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1.
BACKGROUND: Administration of antiepileptic drugs for coma induction in refractory status epilepticus (RSE) has not been widely studied. Moreover, the effect on outcome of electroencephalographic (EEG) burst suppression remains unclear. OBJECTIVE: To investigate whether various coma-inducing options are associated with different prognoses after RSE. DESIGN: Retrospectively assessed case series. SETTING: Two tertiary referral hospitals in Boston, Mass. PATIENTS: Among 127 consecutive episodes (107 patients) of status epilepticus, we identified episodes that were refractory to first-line and second-line antiepileptic drugs, needing induced coma with barbiturates, propofol, or midazolam for clinical management. MAIN OUTCOME MEASURES: Short-term mortality and prevalence of return to functional baseline after the acute episode of status epilepticus were analyzed in relation to demographic and clinical variables and to treatment option (antiepileptic agents and EEG burst suppression). RESULTS: Forty-nine episodes of RSE (47 patients) were found, occurring more frequently in incident than in recurrent episodes of status epilepticus (P = .06). Mortality was 23% for patients with RSE and 8% for those without RSE (P = .05). Return to baseline occurred more often in the non-RSE group (P = .04). In 20 (61%) of 33 monitored episodes, EEG burst suppression was achieved. Demographic data, clinical variables, and outcome did not differ significantly with the various coma-inducing agents or between episodes with and without EEG burst suppression. CONCLUSIONS: Refractory status epilepticus is more prevalent in incident than in recurrent status epilepticus and is associated with higher mortality; clinical status is less likely to return to baseline than with non-RSE. Outcome was independent of the specific coma-inducing agents used and the extent of EEG burst suppression, suggesting that the underlying cause represents its main determinant.  相似文献   

2.
PURPOSE: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. METHODS: Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications.  相似文献   

3.
Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition.This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se.This article is part of a Special Issue entitled “Status Epilepticus”.  相似文献   

4.
Status epilepticus (SE) is associated with significant mortality and morbidity. A reliable prognosis may help better manage medical resources and treatment strategies. We examined the role of preexisting comorbidities on the outcome of patients with SE, an aspect that has received little attention to date. We prospectively studied incident SE episodes in 280 adults occurring over 55 months in our tertiary care hospital, excluding patients with postanoxic encephalopathy. Different models predicting mortality and return to clinical baseline at hospital discharge were compared, which included demographics, SE etiology, a validated clinical Status Epilepticus Severity Score (STESS), and comorbidities (assessed with the Charlson Comorbidity Index) as independent variables. The overall short‐term mortality was 14%, and only half of patients returned to their clinical baseline. On bivariate analyses, age, STESS, potentially fatal etiologies, and number of preexisting comorbidities were all significant predictors of both mortality and return to clinical baseline. As compared with the simplest predictive model (including demographics and deadly etiology), adding SE severity and comorbidities resulted in an improved predictive performance (C statistics 0.84 vs. 0.77 for mortality, and 0.86 vs. 0.82. for return to clinical baseline); comorbidities, however, were not independently related to outcome. Considering comorbidities and clinical presentation, in addition to age and etiology, slightly improves the prediction of SE outcome with respect to both survival and functional status. This analysis also emphasizes the robust predictive role of etiology and age.  相似文献   

5.
Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.  相似文献   

6.
目的 探讨脑炎后癫痫持续状态(SE)进展为难治性SE(RSE)及超级RSE(SRSE)的早期预测因素.方法 根据疾病进展情况将89例脑炎后SE患者分为非RSE组、RSE组及SRSE组.比较各组临床资料.结果 非RSE组、RSE组及SRSE组年龄、SE严重程度评分量表(STESS)评分、基于流行病学SE病死率评分(EMS...  相似文献   

7.
Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory.  相似文献   

8.
OBJECTIVE: To assess risk factors and prognosis in patients with refractory status epilepticus (RSE). METHODS: We retrospectively analysed all episodes of status epilepticus (SE) treated between 1993 and 2002 on the neurological intensive care unit (NICU) of the Charite-Universitatsmedizin Berlin. The predictive and prognostic features of RSE were compared with non-RSE (NRSE). All patients with "de novo" SE were followed up to identify the possible development of post-SE symptomatic epilepsy. RESULTS: A total of 83 episodes fulfilled our criteria of SE. Of these 43% were refractory to first line anticonvulsants. The mean age of patients with SE was 53.3 (SD 19) years, with only two patients younger than 18 years. Encephalitis was significantly more often the primary cause in RSE (p<0.05), whereas low levels of antiepileptic drugs were significantly more often associated with NRSE (p<0.001). Hyponatraemia within the first 24 hours after onset of status activity was significantly more often associated with RSE (p<0.05). In RSE, compared with NRSE, significantly longer duration of seizure activity (p<0.001), more frequent recurrence of epileptic activity within the first 24 hours after the end of seizure activity (p<0.001), longer stay in the NICU and in hospital (p<0.001 and p<0.01, respectively), and more frequent development of symptomatic epilepsy (p<0.05) were seen. CONCLUSIONS: SE treated in the NICU is frequently refractory to first line anticonvulsant drugs. Encephalitis is a predictor for RSE, which is associated with markedly poor outcome, in particular, the development of post-SE symptomatic epilepsy. Thus prevention of this most severe form of SE should be the primary target of treatment of SE.  相似文献   

