A novel leucine zipper-like transcriptional regulator 1 variant identified in a pair of siblings with familial schwannomatosis.

Background: Schwannomatosis is a rare genetic disorder marked by the emergence or predisposition to developing multiple schwannomas. Patients typically present with chronic pain or a mass in the second or third decade of life. Schwannomatosis is characterized by its associated gene, or if the specific gene is not known, then a descriptor is used. Here, we report a new Leucine zipper-like transcriptional regulator 1 (LZTR1) pathogenic variant identified in a pair of siblings with familial LZTR1-related schwannomatosis. Case Descriptions: A 35-year-old male presented for evaluation of the left lower extremity pain. Magnetic resonance imaging (MRI) demonstrated multiple lesions throughout his body, highly likely for schwannomatosis. He underwent surgical resection of two of these lesions, located in the left femoral nerve and distal shin. Pathology confirmed that the resected lesions were schwannomas. Six months later, his 34-year-old sister was referred and evaluated for a right ankle mass, previously diagnosed as a ganglion cyst. MRI of her right ankle demonstrated a one-centimeter subcutaneous tumor. She underwent surgical resection, and pathology confirmed that the tumor was a schwannoma. Both siblings elected to undergo genetic analysis for pathogenic variants associated with schwannomatosis. Both results were positive for the c.263del pathogenic variant of the LZTR1 gene associated with LZTR1-related schwannomatosis. Additionally, genetic analysis also determined the mother of the siblings also carried the same c.263del pathogenic variant. Conclusion: There are still schwannomatosis cases with novel switch/sucrose non-fermentable-related matrix-associated actin-dependent regulators of chromatin subfamily B member 1 or LZTR1 mutations to be reported. We report the first three cases of the c.263+1del LZTR1 pathogenic variant causing LZTR1-related schwannomatosis initially found in the two siblings. Identifying further LZTR1 pathogenic variants can give more insight into the pathogenicity of each variant.

Assessing Survival, Distribution, and Optimal Loading Technique of Schwann Cell-Derived Exosomes Into Second-generation Axon Guidance Channels.

INTRODUCTION: Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it. MATERIALS AND METHODS: A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging. RESULTS: Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC. CONCLUSIONS: Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.

Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy.

We investigated the role of the N-terminus (residues 1-43) of the myosin essential light chain (N-ELC) in regulating cardiac function in hypertrophic (HCM-A57G) and restrictive (RCM-E143K) cardiomyopathy mice. Both models were cross-genotyped with N-ELC-truncated Δ43 mice, and the offspring were studied using echocardiography and muscle contractile mechanics. In A57G×Δ43 mice, Δ43 expression improved heart function and reduced hypertrophy and fibrosis. No improvements were seen in E143K×Δ43 compared to RCM-E143K mice. HCM-mutant pathology involved an impaired N-ELC tension sensor, disrupted N-ELC-actin interactions, an altered force-pCa relationship, and a destabilized myosin's super-relaxed state. Removal of the malfunctioning N-ELC sensor led to functional rescue in HCM-truncated mutant hearts. However, the RCM mutation could not be rescued by N-ELC deletion, likely due to its proximity to the myosin motor domain, affecting lever-arm rigidity and myosin function. This study provides insights into the role of N-ELC in the development and potential rescue of ELC-mutant cardiomyopathy.

Risk factors for vascular injuries in anterior lumbar interbody fusion: a single-institution retrospective study.

