Neurosurgical Management of Spinal Epithelioid Hemangioendothelioma: Systematic Review and Illustrative Case Presentation.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor predominantly arising in soft tissue. We report a rare case of thoracic spinal EHE with pulmonary metastasis. METHODS: Case report and systematic review of spinal EHE. RESULTS: A 36-year-old man presented with bilateral lower extremity weakness, progressive paresthesia, and urinary incontinence. He underwent open surgical resection of the tumor and decompression of the spinal cord, with subsequent improvement in neurologic function. Systematic review identified 84 cases of spinal EHE, 73 of which were primary, and 14 of which developed extra-spinal metastases. CONCLUSION: EHE is an exceedingly rare tumor that may present with a wide swath of clinical symptoms. At present, no guidelines or formal treatment recommendations have been established. Surgical debulking has demonstrated efficacy as a front-line treatment, particularly in the setting of compressive neurologic dysfunction; data regarding adjuvant chemoradiation are less consistently reported, mandating further study.

Post-pandemic paradigm shift toward telemedicine and tele-education; an updated survey of the impact of Covid-19 pandemic on neurosurgery residents in United States.

Background: Several strategies were implemented during the Covid-19 pandemic to enhance residency training and patient care. Objective: This study aims to assess the post-pandemic landscape of neurosurgical training and practice. Method: A survey consisting of 28 questions examining the challenges faced in neurosurgery and the adaptive measures was conducted among US neurosurgery residents from May 2022 to May 2023. Results: This study encompassed 59 neurosurgical residents, predominantly male (72.9%) and in later years of training (66.1%) and were distributed across 25 states. Telemedicine and tele-education were pivotal during the pandemic, with virtual lecture series, standalone lectures, and virtual discussions highly favored. Remote didactic learning increased for nearly half of the residents, while 54.2% resumed in-person instruction. Telemedicine was deemed effective by 86.4% for evaluating neurosurgical patients. Access to teaching environments was restricted for 61.0% of residents, impacting their training. The pandemic significantly influenced elective surgeries, with complete cancellations reported by 42.4%. Reduced faculty engagement was noted by 35.6% of residents, while 47.5% reported a negative impact on the overall resident experience. The majority (76.3%) considered changes to their training reasonable given the global health situation. Conclusions: Strategies implemented during the peak of the pandemic remain crucial in shaping neurosurgery training. Telemedicine has become indispensable, with widespread adoption. Tele-education has also expanded, providing additional learning opportunities. However, traditional didactic courses and hands-on experiences remain essential for comprehensive training. Balancing technology-driven methods with established approaches is crucial for optimizing neurosurgical education and maintaining high-quality patient care.

Systematic review protocol for complications following surgical decompression of degenerative cervical myelopathy.

BACKGROUND: Degenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation. METHOD: Search will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias. DISCUSSION: This systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

A systematic review of the power of standardization in pediatric neurosurgery.

In the current neurosurgical field, there is a constant emphasis on providing the best care with the most value. Such work requires the constant optimization of not only surgical but also perioperative services. Recent work has demonstrated the power of standardized techniques in limiting complication while promoting optimal outcomes. In this review article, protocols addressing operative and perioperative care for common pediatric neurosurgical procedures are discussed. These articles address how various institutions have optimized procedures through standardization. Our objective is to improve patient outcomes through the optimization of protocols.

Surgical management of pediatric occipital neuralgia: a single-center experience of an uncommon pathology.

