"V体育ios版" Management of post‐traumatic epilepsy: An evidence review over the last 5 years and future directions

Incidence and risk factors

PTE has been described as a particularly heterogeneous condition, specifically because of the heterogeneity associated with TBI. The types of seizures experienced by people with PTE are focal onset seizures with or without secondary generalization to bilateral tonic‐clonic convulsive activity, and some people experience focal nonconvulsive seizures only VSports手机版. 1 Early seizures are often of the generalized tonic‐clonic convulsive type in comparison to late seizures, which are mostly nonconvulsive in nature.

It is well established that the incidence of PTE increases with the severity of TBI. For example, an analysis by Herman3 of the relative risk (RR) for unproved seizures reported that severe TBI confers a RR 29 times that of the general population, and for mild and moderate TBI it was 1 V体育安卓版. 5 and 4, respectively. It has been found that the risk of PTE is the highest within the first 2 years of TBI. 4 However, the risk of developing PTE is still high for more than 10 years later in people with moderate TBI and more than 20 years later in people with severe TBI. 5 Hence, it is not unusual for cases of PTE to occur 30–35 years after TBI, and it is important that people with TBI who live in the community undergo “vigilant long‐term neurologic follow‐ups. ”6 .

Over the last decade, numerous hospital‐ (mostly) and population‐based studies have identified the incidence of PTE (Table 1). 7–17 Four studies of PTE in children only (three from the U. S. A. ) show incidence rates ranging from 11% to 19%; three studies in adults only show varying incidence rates; and four studies involving adults and children with PTE with two studies from China report similar rates (5% and 9%). “Adults” refers to people aged 18 years and older V体育ios版.

Several risk factors have also been studied and documented for PTE, including the following:

1. Personal factors—young age or increasing age from 15 years, family history, depression, and premorbid alcohol abuse18

2. Injury factors—markers of increasing injury severity such as penetrating injuries and depressed skull fracture, seizures occurring within the first week following TBI (early seizures)18

Another risk factor that has recently been identified is the disruption of the blood‐brain barrier (BBB), which has been observed as significant electroencephalography (EEG) slowing in the region of BBB breakdown. 19 There is some controversy as to whether early seizures increase the risk of developing PTE. Annegers et al V体育2025版. 5 have reported that early seizures are not an independent risk factor for late seizures. However, there is stronger evidence for a high risk of seizure recurrence subsequent to the first late seizure: 47% within a month after TBI, and 86% after 2 years following TBI. 20 .

Recently, it has been identified that people with a history of depression, epilepsy, or who experience three or more chronic medical conditions at discharge are at high risk of developing PTE.11 Also, genetic polymorphisms have been reported to increase a person's susceptibility to developing PTE, including variability in the glutamic acid decarboxylase (GAD) 1 gene21 and the C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme.22 A recent study has found an association with genetic variants in the gene for the inflammatory cytokine IL‐1β.23 However, further studies are needed to confirm these findings.

Pathophysiology

The pathogenic mechanisms underlying PTE are still poorly understood. However, what is known is that the pathophysiology following TBI differs depending on the type of injury. Closed head injuries result in diffuse axonal injury, edema, ischemia, and a cascade of secondary damage, including the release of toxic mediators, excitatory amino acids, and cytokines.1, 24 Nonpenetrating head injury has been described as producing focal contusions and intracranial hemorrhage; penetrating head injury results in “a cicatrix in the cortex” or scar tissue.25

There is evidence to suggest that the underlying pathological processes that result in PTE are multifactorial, including the release of excitotoxins, blood‐barrier deterioration with vascular changes, parenchymal hemorrhage, and free radical damage.3 Currently, in people with TBI no reliable molecular biomarkers have been identified that can predict the development of PTE or its outcome. It is clear that further understanding the pathophysiological mechanisms underlying PTE will assist greatly in identifying better therapeutic targets and clinically applicable biomarkers.

