Cellular basis of epilepsy Flashcards Preview

Neuroscience > Cellular basis of epilepsy > Flashcards

Flashcards in Cellular basis of epilepsy Deck (50):
1

Define epilepsy?

Large range of conditions characterised by recurrent unprovoked epileptic seizures

 

A group of neurological diseases with enduring alterations in the brain resulting in abnormally increased predisposition to seizures 

2

What do the clinical manifestations of epilepsy arise from?

Paroxysmal excessive, synchronous, abnormal firing patterns of neurons 

3

Describe the lifetime prevalence of seizures?

9%

9% of people will have a seizure at some stage in their life

 

4

Describe the lifetime incidence of epilepsy?

2-4%

2-4% of people will develop epilepsy

5

What is the most common serious chronic neurologic condition?

Epilepsy

6

What is the point prevalence of epilepsy?

0.5-1%

0.5-1% of people have active epilepsy at any one point in time 

7

In which populations is epilepsy more prevalent?

Underdeveloped countries

Lower socioeconomic groups 

8

Describe the groups of adverse consequences associated with epilepsy?

Physical morbidity: injury, cognitive, medical

Psychiatric morbidity: high rates of depression, anxiety and psychosis

Social morbidity: restrictions of having epilepsy, prejudice

Medication side effects

Mortality

A image thumb
9

Describe the mortality ratio for epilepsy?

Standardised mortality ratio is approximately 3.0 vs general population 

Higher in symptomatic vs idiopathic epilepsies

10

What are the major causes of death associated with epilepsy?

Accidental injury

Drowning

Asphyxia

Staus epilepticus

Suicide

11

What is SUDEP?

Sudden unexplained death in epilepsy

Epileptics found dead, with no explanation 

Could be direct consequence of seizure, but mechanism is unknown

12

In which population is SUDEP significant?

Most common cause of death in young people with epilepsy

13

Define an epileptic seizure?

Transient occurrence of clinical signs and/or symptoms due to excessive and hyper-synchronous activity of populations of neurons in the brain

 

Groupd of neurons that usually fire individually get into a loop and fire as a group, with recurrent activation

A image thumb
14

What determines the clinical manifestations of epilepsy?

The region of the brain involved in the seizure, at onset and from secondary spread

15

What are the three major groups of causes of epilepsy?

Genetic (idiopathic/primary)

Strucural/metabolic (symptomatic/secondary)

Unknown (crytpogenic)

16

Describe the ILAE classification of seizures and epilepsy?

Seizures: based on clinical features and EEG findings

Epilepsies and epileptic syndromes: epileptic disorders with similar signs, symptoms, prognosis and response to treatment  

17

Describe the ILAE classification of seizures?

Partial/focal seizures: arise in a limited number of cortical neurones within one hemisphere

Generalised seizures: appear to arise simultaneously in both hemispheres

Unclassifiable seizures

18

What is the most common cause of partial/focal seizures?

 

Structural or metabolic abnormalities

19

When does epilepsy due to genetic causes usually arise?

Childhood/teenage years

20

Does epilepsy often remit?

Often remits if due to genetic causes

Rarely remits if due to structural or metabolic causes

21

Which causes of epilepsy are well controlled with medication?

Genetic usually controlled

Structural or metabolic often incompletely controlled

22

When does epilepsy due to a structural or metabolic abnormality usually arise?

More common with age >20

Major cause in elderly patients

 

23

Why is diagnosis of epilepsy so important?

Prognosis: treatment response, likelihood of remission, development of co-morbidities

Treatment: medical and surgical

Genetic implications

24

What is the current idea of the cause of epilepsy?

Disturbance in the balance between inhibition and excitation of cortical neurones and neuronal networks

 

Results in neuronal networks that fire in an uncontrolled, hyper-synchronous, self-sustained manner

25

Descibe the alterations in neuronal networks that may occur in epilepsy?

Loss of inhibitory neurons

 

Gain of excitatory neurons (neurogenesis - brain tries to repair itself after injury)

Abberant sprouting

 

Alterations in intrinsic neuronal cellular excitability

Alterations in synaptic transmission

Alterations in the extra-neuronal environment 

 

26

Which is the most sensitive brain stucture to induce seizure activity? 