OBJECTIVE: Occipital neuralgia (ON) is a rare headache disorder characterized by sharp pain in the distribution of the greater occipital nerve (GON), lesser occipital nerve, or third occipital nerve. ON is commonly associated with traumatic injury, and effective identification and diagnosis can be difficult given the infrequent presentation and similarities to other pediatric headache disorders. While GON decompression has been well described in adults for refractory pain, there is a paucity of data in the pediatric population, with no previously published series on ON. The primary aim of this study was to identify the characteristics of pediatric patients with ON prior to surgical intervention and to describe the natural history of postoperative outcomes after decompression or neurectomy in a pediatric population. METHODS: A single-center retrospective case series was performed to evaluate factors predisposing children to refractory ON and the surgical efficacy of GON decompression or neurectomy. Six patients (mean age 15.0 ± 2.2 years) were identified for inclusion from October 2021 to October 2022. All patients had refractory ON as diagnosed by a pediatric neurologist. After medical therapy and repeated occipital nerve blocks failed, the patients were referred for GON decompression. Five patients had a history of trauma. RESULTS: Six patients were identified and treated in our cohort, highlighting the infrequency of this pathology. All had at least one occipital nerve block, with 83% receiving varied relief. All underwent bilateral decompression or neurectomy of the GON and experienced relief, reporting improved visual analog scale scores (mean 8.3 ± 0.9 preoperatively to 1.0 ± 2.2 postoperatively, p = 0.0009). The patients were followed for an average of 10 months, and their mean number of medications decreased from 2.7 ± 0.5 preoperatively to 0.8 ± 0.7 postoperatively (p = 0.019). Each patient reported numbness or tingling in the GON distribution postoperatively, which spontaneously resolved over time. Two patients had recurrent pain in a delayed fashion. CONCLUSIONS: GON decompression and neurectomy are efficacious treatments of refractory ON in the pediatric population.

Robot-Assisted Thoracolumbar Fixation After Acute Spinal Trauma: A Case Series.

BACKGROUND: Pedicle screw fixation has become the workhorse for the stabilization of the thoracolumbar spine. Since accurate pedicle screw placement is necessary for a successful surgery, three-dimensional navigation has become a mainstay for placing pedicle screws. However, the published studies have an overrepresentation of lumbar screws despite the prevalence of thoracic fractures. Furthermore, no robotic-assisted pedicle screw study has focused solely on traumatic fractures. The goal of this study was to address whether (1) robot-assisted pedicle screw placement had comparable accuracy in the thoracic and thoracolumbar region and (2) robot-assisted spine surgery was feasible in an acute, traumatic setting. METHODS: We performed 14 consecutive, thoracolumbar spinal stabilization procedures in which 126 pedicle screws were placed using the Globus ExcelsiusGPS® spine robot in an acute, traumatic setting. Operative times were measured, and the accuracy of pedicle screws was assessed with the Gertzbein and Robbins classification system by two board-certified neuroradiologists. RESULTS: A total of 60-thoracic (T3-T11), the 24-thoracolumbar junction (T12-L1), 40-lumbar (L2-L5), and two-sacral pedicle screws were placed. Pedicle screw placement was accurate with a < 1% (1/126) pedicle breach rate. Thoracolumbar robotic spine surgery in an acute, traumatic setting was demonstrated to have a good safety profile with only one minor neurological deficit which was related to positioning. Furthermore, surgical times were inversely related to the case number. CONCLUSIONS: These results together suggest that robot-assisted spine surgery is accurate in the thoracic spine. Furthermore, placement of thoracolumbar screws in an acute trauma is non-inferior to other methods when based on accuracy.

Torcular pseudomass in a 14-month-old child: illustrative case.

BACKGROUND: "Torcular pseudomass," or redundant soft tissue in the torcular region, is not an infrequent incidental finding on advanced imaging of the brain in infants and young children. It was recently codified among pediatric neuroradiologists; however, its report in the pediatric neurosurgical community has not previously been elucidated. OBSERVATIONS: The authors present a case of a 14-month-old child who presented with fever and a first-time seizure. Computed tomography of the head suggested an epidural abscess; however, magnetic resonance imaging characteristics of the lesion were consistent with torcular pseudomass, a normal variant. At the 3-month follow-up, the child was continuing to do well and had not had another seizure. There have been no indications for surgical intervention or additional radiographic surveillance. LESSONS: The differential diagnosis for torcular pseudomass includes dural venous sinus thrombosis, dermoid cysts, occipital encephalocele, eosinophilic granuloma, and primary and metastatic tumors, such as neuroblastoma. The management of each of these disorders in the differential diagnosis may be much more invasive than continued observation in the case of torcular pseudomass. Therefore, it is important for pediatric neurosurgeons to become familiar with this developmental anomaly of the dura and occipital skull.

