We read with special interest the article by Oaklander and Buchbinder. The authors report a case of an 80-year-old woman who developed nausea, diarrhea, headache, and imbalance 30 hours after discontinuation of pregabalin treatment that she had been taking for postherpetic neuralgia for 49 weeks. Over the following days, she developed visual and auditory hallucinations as well as alexia. There were no signs of infection neither on the blood screen 1 week after the onset of symptoms nor in the cerebrospinal fluid examination 3 weeks later. Three weeks after onset of symptoms, brain magnetic resonance imaging was performed and demonstrated a splenial edema as well as scattered periventricular lesions. The authors draw a comparison between this case and symptoms found in some patients affected by high-altitude cerebral edema (HACE) in which similar splenial lesions have been described. Indeed, Hackett and colleagues have reported several cases of patients with HACE and splenial lesions that they hypothesized as being a reflection of vasogenic edema. However, the exact nature of the lesion (cytotoxic vs vasogenic edema) was not formally determined in that study or in Oaklander and Buchbinder’s study, because no diffusion-weighted imaging (DWI) was performed in Hackett and colleagues’ study and apparent diffusion coefficient (ADC) explorations were not performed in Oaklander and Buchbinder’s study. The authors also compared this case with previously described cases of transient splenial lesions in epileptic patients or nonepileptic patients on antiepileptic drugs (AEDs); however, we feel that such a parallel should be drawn more cautiously. Indeed, all of these cases were fortuitous radiological findings in otherwise asymptomatic patients with normal neuropsychological examination. Moreover, in contradiction to the authors’ assertion, none of the described patients had a documented vasogenic edema, whereas the only four cases explored with DWI/ADC acquisitions demonstrated cytotoxic edema. Thus, even if pregabalin implication in this patient’s encephalopathy is possible, the course and degree of clinical manifestations as well as their persistence is in contrast with previous findings in patients on AED. This implies that either this is the first case of persistent encephalopathy with splenial lesion related to AED discontinuation or that there is a different cause for this patient’s encephalopathy. Indeed, several reports have been published recently describing transient splenial lesions in the context of either viral or bacterial encephalopathy, sometimes associated with gastroenterological manifestation as seen in the present case. Note that a vitamin deficiency was not ruled out in this case, because blood vitamin levels have not been determined and because some patients, particularly of older age, may present a malabsorption syndrome without visible malnutrition. Hence, Marchiafava–Bignami disease may still be another possible cause in this case. Also, a reversible posterior leukoencephalopathy as seen in malignant hypertension, immunosuppression and other disorders could be another differential diagnosis. The incomplete reversibility of symptoms and the fact that the brain MRI was carried out three weeks after the onset of symptions, thus possibly showing only residual lesions, speak in favor of this possibility.