J Neurol (2011) 258:1098–1104 DOI 10.1007/s00415-010-5892-x O R I G I N A L C O M M U N I C A T I O N SMART syndrome: a late reversible complication after radiation therapy for brain tumours Joost P. Kerklaan • Geert J. Lycklama a´ Nijeholt • Ruud G. J. Wiggenraad • Bianca Berghuis • Tjeerd J. Postma • Martin J. B. Taphoorn Received: 7 June 2010 / Revised: 18 December 2010 / Accepted: 20 December 2010 / Published online: 4 March 2011 The Author(s) 2011. This article is published with open access at Springerlink.com Abstract With intensiﬁed treatment leading to longer survival, complications of therapy for brain tumours are more frequently observed. Regarding radiation therapy, progressive and irreversible white matter disease with cognitive decline is most feared. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy). All four patients (males, age 36–60 years) had been treated with focal brain radiation for a primary brain tumour or with whole-brain radiation therapy for brain metastases. Ranging from 2 to 10 years following radiation therapy patients presented with headache and focal neurological deﬁcits, suggestive for tumour recur- rence. Two patients also presented with focal seizures. MRI demonstrated typical cortical swelling and contrast enhancement, primarily in the parieto-occipital region. On follow-up both clinical and MRI features improved spon- taneously. Three patients eventually proved to have tumour recurrence. The clinical and radiological picture of these J. P. Kerklaan (&) B. Berghuis M. J. B. Taphoorn Department of Neurology, Medical Centre Haaglanden, Postbus 432, 2501 CK The Hague, The Netherlands e-mail: J.Kerklaan@mchaaglanden.nl G. J. Lycklama a´ Nijeholt Department of Radiology, Medical Centre Haaglanden, The Hague, The Netherlands R. G. J. Wiggenraad Department of Radiotherapy, Medical Centre Haaglanden, The Hague, The Netherlands T. J. Postma M. J. B. Taphoorn Department of Neurology, VU University medical centre, Amsterdam, The Netherlands 123 patients is compatible with the SMART syndrome, a rare complication of radiation therapy which is probably under recognized in brain tumour patients. The pathophysiology of the SMART syndrome is poorly understood but bears similarities with the posterior reversible encephalopathy syndrome (PRES). These four cases underline that the SMART syndrome should be considered in patients for- merly treated with radiation therapy for brain tumours, who present with new neurologic deﬁcits. Before the diagnosis of SMART syndrome can be established other causes, such as local tumour recurrence, leptomeningeal disease or ischemic disease should be ruled out. Keywords Reversible late effects Radiation therapy Brain tumours Introduction With improved treatments for brain tumours leading to longer survival, late complications of therapy are more frequently observed. The development of new neurological symptoms following brain tumour treatment is primarily suggestive for tumour recurrence, but when this has been ruled out, adverse treatment effects as a cause of the symptoms should be considered. Amongst late complica- tions of radiation therapy, progressive leukoencephalopa- thy with cognitive decline and focal radiation necrosis mimicking recurrent tumour growth are the most worri- some [1]. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so-called SMART syndrome: stroke-like migraine attacks after radiation therapy [2–4].