Nontraumatic atlantoaxial rotatory subluxation in adults: Report of two cases.

Background: Nontraumatic infectious atlantoaxial rotatory subluxation (AARS) is rare and less frequently encountered in adults versus children. We utilized a stepwise approach to treat two adults with nontraumatic infectious AARS and summarized the relevant literature. Case Description: Two patients, ages 35 and 66, presented with classic clinical and imaging findings for infectious nontraumatic AARS. Here, we summarized the management for these two patients along with the literature. Conclusion: Nontraumatic infectious AARS in adults requires prompt X-ray diagnosis and timely application of traction to minimize neurological deficits. MR/CT imaging next offers critical information regarding whether operative stabilization is warranted.

Deletion of DJ-1 in rats affects protein abundance and mitochondrial function at the synapse.

DJ-1 is a multifunctional protein affecting different biological and cellular processes. In addition, DJ-1 has roles in regulating mitochondrial function. Loss-of-function mutations in DJ-1 were found to cause an autosomal recessive form of Parkinson's disease. One of the main pathological features of PD is loss of dopamine neurons in the nigrostriatal pathway. DJ-1 knockout (KO) rats exhibit progressive nigral neurodegeneration with about 50% dopaminergic cell loss at 8 months of age. In order to assess the effects of DJ-1 deficiency on neuronal mitochondria prior to neuron loss, we performed proteomic analysis of synaptic mitochondria isolated from the striatum, the location of nigrostriatal pathway nerve terminals, of 3-month-old DJ-1 KO rats. In total, 371 mitochondrial proteins were quantified, and of these 76 were differentially expressed in DJ-1 KO rats. Proteins perturbed by the loss of DJ-1 were involved in several mitochondrial functional pathways, including the tricarboxylic acid cycle and electron transport chain. Thus, synaptic mitochondrial respiration was measured and showed a significant change due to DJ-1 deficiency. The dataset generated here highlights the role of synaptic mitochondria in PD associated with DJ-1. This study improves our understanding of DJ-1 effects in a complex tissue environment and the synaptic mitochondrial changes that accompany its loss.

Quantitative Proteomics of Presynaptic Mitochondria Reveal an Overexpression and Biological Relevance of Neuronal MitoNEET in Postnatal Brain Development.

Although it has been recognized that energy metabolism and mitochondrial structure and functional activity in the immature brain differs from that of the adult, few studies have examined mitochondria specifically at the neuronal synapse during postnatal brain development. In this study, we examined the presynaptic mitochondrial proteome in mice at postnatal day 7 and 42, a period that involves the formation and maturation of synapses. Application of two independent quantitative proteomics approaches - SWATH-MS and super-SILAC - revealed a total of 40 proteins as significantly differentially expressed in the presynaptic mitochondria. In addition to elevated levels of proteins known to be involved in ATP metabolic processes, our results identified increased levels of mitoNEET (Cisd1), an iron-sulfur containing protein that regulates mitochondrial bioenergetics. We found that mitoNEET overexpression plays a cell-type specific role in ATP synthesis and in neuronal cells promotes ATP generation. The elevated ATP levels in SH-SY5Y neuroblastoma cells were associated with increased mitochondrial membrane potential and a fragmented mitochondrial network, further supporting a role for mitoNEET as a key regulator of mitochondrial function.

Proteomic and functional data sets on synaptic mitochondria from rats with genetic ablation of Parkin.

In this paper, we provide proteomic and functional data for synaptic mitochondria from the striatum of rats with Parkin ablation. The quantitative proteomic data was obtained using SWATH-MS methodology and mitochondrial function was assessed through measurement of oxygen consumption rate using the Seahorse XF Analyzer. This data facilitates comparisons with previous proteomic and functional data obtained using the exact same methods. A complete set of proteomic data is contained in Supplementary Table 1.

SWATH-MS proteome profiling data comparison of DJ-1, Parkin, and PINK1 knockout rat striatal mitochondria.

