Patterns of relapse after successful completion of initial therapy in primary central nervous system lymphoma: a case series

Journal of Neuro-Oncology - Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin’s lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of...     

Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Journal of Neuro-Oncology - Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to...     

Bridging the gap in epilepsy care: A single-center experience of 3700 outpatient tele-epilepsy visits

We describe the largest-to-date single-center implementation of tele-epilepsy. Beginning in 2017, all patients at a single tertiary care academic epilepsy center were offered the option to complete outpatient follow-up visits via video-conferencing using personal devices. A retrospective review of all patients who self-selected virtual visits over nearly 3 years showed 2140 patients completed 3698 tele-epilepsy visits, with 41% completing more than one visit during the study period. Based on the distance from the center to the home address, 26.7% of patients were local (≤50 miles), 30.5% were near regional (51-150 miles), 20.1% were far regional (151-270 miles), and 22.7% were remote (>270 miles), from 43 different states. An estimated 928 696 miles of travel was prevented, with a median travel distance saved of 124.5 miles (interquartile range = 45.0-253.0). The mean visit time was 15.7 (±10.4) minutes. More than 90% of patients gave the visit and provider experience the maximum rating, with a nearly 60% response rate on the post-visit survey. Virtual outpatient follow-up care provides a convenient way to connect with epilepsy specialists and reduce the burden of care by cutting travel time. Our experience demonstrates that outpatient tele-epilepsy is feasible, sustainable, and scalable.     

Galectin-3 modulates postnatal subventricular zone gliogenesis

Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.     

Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease

Journal of Neurology - Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for...     

18F-AV1451 PET imaging and multimodal MRI changes in progressive supranuclear palsy

Journal of Neurology - Progressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter (GM) of deep nuclei and cerebellum. We examined the...     

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e., increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10-Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.