Long-term functional outcomes and complications of microsurgical resection of brainstem cavernous malformations: a systematic review and meta-analysis.

Brainstem cavernous malformations (CMs) encompass up to 20% of all intracranial CMs and are considered more aggressive than cerebral CMs because of their high annual bleeding rates. Microsurgical resection remains the primary treatment modality for CMs, but long-term functional outcomes and complications are heterogenous in the literature. The authors performed a systematic review on brainstem CMs in 4 databases: PubMed, EMBASE, Cochrane library, and Google Scholar. We included studies that reported on the long-term functional outcomes and complications of brainstem CMs microsurgical resection. A meta-analysis was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search yielded 4781 results, of which 19 studies met our inclusion criteria. Microsurgery was performed on 940 patients (mean age 35 years, 46.9% females). Most of the brainstem CMs were located in the pons (n = 475). The pooled proportions of improved, stable, and worsened functional outcomes after microsurgical resection of brainstem CMs were 56.7% (95% CI 48.4-64.6), 28.6% (95% CI 22.4-35.7), and 12.6% (95% CI 9.6-16.2), respectively. CMs located in the medulla were significantly (p = 0.003) associated with a higher proportion of improved outcome compared with those in the pons and midbrain. Complete resection was achieved in 93.3% (95% CI 89.8-95.7). The immediate postoperative complication rate was 37.2% (95% CI 29.3-45.9), with new-onset cranial nerve deficit being the most common complication. The permanent morbidity rate was 17.3% (95% CI 10.5-27.1), with a low mortality rate of 1% from the compiled study population during a mean follow-up of 58 months. Our analysis indicates that microsurgical resection of brainstem CMs can result in favorable long-term functional outcomes with transient complications in the majority of patients. Complete microsurgical resection of the CM is associated with a lower incidence of CM hemorrhage and the morbidity related to it.

Brain Tumors Affecting the Orbit Globe and Orbit Tumors Affecting the Brain.

Brain tumors affecting the orbit and orbital tumors affecting the brain are a heterogeneous group of lesions, with histological features, behaviors, diagnostic criteria, and treatments varying from each other. Dermoid cyst and cavernous hemangiomas are considered the most frequent benign lesions, while non-Hodgkin lymphoma is the most common malignant tumor in this region. Sharing the same anatomical region, clinical manifestations of orbital lesions may be often common to different types of lesions. Imaging studies are useful in the differential diagnosis of orbital lesions and the planning of their management. Lesions can be classified into ocular or extra-ocular ones: the latter can be further differentiated into extraconal or intraconal, based on the relationship with the extraocular muscles. Surgical therapy is the treatment of choice for most orbital lesions; however, based on the degree of removal, their histology and extension, other treatments, such as chemotherapy and radiotherapy, are indicated for the management of orbital lesions. In selected cases, chemotherapy and radiotherapy are the primary treatments. This chapter aimed to discuss the orbital anatomy, the clinical manifestations, the clinical testing and the imaging studies for orbital lesions, and the principal pathological entities affecting the orbit together with the principles of orbital surgery.

Maternal and fetal outcomes in women with cerebrovascular malformations in pregnancy: A multicentre retrospective cohort study.

OBJECTIVE: To determine maternal, obstetric and neonatal outcomes in a cohort of women with cerebrovascular malformations (CVMs) that include arterial venous malformations (AVMs) and cavernomas. DESIGN: Retrospective cohort study. SETTING: Six specialist centres managing pregnant women with neurological disorders. POPULATION: Sixty-three women with CVMs in 83 pregnancies of ≥20 completed weeks' gestation. METHODS: Retrospective case notes review. MAIN OUTCOME MEASURES: Neurological outcomes including rates of acute cerebral bleeding in pregnancy and reported seizures during pregnancy. Maternal outcomes included number of women with a livebirth and the proportion of women being delivered by caesarean section. RESULTS: Most women had a good pregnancy outcome with high rates of vaginal delivery (73%) at term. There were no maternal deaths. Six women had an acute cerebral bleed, all of whom were delivered by planned caesarean section. In total, ten women had seizures in pregnancy (of whom four also had a bleed). Six (7%) babies were admitted to a neonatal unit. There was no significant difference in outcomes between women with AVMs and those with cavernomas. CONCLUSION: In the majority of cases, pregnancy outcomes were favourable, with most women having a vaginal delivery. All cases of cerebral bleeds that occurred were at a remove from the peripartum period. TWEETABLE ABSTRACT: Women with cerebrovascular malformations have high rates of vaginal delivery.

