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Background Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). Methods Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). Results The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, −7.7 [6.1]; P  < .001, 95 % CI: −8.4, −7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, −8.2 [−9.4, −7.0]) and numerically exceeds the improvement seen with placebo in that study (−5.7 [−6.8, −4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline ( P  < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were “much” or ”very much” improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. Conclusions DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. Trial registration Clinicaltrials.gov, NCT01799941, registered on 25 February 2013

After publication of the original article [1], the authors noticed that there were errors in the caption of Fig. 3, and the y-axis of Fig. 6 itself. https://static-content.springer.com/image/art%3A10.1186%2Fs12883-016-0679-z/MediaObjects/12883_2016_679_Fig1_HTML.gif Fig. 6 Mean CNS-LS Scores Across DM/Q Studies for PBA Secondary to Diverse Neurologic Conditions. *DM/Q 30/30 mg twice daily; [dagger]DM/Q 20/10 mg twice daily. [double dagger]Improvement from baseline in mean CNS-LS (SE). 99-AVR-102 (4 week study comparing DM/Q to DM or Q monotherapy): End of study is the mean of the CNS-LS scores for Days 15 and 29; P = 0.001 vs. dextromethorphan comparator and P < 0.001 vs quinidine comparator. 02-AVR-106 (12 week DBPC study): End of study is the mean of the CNS-LS scores on Days 15, 29, 57, and 85; P < 0.0001 vs. placebo. 07-AVR-123 (12 week DBPC study): End of study is at Week 12 intent to treat; P < 0.05 vs. placebo. PRISM II: End of study is at Day 90/Final Visit; P < 0.001 vs. baseline in all 3 cohorts. ALS = amyotrophic lateral sclerosis; CNS-LS = Center for Neurologic Study-Lability Scale; DM/Q = dextromethorphan/quinidine; MS = multiple sclerosis; PBA = pseudobulbar affect; TBI = traumatic brain injury; SE = standard error The following statement should not have been included in the caption of Fig. 3: \"CNS-LS scores were not normalized.\" The CNS-LS is a rank-order scale, and is not normalized. This statement was included erroneously and the authors intended on removing it prior to resubmission, but this was unfortunately overlooked. Similarly, the y-axis within Fig. 6 was mislabelled. The CNS-LS scale ranges from 7 to 35, so the y-axis for Fig. 6 should start at a base score of 7 and not zero. The correct and updated version of Fig. 6, in which the data presented remain accurate and are unchanged, is published in this erratum.

Over 90% of childhood ependymomas arise within the cranium, two-thirds below and one-third above the tentorium, and they comprise 8–10% of all childhood CNS neoplasms. This is in contradistinction to the presentation in adults where over 75% of the ependymomas arise within the spinal canal. The incidence of 2.2 cases per million appears to be increasing over the past 30 years. The biology of the disease resembles that of a low-grade glioma where local control measures are most important and less than 5% of children present with metastatic disease. Thus, total resection is the optimum therapy. The value of adjuvant therapy for children with no postoperative residual disease is unclear. Adjuvant radiotherapy is reserved for children with postoperative residual disease and appears to prolong survival. A brief review of our current understanding of the incidence, sites of origin, clinical presentations, prognostic factors and controversial treatment issues will be presented.

The late effects in children with hypothalamic and thalamic tumors relate to the effects of the tumor on the surrounding brain, the effects of surgery, radiotherapy (RT) and, to a lesser extent, chemotherapy. The clinical manifestations of late effects include endocrinologic dysfunction, neurocognitive sequelae, behavioral problems and second neoplasia. The prevention of late effects is an integral part of current treatment strategies. Early diagnosis, a rational use of surgery, and deferral of RT are the mainstays of the modern treatment in these patients. The improvement of RT techniques and the use of radioprotective compounds may further help spare normal brain tissue. A better understanding of chemotherapy use and the development of newer agents may increase efficacy, reduce side effects and allow deferral of RT in a greater percentage of patients. Finally, an aggressive management of endocrinological problems, physical and cognitive rehabilitation as well as psychological and school support help provide these children with maximal function within their potential.

The dose intensity of the PCV regimen can be doubled using peripheral blood stem cell (PBSC) support. This study sought to determine the feasibility of giving dose-intensive PCV concurrently with radiation therapy. Twelve patients, age 3.2-22.7 years, median 7.5 years, with newly diagnosed high grade gliomas were enrolled. Diagnoses included diffuse intrinsic brainstem gliomas (BSG) (n = 6), glioblastoma (n = 4), anaplastic astrocytoma (n = 2). PBSCs were harvested prior to chemotherapy with G-CSF priming. Chemotherapy consisted of CCNU 130 mg/m2 and vincristine 1.5 mg/m2 on day 0, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered every 28 days or when blood counts recovered. The first course was administered the week prior to RT, the second course began on week 3 of RT and the third and fourth course were given after RT. Hematologic toxicity was mild and the majority of courses were given on schedule. Five of six patients with diffuse BSG showed clinical improvement and three showed a radiographic response; however, only one remains alive 12+ months from diagnosis. All four patients with non-brainstem large-volume tumors showed clinical deterioration and radiographic progression during or shortly after RT. MRI scans showed massive edema and enhancement. Median time to radiographic progression was five months. Median overall survival was 11 months. We conclude that dose-intensive, time-compressed PCV given concurrently with large-volume RT appears to result in unacceptable toxicity in patients with large residual tumors.

Surgical resection with or without radiation therapy confers long-term remission in approximately half of the patients newly diagnosed with ependymoma. Chemotherapy has a limited role in the management of ependymoma. In newly diagnosed infants, chemotherapy is utilized as an attempt to defer radiation. The use of chemotherapy in older children has provided no conclusive benefit. The largest experience with chemotherapy in ependymoma has been in children with recurrent disease. In this section, we will analyze the principal institutional and cooperative group phase I, phase II, and phase III clinical trials utilizing single-agent and multiagent chemotherapy in patients with recurrent ependymoma. In addition, future directions relating to novel medical oncologic therapies will also be discussed.