9.
Perry MS  Holt PJ  Sladky JT 《Epilepsia》2006,47(6):1070-1071
PURPOSE: To describe three cases of refractory status epilepticus (RSE) in children responsive to topiramate (TPM). METHODS: Patients with SE refractory to therapeutic doses of at least two antiepileptic medications were given TPM, 10 mg/kg/d, for 2 consecutive days, followed by maintenance doses of 5 mg/kg/d. RESULTS: This protocol has been used in three cases of RSE at our institution. In each case, SE was aborted within 21 h of the initial dose of TPM. Two patients avoided pharmacologic coma, and one was rapidly weaned from continuous benzodiazepine infusion. CONCLUSIONS: Our experience indicates that TPM loading can be effective in the treatment of RSE in children.  相似文献   

10.
Aims. Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first‐line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. Methods. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university‐based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non‐convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator‐dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Results. Among 100 patients, the median dose of LE was 3 mg (IQR: 2–5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=‐0.6; p=0.04) and NCSE with coma (correlation coefficient r=‐0.7; p=0.003). Outcome measures were not influenced by BZD dosing. Conclusion. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital‐wide protocol to guide first responders in the management of SE.  相似文献   

11.
Refractory status epilepticus: frequency, risk factors, and impact on outcome   总被引:24,自引:0,他引:24  
BACKGROUND: Refractory status epilepticus (RSE) is a life-threatening condition in which seizures do not respond to first- and second-line anticonvulsant drug therapy. How often RSE occurs, risk factors that predispose to this condition, and the effect of failure to control seizures on clinical outcome are poorly defined. OBJECTIVE: To determine the frequency, risk factors, and impact on outcome of RSE. DESIGN: Retrospective cohort study. SETTING: Large academic teaching hospital. PATIENTS: Consecutive sample of 83 episodes of status epilepticus in 74 patients (mean age, 63 years). MAIN OUTCOME MEASURES: Refractory status epilepticus was defined as seizures lasting longer than 60 minutes despite treatment with a benzodiazepine and an adequate loading dose of a standard intravenous anticonvulsant drug. Factors associated with RSE were identified using univariate and backward stepwiselogistic regression analyses. RESULTS: In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE (P=.03) and focal motor seizures at onset (P=.04) were identified as independent risk factors for RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line agent (usually phenobarbital). Although mortality was not increased (17% overall), RSE was associated with prolonged hospital length of stay (P<.001) and more frequent functional deterioration at discharge (P=.02). CONCLUSIONS: Refractory status epilepticus occurs in approximately 30% of patients with SE and is associated with increased hospital length of stay and functional disability. Nonconvulsive SE and focal motor seizures at onset are risk factors for RSE. Randomized controlled trials are needed to define the optimal treatment of RSE.  相似文献   

12.
Purpose: Status epilepticus (SE) represents a life‐threatening condition, requiring pharmacologic therapy and neurointensive care. Infectious complications in SE are suspected to be frequent and worsen outcome. However, little is known about their incidence during SE and their impact on course and outcome. The aim of this study was to determine the incidence and time of onset of infections during SE, as well as their association with particular SE courses, length of hospitalization, intensive care unit (ICU) stay, and outcome. Methods: All consecutive ICU patients hospitalized due to SE from 2005 to 2009 at the University Hospital Basel were included. Electroencephalography (EEG) recordings and microbiologic data were extracted from two prospectively established databases. Length of SE, ICU, and hospital stay; development of refractory status epilepticus (RSE); and destinations at discharge or death were assessed by comprehensive medical chart review. Key Findings: Of 160 patients, 23% had infections during SE. Of those, 94% were respiratory tract infections, 29% were ventilator‐associated pneumonias. Patients with infections during SE had longer SE duration (p < 0.0001), longer ICU stay (p = 0.0041), higher risk of RSE (odds ratio [OR] 4.8, p = 0.0002), and higher mortality (OR 5.2, p = 0.0003) than those without infectious complications. Infections during the first 3 days after SE onset were significantly associated with longer SE duration, higher rate of RSE, and higher mortality compared to infections detected before SE. Significance: Infections during SE are frequent and associated with higher mortality, prolonged ICU stay, and higher rates of RSE. Further trials are needed to provide evidence of a causative relation between infections and outcomes of SE, followed by investigations on underlying mechanisms and preventive strategies.  相似文献   

13.
Refractory status epilepticus (RSE) is known to constitute approximately 10–50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053–3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429–0.894) were shown to be the only significant independent predictors of refractoriness.  相似文献   

