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A wide range of acute neurological disorders may present with symptoms similar to a stroke, so-called 'stroke mimics'. Migraine aura and seizures account for the most extensive stroke mimics population. A large number of patients with a definite stroke mimics diagnosis (most commonly those with psychiatric disorders or seizures) had been treated with IV alteplase without adverse related events. We report a case of a man aged 70 years admitted to the emergency room because of acute onset of delirium and a loss of strength in the left arm (National Institutes of Health Stroke Scale {NIHSS}: 10), severe hyponatremia (127 mEq/L), and no evidence of intracranial arterial occlusion at CT scan. He was eligible for intravenous thrombolysis and, after treatment, neurological symptoms improved (NIHSS: 2). The subsequent appearance of "clonus" in the left lower limb, the persistence of hyponatremia, and the presence of electroencephalogram (EEG) abnormalities led to the clinical suspicion of focal motor-onset seizure with impaired awareness. The patient was treated successfully with anti-seizure medications (ASMs): lacosamide 200 mg IV during the acute setting care, followed by oral lacosamide 200 mg bis in die (BID). Since two other focal seizures occurred, brivaracetam 25 mg BID has been added in therapy with subsequent clinical discontinuance and EEG normalization. Two consecutive magnetic resonance imaging (MRI) examinations showed several cortical lesions restricted in high signal in diffusion-weighted imaging (DWI) which corresponding to T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintensities, but without lesions evidence in apparent diffusion coefficient (ADC) map. These radiological changes disappeared at a follow-up MRI performed 20 days after the symptoms' onset. The patient fully recovered was discharged home without developing pharmacological adverse events. In this case, MRI provided an opportunity for early identification of seizure-related alterations. Hence, we discuss how prospective MRI studies during seizures and interictal period would contribute to defining the relationship between the electroclinical characteristics and MRI alteration patterns, and therefore, the potential role of MRI in the differential diagnosis between seizures and stroke mimic.