Acute hyponatremia post craniotomy resulting in a unilateral fixed and dilated pupil: A case study on diagnosis and management.

Background: Postoperative hyponatremia is a known complication of intracranial surgery, which can present with depressed mental status. Hyponatremia resulting in focal neurologic deficits is less frequently described. Case Description: We describe a patient who, after a bifrontal craniotomy for olfactory groove meningioma, developed acute hyponatremia overnight with a decline in mental status from Glasgow coma scale (GCS) score 15 to GCS 7 and a unilateral fixed dilated pupil. Head computed tomography showed expected postoperative changes without new acute or localizing findings, such as unilateral uncal herniation. The patient's mental status and pupil immediately improved with the administration of mannitol; however, there was a subsequent decline in mental status with a preserved pupil later that morning. Hypertonic saline reversed the neurologic change, and the patient was eventually discharged without a neurologic deficit. Focal neurologic deficits need not always arise following a craniotomy from a postoperative hematoma, stroke, or other finding with radiographic correlate. Conclusion: Post-craniotomy hyponatremia should now be seen as a postoperative complication that can result in both a general neurologic decline in mental status, as well as with focal neurologic signs such as a fixed, dilated pupil, which can be reversed with hyperosmolar therapy and correction of the hyponatremia.

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas.

BACKGROUND AND OBJECTIVES: Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas. METHODS: Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200). RESULTS: MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2). CONCLUSION: In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.

Greater improvement in Neck Disability Index scores in women after surgery for cervical myelopathy: an analysis of the Quality Outcomes Database.

OBJECTIVE: There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS: The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS: This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS: Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.

Neuroworsening in the Emergency Department Is a Predictor of Traumatic Brain Injury Intervention and Outcome: A TRACK-TBI Pilot Study.

INTRODUCTION: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization. METHODS: Adult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan <24 h post-injury. Neuroworsening was defined as a decline in motor GCS at ED disposition (vs. ED admission). Clinical and CT characteristics, neurosurgical intervention, in-hospital mortality, and 3- and 6-month Glasgow Outcome Scale-Extended (GOS-E) scores were compared by neuroworsening status. Multivariable regressions were performed for neurosurgical intervention and unfavorable outcome (GOS-E ≤ 3). Multivariable odds ratios (mOR) with [95% confidence intervals] were reported. RESULTS: In 481 subjects, 91.1% had ED admission GCS 13-15 and 3.3% had neuroworsening. All neuroworsening subjects were admitted to intensive care unit (vs. non-neuroworsening: 26.2%) and were CT-positive for structural injury (vs. 45.4%). Neuroworsening was associated with subdural (75.0%/22.2%), subarachnoid (81.3%/31.2%), and intraventricular hemorrhage (18.8%/2.2%), contusion (68.8%/20.4%), midline shift (50.0%/2.6%), cisternal compression (56.3%/5.6%), and cerebral edema (68.8%/12.3%; all p < 0.001). Neuroworsening subjects had higher likelihoods of cranial surgery (56.3%/3.5%), intracranial pressure (ICP) monitoring (62.5%/2.6%), in-hospital mortality (37.5%/0.6%), and unfavorable 3- and 6-month outcome (58.3%/4.9%; 53.8%/6.2%; all p < 0.001). On multivariable analysis, neuroworsening predicted surgery (mOR = 4.65 [1.02-21.19]), ICP monitoring (mOR = 15.48 [2.92-81.85], and unfavorable 3- and 6-month outcome (mOR = 5.36 [1.13-25.36]; mOR = 5.68 [1.18-27.35]). CONCLUSIONS: Neuroworsening in the ED is an early indicator of TBI severity, and a predictor of neurosurgical intervention and unfavorable outcome. Clinicians must be vigilant in detecting neuroworsening, as affected patients are at increased risk for poor outcomes and may benefit from immediate therapeutic interventions.

Flexibility of functional neuronal assemblies supports human memory.

Episodic memories, or consciously accessible memories of unique events, represent a key aspect of human cognition. Evidence from rodent models suggests that the neural representation of these complex memories requires cooperative firing of groups of neurons on short time scales, organized by gamma oscillations. These co-firing groups, termed "neuronal assemblies," represent a fundamental neurophysiological unit supporting memory. Using microelectrode data from neurosurgical patients, we identify neuronal assemblies in the human MTL and show that they exhibit consistent organization in their firing pattern based on gamma phase information. We connect these properties to memory performance across recording sessions. Finally, we describe how human neuronal assemblies flexibly adjust over longer time scales. Our findings provide key evidence linking assemblies to human episodic memory for the first time.

