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week 10 part 2 Flashcards

1
Q

What are some epilepsy?

A
  1. Age dependent
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2
Q

What are the third level of new classification?

A

Diagnosis of epilepsy syndrome

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3
Q

What is epilepsy syndrome?

A

A combination of a specific features:

  1. Clinical presentation
  2. Onset age
  3. Natural course
  4. Seizure types
  5. EEG
  6. Neuroimaging features
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4
Q

What is Epilepsy?

A

A disease of the brain characterised by:

  1. 2 unprovoked seizure occurring more than 24 hours apart
  2. one unprovoked seizure and a probability of further seizure similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures occuring over the next 10 years
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5
Q

What is a seizure?

A

A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

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6
Q

What are the 2 main groups of seizures?

A
  1. Focal

2. Generalised

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7
Q

Focal onset seizure

A
  1. Originating within network limited to one hemisphere
  2. may be discretely localised or more widely distributed
  3. Originate in subcortical structures
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8
Q

Where can focal seizure spread widely in?

A
  1. Brain to engage bilateral network including cortical and subcortical structures
  2. Result in tonic-clonic seizure - loss of consciousness
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9
Q

What is generalised onset seizure?

A
  1. Rapidly engaging bilaterally distributed networks

2. Bilateral network: cortical and subcortical structures - do not necessarily include the entire cortex

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10
Q

What is unknown onset seizures?

A
  1. Classified as motor or non-motor
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11
Q

Why may seizure be unclassified?

A
  1. Inadequate information to allow it to be placed in focal, generalized or unknown onset categories
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12
Q

What 4 types are epilepsies divided into?

A
  1. Focal
  2. Generalised
  3. Combined generalised and focal
  4. Unknown
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13
Q

Why is consciousness important?

A
  1. Awareness
  2. Responsiveness
  3. Memory
  4. Self-aware
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14
Q

What was generalized seizures known as? What was its features?

A
  1. Grand Mal
  2. Lose consciousness
  3. Muscle stiffen
  4. Exhibiting jerking movement
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15
Q

What are the etiology of the ILAE classification of epilepsy?

A
  1. Structural
  2. Genetic
  3. Infectious
  4. Metabolic
  5. Immune
  6. Unknown
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16
Q

Structural etiology

A
  1. MRI using 1.5Tesla magnet - minimum standard investigation for exclusion of structural abnormality
  2. EEG + PET, SPECT, MEG - direct attention to a particular brain region - subtle abnormality to be identified
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17
Q

What are common structural brain abnormalities associated with epilepsy

A
  1. Malformation of the cortical development
  2. Vascular malformation
  3. Hippocampal sclerosis
  4. Hypoxic-ischemic structural abnormalities
  5. TBI, tumours, and porencephalic cyst
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18
Q

Metabolic etiology

A
  1. Cerebral folate deficiency
  2. Neurological syndrome - low CSF 5MTHF
  3. Disturbed folate transport or increased folate turnover within CNS
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19
Q

What are typical features of cerebral folate deficiency?

A
  1. Irritability
  2. Sleep
  3. Deceleration of head growth
  4. Progressive hearing and visual impairment
  5. Dyskinesia
  6. Epilepsy
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20
Q

Immune etiology

A
  1. CNS inflammation - associated with increased risk of developping epilepsy
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21
Q

What is an example of immune etiology?

A
  1. Anti-NMDA receptor encephalitis

2. Antibodies are directed against the NR1 sibunit of NMDA receptor

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22
Q

What does prodrome Anti-NMDAR encephalities symptoms?

A
  1. Fever
  2. Headache
  3. Nausea
  4. Vomitting
  5. Diarrhea
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23
Q

For the symptomatic phase, what are the symptoms?

A
  1. Psychiatric and behavioral symptoms
  2. Anxiety
  3. Bizarre behaviour
  4. Delirium
  5. Paranoia o Insomnia or hypersomnia
    o Altered level of consciousness
    o Seizures (focal or generalized)
    o Movement disorders: oral-motor dyskinesias, choreiform movements
    o Hypoventilation
    o Autonomic instability: incontinence, tachycardia, hypertension, hyperthermia
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24
Q

