Synaptic cell-adhesion molecule latrophilin-2 is differentially directed to dendritic domains of hippocampal neurons.

Hippocampal pyramidal cells possess elaborate dendritic arbors with distinct domains that are targeted with input-specific synaptic sites. This synaptic arrangement is facilitated by synaptic cell-adhesion molecules that act as recognition elements to connect presynaptic and postsynaptic neurons. In this study, we investigate the organization of the synaptic recognition molecule latrophilin-2 at the surface of pyramidal neurons classified by spatial positioning and action potential firing patterns. Surveying two hippocampal neurons that highly express latrophilin-2, late-bursting CA1 pyramidal cells and early-bursting subiculum pyramidal cells, we found the molecule to be differentially positioned on their respective dendritic compartments. Investigating this latrophilin-2 positioning at the synaptic level, we found that the molecule is not present within either the pre- or postsynaptic terminal but rather is tightly coupled to synapses at a perisynaptic location. Together these findings indicate that hippocampal latrophilin-2 distribution patterning is cell-type specific, and requires multiple postsynaptic neurons for its synaptic localization.

Cystic Brain Metastasis Outcomes After Gamma Knife Radiation Therapy.

Purpose: The response of cystic brain metastases (BMets) to radiation therapy is poorly understood, with conflicting results regarding local control, overall survival, and treatment-related toxicity. This study aims to examine the role of Gamma Knife (GK) in managing cystic BMets. Methods and Materials: Volumetric analysis was conducted to measure tumor and edema volume at the time of GK and follow-up magnetic resonance imaging studies. Survival was described using the Kaplan-Meier method, and the cumulative incidence of progression was described using the Aalen-Johansen estimator. We evaluated the association of 4 variables with survival using Cox regression analysis. Results: Between 2016 and 2021, 54 patients with 83 cystic BMets were treated with GK at our institution. Lung cancer was the most common pathology (51.9%), followed by breast cancer (13.0%). The mean target volume was 2.7 cm3 (range, 0.1-39.0 cm3), and the mean edema volume was 13.9 cm3 (range, 0-165.5 cm3). The median prescription dose of single-fraction and fractionated GK was 20 Gy (range, 14-27.5 Gy). With a median follow-up of 8.9 months, the median survival time (MST) was 11.1 months, and the 1-year local control rate was 75.9%. Gamma Knife was associated with decreased tumor and edema volumes over time, although 68.5% of patients required steroids after GK. Patients whose tumors grew beyond baseline after GK received significantly more whole-brain radiation therapy (WBRT) before GK than those whose tumors declined after GK. Higher age at diagnosis of BMets and pre-GK systemic therapy were associated with worse survival, with an MST of 7.8 months in patients who received it compared with 23.3 months in those who did not. Conclusions: Pre-GK WBRT may select for BMets with increased radioresistance. This study highlights the ability of GK to control cystic BMets with the cost of high posttreatment steroid use.

Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases.

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan-Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.

Intricate Connection Among the Valsalva Maneuver, Gastrointestinal Tract, and Hemodynamics: A Rare Case Presentation.

A normal daily routine turns critical in seconds, and a biophysical maneuver that is instinctual leads to a rapid decline in a young healthy patient without any warning or precipitating signs. The Valsalva maneuver is a commonly used term for the act of bearing down that affects the vagus nerve, resulting in systemic changes primarily within the autonomic nervous system. This paper reviews a case in which a young man engaging in the Valsalva maneuver was later found unconscious and presented to the emergency department. Neuroimaging revealed a large middle cerebral artery stroke along with an undiagnosed temporal arachnoid cyst, without any significant historical medical records. The resulting course of this disease remained an interesting area of inquiry. This case highlights a rare but intricate interplay of several major physiological functions that collectively contribute to the unexpected demise of a young and healthy patient.

Case report: Fractional brain tumor burden magnetic resonance mapping to assess response to pulsed low-dose-rate radiotherapy in newly-diagnosed glioblastoma.

