Epilepsy Symposium Flashcards
1
Q
What is epilepsy?
A
- a recurring unprovoked (spontaneous) seizures
- acute symptomatic seizures are provoked by acute insults such as
- stroke, infection, alcohol withdrawal, or a metabolic disturbance
2
Q
What types of seizures are there?
A
- Primary generalized onset: electrical discharges appear to start over the whole brain at the same time on EEG
- Partial/focal onset: electrical discharge appears to start in one cortical region and then may remain localized or may spread over the whole brain - secondary generalized
3
Q
What are the classifications of Idiopathic (Primary) Generalized seizures?
A
- Limited repertoire of seizures
- Tonic-clonic seizures (“grand mal”)
- Absences (“petit mal”)
- Tonic seizures
- Atonic seizures
- Myoclonic seizures
4
Q
Give an overview of what Idiopathic Generalized Seizures are?
A
- Onset in childhood or adolescence
- Usually no focal symptoms/signs
- Often a number of seizure types cluster
- A polygenic cause is presumed with no identifiable structural lesion on imaging
- Generalized (all leads) spike and wave discharges on EEG may be induced by hyperventilation, and on photosensitivity testing
- Provoked by sleep deprivation
5
Q
What is Juvenile Myoclonic Epilepsy (JME? - give an overview
A
- Commonest form of primary generalized epilepsy 3-12% all epilepsy
- Juvenile onset, probably lifelong
- Early morning myoclonic jerks (ask)
- Photosensitive, sleep deprivation triggers
- +/- absences
- generalized tonic-clonic seizures – occur without warning
6
Q
Give an overview of the presentation of Generalised Tonic-Clonic Seizures “grand mal”
A
- sudden onset without warning in primary generalised epilepsy
- Tonic phase
- continuous muscle spasm, fall, cyanosis, tongue biting, incontinence
- Clonic phase
- rhythmic jerking slows and gets larger in amplitude as the attack progresses
- Ends; the duration is typically 1-3 minutes
- Post-ictal (post-seizure) phase
- coma, drowsiness, confusion, headache
- muscle aching
- red/blue, wakes in ambulance/A&E
7
Q
Give an overview of Absences “petit mal”
A
- Abrupt, short, 5-20 seconds
- Multiple times/day, can lead to learning difficulties
- Unresponsive, amnesia for the gap, rapid recovery
- Tone preserved (or mildly reduced)
- If absences only, tend to remit in adulthood (childhood absence epilepsy)
8
Q
What ways are there Focal Onset Seizure?
A
- a simple partial seizure where the patient is aware (used to be an aura)
- focal seizure with awareness
- a complex partial seizure- aura/warning with a level of reduced awareness
- focal seizure with reduced awareness
9
Q
Where d partial seizures frequently present themselves in the lobe?
A
- Temporal lobe - 70%
- Frontal lobe - 25%
- Occipital lobe - 4%
- Parietal lobe - 1%
10
Q
Give temporal lobe seizures by aetiology
A
- Hippocampal sclerosis: 50%
- have a history of febrile convulsion
- Tumour: 18%
- Birth Hypoxia: 10%
- Vascular: 10%
- Post Traumatic: 8%
- Other: 4%
11
Q
What are the symptoms and signs of temporal lobe epilepsy?
A
- hallucinations of taste, speech and /or smell, visual distortion; memory déjà vu and jamais vu
- epigastric rising sensation (over humpback bridge)
- fear, elation, low mood
- pallor/ flushing/ heart rate changes (can mimic panic/hyperventilation attacks)
- automatisms- semi-purposeful limb movements
- Oral automatisms- lip-smacking, chewing movements
- dystonic posturing (limb rises)
- speech disturbance (dominant hemisphere onset) last 1-3 minutes typically
12
Q
What are the symptoms of a frontal lobe seizure?