Endoscopic Endonasal Treatment of Intra-Axial Ventral Brainstem Cavernomas: Case Experience and Literature Review.

INTRODUCTION: Cavernous malformations of the ventral brainstem are a challenging disease to treat. From an anatomical perspective, the best surgical options are endoscopic endonasal approaches. The first reports of their usage for this purpose date back to 2012. In this study, we gathered data on the subject, share our experience, and outline technical notes and tips for this surgery. CASE PRESENTATION: We report a 14-year-old female with a ventral pons cavernoma, treated using an endoscopic endonasal transclival approach and followed-up for 5.9 years. This is the longest reported follow-up for this condition to date. Written informed consent was obtained from the patient for publication of this case report and the accompanying images. DISCUSSION: An endoscopic endonasal transclival approach was used. The skull base was reconstructed using the multilayer grafting technique and a nasoseptal flap. There was no postoperative cerebrospinal fluid leakage. In a literature review, we identified 8 patients who were treated endoscopically: 1 transplanum-transtuberculum, 1 transtuberculum-transclival, and 6 transclival approaches were employed. Skull base closure was achieved using multilayer grafting and a nasoseptal flap in 4 cases, a gasket seal technique combined with nasoseptal flap in 3 cases and a periumbilical fat graft, fibrin sealant patch, and fibrin glue in 1 case. There were 2 cases of leakage, which resolved completely with revision surgery. CONCLUSION: Endoscopic surgery is a reliable alternative to traditional open surgery. It may be the preferred choice for intra-axial ventral brain cavernomas.

Isolated Compressive Sixth Nerve Palsy due to Multiple Intracranial Cavernomas.

Cavernomas or cavernous malformations are the most common clinically significant vascular anomalies, accounting for 8-15% of all brain and spinal vascular malformations. While there are several articles in the literature on cavernomas, most cases report haemorrhage from these lesions as the cause of cranial nerve palsies. We report a rare case of multiple intracranial cavernomas in the brain and pons causing an isolated compressive sixth nerve palsy.

A case of multiple cerebral cavernomas associated with en coup de sabre scleroderma.

Linear scleroderma is a form of localized scleroderma that presents as band-like sclerotic lesions. When it occurs on the scalp or forehead, it is called "en coup de sabre scleroderma" (ECDS). Extracutaneous associations, mostly neurologic, have been described with ECDS. We report a patient with ECDS associated with multiple cerebral cavernomas. This serves to highlight the importance of neuroimaging and multidisciplinary team involvement in patients with ECDS.

[Navigation in vascular neurosurgery]. / Primenenie navigatsii v sosudistoi neirokhirurgii.

Literature review is devoted to the role of frameless neuronavigation in surgery of distal aneurysms, cavernomas, arteriovenous malformations, Kimmerle's anomaly and revascularization surgeries. Visualization methods used in preoperative preparation of patients with vascular lesions compatible with frameless neuronavigation and the methods of intraoperative visualization as an addition to navigation are described.

Could propranolol be beneficial in adult cerebral cavernous malformations?