OBJECTIVE: Vascular injuries in anterior lumbar interbody fusion (ALIF) occur due to the vascular manipulation needed to achieve optimal disc space exposure. In this study, the authors aimed to evaluate intraoperative vascular injuries in patients undergoing single- and multilevel ALIF at a large tertiary academic center. METHODS: Prospectively collected data specifically addressing postoperative complications in patients who underwent ALIF by neurosurgery spine faculty working with a specialized vascular surgeon were retrospectively reviewed. Demographic characteristics and intraoperative data were collected. Patients were split into vascular injury and non-vascular injury groups. Outcome comparisons were conducted using the chi-square exact and Wilcoxon rank-sum tests for categorical and continuous data, respectively. Logistic regression was used to investigate associations with vascular injury, with univariate analysis first conducted to identify candidate associations. Based on these results, variables demonstrating a between-groups test statistic of p < 0.10 were included in the multivariate analysis to determine the independent predictors of vascular injuries. RESULTS: In total, 323 patients who underwent ALIF procedures were identified: 51% were male (n = 166) and 49% were female (n = 157). The mean age was 57.1 years, with 56% (n = 182) having undergone prior lumbar surgery. Vascular injuries were encountered intraoperatively in 7.1% (n = 23) of patients, and the majority (91% [n = 21]) involved the left common iliac vein. Patients with vascular injuries were statistically older (mean 63.6 vs 56.6 years), had greater incidence rates of coronary artery disease, opioid use, multilevel ALIF surgery involving the L2-3 level, and surgery involving multiple disc spaces, had more multilevel anterior instrumentation, and experienced greater blood loss during surgery and longer length of stay (all p < 0.05). Overall, there was 1 death (0.3%) secondary to aortic artery injury. Multivariate analysis identified opioid use, multilevel ALIF involving L2-3, and multiple interbodies as statistically independent predictors of vascular injury (all p < 0.05). CONCLUSIONS: Identifying patient risk factors can reduce the risk of vascular injuries in ALIF. Opioid use, multilevel ALIF involving L2-3, and multiple interbodies were independent predictors of vascular injuries in ALIF.

Resection of a lumbar intradural tumor.

Background: Myxopapillary ependymomas and schwannomas represent the most common tumors of the conus medullaris and cauda equina. Here, we present the surgical resection of a 64-year-old male with a lumbar intradural tumor. Case Description: A 64-year-old male presented with several months of the lower extremity weakness, pain, and bowel/bladder dysfunction. Magnetic resonance imaging demonstrated a large L3-5 intradural lesion, and surgical resection using intraoperative neuromonitoring with somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), free-running electromygraphy (EMGs), and direct sphincter monitoring was recommended. After an L2-S1 laminectomy was performed, intraoperative ultrasound was used to confirm the cranial and caudal extent of the tumor. The dural was opened using a midline approach, and the tumor was quickly visualized. Through careful dissection, the tumor was debulked and gross total resection was ultimately achieved through a piecemeal resection. Hemostasis was frequently required throughout the case, as the tumor was highly vascular. Postoperatively, the patient was at his neurologic baseline and was discharged to rehab on postoperative day 4. The final pathology revealed the intradural lesion was a paraganglioma. Conclusion: Early intervention and gross total resection of spinal intradural tumors are associated with optimal patient outcomes. Additional adjuncts, such as ultrasound, are beneficial and can help achieve gross total tumor resection.

Intraoperative embolectomy of a left illiac artery thrombus during an anterior lumbar interbody fusion.

Background: Anterior lumbar interbody fusion (ALIF) offers direct midline access to the lumbar intervertebral discs utilizing an anterior retroperitoneal approach. Here, a 33-year-old female undergoing ALIF developed an acute intraoperative left iliac artery thrombus and underwent immediate successful embolectomy. Case Description: A 33-year-old female was undergoing routine L5-S1 ALIF when an acute intraoperative left iliac vein injury occurred, requiring immediate repair by a vascular surgeon. Her left foot pulse oximeter showed a decreased reading, and her Doppler ultrasound confirmed reduced flow in the distal external iliac artery due to a thrombus. She required an immediate left iliac artery embolectomy, and flow was immediately restored. Postoperatively, she recovered well, and 3 months postoperatively, she remained neurologically intact without any further complications. Conclusion: Using pulse oximeters in patients undergoing ALIF surgery can aid in facilitating the diagnosis and treatment of acute artery thrombi. When such vascular injuries arise, having immediate access to experienced vascular surgeons is critical to obtain expeditious treatment and optimize patient outcomes.