J Neurol (2011) 258:1098–1104 Table 1 Clinical details of reported cases with the SMART syndrome 1099 Age (years) Patient 1 male, 36 Tumour Pinealoma CSF studies Protein 0.33 leukocytes 1 None Patient 2 male, 60 Brain metastases from small-cell lung cancer Protein 0.81 leukocytes 1 Patient 3 male, 42 Patient 4 male, 39 Oligodendroglioma Astrocytoma Protein 0.43 leukocytes 1 Protein 0.71 leukocytes 2 Diffuse white matter changes Deep white matter disease None MRI radiation Toxicity Interval Symptoms (years) Original tumour site Radiation type and dose 4 10 2 and 5 5 and 10 Headache neurologic deﬁcit seizures Headache neurologic deﬁcit seizures Headache neurologic deﬁcit seizures Neurologic deﬁcit seizures Pineal region Craniospinal axis 36 Gy (20 9 1.8) tumour booster 18 Gy (10 9 1.8) Both hemispheres WBRT 30 Gy (10 9 3) Left parietal Focal 60 Gy (30 9 2) lobe Right temporal lobe Focal 50 Gy (20 9 2.5) Protein level in g/l Interval, years between irradiation and the ﬁrst symptoms; Gy, radiation dose in Grays; X, number of radiation fractions; WBRT, whole-brain radiation therapy; Focal, focal radiation on the original tumour site Case reports Patient 1 In 1999 at age 32 years, this man had progressive headache and diplopia due to an obstructive hydrocephalus caused by a pineal tumour. Following resection a pineoloma with malignant histological features was diagnosed. MRI of the craniospinal axis and CSF examination demonstrated no other tumour localizations. He was subsequently treated with craniospinal irradiation (36 Gy in 20 fractions with a boost of 18 Gy to the original tumour site). Following a minor head trauma 4 years after RT he developed increasing headache over the following days and a left hemianopia. No tumour recurrence was observed on MRI, nor in the cerebrospinal ﬂuid (CSF) (Table 1). Additional imaging ruled out ischemic stroke, vertebral artery dissection and venous sinus throm- bosis. However, on MRI, gyral thickening of the right parieto- occipital cortex with contrast enhancement was seen (Fig. 1a, b). During hospitalisation he developed several generalized seizures with persistent post-ictal weakness of the left arm and confusion, lasting for several weeks. He was treated with valproate and levetiracetam. EEG showed slowing over the right hemisphere but no epileptic activity. The observed MRI abnormalities recovered over the weeks thereafter, with concomitant clinical improvement (Fig. 1c, d). Two years later he developed a similar clinical episode for which he was admitted once more, this time without seizures. The same imaging abnormalities were observed which resolved once again over the following months without any treatment. Again, no tumour recurrence could be demonstrated. However, in 2008, 8 years after the initial presentation he did develop spinal leptomeningeal metastases, for which he was treated with focal RT and systemic chemotherapy. Fig. 1 36-year-old man who was treated 4 years previously for pineal tumor with radiation therapy, now presenting with headache and left hemianopia. a T2 weighted, ﬂuid attenuated inversion recovery (FLAIR) MR image showing diffuse gyral swelling and signal increase in the right occipital lobe. b T1 weighted MR image after gadolinium administration showing diffuse gyral and leptome- ningeal enhancement. MR images obtained 9 month later showing non residual signal abnormalities on FLAIR (c) and no abnormal enhancement (d) Patient 2 In 1997 at age 50 years, this man was treated for small cell lung cancer and two brain metastases with systemic che- motherapy and whole-brain radiation (30 Gy in 10 fractions). 123