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 gt5 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