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B3 CTB > Epilepsy: Physiology and Pharmacology > Flashcards

Epilepsy: Physiology and Pharmacology Flashcards

1
Q

What is epilepsy?

A

A common neurological disorder characterised by recurrent seizures. They occur as a result of abnormally large, synchronous neuronal activity.

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2
Q

What are seizures?

A

Aberrant electrical activity within the brain, an ‘electrical storm’.

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3
Q

What is the main excitatory neurotransmitter in the brain? What is the receptor?

A

Glutamate, NMDA receptor.

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4
Q

What is the main inhibitory neurotransmitter in the brain? What is the receptor?

A

GABA, GABA receptors.

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5
Q

1 in how many people have epilepsy in the UK?

A

103

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6
Q

What are most diagnoses of epilepsy based on?

A

Signs and symptoms of the episodes described by friends and family.

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7
Q

Which synapses play a pivotal role in the generation of seizure activity?

A

Electrical synapses formed by gap junctions.

Help to coordinate activity across the network.

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8
Q

What are the two principal groups of seizure types?

A
  1. Focal - seizure in a specific region.
    - Simple - remains conscious.
    - Complex - impaired consciousness.
  2. Generalised - seizure activity is global, affecting one or both hemispheres.
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9
Q

What are focal aware seizures characterised by?

A
  • No loss of consciousness.
  • No post-ictal confusion.
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10
Q

What does ictal mean?

A

Period of seizure activity.

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11
Q

Symptoms of focal aware seizures depend on the ?.

A

focal site

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12
Q

Outline the characteristic symptoms experienced during temporal focal seizures.

A
  • Auras – smell/ taste. ‘déjà vu’, ‘jamais vu’, emotional changes.
  • Oral automatisms – gestures e.g. dystonic or fidgeting.
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13
Q

Outline the characteristic symptoms experienced during frontal focal seizures.

A
  • Motor seizures – brief, frequent, cluster.
  • Often bilateral e.g. kicking, cycling, violent, bizarre.
  • Commonly on waking form sleep.
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14
Q

Outline the characteristic symptoms of a parietal focal aware seizure.

A
  • Sensory seizures – somatosensory (tingling/ warmth).
  • Auras – nausea, choking, sinking sensations, illusions of body distortion.
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15
Q

Outline the characteristic symptoms of a occipital focal aware seizure.

A
  • Visual hallucinations – simple or complex.
  • Vision may black out.
  • Visuo-spatial distortions.
  • Head turning, headache, nausea.
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16
Q

What might you see on an EEG during a focal aware seizure?

A

Increase in activity in waveform from the focal area.

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17
Q

How are ‘focal with impaired awareness’ seizures characterised?

A

Altered consciousness during the episode, but the patient may seem fully aware.

Following the seizure there may be some post-ictal confusion.

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18
Q

Prior to the onset of focal seizures with impaired awareness, patients may experience ?, which can be used as warning signs.

A

auras

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19
Q

What is a common symptom of focal seizures with impaired awareness?

A

Automatisms (chewing, swallowing, repeated displacement behaviour) are often exhibited during altered consciousness state, but these depend on the focal region.

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20
Q

What are focal to bilateral tonic-clonic seizures?

A

Focal to generalised seizures - start in one place but then progress and rapidly spread to the whole brain (or hemisphere) via the large fasciculi or the thalamus.

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21
Q

Can patients experience auras in focal to bilateral tonic-clonic seizures?

A

Yes, because it starts as a focal seizure.

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22
Q

What are generalised bilateral tonic-clonic seizures?

A

Easiest seizure type to diagnose.

Whole brain is normally involved (but can be in one hemisphere).

Symptoms include tonic phase and clonic phase.

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23
Q

What are tonic and clonic phases?

A

Tonic - whole body stiffens, breathing may stop (cyanosis), loss of bladder control.

Clonic - muscle jerks.

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24
Q

What are the characteristic symptoms of generalised bilateral tonic clonic seizures?

A

Seizure activity is followed by unconsciousness, muscle relaxation, slow regain of consciousness, confusion, sleepy, headaches and aching limbs.

Patient has no recollection.

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25
Q

What are generalised non-motor typical seizures (absence)?

A

Whole brain is involved but has low level of activity compared to classic generalised tonic-clonic seizure.

Rare in adults, generally starts between 6 - 12.

Looks like day dreaming.

