Evidence map›Paper›PMID 41626781›Full record

ArticleEpilepsia2026

Preclinical signal for a disease-modifying effect on seizure cluster severity with intermittent diazepam treatment.

Qian Wu, Michelle Guignet, Jonathan Vuong, H Steve White, Wesley T Kerr, Evelyn K Shih, Leock Y Ngo, Enrique Carrazana, Adrian L Rabinowicz

Abstract read
In one paragraph

Article in Epilepsia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Qian WuDepartment of Pharmacy, Center for Epilepsy Drug Discovery, University of Washington, Seattle, Washington, USA.ORCID https://orcid.org/0000-0002-6259-7434
Michelle GuignetDepartment of Pharmacy, Center for Epilepsy Drug Discovery, University of Washington, Seattle, Washington, USA.ORCID https://orcid.org/0000-0003-4788-0175
Jonathan VuongDepartment of Pharmacy, Center for Epilepsy Drug Discovery, University of Washington, Seattle, Washington, USA.
H Steve WhiteDepartment of Pharmacy, Center for Epilepsy Drug Discovery, University of Washington, Seattle, Washington, USA.ORCID https://orcid.org/0000-0003-4550-4408
Wesley T KerrDepartments of Neurology and Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-5546-5951
Evelyn K ShihNeurelis, San Diego, California, USA.ORCID https://orcid.org/0000-0002-8455-0231
Leock Y NgoNeurelis, San Diego, California, USA.ORCID https://orcid.org/0000-0002-8184-1367
Enrique CarrazanaNeurelis, San Diego, California, USA.ORCID https://orcid.org/0000-0001-8788-0722
Adrian L RabinowiczNeurelis, San Diego, California, USA.ORCID https://orcid.org/0000-0003-1299-0606

Funding

Neurelis
6 · The paper itself

Abstract

objectiveIn epilepsy, daily treatment provides only symptomatic seizure control, leaving a significant unmet need for a treatment that affects the underlying predisposition to seizures. Here, in a first-of-its-kind study, we test the hypothesis that intermittent treatment of seizure clusters with diazepam in the kainic acid post-status epilepticus rat model of acquired epilepsy has an enduring effect on the seizure cluster phenotype, suggestive of potential disease modification.

methodsFollowing kainic acid-induced status epilepticus, rats with epilepsy were monitored for occurrence of seizure clusters (≥2 seizures in 24 h) for a 3-week baseline period before entering a 6-week treatment period using a previously established multidose regimen of diazepam (n = 7) or vehicle (n = 9) upon identification of a seizure cluster. In a subsequent 2-week outcome period during which no rats received diazepam, we evaluated changes in seizure cluster size, burden (cluster size × severity), duration, and other phenotype parameters.

resultsA total of 3396 seizures and 216 seizure clusters were included for analysis. During the outcome period, time between seizures in a cluster (also interseizure interval [ISI]) was significantly longer in the diazepam group (log ISI = .25 longer, SE = .08, p < .0001), and the proportion of clustered seizures with an ISI of ≤30 min increased in the outcome period in the vehicle group (p = .023) but was stable in the diazepam group. Despite the occurrence of rebound seizures during the treatment period, improvement in several phenotypical parameters, including severity and proportion of seizures in a cluster, supported a positive impact of intermittent diazepam treatment on seizure cluster biology. SIGNIFICANCE: Changes in several seizure cluster phenotypical parameters were suggestive of an enduring disease-modifying effect of diazepam, despite an apparent rebound effect of intermittent diazepam treatment on seizure frequency. Further study is warranted using a model incorporating a background antiseizure medication regimen to potentially attenuate the unexpected rebound seizures.

Indexed as

AnticonvulsantsDiazepamSeizuresStatus EpilepticusAnimalsDisease Models, AnimalKainic AcidMaleRatsRats, Sprague-DawleySeverity of Illness IndexAnticonvulsantsDiazepamKainic Acidbenzodiazepinedisease‐modifying effectimmediate‐use seizure medicationrescue therapyseizure clusters

Identifiers

PMID41626781
PMCPMC13007841

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.