Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial

Kim, Lois; Johnson, Tony; Marson, Anthony G; Chadwick, David

doi:10.1016/s1474-4422(06)70383-0

Cited by 265 publications

(198 citation statements)

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“…In addition, inclusion of patients with a single seizure is consistent with the new definition of epilepsy by the International League Against Epilepsy (ILEA), 22 that is, the requirement of a significant risk of seizure recurrence based on EEG and imaging, factors which significantly increase the likelihood of seizure recurrence. 34 This definition was adopted because it reflects current clinical practice, in particular in the elderly population with a frequent structural etiology of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

A randomized, double‐blind comparison of antiepileptic drug treatment in the elderly with new‐onset focal epilepsy

et al. 2015

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SUMMARYObjective: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy. Methods: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency. Results: Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0). Significance: In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov.

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Section: Discussionmentioning

confidence: 99%

A randomized, double‐blind comparison of antiepileptic drug treatment in the elderly with new‐onset focal epilepsy

et al. 2015

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“…In patients affected by craniocerebral trauma or intracranial infection, a single seizure can be a harbinger of a gradual increase in seizure probability [1][2][3][4]. This apparent facilitation of epileptogenesis may be due to changes in the neuronal microenvironment, such as seizure-induced inflammatory responses and changes in glutamate metabolism [4,5].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

Liu

Zhang

et al. 2018

Neurotherapeutics

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Inflammation is implicated in epileptogenesis. Activated microglia and macrophages (MG/MΦ) are found in the brains of patients with epilepsy-related diseases and animal models of epilepsy. It is not yet known how the MG/MΦ activation phenotype affects pathological changes in the brain after a single seizure. In this study, we had 2 main purposes: first, to characterize poststatus epilepticus (SE) inflammation by tracking MG/MΦ polarization, and, second, to explore the role of an innate immune receptor adaptor protein, namely, myeloid differentiation primary response gene 88 (MyD88), in the induction of SE in a mouse model. A lithium-pilocarpine model of seizure conditions was generated in C57BL/6 mice. The intensity and distribution of MG/ MΦ polarization were tracked by fluorescent immunohistochemistry and Western blotting for the polarization markers inducible nitrogen oxygenized synthase, arginase-1, CD163, and mannose receptor. We observed steadily increasing M1 MG/MΦ along with MyD88 signal upregulation after SE in the hippocampi of mice, whereas the M2 marker arginase-1 was localized mainly in astrocytes rather than in MG/MΦ. Inhibition or gene knockout of MyD88 reduced M1 MG/MΦ and gliosis although increasing M2 MG/MΦ in the hippocampi of SE mice. MyD88 inhibition also augmented glutamate transporter 1 expression and reduced N-methyl-D-aspartate receptor NR1 subunit expression in the hippocampus to protect pyramidal neurons from apoptosis. These data suggest that MG/MΦ polarization after SE impacts the pathological outcome of the hippocampus via MyD88 signaling and point to MyD88 as a potential neuroprotective target for epilepsy therapy.

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“…Early seizure frequency, etiology of seizures, and an abnormal EEG are known to be predictive factors for seizure recurrence 12 and long term outcomes as observed in the MESS trial 13 and a long term follow-up study 14 ; recurrence in our study was altered by the early use of AEDs in patients with abnormal EEGs and/or abnormal MRIs. The high rate of neuroimaging and EEG abnormalities in this study most likely reflects the highly selective nature of the group; considered high risk for seizure recurrence or likely focal seizure in origin, as not all patients with first unprovoked seizures are referred to the epileptologist in the province of Saskatchewan.…”

mentioning

confidence: 53%

Single Unprovoked Seizure: Wait Time to Full Medical Assessment, Does It Matter?

Anang¹,

Téllez‐Zenteno²

2012

Neurol. Bull.

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IntroductionSingle unprovoked seizures occur in about 4% of the population and they have significant psychosocial consequences for the patients and their families. Little information is available on the timeliness and safety of assessment of first unprovoked seizures. In this study, we review the timeliness of the referral and evaluation of patients with first unprovoked seizure in a Canadian neurological provincial referral center. MethodRetrospective analysis of 51 patients over a 3.5 year period was performed and data were collected on patient demographics, date of event and time to evaluation by the epileptologist, evaluations completed, treatments initiated, and patient outcomes. ResultsWe found that most patients were seen by the epileptologist within 6 months, there was only a 9% discrepancy in final diagnoses between the epileptologist and the referring physician, and there were no fatalities or serious complications in the patients we studied. However, a few patients waited very long periods before imaging and evaluation by the epileptologist, and restrictions on driving privileges were recommended in only 3% of the patients. ConclusionsWe conclude that the referral process for a first unprovoked seizure is timely. Primary care providers need further education with regards to the consequences of seizures and some areas of the referral region need better access to imaging and epileptologists.

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Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial

Abstract: The model shows that there is little benefit to immediate treatment in patients at low risk of seizure recurrence, but potentially worthwhile benefits are seen in those at medium and high risk.

Cited by 265 publications

References 11 publications

A randomized, double‐blind comparison of antiepileptic drug treatment in the elderly with new‐onset focal epilepsy

A randomized, double‐blind comparison of antiepileptic drug treatment in the elderly with new‐onset focal epilepsy

Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in Mice

Single Unprovoked Seizure: Wait Time to Full Medical Assessment, Does It Matter?

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