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.

An update on stem cell therapy for stroke patients: Where are we now?

With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise in promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological and behavioral deficits that frequently accompany ischemic stroke. These findings have led to a number of clinical trials that have thoroughly supported a strong safety profile for stem cell therapy in patients but have generated variable efficacy. As preclinical evidence continues to expand through the investigation of new cell lines and optimization of stem cell delivery, it remains critical for translational models to adhere to the protocols established through basic scientific research. With the recent shift in approach towards utilization of stem cells as a conjunctive therapy alongside standard thrombolytic treatments, key issues including timing, route of administration, and stem cell type must each be appropriately translated from the laboratory in order to resolve the question of stem cell efficacy for cerebral ischemia that ultimately will enhance therapeutics for stroke patients towards improving quality of life.

Anatomic Variations of Foramen Ovale as a Predictor of Successful Cannulation in Percutaneous Trigeminal Rhizotomies.

BACKGROUND AND OBJECTIVES: Percutaneous trigeminal rhizotomies are common treatment modalities for medically refractory trigeminal neuralgia (TN). Failure of these procedures is frequently due to surgical inability to cannulate the foramen ovale (FO) and is thought to be due to variations in anatomy. The purpose of this study is to characterize the relationships between anatomic features surrounding FO and investigate the association between anatomic morphology and successful cannulation of FO in patients undergoing percutaneous trigeminal rhizotomy. METHODS: A retrospective analysis was conducted of all patients undergoing percutaneous trigeminal rhizotomy for TN at our academic center between January 1, 2010, and July 31, 2022. Preoperative 1-mm thin-cut computed tomography head imaging was accessed to perform measurements surrounding the FO, including inlet width, outlet width, interforaminal distance (a representation of the lateral extent of FO along the middle fossa), and sella-sphenoid angle (a representation of the coronal slope of FO). Mann-Whitney U tests assessed the difference in measurements for patients who succeeded and failed cannulation. RESULTS: Among 37 patients who met inclusion criteria, 34 (91.9%) successfully underwent cannulation. Successful cannulation was associated with larger inlet widths (median = 5.87 vs 3.67 mm, U = 6.0, P = .006), larger outlet widths (median = 7.13 vs 5.10 mm, U = 14.0, P = .040), and smaller sella-sphenoid angles (median = 52.00° vs 111.00°, U = 0.0, P < .001). Interforaminal distances were not associated with the ability to cannulate FO surgically. CONCLUSION: We have identified morphological characteristics associated with successful cannulation in percutaneous rhizotomies for TN. Preoperative imaging may optimize surgical technique and predict cannulation failure.

Clival-Meckel's Cave Angle: A Predictor of Glycerol Displacement in Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: Percutaneous glycerol rhizotomy successfully treats trigeminal neuralgia although failure rates and durability of the procedure are variable. Some of this variability in clinical outcome might be due to egress of glycerol from Meckel's cave (MC) because of surgical positioning and individual patient anatomy. In this article, we quantitatively analyzed the anatomic variances that affect glycerol fluid dynamics to better predict patients more amenable for percutaneous glycerol injections. METHODS: Computed tomography imaging of 11 cadaveric heads was used to calculate bilateral Clival-Meckel's cave (CMC) and sella-temporal (ST) angles. Twenty-two cadaveric percutaneous injections of dyed glycerol into the Meckel's cave were performed using Härtel's approach, and the fluid movement was documented at prespecified intervals over 1 hour. The relationship between the angles and glycerol migration was studied. RESULTS: Specimens with basal cistern involvement by 60 minutes had significantly greater CMC angles (median [IQR]: basal cistern involvement = 74.5° [59.5°-89.5°] vs no basal cistern involvement = 58.0° [49.0°-67.0°]), U = 6.0, P < .001. This model may predict which patients will experience glycerol migration away from the Gasserian ganglion (area under the curve: 0.950, SE: 0.046, CI: 0.859-1.041, P < .001). Increased ST angle was associated with lateral flow of glycerol (r s = 0.639, P = .001), and CMC angle was associated with total area of dispersion (r s = -0.474, P = .026). CONCLUSION: Anatomic variation in skull base angles affects glycerol migration. Specifically, a more obtuse CMC angle was associated with a higher risk of posterior migration away from the Gasserian ganglion. This may be a reason for differing rates of surgical success. These results suggest that anterior head flexion for 60 minutes may prevent percutaneous glycerol rhizotomy failures and some patients with large CMC angles are more likely to benefit from postinjection head positioning. However, this clinical effect needs validation in vivo.

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.

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.