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10. Post-Traumatic Seizure Disorder Following Acquired Brain Injury

Robert Teasell MD FRCPC, Shannon Janzen MSc, Heather MacKenzie MD, Pavlina Faltynek MSc, Shawn Marshall MSc MD FRCPC, Nora Cullen MSc MD FRCPC

Abbreviations

ABI          Acquired Brain Injury
GCS        Glasgow Coma Scale
LPTS       Late Post-Traumatic Seizure
PTE        Post-Traumatic Epilepsy
PTS        Post-Traumatic Seizure
RCT        Randomized Controlled Trial
TBI         Traumatic Brain Injury

Key Points


Phenytoin may be an effective prophylactic drug for early post-traumatic seizures, however its effectiveness to treat late post-traumatic seizures has not been established.

Phenytoin is more effective than valproate as a prophylactic anti-seizure medication.

Levetiracetam is as effective as phenytoin in treating and preventing seizures in individuals in the intensive care unit post ABI.

First generation anti-epileptic drugs are as effective as new generation anti-epileptic drugs in reducing post-traumatic seizures.

Glucocorticoid administration may increase seizure frequency.

Injections of midazolam may reduce active seizure activity.

Carbamazepine may be effective in reducing seizure recurrence.

Methylphenidate may be effective in reducing rate of post-traumatic seizures.

Surgical resection may reduce seizures if the focus of the seizures can be localized.

There is no difference in effectiveness between early craniectomy versus craniotomy for the reduction of the frequency of seizures.

Introduction

Post-traumatic seizures (PTS), although identified as a serious consequence of traumatic brain injury (TBI), remain an understudied problem (Ferguson et al., 2010). Post-traumatic seizure disorders have been defined in the Practice Parameter of the Antiepileptic Drug Treatment of Post-traumatic Seizures by the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation (1998) and can be found in Table 10.1. This module is intended to provide insight into the frequency and clinical presentation of PTS, as well as any evidence-based interventions that exist.

Evidence Table(s)
Table 10.1 Definitions of Post-Traumatic Seizures (p. 595; Brain Injury Special Interest Group, 1998)

10.1 Incidence of Post-Traumatic Seizures

It is believed that up to 20% of structural epilepsy in the general population is a result of TBI (Bushnik et al., 2012). Of all patients with TBI who are hospitalized, 5% to 7% will experience PTS. However, the incidence of PTS is much higher on rehabilitation units (as high as 18%), which reflects increased injury severity and the presence of a higher number of risk factors in this population (Armstrong et al., 1990; Bontke et al., 1993; Cohen & Groswasser, 1991; Kalisky et al., 1985; Sazbon & Groswasser, 1990; Sundararajan et al., 2015; Wang et al., 2013a). The incidence of late post-traumatic seizures (LPTS) ranges from 5% to 19% (Bushnik et al., 2012; Zhao et al., 2012). Zhao and colleagues (2012) found that when seizures occurred post injury, 88.7% were diagnosed as late seizures; with the majority of those (66%) occurring between 10 days and three years post-injury. A study examining 236,164 individuals with TBI found that 2.4% had pre-existing epilepsy or a seizure disorder (Wilson & Selassie, 2014); unfortunately, the consequences of a TBI may be more severe in this population.

For those who sustain a severe non-penetrating TBI, approximately 11% will experience LPTS and for those who have a TBI as the result of a penetrating injury, the incidence increases to 13-50% (Ascroft, 1941; Caveness & Liss, 1961; Malav et al., 2015; Yablon, 1993). In young adults TBI is the leading cause of epilepsy (Annegers, 1996). Following acquired brain injury (ABI), seizures have been associated with secondary accidental injury, depression, a loss of independence (i.e., driving privileges) and a reduction in employability (1998).