Background: Pulsed low-dose-rate radiotherapy (pLDR) is a commonly used reirradiation technique for recurrent glioma, but its upfront use with temozolomide (TMZ) following primary resection of glioblastoma is currently under investigation. Because standard magnetic resonance imaging (MRI) has limitations in differentiating treatment effect from tumor progression in such applications, perfusion-weighted MRI (PWI) can be used to create fractional tumor burden (FTB) maps to spatially distinguish active tumor from treatment-related effect. Methods: We performed PWI prior to re-resection in four patients with glioblastoma who had undergone upfront pLDR concurrent with TMZ who had radiographic suspicion for tumor progression at a median of 3 months (0-5 months or 0-143 days) post-pLDR. The pathologic diagnosis was compared to retrospectively-generated FTB maps. Results: The median patient age was 55.5 years (50-60 years). All were male with IDH-wild type (n=4) and O6-methylguanine-DNA methyltransferase (MGMT) hypermethylated (n=1) molecular markers. Pathologic diagnosis revealed treatment effect (n=2), a mixture of viable tumor and treatment effect (n=1), or viable tumor (n=1). In 3 of 4 cases, FTB maps were indicative of lesion volumes being comprised predominantly of treatment effect with enhancing tumor volumes comprised of a median of 6.8% vascular tumor (6.4-16.4%). Conclusion: This case series provides insight into the radiographic response to upfront pLDR and TMZ and the role for FTB mapping to distinguish tumor progression from treatment effect prior to redo-surgery and within 20 weeks post-radiation.

Utilization of Cerebral Blood Flow Study With Computed Tomography for Subdural Hematoma Management.

Stroke is among the leading causes of death in the United States, and with our aging population, it will remain a pertinent obstacle in the acute setting. While the field of neuroradiology has advanced tremendously over the years, particularly in improving what we can visualize and quantify, the phrase "time is brain" yet dominates acute stroke management. Optimizing diagnostic protocols for suspected stroke requires a careful balance of data acquisition and speed, as well as taking into account available resources. We present a case of a middle-aged patient with notable risk factors for stroke presenting to the emergency department with altered mental status and suspected stroke. Radiography revealed a large subacute subdural hematoma (SDH) with a mild mass effect on the surface of the brain. The evaluation was supplemented by a computed tomography (CT) and perfusion cerebral blood flow (CBF) study indicating cortical ischemia with penumbra from the SDH compression. SDH evacuation was successfully performed, and patient recovery was achieved within the intensive care unit (ICU). Rapid data acquisition via CBF with CT imaging is crucial for guiding treatment decisions for SDHs. While protocols for ischemic stroke are well-established, SDH protocols are not studied. Thus, we discuss the value of a multimodal CT imaging approach, including CBF studies, in SDH evaluation.

Hepatic Transplantation Raises Concern for Vascular Infrastructure Compromise: A Case Study of Debilitating Arteriovenous Malformation.

The post-operative realm for hepatic transplant patients presents many challenges, but of them all, we take a deeper dive into an increased risk of associated cerebrovascular events. Cerebrovascular diseases, such as cerebral arteriovenous malformation (AVM), are a leading cause of death following a liver transplant. We present a unique case of a liver transplant patient who presented with no brainstem reflexes three months into the post-transplant period. Imaging studies revealed a ruptured AVM within the foramen magnum and cervicomedullary junction, as well as substantial cerebral hemorrhage. While establishing the exact cause of the AVM is not as trivial as it may appear, side effects associated with post-transplantation management regimens and possible congenital factors do shed some light on notable considerations. Given the potential damage associated with ruptured AVMs, poor patient outcomes are unfortunately not as rare as one would hope. This case highlights a rare but highly possible occurrence for cerebrovascular complications, specifically AVM rupture linked to liver transplantation and the systemic changes associated with a procedure as invasive as liver transplantation.

The Aging Population Faces Increased Risk for Musculoskeletal Pathologies: The Problematic Atlas-Axis Instability.

Spinal cord injury (SCI), particularly of the traumatic variety, is a relatively common condition that disproportionately affects the elderly. Cases of SCI with nontraumatic etiologies in the geriatric population have increased over the last 20 years, however. Pannus formation, resulting from chronic inflammation of the spine, is one such etiology that may progress to SCI and potentially result in rapid neurological degeneration. Here we describe a case of an elderly woman who presented with a sudden onset of quadriplegia without a history of trauma. Radiography revealed upper cervical instability and fracture due to the presence of a large erosive pannus formation. Unfortunately, in the context of severe SCI, the reversibility of neurological decline is not always guaranteed. Additionally, surgical intervention is not always appropriate, especially among the elderly population, where medical management and end-of-life care are more often delivered.

