Keywords posttraumatic seizures - skull fracture - fracture seizure index
Introduction
Skull fracture (SF) is a known clinical manifestation of the mechanical deformations
accompanying head injury (HI). Its occurrence indicates a substantial and potentially
harmful energy transfer to the skull as well as the underlying intracranial structures.[1 ]
[2 ] Although SFs may occur with no accompanying neurologic injury,[3 ] and conversely, significant injury to the brain and its coverings sometimes with
fatal outcome have been reported without SFs[3 ]
[4 ]
[5 ]; however, SFs occurring in association with life-threatening conditions including
intracranial hematoma, parenchyma contusions seizures, cerebral edema, subarachnoid
hemorrhage, and hydrocephalus are a frequently reported experience among patients
with craniocerebral trauma.[3 ]
[4 ] The frequency of association between cranial vault fractures and these lesions generally
and seizures specifically is variable judging from previously reported studies.[5 ]
[6 ]
[7 ] This study evaluates and scores the association between seizures, calvarial fractures,
and acute traumatic intracranial lesions through an index—fracture seizure index (FSI)—in
an attempt to predict the risk of seizures in HI patients with cranial vault fractures.
FSI may provide a guide for decisions on seizure prophylaxis in HI patients with cranial
vault fractures.
Aims/Objectives
To study SFs and associated lesions, determine the predictors of posttraumatic seizures
(PTS) in HI patients with skull vault fractures over a 5-year period from March 2012
to February 2017.
Materials/Methods
A prospective observational cohort study of patients with head trauma and calvarial
fracture was presented to the University of Nigeria, Teaching Hospital Enugu, from
March 2012 to February 2016.
Inclusion criteria : Patients with history of trauma and HI with computed tomographic (CT) evidence of
calvarial fractures were enrolled into the study.
Exclusion criteria : Patients with skull base fractures, history of seizures, or previous admissions
for HI. Enrolled patients were evaluated on the basis of age, sex, etiology of HI,
level of consciousness (assessed using the Glasgow coma scale [GCS] score), occurrence
of seizures and seizure type, electroencephalogram (EEG) reports, and neuroim-aging
findings on CT scan. Data acquisition and analysis were performed using Statistical
Package for the Social Sciences (SPSS; IBM Inc.) version 21. The seizure risk for
fractures and associated conditions as well as statistical ass ociations were evaluated
using risk ratio estimation, chi-square test, and confidence limits where appropriate
and p values were set at the 95% level of confidence. For each associated lesion, a seizure
index—SI (x )—was calculated using the relative risk of seizure occurrence associated with the
lesion. The fracture seizure index–FSI (T )—the overall risk of seizure in patients with calvarial fracture and associated conditions
was estimated by a summation of the relative risk (risk ratio) of seizure occurrence
among the associated lesions.
where fx = relative risk or risk ratio (rr) of each associated lesion. Overall risk was graded
as low risk (low), moderate risk (intermediate), and high risk (major). Risk of seizures
based on FSI was used to design a simple guide for seizure prophylaxis in head-injured
patients with calvarial fractures and seizures.
Ethical approval : Informed consent was obtained from every prospective patient or caregiver in the
case of a patient(s) incapable of providing consent. Ethical approval for this study
was obtained from the institutional review board (IRB) of the hospital.
Results
A total of 637 patients with HI were studied over a 5-year period, 135 (21.2%) of
them sustained calvarial fractures, and 91 (71.4%) of fractures resulted from road
traffic accidents (RTAs) ([Table 1 ]). The age range was 5 months to 65 years ([Table 2 ]). There was a strong male predilection, M:F = 11.6:1 (124 males and 11 females)
among the fracture subgroup compared with the nonfracture group 2.6:1 (361 males and
141 females) (χ2
= 13.0, p < 0.05, df = 1). Cranial CT scans showed 69 (54.8%) patients with linear fractures,
50 (39.7%) with depressed fractures, 7 (5.6%) with elevated fractures, and 8 (5.9%)
patients with more than one fracture type. Among those with fractures, 77 (61.1%)
had cerebral contusions, 11 (8.7%) intracerebral hematoma, 12 (9.5%) subdural hematoma,
and 31 (24.6%) had extradural hematoma (EDH). Sixty-nine (51.1%) patients with fracture
had mild HI, 45 (33.3%) sustained moderate HI, whereas 21 (15.6%) sustained severe
HI GCS ≤8. Thirty (22.2%) patients had PTS, 25 (18.5%) suffered PTS, and 5 (3.7) had
late PTS. Among nonfracture patients (361), 31 (8.6%) suffered seizures, 27 of them
were early PTS and 4 were late PTS. Seizures occurred significantly more in the fracture
subgroup (χ2
= 10.1, p < 0.05, df = 1, hazard ratio [HR] = 2.58).
