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Pediatric Epilepsy
Ashley MasseArif Mohamed
Rosalie NguyenYusuf Majumder
PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson
Epilepsy is a neurological disorder change in normal brain function.
Epilepsy is not generally an inherited disease.
Typically characterized by seizures. About 0.6% of the Canadian population has
Epilepsy.
What is Epilepsy?
There are two major types of epilepsy Idiopathic Epilepsy- no known cause Secondary/Somatic Epilepsy- the cause is
attributed to a specific event (such as genetic conditions, hitting ones head, or stroke).
Epilepsy is further classified by the type of seizure the person experiences.
Types include: generalized tonic-clonic, absence, myoclonic, and partial.
Types of Epilepsy/ Classifications
Who Does it Affect? It is estimated that there are 15,500 new cases of
epilepsy diagnosed each year in Canada. 44% are diagnosed before the age of 5. 55% before the age of 10. 75-85% before age 18.
Age (years) Prevalence (%)*
0-11 0.3
12-14 0.6
16-24 0.6
25-44 0.7
46-64 0.7
> 65 0.7
About 50% of children “grow out” of the disorder and experience a complete disappearance of seizures.
Some of those who continue to have seizures into adulthood often notice a decrease in intensity and frequency.
Childhood Epilepsy
Neonatal period BENIGN IDIOPATHIC NEONATAL SEIZURES (BINS)
Rare idiopathic syndrome often generalized BENIGN FAMILIAL NEONATAL-INFANTILE
SEIZURES (BFNIS) Genetic based idiopathic syndrome
EARLY INFANTILE EPILEPTIC ENCEPHALOPATH (EIEE) Rare, but severe encephalopathic form with
symptomatic root
Epilepsy Syndromes By Age of Onset
Infancy• WEST SYNDROME
• symptomatic, cryptogenic (nonidentifiable hidden cause)
• Between 4 and 7 month• MYOCLONIC EPILEPSY IN INFANCY (MEI)
• Rare, idiopathic generalized• Between the ages of 6 months and 3 years
• DRAVET SYNDROME• Rare, symptomatic• Cases with mutations in the SCN1A gene
Epilepsy Syndromes By Age of Onset
Childhood• BENIGN CHILDHOOD EPILEPSY WITH
CENTROTEMPORAL SPIKES• Most common idiopathic epilepsy syndrome,
representing 24% of epilepsy cases among school age children
• LENNOX-GASTAUT SYNDROME (LGS)• Onset is 2nd to 6th year of life• accompanied by developmental delay and
psychological and behavioral problems• LANDAU-KLEFFNER SYNDROME (LKS)
• Peak onset between the ages of 3 and 7 years• Two-thirds of affected children are male
Epilepsy Syndromes By Age of Onset
Underlying Causes of Pediatric Epilepsy
1) Abnormalities in the glial cells (Glial cells and the blood-brain barrier are still developing).
2) Differences in the activity of ion channels as well as the release of neurotransmitters (Glutamate and GABA).
3) Role of structural anomalies (Lesions)
4) Genetic predisposition (Monogenic channelopathies)
5) Exposure to epileptogenic stimuli (fever, infection or hypoxia during development)
Description of epilepsy in general
Primarily affects the cerebral cortex.
In all cases, epilepsy can be described as “abnormal hypersynchronous electrical activity” due to an imbalance between excitation and inhibition.
The main characteristic of epileptic neurons is their increase in excitability, which leads to excessive discharges.
Neurotransmitters- GABA
Can be inhibitory or excitatory depending on the neurotransmitter and the receptor that it binds.
• Main inhibitory- GABA= Opening of chloride channels (GABA A receptor) or reduction in amount of neurotransmitter released and opening of potassium channels (GABA B receptor).
Reduction in GABA inhibition either by: Decrease in GABA (neurotrasmitter) release. GABA receptors can no longer respond to GABA. Changes in ionic gradient due to “intracellular
accumulation of chloride ions”.
Overview of the Mechanisms of Epilepsy-Paroxysmal Depolarizing Shift (PDS), Spreading and Termination
PDS is composed of two components:* Slow component:- Long lasting, and sustained depolarization* Rapid component:- Additional rapid and sharp depolarizations. Spreading of seizures possible due to more
activation and/or loss of inhibition leading to:-The extracellular potassium level is increased,
and thus it is more difficult for potassium to leave the cell.
-The net current will be inward leading to depolarization that will occur to the extent that calcium currents will “be triggered”, so more neurotransmitter released.
- Activation of NMDA receptors by glutamate. Termination- Inactivation of the inward current.- Activation of the potassium outward current.
- Increase in chloride current into the cell.
Several tests can be performed to diagnose a patient following a seizure. EEG: to verify that person had a
seizure and to determine if seizures are partial or general. (Looks at changes in electrical patterns).
MRI or CT scan: these methods are used to rule out other abnormalities that may cause seizures (such as a tumor).
