Lecture 20 Epilepsy

Question 1

What is the defining feature of Epileptic seizure?

Answer 1

Abnormal, excessive electrical discharge from neurones,

Not always producing loss of consciousness/the loss of consciousness isn’t due to epilepsy.

Epilepsy is a tendency to recurrent seizures. Can be considered as imbalance between excitation and inhibition.

Question 2

What are the possible causes of epilepsy (symptom of brain dysfunction)

Answer 2

Epilepsy is a symptom of brain dysfunction

Possible cause:

• structural
• acquired (abscess, stroke),
• genetic factors increasingly important
• metabolic/ functional
• the longer you live more likely to have seizure of any kind (1/20 have seizures in 80+yr)

Question 3

How do seizures happen (epileptogensis)

Possible of every mammal.

Answer 3

Occur as a result of abnormal synchronous activation of large numbers of hyperexcitable neurons which are connected in networks.

These networks can be

• normal or abnormal
• via synaptic or gap junction pathways.

Question 4

How does post traumatic epilepsy occur after traumatic brain injury

Answer 4

1. Traumatic brain injury triggers inflammatory cascades via microglia activation which can be pro or anti inflammatory depending on mediators released.
2. These may influence brain repair processes which can cause seizures, but final pathway is too much excitation or not enough inhibition

Question 5

How are epileptic seizures classified electroclinically?

Answer 5

• Focal (partial): seizures starts in one part of the brain, can remain localised or can spread with symptoms reflecting which part of the brain - lobe being activated:
  eg. motor twitching of the hand on other side

-Generalised: seizures in networks involving extensive regions of both hemispheres from the outset with greatly varying symptoms.

Question 6

What are some symptoms of focal aware seizures in the visual, auditory, temporal lobe and others

Answer 6

Simple partial seizures: they are aware.

Visual: blindness, hallucinations, dim shapes.

Auditory: hallucinations, tinnitus

Temporal lobe:
get fear/memory, language processing (on left side) , dejavu

Also has Focal impaired awareness seizure- subsequent amnesia. (complex partial)

Question 7

What is Electroencephalogy and how is it helpful for diagnosing epilepsy

Answer 7

• 1/2 hr recording from 21 electrodes placed on the scalp.
• A single EEG will show epileptiform activity in 30-70% of epilepsy patients. More caught in sleep recordings.
• Important for identifying seizure type and hence correct seizure syndrome.

Question 8

What are the main type of seizures from Generalised seizures

Answer 8

• Tonic (stiff)
• Clonic (jerking)
• Tonic/clonic
• Myoclonic
• Atonic seizures (sudden loss of tone)
• Myoclonic astatic seizure
• Absence seizures (blank patient)

Question 9

What are the 2 types of ionotropic excitatory amino acid receptors at the glutamergic synapse comparing speed of activation and ions let through

Answer 9

1. NMDA receptors for Glutamate.
   Slow acting- has Mg2+ usually blocking then releases channel when partial depolarisation of membrane. selective for Ca2+ entry with positive feedback loop.
2. Non NMDA: AMPA and Kainate receptors mainly.
   Fast on and off. Most cations but not Ca2+

Question 10

What is the inhibitory receptor for neurotransmission, what ion does it let through and why

Answer 10

1. GABA receptors bind 2 molecules of GABA.
2. Opens Cl- channels to hyperpolarise neurons.
3. Inhibition promotes neuronal synchronisation

(Barbuitates and benzodiazepene epileptic drugs bind here)

Question 11

What is Dravet syndrome (severe myoclonic epilepsy of infancy) caused by

Answer 11

Mutation in voltage gated Na+ channel SCN1A.

Causes motor and intellectual impairment (SCN1A)
Generalised Epileptic febrile seizures +6m-5yrs. Some can go on to have severe epilepsy others not.

Question 12

What causes absence seizures (unusual in adults)

Answer 12

Mutations in Ca2+ channels have abnormal activation, leading to hyperpolarisation of thalamic relay neurones, producing synchronous depolarisation of cortex via excitatory pathways.

These are generalised seizures where their awareness has lapsed but not confused,

Question 13

What drugs induce seizures (Proconvulsant) - 3 types and give an eg

Answer 13

1. Blockade of GABAa receptors: reduce inhibition of excitatory signals. eg. High doses of penicillin (rare)
2. Stimulation of Glutamate receptors
   eg. kainate, domoic acid (shellfish)
3. Blockade of K currents with 4 aminopyridine can be used to treat some M-sclerosis

Question 14

What are the 4 types of drugs used to treat seizures and give an eg

Answer 14

1. Na+ channel blockers at the presynaptic neuron: prevent sustained and repetitive firing by extending depolarisation
   eg. Carbamazepine, phenytoin
2. Enhancement of GABA transmission: eg. diazepam (benzodiazepine), sv
3. Action on Ca2+ channels
   eg. Ethosuxamide, sodium valproate
4. Blocking glutamate transmission: reduce amount released in response to AP depolarising the exictatory neuron
   eg. Topirimate

Question 15

What are the two main types of Auto-antibody induced epilepsy syndromes and some main symptoms

Answer 15

1. Anti-voltage gated K channels (LG1)
   - prominent amnesia, complex partial seizures, hyponatraemia.
2. Anti-NMDA receptor:
   - psychiatric features, dyskinsia, complex partial seizures

Question 16

What are the main effects of having seizures

Answer 16

1. Kindling:
   Repetitive exposure to initial sub-threshold electrical stimulation eventually produces spontaneous seizures -not concrete in
2. Anatomic rearrangement of local circuits: excitatory axons have collateral branches, with feedback inhibition and or excitation. Inhibition usually more powerful.
3. With neuronal death there is sprouting of unlesioned axons to fill dendritic regions.
   In the dentate gyrus this can make recurrent excitatory connections which alter normal balance between feedback excitation and inhibition- compromise the inhibitory pathways