Intramedullary spinal cord abscess as postoperative complication: A case report.

Background: Intramedullary spinal cord abscesses (ISCA) can result in high morbidity and mortality if not treated in a timely manner. The incidence and outcomes of postsurgical ISCA are unknown. We present a case of a 52-year-old male patient with neurofibromatosis type 1 who developed an intramedullary spinal cord abscess after a previous resection of a cervical intradural, extramedullary neurofibroma. Case Description: A 52-year-old male with a history of neurofibromatosis type 1 had previously undergone multiple resections of cervical intradural, extramedullary neurofibromas with internal stabilization. Sixteen months after his initial surgery, he developed acute-onset interscapular pain with bilateral lower extremity pain and left hemi-body weakness. Magnetic resonance imaging (MRI) of the cervical spine demonstrated an enlarging contrast-enhancing intramedullary lesion. Surgical exploration and evacuation of the lesion were completed. Intramedullary cultures confirmed a Serratia marcescens abscess. After abscess evacuation and intravenous antibiotics, the patient's symptoms resolved. Conclusion: Given the potential for permanent neurologic damage and loss of independence with intramedullary spinal cord abscess, we advocate that clinicians maintain a high index of suspicion in the postsurgical patient. Diagnostic imaging through contrasted MRI or computed tomography myelogram should be obtained, and prompt intervention, including evacuation and/or antibiotics, should be implemented for the best chance of a favorable outcome.

Improvement in Hearing Loss Following Posterior Fossa Arachnoid Cyst Fenestration: A Case Study.

Arachnoid cysts are abnormal intradural collections of cerebrospinal fluid. For posterior fossa arachnoid cysts (PFACs), symptoms vary greatly, often relating to cranial nerve impingement and/or hydrocephalus. Literature on long-term symptomatic and radiographic follow-up of PFACs is lacking. This case study describes a 32-year-old man who presented with headaches and left-sided hearing loss and was found to have a large left-sided cerebellopontine angle arachnoid cyst with syrinx and ventriculomegaly. After PFAC fenestration and excision, his headaches resolved and his hearing markedly improved. At the one-year postoperative evaluation, symptom improvement persisted, and MRI demonstrated a stable decreased cyst and near-complete resolution of his syrinx.

Mixed reality in neurosurgery: redefining the paradigm for arteriovenous malformation planning and navigation to improve patient outcomes.

OBJECTIVE: Brain arteriovenous malformations (AVMs) present significant challenges in neurosurgery, requiring detailed planning and execution. In this study, the authors aimed to evaluate the efficacy of mixed reality (MxR), a synergistic application of virtual reality (VR) and augmented reality (AR), in the surgical management of AVMs. METHODS: A retrospective review was conducted on 10 patients who underwent AVM resection between 2021 and 2023. Preoperative planning used patient-specific 360° VR models, while intraoperative guidance used AR markers for targeted disconnection of arterial feeders. Data were analyzed for surgical duration, blood loss, and postoperative outcomes, stratified by Spetzler-Martin (SM) and supplemented Spetzler-Martin (Supp-SM) grades. RESULTS: In 10 patients with cerebral AVMs, MxR significantly facilitated the identification of 21 arterial feeders, including challenging deep feeders. MxR-assisted surgeries demonstrated efficient identification and disconnection of arterial feeders, contributing to precise AVM resection. The mean surgical duration was approximately 5 hours 11 minutes, with a mean intraoperative blood loss of 507.5 ml. Statistically significant variations in surgical duration and blood loss were observed based on SM and supplemented Supp-SM grades. Two patients experienced worsened postoperative neurological deficits, underscoring the inherent risks of AVM surgeries. The marked difference in hospital stays between patients with ruptured and those with unruptured AVMs, particularly for SM grade III, highlights the significant impact of rupture status on postoperative recovery. CONCLUSIONS: In this study, the authors delineated a novel paradigm using MxR for the surgical intervention of AVMs. Using 3D VR for preoperative planning and AR for intraoperative guidance, they achieved unparalleled precision and efficiency in targeting deep arterial feeders. While the results are promising, larger studies are needed to further validate this approach.

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.

Identifying the Target Traumatic Brain Injury Population for Hyperbaric Oxygen Therapy.

Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds. HBOT consists of 100% oxygen administration, usually between 1.5 and 3 atm and has been found to increase brain oxygenation levels after hypoxia in addition to decreasing levels of inflammation, apoptosis, intracranial pressure, and edema, reducing subsequent secondary injury. The following review examines recent preclinical and clinical studies on HBOT in the context of TBI with a focus on contributing mechanisms and clinical potential. Several preclinical studies have identified pathways, such as TLR4/NF-kB, that are affected by HBOT and contribute to its therapeutic effect. Thus far, the mechanisms mediating HBOT treatment have yet to be fully elucidated and are of interest to researchers. Nonetheless, multiple clinical studies presented in this review have examined the safety of HBOT and demonstrated the improved neurological function of TBI patients after HBOT, deeming it a promising avenue for treatment.

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.

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.