Surgery is the only therapeutic option for cerebral cavernous malformations (CCM) and is proposed, whenever possible, after haemorrhagic events, neurological symptoms, or epilepsy, radiosurgery being a controversial alternative in some cases. However, there is no treatment for non-accessible lesions, such as brainstem CCM, multiple CCM, or those located in functional areas. Propranolol, a non-selective beta-blocker used as first-line treatment for infantile haemangiomas, has proved spectacularly effective in a few cases of adult patients with CCM. We herein review the histological, in vitro data and clinical findings that support the idea of propranolol as a potential treatment for CCM. Since one retrospective study has not been conclusive, we support the idea that prospective trials are necessary.

A retrospective and consecutive analysis of the epidemiology and management of spinal cavernomas over the last 20 years in a single center.

Spinal cavernous malformations (SCM) are rare lesions often presenting with acute onset of symptoms and progressive neurological deterioration due to hemorrhage into the spinal cord. With the aid of modern techniques, their surgical removal became much safer. The present study was undertaken to analyze the outcome of our series of surgically and conservatively treated patients with SCM. Over a period of 20 years, 20 surgically treated and 5 conservatively managed patients with spinal cavernous malformations were identified and enrolled into this analysis. Demographic data, clinical symptoms, localization and extension of the cavernoma, as well as pre- and postoperative neurological status were obtained. The clinical status was assessed using the Frankel score. Patients were followed up clinically and by MRI. Before surgery, 90% (18/20) of our surgical patients were classified as Frankel D (93.8%), whereas two patients (10%) were graded C. None of the patients had a worse Frankel score at the time of discharge. Eighty percent of them (16 cases) remained unchanged, and 20% (4 patients) improved during the first follow-up (mean 6.3 months, range 2-17 months). All improved patients had a superficially located SCM and were operated early (≤3 months). No worsening was observed during extended follow-up (range 9-134 months, mean 44.7 months). Five nonsurgically treated patients showed no significant clinical deterioration over a period of 6.7 years (mean, range 2.9-8 years). SCM localization and number of involved segments had no influence on outcome. Our data show that SCM can be resected with favorable neurological outcome by using intraoperative neuromonitoring. Within the follow-up period, patients treated conservatively remained in a stable neurological condition.

Utility of electrocorticography in the surgical treatment of cavernomas presenting with pharmacoresistant epilepsy.

AIM: To describe the general aspects of cavernomas and epilepsy and review the available literature on the utility of electrocorticography (ECoG) in cerebral cavernoma surgery. METHODS: We searched studies in PubMed, MedLine, Scopus, Web of Science, and Google Scholar (from January 1969 to December 2013) using the keywords "electrocorticography" or "ECoG" or "prognosis" or "outcome" and "cavernomas". Original articles that reported utility of ECoG in epilepsy surgery were included. Four review authors independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, and Jadad Scale. A meta-analysis was not possible due to methodological, clinical, and statistical heterogeneity of included studies. We analysed six articles with a total of 219 patients. RESULTS: The most common surgical approach was lesionectomy using ECoG in the temporal lobe with Engel I outcome range from 72.7 to 100%. CONCLUSIONS: Small controlled studies suggest that ECoG-guided resection offers the best functional results in seizure control for subjects undergoing cavernoma surgery, especially in the temporal lobe.

Cystic Cerebral Cavernous Malformations: Report of Five Cases and a Review of Literature.

