RESUMEN
Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model. Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2). Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001). Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.
RESUMEN
BACKGROUND: Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the most common clinical presentation, though people may also present with headache, symptoms of raised intracranial pressure, hydrocephalus, and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, antiepileptic drugs (AEDs), and anti-oedema drugs, such as steroids, form the mainstay of treatment. This is an updated version of the Cochrane Review previously published in 2019. OBJECTIVES: To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis. For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in people who had neurocysticercosis but had not had a seizure. For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in people who had had at least one seizure due to neurocysticercosis. As part of primary prevention studies, we also aimed to examine which AED was beneficial in people with neurocysticercosis in terms of duration, dose, and side-effect profile. SEARCH METHODS: For the 2021 update of this review, we searched the Cochrane Register of Studies (CRS Web), MEDLINE, and LILACS to January 2021. CRS Web includes randomised or quasi-randomised, controlled trials from CENTRAL, the Specialised Registers of Cochrane Review Groups, including Epilepsy, PubMed, Embase, ClinicalTrials.gov, and the World Health Organisation International Clinical Trials Registry Platform. We also checked the reference lists of identified studies, and contacted experts and colleagues in the field to search for additional and ongoing studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials. Single-blind, double-blind, or unblinded studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion and extracted the relevant data. The primary outcomes of interest were: proportion of individuals experiencing seizures, and time to first seizure post randomisation. Secondary outcomes included: seizure freedom, number of withdrawals, side effects, number of people seizure free with short or long durations of treatment, quality of life, therapy costs, hospitalisations, and mortality. We used an intention-to-treat analysis for the primary analysis. We calculated odds ratio (OR) for dichotomous data (proportion of individuals who experienced seizures, were seizure free for a specific time period (12 or 24 months), withdrew from treatment, developed drug-related side effects or complications, were seizure-free with each treatment policy, mortality), and planned to use mean difference (MD) for continuous data, if any continuous data were identified (quality of life, cost of treatment). We intended to evaluate time to first seizure after randomisation by calculating hazard ratios (HRs). We assessed precision using 95% confidence intervals (CIs). We stratified the analysis by treatment comparison. We also considered the duration of drug usage, co-medications, and the length of follow-up. MAIN RESULTS: We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures. We did not find any trials that directly compared individual AEDs for primary prevention in people with neurocysticercosis. We included four trials that evaluated the efficacy of short-term versus longer-term AED treatment for people with solitary neurocysticercosis (identified on computed tomography (CT) scan) who presented with seizures. In total, 466 people were enrolled. These studies compared AED treatment durations of 6, 12, and 24 months. The risk of seizure recurrence with six months of treatment compared with 12 to 24 months of treatment was inconclusive (odds ratio (OR) 1.34, 95% confidence interval (CI) 0.73 to 2.47; three studies, 360 participants; low-certainty evidence). The risk of seizure recurrence with six to 12 months of treatment compared with 24 months of treatment was inconclusive (OR 1.36, 95% CI 0.72 to 2.57; three studies, 385 participants; very low-certainty evidence). Two studies compared seizure recurrence with CT findings, and suggested that persistent and calcified lesions had a higher recurrence risk, and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of the drugs. None of the studies addressed the quality of life of the participants. These studies had methodological deficiencies, such as small sample sizes, and a possibility of bias due to lack of blinding, which affect the results of the review. AUTHORS' CONCLUSIONS: Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as seizure prophylaxis among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. Therefore, there is a need for large scale randomised controlled trials to address these questions.
