Epilepsy

1. Epilepsy Rady

2. Introduction • Epilepsy is chronic neurological disorder • Characterized by recurrent unprovoked seizures • Seizures are transient signs of abnormal, excessive or synchronous neural activity • 50 million worldwide. 90% in developing countries • More in young children and over 65, but can occur anytime.

3. Epilepsy can only be controlled, not cured. • However 30 % are not able to be controlled. • Not a single disorder but convergence of vastly divergent symptoms involving episodic abnormal electrical activity in brain. • Classified by • Cause • Observable manifestations • Location • Identified medical syndromes • Trigger

4. Can be partial or generalized • 40 different types • Children behaviors include • Inattentive staring • Benign shudders • Nodding, rocking, head banging • Conversion disorder (flailing and jerking of the head)

5. Management of seizure • Prevent patient from self-injury • Snoring indicates normal breathing • If reguritation occurs, place in recovery position • Emergency medical treatment needed for >5 mins • Do not place objects in mouth. • Let seizure take its own course • Surgery very rare, for those meds cannot control – or tumor or arteriovenous malformations

6. Patients often exhausted and confused • Occasionally, patients lose bladder and or bowel control • Anticonvulsant medication • Often lifelong • Can have major effects on quality of life • Earliest is bromide (1857) • Potassium bromide – impotence in men. • Phenobarbital (1912) • Phenytoin (1930) • Currently about 20 common ones

7. The genetics • Mutations in several genes linked to some types of epilepsy • Mainly in protein subunits of voltage-gated and ligand-gated ion channels • Some inherited ones believed to be genes for: • sodium ion channels (stay open too long) • Glutamate neurotransmitter (Ca2+) • GABA

8. Chromosome 10 • Partial epilepsy - originally thought to be from head injury, vascular disease or brain development problems • Chromosome 10 • Single family study (8-19 yrs old onset for 11 members) • Humming noise before seizure, twitching on one side. • Actual mutation not found, but narrowed to Chromosome 10

9. Extra X, Y and epilepsy • Extra X in women • Extra Y in men • XO women • Sex chromosome extra or lacking thereof, linked with higher epilepsy counterparts than their healthy counterparts.

10. Chromosome 15 • Microdeletions in chromosome 15q13.3 • Deletions found only in patient and not in controls. • Study in 2009 in Nature Genetics

11. Chromosome 3, 18 • Febril seizures most common of children. • 2-5% children affected in USA. • Mostly no permanent damage, but small develop epilepsy later in life. • French family study – 4 Generation • Chromosome 3 and 18. • Gene on 18 believed to be modifier. • Exact gene not found

12. Chromosome 8p • Progressive epilepsy with mental retardation (EPMR) is autosomal recessive disorder • EPMR mapped to chromosome 8p23. • Childhood onset epilepsy and mental retardation (ages 5-10) tonic-clonic seizures. • EPMR in telomeric region of 8p

13. Chromosome 6 • LaFora disease – aggressive epilepsy • Presence of glycogen-like Lafora bodies in brain • Autosomal recessive mutation of EPM2A on chromosome 6 • Gene produces phosphatase laforin • Loss of function EPM2A function results in disease

14. Ring Chromosomes • RC20 – not all develop epilepsy, but present in many. • Refractory epilepsy • Fusion by 2 arms of the chromosome during development • RC17 also found • Deletion at 17p • 17q telomere undeleted. • Ring chromosome and epilepsy linkage?

15. Conclusion • Many types of epilepsy • Many chromosomes, many genes • Not all found or known • Not all genotype problems results in phenotype