Infection etiology

A
  1. Bacterial Meningitis
  2. Meningococus, pneumococcus, haemophilus infleunza B
  3. Acute seizure - related to fever or subdural collection, cerebritis or cerebral infarction
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25
What may reduce the incidence of specific bacterial meningitides?
Immunization programs
26
What is another example of infection etiology?
Cerebral malaria 1.• Plasmodium falciparum in sub-Saharan Africa Plasmodium vivax in Asia causes similar neurological complications and epilepsy
27
Genetic etiology
1. SCN1A | 2. sodium channel, voltage gated, type 1, alpha subunit gene located on chromosome 2q24.3
28
What is the SCN1A gene product?
Alpha subunit of the NaV1.1 sodium channel
29
What is Nav1.1 sodium channel important for?
Controlling sodium transport into neurons
30
What may polymorphosm in SCN1A gene affect?
Efficacy and adverse effects of sodium channel blocking anti-seizure medication
31
Animal models have been very successful and crucial in development of what?
Numerous clinical effective anti-epileptic drugs (AEDs) Need to have better efficacy and tolerability
32
What happens when you take 1 to 3 AEDs ?
About 70% patients obtain good seizure control about 40-60% patients experience adverse effects e.g. cognitive impairment, tiredness, skin rash, dizziness, weight gain
33
What is treated with valproate since it is cheap and effective?
Generalised epilepsies with tonic-clonic convulsuons
34
What can valproate cause?
1. Foetal malformations | 2. Affect fetal brain development
35
What can change AEDs put patients in?
1. Risk of injury | 2. Sudden unexpected death in epilepsy
36
What are the several purpose that animal model serve?
1. Discovery of novel AED 2. Evaluate the efficacy of drugs against different types of seizure or epilepsy 3. Test in specific model of AED-resistant seizure to identify difficult-to-treat types of seizure or epilepsies 4. Evaluate the effective plasma concentration of new AED for first clinical trial
37
Facial clonus (myoclonus)
1. Involuntary twitching of facial muscles
38
Convulsive seizure
A sudden, violent, irregular movement of body
39
Tonic seizure
Body, arms, legs suddenly tense
40
Clonic seizure
Jerking movements-rapidly and rhythmically
41
Electroconvulsant model: method and current used
2. Method - Place electrodes onto corneal/ear and deliver an electrocurrent for 0.2 second using an electroconvulsiometer 3. Current used - Rat: 150mA - Mouse: 50mA 4. Effective in 100% animals
42
What would the normal mouse express in the electroconvulsant model?
5. The normal mouse would typically express the following: - Clonic without losing posture - Clonic with losing posture - Tonic (Forelimb extension) and hindlimb flexion - Tonic (Forelimb extension) and partial hindlimb extension - Tonic with both forelimb and hindlimb extension
43
What does maximal electroshock seizure generate?
1. Tonic-clonic convulsion via the brainstem
44
What is the clonic movement of the forelimb related to?
Activation of structures not only in the limbic system but also the: 1. Thalamus 2. Neocortex 3. Nucleus basalis
45
Maximal electroshock seizure
1. No gross morphological change | 2. Molecular level: changes in gene expression
46
What is effective in MES?
1. phenytoin 2. Carbamazepine 3. Phenobarbital
47
What is ineffective in MES?
1. Ethosuximide
48
Phenytoin
1. prevent and control seizure | 2. Reduce spread of seizure activity in the brain
49
Carbamazepine
2. prevent and control seizure 2. known as anticonvulsant or anti-epileptic drug 3. Relieve certain types of nerve pain
50
phenobarbital
1. belongs to barbiturate 2. Treat insomnia 3. Sedative to relieve symptoms of anxiety or tension 4. Control certain types of seizure 5. Slowing down the brain and nervous system
51
Ethosuximide
1. treat absence seizures 2. can be used with valproic acid 3. Taken by mouth
52
Chemoconvulsant model - method
- 1% pentylenetetrazol (PTZ) (80-100mg/kg) | - Effective in 97% animals
53
What will the normal mice in chemoconvulsant model express?
1. Facial automatism 2. Facial and head clonus 3. Forelimb clonus 4. Forelimb clonus and rearing 5. Bilateral forelimb clonus with loss of posture 6. Jumping 7. Running and jumping 8. Running and jumping followed by tonic seizures 9. Multiple running and jumping followed by tonic seizures
54
pentylenetetrazol induced seizures
1. Induces generalised non-convulsive seizures 2. lack information on mechanism of drug action 3. Antagonise GABAergic transmission 4. Used to test for absence seizure
