J Neurol (2011) 258:1098–1104 could be ruled out. Also post-ictal imaging changes (swelling and enhancement) and posterior reversible encephalopathy syndrome (PRES) as observed in patients with hypertensive encephalopathy or following the use of immunosuppressive agents should be considered [8, 9]. The episodic nature of the deﬁcits with spontaneous resolution over weeks in combination with unilateral enhancement and thickening of the posterior cortex on MRI might suggest focal epileptic activity with long-last- ing post-ictal deﬁcit as the cause of the clinical symptoms. Yaffe and Ferreiro described eight patients who had all been treated with systemic chemotherapy with comparable reversible MRI changes following seizures. The majority of the lesions involved grey and white matter, predomi- nantly in the posterior vascular boundary zones [10]. This phenomena was attributed to damage to the blood–brain barrier by systemic chemotherapy in combination with seizures. In our patients, however, damage to the parieto- occipital blood brain barrier was presumably due to radi- ation therapy. Irradiation affects primarily the vasculature or the trigeminovascular system and engender a reversible disturbance of homeostasis. Most previously presented cases [2–4] had been treated with posterior fossa irradia- tion, and it is presumed that the posterior lobes are speciﬁc vulnerable for radiation damage. Regarding epileptic sei- zures as the underlying mechanism, in two of our patients the seizures occurred either before the development of MRI abnormalities or after the MRI abnormalities had subsided. Also, repeated EEG in three of four patients did not show epileptic activity during the symptoms. Additionally, post- ictal MRI abnormalities in patients without previous radi- ation therapy or chemotherapy are not conﬁned to the pa- rieto-occipital region [8]. We therefore argue that the MRI ﬁndings as observed in our patients cannot be explained by post-ictal enhancement alone. Reversible white matter enhancement, but not cortical enhancement has been described in patients with migraine [11, 12]. The under- lying mechanisms of these transient imaging abnormalities in migraine include meningeal and parenchymal hyper- perfusion, edema or inﬂammatory plasma protein extrav- asation after disruption of the blood brain barrier. Besides, the prolonged duration of the symptoms in our patients, who had no history of migraine headaches, are unlikely due to migraine. Otherwise, the clinical and radiological picture of these patients is compatible with the SMART syndrome. SMART syndrome involves transient, reversible neurological dys- function which may include migrainous headache, at times preceded by aura, prolonged hemispheric neurological impairment and sometimes seizure activity [2, 3]. Neuro- imaging studies of patients with SMART syndrome typi- cally show focal gyral thickening of the affected cortex and gyriform contrast enhancement. Before SMART was 1103 deﬁned as a distinct syndrome, similar patients with sort- like reversible MRI changes and clinical symptoms after radiation were reported [5, 13–15]. The pathophysiology of the SMART syndrome is poorly understood. A speciﬁc vulnerability of the parieto-occipital cortex for radiation or chemotherapy, similar to that observed in PRES, may explain why the imaging ﬁndings are preferentially observed in this region [1]. Patient 2 had been treated with whole-brain radiation and developed parieto-occipital abnormalities in the left hemisphere, not related to the original site of the brain metastases, which supports this concept. The clinical presentation of PRES has similarities with SMART, including headaches, neu- rological deﬁcits and, more frequently than in SMART, seizures. The pathophysiology of PRES is combined vasoconstriction and vasodilation and has the same patterns as seen in vasculopathy [9]. This results in blood brain barrier disruption leading to symmetric hemispheric edema and contrast enhancement on MRI [9]. Since radiation may preferentially damage endothelial cells, the SMART syn- drome might be a reversible radiation vasculopathy com- parable with PRES. An alternative hypothesis is that post- radiation neuronal dysfunction is the underlying mecha- nism, such as in migraine or epilepsy, with impairment of the trigeminovascular system or a lowered threshold for cortical spreading depression [21].The parieto-occipital cortical damage might even be the cause of epileptic sei- zures rather than being the result of seizures [13]. Development of the SMART syndrome has been related to a radiation dose of at least 50 Gy, as described in most of the previous cases [3–5]. In our cases, a dose exceeding 50 Gy had only be applied to patients 1 and 3. In the other two patients, however, the daily fraction doses were rela- tively high (3 Gy in patient 2 and 2.5 Gy in patient 4, respectively), which may have attributed to the radiation toxicity. Late effects of radiotherapy have mainly been blamed on vascular endothelial injury and demyelination, and include diffuse white matter changes or focal necrosis with mass effect [16–18]. In contrast with the SMART syndrome these late effects of radiation therapy are gradual in onset and may have a progressive nature [19, 20]. If these reversible, stroke-like migraine attacks are related to remote radiation therapy, this relationship may be under recognized so far because many patients did not live long enough to experience these late treatment effects. Conﬂict of interest None declared. 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