Management of post‐traumatic epilepsy: Assessment/diagnosis

Diagnostic testing assists in the assessment of PTE so that appropriate treatments can be provided to people with PTE. Electroencephalography (EEG), which is usually used as a short (<1 h) recording but that can also be used for continuous video monitoring of seizures in epileptic conditions, has been found to be mostly nonspecific for people following TBI. Studies have concluded that it is not effective for predicting the development of PTE or disability outcome.26, 27 In the acute setting, computed tomography (CT) has been shown to be effective for assessment of areas of brain injury in people following moderate to severe TBI, but not for mild TBI cases.1 Magnetic resonance imaging (MRI) has the highest sensitivity to detect structural brain changes and is the imaging modality of choice in people with PTE. It is also being used in a research context to investigate the effectiveness of treatments and outcomes in people with PTE.6

Current clinical practice guidelines

Several recommendations have been produced by the American Academy of Neurology for the management of epilepsy both in adults and in children. There is only one clinical practice guideline containing recommendations for seizure prophylaxis following TBI.28

“For adult patients with severe TBI (typically with prolonged loss of consciousness or amnesia, intracranial hematoma or brain contusion on CT scan, and/or depressed skull fracture):

• Prophylactic treatment with phenytoin, beginning with an IV loading dose, should be initiated as soon as possible after injury to decrease the risk of posttraumatic seizures occurring within the first 7 days (Level A).

• Prophylactic treatment with phenytoin, carbamazepine, or valproate should not routinely be used beyond the first 7 days after injury to decrease the risk of post‐traumatic seizures occurring beyond that time (Level B)” (page 14).28

Other recommendations relevant to the management of PTE in adults include the following:

• “Adults presenting with an unprovoked first seizure should be informed that the chance for a recurrent seizure is greatest within the first 2 years after a first seizure (21–45%) (Level A).

• Clinicians should also advise such patients that clinical factors associated with an increased risk of seizure recurrence include a prior brain insult such as a stroke or trauma (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain‐imaging abnormality (Level B), or a nocturnal seizure (Level B).

• Clinicians should advise patients that, although immediate AED therapy, as compared with delay of treatment pending a second seizure, is likely to reduce the risk of a seizure recurrence in the 2 years subsequent to a first seizure (Level B), it may not improve QOL (Level C).

• Clinicians should advise patients that over the longer term (3 years), immediate AED treatment is unlikely to improve the prognosis for sustained seizure remission (Level B). Patients should be advised that their risk for AED adverse effects (AEs) ranges from 7% to 31% (Level B) and that these AEs are predominantly mild and reversible” (page 1709).29

All of these study findings indicate that the management of PTE should be focused on providing people with an improved quality of life in conjunction with standard treatment. The aim of this rapid review is threefold:

1. To provide an overview of the effectiveness of assessment tools and treatment interventions for the prevention of PTE in people with moderate to severe TBI

2. To increase the awareness and understanding of this important delayed complication

3. To inform future research opportunities and considerations for best clinical practice

VSports最新版本 - Steps 1 and 2: Needs assessment and question development and refinement

The topic was nominated to members of a research advisory council—the Victorian Neurotrauma Advisory Council—following an open consultation with health professionals, researchers, and funders in the Australian neurotrauma community. It was identified among 16 other topics as one of importance for pursuing as part of the Forum program of the National Trauma Research Institute (NTRI). The research methodology employed by the NTRI Forum program has been published,31 and further information is available at http://www.ntriforum.org.au/ntri-forums. Following consultation with experts, the research question was developed and refined.

Step 3: Proposal development and approval

A proposal for the topic, including the research question, was provided to an expert panel for approval. Following approval, a search strategy was developed.

Step 4: Systematic literature search

A search was conducted with the following electronic databases: MEDLINE (See Appendix); All EBM; CINAHL; PsycINFO; and EMBASE. Search terms included brain injuries and epilepsy and post‐traumatic. Google Scholar was also searched using the term post‐traumatic epilepsy and variations relating to it. The first 100 results were screened because they were the most relevant. Articles were limited to English language and in the date range January 2010–April 2015.

Step 5: Screening and selection of studies (VSports注册入口)

Studies were screened by two independent reviewers using the inclusion/exclusion criteria described below. Reference lists of included studies were also scanned to identify further relevant references. The review process took approximately 4–6 weeks to complete, from April to May 2015.

Steps 6 and 7: Narrative synthesis of included studies and report production

Data were extracted from the systematic reviews and evidence‐based reviews using the following headings: (1) number of included studies, (2) type of intervention, and (3) conclusion/key findings and level of evidence. They were also categorized according to adult‐ or children‐focused studies and pharmacological and nonpharmacological studies. Data were also extracted from the primary included studies using the following headings: (1) country, (2) type of injury, (3) number of participants, (4) intervention, (5) results, and (6) conclusions. A narrative synthesis was performed using the extracted data to identify the effectiveness of diverse pharmacological and nonpharmacological interventions in adults and children for PTE and is provided in the results section that follows.

