Seizures symposium Flashcards
What is epilepsy?
Recurring, unprovoked seizures
What are some acute insults that can provoke acute symptomatic seizures?
Stroke Alcohol withdrawal Infections High fever Metabolic disturbance Recreational drugs
What does a generalised onset mean?
Electrical discharges appear to start over the whole brain at the same time
What does a partial / focal onset mean?
Electrical discharges appear to start in one cortical region & then may remain localised or spread over whole brain
What are the 6 types of idiopathic generalised seizures?
Tonic-clonic Tonic Clonic Atonic Myoclonic Absences
Describe idiopathic generalised seizures
Onset in childhood or adolescence Usually no focal symptoms / signs Often a cluster of seizures Generalised (all leads) spike & wave dischargers on EEG Photosensitivity may be present
Describe Juvenile myoclonic epilepsy
Commonest form of primary generalised epilepsy
3-12% of all epilepsy
Begins in adolescence
Early morning myoclonic jerks
Photosensitive, sleep deprivation triggers
Possible absences
Generalised tonic-clonic seizures which occur without warning
Describe the tonic phase in a tonic-clonic seizure
Continuous muscle spasm Will fall May have cyanosis due to thorax muscles contracting Tongue biting Incontinence
Describe the clonic phase in a tonic-clonic seizure
Rhythmic jerking slows & gets larger in amplitude as the seizure ends
Describe the postictal phase in a tonic-clonic seizure
Coma Drowsiness Confusion Headache Muscle aching
Describe an absence seizure
Abrupt
5-20 seconds
Multiple times a day, can lead to learning difficulties
Unresponsive, amnesia for the gap, rapid recovery
Tone preserved or mildly reduced
Eyelid flickering
Tend to stop in adulthood
What are the types of partial seizures?
Simple partial seizure - patient is aware
Complex partial seizure - aura / warning with reduced awareness
What is the frequency of partial seizures in each lobe?
Parietal - 1%
Occipital - 4%
Frontal - 25%
Temporal - 70%
Describe a secondary generalised tonic-clonic seizure
Warning / aura
Can’t abort attack
Sudden onset
Last 1-3 minutes
Falls, loses consciousness as seizure generalises
Rigidity, convulsive jerks, excessive salivation
Incontinence, tongue biting
What is the aetiology of temporal lobe seizures?
Hippocampal sclerosis - 50% Tumour - 18% Birth hypoxia - 10% Vascular - 10% Post-traumatic - 8% Other - 4%
What are the risk factors for epilepsy in those with temporal lobe seizures?
Febrile convulsions below 6 months Duration greater than 15 minutes Recurrence within 24 hours Focal features Developmental delay
What are the physical symptoms of temporal lobe epilepsy?
Hallucination of taste, speech, smell, visual distortion Epigastric rising sensation Pallor, flushing, heart rate changes Automatisms - semi-purposeful movements Oral - lip smacking, chewing movements Dystonic posturing
What are the cognitive symptoms of temporal lobe epilepsy?
Deja vu
Speech arrest
Formed words during the seizure implies a non-dominant hemisphere focus
Describe frontal lobe seizures
Brief: 10-30 seconds Rapid recovery Frequent Predominantly nocturnal Forced head / eye deviation to contralateral side Motor activity described as bizarre. thrashing EEG during the seizure is often normal Jacksonian spread with Todd's paresis Automatisms, dystonic posturing
Describe the symptoms of parietal lobe epilepsy
Positive sensory symptoms
Tingling, pain
Distortion of body shape / image
Jacksonian march of positive sensory symptoms
Describe the symptoms of occipital lobe epilepsy
Typically simple visual hallucinations
Amaurosis at onset
What patients should be scanned?
New onset of Jacksonian motor or sensory seizures
Patients with focal neurological deficit
Alcohol withdrawal seizure if haematoma is suspected
What is the definition of epileptogenesis?
Process by which parts of a normal brain are converted to a hyper excitable brain
What is an epileptic seizure?
Explosion of synchronous activity by lots of neutrons at once which has a tendency to spread throughout the cerebral cortex causing an electrical-brain storm
Why is the brain prone to seizure activity?