10.2 Risk Factors for Post-Traumatic Seizures and Post-Traumatic Epilepsy

There are several patient and injury characteristics that increase the likelihood of developing PTS. These include increased injury severity (Glasgow Coma Scale (GCS) score of less than 10, prolonged length of coma, prolonged length of post-traumatic amnesia), depressed skull fractures, cortical contusions, subdural hematomas, epidural hematomas, intracerebral hematomas, penetrating injuries and wounds with dural penetration, a seizure within the first week of injury, being male, age, and having had multiple neurosurgical procedures (Brain Injury Special Interest Group, 1998; Dikmen et al., 1991; Englander et al., 2003; Krause-Titz et al., 2016; Walker et al., 2015; Wang et al., 2013a; Yablon, 1993; Yeh et al., 2013; Zhao et al., 2012). Ferguson et al. (2010) also found those who had other concomitant injuries or comorbid conditions, previous head injuries, stroke, or depression were more likely to develop LPTS, which is congruent with the findings of previous studies (Andelic et al., 2009; Annegers et al., 1998; Weiss et al., 1983). The risk of unprovoked epileptic seizures is greatest during the first six months post injury and higher for individuals with severe injuries (Mahler et al., 2015).

The first year post injury is often when post-traumatic epilepsy (PTE) develops (Di Luca & de Lacerda, 2013; Lamar et al., 2014; Lucke-Wold et al., 2015), however, the risk remains high within two years of injury (Lamar et al., 2014). In a cohort study conducted by Ferguson et al. (2010), the incidence of PTE was highest in individuals 30 to 54 years of age. Higher rates of PTE have also been reported for those 50 to 59 and 60 to 69 years of age (Zhao et al., 2012). According to a meta-analysis conducted by Xu and colleagues (2017), risk factors for PTE include: male gender, previous alcohol abuse, loss of consciousness at time of TBI, post-traumatic amnesia, and focal neurological signs. Moreover, Diamond et al. (2014) recently explored genetic variance and PTE development in 256 individuals with moderate to severe TBI. The study found that higher cerebrospinal fluid and serum IL-1β (a potential biomarker for epilepsy) ratios were associated with an increased risk of PTE (Diamond et al., 2014). Due to this study being one of the first studies to explore genetic variability, more studies are needed before firm conclusions can be made.

It is important to identify patients who are at high-risk of developing PTS since these patients may benefit from pharmacological seizure prophylaxis. According to Yablon and Dostrow (2001) the clinical characteristics of the patient, the injury, and information obtained from neuroimaging and electrophysiologic assessment techniques can be used to identify those at high risk for developing seizure disorders post injury.

10.2.1 Onset

The risk of epilepsy is highest within the first two years following brain trauma (Dikmen et al., 1991; Englander et al., 2003; Yablon, 1993). Yablon and Dostrow (2001) have noted that one-half to two-thirds of individuals who suffer PTS will experience seizure onset within the first 12 months, and 75-80% will have seizures within two years of their TBI (Caveness et al., 1979; da Silva et al., 1992; da Silva et al., 1990; Pohlmann-Eden & Bruckmeir, 1997; Walker & Yablon, 1959; Walker & Yablon, 1961). Similarly, of those patients with PTE, Zhao et al. (2012) reported that 66% developed seizures within the first 6 months, 9.9% between 7 and 12 months, 11.7% between 13 and 24 months, and 8.5% between 25 and 36 months. Further, Wang et al. (2013b) examined 3039 individuals with TBI and of the 9.8% that experienced PTS within the first 2 years, occurrence rates at 6 months and 1 year were 59.9% and 78.1%, respectively.

Although the risk of developing PTS is highest within months after the injury (Temkin, 2001), the risk remains high for a period of years. As brain injury severity increases, the period of time for which a survivor is at risk of developing PTS also increases. After 5 years, adults with mild TBI no longer have a significantly increased risk relative to the general population (Annegers et al., 1998), whereas those with moderate or severe TBI, or penetrating TBI remain at increased risk for more than five years post injury (Annegers et al., 1998; da Silva et al., 1992; Pagni, 1990; Salazar et al., 1985). Moreover, military personnel suffering severe penetrating missile brain injuries show an elevated risk for more than 15 years after the injury (Annegers et al., 1998; Caveness et al., 1979; Feeney & Walker, 1979; Salazar et al., 1985; Weiss et al., 1983). The incidence of seizures beginning later than three years post injury is 5% (Zhao et al., 2012).

