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

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.

Local glucose metabolism is unaltered in reversible splenial lesion syndrome

“…In all patients with RESLES, the presumed cause was the rapid reduction in antiseizure medications for diagnostic reasons. No patient exhibited any overt neurological deficits attributable to splenial oedema, as previously reported [6]. Age, sex, and clinical epilepsy subtypes (temporal vs. extratemporal lobe epilepsy) did not differ significantly between groups (Table 1).…”

“…No patient exhibited any overt neurological deficits attributable to splenial oedema, as previously reported [6]. Age, sex, and clinical epilepsy subtypes (temporal vs. extratemporal lobe epilepsy) did not differ significantly between groups (Table 1).…”

“…Further insights into the probable pathophysiology of RESLES can be obtained from a purely clinical perspective. Typically, intracellular cytotoxic but not intercellular intramyelinic oedema compromises gross neuronal functional integrity, and clinical experience suggests a lack of overt neurological deficits in RESLES [6,15], despite the central role played by the corpus callosum in interhemispheric communication. The appearance of RESLES in the context of acute encephalitic or encephalopathic diseases can make determining the contributions of RESLES to neurological deficits challenging.…”

“…The appearance of RESLES in the context of acute encephalitic or encephalopathic diseases can make determining the contributions of RESLES to neurological deficits challenging. However, the occurrence of RESLES following the discontinuation of antiseizure medication is not associated with any specific overt neurological deficits [6,15].…”

“…On MRI, RESLES presents with restricted proton diffusion in diffusion‐weighted imaging (DWI), with increased intensity in T2‐weighted imaging and reduced intensity in T1‐weighted imaging, and without gadolinium enhancement [5]. RESLES can appear after reductions in antiseizure medications (especially sodium‐channel blockers) [6] and in cases of systemic infections, intoxications and metabolic disorders [1,3,4]. Due to the broad spectrum of conditions associated with RESLES, its clinical significance and diagnostic consequences remain unclear [7].…”