Predictors of Extreme Hospital Length of Stay After Traumatic Brain Injury.

BACKGROUND: Hospital length of stay (HLOS) after traumatic brain injury (TBI) is an important metric of injury severity, resource utilization, and access to post-acute care services. Risk factors for protracted HLOS after TBI require further characterization. METHODS: Data regarding adult inpatients admitted to a single U.S. level 1 trauma center with a diagnosis of acute TBI between August 1, 2019, and April 1, 2022, were extracted from the electronic health record. Patients with extreme HLOS (XHLOS, >99th percentile of institutional TBI HLOS) were compared with those without XHLOS. Socioeconomic status (SES), clinical/injury factors, and discharge disposition were analyzed. RESULTS: In 1638 patients, the median HLOS was 3 days (interquartile range [IQR]: 2-8 days). XHLOS threshold was >70 days (N = 18; range: 72-146 days). XHLOS was associated with younger age (XHLOS/non-XHLOS: 50.4/59.6 years; P = 0.042) and greater proportions with severe TBI (55.6%/11.4%; P < 0.001), low SES (72.2%/31.4%; P < 0.001), and Medicaid insurance (77.8%/30.1%; P < 0.001). XHLOS patients were more likely to die in hospital (22.2%/8.1%) and discharge to post-acute facility (77.8%/16.3%; P < 0.001). No XHLOS patients were discharged to home. In XHLOS patients alive at discharge, medical stability was documented at median 39 days (IQR: 28-58 days) and were hospitalized for another 56 days (IQR: 26.5-78.5 days). CONCLUSIONS: XHLOS patients were more likely to have severe injuries, low SES, and Medicaid. XHLOS is associated with in-hospital mortality and need for post-acute placement. XHLOS patients often demonstrated medical stability long before placement, underscoring complex relationships between SES, health insurance, and outcome. These findings have important implications for quality improvement and resource utilization at acute care hospitals and await validation from larger trials.

Evacuation of a multi-loculated acute-on-chronic subdural hematoma using tandem bedside subdural evacuation port systems.

Background: Traumatic subdural hematomas (SDH) can have devastating neurologic consequences. Acute-on-chronic SDHs are more frequent in the elderly, who have increased comorbidities and perioperative risks. The subdural evacuation port system (SEPS) procedure consists of a twist drill hole connected to a single drain on suction, which can be performed at bedside to evacuate SDHs without requiring general anesthesia. However, a single SEPS can be limited due to inability to evacuate across septations between SDHs of different ages. Purpose: We present to our knowledge the first case of using tandem SEPS to evacuate a multi-loculated SDH. We discuss the technical nuances of the procedure as a treatment option for complex SDHs. Findings: An 86-year-old man with cognitive impairment and recurrent falls presented acutely after ground-level fall with worsening dysarthria and right hemiparesis. Computed tomography scan showed a 11 mm left holohemispheric mixed-density SDH with loculated acute and subacute/chronic components with 2 mm midline shift. Following two interval stability scans, the patient underwent drainage of a superficial chronic component, and a posterolateral acute/subacute component using two sequential SEPS drains at bedside in the intensive care unit. The patient's symptoms markedly improved, drains were removed, and the patient was discharged home with home health on post-procedure day 6. Conclusions: Judicious patient selection and pre-procedural planning can enable the use of tandem SEPS to evacuate multi-loculated SDHs under moderate sedation. Using multiple subdural ports to evacuate complex SDHs should be an option for proceduralists in settings where general anesthesia is not feasible.

Episodic boundary cells in human medial temporal lobe during the free recall task.

A necessary condition for forming episodic memories is the construction of specific episodes demarcated from other episodes in space and time. Evidence from studies of episodic memory formation using rodent models suggest that the medial temporal lobe (MTL) supports the representation of boundary information. Building on recent work using human microelectrode recordings as well, we hypothesized of human MTL neurons with firing rates sensitive to episodic boundary information. We identified 27 episodic boundary neurons out of 736 single neurons recorded across 27 subjects. Firing of these neurons increased at the beginning and end of mnemonically relevant episodes in the free recall task. We distinguish episodic boundary neurons from a population of ramping neurons (n = 58), which are time-sensitive neurons whose activity provides complementary information during episodic representation. Episodic boundary neurons exhibited a U-shaped activity pattern demonstrating increased activity after both beginning and end boundaries of encoding and retrieval epochs. We also describe evidence that the firing of boundary neurons within episodic boundaries is organized by hippocampal theta oscillations, using spike-field coherence metrics.

