High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells.

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes.

Diffuse midline glioma, H3K27-altered, of the conus medullaris presenting as acute urinary retention: illustrative case.

BACKGROUND: Diffuse midline glioma (DMG), H3K27-altered, is a rare, highly malignant central nervous system neoplasm that arises in midline structures. They are more commonly encountered in children and are rarely encountered in adults, usually in the thalamus or spinal cord. The presence of the H3K27 mutation in the H3F3A gene automatically classifies a tumor as World Health Organization grade IV. These tumors carry a grim prognosis, with an overall median survival of less than 1 year. OBSERVATIONS: The authors report the case of a 38-year-old male presenting with acute-onset urinary retention who was found to have an expansile, well-circumscribed mass involving the conus medullaris at the level of T12-L1. A T12-L1 laminectomy and tumor debulking were performed. Pathology revealed glial cells with astrocytic morphology among Rosenthal fibers, microvascular proliferation, and cellular atypia. The H3K27 mutation was confirmed. LESSONS: DMG, H3K27-altered, is a rarely encountered entity that can present in numerous midline structures. If localized to the conus medullaris, it may present as acute-onset urinary retention in a previously asymptomatic patient. Further investigation is needed to characterize its molecular and clinical features in adults to improve the management of those presenting with these tumors.

Thalamo-Prefrontal Connectivity Correlates With Early Command-Following After Severe Traumatic Brain Injury.

Recovery of consciousness after traumatic brain injury (TBI) is heterogeneous and difficult to predict. Structures such as the thalamus and prefrontal cortex are thought to be important in facilitating consciousness. We sought to investigate whether the integrity of thalamo-prefrontal circuits, assessed via diffusion tensor imaging (DTI), was associated with the return of goal-directed behavior after severe TBI. We classified a cohort of severe TBI patients (N = 25, 20 males) into Early and Late/Never outcome groups based on their ability to follow commands within 30 days post-injury. We assessed connectivity between whole thalamus, and mediodorsal thalamus (MD), to prefrontal cortex (PFC) subregions including dorsolateral PFC (dlPFC), medial PFC (mPFC), anterior cingulate (ACC), and orbitofrontal (OFC) cortices. We found that the integrity of thalamic projections to PFC subregions (L OFC, L and R ACC, and R mPFC) was significantly associated with Early command-following. This association persisted when the analysis was restricted to prefrontal-mediodorsal (MD) thalamus connectivity. In contrast, dlPFC connectivity to thalamus was not significantly associated with command-following. Using the integrity of thalamo-prefrontal connections, we created a linear regression model that demonstrated 72% accuracy in predicting command-following after a leave-one-out analysis. Together, these data support a role for thalamo-prefrontal connectivity in the return of goal-directed behavior following TBI.

Burr-Hole Evacuation of an Acute Epidural Hematoma using the Artemis Neuroevacuation Device With Flexible Endoscopic Visualization: 2-Dimensional Operative Video.

Minimally invasive (MIS) endoscopic burr-hole evacuation of both acute and subacute subdural hematomas (SDHs) has been demonstrated as a way to avoid large craniotomies and additional morbidity, particularly for patients who are poor surgical candidates.1,2 Although generally safe and effective, there are risks of complications including SDH recurrence or new hemorrhage including epidural hematoma (EDH).3,4 Acute intraparenchymal hemorrhage has also been successfully treated using MIS endoscopic techniques with the assistance of aspiration devices; however, acute EDHs generally still necessitate a craniotomy for evacuation, nullifying many of the advantages of burr-hole craniostomy.5,6 In this surgical video, we demonstrate-to our knowledge-the first case of endoscopic burr-hole evacuation of an acute EDH using an Artemis Neuro Evacuation device (Penumbra, Alameda, CA). We present the case of a 40 year-old man with a left anterior middle cranial fossa arachnoid cyst who developed a traumatic left subacute SDH and hemorrhage into the cyst. He underwent burr-hole craniostomy for endoscopic evacuation of subacute SDH, evacuation of hemorrhage within the cyst, and fenestration of arachnoid cyst. On postoperative day 2, he developed an acute left EDH with midline shift. An Artemis device was inserted into 1 of the pre-existing burr-holes and used to evacuate the acute EDH with direct visualization from a flexible endoscope inserted into the second burr-hole. The patient did well, was discharged 2 days later, and demonstrated complete resolution of hemorrhage 5 weeks post-procedure. The video also provides a brief background on arachnoid cysts, their association with hemorrhage, and MIS techniques for hemorrhage evacuation.7-12 There is no identifying information in the video. The patient provided informed consent for both procedures (Video 1).

Hypothalamic Cavernomas: Pediatric Case Report with 8.5-Year Follow-up and Review of the Literature.

BACKGROUND: Cavernous malformations (cavernomas) are angiographically occult vascular lesions that can present symptomatically or be discovered incidentally. Rarely, they present in the hypothalamus or in children. CASE DESCRIPTION: We describe the case of a 14-year-old male patient who presented with headaches and fever and was found to have a hypothalamic cavernoma that hemorrhaged. It was managed expectantly, with 1 rehemorrhage 21 months later, and the patient remains asymptomatic to this day aside from headaches. CONCLUSIONS: This is to our knowledge the youngest case of a hypothalamic cavernoma to be reported and includes 8.5 years of follow-up and imaging. In addition, a literature review is performed that summarizes the 11 previously reported cases of hypothalamic cavernomas, including associated symptoms, management options, and outcomes.