Those with penetrating trauma typically have their first unprovoked seizure sooner than those patients with non-penetrating trauma (Kazemi et al., 2012). Unprovoked seizures occurred at a median time of one year post injury in a study of 50 participants (Di Luca & de Lacerda, 2013); the former was influenced by injury severity, as well as age at the time of injury (Di Luca & de Lacerda, 2013). In contrast, a study by Kazemi et al. (2012) found that for those with penetrating trauma, 78% had their first seizure within 1 year and 22% after 1 year. The mean latency to epilepsy onset was found to be shorter for mesial temporal sclerosis compared to lesional neocortical trauma (Gupta et al., 2014).

10.2.2 Recurrence

Seizure recurrence is an important factor in the determination of disability, likelihood of employment, and quality of life, and has been associated with increased health care costs (Baker et al., 1997; Yablon & Dostrow, 2001). After a brain insult, there is a latency period where epileptogenesis can begin, which may progress into unprovoked recurrent seizures. Early seizures are likely due to brain insult and the recurrent rate of seizures in this time period is low (Lamar et al., 2014). Some studies have reported that in patients who experienced early PTS, only one-half had a recurrence while another quarter experienced a total of only two to three seizures (De Santis et al., 1979; Kollevold, 1979). After a latent period, epileptogenesis may occur, where a non-epileptic brain increases in excitability due to molecular and cellular alterations from a brain injury. Such alterations in the brain may eventaully lead to spontaenous recurrent seizures (Lamar et al., 2014; Lucke-Wold et al., 2015). The risk of seizure recurrence in the late stage post injury is higher compared to the early stage and may be more representative of epilepsy (Lamar et al., 2014). In a study conducted by Zhao et al. (2012), 5.7% of patients with TBI experienced seizures more than once a week, 69.5% more than once a month, and 24.8% had a seizure frequency greater than once a year. After vagus nerve stimulation, patients with PTE demonstrated a greater reduction in seizure frequency, with 50% fewer seizures occurring at three months and 7% fewer at two years than individuals with non-PTE who received vagus nerve stimulation (Englot et al., 2012).

The following table provides a summary of the natural history for the onset and recurrence of PTS (Yablon & Dostrow, 2001).

10.3 Clinical Presentation of Post-Traumatic Seizures

Wiedemayer et al. (2002) retrospectively analyzed a consecutive series of 1868 adult patients with head injury and found that the first epileptic seizure was generalized in 69 patients (63.3%) and partial in 40 patients (36.7%). Fifty-eight patients (53.2%) experienced a second early seizure during the follow-up period. Based on multiple studies, the incidence by seizure type is as follows: complex or simple partial seizures with secondary generalization, 16%-77% (Di Luca & de Lacerda, 2013; Kazemi et al., 2012; Sapina et al., 2014; Zhao et al., 2012); generalized tonic-clonic seizures, 30%-53.6% (Di Luca & de Lacerda, 2013; Zhao et al., 2012; Zheng et al., 2013); simple partial seizures, 14%-42.3% (Zhao et al., 2012; Zheng et al., 2013); complex partial seizures, 4.1%-16% (Sapina et al., 2014; Zhao et al., 2012; Zheng et al., 2013); and generalized atonic seizures, 2% (Di Luca & de Lacerda, 2013).

There has also been a correlation found between the type and frequency of seizures; those with simple or complex partial seizures experience a higher frequency of seizures (Kazemi et al., 2012). In a study examining 66 individuals who developed LPTS, it was determined that 79% had generalized seizures and 21% had focal seizures (Englander et al., 2003). Another study found focal epilepsy was the most common subtype of PTE, diagnosed in 93% of patients and arising most commonly from the temporal lobes and frontal lobes (Gupta et al., 2014). More specifically, 57% had temporal lobe epilepsy, 35% had frontal lobe epilepsy, 3% had parietal lobe epilepsy, and another 3% had occipital lobe epilepsy (Gupta et al., 2014).

Seizures following TBI may themselves be a source of significant morbidity and it has been noted that the recurrence of seizures is an important cause of non-elective hospitalization in patients with severe TBI (Cifu et al., 1999). Potential complications include deterioration in cognitive and behavioural functioning and overall functional status, impaired neurological recovery, status epilepticus, and death.

