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0

define seizure:

clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurones

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define: epilepsy

a chronic disorder characterised by recurrent unprovoked seizures- more than 2 in a year

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define epileptogenesis:

sequence of events that converts a normal neuronal network into a hyperexcitable network
- process by which a normal brain becomes epileptic

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where do majority of seizures predominate ?

in the cerebral cortex

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where can the cortical discharges of a seizure be transmitted to ?

muscles causing twitches or convulsions
- the seizures manifest themselves in different ways depending on the site of origin and the spread

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if the seizure is localised to the left hemisphere where will effects of the seizure be seen ?

it will affect the right side of the body

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what is chadwicks definition of an epileptic seizure ?

an intermittent, stereotyped, disturbance of consciousness, behaviour, emotion, motor function or sensation that on clinical grounds is believed to result from cortical neuronal discharge

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what can epilepsy be defined as ?

a condition in which seizures recur usually spontaneously
- a single episode is not considered to be epilepsy

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what type of disorder is epilepsy?

a heterogenous group of debilitating neurological disorders

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how many different epilepsies are there ?

there are about 10 types of recurrent seizures
about 40 forms of epilepsy syndromes
- this diversity reflects the numerous cellular and networks to seizure genesis

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what is the risk of recurrence of seizures after the first unprovoked seizure and the second unprovoked seizure ?

30-35% -first
60% -second

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what can infant suffer from but adults cant and why ?

benign fibrile convulsions- caused by a fever
- adults dont have them because the infant brain is more excitable so its more susceptible to these convulsions

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what is the incidence of epilepsy?

about 45/100000 per year

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what is the point prevalence of epilepsy ?

0.5-1%- it is a measure of the portion of people in a population who have a disease at a particular time

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what are the causes of epilepsy?

many different causes
- disturbances of the normal pattern of neuronal activity= traumatic brain injury, stroke, CNS infection, neoplasm and fever
- genetic forms- underlying genetic predisposition
-

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what can lead to epilepsy?

one inciting event may be sufficient or mutiple factors can lead to it

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what factors have been shown to modulate progression to epilepsy?

family history of seizures
age - people over 60 are more susceptible and children under 5
sex
organic brain disease- e.g tubersclerosis
psychiatric comorbidity- bipolar disorder

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in epileptogenesis what followed an initial insult?

followed by a clinically latent period lasting weeks to months or even years before the onset of spontaneous seizures

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what happens during the latent period ?

a cascade of molecular and cellular events occur that alter the excitability of the neuronal network - leading to spontaneous epileptiform activity

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how might epilepsy develop?

because of an abnormality in neuronal circuitry- imbalance of neurotransmitters or some combination of factors

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what is the prevalence of epilepsy ?

40 to 70 per thousand
about 3% of the UK pop

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what are the probabilities of having a second seizure after only seizure and what is the probability of having another seizure after having had 2?

1 seizure previously- less than 15% chance of another one
2 seizurespreviously - greater than 85% of another one

22

what are some potential causes of epilepsy in infancy and childhood?

- prenatal or birth injury
- inborn error of metabolism
- congential malformation

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what are the aetiologies for epilepsy in childhood and adolescence ?

- idiopathic/genetic syndrome
- CNS infection
- trauma

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what are the aetiologies for epilepsy in adolescence and young adults?

head trauma
drug intoxication and withdrawal- alcoholics that completely stop taking alcohol can lead to seizures

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what are the aetiologies of epilepsy in older adults ?

stroke
brain tumour
neurodegeneration
acute metabolic disturbances

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what is the classification of seizures based on and what are they ?

based on site of seizure onset in the brain
- PARTIAL- initial activation of a limited number of neurones in a part of 1 hemisphere
- GENERALIZED- initial activation of neurones throughout both hemispheres
-SECONDARY GENERALIZED- partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres

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what does an epileptic patients experience of a seizure depend on ?

depends on what part of the brain the epileptic activity starts and how widely it spreads from that area

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what are the effects caused by a partial seizure ?

SIMPLE- seizure activity while the person is still alert
COMPLEX- seizure activity with a change in the awareness of surroudings hippocampus has been affected
WITH SECONDARY GENERALIZATION- seizure activity begins in one area and spreads

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what are the effects caused by generalised seizures?