Neurons in the human medial temporal lobe track multiple temporal contexts during episodic memory processing.

Episodic memory requires associating items with temporal context, a process for which the medial temporal lobe (MTL) is critical. This study uses recordings from 27 human subjects who were undergoing surgical intervention for intractable epilepsy. These same data were also utilized in Umbach et al. (2020). We identify 103 memory-sensitive neurons in the hippocampus and entorhinal cortex, whose firing rates predicted successful episodic memory encoding as subjects performed a verbal free recall task. These neurons exhibit important properties. First, as predicted from the temporal context model, they demonstrate reinstatement of firing patterns observed during encoding at the time of retrieval. The magnitude of reinstatement predicted the tendency of subjects to cluster retrieved memory items according to input serial position. Also, we found that spiking activity of these neurons was locked to the phase of hippocampal theta oscillations, but that the mean phase of spiking shifted between memory encoding versus retrieval. This unique observation is consistent with predictions of the "Separate Phases at Encoding And Retrieval (SPEAR)" model. Together, the properties we identify for memory-sensitive neurons characterize direct electrophysiological mechanisms for the representation of contextual information in the human MTL.

Transforming Growth Factor-induced Protein Promotes NF-κB-mediated Angiogenesis during Postnatal Lung Development.

Pulmonary angiogenesis is a key driver of alveolarization. Our prior studies showed that NF-κB promotes pulmonary angiogenesis during early alveolarization. However, the mechanisms regulating temporal-specific NF-κB activation in the pulmonary vasculature are unknown. To identify mechanisms that activate proangiogenic NF-κB signaling in the developing pulmonary vasculature, proteomic analysis of the lung secretome was performed using two-dimensional difference gel electrophoresis. NF-κB activation and angiogenic function was assessed in primary pulmonary endothelial cells (PECs) and TGFBI (transforming growth factor-ß-induced protein)-regulated genes identified using RNA sequencing. Alveolarization and pulmonary angiogenesis was assessed in wild-type and Tgfbi null mice exposed to normoxia or hyperoxia. Lung TGFBI expression was determined in premature lambs supported by invasive and noninvasive respiratory support. Secreted factors from the early alveolar, but not the late alveolar or adult lung, promoted proliferation and migration in quiescent, adult PECs. Proteomic analysis identified TGFBI as one protein highly expressed by the early alveolar lung that promoted PEC migration by activating NF-κB via αvß3 integrins. RNA sequencing identified Csf3 as a TGFBI-regulated gene that enhances nitric oxide production in PECs. Loss of TGFBI in mice exaggerated the impaired pulmonary angiogenesis induced by chronic hyperoxia, and TGFBI expression was disrupted in premature lambs with impaired alveolarization. Our studies identify TGFBI as a developmentally regulated protein that promotes NF-κB-mediated angiogenesis during early alveolarization by enhancing nitric oxide production. We speculate that dysregulation of TGFBI expression may contribute to diseases marked by impaired alveolar and vascular growth.

Time cells in the human hippocampus and entorhinal cortex support episodic memory.

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of "time cells" in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism for the representation of temporal information in the human brain needed to form episodic memories.

Longitudinal Differences in Human Hippocampal Connectivity During Episodic Memory Processing.