10.3.1 Influence on Neurologic Recovery

Neurological recovery can be influenced by PTS (Hernandez & Naritoku, 1997; Yablon & Dostrow, 2001). Yablon and Dostrow (2001) have noted that, in rodent models, brief and infrequent PTS occurring early after brain damage do not appear to impact functional recovery; however, more severe and widespread seizures occurring within the first 6 days post brain injury result in permanent impairments of functional recovery. Seizures occurring after the sixth day result in no change in somatosensory recovery (Hernandez & Naritoku, 1997).

10.3.2 Cognitive and Functional Status

Post-traumatic seizure disorders may lead to cognitive and behavioural disorders (Yablon & Dostrow, 2001). Cognitive problems may arise during the interictal state in the absence of active seizures (Aarts et al., 1984; Binnie & Marston, 1992). Patients with PTS can experience persistent behavioural abnormalities and a higher incidence of psychiatric-related hospitalizations even compared to patients with penetrating TBI who do not experience PTS (Swanson et al., 1995). Recurrent PTS may exert a negative impact on functional status following TBI, an adverse effect independent of the severity of the injury (Barlow et al., 2000; Schwab et al., 1993). In the case of penetrating TBI, PTS have been reported to be an important and independent factor which affects both employment status and cognitive performance (Schwab et al., 1993). However, in the case of non-penetrating TBI, the impact of PTS on functional prognosis and cognition is less clear (Armstrong et al., 1990; Asikainen et al., 1999). Within a population of individuals with LPTS, Kolakowsky-Hayner and colleagues (2013) discovered that occupational and social integration were the most difficult areas for recovery post injury. However, Haltiner et al. (1997) found no significant differences at 1 year as a consequence of LPTS in terms of neuropsychological performance and psychosocial functioning when adjusted for injury severity. Asikainen et al. (1999) found that patients with PTS did have poorer outcomes on the Glasgow Outcome Scale. A more recent study found that of individuals with LPTS, 20% were severely disabled, 52% moderately disabled, and 28% had a good recovery, as measured by the Glasgow Outcome Scale Extended. No significant differences in employment outcome associated with the presence of PTS have been found (Asikainen et al. (1999). Further, Kolakowsky-Hayner et al. (2013) found that among a group of individuals with TBI-LPTS, 40% (7 of 20) of individuals who were driving prior to injury had their license suspended due to their first seizure, and 3 were able to re-obtain their license.

10.3.3 Status Epilepticus

Status epilepticus can be defined as either more than 5 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between seizures. Status epilepticus is regarded as the most serious of the complications of PTS and may actually lead to additional neurological damage. Simple partial status epilepticus is a subset of status epilepticus characterized as a partial focal seizure that does not cause loss of consciousness or secondary generalization (Hadjigeorgiou et al., 2013). Fortunately, clinically apparent status epilepticus and simple partial status epilepticus are infrequent complications of PTS (Kollevold, 1979), with only 0.16% of individuals hospitalized with TBI with status epilepticus (Dhakar et al., 2015).

10.3.4 Mortality

In earlier studies, mortality was reported to be high among those who sustain a TBI and develop PTS (Corkin et al., 1984; Walker & Blumer, 1989; Walker & Erculei, 1970). More recently, Englander et al. (2009) found mortality rates to be higher for patients with TBI who had been diagnosed with LPTS when compared with those who had no recorded history of LPTS. Those in the LPTS group who died tended to be younger than individuals who did not have LPTS. Earlier studies found that patients with penetrating TBIs had a higher risk of dying; however, this is more likely due to the initial trauma rather than PTS (Rish & Caveness, 1973; Rish et al., 1983). Yablon and Dostrow (2001) have noted that the complications of a single LPTS are no different than those seen after any seizure and are generally minimal. However, increased seizure frequency and severity are associated with an increased risk of mortality and morbidity in the form of worsened cognition and overall function.

10.4 Treatment of Post-Traumatic Seizures

Schierhout and Roberts (2001) reported that a seizure occurring soon after head injury may cause secondary brain damage by increasing metabolic demands of the brain, increasing intracranial pressure, and leading to excessive amounts of neurotransmitter release. For this reason, the primary therapeutic objective in the use of anticonvulsant drugs has been the prevention of early seizures in an attempt to minimize the extent of secondary brain damage following TBI.