Introduction Cerebral cavernous malformations (CCMs) account for about 5 to 13% of intracranial vascular malformations. Cystic cerebral cavernous malformations (cCCMs) are a rare morphological variant and can cause diagnostic and therapeutic dilemmas. We describe our five such cases and review the existing literature on this entity. Methods A search of the PubMed database for cCCMs was done, and all articles in English emphasizing the reporting of cCCMs were selected. A total of 42 publications describing 52 cases of cCCMs were selected for analysis. Epidemiological data, clinical presentation, imaging features, the extent of resection, and outcome were analyzed. Radiation-induced cCCMs were excluded. We have also described five of our cases of cCCMs and reported our experience. Results The median age at presentation was 29.5 years. Twenty-nine patients had supratentorial lesions, 21 had infratentorial lesions, and 2 had lesions in both compartments. Among our four patients, three had infratentorial lesions, whereas one had a supratentorial lesion. Multiple lesions were seen in four patients. A majority (39) had symptoms of mass effect (75%), and 34 (65.38%) had raised intracranial pressure (ICP), whereas only 11 (21.15%) had seizures. Among our four operated patients, all of them had symptoms of mass effect, and two of them also had features of raised ICP. The extent of resection was gross total in 36 (69.23%), subtotal in 2 (3.85%), and not reported in 14 (26.93%). All four of our operated patients underwent gross total resection, but two of them underwent a second surgery. Of the 48 patients in whom the surgical outcome was reported, 38 improved (73.08%). One showed a transient worsening followed by improvement, one developed a worsening of the pre-existing focal neurological deficit (FND), two developed a new FND, and 5 had no improvement in their FNDs. Death occurred in one patient. All four of our operated patients improved after surgery, although three of them showed a transient worsening of FNDs. One patient is under observation. Conclusion cCCMs are rare morphological variants and can cause considerable diagnostic and therapeutic dilemmas. They should be considered in the differential diagnosis of any atypical cystic intracranial mass lesion. Complete excision is curative, and the outcome is generally favorable; although transient deficits may be seen.

Tailored Treatment Options for Cerebral Cavernous Malformations.

The diagnosis and treatment of cerebral cavernous malformations (CCMs), or cavernomas, continues to evolve as more data and treatment modalities become available. Intervention is necessary when a lesion causes symptomatic neurologic deficits, seizures, or has high risk of continued hemorrhage. Future medical treatment directions may specifically target the pathogenesis of these lesions. This review highlights the importance of individualized treatment plans based on specific CCM characteristics.

Vascular Lesions of the Pineal Region: A Comprehensive Review of the Therapeutic Options.

OBJECTIVE: Vascular lesions of the pineal region comprise aneurysms of the pineal region, arteriovenous malformations, cavernous malformations, and vein of Galen malformations. In the present report, we have offered an extensive review of each vascular pineal region lesion. METHODS: We performed an extensive literature review, focusing on the current therapeutic options available for the different vascular lesions of the pineal region. RESULTS: Vascular lesions of the pineal region are rare. Microneurosurgery remains a valid treatment of cavernomas, arteriovenous malformations, and aneurysms. Endovascular treatments seem to be the first option for the vein of Galen malformations, followed by microneurosurgery. Radiosurgery seems beneficial for small-size arteriovenous malformations. Complex and large vascular lesions will require a combination of multiple treatments. CONCLUSIONS: Vascular lesions of the pineal region are complex, uncommon diseases. Thus, definitive therapeutic modalities for these lesions require further research.

Management of Central Nervous System Cavernomas: An Experience of the Department of Neurosurgery at the Ibn Tofail Hospital, Mohammed VI University Hospital.

INTRODUCTION: Central nervous system cavernomas are congenital vascular anomalies posing a challenge not only in their diagnosis but also in their therapeutic management. The latter depends largely on their natural evolution and specifically their hemorrhagic potential. MATERIAL AND METHODS: This paper reports the experience of the Department of Neurosurgery at the Ibn Tofail Hospital, Mohammed VI University Hospital at Marrakech in the management of central nervous system cavernomas from January 2011 to December 2018. We collected and analyzed epidemiological, clinical, radiological, therapeutic, and evolution data from 16 cases of central nervous cavernomas using a pre-established sheet.  Results: Sixteen cases of cavernomas were treated in a period of eight years; 14 patients had cerebral cavernomas and two had brainstem cavernomas. The sex ratio was 1.66 with a male predominance, and the mean age of our patients was 42 years. The clinical presentation was dominated by epileptic seizures. Cerebral MRI was performed on all our patients. In all 16 cases, the cavernomas were solitary with the majority being supra-tentorial (13 cases) and bleeding was apparent on imaging in one case. Microsurgery was performed in 13 cases, while three patients benefited from stereotactic radiosurgery. Complete resection was obtained in all patients and pathology examination showed a radio-histological correlation in 87.5% of cases. The overall evolution in operated patients was favorably marked by neurological improvement in 87.5% of cases, deterioration in 6.2% of cases, and no clinical improvement in 6.2% of the cases. CONCLUSION: Early diagnosis coupled with macroscopically complete resection and long-term follow-up with MRI are all crucial steps to ensure the proper management of central nervous cavernomas, especially considering their risk of recurrence.

