A feared complication of ventricular access for drainage or shunting is ventriculitis. Early diagnosis and treatment is vital to prevent morbidity and mortality. Efficacy of directed antibiotic therapy in ventriculitis is limited by increasing multidrug resistant microorganisms and insufficient systemic antibiotic absorption into the cerebrospinal fluid. Treatment may involve intravenous and/or intrathecal antibiotics as well as external ventricular drainage. We present the first case report suggesting a potential role of a novel technique - direct ventricular catheter-mediated continuous saline irrigation and serial prone patient positioning - to treat a fulminant bacterial ventriculitis. This novel technique promotes egress of purulence from the ventricles and may result in more rapid control of intraventricular infectious burden.

Dorsal thoracic arachnoid webs are rare clinical entities caused by a thickened intradural extramedullary band of arachnoid tissue that compresses the spinal cord, and often present with progressive back pain, paresthesias, and lower extremity weakness. In this report, we review the radiographic features of the "Scalpel Sign" and describe the case of a 47-year-old male that failed conservative therapy and was found to have dorsal thoracic arachnoid web. The patient underwent laminectomy and microsurgical release of the compressing arachnoid band. Postoperatively, the patient had complete resolution of his pain. Intraoperatively, the somatosensory evoked potentials were improved once the band was released. The prompt diagnosis of dorsal arachnoid webs remains critical because surgical treatment arrests and potentially reverses the pathology.

The Optune® transducer array (Novocure Ltd., Haifa, Israel) is an FDA-approved noninvasive regional therapy that aims to inhibit the growth of glioblastoma multiforme (GBM) cells via utilization of alternating electric fields. Some patients with GBM may develop hydrocephalus and benefit from subsequent shunt placement, but special attention must be paid to patients in whom programmable valves are utilized, given the potential effect of the magnetic fields on valve settings. We present the first case report illustrating the stability of programmable shunt valve settings in a neurosurgical patient undergoing therapy with the Optune device. In this study, shunt valve settings were stable over a period of five days despite Optune therapy. This is reassuring for patients with GBM who require simultaneous treatment with both the Optune device and a programmable shunt system.

The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy. Five years following his initial presentation, surveillance imaging revealed a new asymptomatic lung mass for which the patient underwent thoracotomy and resection of the mass. Histological examination of the lung mass revealed findings consistent with a de-differentiated chordoma, confirming extraneural metastasis from the original tumor without evidence of local recurrence. Chest wall and scalp metastases subsequently developed, and the patient was started on an adjuvant chemotherapy regimen that included imatinib and rapamycin followed by subsequent nivolumab and an EZH2 inhibitor for recurrent, disseminated disease. Despite this patient's remote and distant metastases, primary gross-total resection for chordoma remains a critical treatment objective, followed by proton beam radiotherapy. This case illustrates the importance of interval posttreatment imaging and the emerging potential to treat chordoma with molecularly targeted therapies.

The human genome produces thousands of long noncoding RNAs (lncRNAs)-transcripts >200 nucleotides long that do not encode proteins. Although critical roles in normal biology and disease have been revealed for a subset of lncRNAs, the function of the vast majority remains untested. We developed a CRISPR interference (CRISPRi) platform targeting 16,401 lncRNA loci in seven diverse cell lines, including six transformed cell lines and human induced pluripotent stem cells (iPSCs). Large-scale screening identified 499 lncRNA loci required for robust cellular growth, of which 89% showed growth-modifying function exclusively in one cell type. We further found that lncRNA knockdown can perturb complex transcriptional networks in a cell type-specific manner. These data underscore the functional importance and cell type specificity of many lncRNAs.

Background

Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.

Results

We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy.

Conclusions

These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.