Elsevier

Revue Neurologique

Volume 173, Issues 1–2, January–February 2017, Pages 67-73
Revue Neurologique

Short communication
SMART syndrome: Classic transient symptoms leading to an unusual unfavorable outcome

https://doi.org/10.1016/j.neurol.2016.09.014Get rights and content

Abstract

Background

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of cerebral radiation therapy that usually presents > 10 years after treatment as reversible paroxysmal episodes of neurological dysfunction associated with headaches.

Cases

We report here on two cases of SMART syndrome in long-term survivors of high-grade glioma for whom neuropathological data were available. The course of the disease was unfavorable. Although the clinico-radiological picture of SMART syndrome clearly differs from classic cerebral radionecrosis, the gross neuropathological lesions observed in our two patients appeared to be similar to those described in focal radionecrosis.

Conclusion

SMART syndrome may progress from a benign reversible form to a severe and eventually irreversible form. This severe course may also be confused with tumor progression, and lead to permanent disability and inadequate antitumor treatment. Clinicians should be aware of this latter atypical presentation.

Introduction

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a complication of cerebral radiation therapy that usually presents at 2 to > 10 years after treatment. It was originally referred to as “complicated migraine-like episodes” by Shuper and colleagues in 1995 [1]. The clinical picture is characterized by reversible paroxysmal episodes of neurological dysfunction associated with headaches [2], [3]. The neurological symptoms can take the form of typical aura but, often, the neurological impairment is more prolonged, and patients may sometimes also present with seizures [4], [5]. On magnetic resonance imaging (MRI), a pattern of gyral enhancement is frequently seen after such an attack [2], [3], [5], [6], [7], [8], [9], [10], [11], [12], [13], while 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET) may reveal hypermetabolism in symptomatic regions that resolve on follow-up studies [4].

The differential diagnosis from other complications of cerebral radiotherapy with contrast enhancement requires careful analysis of the clinical presentation (Table 1). Nevertheless, the pathophysiology of SMART syndrome remains to be elucidated and, to date, the neuropathological lesions underlying the syndrome are as yet unknown.

We report here on two cases of SMART syndrome in long-term survivors of high-grade glioma, both of whom enjoyed prolonged survival after the onset of SMART syndrome and for whom neuropathological data were available. In both patients, the course of disease was unfavorable, and eventually led to severe and permanent neurological damage.

Section snippets

Case 11

A 64-year-old woman with a history of common migraine presented with partial seizures in 2001. MRI showed a contrast-enhanced left parietal mass (Fig. 1A). Partial resection and histological examination revealed glioblastoma (GBM). The patient subsequently received a course of focal cranial irradiation (60 Gy in 30 fractions) and five courses of chemotherapy with carmustine. In 2002, a recurrent tumor was suspected on MRI, and she received 24 courses of temozolomide with good tolerance and

Neuropathology

Histological examination of Case 1 was performed with biopsy samples containing both cortex and white matter (Fig. 4). There were no signs of malignancy in the material examined. The main finding was an irregular necrotic lesion involving both white and gray matter, with massive infiltration by macrophages (CD68+ cells; Dako 1/1000, KPL; Fig. 4B). This coagulation necrosis was associated with significant vascular proliferation. Vessel walls were markedly thickened by fibrinoid necrosis, and

Discussion

Our two patients fulfilled the diagnostic criteria for SMART syndrome [2]: (i) past history of cerebral external beam radiation therapy; (ii) development of new lesions in the radiation field years after the treatment in the absence of recurrent tumor or any other identifiable cause; (iii) a prolonged and reversible period of signs and symptoms related to the involved radiation field (visuospatial deficits, sensorimotor deficits, aphasia, etc.) with associated headaches (during or after

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgments

The authors thank doctor Guido Ahle and doctor Elsa Pons for their contribution in the follow-up and imaging analysis of patient 1.

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