Surgical management of simultaneous supra- and infratentorial hemorrhages in a pediatric patient with multiple cavernomas.

Multiple intracranial cavernomas are rare and occur mostly in familial cases. Clinical presentation with simultaneous rupture of two or more lesions has only been reported in four cases to date. A 15-year-old boy presented with simultaneous right frontal and superior vermian hematomas with hydrocephalus. The patient underwent a ventriculoperitoneal shunt, and his magnetic resonance imaging (MRI) revealed multiple cavernomas with bleed in the above-mentioned locations. The patient underwent a midline suboccipital craniotomy and excision of the cavernoma. The supratentorial lesions were left in situ in lieu of small size, no history of seizures, mass effect, or other neurological deficits. The patient recovered well from surgery with significant improvement in truncal ataxia. He remained asymptomatic for supratentorial lesions at follow-up. Cavernomas should be considered as differential diagnoses in cases of multiple intraparenchymal hemorrhages, especially in pediatric patients. The surgical management should be rationalized based on the lesion location, the eloquence of the surrounding parenchyma, mass effect, and the risks of re-rupture. Due to the rarity of multiple simultaneous hemorrhages, the management of multiple cavernomas remains controversial. The patient's relatives can be screened with MRI to rule out the familial form of the disease. Strict clinical and radiological follow-up is a must in such patients.

Cervical spine arachnoid cyst complicated by spontaneous intracystic hemorrhage: Case report and review of the literature.

Background: Spinal intradural extramedullary arachnoid cysts represent about 1-3% of all primary spinal space-occupying lesions often causing spinal cord and/or radicular nerve compression. Spontaneous intralesional hemorrhages are extremely rare and are typically found within intracranial arachnoid cysts. Here, a 55-year-old female presented with a spontaneous hemorrhage into a cervical spine arachnoid cyst warranting surgical intervention (i.e., fenestration/excision/occlusion). Case Description: A 55-year-old female presented with 3 weeks of dull pain in the cervicothoracic region. She subsequently developed paresthesias and progressive lower extremity weakness with (urinary incontinence. The cervical magnetic resonance revealed a right anterolateral intradural extramedullary "cystic" lesion extending from C7 to T2; it contained a heterogeneous signalon T2W sequences, and a fluid-fluid level was documented on the T2-GRE and FLAIR sequences. At surgery, consisting of a laminectomy, two hemorrhagic cystic lesions were identified and removed. Histological findings were consistent with hemorrhagic into an arachnoid cyst. Conclusion: Only rarely hemorrhages develop in intraspinal intradural extramedullary spinal arachnoid cysts.

Cerebral developmental venous anomalies in children with mismatch repair deficiency.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is one of the rare cancer predisposition syndromes. The aim of this study was to evaluate the cerebral developmental venous anomalies in children with central nervous system tumors associated with CMMRD, an area in which there is extremely little experience. METHODS: Data from children diagnosed with medulloblastoma and high grade central nervous sytem tumor were retrospectively collected. According to the European CMMRD criteria, nine patients were diagnosed as CMMRD syndrome and the others consisted of the group without CMMRD. All radiological examinations of these children were retrospectively reviewed. Whole exome sequencing was performed to index cases` germline DNA. RESULTS: Nine children from four families, six females and three males, were studied. The median age at the first tumor diagnosis was 4.5 years (range, 9 months to 14 years). All CMMRD patients had café au lait spots, but none fulfilled the diagnostic criteria for neurofibromatosis. The patients developed high-grade glial tumor (n: 7) and medulloblastoma (n: 2). The affected genes in the three families were MSH6 [c.478C > T (p.Gln160Ter)], MSH6 [c.2871dupC (p.Phe958LeufsTer5)] and MLH1 [c.236G > A(p.Arg79Lys)], respectively. Seven patients had multiple developmental venous anomalies; six patients had leptomeningeal enhancement; and five patients had cavernomas. None of these findings were present in the group without CMMRD. CONCLUSIONS: Constitutional mismatch repair deficiency should be considered when multiple developmental venous anomalies, cavernomas, and leptomeningeal enhancement are detected, especially in patients with café au lait spots.