Table 1
Etiology
Etiology
Frequency (%)
Road traffic accident
97 (71.4)
Motorcycle
63 (46.8)
Motor vehicle Tricycle
32 (23.8)
2 (0.8)
Assault
26 (19.0)
Machete cuts
19 (13.5)
Gunshot
4 (3.2)
Other
3 (2.4)
Fall from height
11 (8.7)
Other (recreational)
1 (0.8)
Total
135 (100)
Table 2
Age distribution (years)
Age groups (y)
Frequency
Percentage
Cumulative percentage
Mean age: 29.1 ± 2.3 years; 95% CL range: 5 months to 65 years.
0–10
13
9.6
9.6
11–20
18
13.3
22.9
21–30
45
33.3
56.2
31–40
41
30.4
86.6
41–50
8
6.0
92.6
51–60
4
3.0
95.6
61–70
6
4.4
100.0
Total
135
100.0
The mean injury-to-ictus interval in the fracture group was 1.94 ± 0.90 days (95%
confidence interval [CI]) for early seizures and 21.0 ± 3.5 days for late PTS, whereas
among the nonfracture group, 3.1 ± 1.7 days (95% CI) were for early seizures and 19
± 2.7 days for late seizures. Early seizures also occurred significantly earlier in
the fracture group (χ2
= 5.9, p = 0.027, df = 1). However, there was no statistical difference between mean injury
to ictus interval for late seizures among the fracture and no fracture subgroups (χ2
= 1.66, p > 0.05, df = 1). Early seizures were generalized in 13, focal in 7, and secondarily
generalized in 5 patients, whereas late seizures in the fracture subgroup were focal
in 3 and secondarily generalized in 2 patients respectively. Among patients with fracture
and early seizures, 11 (47.8%) had GCS score ≤8 (odds ratio [OR] = 4.9, rr for seizure
risk = 8), 12 (52%) had depressed SFs (OR = 3.2, rr = 4.1), and 14 (60.9%) sustained
multifocal cerebral contusions (OR = 3.5, rr = 5.2). The occurrence of late PTS did
not show a statistical relationship with early PTS in both the fracture (χ2
= 2.98, DF = 1, p > 0.05) and nonfracture subgroups (χ2
= 1.17, df = 1, p > 0.05). The statistical association between calvarial fractures, seizures, and acute
traumatic lesions are depicted in [Tables 3 ] and [4 ] For associated lesions, an SI (x ) was estimated, and FSI(T ) as summation of seizure risk is depicted in [Table 3 ]. Based on FSI, we propose a seizure prophylaxis guide for patients with skull vault
fractures—low risk-watchful surveillance, no seizure prophylaxis.
Table 3
Fracture seizure index, associated lesions, and seizure prophylaxis guide
A. Lesion
Seizure risk (rr)
SI (x)
Abbreviations: FSI, fracture seizure index; rr, or risk ratio; SI, seizure index.
No fracture or associated lesions
0.97
1.0
Linear fracture
2.2
2.0
Hemorrhages or focal contusion
3.1
3.0
Depressed fracture
4.0
4.0
Multifocal contusions
5.4
5.0
Severe head injury
8.3
8.0
B. Seizure risk
FSI(T ) = Σfx
Low
0–2
Intermediate
3–5
High risk
> 5
C. Seizure prophylaxis based on FSI
Risk
Total
FSI(T ) = Σfx
Not advisable
Low
0–2
Advised for 1 wk
Intermediate
3–5
Advised for 2 wk
High
> 5
Table 4
Markers and associations of posttraumatic seizure
Seizure
No seizure
Total
Significance
Relative risk
Abbreviation: GCS, Glasgow coma scale.