Overview of evidence from systematic reviews (VSports手机版)

Two systematic reviews (SRs)36, 37 were identified as being of the highest level of evidence.55 However, one of these SRs was at protocol stage only and thus has no reported results; hence, it is not utilized in the current rapid review.37 One meta‐analysis and two evidence‐based reviews were identified that provide the most recent, comprehensive overview of the management of PTE, and hence are utilized in the current rapid review.30 Assessments and treatments for late seizures, which are the true definition of PTE, are discussed.

Pharmaceutical approaches

"V体育2025版" Phenytoin

A total of 10 RCTs investigated the efficacy of PHT for seizure prevention following PTE (Table 3). Two RCTs investigated PHT efficacy for early seizure prevention: one compared the efficacy of PHT or LEV56 and one looked at PHT in comparison to placebo.18, 57 In both studies, no difference was observed for occurrence of early seizures following either treatment; however, people receiving LEV reported fewer side effects. In the RCT that utilized PHT and LEV, after 3 and 6 months of follow‐up, people treated with LEV versus PHT performed better on the Disability Rating Scale (DRS), p = 0.042, and the Glasgow Outcome Scale (GOS), p = 0.039; however, their neurological status was worse (p = 0.024). Another RCT58 did observe a reduction in seizures in the first week of PHT treatment in comparison to no effect with placebo (3.6% vs. 14.2%, p < 0.001), but this same effect was not observed following 1 year of treatment and at 2 years of follow‐up.18

Carbamazepine and phenobarbital

Two RCTs were identified using carbamazepine63 and phenobarbital,64 and one non‐RCT was identified for carbamazepine in comparison to placebo.18, 65 Both RCTs and the non‐RCT reported no difference between carbamazepine and phenobarbital in comparison to placebo in seizure occurrence after 2 years of treatment.

Sodium valproate

Two RCTs compared treatment with valproate for 1 month and 6 months with placebo.66, 67 There was no difference among the groups in seizure occurrence at any time point; however, a trend of higher mortality following treatment with valproate was observed.

One retrospective study investigated intravenous sodium valproate for seizure prophylaxis in adults and children with TBI.51 Most of the population were adults, with only 7 children included. Ma et al.51 found that people who received sodium valproate did not experience any seizures; however, when compared to those who did not receive any treatment there was no statistically significant difference. In people who did not receive treatment, 6 people who had severe TBI and 1 person with mild to moderate TBI experienced seizures (Table 3). Because this is only one lower‐quality study, further prospective studies are needed to confirm any effectiveness of sodium valproate for the treatment of PTE.

Other pharmacological agents (methylphenidate, glucocorticoids, midazolam)

Two studies investigated the efficacy of other pharmacological agents, such as methylphenidate and glucocorticoids, for seizure prophylaxis following PTE.18, 68, 69 There was no difference in the occurrence of seizures following glucocorticoid treatment; however, there was an observed trend for a lower incidence of seizures with methylphenidate treatment (p = 0.063).

Another study utilized midazolam intramuscularly (0.5–20 mg) for the treatment of late seizures when they occurred in people with PTE.18, 70 There was a significant cessation observed following treatment, showing an effect within minutes. Treatment with midazolam also prevented prolonged seizures (or status epilepticus). This has been the only study to treat seizures acutely when they occur in people with PTE. However, there were only 10 people with PTE; therefore, further higher‐quality studies are needed to confirm these results.

Surgical approaches

Some people with seizures following PTE do not see any great improvement of their seizures or their seizures cannot be completely controlled with the use of AEDs. In these cases of drug‐resistant epilepsy, surgical treatment may be considered as an option to attain seizure control and potentially reduce the amount of AEDs required. However, it should also be noted that certain issues, including bone flaps and dural adhesions, can result from surgery.

