Fatal subarachnoid hemorrhage after ventriculoperitoneal shunt placement to manage communicating hydrocephalus due to melanoma leptomeningeal disease

Leptomeningeal disease (LMD) is a rare, late complication of malignant cancers. In addition to causing significant neurosurgical morbidity, LMD can cause communicating hydrocephalus by disrupting the cerebrospinal fluid (CSF) outflow. We report an 18-year old female with a metastatic melanoma presenting with headaches, altered mental status, nausea, and vomiting three months following a craniotomy for a temporal melanoma brain metastasis that had extended into the lateral ventricle. A diagnosis of communicating hydrocephalus was made after brain MRI demonstrated ventriculomegaly, thus necessitating placement of a ventriculoperitoneal shunt. Despite an initial improvement in symptoms, the patient quickly deteriorated within six hours following shunt placement and expired following a diffuse subarachnoid hemorrhage. This represents an important complication to consider in patients with leptomeningeal metastases and warrants future exploration to determine incidence and etiology

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

The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease

Despite the reality that a death from cerebrovascular accident occurs every 3.5 min in the United States, there are few therapeutic options which are typically limited to a narrow window of opportunity in time for damage mitigation and recovery. Novel therapies have targeted pathological processes secondary to the initial insult, such as oxidative damage and peripheral inflammation. One of the greatest challenges to therapy is the frequently permanent damage within the CNS, attributed to a lack of sufficient neurogenesis. Thus, recent use of cell-based therapies for stroke have shown promising results. Unfortunately, stroke-induced inflammatory and oxidative damage limit the therapeutic potential of these stem cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated in endogenous antioxidant and anti-inflammatory activity, thus presenting an attractive target for novel therapeutics to enhance stem cell therapy and promote neurogenesis. This review assesses the current literature on the concomitant use of stem cell therapy and Nrf2 targeting via pharmaceutical and natural agents, highlighting the need to elucidate both upstream and downstream pathways in optimizing Nrf2 treatments in the setting of cerebrovascular disease

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

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

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\u27s 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

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

Percutaneous Vertebroplasty and Upper Instrumented Vertebra Cement Augmentation Reducing Early Proximal Junctional Kyphosis and Failure Rate in Adult Spinal Deformity: Case Series and Literature Review.

BACKGROUND AND OBJECTIVES: One of the risks involved after long-segment fusions includes proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). There are reported modalities to help prevent this, including 2-level prophylactic vertebroplasty. In this study, our goal was to report the largest series of prophylactic cement augmentation with upper instrumented vertebra (UIV) + 1 vertebroplasty and a literature review. METHODS: We retrospectively reviewed our long-segment fusions for adult spinal deformity from 2018 to 2022. The primary outcome measures included the incidence of PJK and PJF. Secondary outcomes included preoperative and postoperative Oswestry Disability Index, visual analog scale back and leg scores, surgical site infection, and plastic surgery closure assistance. In addition, we performed a literature review searching PubMed with a combination of the following words: cement augmentation, UIV + 1 vertebroplasty, adjacent segment disease, and prophylactic vertebroplasty. We found a total of 8 articles including 4 retrospective reviews, 2 prospective reviews, and 2 systematic reviews. The largest cohort of these articles included 39 patients with a PJK/PJF incidence of 28%/5%. RESULTS: Overall, we found 72 long-segment thoracolumbar fusion cases with prophylactic UIV cement augmentation with UIV + 1 vertebroplasty. The mean follow-up time was 17.25 months. Of these cases, 8 (11.1%) developed radiographic PJK and 3 (4.2%) required reoperation for PJF. Of the remaining 5 patients with radiographic PJK, 3 were clinically asymptomatic and treated conservatively and 2 had distal fractured rods that required only rod replacement. CONCLUSION: In this study, we report the largest series of patients with prophylactic percutaneous vertebroplasty and UIV cement augmentation with a low PJK and PJF incidence of 11.1% and 4.2%, respectively, compared with previously reported literature. Surgeons who regularly perform long-segment fusions for adult spinal deformity can consider this in their armamentarium when using methods to prevent adjacent segment disease because it is an effective modality in reducing early PJK and PJF that can often result in revision surgery

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