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26
Q

What is the characteristic symptom of a generalised non-motor typical seizure?

A

Patient seems to switch off briefly but cannot be alerted or woken during this period.

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27
Q

What are Jacksonian seizures?

A

Seizures that travel across the cortex.

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28
Q

What are the two main forms of jacksonian seizure?

A
  • Focal aware motor (Jacksonian).

Short lasting, ripple of muscle activity, may be localised to one group of muscles or progress, usually distal to proximal, through the limbs and trunk (following HAL).

  • Focal aware sensory (Jacksonian).

Short lasting sensory changes, may be localised to one area or progress, usually distal to proximal, through the limbs and trunk (following HAL).

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29
Q

Is static epilepticus a medical emergency?

A

Yes.

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30
Q

What is static epilepticus?

A

Prolonged seizure state which ca over-activate the neurons leading to cell death.

Usually tonic clonic type of seizure.

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31
Q

How is status epilepticus diagnosed in generalised tonic-clonic seizures?

A
  • Ictal period > 5 minutes.
  • Releated seizures with no recovery between (> 30 minutes).
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32
Q

Forms of status epilepticus such as ? or ? are lower levels of activity and so speed of treatment is not so necessary. Generally treated with standard antiepileptics.

A

long-lasting absence, focal-type seizures

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33
Q

How do generalised myoclonic seizures present?

A

Patient experiences sudden jerks.

Possible familial component to these.

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34
Q

How do generalised clonic seizures present?

A

Patient experiences repeated twitches but no stiffness.

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35
Q

How do generalised tonic seizures present?

A

Whole body stiffness and all muscles contract, usually bilaterally.

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36
Q

What are generalised atonic seizures?

A

Drop attacks’ - muscle tone is lost and patient collapses to the floor.

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37
Q

What mutations are linked to congenital forms of seizures?

A

Mutations in channel structure (voltage gated Na+ channels, K+ channels, ACh and GABA receptors).

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38
Q

What is non-epileptiform attack disorder (NEAD)?

A

Episodes that resemble seizure activity, but there is no physical reason or changes in brain activity associated with the behaviour.

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39
Q

What is the only way to diagnose NEAD?

A

Using EEG, treated with psychological councelling and not through medication.

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40
Q

Do generalised seizures have warning signs?

A

No, involve rapid transmission of seizure activity throughout the brain and via the large fibre tracts and thalamus.

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41
Q

What is Todd’s paralysis/ paresis?

A

Post-ictal paralysis, usually limited to one side of the body.

On average lasts for 15 hours.

42
Q

A patient attends the GP to discuss the episodes he has been experiencing recently. He describes the episode as starting as a feeling of ballooning in his finger after which he can’t remember a thing. His partner, who accompanied him to the appointment, described what happened during this blank period: the patient seemed to go completely limp and fell to the floor. This lasted for about thirty seconds after which the patient began to ‘come to’ and started to recover. He was confused for a short while after the episode, but seemed ‘right as rain’ within about half an hour.

What class of seizure is this?

A

Focal aware sensory bilateral atonic (called focal to bilateral atonic in clinic).

43
Q

A patient describes episodes where the experience a tingling that runs up their left arm. It happens most mornings but has no impact on the patient.

What type of seizure is this?

A

Focal aware non-motor (Jacksonian).

44
Q

Seizure location: As a general rule, any sort of visual hallucinations are ?, motor are ?, sensory are ? and memory/emotion are ?.

A

occipital, frontal, parietal, limbic/temporal

45
Q

Most bilateral seizures originate in, or close to, the ?.

A

thalamus

46
Q

? recording is very useful for determining type of epilepsy as seizure or epileptiform activity shows distinct patterns according to which type of seizure is being experienced.

A

EEG

47
Q

Activity of neurons in the cerebral cortex is synchronised to some extend, firing regular rhythms. What are these called?

A

Brain waves/ rhythms and are measured in cycles per second (Hz).

48
Q

Explain the principals underlying EEGs (electroencephalograms).

A

Electrodes placed in pairs on the scalp can pick up variations in electrical potential that derive from this underlying cortical activity.

49
Q

What affects EEG signals?

A

The state of arousal of the cerebral cortex.

Show characteristic changes in different stages of sleep.

In general, the more active the brain, the higher the frequency and lower the amplitude of the EEG (and vice versa).

50
Q

What is electroencephalography used for?

