Dreams interrupted: characteristics of REM sleep-associated seizures and status epilepticus.

STUDY OBJECTIVES: Seizures are rare in rapid eye movement sleep (REM). However; seizures sometimes occur in REM, and a small number of focal epilepsy patients display their maximum rate of interictal epileptiform discharges in REM. We sought to systematically identify and characterize seizures in REM. METHODS: We reviewed all admissions to the Epilepsy Monitoring Unit (EMU) at the Winnipeg Health Sciences Centre over 12-months in 2014-2015. American Academy of Sleep Medicine sleep-stage scoring was initially applied in the standard 30-second epochs. Then, to capture sudden changes in sleep-wake state on shorter timescales that are associated with seizure formation and propagation, we re-scored ictal and peri-ictal EEG epochs every 1 second. Patients found to have seizures in REM were subject to chart review spanning three years pre- and post-admission. RESULTS: REM seizures occurred in 3/63 EMU patients. Notably, one patient exhibited continuous epileptiform activity, consistent with focal nonconvulsive electrographic status epilepticus, throughout REM cycles for each night of her admission. Otherwise, discrete REM seizures constituted a small fraction of the other patients' total seizures (range 5.0-8.3%), occurred shortly after REM onset from non-REM 2, and were manifest as minor epileptic arousals. CONCLUSIONS: Our results confirm that REM seizures are rare, while highlighting outliers who widen the known spectrum of heterogeneous sleep effects on seizures/epilepsy. We also report the first case of paradoxical status epilepticus in REM.

Extensive Mirror-Image Neurofibromas of Entire Spine Resulting in Spastic Tetraplegia.

Neurofibromatosis 1 (NF1) is associated with increased incidence of spinal tumors including neurofibromas. The majority of NF1-associated spine neurofibromas are asymptomatic; however, a minority of patients will experience neurologic symptoms that can range from mild paresthesia, radiculopathy, myelopathy, and focal weakness to quadriplegia in extreme cases. We present a 21-year-old male diagnosed with NF1 in infancy and followed for multiple mirror-image neurofibromas involving the entire spine. He was asymptomatic until age 14 when he developed neck pain and progressive tetraplegia with magnetic resonance imaging showing severe cord compression secondary to bilateral C2 neurofibromas. Emergent cervical decompression was performed at C1-C3 along with debulking of bilateral neurofibromas. Postoperatively he regained full strength with no signs of myelopathy several years postoperatively. This case demonstrates a dramatic neuroimaging finding and emphasizes the potential for significant neurologic deterioration in previously asymptomatic NF1 patients, highlighting the need for long-term follow-up.

Relapsed or refractory primary central nervous system lymphoma radiosurgery: Report of the International Gamma Knife Research Foundation.

Stereotactic radiosurgery (SRS) can be used as part of multimodality management for patients with primary central nervous system lymphoma (PCNSL). The objective of this study is to evaluate outcomes of SRS for this disease. The International Gamma Knife Research Foundation identified 23 PCNSL patients who underwent SRS for either relapsed (intracerebral in-field or out-of-field tumor recurrences) or refractory disease from 1995-2014. All 23 patients presented with RPA Class I or II PCNSL, and were initially treated with a median of 7 cycles of methotrexate-based chemotherapy regimens (range, 3-26 cycles). Ten received prior whole brain radiation (WBRT) to a median dose of 43 Gy (range, 24-55 Gy). Sixteen presented with relapsed PCNSL, and seven presented with refractory disease. Twenty-three received 26 procedures of SRS. The median tumor volume was 4 cm3 (range, 0.1-26 cm3), and the median margin dose was 15 Gy (range, 8-20 Gy). Median follow-up from SRS was 11 months (interquartile range, 5.7-33.2 months). Twenty presented with treatment response to twenty-three tumors (12 complete, 11 partial). Fourteen patients relapsed or were refractory to salvage SRS, and local control was 95%, 91%, and 75% at 3, 6, and 12 months post SRS. Intracranial (in-field and out-of-field) and distant (systemic) PFS was 86%, 81%, and 55% at 3, 6, and 12 months post SRS. Toxicity of SRS was low, with one developing an adverse radiation effect requiring no additional intervention. Although methotrexate-based chemotherapy regimens with or without WBRT is the first-line management option for PCNSL, SRS may be used as an alternative option in properly selected patients with smaller relapsed or refractory PCNSL tumors.

Guanidylation and tail effects in cationic antimicrobial lipopeptoids.

BACKGROUND: Cationic antimicrobial peptides (CAMPs) are attractive scaffolds for the next generation of antimicrobial compounds, due to their broad spectrum of activity against multi-drug resistant bacteria and the reduced fitness of CAMP-insensitive mutants. Unfortunately, they are limited by poor in vivo performance, including ready cleavage by endogenous serum proteases. METHODOLOGY/PRINCIPAL FINDINGS: To explore the potential for peptoid residues to replace well studied CAMP scaffolds we have produced a series of antimicrobial lipopeptoids, with sequences similar to previously reported lipopeptides. The activity of the peptoids was assessed against a panel of clinically relevant and laboratory reference bacteria, and the potential for non-specific binding was determined through hemolytic testing and repeating the antimicrobial testing in the presence of added bovine serum albumin (BSA). The most active peptoids displayed good to moderate activity against most of the gram positive strains tested and moderate to limited activity against the gram negatives. Antimicrobial activity was positively correlated with toxicity towards eukaryotic cells, but was almost completely eliminated by adding BSA. CONCLUSION/SIGNIFICANCE: The lipopeptoids had similar activities to the previously reported lipopeptides, confirming their potential to act as replacement, proteolytically stable scaffolds for CAMPs.