`
` Tbejoumal ofTRAU MA® Injury, Infection, and Critical Care
`
`Factors PI‘BlllGllVB 0l Outcome lll Postiraumatic SBTZIII‘BS
`
`Hung-Chen Wang, MD, Wen-Neng Chang, MD, Hsueh-Wen Chang, PhD, Jih-Tsun H0, MD, PhD,
`Tat—Ming Yang, MD, Wei-Che Lin, MD, Yew-Chung Chuang, MD, and Cheng-Hsien Lu, MD
`
`Background: Seizures are important
`neurologic complications of traumatic brain
`injury (TBI). There is a need for better de-
`lineation of potential prognostic factors and
`outcomes in patients with posttraumatic sei-
`zures (PTS) who could receive treatment
`when brought to the hospital.
`Methods: In this 10-year retrospec-
`tive study, 170 adult patients with PTS
`were enrolled in this study. The degree of
`
`seizure control was analyzed using a Sei-
`zure Frequency Scoring System, which
`classified them into excellent and nonex-
`cellent outcomes.
`
`BGSUITS: There were 170 patients with
`acute symptomatic seizure enrolled in this
`study, 106 of whom had early PTS, whereas
`64 had late PTS. Of the 106 early PTS, 58%
`(61 of 106) occurred within 24 hours of
`trauma. Risk factors for developing nonex-
`
`cellent outcome included patients who un-
`dergo surgical intervention and presence of
`late-provoked seizures during the acute
`phase of TBI.
`conclusions: Seizures are an impor-
`tant neurologic complication of TBI. Re-
`garding the potentially side effects of
`antiepileptic drugs, antiepileptic therapy
`should be carefully administrated in those
`nonexcellent outcome patients.
`J Trauma. 2008;64:883—838.
`
`raumatic brain injury (TBI) is one of the major causes of
`disability, morbidity, and mortality among individuals
`younger than 45 years and is responsible for a significant
`proportion of traumatic deaths in developed countriesl’2 The
`overall risk of seizures after TBI ranges from 2% to 5% in the
`general population3’4 but is from 7% to 39% in patients with
`cortical injury and neurologic sequelae.5
`One population—based study demonstrates that 86% of
`patients with a single late posttraumatic seizure (PTS) had a
`second seizure within 2 years.6 Because of the possible ben—
`efits of antiepileptic drugs (AED) to reduce the degree of
`functional morbidity after TBI,
`there is a need for better
`delineation of potential prognostic factors and outcomes in
`nonselected patients admitted to the hospital who could re-
`ceive treatment.
`
`In this study, the role of a number of clinical observations,
`neuroimaging findings, and Glasgow Coma Scale (GCS) score
`measurements were analyzed in terms of predicting the outcome
`of PTS. We chose to study (1) the clinical relevance of PTS and
`other neurologic complications that occur after TBI; (2) the
`types of seizures that occur during acute phase of TBI; and (3)
`the potential prognostic factors during the acute illness for the
`longeterm outcome.
`
`Submitted for publication July 18, 2006.
`Accepted for publication February 12, 2007.
`Copyright © 2008 by Lippincott Williams & Wilkins
`From the Departments of Neurosurgery (H.-C,W., J.-T,H., T.-M.Y.),
`Neurology (W.-N.C., Y.-C.C., C.«H.L.), and Radiology (W.«C.L,), Chang
`Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung Univer-
`sity College of Medicine, Kaohsiung, Taiwan, China; and Department of
`Biological Science (H.—W.C.), National Sun Yat-Sen University, Kaohsiung,
`Taiwan, Republic of China.
`Address for reprints: Cheng-Hsien Lu, Department of Neurology, Chang
`Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung
`Hsien, Taiwan, Republic of China; email: chlu99@ms44.url.com.tw.
`DOI: 10.1097/TA.0b013e31804a7fa4
`
`PATIENTS AND METHODS
`During a period of 10 years (1994—2003), 9,212 patients
`who suffered from first event TBI were admitted to the
`
`Department of Neurosurgery at the Chang Gung Memorial
`Hospital
`in Kaohsiung. Chang Gung Memorial Hospital—
`Kaohsiung is a 2,482-bed acute-care teaching hospital, which
`is the largest medical center in southern Taiwan that provides
`both primary and tertiary referral care to patients. Of the
`9,212 patients, 190 suffered from acute symptomatic seizures
`during the acute phase of TBI.
