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