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.

Prospective Hemorrhage Rates of Cerebral Cavernous Malformations in Children and Adolescents Based on MRI Appearance.

BACKGROUND AND PURPOSE: Current classifications of cerebral cavernous malformations focus solely on morphologic aspects. Our aim was to provide a morphologic classification that reflects hemorrhage rates. MATERIALS AND METHODS: We retrospectively categorized 355 cavernous malformations of 70 children and adolescents according to their morphologic appearance on MR imaging and calculated prospective hemorrhage rates on the basis of survival functions for 255 lesions in 25 patients with a radiologic observation period of >180 days. RESULTS: Overall, there were 199 MR imaging examinations with 1558 distinct cavernous malformation observations during a cumulative observation period of 1094.2 lesion-years. The mean hemorrhage rate of all 355 cavernous malformations was 4.5% per lesion-year. According to Kaplan-Meier survival models, Zabramski type I and II cavernous malformations had a significantly higher hemorrhage rate than type III and IV lesions. The presence of acute or subacute blood-degradation products was the strongest indicator for an increased hemorrhage risk (P = .036, Cox regression): The mean annual hemorrhage rate and mean hemorrhage-free interval for cavernous malformations with and without signs of acute or subacute blood degradation products were 23.4% and 22.6 months and 3.4% and 27.9 months, respectively. Dot-sized cavernous malformations, visible in T2* and not or barely visible in T1WI and T2WI sequences, had a mean annual hemorrhage rate of 1.3% and a mean hemorrhage-free interval of 37.8 months. CONCLUSIONS: It is possible to predict hemorrhage rates based on the Zabramski classification. Our findings imply a tripartite classification distinguishing lesions with and without acute or subacute blood degradation products and dot-sized cavernous malformations.

Genomic causes of multiple cerebral cavernous malformations in a Japanese population.

Cerebral cavernous malformation (CCM) is a hamartomatous vascular disease affecting the central nervous system. A fraction of CCM are thought to arise in association with genomic mutations in the cerebral cavernous malformation 1 (CCM1) (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) genes. In the present study, 18 Japanese patients with multiple CCM (10 with familial type and eight with sporadic type), underwent genomic analysis for CCM1, CCM2 and CCM3 mutations with blood samples and surgical specimens. MRI showed CCM in the cerebral hemisphere in 17 patients, the cerebellum in 10, the brainstem in 10 and the spinal cord in eight. CCM2 mutations were the most prominent, followed by CCM1 and CCM3. CCM1, CCM2 and CCM3 mutations were not identified in seven patients. Among the 10 patients with familial CCM, CCM1, CCM2 and CCM3 mutations were found in two, three and one patient, respectively, whereas four patients lacked these mutations. Among the eight patients with sporadic CCM, these mutations were found in one, three, and one patients, respectively, whereas three patients lacked these mutations. Most of the patients had a stable course during the follow-up period. Genomic mutations other than CCM1, CCM2 and CCM3 may be frequent in patients with multiple CCM in the Japanese population.

Malformación cavernomatosa: revisión de una patología clásica / Cavernomatous malformations: a classical disease review

Las malformaciones cavernomatosas (MC) son hamartomas vasculares de aspecto mamelonado, inicialmente descritos por Virchow, que son consideradas la malformación vascular más frecuente, después de las anomalías del desarrollo venoso, con una prevalencia de 0,5-0,7 porciento en la población general, sin predilección entre géneros. Se presentan con un amplio comportamiento dinámico en las imágenes dado su diverso grado de crecimiento, la posible regresión, la formación de novo y el riesgo de sangrado. En estas circunstancias, la resonancia magnética (RM), especialmente las potenciaciones en T2 gradiente (T2GRE) y susceptibilidad (SWI), cobran gran importancia en su búsqueda y seguimiento. Se revisa y actualiza su epidemiología y patología; además se presentan sus diversas ubicaciones y características, de tal forma que su diagnóstico no sea complejo.

Cavernomatous malformations (CM) are mamelonated vascular hamartomas, initially described by Virchow, which are considered the most common vascular malformation after developmental venous anomalies, with a prevalence of 0.5-0.7% in the overall population, without gender predilection. In imaging they show a broad range of dynamic behavior given their different levels of growth, possible regression, de novo formation and the risk of bleeding. In these circumstances, magnetic res onance imaging (MRI), especially T2 gradient echo sequence (T2GRE) and susceptibility weighted imaging (SWI), become very important for the detection and follow-up/monitoring of CM.This article reviews and updates the epidemiological and pathological features of CM; as well as presenting its various locations and characteristics, so that the diagnosis is not complicateD.

A proposed grading system of brain and spinal cavernomas.

BACKGROUND: Most cavernomas in the central nervous system are characterized by a benign natural course. Progressive symptoms warrant surgical removal. In the literature, the factors affecting long-term postoperative outcome are not statistically well confirmed. OBJECTIVE: To perform a multifactorial analysis of risk factors on a large patient series and to use the results to propose a simple grading scale to predict outcome. METHODS: We studied 303 consecutive patients with cavernomas treated surgically at our department from 1980 to 2009. Follow-up assessment was performed on average 5.7 years postoperatively (range, 0.2-36 years). The main outcome measure was the patients' condition at the last follow-up on Glasgow Outcome Scale. For statistical analysis, the outcome measure was dichotomized to favorable (Glasgow Outcome Scale 5) and unfavorable (Glasgow Outcome Scale 1-4). Binary logistic regression analysis was used to estimate the effect of age, sex, seizures, preexisting neurological deficits, hemorrhage, and size and location of cavernoma on long-term outcome. RESULTS: Infratentorial, basal ganglia, or spinal location and preexisting neurological deficit were the only independent risk factors for unfavorable outcome, with relative risks of 2.7 (P = .008) and 3.2 (P = .002), respectively. We formulated a grading system based on a score of 1 to 3. When applied to our series, the proposed grading system strongly correlated with outcome (P < .001, Pearson χ test). The risk for long-term unfavorable outcome was 13%, 22%, and 55% for grades 1 through 3, respectively. CONCLUSION: The proposed grading system showed a convincing correlation with postoperative outcome in surgically treated cavernoma patients.

Are cavernous sinus hemangiomas and cavernous malformations different entities?

Cavernous hemangiomas that occur within the cavernous sinus (CS) are different from cerebral cavernous malformations (CMs) clinically, on imaging studies, and in their response to treatment. Moreover, CMs are true vascular malformations, whereas hemangiomas are benign vascular tumors. Because of these differences, the authors suggest that these two entities be analyzed and grouped separately. Unfortunately, despite these differences, much confusion exists in the literature as to the nature, behavior, and classification of these two distinct lesions. This confusion is exacerbated by subtle histological differences and the inconsistent use of nomenclature. The authors use the term "cavernous malformation" to refer to intraaxial lesions only; they prefer to use the term "cavernous sinus hemangioma" to refer to extraaxial, intradural hemangiomas of the CS.