Cellular Basis of Epilepsy Flashcards
What is epilepsy?
Large range of conditions characterised by recurrent unprovoked epileptic seizures
What does the clinical presentation of epilepsy result from?
Paroxysmal excessive, synchronous, abnormal firing patterns of neurons
What does the specific presentation of epilepsy depend on?
Which part of brain affected
What is the most common serious chronic neurological condition?
Epilepsy
What is the epidemiology of epilepsy?
Affects all societies and strata, globally
Increased in underdeveloped countries and lower SE groups
Why is the prevalence of epilepsy higher in underdeveloped countries and lower SE groups?
Primarily because people in this group develop more conditions that injure their brain > seizures
What are the significant adverse consequences of epilepsy?
Physical morbidity Psychiatric morbidity Social morbidity Medication side effects Mortality
What is an epileptic seizure?
Transient occurrence of clinical signs and/or symptoms due to excessive and hyper-synchronous activity of populations of neurons in brain
Does everyone have the same sort of seizure?
No, seizures vary from person-person and type-type
What are the different categories of epilepsy?
Genetic = idiopathic/primary Structural/metabolic = symptomatic/secondary Unknown = cryptogenic
What is the classification of the type of epilepsy based on?
Similar
- Signs
- Symptoms
- Prognosis
- Response to treatment
Why is it important to classify the type of epilepsy a person has?
Choosing treatment options Counselling patients regarding - Aetiology - Genetics - Likely prognosis
What is a partial (focal) seizure?
Arise in limited number of cortical neurons in one hemisphere
What is usually the cause of a focal seizure?
Focal brain lesion
Are focal seizures easy to control?
No, tend to be more difficult to control
What is a generalised seizure?
Arise simultaneously in both hemispheres
What is usually the cause of a generalised seizure?
Genetic
What is genetic (idiopathic) epilepsy?
Underlying brain structurally and functionally normal
When is the usual onset in genetic epilepsy?
Childhood/teenage
Can genetic epilepsy remit?
Possible
Does genetic epilepsy respond well to medication?
Yes
What is structural/metabolic (symptomatic) epilepsy?
Seizures result from identifiable structural/functional brain abnormality
Does structural/metabolic epilepsy remit?
Not commonly, because brain injury doesn’t go away
Does structural/metabolic epilepsy respond well to medication?
Incompletely controlled
What causes epilepsy?
Disturbance in balance between inhibition and excitation of cortical neurons and neuronal networks
What does the imbalance between excitation and inhibition of neurons cause?
Neuronal networks fire in uncontrolled, hyper-synchronous, self-sustained way
What are the possible causes of the imbalance between excitation and inhibition of neurons?
Genetic Congenital/developmental Traumatic Infectious Metabolic Drugs
What can alter in neuronal network components to produce epileptic neuronal networks?
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
What are the mechanisms by which epileptic neuronal networks are generated?
Alterations in neuronal network parts
Alterations in intrinsic neuronal cellular excitability
Alterations in synaptic transmission
Alterations in extra-neuronal environment
What is the most sensitive structure to induce seizure activity?
Hippocampus
What is the epileptic remodelling that takes place in the hippocampus?
Cell loss
Mossy fibre sprouting
Gliosis
What is the relationship between epileptogenesis and disease progression?
Seizures beget seizures
What is the disease progression of epilepsy?
Drug resistance Neuronal loss Synaptic reorganisation Neurocognitive changes Psychiatric changes
When is the onset of epilepsy?
Common at all ages
Peaks in young and old
What is the aetiology of new onset epilepsy in infancy and early childhood?
Most commonly congenital or perinatal CNS insults
What is the aetiology of new onset epilepsy in late childhood and early adulthood?
Most commonly idiopathic/genetic
What is the aetiology of new onset epilepsy in adulthood and the elderly?
Most symptomatic
- Trauma
- Ischaemia
- Tumours
- Haemorrhange
- Degenerative diseases
What is the cause of genetic epilepsies?
5-10% Mendelian monogenic inheritance pattern
Most have complex inheritance patterns
How are pathologies of the brain identified in focal epilepsy?
MRI
What is the most common pathology in adults with partial epilepsy?
Mesial temporal sclerosis
What is the prognosis of epilepsy when the pathology is mesial temporal sclerosis?
Most patients continue to have seizures despite medication
Good prognosis with surgery
What are the MRI features of partial epilepsy with a pathology of mesial temporal sclerosis?
Unilateral hippocampal atrophy
Increased T2 signal
Decreased T1 signal
Loss of internal architecture
What is focal cortical dysplasia?
Focal regions of disturbed cortical development and architecture
What is the aetiology of focal cortical dysplasia?
Uncertain
What are the MIR features of focal cortical dysplasia?
Focal thickening of cerebral cortex
Blurring of grey/white interface
Gyral abnormalities
May be associated with region of increased T2 signal
What is the prognosis of focal cortical dysplasia?
Almost always drug resistant
If focal, respond well to surgery
What is periventricular nodular heterotopia?
Generalised malformation due to abnormal neuronal migration
Nodular masses of grey matter diffusely lining ventricular walls
- Bilateral or focal
What is the cortical and neurological functioning like in periventricular nodular heterotopia?
Normal
What proportion of people with partial epilepsy have low grade tumours?
15%
What proportion of people with chronic drug resistant partial epilepsy have vascular lesions?
10%
What is focal encephalomalacia?
Focal lesion from previous destructive insult, especially
- Trauma
- Stroke
- Infection
What are the MRI features of focal encephalomalacia?
Irregular area of atrophy of cerebral cortex and underlying white matter
Surrounding region of increased T2 signal
May be associated with large cystic region
What are anti-epileptic drugs?
Decrease frequency and/or severity of seizures in people with epilepsy
Do anti-epileptic drugs treat the underlying epileptic condition?
No, treat symptoms; ie: seizures
What proportion of people have drug resistant epilepsy?
30%
What are non-medical treatments for epilepsy?
Often adjunct to medications
Surgery
Neurostimulators
Dietary
What kinds of epilepsy can be treated with surgery?
Focal epilepsy where origin of seizures can be localised to brain region that can be resected with low risk of significant damage afterwards