Some anticonvulsant drugs have been shown to have neuroprotective properties in animal studies. For example, following hypoxia, phenytoin has been linked with reduced neuronal damage in neonatal rats (Vartanian et al., 1996) and in rat hippocampal cell cultures (Tasker et al., 1992). Experimental evidence suggests that the neuroprotective effects of phenytoin are related to a blockage of voltage dependent sodium channels during hypoxia (Tasker et al., 1992; Vartanian et al., 1996) which would be expected to decrease the spread of calcium-induced neurotoxicity following hypoxic brain injury. As noted by Schierhout and Roberts (2001), this suggests that anti-epileptics may have beneficial properties which may be independent of their proposed anti-seizure activity.

Conversely, anti-epileptic drugs have shown toxic effects in stable patients, with impaired mental and motor function being the most common adverse effects; serious adverse effects, including deaths as a result of hematological reactions, have been also reported (Reynolds et al., 1998). Schierhout and Roberts (2001) have suggested that the injured brain’s response to anticonvulsants may be such that toxic effects could be more pronounced and neurological recovery may be delayed.

10.4.1 Seizure Prophylaxis

Initially, retrospective and nonrandomized clinical trials in humans showed favourable results for the efficacy of anti-epileptic drug prophylaxis; however, prospective investigations of chronic prophylaxis for LPTS have been less impressive. This section summarizes the literature to date which has explored the use of various drugs for seizure prevention.

10.4.1.1 Phenytoin

Key Points

Phenytoin may be an effective prophylactic drug for early post-traumatic seizures, however its effectiveness to treat late post-traumatic seizures has not been established.

Phenytoin is more effective than valproate as a prophylactic anti-seizure medication.

Levetiracetam is as effective as phenytoin in treating and preventing seizures in individuals in the intensive care unit post ABI.

Discussion

When the administration of phenytoin is compared to a placebo, its effect on the occurrence of early seizures is not encouraging; several studies did not find phenytoin to be effective (Bhullar et al., 2014; Temkin et al., 1990; Young et al., 1983). However, one RCT by Temkin et al., (1990) did find that phenytoin reduced the rate of early seizures only compared to placebo. A systematic review by Thompson et al. (2015) found that the traditional antiepileptic drugs, phenytoin or carbamazepine, decreased the risk of early seizures compared to controls (RR 0.42; 95% CI, 0.23 to 0.73, p=0.003); however, the evidence was low quality. Moreover, phenytoin was found to be no more effective than placebo in preventing late seizures (McQueen et al., 1983; Temkin et al., 1990; Young et al., 1983). In fact, Formisano et al. (2007) found that the occurrence of late seizures was significantly higher in patients treated with anti-epileptic medications than those who were not. It should be noted that phenytoin has been shown to have a negative impact on recovery. Further, those taking phenytoin had longer hospital stays and worse functional outcomes at discharge than individuals receiving no treatment (Bhullar et al., 2014). Overall, the evidence for the use of phenytoin for the prevention of seizures is not favorable. There was no significant difference in mortality between those treated with antiepileptic drugs (phenytoin and carmazepam) and control subjects (RR 1.08; 95% CI, 0.79 to 1.46, p=0.64)(Thompson et al., 2015).

When phenytoin was compared to levetiracetam, many studies have shown the two drugs to be comparable in terms of seizure rates (Inaba et al., 2013; Javed et al., 2016; Jones et al., 2008; Kruer et al., 2013; Radic et al., 2014), complications, adverse drug reactions, mortality rates (Inaba et al., 2013), and length of hospital stay (Kruer et al., 2013). A randomized controlled trial (RCT) by Szaflarski et al. (2010) found similar results in terms of there being no difference for early seizure rates, death, or adverse events between the two drugs; however, the authors found that those on levetiracetam performed significantly better on the Disability Rating Scale at 3 and 6 months (p=0.042), and the GOS at 6 months (p=0.039) post intervention compared to the phenytoin group. A large RCT by Younus et al. (2018) found that individuals on levetiracetam has a significant decrease in seizure activity at follow-up, and fewer abnormal EEGs compared to those on phenytoin. Furthermore, upon differentiation Radic et al. (2014) found that individuals with any evidence of a midline shift were at a higher risk for electrographic seizures and a lower risk for adverse drug reactions on levetiracetam compared to phenytoin. Overall, a meta-analysis by Zafar et al. (2012) concluded that there was no superiority of either drug at preventing early seizures.

