Pharmacological treatments for preventing epilepsy following traumatic head injury.

BACKGROUND: Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy. Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown. This review attempted to address the effectiveness of these treatment interventions. This review updates and expands on the earlier Cochrane review. OBJECTIVES: To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo, usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury. SEARCH METHODS: We searched The Cochrane Epilepsy Group's specialized register, CENTRAL, MEDLINE, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) in January 2015. We searched EMBASE, Biological Abstracts and National Research Register in September 2014 and SCOPUS in December 2013. The Cochrane Epilepsy Group performed handsearches of relevant journals. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that include AEDs or neuroprotective agents compared with placebo, another pharmacologic agent or a usual care group. The outcomes measured included a seizure occurring within one week of trauma (early seizure), seizure occurring later than one week post-trauma (late seizure), mortality and any adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted the data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for each outcome. We used random-effects models in the meta-analyses and performed pre-defined subgroup and sensitivity analyses. MAIN RESULTS: This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable.Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all-cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30).Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons. AUTHORS' CONCLUSIONS: This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post-traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED.

Ictal-Interictal Continuum.

The term "ictal-interictal" continuum has seen wide adoption in the critical care EEG domain, referring to the presence of abnormal periodic activity on the scalp EEG variably associated with seizures. The historical origin of the ictal-interictal continuum concept is discussed with a review of known and surmised physiological mechanisms for their origin and relationship to seizures. Therapeutic approaches to patients exhibiting ictal-interictal continuum EEG patterns are reviewed, and some open scientific questions highlighted. Further understanding of the ictal-interictal continuum is likely to significantly improve the care of the critically ill neurological patient.

Role of neuroimaging in first seizure diagnosis.

The primary goal of neuroimaging in a first, unprovoked seizure is to identify a lesion that can explain the seizure. Secondarily, neuroimaging may be used to predict seizure recurrence and assist with the diagnosis of epilepsy. However, the events leading from a first seizure to epilepsy, with or without an identifiable epileptogenic lesion, are not well understood, and it is not always clear which lesions are epileptogenic as opposed to incidental. Much neuroimaging research to date has focused on findings in chronic epilepsy, rather than first seizure. Dedicated epilepsy imaging with high quality MRI protocols maximizes the likelihood of a diagnosis. However, a significant proportion of patients are MRI-negative, prompting researchers in the field to continue the search for better imaging strategies. Here we describe the role of neuroimaging in the assessment of a first seizure, the current state of the art and possible future directions.

The "natural" history of medically treated temporal lobe epilepsy: what can an evidence-based approach tell us?

We systematically reviewed the literature to describe the "natural" history of medically treated temporal lobe epilepsy (TLE). No population-based studies recruiting incident cases of TLE irrespective of age exist. Prospective, population-based studies were limited to those recruiting only childhood-onset TLE or those reporting TLE as a subgroup of cohorts of focal epilepsies. Few studies have been performed in the "MRI era" limiting information on natural history secondary to specific pathologies. Available data suggests that TLE is highly variable, with unpredictable transient remissions and low rates of seizure freedom (30 to 50%). Etiology and failure of first and second drug seem to be the most important predictors for treatment prognosis. The role of initial precipitating injuries remains speculative, as imaging information of related events is either missing or conflicting. Prospective cohorts of new-onset TLE with long-term followup using advanced MRI techniques, timely EEG recordings, and assessments of psychiatric comorbidities are needed.