Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known

Hypertensive posterior reversible encephalopathy syndrome causing posterior fossa edema and hydrocephalus.

Posterior reversible encephalopathy syndrome (PRES) is a well characterized entity resulting from the inability of cerebral autoregulation to adequately protect the brain from uncontrolled hypertension. It primarily affects the occipital lobes, but can also involve the structures in the posterior fossa including the brainstem and cerebellum. Treatment usually consists of strict blood pressure control, but more aggressive management may be indicated with acutely worsening neurological status. We present a patient with hypertensive encephalopathy that resulted in hydrocephalus and brainstem compression necessitating surgical decompression requiring ventriculostomy and suboccipital craniectomy. In rare cases, PRES can present with severe brainstem compression requiring emergent posterior fossa decompression. When brainstem signs are present on exam, emergent posterior fossa decompression may be safer than ventriculostomy alone

Risk Factors and Outcomes in Thoracic Stenosis with Myelopathy. A Single Center Experience.

OBJECTIVE: Identify risk factors predisposing to thoracic spinal stenosis and myelopathy (TS) and address treatment options and outcomes. METHODS: A retrospective review of our center\u27s experience with TS over 10 years. Clinical and magnetic resonance imaging (MRI) data, surgical intervention and outcomes using Frankel and Japanese Orthopedic Association (JOA) scales were collected. RESULTS: A total of 44 patients with TS were identified. There were 30 men and 14 women with a mean age±SD of 66±15years. Neurological performance was evaluated using the Frankel scale (A-E or 1-5), and JOA scale for myelopathy (0-11). Frankel scores (1-5) and JOA scores (0-11) on admission were 3.5±0.9 and 6.8±2.6 respectively. At follow-up, Frankel scores had improved to 4.1±0.8 (p=0.041) and JOA scores had improved to 8.3±2.4 (p=0.021). The presence on admission of increased signal from the cord on T2-weighted MRI was associated with lower Frankel and JOA scores (3.3±0.9, and 6.2±2.5 respectively) than in those with absent increased signal (4.0±0.4 and 8.6±2.1, p=0.02 and p=0.008 respectively). There were 4 complications, requiring exploration and debridement for dehiscence in 3 and an epidural hematoma in the fourth that necessitated evacuation, with a good outcome. A fifth patient underwent reoperation at the same level 18 months later for persistent stenosis. CONCLUSION: Thoracic stenosis with myelopathy should be entertained in patients with myelopathy. Over half of our patients with TS were over the age of 70, and men outnumbered women by a ratio of 2:1. Nearly half the patients with TS had concomitant cervical and/or lumbar degenerative disease warranting surgery also. Increased signal intensity on T2-weighted MRI images correlated with lower Frankel and JOA scores compared to those without. Decompression for thoracic stenosis is associated with neurological improvement

Traumatic intracranial hemorrhage in patients taking dabigatran: report of 3 cases and review of the literature.

BACKGROUND AND IMPORTANCE: Dabigatran is a direct thrombin inhibitor gaining popularity as a stroke prevention agent in patients with atrial fibrillation. In comparison with warfarin, dabigatran showed superiority in stroke prevention, but lower rates of major hemorrhage and intracerebral hemorrhage. Although warfarin has a well-established reversal strategy, there is far less experience reversing dabigatran. CLINICAL PRESENTATION: We present our experience with 3 patients who experienced an intracranial hemorrhage either spontaneously or after low-energy cranial trauma and review the available literature describing dabigatran use in patients with traumatic brain injury. CONCLUSION: Intracranial hemorrhage in patients taking anticoagulants and/or antiplatelets can have either a benign or malignant clinical course. At this time, there is little experience with dabigatran reversal; however, several strategies for rapid reversal have been proposed. All patients with intracranial hemorrhage taking dabigatran should be admitted for close neurological monitoring and serial imaging

Heterogeneity within the PF-EPN-B ependymoma subgroup

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