A Hematological Travesty in the Setting of Alcohol Use Disorder and Liver Cirrhosis.

Excessive ethanol consumption is associated with an increased risk of developing health complications, especially in individuals with pre-existing thrombocytopenia and cirrhosis. Here, we describe a case of a patient with a history of alcoholic cirrhosis, hypertension, and thrombocytopenia, presenting with significant decline following an incidence of binge drinking. Radiography identified a large non-lobar intraparenchymal hemorrhage. However, due to severe thrombocytopenia that was unresponsive to platelet therapy, the possibility of pursuing any form of surgical intervention was negated. Surgical contraindication and a lack of response to subsequent medical management contributed to the family's decision to opt for conservative medical treatment and comfort care. This case showcases the potential for liver cirrhosis in the setting of chronic alcohol use disorder to pave the way for terminal intracerebral hemorrhage.

COVID-19-Induced Hypoxia With Accompanying Syncope Event and Traumatic Injury.

The Centers for Disease Control and Prevention identified the first case of the novel coronavirus disease 2019 (COVID-19) on January 21, 2020 in the United States. Since its arrival, the virus has caused widespread havoc on the nation as a whole as well as on all individuals. The coronavirus family is not new to the field of medicine. In fact, the viral pathogenicity dates back to the early 1960s, with more information on the respiratory preference and the ability to cause acute respiratory pathology coming later in 2002. The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causes a disease commonly referred to as COVID-19, which has a well documented course of severe respiratory pathology along with interesting systemic consequences that often complicate the clinical picture. This case presents an otherwise healthy young 35-year-old male who contracted the novel coronavirus, leading to multi-organ hypoxia and triggering a syncopal episode which resulted in physical trauma to the head leading to a minor subarachnoid hemorrhage.

Parahippocampal latrophilin-2 (ADGRL2) expression controls topographical presubiculum to entorhinal cortex circuit connectivity.

Brain circuits are comprised of distinct interconnected neurons that are assembled by synaptic recognition molecules presented by defined pre- and post-synaptic neurons. This cell-cell recognition process is mediated by varying cellular adhesion molecules, including the latrophilin family of adhesion G-protein-coupled receptors. Focusing on parahippocampal circuitry, we find that latrophilin-2 (Lphn2; gene symbol ADGRL2) is specifically enriched in interconnected subregions of the medial entorhinal cortex (MEC), presubiculum (PrS), and parasubiculum (PaS). Retrograde viral tracing from the Lphn2-enriched region of the MEC reveals unique topographical patterning of inputs arising from the PrS and PaS that mirrors Lphn2 expression. Using a Lphn2 conditional knockout mouse model, we find that deletion of MEC Lphn2 expression selectively impairs retrograde viral labeling of inputs arising from the ipsilateral PrS. Combined with analysis of Lphn2 expression within the MEC, this study reveals Lphn2 to be selectively expressed by defined cell types and essential for MEC-PrS circuit connectivity.

Not Everything Requires a Psychiatry Consult: Subdural Hematoma as a Cause of Transient Acute Quadriplegia.

While subdural hematoma (SDH) is a commonly encountered emergent pathology that is often in the setting of trauma, its ability to present with a wide variety of symptoms, or no symptoms at all, may delay diagnosis. SDH symptoms progress in a stepwise manner, potentially resulting in rapid neurological degeneration and can result in irreversible damage. Here we describe a case of an elderly woman with bilateral chronic SDH with mass effect who initially presented with severe headaches and a mild altered mental status, notably without a history of head trauma. Diagnosis was achieved through radiographic imaging. Within 24 hours, the patient suddenly became quadriplegic. Emergent bilateral evacuation of SDH was performed. Full neurological recovery of both arms and legs was achieved without delay, demonstrating the ability of this approach to reverse the development of acute quadriplegia attributed to SDH in such patients. Comprehensive and timely medical screening on initial presentation accompanied by radiographic studies, especially of patients presenting with altered mental status is crucial for identifying any underlying pathology, such as SDH. Altered mental status without head trauma is not always psychologic in nature and a psychiatric consult is insufficient in identifying lesions of the central nervous system (CNS). Altered mental status encompasses a broad differential diagnosis that seeks to find organic causes of altered state. While mortality from symptomatic chronic SDH is high, especially in the geriatric patient population, our findings support the position that rapid diagnosis and intervention to reverse neurological deterioration is an essential component of improving patient outcomes.

