Seizures after Very Mild Head or Spine Trauma

Abstract

Traumatic brain injury (TBI) is a major cause of seizures in the general population. Several studies have shown an increased risk of epilepsy after traumatic brain injury, depending on risk factors, such as severity and time post trauma. The aim of our study was to evaluate the appearance of late seizures after a very mild head trauma or whiplash injury. All patients admitted to the emergency room after a very mild head trauma or whiplash injury during 2008–2010 were evaluated prospectively within 24 hours of the event and followed up 1 year later for evaluation of seizure appearance. The appearance of seizures in the head trauma or whiplash injury group was compared to a control group of orthopedic injury patients. A total of 2999 patients were included in the study—2005 patients with involvement of head and spine trauma and 994 in an orthopedic control group. Three patients (0.1%) out of the whole study group developed seizures: 2 (0.18%) in the head trauma group and 1 (0.1%) in the control group. The conclusion of the study was that post trauma seizure incidence is not significantly different in patients with very mild head or spine trauma and is similar respective to subjects with no non-head or cervical spine injury. This may have medico-legal repercussions.

Introduction

T raumatic brain injury (TBI) is a major cause of acquired epilepsy. TBI is defined as head trauma requiring some degree of medical attention.^1,2 In the US, the incidence of TBI is estimated at 1.8–02.5 per 1000 person years, and higher rates have been reported for Europe and South Africa.³ Post-traumatic epilepsy (PTE) is defined as recurrent, spontaneous seizures that follow TBI. About 6% of epilepsy in the general population is attributed to traumatic brain injury. According to some studies, mild TBI increases the risk of epilepsy by about 50%.⁴ PTE accounts for about 20% of symptomatic epilepsy in the general population.⁵ The incidence of epilepsy after TBI ranges from 1.9% to over 30% depending on age, severity, and duration of follow-up.³ Others have reported an incidence rate of 4%–53%.¹ In civilian populations, the overall risk of epilepsy has been estimated at 2%.⁶ Some PTE studies have defined the endpoint as occurrence of only one unprovoked seizure; however, this is not the generally accepted definition of epilepsy, which requires the occurrence of at least two seizures.⁷

Post-traumatic seizures can be categorized as “immediate seizures” (less than 24 hours after injury); “early seizures” (<1 week after injury); and “late seizures” (>1 week after injury). Trauma can be characterized according to severity as follows: 1) mild trauma: loss of consciousness (LOC) less for than 30 min and no skull fracture; 2) moderate trauma: loss of consciousness for more than 30 min and less than 24 h with or without skull fracture; and 3) severe trauma: loss of consciousness for more than 24 h with brain contusion, hematoma, or skull fracture.⁸ Approximately 80% of individuals who develop PTE, have their first seizure within the first 12 months post injury, and more than 90% by the end of the second year.⁹

As for prophylactic drug treatment, clinical trials have shown that conventional antiepileptic drugs did not protect or prevent late development of epilepsy.¹⁰ There are numerous studies in the literature regarding the incidence of early and late post-traumatic seizures. The studies are diverse in design and population studied, including different patient ages, different types of populations, and different inclusion criteria. These important differences may explain the wide range of findings reported in the literature.

Risk factors for seizures post-head injury have been identified, including duration of loss of consciousness, intracerebral hemorrhage, diffuse cerebral contusions, prolonged post-traumatic amnesia, early PTS, and depressed skull fractures.¹¹ One important population-based study published by Annagers et al.¹² showed that the cumulative probability of unprovoked seizures 5 years post injury in patients with mild TBI was 0.7%. The aim of our study was to evaluate the appearance of late seizures after a very mild brain or whiplash injury within a follow-up period of 1 year prospectively. This research is significant for understanding and/or treating epilepsy because for medico-legal purposes, it is important to investigate whether seizures post mild trauma are more frequent than in other traumatic lesions.

Methods

All patients arriving at the Edith Wolfson Medical Center emergency room due to mild head trauma or whiplash injury from 2008–2010 were considered for study inclusion. Data were collected from the emergency room records within 24 h of patient arrival. The study was approved by the medical center's ethics committee. The data collected included the type of injury, Glasgow Comma Scale (GLS), neurological examination, and past history of diseases and drug therapy.

Inclusion criteria

All consecutive adults (18 years and older) arriving at the E. Wolfson Medical Center emergency room after very mild head or cervical spine injury with no loss of consciousness (e.g., confusion), with a Glasgow Coma Scale of 15 and normal neurological examination, were included. The patients included were those who were involved in a road accident or a falling event according to their medical history, and/or who had some physical trauma, such as a skin abrasion or local bleeding, but did not lose consciousness. For inclusion, injury had to have occurred within the 24 h prior to emergency room arrival.

