A retrospective analysis of recurrent intracranial ependymoma.

BACKGROUND: Recurrence occurs in almost 50% of patients with intracranial ependymoma, and their outcome following recurrence is poor. METHODS: We retrospectively reviewed the medical records of 22 patients with intracranial ependymoma and subsequent relapse(s) (59 recurrences) treated at Children's Hospital Los Angeles or New York University between January 1997 and December 2012. RESULTS: Median duration of follow-up was 52 months (7-171 months). Median age at initial diagnosis was 4 years (0.3-19 years) with 8 patients younger than 3 years at presentation. Eleven patients had anaplastic and 11 cellular pathologies. Eighteen patients had infratentorial tumors at diagnosis and 3 (all infratentorial) had metastatic spinal cord involvement at presentation. Cerebrospinal fluid involvement was not identified at diagnosis or relapse. Median time to first recurrence was 16 months (1.3 to 115 months). The number of recurrences in each patient ranged from 1 to 9 (median = 2). Thirty-seven recurrences (63%) were detected asymptomatically by surveillance imaging. Fifteen recurrences (26%) arose outside the initial tumor site. Recurrences were treated by surgical resection (45), with irradiation (30), and with various oral chemotherapies (23) with (7) or without (16) conventional chemotherapy. The 5 and 10 year overall survival rates from first recurrence were 0.37 ± 0.14 and 0.25 ± 0.14. CONCLUSION: Prolonged (5-10 year) survival from first relapse was noted in over one-quarter of our patients. It remains unclear whether early radiographic diagnosis, differing treatment modalities beyond radical surgical resection or possibly unrecognized biological differences contributed towards this prolonged survival.

Supratentorial ependymoma in children: to observe or to treat following gross total resection?

BACKGROUND: The standard treatment for ependymoma is surgical resection followed by postoperative irradiation to the local site. The role of radiation therapy in completely resected supratentorial ependymoma has been questioned over the past two decades. PROCEDURE: Retrospective review of the medical records of all consecutively diagnosed supratentorial ependymoma patients at Children's Hospital Los Angeles between January 1999 and December 2009. RESULTS: Ten patients (three females) were included. The median age at presentation was 5.6 years (range 1.8-15.6 years). Reviewed histology was anaplastic ependymoma in seven patients and cellular ependymoma in three patients. Gross total resection was achieved in six patients; five were observed and one received chemotherapy. In the four patients who underwent subtotal resection, one was observed, two received local irradiation and one received irradiation and chemotherapy. The median length of follow up was 43 (range 22-81) months. Four relapses were observed; two patients who underwent initial gross total resection. All patients who underwent gross total resection were alive at the time of preparation of this article. The 5-year progression-free and overall survival rates were 53 ± 19% and 86 ± 13% respectively. CONCLUSIONS: Radiation therapy was avoided in five patients following gross total resection, four of whom had anaplastic histology. In some children with completely resected supratentorial ependymoma, surgery alone may be an acceptable treatment option.

Treatment of primary CNS germinomatous germ cell tumors with chemotherapy prior to reduced dose whole ventricular and local boost irradiation.

BACKGROUND: The purpose of this study was to evaluate a reduced irradiation dose strategy for newly diagnosed primary central nervous system (CNS) germinomas. METHODS: Twenty patients with histologically diagnosed localized pure germinoma (n = 19) or germinoma with a mature teratoma component (n = 1) received four cycles of carboplatin and etoposide at 3-week intervals. In 18 patients, chemotherapy was followed by whole ventricular irradiation to 21.6-25.5 Gy with a simultaneous integrated or sequential primary site boost to 30-30.6 Gy. Initial tumor markers for beta-human chorionic gonadotrophin (HCGbeta) and alpha-fetoprotein (AFP) were evaluated in serum and lumbar cerebrospinal fluid (CSF). Endoscopic biopsies were performed in 12 patients and partial resections in the remaining 8 patients at diagnosis. Neurocognitive function was evaluated periodically following treatment. RESULTS: Eighteen of 20 patients are without evidence of residual or recurrent tumor. Both relapsing patients were subsequently determined to harbor malignant non-germinomatous germ cell tumor (NGGCT). This retrospective study shows that the Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS) at 3 years for all 20 patients were 89.5 +/- 7.1% and 100%, respectively. Neurocognitive function was well preserved in all 19 evaluable patients. CONCLUSION: Chemotherapy followed by reduced dose whole ventricular and local boost irradiation appears to be effective in patients with localized pure CNS germinoma with evidence of preservation of neurocognitive function.

Directed energy system technology for the control of soilborne fungal pathogens and plant-parasitic nematodes.

BACKGROUND: It is challenging to manage soilborne pathogens and plant-parasitic nematodes using sustainable practices. Here, we evaluated a novel energy application system, Directed Energy System (DES). This system generates pulses of energy capable of impacting selected biological organisms. The oomycete Phytophthora cinnamomi, the fungus Verticillium dahliae, and the plant-parasitic nematodes Meloidogyne hapla and Globodera ellingtonae were added to soil. Then DES-generated energy was applied to soil and impacts on target organisms were determined. RESULTS: DES applied at 20, 40 and 70 J cm-3 to P. cinnamomi and V. dahliae resulted in ≥50% and 92% reductions (respectively) of propagules per gram of soil in comparison to the untreated control. There was a significant reduction of M. hapla eggs per gram of host tomato root between the untreated control, and 2.2, 13 and 25 J cm-3 DES dosages applied pre- or post-planting. Additionally, an 84% reduction in hatch from G. ellingtonae encysted eggs after treatment with 70 J cm-3 DES was observed. The dosages ranged from 40 or 80V mm-1 for nematodes to 200 V mm-1 for fungi. CONCLUSION: DES-generated energy reduced survival of the soilborne pathogens P. cinnamomi and V. dahlia, and the plant-parasitic nematodes M. hapla and G. ellingtonae. The application of this technology to a field setting remains to be considered. Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Pest Management Science published by Wiley Periodicals, Inc. on behalf of © 2020 Society of Chemical Industry.

