The identification of a Distinct Astrocyte Subtype that Diminishes in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the presence of two hallmark pathologies: the accumulation of Amyloid beta (Aß) and tau proteins in the brain. There is a growing body of evidence suggesting that astrocytes, a type of glial cell in the brain, play crucial roles in clearing Aß and binding to tau proteins. However, due to the heterogeneity of astrocytes, the specific roles of different astrocyte subpopulations in response to Aß and tau remain unclear. To enhance the understanding of astrocyte subpopulations in AD, we investigated astrocyte lineage cells based on single-nuclei transcriptomic data obtained from both human and mouse samples. We characterized the diversity of astrocytes and identified global and subpopulation-specific transcriptomic changes between control and AD samples. Our findings revealed the existence of a specific astrocyte subpopulation marked by low levels of GFAP and the presence of AQP4 and CD63 expression, which showed functional enrichment in Aß clearance and tau protein binding, and diminished in AD. We verified this type of astrocytes in mouse models and in AD patient brain samples. Furthermore, our research also unveiled significant alterations of the ligand-receptor interactions between astrocytes and other cell types. These changes underscore the complex interplay between astrocytes and neighboring cells in the context of AD. Overall, our work gives insights into astrocyte heterogeneity in the context of AD and reveals a distinct astrocyte subpopulation that holds potential for therapeutic interventions in AD. Targeting specific astrocyte subpopulations may offer new avenues for the development of novel treatments for AD.

Characterization of the influence of spinopelvic parameters on thoracolumbar trauma.

OBJECTIVE: The current Roussouly classification identifies four groups of "normal" sagittal spine morphology, which has greatly expanded the understanding of normal heterogeneity of the spine. While there has been extensive characterization of the influence of spinopelvic parameters on outcomes after degenerative spine surgery, the influence of spinopelvic parameters on thoracolumbar trauma has yet to be described. The goal of this study was to determine if spinopelvic parameters and global spine morphology influence fracture location, fracture morphology, and rate of neurological deficit in the setting of thoracolumbar trauma. METHODS: Of 2896 patients reviewed in the authors' institutional spine database between January 2014 and April 2020 with an ICD-9/10 diagnosis of thoracolumbar trauma, 514 met the inclusion criteria of acute thoracolumbar fracture on CT and visible femoral heads on sagittal CT. Pelvic incidence (PI) was calculated on sagittal CT. Demographic and clinical data including age, sex, BMI, smoking status, concomitant cervical fracture, mechanism of injury, major fracture location, neurological deficit, AO Spine thoracolumbar injury classification, and management type (operative vs nonoperative) were collected. Patients were stratified into high-PI (≥ 50°) and low-PI (< 50°) groups. RESULTS: Patients with high PI had a lower incidence of fractures in the lower lumbar spine (below L2) compared with patients with low PI (16% vs 8%, p < 0.01). The last lordotic vertebrae were observed between T10 and L4, and of fractures that occurred at these levels, 75% were at the last lordotic vertebrae. Fall from height was the most common cause of neurological deficit, accounting for 47%. Of the patients presenting with a fall from height, AO Spine type B distraction injuries were more common in the high-PI group (41% vs 18%, p = 0.01). Similarly, within the same subgroup, AO Spine type A compression injuries were more common in the low-PI group (73% vs 53%, p = 0.01). CONCLUSIONS: Spinopelvic parameters and sagittal balance influence the location and morphology of thoracolumbar fractures. Fractures of the thoracolumbar junction are strongly associated with the inflection point, which is defined by sagittal alignment. While the importance of considering sagittal balance is known for decision-making in degenerative spinal pathology, further studies are required to determine if spinopelvic parameters and sagittal balance should play a role in the decision-making for management of thoracolumbar fractures.

Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury.

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.

Intraoperative massive pulmonary embolism during revision lumbar fusion managed with extracorporeal membrane oxygenation.

STUDY DESIGN: Case report. PURPOSE: The purpose of this case report is to illustrate the utility of ECMO as possible treatment in the management of perioperative massive pulmonary embolism (PE) during spine surgery. We present a case report of an intra-operative massive PE managed with ECMO and review relevant literature of perioperative massive PE. Treatment poses substantial risk given the need for anticoagulation. ECMO has not previously been described in the management of this condition in spine surgery. METHODS: The patient is a 75-year-old male with hypertension, diabetes mellitus type II, chronic obstructive pulmonary disease, and prior cerebral infarction with minimal residual deficits who presented for Lumbar 2-Sacral 1 (L2-S1) revision posterior spinal decompression and fusion with L3-4 TLIF (Transforaminal Lumbar Interbody Fusion). The operation was routine until removing him from the operative table when he suffered a massive pulmonary embolism. RESULTS: The patient became extremely unstable hemodynamically requiring massive doses of three vasopressors. He was too unstable for additional imaging or to transport for mechanical thrombectomy so with the guidance of our cardiologist we initiated ECMO. The patient ultimately recovered well and was discharged from the hospital at his neurological baseline and preserved cardiac function. CONCLUSION: ECMO is a viable option for management of acute perioperative massive pulmonary embolism when less invasive treatments are not sufficient.

Case report of hyperacute edema and cavitation following deep brain stimulation lead implantation.

