Three-column osteotomy in long constructs has lower rates of proximal junctional kyphosis and better restoration of lumbar lordosis than anterior column realignment.

PURPOSE: Three-column osteotomies (TCOs) and minimally invasive techniques such as anterior column realignment (ACR) are powerful tools used to restore lumbar lordosis and sagittal alignment. We aimed to appraise the differences in construct and global spinal stability between TCOs and ACRs in long constructs. METHODS: We identified consecutive patients who underwent a long construct lumbar or thoracolumbar fusion between January 2016 and November 2021. "Long construct" was any construct where the uppermost instrumented vertebra (UIV) was L2 or higher and the lowermost instrumented vertebra (LIV) was in the sacrum or ileum. RESULTS: We identified 69 patients; 14 (20.3%) developed PJK throughout follow-up (mean 838 days). Female patients were less likely to suffer PJK (p = 0.009). TCO was more associated with open (versus minimally invasive) screw/rod placement, greater number of levels, higher UIV, greater rate of instrumentation to the ilium, and posterior (versus anterior) L5-S1 interbody placement versus the ACR cohort (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, respectively). Patients who developed PJK were more likely to have undergone ACR (12 (32.4%) versus 2 (6.3%, p = 0.007)). The TCO cohort had better improvement of lumbar lordosis despite similar preoperative measurements (ACR: 16.8 ± 3.78°, TCO: 23.0 ± 5.02°, p = 0.046). Pelvic incidence-lumbar lordosis mismatch had greater improvement after TCO (ACR: 14.8 ± 4.02°, TCO: 21.5 ± 5.10°, p = 0.042). By multivariate analysis, ACR increased odds of PJK by 6.1-times (95% confidence interval: 1.20-31.2, p = 0.29). CONCLUSION: In patients with long constructs who undergo ACR or TCO, we experienced a 20% rate of PJK. TCO decreased PJK 6.1-times compared to ACR. TCO demonstrated greater improvement of some spinopelvic parameters.

Nasofrontal meningiomas: retrospective series and review of literature.

INTRODUCTION: Lesions affecting the anterior skull base and involving the paranasal sinuses (PNS), nasal cavity (NC), and orbit are infrequent and include predominantly a wide variety of sinonasal malignancies. Less than 3% of intracranial meningiomas extend extracranially and involve PNS and NC. Given their relatively low incidence, little is known about the treatment outcome of this subset of meningiomas. METHODS: Systematic literature and retrospective review of own institutional series of midline anterior skull base meningiomas with significant PNS and NC involvement were performed. RESULTS: Overall, 21 patients-16 in the literature review group and 5 of our institutional series-were included. Eleven (52.4%) patients had had a prior surgery for midline anterior skull base meningioma. Of patients having reported WHO grade, two were WHO II. Gross total resection was achieved in 16 (76.2%) of patients, utilizing solely transcranial approach in 15 patients, combined endoscopic and transcranial in five patients and purely endoscopic in one patient. Postoperative radiotherapy was administered in three (14.3%) patients, all after total resection via transcranial route, without a history of prior treatment. A postoperative cerebrospinal fluid leak was reported in four (10%) patients, requiring surgical repair in two. There were no reports of postoperative meningitis. No neurological complications were observed except of a reported worsening of vision in one patient. CONCLUSION: Midline anterior skull base meningiomas infrequently extend significantly into the PNS and NC. Despite their significant involvement, along with concomitant involvement of orbit, gross total resection is possible in the majority of cases with low morbidity using either purely transcranial or combined endoscopic/transcranial approach.

Neuroinflammation, Stem Cells, and Stroke.

Stroke remains a significant unmet clinical need with few treatment options that have a very narrow therapeutic window, thereby causing massive mortality and morbidity in the United States and around the world. Accordingly, finding safe and effective novel treatments with a wider therapeutic window stands as an urgent need in stroke. The progressive inflammation that occurs centrally and peripherally after stroke serves as a unique therapeutic target to retard and even halt the secondary cell death. Stem cell therapy represents a potent approach that can diminish inflammation in both the stroke brain and periphery (eg, spleen), advancing a paradigm shift from a traditionally brain-focused therapy to treating stroke as a neurological disorder with a significant peripheral pathology. The purpose of this review article is to highlight the inflammation-mediated secondary cell death that plagues both brain and spleen in stroke and to evaluate the therapeutic potential of stem cell therapy in dampening these inflammatory responses.

