對對 Posttraumatic epilepsy Posttraumatic epilepsy (PTE)(PTE) 的危險因子及其預後的危險因子及其預後

之探討 之探討

R2R2 詹博棋詹博棋 , 2005/08/08, 2005/08/08

臨床問題臨床問題 臨床上對於頭部外傷後的病人臨床上對於頭部外傷後的病人 , , 其發生癲其發生癲

癇的危險因子有哪些？癇的危險因子有哪些？ 對於腦傷後癲癇對於腦傷後癲癇 (PTE)(PTE) 病人病人 , , 其癲癇控制其癲癇控制

的預後又是如何？的預後又是如何？

背景說明背景說明 對於頭部外傷後的病人對於頭部外傷後的病人 , , 臨床上偶而會遇到臨床上偶而會遇到

在數年後其發生初次在數年後其發生初次 seizureseizure 的情形的情形 ; ; 因此因此 , , 希望藉由文獻搜尋來探討希望藉由文獻搜尋來探討 PTEPTE 的危險因子的危險因子 , , 發生率發生率 , , 及其相關的預後因子及其相關的預後因子 ..

Posttraumatic epilepsy (PTE)Posttraumatic epilepsy (PTE)

Immediate epilepsy: Immediate epilepsy: • within moments of injurywithin moments of injury• Represent of true epilepsy? orRepresent of true epilepsy? or• The result of arrest of cerebral blood flow or a The result of arrest of cerebral blood flow or a

transient brainstem dysfunction?transient brainstem dysfunction? Early epilepsy: Early epilepsy:

• within first weekwithin first week Late epilepsy (Posttraumatic epilepsy, PTE)Late epilepsy (Posttraumatic epilepsy, PTE)

• Several weeks or months (1 to 3 months mostly)Several weeks or months (1 to 3 months mostly)

期待目標期待目標 希望能搜尋到相關希望能搜尋到相關 PTEPTE 的危險因子及預後因的危險因子及預後因

子子 , , 進而幫助我們對於腦傷後癲癇進而幫助我們對於腦傷後癲癇 (PTE)(PTE) 診診斷的確立斷的確立 ..

搜尋步驟搜尋步驟 (1)(1)

Cochrane central register of controlled trials:Cochrane central register of controlled trials: Combine “traumatic brain injury” with “epilepsy”Combine “traumatic brain injury” with “epilepsy”0/30/3 Combine “traumatic brain injury” with “seizure”Combine “traumatic brain injury” with “seizure” 0/2 0/2 Posttraumatic epilepsy Posttraumatic epilepsy 1/3 , no abstract 1/3 , no abstract

• Manaka S Cooperative prospective study on posttraumatic eManaka S Cooperative prospective study on posttraumatic epilepsy: risk factors and the effect of prophylactic anticonvulspilepsy: risk factors and the effect of prophylactic anticonvulsant. [Clinical Trial. Journal Article. Multicenter Study. Randoant. [Clinical Trial. Journal Article. Multicenter Study. Randomized Controlled Trial] mized Controlled Trial] Japanese Journal of Psychiatry & NeJapanese Journal of Psychiatry & Neurology. 46(2):311-5, 1992 Jun.urology. 46(2):311-5, 1992 Jun.

Posttraumatic seizure Posttraumatic seizure 0/1 0/1• Side effects and mortality associated with use of phenytoin foSide effects and mortality associated with use of phenytoin fo

r early posttraumatic seizure prophylaxis.r early posttraumatic seizure prophylaxis.

搜尋步驟搜尋步驟 (2)(2)

Cochrane Database of Systemic Reviews:Cochrane Database of Systemic Reviews: Combine “traumatic brain injury” with “epilepsCombine “traumatic brain injury” with “epileps

y”y”0/30/3 Combine “traumatic brain injury” with “seizure”Combine “traumatic brain injury” with “seizure”

0/1 0/1 Posttraumatic epilepsy Posttraumatic epilepsy 0 0 Posttraumatic seizure Posttraumatic seizure 0/2 0/2

搜尋步驟搜尋步驟 (3)(3)