The question of longitudinal hippocampal functional specialization is critical to human episodic memory because an accurate understanding of this phenomenon would impact theories of mnemonic function and entail practical consequences for the clinical management of patients undergoing temporal lobe surgery. The implementation of the robotically assisted stereo electroencephalography technique for seizure mapping has provided our group with the opportunity to obtain recordings simultaneously from the anterior and posterior human hippocampus, allowing us to create an unparalleled data set of human subjects with simultaneous anterior and posterior hippocampal recordings along with several cortical regions. Using these data, we address several key questions governing functional hippocampal connectivity in human memory. First, we ask whether functional networks during episodic memory encoding and retrieval are significantly different for the anterior versus posterior hippocampus (PH). We also examine how connections differ across the 2-5 Hz versus 4-9 Hz theta frequency ranges, directly addressing the relative contribution of each of these separate bands in hippocampal-cortical interactions. While we report some overlapping connections, we observe evidence of distinct anterior versus posterior hippocampal networks during memory encoding related to frontal and parietal connectivity as well as hemispheric differences in aggregate connectivity. We frame these findings in light of the proposed AT/PM memory systems. We also observe distinct encoding versus retrieval connectivity patterns between anterior and posterior hippocampal networks, we find that overall connectivity is greater for the PH in the right hemisphere, and further that these networks significantly differ in terms of frontal and parietal connectivity. We place these findings in the context of existing theoretical treatments of human memory systems, especially the proposed AT/PM system. During memory retrieval, we observe significant differences between slow-theta (2-5 Hz) and fast-theta (4-9 Hz) connectivity between the cortex and hippocampus. Finally, we test how these distinct theta frequency oscillations propagate within the hippocampus, using phase slope index to estimate the direction slow-theta and fast-theta oscillations travel during encoding and retrieval. We uncover evidence that 2-5 Hz oscillations travel in the posterior-to-anterior direction, while 5-9 Hz oscillations travel from anterior-to-posterior. Taken together, our findings describe mnemonically relevant functional connectivity differences along the longitudinal axis of the human hippocampus that will inform interpretation of models of hippocampal function that seek to integrate rodent and human data.

Extraneural metastatic anaplastic ependymoma: a systematic review and a report of metastases to bilateral parotid glands.

BACKGROUND: Anaplastic ependymoma with extraneural metastases is associated with a poor clinical outcome. Metastatic spread to the parotid gland is a rare clinical entity that requires multidisciplinary intervention. Herein, we present a systematic review of anaplastic ependymoma with extraneural metastases and report on a case with metastases to both parotid glands. METHODS: Electronic databases were searched from their inception to February 2019. Inclusion criteria included reports of anaplastic ependymoma with extraneural metastasis. Studies were excluded if the tumor grade was not reported. A case illustration is provided. RESULTS: The search yielded 15 cases of anaplastic ependymoma with extraneural metastases, including the present case. Mean age at diagnosis was 15 years. The initial tumor location was predominantly supratentorial (93.3%). All cases demonstrated leptomeningeal seeding before extraneural metastasis. Mean survival from initial diagnosis was 4.5 years. Metastasis to the parotid gland occurred in 2 cases, including the present case. We present a 17-year-old female patient who underwent gross total resection of a supratentorial, paraventricular anaplastic ependymoma followed by adjuvant external beam radiation therapy. The patient developed recurrent leptomeningeal seeding, treated with Gamma Knife radiosurgery over a 5-year period. She returned with a parotid mass and cervical lymphadenopathy and underwent parotidectomy and modified radical neck dissection. She continued to experience recurrences, including the left parotid gland, and was ultimately placed in hospice care. CONCLUSIONS: Anaplastic ependymoma with extraneural metastasis is rare. A combination of repeated surgical resection, radiation therapy, and chemotherapy can be used to manage recurrent and metastatic disease, but outcomes remain poor.

Gamma oscillations during episodic memory processing provide evidence for functional specialization in the longitudinal axis of the human hippocampus.

The question of whether the anterior and posterior hippocampus serve different or complementary functional roles during episodic memory processing has been motivated by noteworthy findings in rodent experiments and from noninvasive studies in humans. Researchers have synthesized these data to postulate several models of functional specialization, However, the issue has not been explored in detail using direct brain recordings. We recently published evidence that theta power increases during episodic memory encoding occur in the posterior hippocampus in humans. In our current investigation we analyzed an expanded data set of 32 epilepsy patients undergoing stereo EEG seizure mapping surgery with electrodes precisely targeted to the anterior and posterior hippocampus simultaneously who performed an episodic memory task. Using a repeated measures design, we looked for an interaction between encoding versus retrieval differences in gamma oscillatory power and anterior versus posterior hippocampal location. Our findings are consistent with a recently articulated model (the HERNET model) favoring posterior hippocampal activation during retrieval related processing. We also tested for encoding versus retrieval differences in the preferred gamma frequency band (high versus low gamma oscillations) motivated by published rodent data.