A

Diagnosing epilepsy, sleep disorders and in the diagnosis of brain death.

51
Q

How do EEGs originate?

A

From slow changes in the membrane potentials of cortical neurons, especially the excitatory and inhibitory post-synaptic potentials (EPSPs and IPSPs).

Very little contribution normally comes from action potentials propagated along nerve axons.

52
Q

As with the ECG, the EEG reflects the ? of the electrical potential changes occurring from large populations of cells.

A

algebraic sum

53
Q

On EEGs, the rhythmic events that waves reflect often arise in the ?, whose activity is in turn affected by a variety of inputs, including structures in the brainstem reticular formation.

A

thalamus

54
Q

What are the five different types of brain waves recorded on EEGs. What are their frequencies?

A

Delta: 0.5 to 4 Hz, up to 100 - 200 microvolts peak to peak.

Theta: 4 - 7 Hz, <30 microvolts peak to peak.

Alpha: 8 - 13 Hz, average amlitude of 30 - 50 microvolts peak to peak.

Beta: 14 - 30 Hz, <20 microvolts peak to peak.

Gamma: 30 - 50 Hz.

55
Q

Is it possible to relate EEG waves to specific underlying neuronal activity?

A

No

56
Q

What is the dominant EEG rhythm in sleep stages three and four (not seen in consious adults)?

A

Delta

57
Q

Which freqency of waves on an EEG are seen in awake children but not adults?

A

Theta.

Rhythm is normal during sleep at all ages.

58
Q

Which frequency of waves on an EEG is seen when the eyes are closed and the patient is relaxed?

A

Alpha.

Abolished by eye opening and by mental effort.

The greater the cortical activation, the lower the alpha activity.

59
Q

Which frequency of waves are prominent in alert individuals with their eyes open?

A

Beta.

60
Q

Which freuqency of waves is thought to be associated with higher mental activity, including perception and consciousness?

A

Gamma.

Disappears under general anaesthesia.

61
Q

How do you tell the difference between generalised absence and generalised tonic clonic on an EEG?

A

Activity mimics the behaviours observed.

Absence – the pattern of activity is abnormal, but low level and occur across the cortex.

Tonic clonic – oscillations of activity are huge and occur across the cortex in large swathes of activity.

Focal seizures – localised waveforms, limited in extent across the cortex.

62
Q

What are the three main groups of drugs used to treat epilepsy?

A
  • Sodium channel blocker.
  • Calcium channel blocker.
  • GABA modulator.
63
Q

Excess ? or lack of ? can cause neurons to become hyper-excitable and a seizure may result.

A

glutamate, GABA

64
Q

What is the first line treatment for focal and focal to generalised seizures?

A

Sodium channel blocker:

  • Carbamazepine.
  • Lamotrigine.
  • Sodium valproate.
65
Q

If first line drugs are unstable when treating focal and focal to generalised seizures, what drugs are used?

A
  • Oxcarbazepine.
  • Sodium valproate.
  • Levetiracetam.
66
Q

What second line drugs are used to treat focal and focal to generalised seizures?

A
  • Gabapentin.
  • Topiramate.
67
Q

What are the first line drugs for generalised tonic clonic seizures?

A
  • Sodium valproate.
  • Lamotrigine.
68
Q

If first line drugs are ineffective when treating generalised tonic clonic seizures, what drugs are used?

A
  • Carbamazepine.
  • Oxcarbazepine.
69
Q

What second line drugs are used to treat generalised tonic clonic seizures?

A
  • Clobazam.
  • Levetiracetam.
  • Topiramate.
70
Q

What first line drugs are used to treat generalised non-motor typical seizures (absence)?

A
  • Ethosuximide.
  • Sodium Valproate.
71
Q

What second line drugs are used to treat generalised non-motor typical seizures (absence)?

A
  • Lamotrigine.
72
Q

How do you treat status epilepticus? (emergency)

A

Aiming to dampen down the epileptiform activity quickly.

GABA PAMs (positive allosteric modulators, which enhance GABA activity) are key.

Use a benzodiazepine:

  • IV Lorazepam (repeated after 10 minutes) or
  • Buccal Midazolam/ rectal diazepam (if resuscitation facilities are not available).

If this hasn’t worked, after 25 minutes give phenytoin sodium or phenobarbital sodium (phenobarbitone, a barbiturate).

After 45 minutes of seizure activity, anaesthetize the patient.

