SMART syndrome, an acronym for stroke-like migraine attacks after radiation therapy syndrome, is an uncommon delayed complication of cerebral radiation therapy. It is probably a more severe manifestation of peri-ictal pseudoprogression (PIPG).
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Epidemiology
SMART syndrome is encountered in individuals who have received therapeutic cerebral irradiation (>50 Gy), typically years later (6-30 years) 1,2,6. In most instances, patients have a history of seizures 6.
Diagnosis
The diagnosis of SMART syndrome is essentially one of exclusion and can only be entertained in the correct clinical setting. Various criteria have been proposed 2,8 although these are evolving. They can be generally summarized as follows:
patient: history of cranial irradiation (typically years ago) with no residual/recurrent tumor
clinical: prolonged (usually reversible) symptoms referable to a unilateral cortical area that has been irradiated
imaging: prominent gyral enhancement (usually transient) within an area of previously irradiated brain
Clinical presentation
Patients usually present with seizures and subacute stroke-like episodes with symptoms such as hemiplegia, aphasia, and hemianopia 6. These episodes have been associated with headaches and are often preceded by a migraine-like aura 1,2.
Pathology
The precise mechanism that underlies SMART syndrome is uncertain and biopsies obtained from some patients do not reveal specific abnormalities above and beyond those expected in previously irradiated brain 6.
It is hypothesized that SMART syndrome represents an exacerbation of normal postictal phenomena due to prior radiotherapy 6.
Radiographic features
MRI is the modality of choice to investigate SMART syndrome. Importantly, imaging abnormalities do not precede or coincide with symptom onset; rather, it takes 2-7 days for imaging abnormalities to develop 6. As such, if imaging is performed early, a repeat scan is advisable a week later to have a better chance of identifying abnormalities.
CT
On initial imaging, a region of relatively minor low density with mass effect can be seen. Features of laminar necrosis in the involved territory, such as cortical calcifications, can be seen following the initial episode.
MRI
The hallmark of SMART syndrome is prominent gyral enhancement with mild mass effect cortical thickening (hyperintense in T2 and FLAIR) with or without diffusion restriction. It is usually unilateral and confined to the areas of the brain that underwent irradiation.
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T1:
initially low signal
hyperintense signal within the cortex can be seen if associated with cortical reparative changes on follow-up imaging
T2/FLAIR: hyperintense signal, often with cortical thickening
DWI/ADC: diffusion restriction is minor and variable, dominated by T2 shine through effects 6
SWI: foci of susceptibility artifacts may be seen, thought to be related to cavernous malformations induced by remote radiotherapy rather than SMART syndrome directly
T1C+ (Gd): prominent gyral enhancement (cortical and leptomeningeal)
Treatment and prognosis
SMART syndrome was initially thought to be self-limiting with gradual and complete resolution over the course of several weeks; typically occurring within 2-5 weeks but can take up to 3 months 4,6.
However, incomplete clinical recovery is not uncommon (up to ~45% of subjects in one series 6). In a smaller proportion of patients (~27%) permanent imaging sequelae are also encountered consistent with irreversible cortical injury and paramagnetic substrate, visible within a few weeks of presentation 6.
Differential diagnosis
non-convulsive status epilepticus and repeated focal seizures: may demonstrate similar imaging and clinical features
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similar to non-convulsive status epilepticus and repeated focal seizures, but occurring in patients with brain tumors 6,7
lacks headache as a prominent clinical feature 6
less cortical enhancement and more leptomeningeal enhancement 6
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