Acute Alcohol Intoxication With Accompanying Neurovascular Decline in Young Adults: A Sobering Case Series.

With an increase in both popularity and incidence, young adults continue to consume increasing amounts of ethanol-containing beverages at alarmingly short intervals, at times, far surpassing the threshold of binge drinking. From mixed beverages to party delights, high-concentration ethanol consumption continues to wreak havoc on the health of the younger generation. In this dual case series, we discuss two unique cases of alcohol-induced neurovascular compromise following episodes of high-volume ethanol consumption and acute neurovascular decline with varying outcomes. These cases highlight the hyperacute onset of severe pathology and the dire need for immediate medical intervention. While outcomes vary from case to case, our findings are congruent with those of vast medical literature that supports the consensus that immediate intervention to restore neurovascular flow is crucial for desired outcomes. At the end of the day, we cannot control the amount of alcohol that enters the mouths of our patients, but rather, we can educate them on safer practices while highlighting the risk and life-changing consequences of such risky behavior.

A Rare Form of Pott's Disease With Multifaceted Pathological Complications.

While tuberculosis is globally very prevalent, especially in the developing world, tuberculosis of the central nervous system (CNS) (including Pott's `disease) is an extremely rare occurrence for neurology/neurosurgery departments in the modern era. It is normally treated via rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy with the need for surgical intervention deemed by the presence of neurological deficiency or abscess, spinal instability, or significant kyphosis. Here we describe a case of an elderly woman with Pott's disease and a history of HIV presenting with neurologic deficiencies in both legs and an infected mass causing mid-thoracic compression and kyphotic deformity. The presence of a compromised immune system greatly complicates treatment and worsens outcomes. The patient underwent trans-thoracic corpectomy for decompression and mass removal. Spinal realignment was accomplished with an anterior graft, using the patient's rib, preceding posterior stabilization with instrumentation. Postoperatively, the patient received RIPE therapy. Despite a compromised immune system, the full neurologic function of both legs was restored in four months.

Iatrogenic Acute Ischemic Necrosis Due to Emergent Bleeding Control in Ventral Foramen Magnum Meningioma with Spinal Instability.

Meningiomas are the most common benign intracranial tumors. They often require surgical resection and postoperative radiation/chemotherapy based on their histologic grade. While necrosis caused by preoperative embolization and spontaneous tumor infarction is appreciated by pathologists when staging meningiomas, intraoperative events including large bore artery occlusion may also alter the histopathologic picture of a benign meningioma. Hence, they should be considered when signs of unexpected ischemia and necrosis are found, as these same phenotypes are also hallmarks of a higher-grade disease. We describe a case of a man with a large ventral foramen magnum meningioma who underwent temporary intraoperative occlusion of the vertebral artery, leading to ischemic tumor necrosis with abundant neutrophil invasion when the tumor was eventually examined histologically.

Gliomatosis Cerebri: A Unique Presentation with Accompanying Clinical Nuance.

Gliomatosis cerebri (GC) has classically been considered a rare malignancy with a poor prognosis and is developmentally unique from solid tumors. More recently, GC has become better understood as a phenotype along the spectrum of gliomas and, most importantly, not mutually exclusive from the more common presentation of a tumor mass. The following case report illustrates not only the implications of the ontogeny of gliomas in clinical practice but also the successes that can accompany the early recognition of such a disease. Here, we report the presentation of a solid temporal lobe glioma, which, on presentation, was disseminating along well-defined mesolimbic white matter tracts. Once properly diagnosed and managed, the patient remarkably proceeded to achieve an impressive outcome given the extent of her pathology.