`The definition of PTS was set according to that in previous
`studies: seizure occurring after head trauma that is causally
`related to the trauma itself.7'8 A provoked (acute symptomatic
`seizure) seizure is one that occurs in close temporal relation with
`TBI, which is presumed to be the underlying cause. In contrast,
`an unprovoked seizure is a seizure occurring in the absence of
`one or more precipitating factors, and it includes events occur—
`ring in patients with antecedent stable (nonprogressing) CNS
`insults, including TBI (remote symptomatic seizures).7’8
`The definition of onset of acute symptomatic seizure
`during hospitalization was modified from those of a previous
`study9 classification into two subtypes: early—provoked sei—
`zures as seizures occurring within the first 7 days after injury,
`and late-provoked seizures as those occurring 7 days later but
`before discharge. In contrast, an unprovoked seizure is a
`seizure occurring in the absence of one or more precipitating
`factors, while epilepsy is the occurrence of repeated unpro-
`voked seizures.10 Status epilepticus was modified from those
`of previous reports and defined as both of the following: (1)
`continuous seizures lasting at least 5 minutes; and (2) two or
`more discrete seizures between which there is incomplete
`recovery of consciousness. 1 1’12
`Patients initially treated in other hospitals but subse-
`quently transferred to our hospital for further therapy were
`also included in the study and their initial clinical and labo-
`ratory data at the previous hospital were used for analysis.
`
`Volume 64 0 Number 4
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`883
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`The/oumal ofTRAU MA® Injury, Infection, and Critical Care
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`= P
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`atients were excluded from the study if (1) they had a history
`of TBI; (2) preexisting epilepsy; (3) gunshot wounds or pene-
`trating head injuries; (4) preexisting neurologic conditions with
`various neurologie deficits; and (5) death within 1 month. The
`study had enrolled a total of 170 patients.
`Demographic data of the 170 patients, characteristics and
`circumstances, time interval from TBI to first seizure,
`the
`types of seizure, and several other features were documented,
`including length of hospital stay, the presence and duration of
`chronic epilepsies, neurosurgieal interventions, and systemic
`underlying diseases associated with seizures. The GCS score
`
`was analyzed by neurosurgeons when the patient arrived in
`the emergency room.
`TBI was defined as an alteration in brain function man—
`
`ifesting as confusion, altered consciousness, seizure, coma, or
`focal sensory or motor neurologic deficit resulting from blunt
`or penetrating force to the head.13 TBI was classified as mild
`(loss of consciousness or amnesia lasting less than 30 min-
`utes), moderate (loss of consciousness for 30 minutes to 24
`hours or a skull fracture), or severe (loss of consciousness or
`amnesia for more than 24 hours, subdural hematoma, intra-
`cerebral hematoma, or brain contusion).2
`All of the patients received brain computed tomography
`(CT) scans soon after arrival at the emergency room. Fur-
`thermore, follow-up brain CT scans were performed if clin-
`ical deterioration was noted, including acute onset of focal
`neurologic deficits, seizures or status epilepticus, and a pro—
`gressively disturbed conscious state. All diagnoses of intra-
`cranial contusion or hematoma were based on brain CT
`evidence.