A
- brief 10-30 seconds, rapid recovery, frequent
- predominantly nocturnal
- forced head /eye deviation to the contralateral side
- motor activity often bizarre, thrashing
- often misdiagnosed as non-epileptic
- ictal EEG (during the seizure) is often normal
- Jacksonian spread with Todd’s paresis
- automatisms, dystonic posturing for example
- a fencing posture (overlap TLE)
13
Q
What are Parietal lobe epilepsy symptoms?
A
- positive sensory symptoms (unlike TIA/stroke)
- tingling, pain
- distortion of body shape/image
- Jacksonian march of positive sensory symptoms
14
Q
What are Occipital lobe epilepsy symptoms?
A
- typically simple visual hallucinations -balls of coloured or flashing lights
- amaurosis (blackout or whiteout) at onset -25%
15
Q
What anti-epileptic drugs make myoclonic jerks and absences worse?
A
- Phenytoin
- treats tonic-clonic seizures
- safe to use in status epilepticus (when a seizure lasts more than 5 minutes or are close together)
- Carbamazepine,
- Gabapentin,
- Pregabalin
16
Q
Which type of seizure patient would you give a scan to?
A
- Jacksonian motor or sensory seizures
- Patients with focal neurological deficit (including a temporary unilateral Todds paresis)
- Alcohol withdrawal seizure; only scan if subdural haematoma suspected fall, hit head, found on the floor, bruising on head
17
Q
What is the physiological representation of Epilepsy?
A
- Epilepsy represents a hyperexcitation or a failure of inhibitory regulation, either focally (e.g. motor cortex, temporal cortex) or generally (whole cortex at once)
18
Q
How are epileptic episodes physiological caused?
A
- Na+ channel inactivation too slow in excitatory neurons
- Reduced number of functional Na+ channels in inhibitory neurons
- Reduced number of functional K+ channels in excitatory neurons
- Mutated ion channels: voltage-gated and ligand-gated ion channels
19
Q
How do Na+ channel dysfunctions lead to epilepsy?
A
Na+ channel inactivation too slow in excitatory neurons
- e.g., generalized epilepsy with febrile seizures plus (GEFS+)
- a point mutation in part of Na+ channel (β subunit) –> abnormally slow inactivation
- action potential repolarization impaired
Reduced number of functional Na+ channels in inhibitory neurons
- e.g., generalized epilepsy with febrile seizures plus (GEFS+)
- missense mutations or truncated protein results in reduction or loss of Na+ channel function
- action potential generation impaired
20
Q
How do K+ channelopathies lead to epilepsy?
A
Reduced number of functional K+ channels in excitatory neurons
- e.g., benign familial neonatal convulsions
- defect in KCNQ2 or KCNQ3 K+ channel subunit –> impaired activation
- action potential repolarization impaired
21
Q
Explain the development of Focal (partial) seizures
A
- synchronized ‘paroxysmal depolarizing shift’ (PDS, 20 to 40 mV, lasting 50 to 200 ms) overcomes inhibition
- increased extracellular K+ due to neuronal damage or reduced uptake by the astrocytes as well as glutamate release from neurons or astrocytes contribute to PDS
- during the PDS trains of action, potentials occur
- hippocampal neurons have similar responses under normal conditions, making the hippocampus more prone to seizures than the neocortex
- Focal seizures may spread to other brain regions along the normal neuronal pathways and may also show secondary generalization if the activity spreads to the thalamus (tonic clonic seizure)
22
Q
Explain the development of Primary Generalized seizures.
A
- Primary generalized seizures reach the cerebral cortex via normal neuronal pathways from the thalamus
- e.g. tonic clonic seizure; absence; juvenile myoclonic epilepsy
- pathways originate in the brainstem and are normally involved in regulating the sleep/wake cycle and arousal of the cerebral cortex
- Ca2+ channels and inhibitory GABA receptors in thalamic neurons have been implicated in ‘spike and wave’ seizures, showing that inhibition (the wave) is preserved
23
Q
What is the general action of Anti-epileptic drugs?