Sequestration of Inflammation in Parkinson's Disease via Stem Cell Therapy.

Parkinson's disease is the second most common neurodegenerative disease. Insidious and progressive, this disorder is secondary to the gradual loss of dopaminergic signaling and worsening neuroinflammation, affecting patients' motor capabilities. Gold standard treatment includes exogenous dopamine therapy in the form of levodopa-carbidopa, or surgical intervention with a deep brain stimulator to the subcortical basal ganglia. Unfortunately, these therapies may ironically exacerbate the already pro-inflammatory environment. An alternative approach may involve cell-based therapies. Cell-based therapies, whether endogenous or exogenous, often have anti-inflammatory properties. Alternative strategies, such as exercise and diet modifications, also appear to play a significant role in facilitating endogenous and exogenous stem cells to induce an anti-inflammatory response, and thus are of unique interest to neuroinflammatory conditions including Parkinson's disease. Treating patients with current gold standard therapeutics and adding adjuvant stem cell therapy, alongside the aforementioned lifestyle modifications, may ideally sequester inflammation and thus halt neurodegeneration.

Probing Interleukin-6 in Stroke Pathology and Neural Stem Cell Transplantation.

Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3-4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction size, improve neurobehavioral performance, and reduce inflammatory agents including interleukins. Typically, interleukin-6 (IL-6) is regarded as proinflammatory, and thus, preclinical studies often discuss it as beneficial for neurological recuperation when stem cells reduce IL-6's expression. However, some studies have also demonstrated neurological benefit with upregulation of IL-6 or preconditioning of stem cells with IL-6. This review specifically focuses on stem cells and IL-6, and their occasionally disparate, occasionally synergistic roles in the setting of ischemic cerebrovascular insults.

Minor Changes for a Major Impact: A Review of Epigenetic Modifications in Cell-Based Therapies for Stroke.

Epigenetic changes in stroke may revolutionize cell-based therapies aimed at reducing ischemic stroke risk and damage. Epigenetic changes are a novel therapeutic target due to their specificity and potential for reversal. Possible targets for epigenetic modification include DNA methylation and demethylation, post-translational histone modification, and the actions of non-coding RNAs such as microRNAs. Many of these epigenetic modifications have been reported to modulate atherosclerosis development and progression, ultimately contributing to stroke pathogenesis. Furthermore, epigenetics may play a major role in inflammatory responses following stroke. Stem cells for stroke have demonstrated safety in clinical trials for stroke and show therapeutic benefit in pre-clinical studies. The efficacy of these cell-based interventions may be amplified with adjunctive epigenetic modifications. This review advances the role of epigenetics in atherosclerosis and inflammation in the context of stroke, followed by a discussion on current stem cell studies modulating epigenetics to ameliorate stroke damage.

Chiari malformation presenting with subarachnoid hemorrhage: a case report.

Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM.

Intraoperative View of a Multinodal, Paralysis-Inducing Spinal Melanocytoma: Case Report and Literature Review.

Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year.1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules.14.

No change in network connectivity measurements between separate rsfMRI acquisition times.

The role of resting state functional MRI (rsfMRI) is increasing in the field of epilepsy surgery because it is possible to interpolate network connectivity patterns across the brain with a high degree of spatial resolution. Prior studies have shown that by rsfMRI with scalp electroencephalography (EEG), an epileptogenic network can be modeled and visualized with characteristic patterns of connectivity that are relevant to both seizure-related and neuropsychological outcomes after surgery. The aim of this study is to show that a 5-min acquisition time provides reproducible results related to the relevant connectivity metrics when compared to a separately acquired 5-min scan. Fourteen separate rsfMRI sessions from ten different patients were used for comparison, comprised of patients with temporal lobe epilepsy both pre- and post-operation. Results showed that there was no significant difference in any of the connectivity metrics when comparing both 5-min scans to each other. These data support the continued use of a 5-min scan for epileptogenic network modeling in future studies because the inter-scan variability is sufficiently low as not to alter the output metrics characterizing the network connectivity.