55
What is effective for pentylenetetrazol?
1. Ethosuximide | 2. valproate
56
What is ineffective for pentylenetetrazol?
1. Carbamazepine
57
at a molecular level, what is PTZ?
1. non-competitive antagonist of GABA A receptor | 2. Reduces the chloride conductance - minor extent the sodium and potassium conductance
58
What other receptor symptoms does PTZ affect?
1. Decrease Benzodiazepine bind capacity 2. Ionotropic and metabotropic glutamate receptors 3. ACH 4. Dopamine 5. Noradrenaline
59
What is focal seizure in rodent?
1. Direct cortical application of metal e.g. cobalt, iron 2. Direct cortical application of chemical e.g. kainate 3. Direct implantation of electrode e.g. kindled seizure
60
What is kindling?
Lasting change in brain function that results from repeated focal stimulation and leads to development of a predisposition to epileptiform convulsions
61
Kindling seizure model: electrical kindling: method
1. implantation of bipolar electrode into brain e.g. amygdala, hippocampus 2. Repetitive sub-convulsive electrical stimulation top cause a post-stumulating EEG discharge (after discharge) 3. Continue stimulation daily - eventually cause generalised convulsion
62
What would the normal rat typically express in kindling seizure model?
1. Immobility - eye closure, Twitching of vibrissae, stereotpying sniffing 2. Facial clonus and head nodding 3. Facial clonus, head nodding and forelimb clonus 4. Rearing, - bilateral forelimb clonus 5. Rearing with loss of balance and falling accompanied by generalised clonic seizure
63
What is kindling
The phenomenon of generating epilepsy in laboratory animals by means of repeated sub-threshold electrical stimulation of brain
64
What is the process of kindling very similar to?
Long term potentiation
65
What can block the process of kindling?
NMDA receptor which can be blocked by MK801
66
What are the neurophysiological changes induced by kindling?>
1. sprouting 2. Axonal growth 3. synaptic reorganisation
67
What is effective in Kindling?
1. Ethosuximide | 2. Valproate
68
What is ineffective in Kindling?
1. Carbamazepine
69
What is status epilepticus?
A seizure that last longer than 5 minutes or cluster of shorter seizures that last for 30 minutes or more
70
What is the method 1 for status epilepticus seizure model?
1. single inject with pilocarpine Rat - 400 mg/kg Mouse- 300 mg/kg
71
What is method 2 for status epilepticus seizure model?
1. Inject lithium chloride (3mmol/kg) 24 hr before pilocarpine 2. Repeatedly daily until develop status epilepticus
72
What will the normal rat express in status epliepticus seizure model?
1. An acute period that build up progressively into limbic status epilepticus which can last for 24 hr 2. A silent phase with progressive normalization of EEG and behaviour which varies from 4-44 days 3. A chronic phase with spontanous reccurent seizures
73
What has become the most popular and widely used rodent model of difficult-to-treat type of epilepsy?
1. pilocarpine model of temporal lobe epilepsy
74
What is pilocarpine?
A potent muscarinic agonist 1. trigger cholinergic activation of excitatory neurons in specific brain regions
75
What is lithium?
1. pro-inflammatory agent and cause extravasation
76
What are examples of idiopathic (spontaneous) genetically predisposed animal species?
1. Epileptic dog (generalised tonic-clonic seizure) 2. Lethargic mice (generalised absence seizure) 3. Drosophila Shaker (generalised tonic-clonic seizure)
77
What are examples of sensory stimulation of genetically predisposed animal models>
1. Senegalese baboons 2. Fayoumi epleptic chickens 3. DBA/2 mice 4. GEP rats
78
What does the treatment type of epileptic dog depend on?
1. seizure type 2. efficacy 3. Tolerability
79
Phenobarbitol (a barbiturate) in epileptic dog
1. longest history 2. First line AED in dogs 3. Oral administration 4. Chronic use 5. High bioavailability 6. Inexpensive
80
What is side effect of epileptic dog?
Sedation
81
What is risk of epileptic dog?
Hepatotoxicity
82
Pathology and mechanism of audiogenic seizures
1. All AED have been tested successfully in GEP rats
83
What is effect of AED via?
1. Na+ channel blockade 2. GABA/cl- enhancement 3. Glutamate antagonism
84
What does drug-resistance mechanism include?
1. Neuroinflammation 2. Network alteration 3. Target alteration 4. Efflux transporters

Brain PD (15 decks)

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