A
- work to inhibit Glutamate
- this is an excitatory molecule in the brain
- work to increase GABA activity
- this is an inhibitory molecule in the brain
24
Q
What AEDs work by inhibiting the excitatory process in neurons?
A
- Phenytoin, Carbama/ Oxcarba-zepine, Eslicarbazepine acetate, Lamotrigine, Lacos/ Zonis-amide
- inhibits voltage-gated Na+ ion channel
- Ethosuximide
- inhibits Ca2++ entry into postsynaptic neuron
- Retigabine
- increases excite of K+ from the postsynaptic neuron
- Perampanel
- inhibits the AMPA receptor which glutamate binds to and allows NA+ into the postsynaptic neuron
25
Q
What AEDs work by increasing the activity of the inhibitory process in neurons?
A
- Levetiracetam
- increases activity of SV2A- regulates action potential-dependent neurotransmitter release
- Retigabine
- increases the activity of KCNQ K+ channels in the pre and postsynaptic neuron
- Gabapentin, Pregabalin
- inhibit alpha-2-beta-subunit of Ca2+ channels in the presynaptic neuron
- Tiagabine
- Inhibits GAT-1 in presynaptic neurons and on glial cells
- Benzodiazepines, Barbiturates
- increases activity of GABAA more Cl- moved into the postsynaptic neuron
26
Q
Perampanel as an AED
A
- non-competitive blockade of AMPA glutamate receptor
- release of glutamate cannot overcome the block
- reduce spread/generalisation of seizure
- can also affect behaviour and mood
27
Q
What role or lack thereof does GABA play in the occurrence of a full-blown seizure?
A
- Focal epilepsy characterised by intermittent high amplitude discharges at site of epileptic focus during inter-ictal (seizure) periods.
- Two phases:
- synchronous depolarisation (caused by strong excitatory inputs to the region of the focus),
- followed by a period of hyperpolarisation, (activation of GABA inhibition)
- Transition from inter-ictal discharges to full-blown seizure is a decrease in the hyper-polarisation phase
- failure of inhibition to kick in, therefore treating with GABA stimulants helps control the seizure
28
Q
What drugs enhance GABA-ergic synaptic transmission?
A
- sodium valproate (sodium channels)
- benzodiazepines (clobazam, lorazepam)
- barbiturates/ primidone pro drug
- tiagabine (inhibits GABA re-uptake)
- vigabatrin (inhibits GABA –T breakdown)
29
Q
What is Levetiractem?
A
- high-affinity synaptic vesicle protein-2A ligand that modulates glutamate neurotransmitter release
- rapidly up titrated and is effective
- IV formulation; no drug-drug interactions
- keeps patients alert but causes mood lowering/agitation side-effects
- brivaracetam second-generation version
30
Q
What drugs would be suitable for Primary Generalized Epilepsy?
A
First line
- Sodium valproate
- Lamotrigine
Second line
- levetiracetam, topiramate, zonisamide, benzodiazepines
31
Q
What drugs would be suitable for Partial (focal onset) epilepsy?
A
First line
- Carbamazepine
- Lamotrigine
- all other AEDs have efficacy
32
Q
Go over the toxicity effects of Benzodiazepines
A
Dose related (acute)
- Drowsiness
- Ataxia
- Hyperactivity
- cognitive impairment
Long term
- Tolerance/ Dependence
33
Q
Go over the toxicity effects of Phenytoin
A
Dose-related (acute)
- Ataxia
- Diplopia
- Nystagmus
Long-term
- Gingival hyperplasia
- Osteomalacia
- Cerebellar atrophy
34
Q
Go over the toxicity effects of Sodium Valproate
A
Dose-related (acute)
- Sedation
- Tremor
Long-term
- Hair thinning
- Weight gain
- Menstrual irregularities
- Encephalopathy
- Parkinsonism
(is an enzyme inhibitor)
