Cardiac magnetic resonance imaging features prognostic information in patients with suspected myocardial infarction with non-obstructed coronary arteries.

BACKGROUND: To assess the prognostic implications of cardiac magnetic resonance imaging (CMR) in patients with clinical suspicion of myocardial infarction with non-obstructed coronary arteries (MINOCA). METHODS: A total of 145 patients (58 ± 15 years, 97 men) were retrospectively enrolled in this single-center, longitudinal observational study. All patients underwent CMR including cine, edema-sensitive, and late gadolinium enhancement acquisitions, within a median of 3 days after cardiac catheterization. Follow-up was performed by medical records chart review and phone interviews; the median follow-up time was 4.2 years. The primary endpoint was defined as a combination of death, stroke, new onset of congestive heart failure, recurrent hospitalization, or the need for an invasive cardiac procedure. RESULTS: In 143 (98.6%) cases, CMR revealed the following cardiac pathologies: myocarditis (n = 48, 33.1%), structural cardiomyopathies (n = 40, 27.6%), "true" myocardial infarction (n = 22, 15.1%), hypertensive heart disease (n = 19, 13.1%), and Tako-Tsubo cardiomyopathy (n = 14, 9.7%). Only two patients (1.4%) had a normal CMR examination. There were significant prognostic differences between different etiologies, e.g. myocarditis and Tako-Tsubo cardiomyopathy had a more favorable prognosis then structural cardiomyopathies. Age, end-diastolic volume index and time-to-CMR showed significant association with the primary endpoint in multi-variate Cox regression. CONCLUSIONS: CMR performed early after the onset of clinical symptoms allows discrimination between acute myocardial injury from "true" MINOCA in patients presenting with chest pain and elevated cardiac biomarkers, thereby helping to identify the underlying pathology in suspected MINOCA and allowing risk stratification based on the established diagnosis. Furthermore, CMR parameters allow for improved prediction of adverse events compared to clinical and laboratory parameters.

Extensive calcification of the ligamentum flavum causing cervical myelopathy in a Caucasian woman.

Calcification of the ligamentum flavum (CLF) can cause myelopathy due to spinal cord compression. Only several cases in Caucasian patients have been described. Neurological deterioration can only be stopped by surgical decompression. We report a 63-year-old Caucasian woman presenting with progressive pins-and-needles sensations in both hands, worsened by painful paresthesia in both lower extremities. MRI showed a dorsal compressive mass extending from C2 to Th3 vertebrae with myelopathy at the level of C6. A laminectomy was performed, which improved clinical symptoms. Histological examination showed CLF. Early recognition of CLF and early spinal cord decompression are needed to improve neurological outcome.

Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma.

PURPOSE: Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. PATIENTS AND METHODS: We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. RESULTS: TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; ± SE) was 41% ± 9% and 81% ± 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P < .001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% ± 9% and 97% ± 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors. CONCLUSION: Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.

Molecular subtypes of glioma identified by genome-wide methylation profiling.

Recent studies have indicated a prognostic role for genome-wide methylation in gliomas: Tumors that show an overall increase in DNA methylation at CpG sites (CIMP+; CpG island methylator phenotype) have a more favorable prognosis than CIMP- gliomas. Here, we have determined whether methylation profiling can identify more and clinically relevant molecular subtypes of glioma by performing genome-wide methylation profiling on 138 glial brain tumors of all histological diagnosis. Hopach (Hierarchical ordered partitioning and collapsing hybrid) clustering using the 1,000 most variable CpGs identified three distinct glioma subtypes (C+(1p19q), C+(wt), and C-) and one adult brain subtype. All "C+(1p19q) " and "C+(wt)" tumors were CIMP+ whereas most (50/54) "C-" tumors were CIMP-. The C- subtype gliomas contained many glioblastomas and all pilocytic astrocytomas. 1p19q LOH was frequent in the C+(1p19q) subtype. Other genetic changes (IDH1 mutation and EGFR amplification) and gene-expression based molecular subtypes also segregated in distinct methylation subtypes, demonstrating that these subtypes are also genetically distinct. Each subtype was associated with its own prognosis: median survival for C-, C+(1p19q), and C+(wt) tumors was 1.18, 5.00, and 2.62 years, respectively. The prognostic value of these methylation subtypes was validated on an external dataset from the TCGA. Analysis of recurrences of 14 primary tumors samples indicates that shifts between some C+(wt) and C+(1p/19q) tumors can occur between the primary and recurrent tumor, but CIMP status remained stable. Our data demonstrate that methylation profiling identifies at least three prognostically relevant subtypes of glioma that can aid diagnosis and potentially guide treatment for patients.

Sonographic detection of the optic radiation.

OBJECTIVE: To describe a region of hyperechoic white matter adjacent to the atrium of the lateral ventricle of preterms, and to speculate on the relevance of detecting preterm white matter injury. PATIENTS AND METHODS: Cranial ultrasound images of 92 preterms of gestational age (GA) 32 wk or less were reviewed. For each infant, one first week standard coronal image was used for measurement of grey values around the para-atrial region of interest (PAROI) relative to the choroid plexus. For verification of the sonographic anatomy, MR images of an adult brain were used. For reference, neuro-anatomical images were compared in several atlases. In a group of nine preterms of similar GA with cystic periventricular leukomalacia (PVL) or MR-confirmed white matter disease, the disappearance of the PAROI was examined. RESULTS: The hyperechoic para-atrial area, subjectively detected in 84% of the patients, was situated bilaterally between the inner end of the lateral fissure and the upper third of the choroid plexus. In white matter caudal to the atrium, the hyperechoic band could be pursued towards the calcarine area. The average ratio of grey value around the PAROI to the choroid plexus was 0.787 (SD = 0.072, median 0.791). There was no correlation between PAROI grey value and gestational age. At 26 wk gestational age, the average ratio was 0.781 (n = 14), and 0.789 (n = 17) at 31 wk. Location of the PAROI agrees with the angle of the upper loop of the optic radiation. None of the nine infants with white matter damage had PAROIs clearly distinguishable from flaring. CONCLUSION: The symmetrical and unchanged acoustic character between 26 and 31 wk of gestational age argues in favour of the hypothesis that the PAROI is an anatomical structure. The localization of the hyperechoic band supports the hypothesis that it represents part of the optic radiation. Further study is needed to examine the absence of a hyperechoic para-atrial band as a prognostic marker of the extension and severity of white matter injury.

Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir.

Between November 1998 and December 2001, we treated 14 patients with advanced recurrent high-grade gliomas with a total dose of 4.6 x 10(8), 4.6 x 10(9), 4.6 x 10(10), or 4.6 x 10(11) viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All patients had recurrence or progression of the tumor 1-24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four patients survived longer than 1 year following gene therapy. One patient is still alive, with histologically confirmed progression of the tumor, 29 months after treatment. Ten patients died within 8 months of treatment, all from progression of the tumor. In 5 patients residual and measurable tumor was visible on the direct (<48 h) postoperative MRI. No objective radiological response was documented on subsequent MRI. None of the patients came to autopsy. In conclusion, the administration of 4.6 x 10(11) VP of IG.Ad.MLPI.TK by 50 injections into the wound bed following resection of recurrent malignant glioma, followed by GCV treatment, was well tolerated.