Teasell et al.18 identified only one case series of patients with PTE who had surgical treatment73. The study involved 9 people who had their seizure foci identified with a variety of presurgical assessments (including MRI and EEG monitoring) and consequently underwent surgical resection. Although not specially reported in all people who underwent surgery, when the target of seizures was accurately identified and the focus removed a reduction in the occurrence of seizures was observed. In patients whose seizure focus was localized in the hippocampus and temporal neocortex, surgical resection was more successful because the area was easier to accurately identify. However, this is only one small study and requires further evidence to confirm this treatment approach as part of unresolved management. This type of approach is not applicable to all people with PTE; in many patients the seizure focus can be difficult to localize, may arise from multiple locations, or may involve brain regions responsible for key functions, such as the motor or language cortex.6

Two surgical intervention studies were identified for the treatment of adults with PTE.44, 47 One study was a retrospective case‐control study of 317 adults with drug‐resistant PTE compared with 1,763 patients with drug‐resistant non‐PTE who were treated with a vagal nerve stimulator (VNS) (Table 3).44 Englot et al.44 reported a significant reduction in seizures (of 73% at 2 years follow‐up) following VNS therapy in people with PTE, which was higher than that in patients treated for non‐PTE (61%). These promising findings require further higher‐level studies to confirm the effectiveness of VNS specifically for PTE.

Hakimian et al.47 conducted a retrospective review of 21 adults with PTE to investigate the effectiveness of extratemporal resective epilepsy surgery. It was found that at 1 year postsurgery most people had a reduction in seizures, with 6 people being completely seizure‐free (Table 3). However, 4 people did not have any reduction in their seizures. People who had good outcomes were those in which their seizure focus was identified accurately by MRI and intracranial EEG electrodes. People who had multiple seizure foci had worse outcomes. The study involved a small sample of subjects (n = 21); hence, larger higher‐quality studies are needed.

Bellon and Rees40 conducted a non‐RCT in 16 people with PTE to investigate the effectiveness of a psychoeducational intervention for improving psychosocial and cognitive functioning. Although the results showed an improved self‐awareness and understanding of PTE and better management of seizures, the effect was not sustained at 6 months following treatment (Table 3). A higher‐level study with a larger sample is needed to confirm these promising results.

The challenge of translation of treatments from “bench to bedside”

One of the major challenges limiting the development of improved diagnosis and treatment of PTE is that the pathophysiology is relatively unknown and understudied in humans.11 However, the use of animal models with PTE have greatly assisted in uncovering underlying consequences that result from PTE and, hence, potential therapeutic targets. Models used for TBI include lateral fluid percussion, weight drop, and controlled cortical impact.75 There is wide use of the lateral fluid percussion injury model in rats, but the model does not have all the clinical features of PTE observed in humans. In particular, although a latent period is seen in most animal models of epilepsy, the period is not as long as can be experienced in human PTE, that is, 2–20 years following TBI. A lack of consensus currently exists for a well‐accepted animal model that is truly reflective of the mechanisms and events occurring in humans experiencing PTE.

Evidence exists for a potential genetic susceptibility to PTE; however, currently no genetic animal models investigate potential therapies for management. Three studies have found significant genetic variations in the adenosine A1 receptor,76 methylenetetrahydrofolate reductase (MTHFR) enzyme,22 and glutamic acid decarboxylase (GAD)21 in humans who develop PTE. These findings may be useful in establishing therapeutic targets for the treatment of PTE and they require further investigation.

Although in animal models of PTE pharmacological interventions have been reported to prevent PTE from occurring, none has been shown to be effective in humans. The treatments studied in clinical trials were designed primarily to symptomatically control seizures (i.e., AEDs), so their mechanisms of action may be different from that associated with the development of PTE and consequently ineffective.75 This may also be related to the time in which the treatment is administered in humans. For example, studies of valproate indicate that a continuous administration for 24 h following a seizure occurrence provides better protection in affected regions of the brain than administration before a seizure has occurred (prevention).75 It is important that the therapeutic window is accurately identified for the treatment to have an optimal effect. Animal models need to be clinically validated, and treatments that show effectiveness in one model should reflect the same effectiveness in other models. This is particularly true in animal studies that use multiple treatments at the same time.75 The development of PTE is generally believed to be a multifactorial process, so more than one treatment (or a combination of treatments) may prove to be more effective for the treatment of PTE.

What impact does PTE have on quality of life? (V体育安卓版)

PTE can have a significant negative effect on the quality of life (QoL) of people with TBI. Following a return to the community, people with TBI have to learn to cope with and adjust to major changes in their life, including the reestablishment of their self‐identity. PTE adds a complexity to the existing consequences of TBI, making reintegration into the community difficult and challenging. The fact that the onset of epilepsy occurs months or years after the TBI means that it usually occurs at a time when people are well along the road to reestablishment of their life postinjury. The development of epilepsy represents a serious setback that can affect people's independence, job opportunities, recreational pursuits, mental health, and safety.77 The impact is exacerbated by a disconnection from the supports originally in place for the TBI, which usually have been discontinued by the time of seizure onset. Furthermore, PTE usually requires the taking of AEDs on a long‐term basis, and these can have negative side effects that influence a person's QoL and neuropsychiatric symptoms.

