Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

A longitudinal MRI study of traumatic axonal injury in patients with moderate and severe traumatic brain injury.

OBJECTIVE: To study the evolution of traumatic axonal injury (TAI) detected by structural MRI in patients with moderate and severe traumatic brain injury (TBI) during the first year and relate findings to outcome. METHODS: 58 patients with TBI (Glasgow Coma Scale score 3-13) were examined with MRI at a median of 7 days, 3 months and 12 months post injury. TAI lesions were evaluated blinded and categorised into three stages based on location: hemispheres, corpus callosum and brainstem. Lesions in T2* weighted gradient echo (GRE), fluid attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) were counted and FLAIR lesion volumes were estimated. Inter-rater reliability score was calculated. Outcome was assessed 12 months post injury using the Glasgow Outcome Scale Extended. RESULTS: In the initial MRI, 31% had brainstem lesions compared with 17% at 3 months (p=0.008). In the FLAIR sequences, number and volumes of lesions were reduced from early to 3 months (p<0.001). In T2*GRE sequences, the number of lesions persisted at 3 months but was reduced at 12 months (p=0.007). The number of lesions in DWI and volume of FLAIR lesions on early MRI predicted worse clinical outcome in adjusted analyses (p<0.05). CONCLUSION: This is the first study to demonstrate and quantify attenuation of non-haemorrhagic TAI lesions on structural MRI during the first 3 months after TBI; most importantly, the disappearance of brainstem lesions. Haemorrhagic TAI lesions attenuate first after 3 months. Only early MRI findings predicted clinical outcome after adjustment for other prognostic factors. Hence valuable clinical information may be missed if MRI is performed too late after TBI.

Congenital tumors of the central nervous system.

Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into "definitely congenital" (present or producing symptoms at birth), "probably congenital" (present or producing symptoms within the first week of life), and "possibly congenital" (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease-free survival.

Prognostic value of pretreatment dynamic contrast-enhanced MR imaging in breast cancer patients receiving neoadjuvant chemotherapy: overall survival predicted from combined time course and volume analysis.

BACKGROUND: The prognostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in breast cancer has been explored, and the results are promising. PURPOSE: To investigate the possible correlation between pretreatment DCE-MRI and overall survival 5 years after diagnosis in breast cancer patients receiving neoadjuvant chemotherapy (NAC) using combined time course analysis and volume measurement from DCE-MRI data acquired with 1 min temporal resolution. MATERIAL AND METHODS: Pretreatment DCE-MR images of 32 female patients were examined. The total enhancing volume was calculated by including the voxels with >60% signal enhancing 1 min postcontrast. The signal intensity time course data were automatically classified on a voxel-by-voxel basis according to the enhancing characteristics: persistent (type I), plateau (type II) or washout (type III), and the resulting volumes of each enhancement type were calculated. RESULTS: A significant correlation between total enhancing volume and 5-year survival was found, P=0.05 (log-rank). The survival was 51 +/-15 months (mean +/-95% confidence intervals (CI)) and 73+/-12 months in patients with a total enhancing volume >41 cm(3) and < or =41 cm(3), respectively. A two-dimensional discriminator, taking both total enhancing volume and type III enhancing volume into account, improved the prediction of survival, resulting in a P value (log-rank) between survivors and non-survivors of <0.001. The survival was 44+/-16 months (mean +/-95% CI) and 74+/-11 months in patients with a total enhancing volume >58 cm(3) and/or a type III volume >8 cm(3), and < or =58 cm(3) and < or =8 cm(3), respectively. CONCLUSION: Pretreatment DCE-MRI might help in predicting prognosis in breast cancer patients receiving NAC.

Incidental Intracranial Findings and Their Clinical Impact; The HUNT MRI Study in a General Population of 1006 Participants between 50-66 Years.

