Reversible Cytotoxic Edema in the Splenium of the Corpus Callosum Related to Antiepileptic Treatment: Report of Two Cases and Literature Review

Abstract

Summary:Purpose: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology.Methods: We report two cases including a 25-year-old male patient and a 12-year-old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation.Results: Comprehensive MRIs, including diffusion tensor imaging-based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient.Conclusions: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion. key Words: Epilepsy-MRISplenium-Corpus callosum-Antiepileptic drugs-Arginine vasopressin-Cytotoxic edema.Several reports of clinically silent lesions in the splenium of the corpus callosum (SCC) of patients receiving antiepileptic treatment have been recently published (Table 1). Different pathophysiologic hypotheses have been put forward as possible etiologic explanations, such as vasogenic edema secondary to blood-brain barrier breakdown (1), cytotoxic edema secondary to seizure spread (2-4), or antiepileptic drugs (AED) toxicity (5,6), demyelinating disease secondary to vitamin B deficiency, as well as edema secondary to arginine vasopressin (AVP) imbalance induced by rapid AED changes (7). Here we report two cases of epilepsy patients with splenial lesions discovered in the context of presurgical epilepsy evaluation. CASE REPORT Patient 1A 25-year-old male patient with an anxiety disorder and pharmacoresistant epilepsy since age 12 years was , combined with repeated sleep deprivation, no seizure occurred during our evaluation. Six days after the beginning of AED discontinuation, CBZ was reintroduced, and a control brain MRI was carried out. Aside from the postsurgical status in the right temporal lobe, a circumscribed lesion in the SCC, hypointense on T 1 and hyperintense on T 2 -weighted sequences, was noted. A diffusion-weighted acquisition showed a hyperintense lesion corresponding to a decreased apparent diffusion coefficient, which suggested the presence of a cytotoxic edema (Fig. 1). The patient's neurologic status was normal. Neuropsychological evaluation ruled out a disconnection syndrome. Routine laboratory tests, including hematologic analysis, were normal as were vitamin B 1 , B 2 , and B 6 levels. A repeated brain MRI 10 days after the first imaging showed an almost resolved lesion that completely disappeared on a MRI control 1 year later. A ...

Mild Encephalitis/Encephalopathy With a Reversible Splenial Lesion: Evaluation by Diffusion Tensor Imaging -Three Case Reports-

“…8) Diffusion tensor imaging findings for the early phase were reported in one case with reversible lesion of the splenium of the corpus callosum related to antiepileptic treatment. 7) Fractional anisotropy was normal in the lesion in the acute phase, and may reflect the presence of nondegenerative intramyelinic edema. However, even in degenerative disorders such as ischemic lesions, fractional anisotropy values are not decreased markedly in the early phase, because the decrease in diffusion anisotropy occurs much later than that of ADC.…”

“…7,8) In some cases, including our Cases 2 and 3, reversible lesions detected with diffusion-weighted imaging extended into the entire corpus callosum and deep white matter as well as the splenium of the corpus callosum. 5,12) Moreover, in Case 2, the initial MR imaging showed lesions in the whole corpus callosum and symmetric centrum semiovale lesions, and MR imaging on day 4 revealed lesions only in the splenium, as previously mentioned in a similar case.…”

Transient Splenial Lesion after Recovery of Cerebral Vasoconstriction and Posterior Reversible Encephalopathy Syndrome: A Case Report of Eclampsia

“…The exact time of TSL appearance remains unclear because no signs indicating splenial damage have been mentioned in the present and previous patients with TSL (14)(15)(16)(17)(18)(19)(20)(21). In general, restricted water diffusivity could play a major role in the pathogenesis of TSL (14,15,17,(19)(20)(21). In the present patient, ADC map did not show a hypointensity lesion in the splenium.…”

“…TSL is well known to appear in epi- leptic patients with and without AED treatment (14)(15)(16)(17)(18)(19)(20)(21). Toxic effects or rapid changes in the concentration of AED may be implicated in TSL development (14,16,17,20). The present patient had a generalized seizure at 1 month before the appearance of TSL, but did not receive AED throughout the entire course.…”

Commentary: Mycoplasma pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion: Report of two pediatric cases and a comprehensive literature review

“…Since it occurred in only 31.0% -60.0% 3,27,28 of MERS cases although high prevalence (83.3 %) was reported 25 , hyponatremia may be a predisposing but not causative factor. Electrolyte-water imbalance 25 by arginine vasopressin suppression 29 is proposed as a cause, but this awaits further investigations.…”