This article reports changes in the striatal non-synaptic mitochondrial proteome of DJ-1, Parkin, and PINK1 knockout (KO) rats at 3 months of age. DJ-1, Parkin, and PINK1 mutations cause autosomal-recessive parkinsonism. It is thought that loss of function of these proteins contributes to the onset and pathogenesis of Parkinson׳s disease (PD). As DJ-1, Parkin, and PINK1 have functions in the regulation of mitochondria, the dataset generated here highlights protein expression changes, which can be helpful for understanding pathological mitochondrial alterations. In total, 1281 proteins were quantified and 25, 37, and 15 proteins were found to exhibit differential expression due to DJ-1, Parkin, and PINK1 deficiency, respectively. All quantification can be found in the supplemental table and can be searched online at http://genome.unmc.edu/mitorat/index.html. Further, mitochondrial respiration was measured to evaluate mitochondrial function in the striatum of DJ-1, Parkin, and PINK1 KO rats, which was significantly changed only in the DJ-1 KOs.

Loss of Pink1 modulates synaptic mitochondrial bioenergetics in the rat striatum prior to motor symptoms: concomitant complex I respiratory defects and increased complex II-mediated respiration.

PURPOSE: Mutations in PTEN-induced putative kinase 1 (Pink1), a mitochondrial serine/threonine kinase, cause a recessive inherited form of Parkinson's disease (PD). Pink1 deletion in rats results in a progressive PD-like phenotype, characterized by significant motor deficits starting at 4 months of age. Despite the evidence of mitochondrial dysfunction, the pathogenic mechanism underlying disease due to Pink1-deficiency remains obscure. EXPERIMENTAL DESIGN: Striatal synaptic mitochondria from 3-month-old Pink1-deficient rats were characterized using bioenergetic and mass spectroscopy (MS)-based proteomic analyses. RESULTS: Striatal synaptic mitochondria from Pink1-deficient rats exhibit decreased complex I-driven respiration and increased complex II-mediated respiration compared with wild-type rats. MS-based proteomics revealed 69 of the 811 quantified mitochondrial proteins were differentially expressed between Pink1-deficient rats and controls. Down-regulation of several electron carrier proteins, which shuttle electrons to reduce ubiquinone at complex III, in the Pink1-knockouts suggests disruption of the linkage between fatty acid, amino acid, and choline metabolism and the mitochondrial respiratory system. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that complex II activity is increased to compensate for loss of electron transfer mechanisms due to reduced complex I activity and loss of electron carriers within striatal nerve terminals early during disease progression. This may contribute to the pathogenesis of PD.

Neonatal mitochondrial abnormalities due to PINK1 deficiency: Proteomics reveals early changes relevant to Parkinson׳s disease.

Parkinson׳s disease (PD), the second most common neurodegenerative disorder, affects roughly 7-10 million people worldwide. A wide array of research has suggested that PD has a mitochondrial component and that mitochondrial dysfunction occurs well in advance of the clinical manifestation of the disease. Previous work by our lab has categorized the mitochondrial disorder associated with Parkinson׳s disease in a PINK1 knockout rat model. This model develops Parkinson׳s disease in a spontaneous, predictable manner. Our findings demonstrated PINK1-deficient rats at 4 months of age had mitochondrial proteomic and functional abnormalities before the onset of Parkinsonian symptoms (6 months) such as the movement disorder, loss of midbrain dopaminergic neurons, or the progressive degeneration present at 9 months. With this in mind, our group investigated the PINK1 knockout genetic rat model at postnatal day 10 to determine if the observed alterations at 4 months were present at an earlier time point. Using a proteomic analysis of brain mitochondria, we identified significant mitochondrial proteomic alterations in the absence of mitochondrial functional changes suggesting the observed alterations are part of the mitochondrial pathways leading to PD. Specifically, we identified differentially expressed proteins in the PINK1 knockout rat involved in glycolysis, the tricarboxylic acid cycle, and fatty acid metabolism demonstrating abnormalities occur well in advance of the manifestation of clinical symptoms. Additionally, 13 of the differentially expressed proteins have been previously identified in older PINK1 knockout animals as differentially regulated suggesting these proteins may be viable markers of the PD pathology, and further, the abnormally regulated pathways could be targeted for therapeutic interventions. All raw data can be found in Supplementary Table 1.

HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution.

With the advent of the combination antiretroviral therapy era (cART), the development of AIDS has been largely limited in the USA. Unfortunately, despite the development of efficacious treatments, HIV-1-associated neurocognitive disorders (HAND) can still develop, and as many HIV-1 positive individuals age, the prevalence of HAND is likely to rise because HAND manifests in the brain with very low levels of virus. However, the mechanism producing this viral disorder is still debated. Interestingly, HIV-1 infection exposes neurons to proteins including Tat, Nef, and Vpr which can drastically alter mitochondrial properties. Mitochondrial dysfunction has been posited to be a cornerstone of the development of numerous neurodegenerative diseases. Therefore, we investigated mitochondria in an animal model of HAND. Using an HIV-1 transgenic rat model expressing seven of the nine HIV-1 viral proteins, mitochondrial functional and proteomic analysis were performed on a subset of mitochondria that are particularly sensitive to cellular changes, the neuronal synaptic mitochondria. Quantitative mass spectroscopic studies followed by statistical analysis revealed extensive proteome alteration in this model paralleling mitochondrial abnormalities identified in HIV-1 animal models and HIV-1-infected humans. Novel mitochondrial protein changes were discovered in the electron transport chain (ETC), the glycolytic pathways, mitochondrial trafficking proteins, and proteins involved in various energy pathways, and these findings correlated well with the function of the mitochondria as assessed by a mitochondrial coupling and flux assay. By targeting these proteins and proteins upstream in the same pathway, we may be able to limit the development of HAND.

The Proteomic Characterization of Plasma or Serum from HIV-Infected Patients.

Proteomics holds great promise for uncovering disease-related markers and mechanisms in human disorders. Recent advances have led to efficient, sensitive, and reproducible methods to quantitate the proteome in biological samples. Here we describe the techniques for processing, running, and analyzing samples from HIV-infected plasma or serum through quantitative mass spectroscopy.

Early Expression of Parkinson's Disease-Related Mitochondrial Abnormalities in PINK1 Knockout Rats.

PTEN-induced kinase 1 (PINK1) mutations are responsible for an autosomal recessive, familial form of Parkinson's disease. PINK1 protein is a Ser/Thr kinase localized to the mitochondrial membrane and is involved in many processes including mitochondrial trafficking, mitophagy, and proteasomal function. Using a new PINK1 knockout (PINK1 KO) rat model, we found altered brain metabolomic markers using magnetic resonance spectroscopy, identified changes in mitochondrial pathways with quantitative proteomics using sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry, and demonstrated mitochondrial functional alterations through measurement of oxygen consumption and acidification rates. The observed alterations included reduced creatine, decreased levels of complex I of the electron transport chain, and increased proton leak in the electron transport chain in PINK1 KO rat brains. In conjunction, these results demonstrate metabolomic and mitochondrial alterations occur during the asymptomatic phase of Parkinson's disease in this model. These results indicate both potential early diagnostic markers and therapeutic pathways that can be used in PD.

Data for mitochondrial proteomic alterations in the aging mouse brain.

Mitochondria are dynamic organelles critical for many cellular processes, including energy generation. Thus, mitochondrial dysfunction likely plays a role in the observed alterations in brain glucose metabolism during aging. Despite implications of mitochondrial alterations during brain aging, comprehensive quantitative proteomic studies remain limited. Therefore, to characterize the global age-associated mitochondrial proteomic changes in the brain, we analyzed mitochondria isolated from the brain of 5-, 12-, and 24-month old mice using quantitative mass spectrometry. We identified changes in the expression of proteins important for biological processes involved in the generation of precursor metabolites and energy through the breakdown of carbohydrates, lipids, and proteins. These results are significant because we identified age-associated proteomic changes suggestive of altered mitochondrial catabolic reactions during brain aging. The proteomic data described here can be found in the PRIDE Archive using the reference number PXD001370. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis and functional characterization of mouse brain mitochondria during aging reveal alterations in energy metabolism" in PROTEOMICS.