The central role of peripheral inflammation in ischemic stroke.

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to the brain. To this end, peripheral inflammation has emerged as an equally potent contributor to the onset and progression of stroke secondary cell death. Here, we review novel concepts on peripheral organs displaying robust inflammatory response to stroke. These inflammation-plagued organs include the spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, and adrenal glands, likely converging their inflammatory effects through B and T-cells. Recognizing the significant impact of this systemic inflammation, we also discuss innovative stroke therapeutics directed at sequestration of peripheral inflammation. This review paper challenges the paradigm of a brain-centered disease pathology and treatment and offers a peripheral approach to our stroke understanding.

Stem Cells Attenuate the Inflammation Crosstalk Between Ischemic Stroke and Multiple Sclerosis: A Review.

The immense neuroinflammation induced by multiple sclerosis (MS) promotes a favorable environment for ischemic stroke (IS) development, making IS a deadly complication of MS. The overlapping inflammation in MS and IS is a prelude to the vascular pathology, and an inherent cell death mechanism that exacerbates neurovascular unit (NVU) impairment in the disease progression. Despite this consequence, no therapies focus on reducing IS incidence in patients with MS. To this end, the preclinical and clinical evidence we review here argues for cell-based regenerative medicine that will augment the NVU dysfunction and inflammation to ameliorate IS risk.

Mitochondria in Cell-Based Therapy for Stroke.

Despite a relatively developed understanding of the pathophysiology underlying primary and secondary mechanisms of cell death after ischemic injury, there are few established treatments to improve stroke prognoses. A major contributor to secondary cell death is mitochondrial dysfunction. Recent advancements in cell-based therapies suggest that stem cells may be revolutionary for treating stroke, and the reestablishment of mitochondrial integrity may underlie these therapeutic benefits. In fact, functioning mitochondria are imperative for reducing oxidative damage and neuroinflammation following stroke and reperfusion injury. In this review, we will discuss the role of mitochondria in establishing the anti-oxidative effects of stem cell therapies for stroke.

Contemplating IL-6, a double-edged sword cytokine: Which side to use for stroke pathology?

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points.

Getting the guts to expand stroke treatment: The potential for microbiome targeted therapies.

AIMS: This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke. DISCUSSION: Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke. Additionally, hyperglycemic conditions may play a significant role in worsening stroke outcomes due to microbiome dysbiosis. CONCLUSION: Recent research has illuminated the vital role of the GBA in propagating poor clinical outcomes, such as hemorrhagic transformation, following ischemic stroke. Considering this detrimental consequence of stroke, and the apparent role of the GBA role, future therapeutics should aim to mitigate this peripheral contribution to stroke complications.

Factors associated with hardware failure after lateral thoracolumbar fusions - A ten year case series.

