Class 8: Neurogenetics Course Disease Focus
Epilepsy
Epilepsy
- Frequent
o Prevalence 4-10/1000
o 1/26 develops epilepsy during life
- Central symptom = epileptic attack, seizure
o Abnormal excitation somewhere in the brain and synchronization of
(sub)population of cortical neurons
§ Cortical disorder = disease of the cortical neurons
o Paroxysmal and uncontrolled
o Stereotypic seizures within people
§ Very diverse between people
o Recurrent
§ 5-10%single epileptic attack
§ Epilepsy=≥2spontaneous epileptic attacks in <24h
- ≠ 1 disease, but group of disorders
- Many diTerent
o Etiologies
o Presentations: generalized seizures, focal seizure…
o Prognoses between epilepsies can diTerent
§ Age dependent/Lifelong
§ Treatable/Therapy resistant (30%)
• A lot of people are resistant
§ Only epilepsy/Associated symptoms
§ Mental retardation, ataxia, dyskinesia...
- Examples; drop seizures, hypermotor seizures (start in the frontal lobar node), very
long seizures …
EEG
- Technical examination
- Measures electricity of the brain mostly of the superficial cortex -> so it has its
limitations
, - During seizure we can measure epileptic activity and zonetimes between seizures
we can detect interictal activity -> tells something about the location or onset of
the seizures
- It can tell us something about the type of epilepsy
o Focal: localized at a specific part of the brain
- Treatment: pure symptomatic, work on the ion channels
Challenges
- > 6 million people with epilepsy in Europe, > 50 million worldwide
- Estimated annual health care and societal cost of 16 billion euros
- >20 anti-seizure drugs=>seizure control in 2/3 of patients
o No treatments that prevent development of epilepsy
o 30% of patients treatment resistant
o 30% of patients adverse advents
o Symptomatic treatment until now -> 30% shows resistant and all the drugs
influence neuronal activity which lead to adverse eTects
- Need/Opportunity for studies on disease mechanisms and identification of novel
drug targets
=> Precision Medicine
Etiology of epilepsy – role of genetics
- How knowledge about epilepsy has changed over time.
- Epilepsy can have an infectious cause, tumors…
- Idiopathic = cause not know -> now: part because of lesions, but most of them
have a genetic cause (monogenetic and epilepsies with a more complex
architecture)
Genetic architecture of the epilepsies
- It is a spectrum: epilepsies that are purely genetic (these are rare), epilepsies that
are purely acquired but then you have also much in between
o Polygenetic epilepsy
o Not everyone with a stroke will have epilepsy -> genetic will play a role
Epilepsy
Epilepsy
- Frequent
o Prevalence 4-10/1000
o 1/26 develops epilepsy during life
- Central symptom = epileptic attack, seizure
o Abnormal excitation somewhere in the brain and synchronization of
(sub)population of cortical neurons
§ Cortical disorder = disease of the cortical neurons
o Paroxysmal and uncontrolled
o Stereotypic seizures within people
§ Very diverse between people
o Recurrent
§ 5-10%single epileptic attack
§ Epilepsy=≥2spontaneous epileptic attacks in <24h
- ≠ 1 disease, but group of disorders
- Many diTerent
o Etiologies
o Presentations: generalized seizures, focal seizure…
o Prognoses between epilepsies can diTerent
§ Age dependent/Lifelong
§ Treatable/Therapy resistant (30%)
• A lot of people are resistant
§ Only epilepsy/Associated symptoms
§ Mental retardation, ataxia, dyskinesia...
- Examples; drop seizures, hypermotor seizures (start in the frontal lobar node), very
long seizures …
EEG
- Technical examination
- Measures electricity of the brain mostly of the superficial cortex -> so it has its
limitations
, - During seizure we can measure epileptic activity and zonetimes between seizures
we can detect interictal activity -> tells something about the location or onset of
the seizures
- It can tell us something about the type of epilepsy
o Focal: localized at a specific part of the brain
- Treatment: pure symptomatic, work on the ion channels
Challenges
- > 6 million people with epilepsy in Europe, > 50 million worldwide
- Estimated annual health care and societal cost of 16 billion euros
- >20 anti-seizure drugs=>seizure control in 2/3 of patients
o No treatments that prevent development of epilepsy
o 30% of patients treatment resistant
o 30% of patients adverse advents
o Symptomatic treatment until now -> 30% shows resistant and all the drugs
influence neuronal activity which lead to adverse eTects
- Need/Opportunity for studies on disease mechanisms and identification of novel
drug targets
=> Precision Medicine
Etiology of epilepsy – role of genetics
- How knowledge about epilepsy has changed over time.
- Epilepsy can have an infectious cause, tumors…
- Idiopathic = cause not know -> now: part because of lesions, but most of them
have a genetic cause (monogenetic and epilepsies with a more complex
architecture)
Genetic architecture of the epilepsies
- It is a spectrum: epilepsies that are purely genetic (these are rare), epilepsies that
are purely acquired but then you have also much in between
o Polygenetic epilepsy
o Not everyone with a stroke will have epilepsy -> genetic will play a role
