Evolution of cerebral microbleeds after cranial irradiation in medulloblastoma patients

Abstract

Objective: To characterize the temporal and spatial pattern of cerebral microbleeds (CMBs) after cranial irradiation in patients with medulloblastoma. Methods:We retrospectively identified patients with medulloblastoma treated with craniospinal irradiation at the Massachusetts General Hospital between 1999 and 2015. Longitudinal MRI including T2*-weighted gradient-recalled echo (GRE) sequences were reviewed, and the prevalence, spatial pattern, and risk factors associated with CMBs were characterized.Results: We identified a total of 27 patients; 5 patients were children (median age 6.3 years) and 22 patients were adults (median age 28.8 years). CMBs were found in 67% (18/27) of patients, who were followed for a median of 4.1 years. Patients with CMBs had longer GRE follow-up time compared to those without CMBs (4.9 vs 1.7 years, p 5 0.035). The median latency of the appearance of CMBs was 2.79 years (interquartile range 1.76-4.26). The prevalence of CMBs increased with each year from time of radiation therapy, and the cumulative prevalence was highest in patients age ,20 years (100% cumulative prevalence, vs 59% in adult patients treated at age $20 years). CMBs were mostly found in lobar distribution and predominately in bilateral occipital lobes. Patients using antithrombotic medications developed CMBs at a significantly higher rate (p 5 0.041).Conclusions: Our data demonstrate a high prevalence of CMBs following cranial irradiation, progressively increasing with each year from time of radiation therapy. Medulloblastoma is one of the most common malignant brain tumors in children, accounting for approximately 20% of all pediatric brain tumors, and the incidence rate in children is 10-fold higher than in adults.1 Standard treatment for medulloblastoma includes maximal safe surgical resection, followed by craniospinal irradiation (CSI) with a focal boost to the tumor bed or posterior fossa. Adjuvant chemotherapy is commonly offered to patients with high-risk features.2,3 Current overall survival rates at 5 years range from 50% to 80%.2-5 Neurotoxicity from cancer therapy remains an important issue in patient management and is in particular a concern in long-term survivors.Cerebral microbleeds (CMBs) are a type of radiation-induced vascular complication thought to represent microvascular injury.6-8 Radiologically, CMBs are characterized by small foci of signal hypointensity visualized on T2*-weighted gradient-recalled echo (GRE) sequences on MRI. 9,10 Previous pathologic studies have demonstrated that CMBs were iron-positive blood breakdown products from prior hemorrhage, most commonly in form of hemosiderin-laden macrophages, or evidence of vasculopathies, such as fibrinoid necrosis, microaneurysm, dissection in the wall of a distended vessel, or cavernoma.

Risk factors of radiotherapy‐induced cerebral microbleeds and serial analysis of their size compared with white matter changes: A 7T MRI study in 113 adult patients with brain tumors

“…In regard to tumor location, occipital, cerebellum, and brainstem tumors combined were associated with the highest rate of CMB development, while frontal lobe tumors were associated with increased rates of development compared with temporal and parietal lobe tumors. This finding suggests that the posterior brain and frontal lobe are the most radiosensitive brain regions in adults, agreeing well with previous findings in pediatric populations …”

“…19 Roongpiboonsopit et al investigated the prevalence of CMBs in younger adults (median age 28.8 years) treated with whole-brain RT for a medulloblastoma; they identified CMBs in 67% (n = 18) of patients followed for a median of 4.1 years. 20 In our recent experience, in an ongoing study using the same methods as in the present study to assess CMB prevalence in adult survivors of pediatric medulloblastomas, we have so far observed a 100% cumulative incidence rate for CMB formation at follow-up times ranging between 1.1 and 15.5 years (median, 6.2 years). This supports early and accurate detection of RTinduced CMBs using advanced imaging and postprocessing methods.…”

Recurrent Thromboembolic Events after Ischemic Stroke in Patients with Primary Brain Tumors

“…In keeping with prior studies,(8) stroke from radiation vasculopathy was defined as stroke ipsilateral to the patient’s site of prior brain radiation, with no other identified mechanism of stroke. Imaging evidence of intracranial stenosis was not required for the diagnosis of radiation vasculopathy because radiation can cause small vessel vasculopathy,(21, 22) and lacunar-appearing strokes have been reported in patients after radiation. (23) Each patient’s stroke mechanism was independently adjudicated by two neurologists (NSP and JEB) with a board-certified stroke neurologist (BBN) serving as the final arbitrator.…”

Susceptibility‐weighted imaging in malignant melanoma brain metastasis

“…Indeed, we found a significantly higher incidence of isolated SWI blooming artifacts in metastatic melanoma patients compared with a screening cohort without BM. Additional analysis of the subgroups stratified by therapy showed that this increase could be explained by prior radiotherapy, which is a well‐known risk factor for the development of intracerebral microbleedings or cavernomas . In the case of MM, it is highly likely that these SWI lesions represent microbleedings but the possibility that such findings might be micrometastases unmasked by irradiation cannot be completely ruled out.…”