14.
Aim. Status epilepticus (SE) can lead to sequelae or even death. Identifying characteristics associated with poor outcome is crucial in guiding patient treatment. Based on our retrospective patient cohorts, potential prognostic factors were analysed. Methods. Patients consecutively treated for refractory convulsive status epilepticus (CSE) between 2001 and 2010 and non‐convulsive status epilepticus (NCSE) between 2004 and 2009 were studied. Outcome was compared to prognostic variables. Index SE episodes were used for the statistical analyses. Crosstabs and independent samples t‐test were applied. Due to sample size, logistic regression was performed for the combined groups. Results. In total, 50% (9/18) of index refractory CSE and 42% (16/38) of index NCSE episodes led to sequelae. Refractory CSE requiring narcosis for >20 hours was associated with poor outcome (p=0.05). De novo presentation (p=0.0001), long‐lasting SE (>2 hours) (p=0.014), age >65 years (p=0.002), and refractory SE (p=0.047) were predictors of poor outcome following NCSE. Based on logistic regression for combined refractory CSE and NCSE, de novo presentation was identified as the strongest predictor of sequelae. Conclusions. Older age and de novo SE are predictors of sequelae following NCSE. Prolonged SE is a risk factor for poor outcome, both for refractory CSE and NCSE. Aggressive initial treatment to terminate seizures during the early phase is therefore essential.  相似文献   

15.
Status epilepticus (SE) still results in significant mortality and morbidity. Whereas mortality depends mainly on the age of the patient as well as etiology, morbidity often results from a myriad of complications that occur during prolonged admission to an intensive care environment. Although SE is a clinical diagnosis in most cases (convulsant), its treatment requires support by continuous electroencephalographic recording to ensure cessation of potential nonconvulsive elements of SE. Treatment must be initiated as early as possible and consists of benzodiazepine administration and supportive measures for the airway and circulation. These initial interventions are followed by effective intravenous antiepileptic drugs. If the SE becomes refractory, more complex intensive care interventions, such as induction of barbiturate coma, need to be pursued. Data regarding the role of more recently available antiepileptic drugs in treating SE also are discussed in this review.  相似文献   

16.
We aimed to evaluate the determinants of outcome in new onset refractory status epilepticus (SE). A retrospective analysis of patients with new onset SE admitted between May 2005 and October 2013 was performed. Regression analysis was used to determine factors that affect progression of new onset SE to refractory status epilepticus (RSE) and mortality. Among 114 patients with new onset SE, 52 patients progressed to RSE. Sixty seven (58.7%) were men. New onset RSE patients were younger than new onset SE patients (mean 35.9 ± standard deviation18.2 versus 28.7 ± 20.2 years; p = 0.050). Cryptogenic aetiology was the most significant determinant of progression of new onset SE to RSE (Exp [β] = 5.68; p = 0.001). The overall mortality in the entire group was 23.7%, significantly higher in new onset RSE group (40.4% versus 9.7%; p < 0.0001). New onset RSE patients with symptomatic and cryptogenic etiology did not differ for clinical characteristics and outcome. Acidosis was the strongest predictor of mortality in the entire cohort (Exp [β] = 8.72; p = 0.005). Nearly half of the patients with new onset SE progressed to RSE. While cryptogenic aetiology determined progression of new onset SE to RSE, acidosis was associated with mortality. The outcome was similar between symptomatic and cryptogenic new onset RSE.  相似文献   

17.
Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure, and identification of etiology. Symptomatic SE is more common in younger children. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Here we emphasize definitions, clinical and electroencephalography stages, early treatment, special circumstances that may require immediate seizure control, and treatment of RSE. Because much clinical research in SE has been done in adults, we indicate the patient population studied.  相似文献   

18.
BACKGROUND: New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients. METHODS: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer-reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV-AED therapy) and mortality according to choice of agent and titration goal (cIV-AED titration to "seizure suppression" versus "EEG background suppression"). RESULTS: Twenty-eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty-eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short-term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV-AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001). CONCLUSIONS: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.  相似文献   

19.
Nam SH  Lee BL  Lee CG  Yu HJ  Joo EY  Lee J  Lee M 《Epilepsia》2011,52(11):e181-e184
Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1-19) days. At one month of KD, two patients were seizure-free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE.  相似文献   

20.
It is unclear whether the outcome of status epilepticus (SE), a neurological emergency associated with high mortality and morbidity, has changed over the past decade. We investigated the difference in prognosis (mortality, functional status at discharge) after adult SE episodes in a large registry between 2 time points (the years 2009 and 2017), exploring factors potentially associated with outcome, with particular attention to use of newer antiepileptic drugs (AEDs). Newer AEDs were more often prescribed in SE episodes in 2017 (80.2% vs 38.5%, P < .001); this independently correlated with year of observation, SE refractoriness, nonconvulsive SE forms, and number of AEDs. We observed a higher proportion of deterioration from baseline conditions in 2017 (67.7% vs 42.3%, P < .001), which was independently associated with, among other variables, use of newer AEDs (odds ratio = 2.91, 95% confidence interval = 1.13‐7.48), whereas mortality seemed more stable over time (16.1% vs 6.3%, P = .08) without any relationship with newer AEDs. These observations suggest that newer AEDs might affect functional status but not mortality. Further investigations are necessary to improve therapeutic strategies, which currently rely on weak evidence.  相似文献   

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