Hepatocyte growth factor mimetic confers protection from aminoglycoside-induced hair cell death in vitro.

Loss of sensory hair cells from exposure to certain licit drugs, such as aminoglycoside antibiotics, can result in permanent hearing damage. Exogenous application of the neurotrophic molecule hepatocyte growth factor (HGF) promotes neuronal cell survival in a variety of contexts, including protecting hair cells from aminoglycoside ototoxicity. HGF itself is not an ideal therapeutic due to a short half-life and limited blood-brain barrier permeability. MM-201 is a chemically stable, blood-brain barrier permeable, synthetic HGF mimetic that serves as a functional ligand to activate the HGF receptor and its downstream signaling cascade. We previously demonstrated that MM-201 robustly protects zebrafish lateral line hair cells from aminoglycoside ototoxicity. Here, we examined the ability of MM-201 to protect mammalian sensory hair cells from aminoglycoside damage to further evaluate MM-201's clinical potential. We found that MM-201 exhibited dose-dependent protection from neomycin and gentamicin ototoxicity in mature mouse utricular explants. MM-201's protection was reduced following inhibition of mTOR, a downstream target of HGF receptor activation, implicating the activation of endogenous intracellular substrates by MM-201 as critical for the observed protection. We then asked if MM-201 altered the bactericidal properties of aminoglycosides. Using either plate or liquid growth assays we found that MM-201 did not alter the bactericidal efficacy of aminoglycoside antibiotics at therapeutically relevant concentrations. We therefore assessed the protective capacity of MM-201 in an in vivo mouse model of kanamycin ototoxicity. In contrast to our in vitro data, MM-201 did not attenuate kanamycin ototoxicity in vivo. Further, we found that MM-201 was ototoxic to mice across the dose range tested here. These data suggest species- and tissue-specific differences in otoprotective capacity. Next generation HGF mimetics are in clinical trials for neurodegenerative diseases and show excellent safety profiles, but neither preclinical studies nor clinical trials have examined hearing loss as a potential consequence of pharmaceutical HGF activation. Further research is needed to determine the consequences of systemic MM-201 application on the auditory system.

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.

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.

Attenuation of amyotrophic lateral sclerosis via stem cell and extracellular vesicle therapy: An updated review.

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration. Though typically idiopathic, familial forms of ALS are commonly comprised of a superoxide dismutase 1 (SOD1) mutation. Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions. Therapies are sparse; those that exist on the market extend life minimally, thus driving the demand for research to identify novel therapeutics. Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials. The underlying mechanism for stem cell therapy presents an exciting venue for research investigations. Most notably, the paracrine actions of stem cell-derived extracellular vesicles (EVs) have been suggested as a potent mitigating factor. This literature review focuses on the most recent preclinical research investigating cell-free methods for treating ALS. Various avenues are being explored, differing on the EV contents (protein, microRNA, etc.) and on the cell target (astrocyte, endothelial cell, motor neuron-like cells, etc.), and both molecular and behavioral outcomes are being examined. Unfortunately, EVs may also play a role in propagating ALS pathology. Nonetheless, the overarching goal remains clear; to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.

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.

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.

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.

Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death.

Hearing loss is the third most common chronic health condition in the United States and largely results from damage to sensory hair cells. Major causes of hair cell damage include aging, noise exposure, and medications such as aminoglycoside antibiotics. Due to their potent antibacterial properties and low cost, aminoglycosides are often used for the treatment of gram-negative bacterial infections, surpassing expensive antibiotics with fewer harmful side effects. However, their use is coupled with permanent hearing loss in over 20% of patients requiring these life-sustaining antibiotics. There are currently no FDA-approved drugs that prevent hearing loss from aminoglycosides. A previous study by our group identified the plant alkaloid berbamine as a strong protectant of zebrafish lateral line hair cells from aminoglycoside damage. This effect is likely due to a block of the mechanotransduction channel, thereby reducing aminoglycoside entry into hair cells. The present study builds on this previous work, investigating 16 synthetic berbamine analogs to determine the core structure underlying their protective mechanisms. We demonstrate that nearly all of these berbamine analogs robustly protect lateral line hair cells from ototoxic damage, with ED50 values nearing 20 nM for the most potent analogs. Of the 16 analogs tested, nine strongly protected hair cells from both neomycin and gentamicin damage, while one conferred strong protection only from gentamicin. These data are consistent with prior research demonstrating that different aminoglycosides activate somewhat distinct mechanisms of damage. Regardless of the mechanism, protection required the entire berbamine scaffold. Phenolic alkylation or acylation with lipophilic groups appeared to improve protection compared to berbamine, implying that these structures may be responsible for mitigating damage. While the majority of analogs confer protection by blocking aminoglycoside uptake, 18% of our analogs also confer protection via an uptake-independent mechanism; these analogs exhibited protection when delivered after aminoglycoside removal. Based on our studies, berbamine analogs represent a promising tool to further understand the pathology of aminoglycoside-induced hearing loss and can serve as lead compounds to develop otoprotective drugs.