Cellular basis of epilepsy Flashcards
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
What do the clinical manifestations of epilepsy arise from?
Paroxysmal excessive, synchronous, abnormal firing patterns of neurons
Describe the lifetime prevalence of seizures?
9%
9% of people will have a seizure at some stage in their life
Describe the lifetime incidence of epilepsy?
2-4%
2-4% of people will develop epilepsy
What is the most common serious chronic neurologic condition?
Epilepsy
What is the point prevalence of epilepsy?
- 5-1%
- 5-1% of people have active epilepsy at any one point in time
In which populations is epilepsy more prevalent?
Underdeveloped countries
Lower socioeconomic groups
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
Describe the mortality ratio for epilepsy?
Standardised mortality ratio is approximately 3.0 vs general population
Higher in symptomatic vs idiopathic epilepsies
What are the major causes of death associated with epilepsy?
Accidental injury
Drowning
Asphyxia
Staus epilepticus
Suicide
What is SUDEP?
Sudden unexplained death in epilepsy
Epileptics found dead, with no explanation
Could be direct consequence of seizure, but mechanism is unknown
In which population is SUDEP significant?
Most common cause of death in young people with epilepsy
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
What determines the clinical manifestations of epilepsy?
The region of the brain involved in the seizure, at onset and from secondary spread
What are the three major groups of causes of epilepsy?
Genetic (idiopathic/primary)
Strucural/metabolic (symptomatic/secondary)
Unknown (crytpogenic)
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
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
What is the most common cause of partial/focal seizures?
Structural or metabolic abnormalities
When does epilepsy due to genetic causes usually arise?
Childhood/teenage years
Does epilepsy often remit?
Often remits if due to genetic causes
Rarely remits if due to structural or metabolic causes
Which causes of epilepsy are well controlled with medication?
Genetic usually controlled
Structural or metabolic often incompletely controlled
When does epilepsy due to a structural or metabolic abnormality usually arise?
More common with age >20
Major cause in elderly patients
Why is diagnosis of epilepsy so important?
Prognosis: treatment response, likelihood of remission, development of co-morbidities
Treatment: medical and surgical
Genetic implications
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
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
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)
Desribe the circuitry of the hippocampus?
Unidirectional circuitry
EC > DG > CA3 > CA1 > EC
Which disease process in the hippocampus most commonly leads to epilepsy?
Mesial temporal sclerosis
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
What are the markers of disease progression in epilepsy?
Refractoriness
Neuronal loss
Synaptic reorganisation
Neurocognitive changes
Psychiatric changes
Describe the relationship between age and epilespy incidence?
New onset epilepsy is common at all ages
Bimodal peak for very young and very old
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)
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
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
What is the most important imaging modality in epilepsy evaluation?
MRI
What is the most common epileptic lesion detected on MRI?
Mesial temporal sclerosis (49.1%)
Describe treatment options for epilepsy due to mesial temporal sclerosis?
Most patients refractory to medical therapy
Good prognosis with surgery
Describe the appearrance of mesial temporal sclerosis on MRI?
Hippocampal atrophy
Increased T2 signal
Decreased T1 singal
Loss of internal architecture
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
What is periventricular nodular heterotopia?
A generalised malformation due to abnormal neuronal migration
Nodular masses of grey matter diffusely lining ventricular walls
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
Which type of low grade tumour most commonly causes epilepsy?
Gliomas (72-88%)
How commonly are vascular lesions the cause of epilepsy?
Approx 10% of patients with chronic drug-resistant partial epilepsy
Which types of vascular lesions can cause epilepsy?
Cavernomas
Arteriovenous malformations
What are cavernomas?
A tangled mass of tightly arranged abnormal vessels made of common hypocellular walls
What is focal encephalomalacia?
Focal lesion resulting from previous destructive insult (eg. trauma, stroke, infection)
Describe the broad classes of treatment options for epilepsy?
Anti-epileptic drugs
Surgery
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
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)
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
