1. PSYC4080 Seizure Disorders 1

2. PSYC4080 Seizure Disorders 2  Abnormal electrical discharge in the brain.  Neurons firing together in synchrony: paroxysmal depolarization shifts (PDS)  Hyperexcitation of glutamate neurons.  Many causes: Seizures are symptoms, not a disease.  Presence of sensory or cognitive dysfunction is dependent on affected area(s)  Prevalence: 0.6% of the population  Incidence: 15,500 new cases per year (Epilepsy Canada)

3. PSYC4080 Seizure Disorders 3 Neuropathology 1.Generalized seizures – involve the entire cerebral cortex 2.Focal (partial) seizures – limited to parts of the brain PDS associated with a spike in the EEG PDS associated with a spike in the EEG

4. PSYC4080 Seizure Disorders 4 Neuropathology Typical Muscle Movements: 1.Tonic: stage of extreme muscle tension related to PDS activity 2.Clonic: contractions and relaxations of muscle, occurring in rapid succession Rapid onset and offset of PDS activity Rapid onset and offset of PDS activity EEG changes during and between seizures (ictal and interictal periods). EEG changes during and between seizures (ictal and interictal periods). 3.Atonic: no muscle tension Level of Consciousness 1.Simple: No loss 2.Complex: Loss of consciousness

5. PSYC4080 Seizure Disorders 5 Neuropathology Hyper-excitability in neurons can accelerative cell death Hyper-excitability in neurons can accelerative cell death High concentration of Ca ++ leads to long-term potentiation of synaptic responses High concentration of Ca ++ leads to long-term potentiation of synaptic responses Activation of genes that cause synaptic reorganizationActivation of genes that cause synaptic reorganization Axonal growth and neo-synaptogenesisAxonal growth and neo-synaptogenesis Lowering of seizure thresholdLowering of seizure threshold Children’s brains are more resistant to these long term effects Children’s brains are more resistant to these long term effects Relative immaturity of biochemical cascadesRelative immaturity of biochemical cascades

6. PSYC4080 Seizure Disorders 6 Childhood Seizure Disorders 1.Neonatal seizures  Occurring up to 2 months of age  Symptoms are acute not chronic  Full body tonic and clonic movements  Loss of consciousness  More common in premature infants  90% of patients die from these seizures.

7. PSYC4080 Seizure Disorders 7 Childhood Seizure Disorders Many different diseases cause infantile seizures:  Birth trauma or head injury  Disorders of metabolism  Infections (I.e. herpes encephalitis)  Anoxic episodes (loss of oxygen)  Genetic factors (I.e. family histories) 40% have no known cause (idiopathic epilepsy) 40% have no known cause (idiopathic epilepsy) 90% have first onset before age 20. 90% have first onset before age 20.

8. PSYC4080 Seizure Disorders 8 Childhood Seizure Disorders 2. Infantile spasms (West Syndrome) Later onset (3-6 months) Full body (tonic) contraction, bending over, stiff muscles May have up to 100 spasms per day Abnormal EEG, MR are associated with this syndrome. More common in males. Poor prognosis for mental development. Developmental disabilities are common: Only 16% can be educated in a normal classroom setting

9. PSYC4080 Seizure Disorders 9 Childhood Seizure Disorders 3. Febrile seizures Common response to elevated body temperature. 2-5% of all children between 6 months and 5 years. Full body seizure, tonic and clonic movements More common in males. Good prognosis: Usually no problems later in life. Exception to this is if the fever was due to a brain infection, or if there is a recurrence of seizures after a fever

10. PSYC4080 Seizure Disorders 10 Childhood Seizure Disorders 1.9% of all children have at least one epileptic episode. Most frequent onset between 6 months and 6 years of age.

11. PSYC4080 Seizure Disorders 11 Adult Disorders Most common types of seizures: 1.Grand mal: loss of consciousness, falling on the ground, and tonic-clonic movements 2.Myoclonic seizures: clonic movements in parts of the body, usually no loss of consciousness 3.Absence seizure: loss of consciousness with no muscle movements 4.Complex partial seizures: loss of consciousness, oral automatisms, preceded by auras (sensory warning of seizure onset).

12. PSYC4080 Seizure Disorders 12 Neuropathology Seizures may be intractable and require regular follow-ups Those at increased risk: 1.Very young age of onset (< 2 years) 2.Frequent generalized seizures 3.Failure to achieve control readily 4.Evidence of brain damage 5.A specific cause 6.Severe EEG abnormality 7.Low IQ 8.Atonic, atypical absence seizures

13. PSYC4080 Seizure Disorders 13 Neuropathology Why are children so vulnerable? GABAergic synapses develop before main glutamate receptors (NMDA, AMPA) GABAergic synapses develop before main glutamate receptors (NMDA, AMPA) In early development, GABA is excitatory-- binding to GABA A receptors causes depolarization. In early development, GABA is excitatory-- binding to GABA A receptors causes depolarization. Shift to inhibitory effects occurs once glutamate receptors have maturedShift to inhibitory effects occurs once glutamate receptors have matured Thus, the neonatal brain operates with very little inhibition.

14. PSYC4080 Seizure Disorders 14 Neuropathology  Overt psychosocial and cognitive consequences  Including a profound fear of having a seizure in public  Higher incidence of adjustment, academic, psychiatric disorders in persons with epilepsy (Bennett, 1992).  Lower IQ is associated with seizures, especially if the onset is early.  Affected by underlying causes and medications used to treat as well.

15. PSYC4080 Seizure Disorders 15 Neuropathology Temporal lobe, and the hippocampus in particular, may be particularly vulnerable Most sensitive to effects of long term potentiation related to memory Memory and learning deficits may be associated with any type of seizure. Worst in complex partial seizures which are caused by temporal lobe lesions. Overall attention levels can be affected by most types of seizures.

16. PSYC4080 Seizure Disorders 16 Neuropathology High “comorbidity” 1.Depression Major depressive episodes are common Major depressive episodes are common May be related to anticonvulsant medications May be related to anticonvulsant medications 2. Anxiety Disorders Almost exclusively based on realistic fear of having a seizure in public Almost exclusively based on realistic fear of having a seizure in public 3. Personality and Psychotic Disorders  Obsessive compulsive  Personality changes

17. PSYC4080 Seizure Disorders 17 Other Information Treatment Options Medications Medications Surgery Surgery Lesioning tissue if seizures are localLesioning tissue if seizures are local Electrode stimulationElectrode stimulation Ketogenic diet (high fat, low carb) - for generalized seizures Ketogenic diet (high fat, low carb) - for generalized seizures By and large, treatment does not address psychosocial issues directly. By and large, treatment does not address psychosocial issues directly.