An interesting finding from the current rapid review is the identification of a nonpharmacological psychoeducational intervention that showed effectiveness in assisting people in managing their seizures.40 This promising intervention in conjunction with pharmacological interventions may be beneficial for some people in improving their quality of life. Psychosocial and cognitive functioning can be significantly impaired following the development of PTE, leading to social withdrawal and issues with returning to or seeking employment. Evidence in support of these effects is increasing, with three studies published within the last 5 years.2, 77, 78 One study conducted a retrospective analysis of QoL in people with PTE (n = 105) 1 year after TBI. Liu et al.78 found a significant decline in the QoL‐31 Scale, the Self‐Rating Depression Scale (SDS), and the Self‐Rating Anxiety Scale (SAS) in people with PTE in comparison to a control group. A multiple regression analysis revealed several major factors that influenced these findings in QoL in people with PTE. These included anxiety, therapeutic compliance, depression, poor control of epileptic seizure, and the site of trauma.

Bushnik et al.2 investigated the impacts of PTE on people with TBI after 1, 2, and 5 years. Two groups of people post‐TBI were compared: those with PTE and those without PTE (n = 91).2 A number of people in both groups reported living alone a year after their injury, and this trend continued after 5 years. People with PTE reported utilizing “more dependent forms of transportation,” such as public transport or transport by another person. Significant impacts were observed in functional outcome measures such as the Disability Rating Scale, with people with PTE showing poorer results. Psychosocial outcomes were also affected, with lower scores in the Satisfaction With Life Scale for people with PTE in comparison to those without PTE.

A prospective multicenter mixed‐method study investigated the impacts of PTE in people 5–13 years after TBI (n = 25).77 Half of the participants did not return to driving and had their license suspended. Interestingly, some participants who had their driver's license reported that they still experienced seizures. Almost half of the participants reported that the occurrence of seizures affected their ability to cope with their brain injury and they felt that as a result their recovery was significantly impaired. Several people reported that the seizures prevented them from engaging in social activities as reflected by the Craig Handicap Assessment and Reporting Technique Short Form (CHART‐SF), which indicates participation or handicap and on which most issues were reflected in the occupation and social integration subscales.77

This could suggest that a multicomponent approach may be more effective and improve the QoL of people with PTE. The paucity of nonpharmacological treatments in this area, however, requires further investigation.

The use of longitudinal studies of the lived experience of people with PTE may also facilitate the design of interventions aimed at improving QoL. Early evidence of the lived experience of PTE on QoL was illustrated in this review by three studies that revealed an effect on recovery and social participation. Unfortunately, the studies mostly looked at people with PTE at 1 or 5 years following injury, with one of the studies looking at a small number of people up to 13 years following injury. The longer‐term effects of living with PTE and the effects in some people who develop PTE more than 10 years after TBI are currently unknown and require further investigation to identify supports to improve QoL.

There is also a need for diagnostic evaluation to confirm PTE if there is any question of the diagnosis, in particular in the case of psychogenic nonepileptic seizures (PNESs). PNESs are “events that resemble epileptic seizures but that are not due to paroxysmal neuronal discharges or other physiologic abnormalities and that have a presumed psychological origin” (page E65).79 As well as being common in the general population, PNESs are common in veterans and returned military service people who may not be diagnosed until much later.80 A retrospective analysis of veterans with a diagnosis of PNES found that over 50% had TBI or PTE in comparison to only 37% of veterans with a diagnosis of epileptic seizures. The TBI was mild for 87% of veterans with PNES, and most of them had a previous diagnosis of post‐traumatic stress disorder (PTSD). This may indicate a role of PTSD in the development of PNES; this should not be ruled out during diagnostic evaluation for PTE.

Identifying biomarkers

Another issue identified is an urgent need to find biomarkers for people at risk of developing PTE. Recent evidence in an animal model of PTE used quantitative MRI biomarkers.81, 82, 83 Immonen et al.81 were able to predict the development of seizures and epileptogenesis at 9 days, 23 days, 2 months, and 1 year using certain MRI biomarkers. Although this is an exciting step in predicting PTE using a widely available diagnostic technique, there are limitations of the animal model used and the findings need to be validated in clinical studies.