`
`Our standard protocol was to administer AEDs only to
`those who had acute symptomatic seizure in TBI, whereas pro-
`phylactic AED therapies were not given to those without such
`symptoms in the acute stage of TBI. We usually administered
`AEDs for less than 7 days to patients who had early-provoked
`seizures, while AEDs were continued for longer periods to
`prevent the development of unprovoked seizures in those with
`late-provoked seizure. The basis of discontinuing AEDs of late-
`provoked seizure patients after hospital discharge included all of
`the following: (1) serial electroencephalogram (EEG) showed
`no evidence of epileptiform discharge or seizure-free clinically
`for more than 2 years; and (2) no risk factors for seizures
`recurrence, which include prolonged duration before seizure was
`controlled; high frequency of seizures before control; focal neu-
`rologic abnormalities; poor mentation; complex partial seizures;
`and consistently abnormal EEGs. ' 4’15
`The follow-up period was terminated by death or by the
`end of the study itself (December 2004). Therapeutic out—
`comes and the degree of seizure control after discharge were
`analyzed by a Seizure Frequency Scoring System, which is
`slightly modified from Engel et al.7 (Table 1). For purposes
`of analysis, a score of 4 or below was defined as an excellent
`outcome, and 5 or more as nonexcellent.7 The outpatient
`department followed up most patients after discharge, with
`
`884
`
`m T
`
`able 1 Scoring System for Seizure Frequency
`
`Seizure Frequency Score
`Excellent outcome
`
`AWN—LO
`
`Seizure free, off antiepileptic drug
`Seizure free, need for antiepileptic drug unknown
`Seizure free, requires antiepileptic drug to remain so
`Nondisabling simple partial seizures
`Nondisabling noetural seizures only
`Non-excellent outcome
`One to three times per yr
`Four to 11 times per yr
`One to three times per mo
`One to six times per wk
`One to three times per d
`10
`Four to 10 times per d
`it
`More than 10 times per d but not status epilepticus
`
`Presence of status epilepticus
`12
`
`(OOJVOEUI
`
`Slightly modified from Engel et al.7
`
`others interviewed through telephone to identify neurologic
`outcome.
`
`The clinical data, including gender and clinical manifes—
`tations between the two patient groups (“excellent outcome”
`and “nonexcellent outcome”) during the acute phase of TBI,
`was analyzed by means of a X2 test or Fisher’s exact test. The
`mean ages between the two patient groups were analyzed by
`Student’s t test. GCS score at
`the time of admission and
`
`duration of hospitalization between the two patient groups
`was analyzed by Wileoxon rank sum test.
`The association between (1) early or late PTSs and (2)
`presence of surgical intervention, and the survival curve be-
`tween the two patient groups (“excellent outcome” and “non-
`excellent outcome”) were assessed with Kaplan-Meier Plots
`and compared by log-rank test. Stepwise logistic regression
`was used in evaluating the relationship between clinical fac—
`tors and outcome of seizure, with adjustments made for other
`potential confounding factors. All statistical analysis was
`conducted using the SAS software package, version 9.1
`(2002, SAS, Inc, Cary, NC).
`
`RESULTS
`
`The 170 patients with acute symptomatic seizure in-
`cluded 126 males (age range, 2 months— 87 years; mean age,
`39.6 years) and 44 females (age range, 3 months—83 years;
`mean age, 46.5 years). Among these, 134 had excellent out—
`come and 36 had nonexcellent outcome (Table 2). The degree
`of seizure control after discharge for all 170 cases is listed in
`Figure l. The mean age at onset was 40.5 years i 24.7 years
`for those who had an excellent outcome and 44.6 years i
`20.9 years for those who had a nonexcellent outcome. The
`mean time length of hospitalization was 21.4 days i 16.8
`days and 33.3 days i 29.7 days for those with excellent and
`nonexcellent outcomes, respectively (p 5 0.001).
`No one was excluded because of loss to follow-up. Fol-
`low-up interval in the 170 patients was 1 month to 204 months
`
`April 2008
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`Senyr'ignt {a Lippineatt Wiiiiams a Wiikias. mastherizee repredueaen at as artiste is massages.