73
Q

What do you do if you encounter an overdose of benzodiazepine?

A

Can be reversed using flumazenil.

74
Q

Sodium valproate is first choice for a number of other generalised seizures including: ?, ? and ? seizures.

A

myoclonic, atonic, tonic

75
Q

Which drug is’t used in pre-menopausal women of child bearing age due to teratogenicity?

A

Sodium valproate.

76
Q

Name a drug that can exacerbate myoclonic seizures.

A

Lamotrigine, carbamazepine and oxcarbazepine.

77
Q

Generalised absence atypical, generalised atonic and generalised tonic seizures generally respond poorly to typical AEDs, but you can try:

A
  • Sodium valproate (first line).
  • Lamotrigine (second line)
78
Q

What are epilepsy syndromes? Whay drug is used to treat them?

A

Specific types of epilepsy (often congenital) that are characterised according to a number of features including seizure type, age of onset and EEG characteristics.

Lamotrigine.

79
Q

As NEAD is a non-epileptic disorder, the key thing is to ?.

A

try and remove any antiepileptics in use

80
Q

What are the main treatment approaches for NEAD?

A
  • Antidepressants/ antipsychotics.
  • Psychotherapy/ CTB.
81
Q

? and ? can occur with all anti-epileptic drugs (side effects).

A

Sedation, dizziness

82
Q

What is antiepileptic hypersensitivity syndrome?

A

One of the most serious side effects of the antiepileptic drugs.

Normally starts 1 - 8 weeks from treatment initiation.

83
Q

What are the initial and severe signs of antiepileptic hypersensitivity syndrome?

A

Initial signs: fever, rash, swollen lymph nodes.

Severe signs: blood, liver, kidney and respiratory abnormalities, vasculitis and organ failure.

84
Q

What is the immediate management for antiepileptic hypersensitivity syndrome?

A
  • Withdrawing drug immediately (beware of rebound seizure activity).
  • Providing topical steroids and antihistamines for rash.
  • Systemic corticosteroids may help.
85
Q

Some of the commonly used antiepileptics are teratogenic. What does this mean?

A

Can induce developmental defects in embryos and foetuses.

Sodium valproate is the worst.

86
Q

GABA mimetics were designed to mimic GABA and include ? and ?, whose actual mechanisms are unclear.

Gabapentin can also act on ? and doesn’t seem to act at the GABA receptor significantly.

A

Gabapentin, Pregabalin, calcium channels

87
Q

Give an example of a GABA modulator.

A

Tiagabine blocks reuptake of GABA.

Viagabatrin blocks breadown.

Both drugs used only under specialists.

88
Q

Diazepam is a ? which acts as a co-agonist, binding to a different site (allosteric) on the GABA receptor and increasing the effect of GABA.

A

benzodiazepine,

89
Q

What is Ethosuximide used for?

A

General non-motor typical seizures (absence).

90
Q

When are benzodiazepines used?

A

In managing generalised status epilepticus.

91
Q

Antiepileptics also used for ? pain.

A

neuropathic

92
Q

What diet can reduce seizure frequency in childhood?

A

Ketogenic.

93
Q

A patient suffers focal seizures which have a focus in the uncus. Which sensory hallucinations is the patient most likely to experience?

A

Olfactory – primary olfactory cortex is located in the periamygdaloid region, in the uncus.

Cacosmia (often a harsh metallic, burning rubber or faecal smell) is a common hallucination for seizures generated in this area.

94
Q

What side effect can vigabatrin cause?

A

Visual field loss.

95
Q

What side effect can lamotrigine cause?

A

Diplopia.

96
Q

Valproic acid, gabapentin and pregabalin can cause ?.

A

Weight gain

97
Q

What is the aetiology of seizures?

A
  1. Increase in Ach transmission.
  2. Increase in Na+ transmission.
  3. Decrease in GABA.
  4. Decrease in K+ transmission.
98
Q

What are different types of treatments for epilepsy?

A
99
Q

What are 2 calcium channel blockers used to treat epilepsy?

A

Ethosuxumide

Gabapentin

100
Q

What are 3 benzodiazepines (GABA modulators) used to treat epilepsy?

A

Midazolam

Lorazepam

Diazepam

101
Q

What are 3 barbiturates (GABA modulators) used to treat epilepsy?

A

Phenobarbitone

Pentobarbitone

Primidone

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