Exclusion criteria

Patients with loss of consciousness, antero- or retrograde amnesia, Glasgow Coma Scale of <15, and requiring hospitalization and/or observation because of the injury were not included in this report. Also excluded were patients with a history of epilepsy or seizures in the past or in any family members; or structural brain lesions that could potentially cause seizures, such as stroke, tumors, intracerebral hemorrhages, neurodegenerative diseases, or drugs. A very mild head trauma was defined as direct or indirect trauma to the head with no change in brain function, including no loss of consciousness, amnesia, confusion, or neurological deficit. A cervical spine injury was defined as that compatible with whiplash injury. This definition is different from the definition of mild traumatic injury and includes very mild head trauma patients who later on develop severe complaints of headaches and vertigo, sometimes late LOC, but with no acute neurological deficits during the event itself.

Upon discharge from the ER, the patients and their caregivers were orientated on the signs and symptoms of seizure activity. If such an event was suspected by the patient or family member, the patient was instructed to arrive at the outpatient clinic to have the patient undergo examination by a neurologist specializing in epilepsy, including syncope and fainting events. Patients were followed-up for 12 months post trauma by telephone and asked questions regarding events of loss of consciousness (how many and type), hospitalizations, confusional state episodes, behavior change episodes, and the results of any brain or spine imaging done during this period. The questionnaire used by the telephone interviewer consisted of ten items according to Ottman et al.¹³ All seizure activity was first documented by a phone call from the patient, together with a family member. Patients with a suspected seizure were then examined in the outpatient clinic with the relevant medical records of their hospitalization.

For comparison, a control group was recruited consisting of patients arriving at the emergency room with orthopedic injury, including fracture of limbs and low back pain (LBP) with no head or cervical pathology. A total of 994 orthopedic patients were included: 183 (18.4%) with lower limb fractures; 199 (20%) with upper limb fractures; and 612 (61.5%) with low back pain. None of the control group subjects had concomitant head trauma or whiplash injury. The groups were matched by sex and age. The control group individuals were also contacted by phone in the same manner as the trauma group by an interviewer who was a neurologist specializing in epilepsy.

The present study was designed to have 80% power to detect a between-group (head injury vs. orthopedic) difference in the proportion of subjects who developed incident seizure within 1 year after injury of 300%. Specifically, we hypothesized that 1.5% of the head injury subjects and 0.05% of orthopedic subjects would experience an event of incident seizure during the first 1 year period following injury. Using these assumptions and employing a case:control ratio of 2 and a two-sided alpha of 0.05, we calculated that the 2000 head injury subjects (cases) and 1000 orthopedic subjects (controls) were required.

Results

A total of 2430 patients admitted to the emergency room in the E. Wolfson Medical Center because of very mild head trauma or whiplash injury between the years 2008–2010 were enrolled. Of these, a total of 2005 patients were included in the study and 425 were excluded (395 because they did not fit the inclusion criteria and 30 were lost for follow-up). Three patients (0.1%) out of the total cohort 2999, 2 (0.18%) out of 1121 head trauma patients, and one (0.1%) in the control group developed seizures during the first year of follow-up. Time from the accident for both patients was 3 and 5 months, respectively. Eighty percent of the total cohort had been admitted to the emergency room after a road accident (75% in the head trauma group, 90% in the whiplash injury group, and 90.4% in the control group). Twenty percent arrived at the emergency room after a fall.

Demographic characteristics are presented in Table 1. There was no difference between groups regarding age and sex. There were only three seizure events in the total patient cohort; two in the head trauma group and one in the control group. These results show that 0.18% of the head trauma and whiplash injury groups respective to 0.1% of the control group showed a risk ration of 1.7 (0.95% CI 0.35–8.5). The analysis of the observed RR of the head trauma patients only respective to the control group was 1.1 (95% CI 0.2–5.47). No association between head trauma and seizure incidence was detected. No difference in seizure rate was found between the head trauma and the orthopedic group. In another analysis, whiplash injury patients were excluded and only the head trauma cases were compared to the orthopedic cases. No difference in incident seizure rate was detected.

Table 1.

Data of Enrolled Patients

Parameters	Total	Head trauma	Whiplash	Control	p
No. (%)	2999	1121 (37.4)	884 (29.5)	994 (33)
Age (y)		39.1±16.3	38.3±15.4	39.4±15.9	0.33
Sex (% m)	1869 (62.3)	695 (62)	522 (59)	666 (67)
Seizures (%)	3 (0.1)	2 (0.18)	0	1 (0.1)	0.46
Type of trauma (%)
Road accident	2399 (80)	840 (75)	795 (90)	828 (90.4)
Falls	600 (20)	281 (25)	89 (10)	96 (9.6)

Characteristics of the patients with seizure

The first patient, a 65-year-old male with HTN in his past medical history, was diagnosed as suffering from a seizure event. During a visit to his general practitioner, he lost consciousness after the doctor noticed left focal seizures on the left side of his face. The patient was then hospitalized for 3 days. An EEG showed right temporal focal slowing with no epileptiform discharges, and a MRI brain scan was normal. His blood tests, ECG, Holter test, and cardiac echo were normal. The only traumatic event was a road accident 3 months previous when he was diagnosed with mild head trauma in the emergency room. The patient did not have a personal or family history of epilepsy.