OBJECTIVES: Evaluate types and prevalence of all, incidental, and clinically relevant incidental intracranial findings, i.e. those referred to primary physician or clinical specialist, in a cohort between 50 and 66 years from the Nord-Trøndelag Health (HUNT) study. Types of follow-up, outcome of repeated neuroimaging and neurosurgical treatment were assessed. MATERIAL AND METHODS: 1006 participants (530 women) underwent MRI of the head at 1.5T consisting of T1 weighted sagittal IR-FSPGR volume, axial T2 weighted, gradient echo T2* weighted and FLAIR sequences plus time of flight cerebral angiography covering the circle of Willis. The nature of a finding and if it was incidental were determined from previous radiological examinations, patient records, phone interview, and/or additional neuroimaging. Handling and outcome of the clinically relevant incidental findings were prospectively recorded. True and false positives were estimated from the repeated neuroimaging. RESULTS: Prevalence of any intracranial finding was 32.7%. Incidental intracranial findings were present in 27.1% and clinically relevant findings in 15.1% of the participants in the HUNT MRI cohort. 185 individuals (18.4%) were contacted by phone about their findings. 40 participants (6.2%) underwent ≥ 1 additional neuroimaging session to establish etiology. Most false positives were linked to an initial diagnosis of suspected glioma, and overall positive predictive value of initial MRI was 0.90 across different diagnoses. 90.8% of the clinically relevant incidental findings were developmental and acquired cerebrovascular pathologies, the remaining 9.2% were intracranial tumors, of which extra-axial tumors predominated. In total, 3.9% of the participants were referred to a clinical specialist, and 11.7% to their primary physician. 1.4% underwent neurosurgery/radiotherapy, and 1 (0.1%) experienced a procedure related postoperative deficit. CONCLUSIONS: In a general population between 50 and 66 years most intracranial findings on MRI were incidental, and >15% of the cohort was referred to clinical-follow up. Hence good routines for handling of findings need to be in place to ensure timely and appropriate handling.

Progressive multifocal leukoencephalopathy in an immunocompetent patient?

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive, potentially fatal, demyelinating disease affecting immunosuppressed patients. PML is rarely reported in cases with no underlying disease or immunosuppression-associated condition. CASE REPORT: We present a 72-year-old previously healthy woman who developed a progressive neurological condition affecting the entire nervous system which led to her death within 5 months. PML was diagnosed at autopsy. CONCLUSION: PML should be considered in patients with progressive neurological disorders involving the white matter, even in the absence of previous immunomodulatory treatment or immunosuppression.

Unruptured intracranial aneurysms in the Norwegian Nord-Trøndelag Health Study (HUNT): risk of rupture calculated from data in a population-based cohort study.

BACKGROUND: Rupture risk of unruptured intracranial aneurysms (UIAs) has been investigated in studies observing the natural history of this condition. Such studies have been prone to selection bias that may influence the results. OBJECTIVE: To calculate the overall rupture risk from data on the prevalence of UIA, which constitutes the population at risk, and the incidence of aneurysmal subarachnoid hemorrhage (aSAH) in the same population. METHODS: Data were collected from the Norwegian Nord-Trøndelag Health Study (HUNT), a large population-based cohort study. The prevalence of UIAs was estimated by performing magnetic resonance angiography in 1006 randomly selected volunteers 50 to 65 years of age from this population cohort. The incidence of aSAH was investigated by searching national and hospital registers with thorough case ascertainment to avoid inclusion of nonaneurysmal subarachnoid hemorrhage. RESULTS: The prevalence of UIAs was 1.9% and incidence of aSAH was 16.4 per 100,000 person-years. Based on these figures, the overall rupture risk in the 50- to 65-year age group in the HUNT population is 0.87% per year. CONCLUSION: This is the first study to estimate rupture risk of intracranial aneurysms from epidemiologic data in a large population-based cohort. This study design is less prone to selection bias and may provide an important supplement to the existing literature of studies of natural history of UIAs.