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`—
`Table 2 Prognostlc Factors of Posttraumafic Seizures
`
`Factors and Outcome in Positraumatlc Seizures
`
`ME
`
`Nonexcelient Outcome,
`xcellent Outcome,
`
`
`N = 36 p Value Odds RatioN = 134 95% C!M
`Age (yrs)
`40.5 i 24.7
`44.6 i 20.9
`0.358
`Gender
`
`
`
`
`
`Male
`Female
`Clinical features
`
`Posttraumatic amnesia
`Brief unconsciousness
`Motor deficits
`Severity of brain injuries*
`Mild
`Moderate
`Severe
`GCS at admission
`Neuroimaging finding:t
`Depressed skull fracture
`Cortical contusion
`Subdural hematoma
`Epidural hematoma
`lntracerebral hematoma
`Acute symptomatic seizure
`Onset of seizure
`
`96
`38
`
`94
`72
`53
`
`19
`10
`105
`10.5 i 3.9
`
`12
`41
`88
`9
`27
`
`30
`6
`
`23
`20
`17
`
`6
`1
`29
`10.4 t 3.7
`
`4
`9
`27
`2
`12
`
`0.155
`
`0.472
`0.845
`0.406
`
`0.577
`
`0.726
`
`0.749
`0.513
`0.288
`1.0
`0.095
`
`0.51
`
`0.19-1.31
`
`0.61—2.88
`0.44—1.95
`0.35—1.53
`
`0.32-2.39
`034—2247
`
`0.24—2.60
`0.57—3.06
`0.28—1.47
`0.25—5.93
`0.22—1.14
`
`Early—provoked seizures (S7 (1)
`Late-provoked seizures (>7 :1)
`Subtype of seizure
`Generalized
`Focal with or without
`generalization
`Status epilepticus
`Surgical intervention
`7
`63
`Nonsurgery
`29
`71
`Surgery
`50.001
`33.3 t 29.7
`21.4 i- 16.8
`Duration of hospitalization
`———~———_._—__.—_—____—__——
`
`50.001
`
`5.54
`
`2.48-12.34
`
`0.982
`
`0.677
`
`0.003
`
`0.47—2.07
`
`0.24—6.50
`
`3.68
`
`1.51 —8.97
`
`95
`39
`
`63
`71
`
`6
`
`11
`25
`
`17
`19
`
`2
`
`The clinical data, including gender and clinical manifestations between the two patient groups (“excellent outcome” and “non-excellent
`outcome”) was analyzed by means of a X2 test or Fisher’s exact test. The mean ages between the two patient groups were analyzed by Student’s
`ttest. GCS at the time of admission and duration of hospitalization between the two patient groups was analyzed by WilcoXon rank sum test.
`* Relative to “severe brain injury".
`* Fifty-one patients had more than one abnormal neuroimaging findings.
`
`curred within 24 hours of trauma. The mean time interval
`
`between the onset of TBI and early PTSs was 2.1 days i
`1.6 days, and 14.7 days i 5.8 days for the late PTSs (p S
`0.001).
`Regarding seizure subtypes, 77 had generalized seizures
`and 93 had focal seizures with or without generalization. The
`77 generalized seizures included generalized tonic—clonic
`seizures in 73 and myoclonic seizure in 4. The latter 93 focal
`seizures included simple focal seizures in 63 and focal sei—
`zures evolving to generalized tonic—clonic convulsions in the
`remaining 30 (Table 3). The frequency of seizures during the
`acute phase of TBI was: 95 had one episode of seizures, 67
`had more than one episode, and 8 progressed to status epi-
`lepticus. Of these eight cases, two had noncxcellent outcome
`and six had excellent outcome (with five seizure-free after
`completing the treatment for TBI). The outcome of PTS was
`strongly associated with the development of early PTSs (p S
`0.001), although no difference was noted between focal and
`generalized seizures (p = 0.982).
`
`885
`
` 5 5
`
` l
`
`0,1000
`0123 456789101112
`SeinmfimumScofinsfiVstan
`
` 2
`
`Perms
`
`088882388
`
`Fig. 1. Results of seizure frequency score. For the purposes of
`analysis, a score of four or below was defined as an excellent
`outcome, and five or more as nonexcellent.
`
`(mean, 29.5 months). Aside from TEL 42 patients had one or
`more other underlying conditions, which included diabetes mel—
`litus (37), hypertension (9), iatrogenic Cushing’s syndrome (6),
`and pneumonia (8).
`
`During hospitalization, 106 had early PTSs, whereas
`64 had late PTSs. Furthermore, 57.5% (61 of 106) oc-
`
`Volume 64 c Number 4
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`Tbejozmml ofTRAU MA® Injury, Infection, and Critical Care
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`——
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`———.__————___
`Table 3 Relations Between Therapeutic Outcomes, Neuroimaging Findings, and Seizure Subtypes
`”—_——————~———~——.—_._—.___—
`Brain CT at the Time of Admission
`Outcomes
`Excellent
`EDH
`Contusion
`lCH
`SDH
`Nonexcellent
`Depressed Skull
`Score 8 8. 4
`Fracture (N = 16)
`(N = 50)
`(N = 11)
`(N = 39)
`(N = 115)
`(N = 35)
`Seizure Free
`(N = 126)
`(N = 8)
`—————————~___——__—__——.__—_—
`Generalized seizures
`(N = 77)
`Tonic—clonic seizure
`(N = 73)
`Myoclonic seizure
`(N = 4)
`Focal seizures with or
`without generalization
`(N = 93)
`Focal seizures (N = 63)
`Focal seizures evolving
`to tonic—clonic convulsions
`
`(N = 30)
`
`Seizure Subtypes
`
`8
`
`O
`
`7
`_l
`
`28 (2)*
`
`0
`
`19
`00
`
`42 (2)
`
`15(1)
`
`54 (4)
`
`3
`
`0
`
`4
`
`3
`
`0
`
`50
`20(1)
`
`13
`11(1)
`
`48
`20(1)
`
`3
`2(1)
`
`16(1)
`
`0
`
`12
`8(1)
`
`* Values in parentheses indicate number of cases progressed to status epilepticus during acute stage of traumatic brain injury.