BACKGROUND: Postoperative cerebral edema around a deep brain stimulation (DBS) electrode is an uncommonly reported complication of DBS surgery. The etiology of this remains unknown, and the presentation is highly variable; however, the patients generally report a good outcome. CASE DESCRIPTION: Here, we report an unusual presentation of postoperative edema in a 66-year-old female who has bilateral dentatorubrothalamic tract (specifically, the ventral intermediate nucleus) DBS for a mixed type tremor disorder. Initial postoperative computed tomography (CT) was unremarkable and the patient was admitted for observation. She declined later on postoperative day (POD) 1 and became lethargic. Stat head CT scan performed revealed marked left-sided peri-lead edema extending into the centrum semiovale with cystic cavitation, and trace right-sided edema. On POD 2, the patient was alert, but with global aphasia, right-sided neglect, and a plegic right upper extremity. Corticosteroids were started and a complete infectious workup was unremarkable. She was intubated and ultimately required a tracheostomy and percutaneous gastrostomy tube. She returned to the clinic 3 months postoperatively completely recovered and ready for battery implantation. CONCLUSION: While this is an unusual presentation of cerebral edema following DBS placement, ultimately, the outcome was good similar to other reported cases. Supportive care and corticosteroids remain the treatment of choice for this phenomenon.

Management of Venous Sinus-Related Epidural Hematomas.

BACKGROUND: Epidural hematomas (EDHs) involving the venous sinuses are uncommon and carry the risk of hemorrhage or venous infarction. We report the largest case series for superior sagittal sinus- and transverse sinus-related EDHs including surgical and nonsurgical management. We compare our findings to the relevant literature. METHODS: A retrospective review of the EDH cases at our center was performed from 2013-2018. Patients were analyzed by surgical versus conservative management, outcomes, and complications. RESULTS: Of the 268 EDH patients identified, 32 involved the venous sinuses (23 supratentorial and 9 infratentorial). Ten of the patients had surgery, and 22 were managed conservatively. No surgical complications occurred, and all had a Glasgow Outcome Scale score of 5 at follow-up. All of the nonsurgical patients had a Glasgow Outcome Scale score of 4 or 5 at follow-up except for 1 patient with prior disability. The literature search resulted in 39 infratentorial and 47 supratentorial EDHs involving venous sinuses. CONCLUSIONS: Surgical and nonsurgical management of EDHs involving the venous sinuses are both viable options with good outcomes. Surgical intervention is based on location, size, neurologic examination, expansion on serial imaging, and vascular imaging findings. Surgery has the potential for significant complications, but all surgical patients in our series had good outcomes at follow-up. Similarly, nonsurgically managed patients had good outcomes and our overall series demonstrates better outcomes with fewer complications than other similar series in the literature.

The Evolution of the Neurosurgical Treatment of Ischemic Stroke.

The neurosurgical approach to the management of ischemic stroke has evolved dramatically over the past century with the bulk of these changes occurring over the past 25 years. With recent advances in technology and continued refinements in neurosurgical techniques there has been significant improvement to the safety and efficacy of our treatment options. The focus of this article will be to review the historical and recent reports in the literature related to revascularization techniques.

Emerging role of extracellular vesicles in musculoskeletal diseases.

Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies. Thus, EVs appear to be involved in a number of degenerative conditions that impact the musculoskeletal system, indicating that the musculoskeletal system is an excellent model for investigating the role of EVs in tissue maintenance and repair. This review highlights the role of EVs in bone, skeletal muscle, and joint health, including both normal tissue metabolism as well as tissue injury repair and regeneration. A consistent theme that emerges from study of musculoskeletal EVs is that various miRNAs appear to mediate a number of key pathological processes. These findings point to a potential therapeutic opportunity to target EV-derived miRNAs as a strategy for improving musculoskeletal function.

Gamma Knife Radiosurgery for Trigeminal Neuralgia Caused by a Cavernous Malformation: Case Report and Literature Review.

OBJECTIVE: Trigeminal neuralgia (TN) related to a brainstem cavernous malformation (CM) is a rare entity. We present the first radiosurgical management of a patient with TN secondary to a CM. CLINICAL PRESENTATION: An 80-year-old female presented with a 33-year history of progressively severe TN refractory to medications. Imaging confirmed a solitary CM located at the pontine dorsal root entry zone of cranial nerve 5. TREATMENT: Stereotactic radiosurgery of the trigeminal nerve was performed using the Leksell gamma knife. A single 4-mm isocenter of radiation was focused on the trigeminal nerve and a maximum dose of 80 Gy (40 Gy at the 50% isodose line) was delivered to the nerve. RESULTS: At 1 year, the patient noted that the severe pain attacks had been reduced by 75%, although a background lingering discomfort persisted. Pain suppression medications had been significantly reduced to lamotrigine 100 mg twice daily. Her preoperative distribution of sensory dysfunction mildly increased. CONCLUSION: For medically refractory TN related to a CM, radiosurgery of the afferent nerve may ameliorate pain without a major decrease in sensation. The more than 30-year history of pain in our patient may have reduced the chance of more significant pain relief.

Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity in the US population. Extracellular vesicles (EVs), including exosomes and microvesicles, are now recognized to play important roles in cell-to-cell communication by transporting various proteins, microRNAs (miRNAs), and mRNAs. EV-derived proteins and miRNAs impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of both OA and RA. Some of the processes by which these membrane-bound vesicles can alter joint tissue include extracellular matrix degradation, cell-to-cell communication, modulation of inflammation, angiogenesis, and antigen presentation. For example, EVs from IL-1ß-stimulated fibroblast-like synoviocytes have been shown to induce osteoarthritic changes in chondrocytes. RA models have shown that EVs stimulated with inflammatory cytokines are capable of inducing apoptosis resistance in T cells, presenting antigen to T cells, and causing extracellular damage with matrix-degrading enzymes. EVs derived from rheumatoid models have also been shown to induce secretion of COX-2 and stimulate angiogenesis. Additionally, there is evidence that synovium-derived EVs may be promising biomarkers of disease in both OA and RA. The characterization of EVs in the joint space has also opened up the possibility for delivery of small molecules. This article reviews current knowledge on the role of EVs in both RA and OA, and their potential role as therapeutic targets for modulation of these debilitating diseases.