When examining the effects of phenytoin compared to valproate Temkin et al. (1999) found no significant differences in rates of early seizures, late seizures, or mortality.  Dikmen et al. (1991) found that severely injured individuals receiving phenytoin performed no more poorly on neuropsychological measures than those taking valproic acid and valproate. The following year (12 to 24 months later), phenytoin was shown to have a small but negative effect on cognition (Dikmen et al., 1991).

Conclusions

There is level 1b evidence that phenytoin is effective in reducing the rate of only early onset post-traumatic seizures in patients with TBI.

There is conflicting evidence regarding whether or not phenytoin is effective in preventing post-traumatic seizure disorder long term compared to placebo treatment in patients with TBI. 

There is level 1a evidence that valproate is not more effective as a prophylactic anti-seizure medication compared to phenytoin in ABI populations.

There is level 1b evidence that levetiracetam and phenytoin do not show significant differences between them as prophylactic anti-seizure medication for individuals with ABI.

10.4.1.2 Miscellaneous Medications for Post-Traumatic Seizures

Key Points

First generation anti-epileptic drugs are as effective as new generation anti-epileptic drugs in reducing post-traumatic seizures.

Glucocorticoid administration may increase seizure frequency.

Injections of midazolam may reduce active seizure activity.

Carbamazepine may be effective in reducing seizure recurrence.

Methylphenidate may be effective in reducing rate of post-traumatic seizures.

Discussion

In terms of other medications studied, phenobarbital alone has been shown to have no prophylactic effect on PTE (Manaka, 1992). Glucocorticoids given within one day post injury may put patients at an increased risk of developing late seizures (Watson et al., 2004); however, there is no association between late seizures and glucocorticoids if given after the first day post injury (Watson et al., 2004).

There appears to be very little research to evaluate the efficacy of anticonvulsants given to treat seizures after they have occurred. Wroblewski et al. (1992) reported on a collection of ten case studies of patients with TBI treated with intramuscular midazolam for acute seizure cessation after other benzodiazepine drugs had failed. The authors reported that in all patients, seizures ceased within minutes of midazolam administration. Midazolam also prevented the onset of prolonged seizures or status epilepticus. Slight to moderate sedation was the only reported side effect. In terms of the efficacy between first generation and new generation anti-epileptic drugs, no significant differences were found (Sapina & Ratkovic, 2017), indicating that the use of first generation drugs may still be appropriate.

Conclusions

There is level 2 evidence that there is no difference in the ability, between first generation and new generation anti-epileptic drugs, in reducing the rate of post-traumatic seizures.

There is level 2 evidence that glucocorticoid administration within 1 day may put patients at a higher risk of late seizure development.

There is level 4 evidence that methylphenidate may be an effective anti-convulsant medication.

There is level 4 evidence that an intramuscular injection of midazolam may be effective in stopping active seizure activity.

There is level 4 evidence that carbamazepine may reduce seizure activity.

10.4.2 Surgical Treatment of Post-Traumatic Seizures

Yablon and Dostrow (2001) reported on a subgroup of ABI patients who experience continued PTS despite treatment with multiple antiepileptic drugs. For this special group of patients, surgical treatment may be a viable option.

10.4.2.1 Surgical Management of Post-Traumatic Seizures

Key Points

Surgical resection may reduce seizures if the focus of the seizures can be localized.

There is no difference in effectiveness between early craniectomy versus craniotomy for the reduction of the frequency of seizures.

Some studies have reported a decrease in seizures following surgical resection among a selected group of PTE patients (Diaz-Arrastia et al., 2000; Doyle et al., 1996). Accurate localization of the exact region responsible for the development of seizures is important but can be a challenge. This is particularly true for patients with severe ABI who frequently show multiple and bilateral sites of brain injury (Diaz-Arrastia et al., 2000).