Leukoencephalopathy with brainstem and spinal cord involvement caused by a novel mutation in the DARS2 gene.

Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) is a rare, autosomal recessive disorder caused by mutations in the gene encoding a mitochondrial aspartyl-tRNA synthetase, DARS2. The disease is characterized by progressive spastic ataxia and magnetic resonance imaging (MRI) shows a highly characteristic leukoencephalopathy with multiple long tract involvement. We describe the clinical and radiological features of two new cases of LBSL and report a novel pathogenic mutation in the DARS2 gene. Both patients had typical clinical and radiological findings, although no elevated lactate was found. The severity of MRI changes did not correlate with clinical course and severity suggesting that, although of highly specific diagnostic value, MRI does not necessarily reflect clinical activity and should not be used to assess disease severity or prognosis in LBSL.

Predicting survival and early clinical response to primary chemotherapy for patients with locally advanced breast cancer using DCE-MRI.

PURPOSE: To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a tool for early prediction of response to neoadjuvant chemotherapy (NAC) and 5-year survival in patients with locally advanced breast cancer. MATERIALS AND METHODS: DCE-MRI was performed in patients scheduled for NAC (n = 24) before and after the first treatment cycle. Clinical response was evaluated after completed NAC. Relative signal intensity (RSI) and area under the curve (AUC) were calculated from the DCE-curves and compared to clinical treatment response. Kohonen and probabilistic neural network (KNN and PNN) analysis were used to predict 5-year survival. RESULTS: RSI and AUC were reduced after only one cycle of NAC in patients with clinical treatment response (P = 0.02 and P = 0.08). The mean and 10th percentile RSI values before NAC were significantly lower in patients surviving more than 5 years compared to nonsurvivors (P = 0.05 and 0.02). This relationship was confirmed using KNN, which demonstrated that patients who remained alive clustered in separate regions from those that died. Calibration of contrast enhancement curves by PNN for patient survival at 5 years yielded sensitivity and specificity for training and testing ranging from 80%-92%. CONCLUSION: DCE-MRI in locally advanced breast cancer has the potential to predict 5-year survival in a small patient cohort. In addition, changes in tumor vascularization after one cycle of NAC can be assessed.

Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial.

PURPOSE: To investigate use of the macromolecular contrast agent feruglose for differentiating and grading of human benign and malignant breast tumors on the basis of their microvascular characteristics. MATERIALS AND METHODS: Sixty-three women with 63 primary breast lesions were examined with dynamic T1-weighted gradient-echo magnetic resonance (MR) imaging after intravenous injection of feruglose. A two-compartment unidirectional kinetic model applied to the dynamic data yielded estimates of the endothelial transfer coefficient, KPS, and the fractional plasma volume of the tumors. These MR imaging-derived parameters were correlated with the histologic tumor grade and quantified according to the Scarff-Bloom-Richardson (SBR) score by means of Pearson product moment correlation analyses. Differences between malignant and nonmalignant breast lesions with respect to KPS for feruglose were evaluated by means of the chi2 test and by calculating the sensitivity, specificity, and positive and negative predictive values. RESULTS: Histologic analysis revealed 26 benign and 37 malignant tumors. A moderate yet statistically significant correlation between KPS and SBR score was found (R = 0.496, P <.001). No significant correlation was observed between fractional plasma volume and SBR score (R = 0.085, P =.507). The KPS values were zero for 19 (73%) of the 26 benign tumors and were greater than zero for 27 (73%) of the 37 carcinomas. This distribution was significantly different (chi2 = 13.035, P =.001). With the criterion KPS > 0 in carcinomas, sensitivity was 0.73, specificity was 0.73, and the positive predictive value was 0.79. CONCLUSION: Quantitative measures of tumor microvascular permeability can be used for breast tumor characterization. The probability of breast tumor microvascular hyperpermeability to be associated with malignancy is 79%.