Transcript Slide 1
Epilepsy Rady 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. • 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 • 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) 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 • 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 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 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 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. Chromosome 15 • Microdeletions in chromosome 15q13.3 • Deletions found only in patient and not in controls. • Study in 2009 in Nature Genetics 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 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 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 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? Conclusion • • • • Many types of epilepsy Many chromosomes, many genes Not all found or known Not all genotype problems results in phenotype