Hippocampus

 

(in picture, the epileptic hippocampus on the left is amller than the control on the right)

A image thumb
27

Desribe the circuitry of the hippocampus?

Unidirectional circuitry

EC > DG > CA3 > CA1 > EC

A image thumb
28

Which disease process in the hippocampus most commonly leads to epilepsy?

Mesial temporal sclerosis

A image thumb
29

Describe the relationship between epileptogensis and disease progression?

Changes continue to evolve as disease becomes chronic

Seizures themselves accelerate changes and lead to the development of more seizures 

A image thumb
30

What are the markers of disease progression in epilepsy?

Refractoriness

Neuronal loss

Synaptic reorganisation

Neurocognitive changes

Psychiatric changes

31

Describe the relationship between age and epilespy incidence?

New onset epilepsy is common at all ages

Bimodal peak for very young and very old 

A image thumb
32

Describe the relationship between age and epilepsy aetiology?

Infancy/early childhood: most common congenital perinatal insults

Late childhood/early adulthood: most common idiopathic/genetic

Adult/elderly: most symptomatic (trauma, ischaemia, tumours, haemorrhage, degenerative disease)

33

Describe the causes of idiopathic generalised epilepsies (IGE)?

Believed to be genetically determined

Thought to be multiple polymorphisms in ion channel or non-ion channel genes

34

Describe the relationship between genetics and those that develop epilepsy after trauma?

Patients that develop epilepsy after trauma are three times more likely to have a genetic disposition to developing epilepsy

35

What is the most important imaging modality in epilepsy evaluation?

MRI

36

What is the most common epileptic lesion detected on MRI?

Mesial temporal sclerosis (49.1%)

37

Describe treatment options for epilepsy due to mesial temporal sclerosis?

Most patients refractory to medical therapy

Good prognosis with surgery 

38

Describe the appearrance of mesial temporal sclerosis on MRI?

Hippocampal atrophy

Increased T2 signal

Decreased T1 singal

Loss of internal architecture 

A image thumb
39

What is focal cortical dysplasia?

Describe its appearance on MRI?

Focal regions of disturbed cortical development and architecture

MRI: focal thickening of cortex, blurring of grey/white interface, gyral abnormalities, increased T2 signal

A image thumb
40

What is periventricular nodular heterotopia?

A generalised malformation due to abnormal neuronal migration 

Nodular masses of grey matter diffusely lining ventricular walls 

A image thumb
41

How commonly are low grade tumours the cause of epilepsy?

Approx 15% of pateints with partial epilepsy

Most common cause of new onset partial seizures 35-55 years

42

Which type of low grade tumour most commonly causes epilepsy?

Gliomas (72-88%)

43

How commonly are vascular lesions the cause of epilepsy?

Approx 10% of patients with chronic drug-resistant partial epilepsy

44

Which types of vascular lesions can cause epilepsy?

Cavernomas

Arteriovenous malformations 

45

What are cavernomas?

A tangled mass of tightly arranged abnormal vessels made of common hypocellular walls 

46

What is focal encephalomalacia?

Focal lesion resulting from previous destructive insult (eg. trauma, stroke, infection)

47

Describe the broad classes of treatment options for epilepsy?

Anti-epileptic drugs

Surgery

48

Describe the rationale and effectiveness of anti-epileptic drugs?

Decrease frequency of seizures by altering innate excitability of neuorns 

Treats the symtpoms, not underlying condition

Need to be taken for years, often lifetime 

49

When is surgery an appropriate treatment option for epilepsy?

Continuing seizures despite adequate trials of several appropriate anti-epileptic drugs

A surgically remediable epileptic syndrome (focal epilepsy where the origin of the seizures can be localised to a brain region that can be resected safely)

50

Describe the current treatment gaps in epilepsy?

Medically refractory seizures are common

Poor medication tolerability

No anti-epileptogenic or disease modifying treaments

No treatments for co-morbidities