Sex
Male
21 (15.5%)
103 (76.3%)
124 (91.8%)
χ2
= 3.303, p = 0.069
Female
4 (3%)
7 (5.2%)
11 (8.2%)
Total
25 (18.5%)
110 (81.5%)
135 (100%)
Type of fracture
Depressed
17 (13.8%)
38 (30.9%)
55 (44.7%)
χ2
= 6.682, p = 0.009
4.0
Linear
8 (6.5%)
60 (48.8%)
68 (55.3%)
χ2
= 0.755 p = 0.873
2.2
Total
25 (20.3%)
98 (79.7%)
123 (100%)
Cerebral contusions
Present
25 (18.5%)
66 (48.9%)
91 (69.5%)
χ2
= 6.59, p = 0.033
Absent
3 (2%)
37 (28.5%)
40 (30.5%)
5.2
Total
27 (20.4%)
103 (78.5%)
131 (100%)
Admission GCS
3–8
11 (8.1%)
10 (7.4%)
27 (20.0%)
χ2
= 10.48, p = 0.001
8.3
9–12
10 (7.4%)
35 (25.9)
108 (80.0%)
2.3
13–15
9 (6.7%)
60 (44.5%)
0.7
Total
30 (22.2%)
105 (77.8%)
135 (100%)
Intracranial hemorrhages
Present
16
25
41
3.1
Absent
16
78
94
χ2
= 5.982, p = 0.014
Total
32
103
135
Moderate risk: seizure prophylaxis for 1 week.
High risk: seizure prophylaxis for 2 weeks.
Discussion
From this series, the incidence of skull vault fractures is 21.2%. A similar incidence
of 21.2% was previously reported by authors from another region of Nigeria.[8 ] The incidence of SFs varies with the severity of HI as well as age group among other
factors.[9 ]
[10 ] The distribution of fracture type shows that linear and depressed fractures are
more common in 54.8 and 39.7% cohorts, respectively.
Some 6% of the patients with HI present with more than one fracture type. Among patients
with vault fractures, a mean age at presentation of 29.1 ± 2.3 years clearly illustrates
its high occurrence among young adult patients and shares some similarity with the
demographic profile for closed HI in the setting and globally.[8 ]
[10 ]
[11 ] The authors also found a greater male predilection for PTS among our cohorts with
vault fracture (M:F = 11.6), when compared with the nonfracture subgroup (M:F = 2.6).
In a longitudinal prospective observational study from the Indian subcontinent, Thapa
et al found a higher association between female sex and PTS. However, their findings
did not specifically describe the sex demographics of HI in patients with vault fractures.[12 ] The authors’ suspicion of a causal association between fractures and early seizures
derives from the following findings.
First, vault fractures and early PTS share a similar trend over the study period ([Fig. 1 ]), and this relationship was confirmed by a HR of 2.58. A more frequent occurrence
of early PTS in the fracture subgroup is also suggestive of some causal association
(χ2
= 10.1, p < 0.05, df = 1). Further, there was a significant temporal association between early
seizures (χ2
= 5.9, p < 0.05, df = 1) and fractures, and this association was absent in patients with late
seizures.
Fig. 1 Line graph showing the profile of fractures and seizures over the study period. HR = 2.58 for early seizures.
These may all suggest a likely role for vault fractures in the etiology of early seizures.
Yeh et al, in a retrospective population-based study, found an adjusted HR of developing
epilepsy of 10.5 among TBI patients with SFs generally.[13 ] About four decades ago, among 1,000 patients with nonmissile depressed fractures,
Jennett et al found a 10% and 15% early and late seizure incidence rates.[14 ] We believe the considerable difference between Jennet's series and early and late
seizure rates of 18.5% and 3.7%, respectively, from this study is a result of dissimilar
study populations as well as times of study.[14 ] We opine that a clear elucidation of the association between vault fractures and
PTS will provide a sound scientific basis for recommendations on the management of
fracture-associated PTS based on scientific evidence. This is the basis of our study.