ABSENCE- staring and blinking without falling
MYOCLONIC- jerking movement of the body
TONIC-CLONIC- stiffening, falling, and jerking of the body
TONIC- falling and jerking of the body
ACONIC- falling heavily to the ground

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what are seizures like if they arise in the parietal lobe ?

tingling in or jerking of legs, arms and face

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what are seizures like if they originate in the occipital lobe ?

flashing lights or spots and vomitting

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what are seizures like if they originate in the temporal lobe ?

strange smell or taste altered behaviour
feeling of deja vu
lip smacking or chewing movements

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what are seizures like if they originate in the frontal lobe ?

JACKSONIAN SEIZURE- tingling feeling in hand or arm
ADVERSIVE SEIZURE- eyes or head both turn to one side

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what does the final outcome of seizures depend on ?

due to the excitiability changes of neurones in specific networks

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what network is affected early on in generalised seizures?

thalamocortical circuitry- involved early in the attack and results in synchronised firing of neurones brain wide, unconsciousness and often violent rhythmic shaking of body parts

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what are thalamocortical fibres and what do they do ?

specialised neurones in the thalamus with profuse connections to the entire brain
-during sleep they disrupt the individual activities of cortical neurones and entrain them all into monotonous rhythmic synchronised discharges

37

what are the competing hypotheses for generealised seizures ?

some have proposed that the primary abnormality lies in the cortex whilst others state it is in the subcortical centrencephalic system

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what are the incidences of seizure types ?

complex partial- 36%
other partial- 7%
generalised tonic-clonic- 23%
other generalised- 8%
myoclonic- 3%
absence-6%
simple partial- 14%

39

how are epilepsy disorders subdivided and what are the distinctions based on ?

subdivided by presumed cause
distinctions are based on clinical ad EEG signs and symptoms

40

what are cryptogenic epilepsies?

thought to arise from an unidentified brain lesion or disorder
- in children it also implies a normal neurological development before the onset of the seizure disorder
cryptogenic and symptomatic are the same, the only distinction is the sophistication of current diagnostic techniques

41

why is epilepsy difficult to diagnose ?

because many other disorders such as migraines and panic attacks have similar symptoms

42

what tests do neurologists normally carry out to diagnose epilepsy?

EEG- look for changes in the brains electrical patterns that are related to the seizures
blood tests- look for certain medical disorders
MRI scan- spot any defects in the structure of the brain

43

what are EEGs?

they use scalp electrodes to record the electrical activity along the scalp produced by the firing neurones in the brain
- electrodes are placed on the scalp and the electrical impulses in the vrain are amplified and summed into waves that can be monitored

44

what is a hallmark of generalised epilepsy ?

typical 3 to 4 hz spike wave discharges over entire surface of the brain

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what is seen in patients with absence seizures ?

no outwardly noticeable symptoms

46

how are experimental seizures induced in animal models?

by some noxious event
- injection of proconvulsant drug(pilocarpine induced) or electrical stimulation( kindling)

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what is the kindling model ?

repeated subthreshold electrical stimulation of limbic regions - usually amygdala, temporal lobe involved in anxiety response
repeated stimulation lowers the threshold for more seizures to occur
therefore aafter a few days only need very low intensityy to get a repsonse
then eventually you get spontaneous seizures

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what initiating agents are used in adult animals to study the long term development of epilepsy ?

-lateral fluid percussion injury- traumatic brain injury
-kainic acid status epilepticus
-lithium-pilocarpine status epilepticus
-intrahippocampal stimulation
-amygdala stimulation
-cortical stroke models

49

define status epilepticus :

30 mins of sustained seizure activity or 2 or more seizures during this time period without full recovery
- people can die from this because it can affect their respiration

50

what is pilocarpine ?

a non-selective muscarinic receptor agonist in the PNS- used to induce chronic epilepsy in rodents

51

what are the strategies to develop genetic models of epilepsy ?

by serendipity- epilepsy observed in a strain of animals and the seizures are characterised and validated as their clinical relevance- through inbreeding a mouse was homozygous with a mutation in a calcium gene and had epilepsy
genetic engineering based on known genetic defects identified in families with epilepsy
hypotheses driven experiments- a given gene is over of under expressed or deleted to test a specific hypothesis

52

what is the racine scale?

is a seziure classification system used to define focal experimental seizures

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what was the racine scale originally developed for ?

to describe electrically evoked motor events and was effective because the time of seizure occurence was under the experimenters control

54

what are the 5 stages of the racine scale?

1) mouth and facial movements
2) head nodding
3) forelimb clonus
4) rearing
5) rearing and falling