Cochrane LibraryCochrane Library Combine “traumatic brain injury” with “epilepsCombine “traumatic brain injury” with “epileps

y”y”0/50/5 Combine “traumatic brain injury” with “seizure”Combine “traumatic brain injury” with “seizure”

0/11 0/11 Posttraumatic epilepsy Posttraumatic epilepsy 0/2 0/2 Posttraumatic seizure Posttraumatic seizure 0/5 0/5

搜尋步驟搜尋步驟 (4)(4)

EBM: ACP Journal club:EBM: ACP Journal club: nil nil Combine “traumatic brain injury” with “epilepsCombine “traumatic brain injury” with “epileps

y”y”00 Combine “traumatic brain injury” with “seizure”Combine “traumatic brain injury” with “seizure”

0 0 Posttraumatic epilepsy Posttraumatic epilepsy 0 0 Posttraumatic seizure Posttraumatic seizure 0 0

搜尋步驟搜尋步驟 (5)(5)

PubMed:PubMed: Combine “posttraumatic epilepsy” with “prognCombine “posttraumatic epilepsy” with “progn

osis ”osis ” 7/29 7/29 Combine “posttraumatic epilepsy” with “risk faCombine “posttraumatic epilepsy” with “risk fa

ctor ”ctor ” 3/5 3/5 Combine “posttraumatic seizure” with “prognoCombine “posttraumatic seizure” with “progno

sis” sis” 2/7 2/7 Combine “posttraumatic seizure” with “risk facCombine “posttraumatic seizure” with “risk fac

tor” tor” 2/3 2/3

結果摘要 結果摘要 (1)(1)

Longitudinal cohort designLongitudinal cohort design Risk of seizure recurrence after the first late Risk of seizure recurrence after the first late

posttraumatic seizure.posttraumatic seizure. (Arch Phys Med Rehabil. 1(Arch Phys Med Rehabil. 1997 Aug;78(8):835-40.)997 Aug;78(8):835-40.)

The cumulative incidence of The cumulative incidence of recurrent late seizurecurrent late seizuresres was was 86%86% by approximately by approximately 2 years2 years. . . .

The The relative riskrelative risk of recurrence was highest in: of recurrence was highest in: a history of acute SDH a history of acute SDH prolonged coma (ie, longer than 7 days). prolonged coma (ie, longer than 7 days).

結果摘要 結果摘要 (2)(2)

Cohort studyCohort study Seizures after head trauma: a population study.Seizures after head trauma: a population study. (Neurol(Neurol

ogy. 1980 Jul;30(7 Pt 1):683-9.) ogy. 1980 Jul;30(7 Pt 1):683-9.)

The risk of posttraumatic seizuresThe risk of posttraumatic seizures SevereSevere (brain contusion, ICH, or >24 hours unconsciousnes (brain contusion, ICH, or >24 hours unconsciousnes

s or amnesia): s or amnesia): • 7.1% within 1 year 7.1% within 1 year • 11.5% in 5 years11.5% in 5 years

ModerateModerate (skull fracture or 30 minutes to 24 hours of uncon (skull fracture or 30 minutes to 24 hours of unconsciousness or amnesia)sciousness or amnesia)

• 0.7% within 1 year 0.7% within 1 year • 1.6% in 5 years1.6% in 5 years

Mild Mild (briefer unconsciousness or amnesia: not significantly (briefer unconsciousness or amnesia: not significantly greater than in the general populationgreater than in the general population

結果摘要 結果摘要 (3)(3)

Cohort studyCohort study A population-based study of seizures after traumatic A population-based study of seizures after traumatic

brain injuriesbrain injuries.(N Engl J Med. 1998 Jan 1;338(1):20-4.).(N Engl J Med. 1998 Jan 1;338(1):20-4.) In the multivariate analysis, significant In the multivariate analysis, significant risk factorsrisk factors for late for late

r seizures were r seizures were brain contusion with subdural hematoma, brain contusion with subdural hematoma, skull fracture, skull fracture, loss of consciousness or amnesia for more than one day, loss of consciousness or amnesia for more than one day, an age of 65 years or older. an age of 65 years or older.

CONCLUSIONSCONCLUSIONS: The increased risk of seizures after tra: The increased risk of seizures after traumatic brain injury varies greatly according to the severitumatic brain injury varies greatly according to the severity of the injury and the time since the injury.y of the injury and the time since the injury.

