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1 Ashley Masse Arif Mohamed Rosalie Nguyen Yusuf Majumder PHM Fall 2012Instructor: Dr. Jeffrey HendersonPediatric EpilepsyAshley MasseArif MohamedRosalie NguyenYusuf Majumder
2 What is Epilepsy?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.
3 Types of Epilepsy/ Classifications There are two major types of epilepsyIdiopathic Epilepsy- no known causeSecondary/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.Generalized tonic-clonic- seizure involving the entire body (grand mal), what people typically think when you say epilepsyAbsence- brief periods of “unconsciousness” (petite mal)Myoclonic- brief muscle “jerks” (likened to the way ones body occasionally jerks when falling asleep)Partial- more individual, depends on the part of the brain involved (anything from physical , motor movement, or emotional changes)
4 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 (%)*0-110.312-140.616-2425-440.746-64> 65
5 Childhood EpilepsyAbout 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.
6 Epilepsy Syndromes By Age of Onset Neonatal periodBENIGN IDIOPATHIC NEONATAL SEIZURES (BINS)Rare idiopathic syndrome often generalizedBENIGN FAMILIAL NEONATAL-INFANTILE SEIZURES (BFNIS)Genetic based idiopathic syndromeEARLY INFANTILE EPILEPTIC ENCEPHALOPATH (EIEE)Rare, but severe encephalopathic form with symptomatic root
7 Epilepsy Syndromes By Age of Onset InfancyWEST SYNDROMEsymptomatic, cryptogenic (nonidentifiable hidden cause)Between 4 and 7 monthMYOCLONIC EPILEPSY IN INFANCY (MEI)Rare, idiopathic generalizedBetween the ages of 6 months and 3 yearsDRAVET SYNDROMERare, symptomaticCases with mutations in the SCN1A gene
8 Epilepsy Syndromes By Age of Onset ChildhoodBENIGN CHILDHOOD EPILEPSY WITH CENTROTEMPORAL SPIKESMost common idiopathic epilepsy syndrome, representing 24% of epilepsy cases among school age childrenLENNOX-GASTAUT SYNDROME (LGS)Onset is 2nd to 6th year of lifeaccompanied by developmental delay and psychological and behavioral problemsLANDAU-KLEFFNER SYNDROME (LKS)Peak onset between the ages of 3 and 7 yearsTwo-thirds of affected children are male
9 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)
10 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.
11 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”.
12 Overview of the Mechanisms of Epilepsy-Paroxysmal Depolarizing Shift (PDS), Spreading and TerminationPDS 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.
13 Diagnostic TestsSeveral 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
14 Treatment of Pediatric Epilepsy Anti-epileptic medicationSurgeryChanges in dietAlthough epilepsy is one of the most common neurophysiology disorders in the world, most types of epilepsy (including pediatric epilepsy) can be easily prevented and controlled. (However, before administering treatment to pediatric epilepsy, it is important to conduct a detailed clinical history and examination of the patient, identify the precipitating causes, and perform an EEG to confirm diagnosis). Once diagnosed, pediatric epilepsy can be treated through the use of anti-epileptic medication, surgery, and through changes in the diet.
15 Treatment of Pediatric Epilepsy Anti-epileptic medication: common typesTypeExampleMode of actionSodium channel blockersCarbamazepine; phenytoinBlocks voltage gated sodium channels that fire action potentials at high frequency.GABA receptor agonistPhenobarbitalProlongs opening of chloride channels.Calcium channel blockerEthosuximideBlocks T-type calcium channels in the thalamus.When treating for pediatric epilespy with medication, it is important to begin with one drug. Switching to another drug should be done with caution by gradually tapering the first drug.Carbamazepine, phenytoin are two common anti-epileptic medications which work in a similar fashion: they prolong the inactivate state by blocking voltage gated sodium channels and decrease the firing rate of action potentials. (Used for tonic-clonic seizures, partial seizures)Phenobarbital is a GABA receptor against which prolongs the opening of GABA-mediated Chloride channels. This in turn results in hyperpolarization and thus limits the rate and frequency of action potentials.Ethosuximide blocks low threshold, t-type calcium channels in the thalamus to prevent depolarization and frequent firing of action potentials.
16 Treatment of Pediatric Epilepsy Surgery: for refractory (intractable) epilepsyCorpus callosotomy: sectioning of the corpus callosum to prevent and block spread of epileptic discharges interhemisphericallyCan be partial or completeSurgery should be considered in pediatric epilepsy only after all medications have failed. Because epileptic discharges travel between hemispheres, corpus callosotomy (or sectioning of the corpus callosum – region that connects the right and left hemisphere) may be performed to treat intractable epilepsy. However, a caveat of this surgery is that the patient will have split brain syndrome if the corpus callosum is completed sectioned off. Therefore should only be considered for drug-resistant pediatric epilepsy.
17 Treatment of Pediatric Epilepsy Ketogenic diet: high fat, low carbohydrate dietUsed to treat difficult-to-control, intractable epilespyThe ketogenic diet has regained popularity in the scientific community as a method of treating intractable pediatric epilepsy. Ketogenic diets, which require a strict intake of high fat and low carbohydrates in the diet, are implemented in children with difficult-to-control seizures. Although the mechanism of action (of how the diet plays a role in the effectiveness of treating epilepsy) is not well understood, recent studies suggest that the ketogenic diet reduces the hyperexcitability of neurons.
18 ReferencesBromfield, 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),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),Kim, D. Y., & Rho, J. M. (2008). The ketogenic diet and epilespy. Current Opinion in Clinical Nutrition and Metabolic Care, 11,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,World Health Organization. (October 2012). Fact Sheet N999. In Epilepsy. Retrieved November 25, 2012, fromEpilepsy Canada. (2012). Living with Epilepsy, Facts, Epidemiology, & Diagnosis and Treatment. In Epilepsy Canada. Retrieved November 25, 2012, from
19 ReferencesBadawy, 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), Retrieved fromBadawy, 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), Retrieved fromPellock, J.M. et al. (2008). Pediatric Epilepsy. New York: Demos Medical Publishing.Blume W. T. (2003). Diagnosis and management of epilepsy. CMAJ, 168:Canadian Pharmacists Association. (2012). , Seizures and Epilepsy, Therapeutic Choices. (pp ) Webcom, Toronto, ON.Deivasumathy Muthugovindan, and Adam L. Hartman. (2010). Pediatric Epilepsy Syndromes. The Neurologist, 16: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:
20 SummaryThere 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.