1. Post-Traumatic Epilepsy Enrique Feoli MD North East Regional Epilepsy Group 2014

2. Videos https://www.youtube.com/watch?v=BfQ8OxErihk https://www.youtube.com/watch?v=BfQ8OxErihk https://www.youtube.com/watch?v=BfQ8OxErihk https://www.youtube.com/watch?v=eW9GRDe4v-Y https://www.youtube.com/watch?v=eW9GRDe4v-Y https://www.youtube.com/watch?v=eW9GRDe4v-Y http://www.youtube.com/watch?v=nZ8p90Bfqng&fea ture=player_detailpage http://www.youtube.com/watch?v=nZ8p90Bfqng&fea ture=player_detailpage http://www.youtube.com/watch?v=nZ8p90Bfqng&fea ture=player_detailpage http://www.youtube.com/watch?v=nZ8p90Bfqng&fea ture=player_detailpage

3. Scope of the issue: USA 1.7 million/Year* (adult and children) 1.7 million/Year* (adult and children) *leading cause of death and disability USA and other industrialized countries *leading cause of death and disability USA and other industrialized countries 3.2-5.3 mill. citizens /w lifelong disability 3.2-5.3 mill. citizens /w lifelong disability 53K Die from TBI (Ann Average) 53K Die from TBI (Ann Average) Firearms 35% 15-34y/o + > 75 y/o(8.5 and 10.5/100K) Firearms 35% 15-34y/o + > 75 y/o(8.5 and 10.5/100K) MVA 31% 15-24 y/o MVA 31% 15-24 y/o Falls 16.7 >75 y/o Falls 16.7 >75 y/o Estimate annual cost of TBI ($60 billion US) Estimate annual cost of TBI ($60 billion US) http://www.cdc.gov/nchs/data http://www.cdc.gov/nchs/data http://www.cdc.gov/nchs/data

4. Terminology Early seizures (1 to 7 days) Early seizures (1 to 7 days) Immediate Sz Late seizures (epilepsy) Immediate Sz Late seizures (epilepsy) ( 0 to 24 hs) (40% in the firs 6 months) ( 0 to 24 hs) (40% in the firs 6 months) Trauma 7 days

5. TBI: Civilian Background Motor vehicles/Falls (75%) Motor vehicles/Falls (75%) Men “excel”: TBI: 2-2 ½ times vs. women Men “excel”: TBI: 2-2 ½ times vs. women Bimodal Bimodal Young Young Old men Old men

6. Criteria for TBI Loss of Awareness (consciousness) Loss of Awareness (consciousness) Sustained focal deficit Sustained focal deficit Imaging abnormality (ICH, Contusion…) Imaging abnormality (ICH, Contusion…)

7. Key Point: Severity of TBI Mild: GCS: 13-15 Mild: GCS: 13-15 Moderate: GCS: 9-12 Moderate: GCS: 9-12 Severe: GCS: 8 or less; obtunded/coma Severe: GCS: 8 or less; obtunded/coma

8. (6) TBI and Seizures

9. Risk of Post Traumatic Epilepsy Mild: 1.5% Mild: 1.5% Moderate: 4.0% Moderate: 4.0% Severe: 28% Severe: 28%

10. Risk Factors for PTE Severity of Head Injury! Severity of Head Injury! > 65 years of age > 65 years of age Brain contusion Brain contusion Intra-cerebral hematoma Intra-cerebral hematoma Early Seizures (1st week post trauma) Early Seizures (1st week post trauma)

11. (6) Evaluation of Seizure Risk Seizure Risk in Brain Injuries

12. PTE-How Long to Develop? Highest: first year. Highest: first year. Decreases each year Decreases each year Mild TBI : Standardized incidence ratio: 1.5 in the first 5 years Mild TBI : Standardized incidence ratio: 1.5 in the first 5 years Mod TBI: SIR: 2.9, inc. Risk lasted 10yrs. Mod TBI: SIR: 2.9, inc. Risk lasted 10yrs. Severe TBI: SIR:17, inc risk lasting 20 yrs Severe TBI: SIR:17, inc risk lasting 20 yrs

13. TBI Symptoms Epilepsy Seizures, Complex Partial Seizures, Complex Partial Simple partial seizures Simple partial seizures Secondary generalized Secondary generalized Psychogenic Non Epileptic events, about 30 % of patient with TBI have PNES

14. TBI Symptoms posttraumatic stress disorder posttraumatic stress disorder anxiety disorders, anxiety disorders, personality disorders, personality disorders, aggressive disorders, aggressive disorders, cognitive changes, cognitive changes, chronic pain, chronic pain, sleep problems, sleep problems, motor or sensory impairments, endocrine dysfunction, gastrointestinal disturbances, motor or sensory impairments, endocrine dysfunction, gastrointestinal disturbances, parkinsonism, parkinsonism,

15. Humeral Fracture after generalized status epilepticus

16. Aspiration Pneumonia after GTC Seizure

17. Burns

18. PTE Treatment Severe TBI Acute Prophylaxis: Severe TBI Acute Prophylaxis: Typically 7 Days (phenytoin) Typically 7 Days (phenytoin) Does not modify course/prevent late seizures Does not modify course/prevent late seizures Acute and Chronic: once established Acute and Chronic: once established Medications (greater than 22 available) Medications (greater than 22 available) Modify lifestyle Modify lifestyle Machines Machines Surgery Surgery

19. Can PTE be Prevented Early seizures (1 to 7 days) Early seizures (1 to 7 days) Immediate Sz Late seizures (epilepsy) Immediate Sz Late seizures (epilepsy) ( 0 to 24 hs) (40% in the firs 6 months) ( 0 to 24 hs) (40% in the firs 6 months) Trauma 7 days

20. (5) Defining TBI and Seizure Mechanism of injury in TBI

21. “Shear” Injury

22. GSW

23. Doc: “I got a headache”….

24. Long Term: Encephalomalacia

25. Brain Trauma

26. Prevention Trials Anti seizure medications Anti seizure medications Hypothermia Hypothermia Magnesium Magnesium

27. Can PTE be Prevented Early seizures (1 to 7 days) Early seizures (1 to 7 days) Immediate Sz Late Dilantin Carbamazepine Phenobarbital Levetiracetam Have all been proven to be effective in decreasing the frequency of early pot- traumatic seizures, however none have shown the decrease the incidence of PTE Trauma 7 days

28. Animals Effect of treatment on the epileptogenesis after TBI in experimental models Rimonabant sinngle dose6 wk Echegoyen et Rimonabant sinngle dose6 wk Echegoyen et Minozac 6 h post-TBI two doses7 d Chrzaszcz et al. 48 Minozac 6 h post-TBI two doses7 d Chrzaszcz et al. 48 Ketogenic diet Schwartzkroin et Ketogenic diet Schwartzkroin et HypothermiaParasagittal FP30 min post-TBI for 4 h12 wk Atkins et al. HypothermiaParasagittal FP30 min post-TBI for 4 h12 wk Atkins et al.

29. Hypothermia No studies in human No studies in human

30. Magnesium No studies in humans No studies in humans

31. Conclusions