Action potentials rely on positive feedback & are unstable
Single neuron can fire spontaneously without external stimulation
Network of excitatory neurons connected in a convergent or divergent pathway can be explosive. Stimulation of any one cell can lead to a chain reaction due to the progressive spread of activity over a large area
Brain requires at least as much inhibition as excitation to avoid this
Epilepsy represents a failure of inhibitory regulation, either focally or generally
Describe the link between ion channels and epilepsy
Point mutation in Na+ channel (beta subunit) –> abnormally slow inactivation –> repolarisation is impaired. Example is generalised epilepsy with febrile seizures in infants
Defect in KCNQ2 or KCNQ3 channel subunit –> impaired activation –> impaired action potential repolarisatin. Example is benign familial neonatal convulsions
What is an electroencephalogram (EEG)?
Array of electrodes on the scalp which gives information about the electrical activity of a large number of neurons in the cerebral cortex
Help determine location of a seizure
Rhythmic oscillations - without sensory inputs the various neural networks feedback upon themselves
When aroused, neuronal activity becomes desynchronised
Hyperexcitation of a seizure –> synchronous activity on EEG
Describe the origin of focal (partial) seizures
Originate within a small group of 1000 neutrons
Synchronised paroxysmal depolarising shift overcomes inhibition
Increased extracellular K+ due to neuronal damage or reduced uptake by astrocytes, plus glutamate release from neurons or astrocytes
During PDS, trains of action potentials occur
Describe the spread of focal seizures
Spread to other brain regions along normal neuronal pathway & may show secondary generalisation if activity spreads to thalamus
Describe the origin of primary generalised seizures
Reach cerebral cortex via normal neuronal pathways from thalamus
Pathways originate in brainstem & are normally involved in regulating sleep/wake cycle & arousal of cerebral cortex
Ca2+ channels & inhibitory GABA receptors in thalamic neutrons have been implicated in spike & wave seizures showing inhibition is preserved
What causes increased activity in the brain?
Increased membrane excitability
Increased efficiency of excitatory synaptic transmission (glutamate)
Decreased efficiency of inhibitory synaptic transmission (GABA)
Give examples of Na+ channel blocker anticonvulsant drugs
Phenytoin Lamotrigine Carbamazepine Zonisamide Lacosamide
What is perampanel and how does it work?
AMPA receptor antagonist
Non-competitive blockade of AMPA glutamate receptor
Reduce spread / generalisation of seizure
Well tolerated with improved alertness
What does Ethosuximide do?
Blocks T-type calcium channels in the thalamus, which are involved in bursting & intrinsic oscillations
Give some examples of anticonvulsant drugs that facilitate GABAergic transmission
Sodium valproate Benzodiazepines - lorzepam Barbiturates Tiagabine Vigabatric
What is Levetiracetam?
High affinity synaptic vesicle protein 2A ligand
Modulates neurotransmitter release
Rapidly titrated & effective
Mood lowering / agitation side effects
What is an ideal antiepileptic agent?
Good efficacy, easy & rapid to titrate No drug-drug interactions No cognitive side effects No bone marrow suppression No affective / drowsy side effects Different routes of administration Cost effective
Describe established drugs
Single mode of action Less selective effects More side effects in cognition / sedation More drug interactions Kinetics / narrow therapeutic range Cheaper
Describe modern drugs
Broad spectrum More selective actions Less sedating side effects Psychiatric side effects Less long-term toxicity Fewer drug interactions Easier titration 10 X more expensive
What is the first line treatment for primary generalised epilepsy?
Sodium valproate
Iamotrigine
What is the first line treatment for partial epilepsy?
Carbamazepine
Iamotrigine
What drugs exacerbate generalised seizure types such as myoclonus and absences?
Phenytoin
Carbamazepine
Gabapentin / pregabalin
What are the side effects of benzodiazepines?
Drowsiness Ataxia Hyperactivity Personality change Cognitive impairment Tolerance / dependence
What are the side effects of phenytoin?
Ataxia Diplopia Nystagmus Gingival hyperplasia Osteomalacia Cerebellar atrophy
What are the side effects of sodium valproate?
Sedation Nausea / vomiting Tremor Hair thinning Weight gain Menstrual irregularities Encephalopathy