Laser Interstitial Thermal Therapy for Cerebral Cavernous Malformations: A Systematic Review of Indications, Safety, and Outcomes.

BACKGROUND: Cerebral cavernous malformations (CCM) in deep eloquent areas present a surgical challenge. Laser interstitial thermal therapy (LITT) may present itself as a safe minimally invasive treatment option. OBJECTIVE: To systematically review the indications, safety, and outcomes of LITT for CCM. METHODS: Electronic databases were searched from inception to October 7, 2021 for articles with CCM and LITT keywords. Studies describing CCMs treated with LITT were included. RESULTS: A total of 32 patients with CCMs in lobar (79%), basal ganglia (12%), and brainstem (9%) locations were treated with LITT. Indications for LITT included drug-resistant seizures (75%), unacceptable surgical risk (22%), recurrent hemorrhage (16%), and early intervention to discontinue antiepileptic drugs (3%). No death or CCM-associated intracranial hemorrhage occurred intraoperatively or postoperatively, and most patients experienced no adverse effects or transient effects that resolved at follow-up (84%). Of those treated for CCM-associated epilepsy, 83% experienced Engel class I seizure freedom and most were class IA (61%). Most patients experienced symptomatic improvement (93%), and a decrease in antiepileptic drugs was reported in more than half of patients (56%), with 28% able to discontinue all antiepilepsy medications after LITT. CONCLUSIONS: LITT seems to be a safe treatment for CCMs located in deep eloquent areas and in lesions presenting with medically refractory seizures or recurrent hemorrhages. Randomized studies are needed to further elucidate its efficacy in treating CCM.

Outcome in Patients with Spinal Cavernomas Presenting with Symptoms Due to Mass Effect and/or Hemorrhage: Conservative versus Surgical Management: Meta-analysis of Direct Comparison of Approach-Related Complications.

OBJECTIVE: We sought to examine the conservative treatment of symptomatic spinal cavernomas and evaluate the efficacy and safety of surgical management of spinal cord cavernous malformations. METHODS: This meta-analysis included articles comparing outcomes of conservative treatment and surgical management of spinal cavernomas, published in the full-text form (from 2000 to June 31, 2020). Collected variables included first author name, country, covered study period, publication year, the total number of patients and at follow-up, bleeding, motor weakness, pain, bladder and/or bowel dysfunction neurologic improvement or deterioration after discharge, and the need for reintervention after subtotal surgical resection or hemorrhage. RESULTS: After the initial searching and applying all exclusion and inclusion criteria, there were 9 articles left in the final article pool. The total number of patients was 396 with 264 (66.6%) undergoing surgical resection and 132 (33.4%) electing conservative management. Regarding motor weakness, bladder/bowel dysfunction, deterioration, and reintervention, the final results demonstrated no potential significant difference between the 2 groups. In regard to the subgroup of patients with bleeding, improvement, and pain, the results of the analysis showed a statistically significant difference between the 2 groups. CONCLUSIONS: Patients who have experienced a hemorrhagic episode should consider surgical intervention, which decreases the risk of recurrent hemorrhage and further neurologic deterioration. In addition, surgical decompression obtained by resection of the hemorrhage and cavernoma seems to lead to slight neurologic improvement in some patients. In nonhemorrhagic cavernomas, conservative treatment might be optimal due to surgery-related morbidity risks.

Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.