OBJECTIVE: Thoracolumbar lateral interbody fusions (tLLIF) are one tool in the spine surgeon's toolbox to indirectly decompress neuroforamina while also improving segmental lordosis in a biomechanically distinct manner from posterior fusions. When part of a concomitant posterior construct, hardware failure (HF), sometimes requiring revision surgery, can occur. We sought to study the relationship between tLLIF and HF. METHODS: We conducted a retrospective study on consecutive patents who underwent tLLIF at a single academic center between January 2012 and December 2021 by seven unique neurosurgeons. Patients were excluded if they had no posterior instrumentation within their construct or if they had less than six months of follow-up. Hardware failure was defined as screw breakage or rod fracture seen on postoperative imaging. RESULTS: 232 patients were identified; 6 (2.6 %) developed HF throughout a mean follow-up of 1182 days (range =748-1647 days). Adjacent segment disease was the most common pathology addressed (75 patients (32.3 %)). The amount of posterior instrumentation both in the surgery in question and in the total construct were significantly higher in the HF cohort (4.33 ± 1.52 levels, 5.83 ± 3.36 levels) versus the non-HF cohort (2.08 ± 0.296 levels, p = 0.014; 2.86 ± 0.316 levels, p = 0.003, respectively). The number of interbody devices added in the index surgery and in the entire construct were both significantly higher in the HF cohort (3.33 ± 0.666 interbody devices, 3.33 ± 0.666 devices) than in the non-HF cohort (1.88 ± 0.152 interbody devices, p = 0.002; 2.31 ± 0.158 devices, p = 0.036, respectively). Higher amounts of lateral levels of fusion approached significance for association with HF (HF: 2.67 ± 0.844 levels, no HF: 1.73 ± 1.26 levels, p = 0.076). On multivariate analysis, only the number of interbody devices added in the index surgery was predictive of HF (Odds ratio=2.3, 95 % confidence interval=1.25-4.23, p = 0.007). CONCLUSION: Greater levels of posterior fusion, and greater numbers of interbody devices in an index surgery and in a construct as a whole, were associated with higher rates of HF in our cohort of patients with tLLIF. Greater numbers of lateral segments fused in this population may also be related to HF.

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons.

Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces "super" mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells.

IL-6 in spinal cord injury: could immunomodulation replace immunosuppression in the management of acute traumatic spinal cord injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Vein of Galen Malformations in adults.

OBJECTIVE: Vein of Galen Malformations (VoGM) are rare vascular malformations, typically seen in pediatric age groups. Even more rarely, VoGM's may be seen later in adulthood. In this case report and systematic review, we provide a thorough description of the current literature as well as provide a case example exploring the diagnosis, imaging, treatment, and management of VoGM in adults. METHODS: In accordance with PRISMA guidelines, we performed a systematic literature search for all relevant cases and case series of VoGM in adult patients. The reference list of all articles were reviewed for additional relevant cases. Articles were included if they described a VoGM of a patient over the age of 18 years old and published in English. 149 articles were originally identified and 26 described cases met our inclusion criteria. RESULTS: In our literature review we found 26 patients that met our inclusion criteria. We found 14 male patients and 12 female patients. The mean age at presentation was 37.2 years (median=34 years, SD= 13.6 years). The most common presenting symptoms of patient were headache (n = 9), seizure (n = 6), and vomiting (n = 4). Of the 12 cases which clearly reported the subtype of VoGM, the choroidal type was more frequently seen (n = 10) compared to the mural type (n = 2). In 3 patients, the VoGM was thrombosed at time of diagnosis. Of the 26 patients, endovascular treatment was performed most frequently (n = 8) but some received microsurgical treatment (n = 4) or were treated conservatively (n = 6). Other treatment modalities included (ventriculoperitoneal shunt, ventriculostomy) (n = 5). In 3 cases treatment was not specified. In comparison to VoGM seen in pediatric or neonatal populations, VoGM in adults generally resulted in more favorable outcomes with only 2 patients reported to have passed away following treatment. CONCLUSION: VoGM remains a rare finding amongst the adult population. Hence, we described the clinical presentation, treatment modalities, and outcomes of the cases described in the English literature. Perhaps due to the rate of thrombosis and the unique angioarchitecture seen in adult VoGM patients, outcomes were generally more favorable than those described in the literature in pediatric or neonate VoGM patients.

Stem Cells: Recent Developments Redefining Epilepsy Therapy.

The field of stem cell therapy is growing rapidly and hopes to offer an alternative solution to diseases that are historically treated medically or surgically. One such focus of research is the treatment of medically refractory epilepsy, which is traditionally approached from a surgical or interventional standpoint. Research shows that stem cell transplantation has potential to offer significant benefits to the epilepsy patient by reducing seizure frequency, intensity, and neurological deficits that often result from the condition. This review explores the basic science progress made on the topic of stem cells and epilepsy by focusing on experiments using animal models and highlighting the most recent developments from the last 4 years.