In a previous population-based study, Annegers and Coan[7 ] attributed a moderate risk of seizure occurrence to HI patients with associated
SFs (relative risk: 2.9); however, they related seizure risk neither to fracture characteristics
nor to other associated lesions in their statistical analysis.
We wish to state that our study is not the first to evaluate the statistical relationship
between PTS, SFs, acute traumatic mass lesions, and HI severity.[15 ] Some other authors have also previously published mathematical methods for predicting
seizure occurrence after HI.[15 ]
[16 ]
[17 ] However, these models were mainly for penetrating HI and also were used to evaluate
war injuries—study population with disparate epidemiologic and etiopathogenic characteristics
when compared with our civilian and peace time cohorts. This study, however, is the
first attempt at defining seizure risk among patients with civilian HI, vault fractures,
and associated lesions using a predictable scientific profile based on relative risk
estimation ([Tables 3 ] and [4 ]). We are unable to explain a direct pathophysiologic link between seizure occurrence
and vault fractures in the absence of cortical injury, presence of an intact dura,
and underanged cerebral cortical homeostasis and biochemical milieu. However, we hold
the opinion that abnormal energy transfer to underlying cortical regions from a fracture-genic
mechanical skull deformation may provide the pathophysiologic substrate for seizure
induction by increasing neuronal excitability in an incompressible brain. This view
is supported by evidence from an experimental HI model.[18 ] The phenomenon of fracture-associated seizure disorder occurs without prejudice
to the seizure-inducing potentials of other associated lesions such as contusions,
intracranial hematoma, and cerebral edema. [Table 3 ] shows the seizure risk indices of the different lesions as well as the FSI, a summation
of seizure risk. From this study, FSI values 0 to 2 suggest low seizure risk. This
subgroup includes patients with either linear fractures alone or no fractures at all
as well as patients with no associated lesions or severe HI.
We do not advocate seizure prophylaxis in this category. However, we advocate watchful
surveillance and EEG for those with linear fractures. Those with intermediate or moderate
risk for seizures have FSI values 3 to 5. This class corresponds to patients with
depressed fractures, multifocal contusions, and intracranial hemorrhages. For the
moderate seizure risk group, we advocate EEG as well as the current practice of seizure
prophylaxis for 1 week. Those with FSI > 5 have the highest seizure risk. This subcategory
includes severe HI patients and shows that the risk of seizures is highest among them
if they sustain fractures as well.
We advocate EEG and seizure prophylaxis for 2 weeks in this category to cover for
the critical period of altered neuroexcitability and trauma-induced neuroinflammation
that has been reported to persist till the second week in patients with severe HI.[19 ] In the estimation of FSI, the concept of risk summation for multiple lesions applies.
For instance, in a patient with multifocal contusions with SI (x ) = 5 and associated depressed fracture with SI (x ) = 4, the FSI (fx ) is 9.0, a value within the high seizure risk category. We are currently applying
this protocol to our patients with HI and vault fractures to evaluate its usefulness
in reducing the current (22.2%) incidence of seizures and hope to publish the results
in a future paper. We also hope that this study will trigger more clinical inquiry
from other authors aimed at verifying the scientific and clinical utility of FSI.
This study did not consider the impact of surgical treatment of SFs in the risk or
outcome evaluation because fracture treatment has not been shown to alter the natural
history of PTS.[20 ] Our study has some limitations including the noninclusion of some other likely risk
factors for PTS such as genetic predisposition.[21 ] We also believe that seizure risk determination in children with HI may require
a modified FSI or different schema altogether because of the influence of age on both
the rate of occurrence and type of PTS based on a previously reported study.[22 ]
Conclusion
Our study suggests that vault fractures may have a causal association with early PTS.
Occurrence of early PTS bears a predictable relationship with vault fractures and
associated lesions defined by the FSI. We believe decisions on prophylaxis for early
seizures in HI patients with vault fractures can be guided by FSI-based risk estimation.