結果摘要 結果摘要 (4)(4)

Review, TutorialReview, Tutorial Epidemiology of posttraumatic epilepsy: a criEpidemiology of posttraumatic epilepsy: a cri

tical reviewtical review.( Epilepsia. 2003;44 Suppl 10:11-7. ) .( Epilepsia. 2003;44 Suppl 10:11-7. )

Significant risk factors, <1st week after injury inclSignificant risk factors, <1st week after injury include:ude: acute ICH (esp.SDH), younger age, increased injury sacute ICH (esp.SDH), younger age, increased injury s

everity, and chronic alcoholism. everity, and chronic alcoholism. Significant risk factors, >1 week after TBI include Significant risk factors, >1 week after TBI include

seizures within the first week, acute ICH (esp.SDH), seizures within the first week, acute ICH (esp.SDH), brain contusion, increased injury severity, and age >6brain contusion, increased injury severity, and age >65 years at the time of injury. 5 years at the time of injury.

結果摘要 結果摘要 (5)(5) Cohort studyCohort study Increased risk of late posttraumatic seizures associated with inheritanIncreased risk of late posttraumatic seizures associated with inheritan

ce of APOE epsilon4 allele.ce of APOE epsilon4 allele.( Arch Neurol. 2003 Jun;60(6):818-22)( Arch Neurol. 2003 Jun;60(6):818-22)

BACKGROUND: BACKGROUND: Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with incrInheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with incr

eased risk of Alzheimer disease, progression to disability in multiple sclerosis, aneased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury. d poor outcome after traumatic brain injury.

The relative risk of late posttraumatic seizures for patients with the epsilon4 The relative risk of late posttraumatic seizures for patients with the epsilon4 allele was allele was 2.41 2.41

CONCLUSIONS:CONCLUSIONS: Inheritance of the APOE epsilon4 allele is associated with increased risk of late pInheritance of the APOE epsilon4 allele is associated with increased risk of late p

osttraumatic seizures.osttraumatic seizures. In this cohort, this risk appears to be independent of an eff In this cohort, this risk appears to be independent of an effect of epsilon4 on functional outcome. A better understanding of the molecular rolect of epsilon4 on functional outcome. A better understanding of the molecular role of APOE in neurodegenerative diseases may be helpful in developing antiepilee of APOE in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.ptogenic therapies.

結果摘要 結果摘要 (6)(6) Predictors and dynamics of posttraumatic epPredictors and dynamics of posttraumatic ep

ilepsy.ilepsy.(Acta Neurol Scand. 1997 May;95(5):257-62.)(Acta Neurol Scand. 1997 May;95(5):257-62.) High risk for PTE: combination of the 3 variablesHigh risk for PTE: combination of the 3 variables

prolonged posttraumatic amnesia prolonged posttraumatic amnesia depression fracturedepression fracture cortical-subcortical lesions cortical-subcortical lesions

poor seizure control: poor seizure control: Combined seizure patternCombined seizure pattern high seizure frequencyhigh seizure frequency AED-noncompliance AED-noncompliance alcohol abuse predictedalcohol abuse predicted

總結總結 (I)(I)

目前證據顯示主要的目前證據顯示主要的 risk factors of PTErisk factors of PTE 如如下下 :: brain contusion brain contusion acute SDH acute SDH skull fracture, depressed fractureskull fracture, depressed fracture loss of consciousness or amnesia for more thaloss of consciousness or amnesia for more tha

n one dayn one day an age of 65 years or olderan age of 65 years or older

Inheritance of the APOE epsilon4 allele is associaInheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizurted with increased risk of late posttraumatic seizureses

總結總結 (II)(II)

對於 對於 PTEPTE 病患病患 ,, 其其 poor prognosis factorspoor prognosis factors 如如下下 :: First seizure > 1 weeksFirst seizure > 1 weeks Combined seizure pattern, Combined seizure pattern, high seizure frequency, high seizure frequency, AED-noncompliance AED-noncompliance alcohol abusealcohol abuse

Thanks for your Thanks for your attention!attention!