The morphology and biochemistry of nanostructures provide evidence for synthesis and signaling functions in human cerebrospinal fluid.

BACKGROUND: Cerebrospinal fluid (CSF) contacts many brain regions and may mediate humoral signaling distinct from synaptic neurotransmission. However, synthesis and transport mechanisms for such signaling are not defined. The purpose of this study was to investigate whether human CSF contains discrete structures that may enable the regulation of humoral transmission. METHODS: Lumbar CSF was collected prospectively from 17 participants: with no neurological or psychiatric disease, with Alzheimer's disease, multiple sclerosis, or migraine; and ventricular CSF from two cognitively healthy participants with long-standing shunts for congenital hydrocephalus. Cell-free CSF was subjected to ultracentrifugation to yield supernatants and pellets that were examined by transmission electron microscopy, shotgun protein sequencing, electrophoresis, western blotting, lipid analysis, enzymatic activity assay, and immuno-electron microscopy. RESULTS: Over 3,600 CSF proteins were identified from repeated shotgun sequencing of cell-free CSF from two individuals with Alzheimer's disease: 25% of these proteins are normally present in membranes. Abundant nanometer-scaled structures were observed in ultracentrifuged pellets of CSF from all 16 participants examined. The most common structures included synaptic vesicle and exosome components in 30-200 nm spheres and irregular blobs. Much less abundant nanostructures were present that derived from cellular debris. Nanostructure fractions had a unique composition compared to CSF supernatant, richer in omega-3 and phosphoinositide lipids, active prostanoid enzymes, and fibronectin. CONCLUSION: Unique morphology and biochemistry features of abundant and discrete membrane-bound CSF nanostructures are described. Prostaglandin H synthase activity, essential for prostanoid production and previously unknown in CSF, is localized to nanospheres. Considering CSF bulk flow and its circulatory dynamics, we propose that these nanostructures provide signaling mechanisms via volume transmission within the nervous system that are for slower, more diffuse, and of longer duration than synaptic transmission.

False-positive magnetic resonance imaging findings in follow-up of pediatric patients with tumors of the central nervous system.

Management of patients with central nervous system tumors relies largely on magnetic resonance imaging scans to document disease progression or recurrence. The finding of new lesions always presents the challenge of differentiating between post-surgical changes, radiation necrosis, gliosis, and tumor, submitting these patients to more aggressive therapy and more toxicity. We reviewed the medical records of three patients with primary central nervous system tumors treated at the Children's Hospital Los Angeles who had new false-positive magnetic resonance imaging findings suggestive of tumor recurrence. All of them had complete total resection of primary tumor, had received involved-field radiation therapy, had biopsies confirming absence of viable tumor, and all three patients are long-term survivors. These cases exemplify that not everything that enhances on brain or spine magnetic resonance imaging is viable tumor, and a biopsy should always be considered in the decision-making process in evaluation of potentially recurrent central nervous system tumors in pediatric patients. A step-wise approach for such challenging cases is presented in this article.

Complications of halo use in children.

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate complications of halo use in children. SUMMARY OF BACKGROUND DATA: Halos have been used in children for correction of spinal deformity and immobilization of the spine. Complications of halo use in children have been reported, including pin-site complications and neurologic injury from halo traction. The purpose of this report is to report on complications of halo use in children. METHODS: The medical records of 68 patients treated with a halo for correction of spinal deformity or immobilization from 1996 to 2005 were reviewed. Mean age of children was 10 (1-20) years. The halo device was used to apply traction for correction of spinal deformity in 31 patients, and immobilization alone with halo vest in 37 patients. RESULTS: The overall rates of complications are significant at 53% (36/68). Pin-site complications included 13 infections successfully treated with oral antibiotics and 4 pins that needed to be removed. Two pins were replaced due to skull penetration, and 1 scar site was surgically revised. There were a total of 9 neurologic complications that occurred in 7 of 31 patients undergoing halo traction (31% incidence), including 3 cranial nerve injuries, 1 Horner syndrome, 4 extremity weaknesses, and 1 bradycardia. All traction-related neurologic problems resolved with removal or decrease of the magnitude of traction, with 4 cases improving immediately, 3 cases within 2 days, and the 2 other cases resolving in 1 and 5 months. Lastly, there were 7 vest-related complications including 5 pressure sores, 1 cracking of the vest, and 1 halo-vest readjustment. CONCLUSION: This is the largest reported series of halo use in children. The overall rate of complications is 53% (36/68), and 10% (7/68) of children required unanticipated surgery for treatment of these complications. The most common complication was pin-site infections, with 76% (13/17) of these resolving with oral antibiotics alone. Traction-related neurologic injuries that occurred were common, 31% (9/31) but all resolved with a decrease or removal of traction weight, with complete resolution occurring immediately in 4 of 9 events. We recommend serial neurologic examinations of children in halo traction, with immediate removal or decrease in weights at the first sign of injury.