A dual biomarker and genetic study in adults with moderate to severe TBI investigated the development of PTE and the involvement of interleukin 1 beta (IL‐1β).84 The ratio of cerebrospinal fluid (CSF) and levels of IL‐1β in serum samples were analyzed and found to vary with the development of PTE over time. This promising association is important to consider as a key target for treatment intervention because of the inflammatory damage following TBI. Therefore, further studies should confirm the role of IL‐1β and associated factors in the development of PTE, in particular because of the heterogeneous nature of TBI.

Strengths and limitations of the current review

This rapid review provides a high‐level synthesis of evidence on the management of PTE from the last 5 years. It finds that there is no evidence of effectiveness of pharmacological treatments for the prevention and treatment of PTE in adults and only a little high‐level evidence for one pharmacological treatment—levetiracetam—in children. These findings suggest that greater collaborative efforts between researchers and health professionals should be pursued to identify novel, more effective treatments. Furthermore, an emphasis on health professional and patient organization awareness of this underappreciated condition will assist in better understanding it and developing strategies (e.g., holistic approaches) to improve the quality of life in people who experience PTE.

A major limitation of this current review is the use of a rapid review methodology that has not yet been validated or universally accepted.30 Currently, there is also “a lack of an accepted or validated definition”30, 85; however, this has not prevented producers of rapid reviews from publishing or disseminating their work for policy or practice change.

Because of the flexible nature of rapid reviews (varying intentions and purposes), several approaches are being used and published. Tricco et al.86 have recently conducted an international survey (and used a modified Delphi approach) among producers of rapid reviews to investigate which approaches/methodologies are used and to explore their perceptions of the comprehensiveness, accuracy, feasibility, and risk of bias of rapid reviews. The authors report that among six different approaches identified, experts reported the most feasible approach and with the lowest perceived risk of bias was one in which the search is limited by date and language, study selection is carried out by one reviewer only, and data abstraction and quality appraisal are conducted by one reviewer and one verifier. The authors also report that the most common approach identified was updating the literature search of previous reviews.86 This is a well‐known limitation of systematic reviews that may have been published several years previously but that have not been updated with relevant evidence or that are awaiting an update by the original review authors or, when the authors are not available, by another group.

With the use of several different approaches for the production of rapid reviews, there can be an associated loss of methodological rigor and objectivity. The systematic review, or gold standard as it is known in evidence synthesis methodology, does employ methodological rigor and transparency as key strengths. It should be noted that rapid reviews have been produced as a solution to the limitations associated with systematic reviews, such as their being costly to conduct and having a long time frame for completion (6 months–2 years).30 A key strength of rapid reviews reported by Lambert et al.87 is their quick production time frames in conjunction with their tailored nature that addresses specific questions in policy. Polisena et al.88 reported that rapid reviews are useful “to inform decision making with regards to funding health care technologies, services and policy, and program development.”

Therefore, further investigation is needed to identify what constitutes a rapid review and what guidelines should be considered for their conduct and reporting. Recent progress has already commenced this year with the Rapid Review Summit Planning Committee, which hosted a rapid review summit in Vancouver, Canada.89 Furthermore, a methods group known as the Cochrane Rapid Reviews Methods Group (RRMG) has just been established by two groups—the Ottawa Methods Centre based at the Ottawa Hospital Research Institute (OHRI) and the Cochrane Collaboration in Austria—to “better inform ‘rapid review’ methodology.”90 It is envisaged that this group will assist Cochrane groups that may want “to undertake abbreviated Cochrane reviews making them more streamlined, timely, and relevant to end‐users.”90

The American Academy of Neurology clinical practice guidelines for seizure prophylaxis in adults with severe TBI are not currently based on the findings of this rapid review. It is important that these guidelines are updated with the existing evidence so that clinicians are guided by the most effective management. The guidelines were published in 2003, more than 10 years ago. There is an urgent need for clinicians to review the existing guidelines using this rapid review.

This rapid review summarizes all assessment and treatment interventions for the management of PTE. Furthermore, it illustrates the significant effect that PTE has on the QoL of people who develop this “second”‐punch consequence and the challenges we face in translating findings from “bench to bedside.” Future research on the pathophysiology of PTE and biomarkers of those at high risk and collaboration among researchers in the epilepsy and brain injury fields are the keys to understanding this disease and in making progress with such an unappreciated consequence of TBI.