`
`Regarding the relationship of the onset of acute symp-
`tomatic seizure (early PTSs and late PTSs) to the frequency
`of seizures during the acute phase of TBI (one episode, more
`than one episode, and presence of status epilepticus), to the
`type of seizures (tonic— clonic seizure, focal seizures evolving
`to tonic— clonic convulsions, and focal seizures), to the sever-
`ity of TBI (mild, moderate, and severe TBI), the statistical
`analysis showed the following: (1) there was no relationship
`between the onset of acute symptomatic seizure (early PTSs
`and late PTSs) and the frequency of seizures (one episode,
`more than one episode, and presence of status epilepticus)
`(p = 0.298); (2) there was a significant relationship between
`the onset of acute symptomatic seizure (early PTSs and late
`PTSs) and the subtypes of seizures (generalized tonic—clonic
`seizure, myoclonic seizure, focal seizures evolving to tonic—
`clonic convulsions, focal seizures, and status epilepticus)
`(p S 0.001); and (3) there was no relationship between the
`onset of acute symptomatic seizure (early PTSs and late
`PTSs) and the severity of TBI (mild, moderate, and severe
`TBI; p = 0.425).
`The other clinical data of the 170 patients are listed in
`Table 2. Furthermore, the mean score of GCS score at ad-
`mission between excellent and nonexcellent outcomes was
`
`10.5 i 3.9 and 10.4 i 3.7, respectively (p = 0.726).
`Among the 170 cases, only 69 had at least one EEGs
`after PIE. Fifty—eight had abnormal EEG readings of which
`38 had EEG readings that showed a predominantly unilateral
`abnormality, whereas 20 had diffuse abnormality. In the 38
`cases, 10 were tonic—clonic seizures, 14 were focal seizures,
`8 were focal seizures evolving into tonic~clonic convulsions,
`2 were myoclonic seizures, and 4 were status epilepticus. Of
`the latter 20 cases, four were focal seizures, four were focal
`seizures evolving into tonic—clonic convulsions, one was
`myoclonic seizure, and two were status epilepticus. Among
`the 11 cases with normal EEG readings after PTS, 6 were
`tonic—clonic seizures, 2 were focal seizures, 2 were focal
`
`886
`
`seizures evolving into tonic—clonic convulsions, and 1 was
`status epilepticus.
`During hospitalization, 160 had abnormal neuroimaging
`findings (Table 2). Of these, 128 had excellent outcome while
`32 did not. In the 10 cases with normal neuroimaging find—
`ings, 6 had excellent outcome. There was no statistically
`significant
`relationship between abnormal neuroimaging
`findings and outcome (excellent and nonexcellent outcomes;
`p = 0.222).
`Of the 170 patients enrolled in this study, 45 received
`more than one AEDs therapy. Of these 45 patients, 36 re-
`ceived 2 AEDs, 7 received 3 AEDs, and 2 received more than
`3 AEDs. The other 125 patients included 103 who received
`phenytoin, 13 who received phenobarbital, 5 who received
`valproic acid, and 4 who received carbamazepine. The mean
`duration of AEDs use in the late-provoked seizure group was
`37.1 months i 36.4 months. The adverse effects of AEDs
`
`included the following: hematologic disorders (leukocytosis
`or eosinophilia) in 12, cognitive impairment in 11, abnormal
`liver function in 10, skin rash in 10 (with one progressing to
`Stevens-Johnson Syndrome), gastrointestinal symptoms in 9,
`lethargy or fatigue in 5, tremor in 3, phlebitis in 2, weight
`change in 1, and gingival hyperplasia in 1.
