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Neuroscience > Cellular basis of epilepsy > Flashcards

Cellular basis of epilepsy Flashcards

1
Q

Define epilepsy?

A

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

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2
Q

What do the clinical manifestations of epilepsy arise from?

A

Paroxysmal excessive, synchronous, abnormal firing patterns of neurons

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3
Q

Describe the lifetime prevalence of seizures?

A

9%

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

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4
Q

Describe the lifetime incidence of epilepsy?

A

2-4%

2-4% of people will develop epilepsy

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5
Q

What is the most common serious chronic neurologic condition?

A

Epilepsy

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6
Q

What is the point prevalence of epilepsy?

A
  1. 5-1%
  2. 5-1% of people have active epilepsy at any one point in time
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7
Q

In which populations is epilepsy more prevalent?

A

Underdeveloped countries

Lower socioeconomic groups

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8
Q

Describe the groups of adverse consequences associated with epilepsy?

A

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

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9
Q

Describe the mortality ratio for epilepsy?

A

Standardised mortality ratio is approximately 3.0 vs general population

Higher in symptomatic vs idiopathic epilepsies

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10
Q

What are the major causes of death associated with epilepsy?

A

Accidental injury

Drowning

Asphyxia

Staus epilepticus

Suicide

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11
Q

What is SUDEP?

A

Sudden unexplained death in epilepsy

Epileptics found dead, with no explanation

Could be direct consequence of seizure, but mechanism is unknown

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12
Q

In which population is SUDEP significant?

A

Most common cause of death in young people with epilepsy

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13
Q

Define an epileptic seizure?

A

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

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14
Q

What determines the clinical manifestations of epilepsy?

A

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

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15
Q

What are the three major groups of causes of epilepsy?

A

Genetic (idiopathic/primary)

Strucural/metabolic (symptomatic/secondary)

Unknown (crytpogenic)

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16
Q

Describe the ILAE classification of seizures and epilepsy?

A

Seizures: based on clinical features and EEG findings

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

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17
Q

Describe the ILAE classification of seizures?

A

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

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18
Q

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

A

Structural or metabolic abnormalities

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19
Q

When does epilepsy due to genetic causes usually arise?

A

Childhood/teenage years

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20
Q

Does epilepsy often remit?

A

Often remits if due to genetic causes

Rarely remits if due to structural or metabolic causes

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21
Q

Which causes of epilepsy are well controlled with medication?

A

Genetic usually controlled

Structural or metabolic often incompletely controlled

22
Q

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

A

More common with age >20

Major cause in elderly patients

23
Q

Why is diagnosis of epilepsy so important?

A

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

Treatment: medical and surgical

Genetic implications

24
Q

What is the current idea of the cause of epilepsy?

A

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
Q

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

A

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
Q

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

A

Hippocampus

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

27
Q

Desribe the circuitry of the hippocampus?

A

Unidirectional circuitry

EC > DG > CA3 > CA1 > EC

28
Q

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

A

Mesial temporal sclerosis

29
Q

Describe the relationship between epileptogensis and disease progression?

A

Changes continue to evolve as disease becomes chronic

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

30
Q

What are the markers of disease progression in epilepsy?

A

Refractoriness

Neuronal loss

Synaptic reorganisation

Neurocognitive changes

Psychiatric changes

31
Q

Describe the relationship between age and epilespy incidence?

A

New onset epilepsy is common at all ages

Bimodal peak for very young and very old

32
Q

Describe the relationship between age and epilepsy aetiology?

A

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
Q

Describe the causes of idiopathic generalised epilepsies (IGE)?

A

Believed to be genetically determined

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

34
Q

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

A

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

35
Q

What is the most important imaging modality in epilepsy evaluation?

A

MRI

36
Q

What is the most common epileptic lesion detected on MRI?

A

Mesial temporal sclerosis (49.1%)

37
Q

Describe treatment options for epilepsy due to mesial temporal sclerosis?

A

Most patients refractory to medical therapy

Good prognosis with surgery

38
Q

Describe the appearrance of mesial temporal sclerosis on MRI?

A

Hippocampal atrophy

Increased T2 signal

Decreased T1 singal

Loss of internal architecture

39
Q

What is focal cortical dysplasia?

Describe its appearance on MRI?

A

Focal regions of disturbed cortical development and architecture

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

40
Q

What is periventricular nodular heterotopia?

A

A generalised malformation due to abnormal neuronal migration

Nodular masses of grey matter diffusely lining ventricular walls

41
Q

How commonly are low grade tumours the cause of epilepsy?

A

Approx 15% of pateints with partial epilepsy

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

42
Q

Which type of low grade tumour most commonly causes epilepsy?

A

Gliomas (72-88%)

43
Q

How commonly are vascular lesions the cause of epilepsy?

A

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

44
Q

Which types of vascular lesions can cause epilepsy?

A

Cavernomas

Arteriovenous malformations

45
Q

What are cavernomas?

A

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

46
Q

What is focal encephalomalacia?

A

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

47
Q

Describe the broad classes of treatment options for epilepsy?

A

Anti-epileptic drugs

Surgery

48
Q

Describe the rationale and effectiveness of anti-epileptic drugs?

A

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
Q

When is surgery an appropriate treatment option for epilepsy?

A

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
Q

Describe the current treatment gaps in epilepsy?

A

Medically refractory seizures are common

Poor medication tolerability

No anti-epileptogenic or disease modifying treaments

No treatments for co-morbidities

Neuroscience (51 decks)

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