Rapid discontinuation of sodium channel-blocking antiseizure drugs evokes focal edema in the splenium corporis callosi: A matched case-control study

Epilepsia. 2019 Jul;60(7):1353-1364. doi: 10.1111/epi.16052. Epub 2019 Jun 6.

Abstract

Objective: Focal edema of the splenium of the corpus callosum (FESCC) is infrequently seen in patients with epilepsy who are undergoing video-electroencephalography (EEG) monitoring. It is diagnosed by qualitative visual inspection of the magnetic resonance imaging (MRI) and is usually assumed to be a dichotomous phenomenon. Rapid reduction of anticonvulsants has been proposed as a cause. In this study we investigate the relationship between dose reduction of anticonvulsants and the occurrence of FESCC, based on absolute drug doses.

Methods: We examined in detail the anticonvulsive therapy of all patients during video-EEG monitoring between 2014 and 2018. We compared patients with a radiologically diagnosed FESCC to controls in a 1:2 case-control analysis matched by age, epilepsy syndrome, and adjacent time of admission. In a separate correlation analysis, we examined quantitative effects of reduction of antiseizure drugs on diffusion restriction in the corpus callosum.

Results: Of 326 patients who had an MRI following video-EEG monitoring, 12 (3.7%) had FESCC. Antiseizure drugs were reduced to a significantly greater extent in FESCC patients than in the 24 controls (P < 0.001). Sodium channel-blocking antiseizure drugs were reduced (P < 0.001) and reintroduced (P < 0.001) significantly faster in FESCC patients, and the duration of anticonvulsant discontinuation was longer in FESCC patients (P < 0.001). The separate correlation analysis in 325 patients shows a weak correlation between diffusion restriction in the splenium and the reduction rate of sodium channel-blocking anticonvulsants (r = -0.15, P = 0.03) as well as the duration of their discontinuation (r = -0.16, P = 0.01). No such effects were found for anticonvulsants with other modes of action.

Significance: Our findings substantiate that FESCC is associated with high rates of dose reduction of anticonvulsants, specifically those acting on sodium channels. Our results cautiously suggest that reducing sodium-channel blockers has a small effect on diffusivity in the splenium below the visual threshold.

Keywords: anticonvulsants; epilepsy; intramyelinic edema; splenium corporis callosi; video-EEG monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Brain Edema / chemically induced*
  • Brain Edema / diagnostic imaging
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Corpus Callosum* / diagnostic imaging
  • Corpus Callosum* / pathology
  • Electroencephalography
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Sodium Channel Blockers / administration & dosage
  • Sodium Channel Blockers / adverse effects*
  • Sodium Channel Blockers / therapeutic use
  • Substance Withdrawal Syndrome / diagnostic imaging
  • Substance Withdrawal Syndrome / etiology*
  • Young Adult

Substances

  • Anticonvulsants
  • Sodium Channel Blockers