`Comparisons of clinical features and laboratory data be—
`tween excellent or nonexcellent outcome of TBI were listed
`
`in (Table 2). Statistical analysis of the clinical manifestations
`and laboratory data between the two patient groups revealed
`the following significant findings: onset of acute symptom-
`atic seizures (early or late PTSs; p S 0.001), whether surgical
`intervention was necessary or not (p = 0.003), and duration
`of hospitalization (p S 0.001). Variables used in the logistic
`regression included onset of acute symptomatic seizures
`(early or late PTSs) and necessity of surgical intervention.
`After analysis of all the aforementioned variables, only onset
`of acute symptomatic seizures (early or late PTSs; p 5 0.001)
`was independently associated with outcome of seizures.
`
`April 2008
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`decadent re téspiseett Wliiiams a Wéikias. Sneeteertaed reeredeation at this: artists is preaieited.
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`Factors and Outcome in Posttraumatic Seizures
`
`‘.
`
`5 0
`
`Logrank P< 0.0001
`
`
`
`Late seizure (n=64)
`
`I
`
`J__L..J_.J_
`
`
`I
`
`0015>?»
`
`
`
`Nonuexcellentoutcome .0 N
`
`.0 A
`
`.0 o
`
`
`
`Early seizure (n=106)
`
`
`"I
`I
`I
`1
`O
`50
`100
`150
`Duration of Follow~up (months)
`Fig. 2. Kaplan-Meier plots indicating the percentage of nonexcel-
`lent outcome in the 170 PTS patients after traumatic brain injury.
`The patients were divided into two groups: those with late PTSs, and
`those with early PTSs. The p value was obtained by log-rank com-
`parison of data.
`
`Among the 170 acute symptomatic seizure cases that were
`enrolled in this study, 44 (26%, 44 of 170) progressed to
`unprovoked seizures, whereas 126 (74%, 126 of 170) became
`seizure-free with or without AED therapy. The percent of
`early and late symptomatic seizures accounted for 62% (106
`of 170) and 38% (64 of 170) of episodes in our study,
`respectively.
`
`The onset of PTSs has significant implications for sub-
`sequent treatment and the quality of life of the patient. An
`important question, therefore, is whether there are prognostic
`factors that can identify the seizure frequencies of patients
`after the first acute symptomatic seizures. The risk of devel—
`oping PTSs is primarily analyzed by the severity of the
`antecedent head injury, with high—risk factors that include
`neurologic characteristics such as acute intracranial hema—
`toma, depressed skull fracture, dural penetration, the presence
`of focal neurologic deficits, a deep and lengthy coma, or
`prolonged impairment of consciousness.“18
`In this study, we demonstrated that early acute symp~
`tomatic seizures (<7 days) during the acute phase of TBI had
`better outcomes than for those who did not, though there was
`no difference noted between focal and generalized seizures.
`The mean duration of hospitalization during the acute phase
`of TBI was shorter among those who had excellent outcomes.
`Our study also demonstrated that
`there was a significant
`relationship between the onset of acute symptomatic seizure
`(early or late PTSs) and seizure subtypes (generalized tonic—
`clonic seizures, myoclonic seizures, focal seizures evolving
`to tonic—clonic convulsions, and focal seizures). We also
`found that
`the necessity of neurosurgical
`interventions
`strongly influenced the outcome of seizure frequency.17 The
`nonexcellent outcome in this study may be attributed to an
`underlying brain pathology, surgical intervention, or a com—
`bination of complications.
`Significant differences in study methods, particularly in
`case ascertainment and inclusion criteria, make study com—
`parisons difficult, particularly among subgroups of TBI pa-
`tients. Furthermore, clinical research for seizure prevention
`have several methodologic disadvantagesfsw2 including: (1)
`the patients are heterogeneous and have different propensities
`in developing unprovoked seizures; (2) prolonged period re—
`quired for the occurrence of unprovoked seizures in several
`individuals, which may affect patient compliance; (3) long—
`term treatment in patients developing seizures during the
`treatment; and (4) the increasingly predominant practice of
`starting AEDs after just one seizure, which may lessen the
`difference seen after the study drugs are discontinued and
`changing the natural history of PTS.
