorder (SAD) - Mild or moderate symptoms of depression related to the lack of sunlight. Usually only affects people in the winter months.

Postpartum Depression – Moderate to severe depression in women after they give birth. Usually occurs within 3 months of delivery but may occur up to a year after birth.

Bipolar Disorder – Alternating periods of elevated or irritable mood and periods of depression.

Question 28

What is the monoamine hypothesis?

• Cause
• Hypothesis
• Example

Answer 28

The exact cause and pathophysiology of depression are unknown.

The major hypothesis with regard to the biochemical basis for depression is the monoamine hypothesis.
- This hypothesis suggests that altered monoamine release, receptor sensitivity, or post-synaptic function lead to symptoms of depression.

An example in support of this hypothesis:
- Jim, a twenty year old university student goes to a rave Saturday night and takes ecstasy, a drug that depletes the neurotransmitter serotonin (5-HT). Jim has a great time at the rave. The next week Jim lacks motivation to study for his classes, doesn’t leave his couch, and thinks his life is going nowhere.

Question 29

How do anti-depressants act?

• How do we measure efficacy?
• Results?

Answer 29

Antidepressant drugs act to increase the synaptic levels of one or more monoamine neurotransmitters.

The efficacy of antidepressants is difficult to assess since it often takes months for effects to occur.

Results from placebo-controlled clinical trials also suggest that as much as 40% of the effects observed may be attributed to the placebo effect.

Question 30

Antidepressant drugs mediate their effects by one of two major mechanisms:

Answer 30

1. Inhibiting monoamine reuptake.

2. Inhibiting monoamine metabolism.

Question 31

There are four major classes of drugs used to treat depression:

Answer 31

1. Tricyclic Antidepressants
2. Selective Serotonin Reuptake Inhibitors (SSRIs)
3. Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
4. Monoamine Oxidase Inhibitors (MAOIs)

Question 32

What is bipolar disorder?

- Symptoms?

Answer 32

• Is a severe illness characterized by recurrent fluctuations between episodes of mania and depression.
• Symptoms usually begin in adolescence or early adulthood.

Question 33

The manic phase consists of symptoms such as:

Answer 33

o Irritation
o Inflated self-esteem (delusions of grandeur)
o Little need for sleep
o Poor control of temper
o Reckless behaviour (binge eating, drinking, drug use)
o Easily distracted

The symptoms experienced during the depressive phase are similar to the ones described in the depression section of this module.

Question 34

Describe the pattern of mood episodes:

- Duration

Answer 34

Not all patients cycle repeatedly between episodes of mania and depression.
- Some patients may experience repeated mania with occasional depression and others may experience repeated depression with occasional mania.

The duration of each episode can also vary substantially from a day to over a year.
- On average, patients with bipolar disorder experience approximately 2 episodes every 5 years.

Question 35

How is bipolar disorder treated?

Answer 35

Bipolar disorder is treated with three major groups of drugs:

1. Mood Stabilizers
2. Antipsychotics
3. Antidepressants

Question 36

Define anxiety:

Answer 36

Anxiety is a normal physiological response to stress.
- It is normal for people to be nervous before an exam or to have “butterflies” in their stomach before a first date.

In contrast, an anxiety disorder exists when the symptoms of anxiety create a functional impairment in a patient’s daily living.
- Anxiety and depression are closely linked so patients that have an anxiety disorder are likely to also suffer from depression.

Question 37

Anxiety disorders fall in 7 general categories:

Answer 37

1. General anxiety disorder – Patient is overwhelmed with uncontrollable worrying. The hallmark is an unrealistic or excessive worry about several activities that lasts 6 months or longer.
2. Panic Disorder – Patients have a sense of impending doom that is unrelated to stressors. They experience panic attacks, which are sudden in onset and may include symptoms like heart palpitations, chest pain, shortness of breath, dizziness. They are often confused for a heart attack.
3. Agoraphobia – An anxiety where the patient feels judged or a situational anxiety where escaping would be difficult or embarrassing.
4. Obsessive-compulsive disorder – Persistent obsession and compulsions that interfere with daily life (i.e. handwashing, checking locks).
5. Social anxiety disorder – Anxiety in social situations. Patients may not be able to talk (or stop talking), eat in front of others, or use public washrooms.
6. Post-traumatic stress disorder – Anxiety that occurs after experiencing a traumatic event. Symptoms may include re-experiencing the event and severe insomnia.
7. Simple Phobia – Symptoms are related to a specific fear (i.e. spiders, elevators).

Question 38

• The major classes of drugs used to treat anxiety include:

Answer 38

1. Benzodiazepines (BDZs)
2. Buspirone
3. Antidepressants

Question 39

• Antidepressant drugs are also useful in the treatment of certain types of anxiety as indicated below:

Answer 39

Generalized anxiety disorder – SSRIs and SNRIs are effective, but like buspirone are slow to generate their effect.

Panic Disorder/Agoraphobia – SSRIs, TCAs and MAO inhibitors are useful but effects take 6-12 weeks to appear. SSRIs are preferred because they are better tolerated than TCAs and MAO inhibitors.

Obsessive Compulsive Disorder (OCD) – SSRIs are the first line therapy. Patients with OCD also require behavioural therapy, which is a very important component of treatment.

Social Anxiety Disorder – SSRIs are the first line therapy although BDZ’s may also be used. BDZ’s provide immediate relief from symptoms whereas SSRIs require time for the effect to occur.

Post-Traumatic Stress Disorder – There is no good evidence that antidepressants or other drugs are effective in treating PTSD.