Blood tests may also be ordered to rule out other disorders or infections
Diagnostic Tests
Anti-epileptic medication Surgery Changes in diet
Treatment of Pediatric Epilepsy
Anti-epileptic medication: common types
Type Example Mode of action
Sodium channel blockers
Carbamazepine; phenytoin
Blocks voltage gated sodium channels that fire action potentials at high frequency.
GABA receptor agonist
Phenobarbital Prolongs opening of chloride channels.
Calcium channel blocker
Ethosuximide Blocks T-type calcium channels in the thalamus.
Treatment of Pediatric Epilepsy
Surgery: for refractory (intractable) epilepsy Corpus callosotomy: sectioning of the corpus
callosum to prevent and block spread of epileptic discharges interhemispherically
Can be partial or complete
Treatment of Pediatric Epilepsy
Ketogenic diet: high fat, low carbohydrate diet
Used to treat difficult-to-control, intractable epilespy
Treatment of Pediatric Epilepsy
Bromfield, E.B., Cavaazos, J.E., & Siven JI. (2006). An Introduction to Epilepsy. West Hartford: American Epilepsy Society.
Czuczwar, S. J., & Patsalos, P. N. (2001). The new generation of GABA enhancers: potential in treatment of epilespy. CNS Drugs, 15(5), 339-350.
Freeman, J. M., Vining, E. P. G., Pillas, D. J., Pyzik, P. L., Casey, J. C., & Kelly, M. T. (1998). The efficacy of the ketogenic diet – 1998: a prospective evaluation of intervention of 150 children. Pediatrics, 102(6), 1358-1363.
Kim, D. Y., & Rho, J. M. (2008). The ketogenic diet and epilespy. Current Opinion in Clinical Nutrition and Metabolic Care, 11, 113-120.
Meldrum, B. S. (1996). Update on the mechanism of action of antiepileptic drugs. Epilepsia, 37, S4-S11.
Wong, T., Kwan, S., Chang, K., Hsiu-Mei, W., Yang, T., Chen, Y., & Yi-Yen, L. (2006). Corpus callosotomy in children. Child’s Nervous System, 22, 99-1011.
World Health Organization. (October 2012). Fact Sheet N999. In Epilepsy. Retrieved November 25, 2012, from http://www.who.int/mediacentre/factsheets/fs999/en/index.html.
Epilepsy Canada. (2012). Living with Epilepsy, Facts, Epidemiology, & Diagnosis and Treatment. In Epilepsy Canada. Retrieved November 25, 2012, from www.epilepsy.ca.
References
Badawy, R. A. B., Harvey, A. S., & Macdonell, R. A. L. (2009). Cortical hyperexcitability and epileptogenesis: Understanding the mechanisms of epilepsy - part 1. Journal of Clinical Neuroscience, 16(3), 355-365. Retrieved from www.scopus.com
Badawy, R. A. B., Harvey, A. S., & Macdonell, R. A. L. (2009). Cortical hyperexcitability and epileptogenesis: Understanding the mechanisms of epilepsy - part 2. Journal of Clinical Neuroscience, 16(4), 485-500. Retrieved from www.scopus.com
Pellock, J.M. et al. (2008). Pediatric Epilepsy. New York: Demos Medical Publishing.
Blume W. T. (2003). Diagnosis and management of epilepsy. CMAJ, 168: 441-448
Canadian Pharmacists Association. (2012). , Seizures and Epilepsy, Therapeutic Choices. (pp 292-301) Webcom, Toronto, ON.
Deivasumathy Muthugovindan, and Adam L. Hartman. (2010). Pediatric Epilepsy Syndromes. The Neurologist, 16: 223-237.
David R. Fish, Shelagh J. Smith, Luis F. Quesney, Frederick Andermann, Theodore Rasmussen ( 2005). Surgical Treatment of Children with Medically Intractable Frontal or Temporal Lobe Epilepsy: Results and Highlights of 40 Years' Experience. Epilepsia, 34: 244-247.
References
There are different types of epilepsy common in different stages of childhood.
Epilepsy can be described as “abnormal hypersynchronous electrical activity” due to an imbalance between excitation and inhibition.
Paroxysmal depolarising shift leads to sustained and repetitive or burst firing. During seizures, 1) It is more difficult for potassium to move outwards 2) Calcium accumulates, so more neurotransmitter is released 3) Activation of NMDA by glutamate. Terminated with chloride entering, potassium leaving or inactivation of inward current.
GABA is a neurotransmitter that regulates inhibition, therefore a reduction in GABA leads to less control.
Pediatric epilepsy can be treated with Na+ channel blockers (carbamazepine, phenytoin), GABA receptor agonist (phenobarbital), Ca++ channel blockers (ethosuximide) to prevent frequent firing of neurons.
Intractable pediatric epilepsy may be treated with corpus callosotomy or with ketogenic diet.
Summary