`Based on the above studies, AED prophylaxis seems to
`control provoked seizures in patients with TBI, although it
`does not seem to prevent the subsequent development of
`unprovoked seizures, which are poorly tolerated and even
`detrimental to cognitive and behavioral function. Our stan-
`dard protocol in administering AEDs is only for those who
`have had seizures in the acute stage of TBI, continuing this to
`
`887
`
`Logrank P: 0.0006
`
`1.0
`
`0.8,
`
`
`
`Non~excellentoutCome
`
`0.6
`
`0.4
`
`0.2
`
` Surgery (n=100)
`
`
`No Surgery (n=70) 0.0
`
`0
`50
`100
`150
`Duration of Follow~up (months)
`
`Fig. 3. Kaplan-Meier plots indicating the percentages of nonexcel—
`lent outcome in the I 70 PTSs patients after traumatic brain injury.
`The patients were divided into two groups: those with and those
`without surgical evacuation. The p value was obtained by log—rank
`comparison of data.
`
`To look at each factor individually, we calculated Kalpan-
`Meier estimates of the fraction developing nonexcellent
`outcome by different times for each subgroup and tested
`for differences by using a log—rank test. Onset of acute
`symptomatic seizures (early or late PTSs) and necessity of
`surgical intervention between the two patient groups (ex-
`cellent and nonexcellent outcome) showed the following:
`onset of acute symptomatic seizures (early or late PTSs;
`p S 0.0001; Fig. 2), and necessity of surgical intervention
`(p = 0.0006; Fig. 3).
`
`DISCUSSION
`
`The occurrence of seizures after head injury is a recog-
`nized complication of TBI and is known to worsen functional
`outcome significantly afterward.16 Much work has been per-
`formed in preventing the development of, or, at least, mini-
`mizing the impact of PTSs. In our study, acute symptomatic
`seizures accounted for 2% (190 of 9,212) of all episodes.
`
`Volume 64 '0 Number 4
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`Thejournal ofTRAUMA® Injury, Infection, and Critical Care
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`prevent the development of later epilepsy. We do not use
`prophylactic AEDs therapy for those who do not have sei~
`zures in the acute stage of TBI.
`Although our study demonstrates that the time of onset
`of acute symptomatic seizures after TBI influences the out-
`come after PTSs, our study has several limitations. First, this
`is a retrospective analysis and is, therefore, subject to bias of
`unmeasured factors. It was also not possible to assess the
`effect of prophylactic AEDs after the acute stage of TBI to
`prevent later epilepsy or draw any conclusions. Second, only
`those who had acute symptomatic seizures during the acute
`phase of TBI were enrolled. Thus, continued uncertainty was
`present in assessing the incidence of unprovoked seizures
`after TBI in nonselected patients. Third, most patients in this
`study were treated with anticonvulsant medication after their
`
`first acute symptomatic seizure, in accordance with our study
`protocols. Thus, our findings may underestimate the “true”
`frequency of seizure associated with the “natural history” of
`untreated unprovoked seizures.
`Several studies focused on the effects of AEDs for pre-
`venting seizure after TBI.8’19‘26 All of their conclusions
`showed that the use of AEDs should be short (usually less
`than 7 days). The adverse effects of AEDs accounted for
`0.6% to 19.4% in different series.25’26 Because this is a
`retrospective study, the start of AED therapy would differ for
`each patient according to the preference of his or her doctor,
`which may cause potential bias in statistical analysis. Fur-
`thermore, our study only focused on patients who had sei-
`zures after acute traumatic head injury. It would be difficult
`to evaluate both the efficacy and adverse effects of AED
`prophylaxis for PTS and draw a conclusion.
`In conclusion, seizures are an important neurologic com—
`plication of TBI. Although antiepileptic therapy is usually
`short—term for patients with early—provoked seizures, 26% (44
`of 170) of cases with early-provoked seizures progress to
`unprovoked seizures. Regarding the potentially side ef-
`fects of AEDs, antiepileptic therapy should be carefully
`administrated in those nonexcellent outcome patients in-
`cluding those patients who undergo surgical intervention
`and have late—provoked seizures during the acute phase of
`TBI.
`
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