The second patient, a 43-year-old woman, from the head trauma group and 5 months after a road accident, was hospitalized suffering from generalized clonic tonic seizures for the first time in her life. Brain MRI was normal. EEG, which was done an hour post seizure, showed mild slowing, suggesting a post ictal state and no other abnormalities. She had no other disease and did not take any medication. Her blood tests were normal, and she had no history of drugs or alcohol abuse.

The third patient, a 51-year-old female, from the control group was referred to the emergency room because of a broken right leg after falling. She had not suffered any head trauma and appeared to be in good condition, so after orthopedic treatment she was discharged. Some 10 months later, she was hospitalized in our department because of a generalized tonic-clonic seizure for the first time in her life. She underwent a neurological examination which was normal, as were the MRI scan and cardiac studies. EEG showed a right temporal slowing with a generalized spike and wave only once immediately after the seizure episode.

Discussion

There is only a limited amount of evidence about an association between seizures and mild TBI. Our study of very mild head trauma and whiplash injury showed that 3 (0.1%) out of 2999, and 2 (0.18%) out of 1121 patients, respective to one (0.1%) out of 994 of the control group with orthopedic injuries developed seizure within 1 year follow-up. In comparison, no difference in the late traumatic seizure rate between the groups was found (p=0.46). These results suggest that patients with a very mild head trauma or whiplash injury (GCS=15) have no increased risk of developing late seizures respective to patients with other types of trauma having no injuries of the head or neck, but the RR of the head trauma group respective to the control group was 1.7.

The incidence of seizures in the mild injury group was very low, even in comparison to the incidence of epilepsy and unprovoked seizures in the general population.⁴ It is known from other studies in the literature that type and severity of TBS is a main factor in predicting the development of late post-traumatic seizure.¹⁴ Excluding the whiplash group, the rest of our results are similar to those reported by Annagers et al.,¹² who reported a standardized incidence ratio of seizures post mild brain injury was 1.5, with no increase over 5 years. In their study, 5 (0.18%) patients out of 2758 patients with mild head injury developed seizures during the first year of follow-up. The author reported that the incidence of seizures was only marginally increased in the group with mild injuries. This study also included children, but in general, their results are similar to ours. Another study regarding post-traumatic epilepsy in children and young adults, Christensen et al.¹⁵ reported a two-fold increase in seizure risk after mild brain injury in a 10-year follow-up period. Thapa et al.¹⁶ showed an incidence of 2.7% in late seizure, but these results were obtained in a pediatric population and included all types of trauma. Another report estimated post-traumatic seizure risk within 1 year after mild injury at 0.1% in adults and concluded that the incidence of seizures was not significantly greater than in the general population—findings consistent with those of the present study.¹⁷

In our prospective study with 1-year follow-up post trauma, no excess of late post-traumatic seizure was detected compared to the control group. Differences in incidence estimates between our study and previous ones may stem from type of injury included. In other studies, mild head trauma was defined as loss of consciousness or amnesia lasting less than 30 min; while in the present study, very mild head trauma was defined as no loss of consciousness and no need for brain CT or hospitalization. All subjects were examined in the emergency room and included patients with very mild head trauma or whiplash injury with no neurological deficit.

The pathogenesis of brain lesions in whiplash injury can be explained by the mechanism of acceleration/deceleration, which causes tearing of efferent veins, diffuse axonal injury, and diffuse vascular injury, and in very mild head trauma, the brain injury and seizures can be explained as probably caused by changes that occurred in neuronal network, including inflammatory changes, axonal sprouting, and dedentratic modifications over days to weeks or even months.¹⁸ Most of our study population suffered from motor vehicle accidents (80%) and the rest from falls or work trauma (20%), which may explain the relatively young age of the patient population.

Findings of the present study must be considered in the framework of the study's limitations. Most importantly, very few cases of post-trauma seizure were observed. Thus, despite the large cohort, incident seizure was so infrequent that the study could not detect a between-group difference. Additionally, the population reflects bias insofar as included patients were those who presented at the emergency room. It is possible that mild head injury subjects who did not present at the emergency room nevertheless experienced post injury seizures, but were not sampled. Thus, our incidence estimates may be biased downward. Finally, the study follow-up was only 1 year. It is possible that the onset of seizure following mild trauma could occur more than 1 year after injury.

The absence of electrographic examinations in this population can indicate that the data do not demonstrate the lack of post-traumatic epilepsy, because there are few studies in the literature showing that continues EEG monitoring raises the incidence of post-traumatic seizures when used in the ICU. The importance of cEEG monitoring is to detect nonconvulsive seizures and/or status epilepticus. Vespa et al. showed that nonconvulsive seizures after traumatic brain injury were associated with hippocampal atrophy suggesting a pathophysiologic siginificance.¹⁹ In our study, the patients suffered from a very mild head trauma or whiplash injury and were not hospitalized at all. Anyway it is important to perform continued EEG monitoring in patients who have the risk of developing seizures in order to detect subclinical seizures.

Nevertheless, the present prospective study conducted in a large cohort of post trauma patients and compared to a matched control group of orthopedic injury patients suggests that post-trauma seizure incidence is quite low after very mild head injury or whiplash seizure, and that the rate may not differ from subjects with non-head or cervical spine injury.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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