Cellular Basis of Epilepsy

Question 1

What is epilepsy?

Answer 1

Large range of conditions characterised by recurrent unprovoked epileptic seizures

Question 2

What does the clinical presentation of epilepsy result from?

Answer 2

Paroxysmal excessive, synchronous, abnormal firing patterns of neurons

Question 3

What does the specific presentation of epilepsy depend on?

Answer 3

Which part of brain affected

Question 4

What is the most common serious chronic neurological condition?

Answer 4

Epilepsy

Question 5

What is the epidemiology of epilepsy?

Answer 5

Affects all societies and strata, globally

Increased in underdeveloped countries and lower SE groups

Question 6

Why is the prevalence of epilepsy higher in underdeveloped countries and lower SE groups?

Answer 6

Primarily because people in this group develop more conditions that injure their brain > seizures

Question 7

What are the significant adverse consequences of epilepsy?

Answer 7

Physical morbidity
Psychiatric morbidity
Social morbidity
Medication side effects
Mortality

Question 8

What is an epileptic seizure?

Answer 8

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

Question 9

Does everyone have the same sort of seizure?

Answer 9

No, seizures vary from person-person and type-type

Question 10

What are the different categories of epilepsy?

Answer 10

Genetic = idiopathic/primary
Structural/metabolic = symptomatic/secondary
Unknown = cryptogenic

Question 11

What is the classification of the type of epilepsy based on?

Answer 11

Similar

• Signs
• Symptoms
• Prognosis
• Response to treatment

Question 12

Why is it important to classify the type of epilepsy a person has?

Answer 12

Choosing treatment options
Counselling patients regarding
- Aetiology
- Genetics
- Likely prognosis

Question 13

What is a partial (focal) seizure?

Answer 13

Arise in limited number of cortical neurons in one hemisphere

Question 14

What is usually the cause of a focal seizure?

Answer 14

Focal brain lesion

Question 15

Are focal seizures easy to control?

Answer 15

No, tend to be more difficult to control

Question 16

What is a generalised seizure?

Answer 16

Arise simultaneously in both hemispheres

Question 17

What is usually the cause of a generalised seizure?

Answer 17

Genetic

Question 18

What is genetic (idiopathic) epilepsy?

Answer 18

Underlying brain structurally and functionally normal

Question 19

When is the usual onset in genetic epilepsy?

Answer 19

Childhood/teenage

Question 20

Can genetic epilepsy remit?

Answer 20

Possible

Question 21

Does genetic epilepsy respond well to medication?

Answer 21

Yes

Question 22

What is structural/metabolic (symptomatic) epilepsy?

Answer 22

Seizures result from identifiable structural/functional brain abnormality

Question 23

Does structural/metabolic epilepsy remit?

Answer 23

Not commonly, because brain injury doesn’t go away

Question 24

Does structural/metabolic epilepsy respond well to medication?

Answer 24

Incompletely controlled

Question 25

What causes epilepsy?

Answer 25

Disturbance in balance between inhibition and excitation of cortical neurons and neuronal networks

Question 26

What does the imbalance between excitation and inhibition of neurons cause?

Answer 26

Neuronal networks fire in uncontrolled, hyper-synchronous, self-sustained way

Question 27

What are the possible causes of the imbalance between excitation and inhibition of neurons?

Answer 27

``` Genetic Congenital/developmental Traumatic Infectious Metabolic Drugs ```

Question 28

What can alter in neuronal network components to produce epileptic neuronal networks?

Answer 28

Loss of inhibitory neurons Gain of excitatory neurons via neurogenesis - often happens after brain injury Aberrant sprouting - can often sprout back on themselves creating auto-excitation

Question 29

What are the mechanisms by which epileptic neuronal networks are generated?

Answer 29

Alterations in neuronal network parts Alterations in intrinsic neuronal cellular excitability Alterations in synaptic transmission Alterations in extra-neuronal environment

Question 30

What is the most sensitive structure to induce seizure activity?

Answer 30

Hippocampus

Question 31

What is the epileptic remodelling that takes place in the hippocampus?

Answer 31

Cell loss Mossy fibre sprouting Gliosis

Question 32

What is the relationship between epileptogenesis and disease progression?

Answer 32

Seizures beget seizures

Question 33

What is the disease progression of epilepsy?

Answer 33

``` Drug resistance Neuronal loss Synaptic reorganisation Neurocognitive changes Psychiatric changes ```

Question 34

When is the onset of epilepsy?