Discussion

Marks et al. (1995) reported that, in a cohort of 25 patients with PTS, it was possible to successfully localize the seizure focus in less than half of the sample. Subsequent surgical excision of the area presumed to be the seizure focus resulted in seizure reduction in all treated patients. In those patients who showed a favourable result, the brain injury lesion was specifically limited to the hippocampus or neocortex (Marks et al., 1995), thus making the identification and surgical resection more accurate. This study supported surgical excision of the seizure focus as a viable treatment option for a subgroup of patients with ABI in whom the site of brain injury can be accurately identified. Patients suffering severe ABI with multiple and bilateral localizations where the seizure focus cannot be accurately identified are not suitable candidates for this surgical approach.

Hakimian et al. (2012) retrospectively examined patients with TBI who had an extratemporal resection for PTE. After the resection 28% of patients were seizure free, approximately 50% had a reduction in seizure frequency, and 19% did not benefit from treatment. Overall, good to excellent outcomes were achieved and the risk of complications was found to be minimal. In another study, Zheng et al. (2013) found that 63.9% of patients with supratentorial meningioma and preoperative seizures were seizure free post-surgery.

Won et al. (2017) retrospectively examined how a craniotomy compared to a craniectomy could influence seizure occurrence and management. It was found that of the cohort examined, 21 out of 53 individuals had preoperative post-traumatic seizures following a subdural hematoma; while 34 had postoperative (two individuals had both). For those with preoperative seizures, 90% saw an elimination of seizures for three months following surgery regardless of craniotomy or craniectomy (Won et al., 2017). However, the majority of individuals who experienced seizures experienced them after surgery. Ultimately, there were no significant differences between groups to suggest a craniectomy or craniotomy reducing the incidence of seizures following an ABI.

Conclusions

There is level 2 evidence that craniectomies are not more effective in reducing the frequency of seizures than craniotomies in TBI populations when performed within the first few days of injury.

There is level 4 evidence that a subgroup of patients with ABI (those in whom the seizure focus can be accurately localized) would benefit from surgical resection for post-traumatic seizures.

There is level 4 evidence that extratemporal resection may be effective for controlling post-traumatic epilepsy in patients with TBI.

10.5 Conclusions

PTS is relatively common post ABI, however there are limited evidence for effective interventions. This does not mean that they are not effective, but most traditional pharmacological prophylactic interventions and newer drugs which show more promise have not been subjected to rigorous evaluation. Surgical interventions, in general, appear to be effective in treating PTS in patients who have failed pharmacological treatment.

Summary


There is level 1b evidence that phenytoin is effective in reducing the rate of only early onset post-traumatic seizures in patients with TBI.

There is conflicting evidence regarding whether or not phenytoin is effective in preventing post-traumatic seizure disorder long term compared to placebo treatment in patients with TBI. 

There is level 1a evidence that valproate is not more effective as a prophylactic anti-seizure medication compared to phenytoin in ABI populations.

There is level 1b evidence that levetiracetam and phenytoin do not show significant differences between them as prophylactic anti-seizure medication for individuals with ABI.

There is level 2 evidence that there is no difference in the ability, between first generation and new generation anti-epileptic drugs, in reducing the rate of post-traumatic seizures.

There is level 2 evidence that glucocorticoid administration within 1 day may put patients at a higher risk of late seizure development.

There is level 4 evidence that methylphenidate may be an effective anti-convulsant medication.

There is level 4 evidence that an intramuscular injection of midazolam may be effective in stopping active seizure activity.

There is level 4 evidence that carbamazepine may reduce seizure activity.

There is level 2 evidence that craniectomies are not more effective in reducing the frequency of seizures than craniotomies in TBI populations when performed within the first few days of injury.

There is level 4 evidence that a subgroup of patients with ABI (those in whom the seizure focus can be accurately localized) would benefit from surgical resection for post-traumatic seizures.

There is level 4 evidence that extratemporal resection may be effective for controlling post-traumatic epilepsy in patients with TBI.

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