Answer 34

Common at all ages | Peaks in young and old

Question 35

What is the aetiology of new onset epilepsy in infancy and early childhood?

Answer 35

Most commonly congenital or perinatal CNS insults

Question 36

What is the aetiology of new onset epilepsy in late childhood and early adulthood?

Answer 36

Most commonly idiopathic/genetic

Question 37

What is the aetiology of new onset epilepsy in adulthood and the elderly?

Answer 37

Most symptomatic - Trauma - Ischaemia - Tumours - Haemorrhange - Degenerative diseases

Question 38

What is the cause of genetic epilepsies?

Answer 38

5-10% Mendelian monogenic inheritance pattern | Most have complex inheritance patterns

Question 39

How are pathologies of the brain identified in focal epilepsy?

Answer 39

MRI

Question 40

What is the most common pathology in adults with partial epilepsy?

Answer 40

Mesial temporal sclerosis

Question 41

What is the prognosis of epilepsy when the pathology is mesial temporal sclerosis?

Answer 41

Most patients continue to have seizures despite medication | Good prognosis with surgery

Question 42

What are the MRI features of partial epilepsy with a pathology of mesial temporal sclerosis?

Answer 42

Unilateral hippocampal atrophy Increased T2 signal Decreased T1 signal Loss of internal architecture

Question 43

What is focal cortical dysplasia?

Answer 43

Focal regions of disturbed cortical development and architecture

Question 44

What is the aetiology of focal cortical dysplasia?

Answer 44

Uncertain

Question 45

What are the MIR features of focal cortical dysplasia?

Answer 45

Focal thickening of cerebral cortex Blurring of grey/white interface Gyral abnormalities May be associated with region of increased T2 signal

Question 46

What is the prognosis of focal cortical dysplasia?

Answer 46

Almost always drug resistant | If focal, respond well to surgery

Question 47

What is periventricular nodular heterotopia?

Answer 47

Generalised malformation due to abnormal neuronal migration Nodular masses of grey matter diffusely lining ventricular walls - Bilateral or focal

Question 48

What is the cortical and neurological functioning like in periventricular nodular heterotopia?

Answer 48

Normal

Question 49

What proportion of people with partial epilepsy have low grade tumours?

Answer 49

15%

Question 50

What proportion of people with chronic drug resistant partial epilepsy have vascular lesions?

Answer 50

10%

Question 51

What is focal encephalomalacia?

Answer 51

Focal lesion from previous destructive insult, especially - Trauma - Stroke - Infection

Question 52

What are the MRI features of focal encephalomalacia?

Answer 52

Irregular area of atrophy of cerebral cortex and underlying white matter Surrounding region of increased T2 signal May be associated with large cystic region

Question 53

What are anti-epileptic drugs?

Answer 53

Decrease frequency and/or severity of seizures in people with epilepsy

Question 54

Do anti-epileptic drugs treat the underlying epileptic condition?

Answer 54

No, treat symptoms; ie: seizures

Question 55

What proportion of people have drug resistant epilepsy?

Answer 55

30%

Question 56

What are non-medical treatments for epilepsy?

Answer 56

Often adjunct to medications Surgery Neurostimulators Dietary

Question 57

What kinds of epilepsy can be treated with surgery?

Answer 57

Focal epilepsy where origin of seizures can be localised to brain region that can be resected with low risk of significant damage afterwards