Intraoperative Neuromonitoring for the Lower-Extremity Region Using Motor-Evoked Potential With Direct Cortical Stimulation in Brain Tumor Surgeries.

PURPOSE: To evaluate the motor function of the lower extremity (LE), we used direct cortical stimulation motor-evoked potential (D-MEP) monitoring with a single six-contact subdural strip electrode placed in the interhemispheric fissure. METHODS: Intraoperative neuromonitoring using D-MEPs in the LE was performed in 18 cases (16 patients) for brain tumor surgery from December 2018 to April 2023 with a follow-up period of at least 3 months. After dural opening, a single six-contact subdural strip electrode was placed inside the interhemispheric fissure. To identify the central sulcus, phase reversal was recorded using somatosensory evoked potentials. Next, direct cortical stimulation was applied to the primary motor cortex. The baseline waveform was defined as a reproducible waveform of 30 µV or higher, and a significant decrease of ≥50% in the amplitude resulted in a warning during surgery. RESULTS: The success rate of central sulcus identification in the LE was 66.7% (12/18 cases). Direct cortical stimulation motor-evoked potential monitoring could record stable contralateral motor-evoked potentials of the tibialis anterior, gastrocnemius, and abductor hallucis in 16 of 18 cases (88.9%). The mean intensity of stimulation for D-MEPs was 20.5 ± 9.9 mA, and the 16 cases showed no significant reduction in amplitude. Seventeen cases showed no deterioration of motor function of the LE at 1 and 3 months postoperatively. In the remaining case with unsuccessful D-MEP, paralysis of the LE worsened at 1 and 3 months postoperatively. CONCLUSIONS: The placement of electrodes in the interhemispheric fissure on the primary motor cortex of the LE enabled motor-function monitoring in the LE with D-MEPs, suggesting that D-MEP-based monitoring may be a reliable approach.

Ventriculoperitoneal shunt tube migration into the heart and pulmonary artery: successful tube removal. Illustrative case.

BACKGROUND: Ventriculoperitoneal (VP) shunt tube migration is recognized as an occasional complication; however, migration into the cardiac system is rare. The authors report a case of VP shunt tube migration into the heart and pulmonary artery and the safe removal of the tube. OBSERVATIONS: The patient had a VP shunt implanted for hydrocephalus after a subarachnoid hemorrhage. The screening chest radiograph taken a few months later showed the migration of the abdominal tube into the heart. Examinations revealed that the abdominal tube had migrated from the left subclavian vein, passed through the superior vena cava, right atrium and ventricle, and looped into the pulmonary artery. The patient had no symptoms; however, there were some risks, such as damage to the valves or fatal arrhythmia. The authors therefore decided to remove the tube. To avoid various intraoperative risks, in particular tube knot formation, the tube was removed under fluoroscopy with a guidewire inserted, which was 0.035 inches for the angiography catheter. The tube was successfully removed without any complications. LESSONS: Knot formation can be one of the fatal complications of shunt tube removal. The authors' technique is an effective method for safe removal. https://thejns.org/doi/10.3171/CASE24127.

Endoscope-Assisted Evacuation of an Acute Subdural Hematoma in an Elderly Patient With Refractory Nonconvulsive Status Epilepticus: An Illustrative Case.

Traumatic brain injuries lead to post-traumatic seizures (PTS), with acute subdural hematomas (ASDH) posing a particularly elevated risk. The development of refractory nonconvulsive status epilepticus (NCSE) in such cases, especially in older patients, requires immediate and effective management. This case report highlights the improvement of refractory NCSE in an elderly patient with ASDH through endoscope-assisted evacuation. An 88-year-old woman was hospitalized for dysarthria and right hemiparesis 3 days after a fall. Computed tomography (CT) revealed a left hemispheric ASDH, 9 mm thick, along with minor traumatic subarachnoid bleeding in the interpeduncular cistern. The initial treatment was conservative, including the administration of lacosamide at 100 mg/day. However, her consciousness deteriorated 4 days after admission, and she experienced convulsions in the right face and arm on day 5. Although the convulsions stopped after the administration of diazepam 10 mg IV and her consciousness temporarily improved, it worsened again on day 6, leading to a diagnosis of NCSE on an electroencephalogram (EEG). Despite aggressive pharmacological interventions with fosphenytoin (750 mg initially followed by 262 mg/day) and phenobarbital (625 mg/day), the patient's cognitive state and EEG findings did not improve. Consequently, on the 13th day, she underwent an endoscopic procedure to remove the SDH, which alleviated her symptoms and ended the seizures. This case demonstrates that even the absence of a significant mass effect from ASDH can trigger NCSE, underscoring the necessity for swift diagnosis and consideration of surgical options when conventional treatment fails. Endoscope-assisted evacuation is a safe and effective treatment option, particularly in older patients.

Transcranial motor-evoked potentials disappear with pons transection.

Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons.

Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma.

Objective: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. Methods: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns-classified as local, diffuse, distant, or multifocal-and time to recurrence were compared between patients with and without VO. Results: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7-38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35). Conclusion: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.

Simple tape-stripping method for highly reliable and quantitative analysis of skin microbiome.

The composition of human skin microbiome profoundly impacts host skin health and disease. However, the relationship between skin homeostasis or the development of skin diseases and daily changes in skin microbial composition is poorly understood. Longitudinal samplings at more frequent intervals would address this issue, while conventional sampling methods have technical difficulties, leading to limitations in sampling opportunities. Here, we developed a simple and stable tape-stripping method regardless of the operator's skill. Our method enables skin microbial sampling within 30 seconds and taking multiple skin microbial samples from the same body site. The amount of microbial DNA among multiple sampling sites could be measured within 13.5%. The sequencing results of multiple sampling showed high consistency, Pearson's correlation coefficient between multiple samples of 0.98. Furthermore, these results were comparable to those collected by the conventional swabbing method. These results demonstrate that our tape-stripping method enables simple microbiome collection and highly reliable quantitative skin microbiome analysis. These features of our method would lead to a further understanding of skin disease development or diagnosis of skin conditions in clinical research by increasing the opportunities for microbial sampling.

Awake Craniotomy for Astrocytoma in the Left Frontal Lobe Using Augmented Reality Superimposing Tumor and White Matter Tracts: 2-Dimensional Operative Video.

Augmented reality (AR) is expected to serve as an assistive intraoperative technology in neurosurgery.1 Awake craniotomy (AC) for gliomas benefits the extent of resection, survival, and postoperative neurofunctional outcomes.2 In AC, it is critical to understand the cortical and subcortical anatomy.3 We describe the use of AR superimposing tumor and deep white matter tracts in AC. A 29-year-old right-handed woman presented to a local hospital after an episode of generalized convulsions. MRI of the head revealed a widely spreading tumor in the left middle frontal gyrus. After a left frontal craniotomy while the patient was asleep, AR was used to indicate the tumor boundary with subcortical fibers including the corticospinal tract, inferior fronto-occipital fasciculus, and cingulate fasciculus. We performed AR-assisted removal of the tumor on the surface of the middle frontal gyrus. On subcortical stimulation (SCS) of the frontal aslant tract and inferior fronto-occipital fasciculus, the patient stopped naming objects in the picture-naming test, while SCS of the left cingulate gyrus caused the patient to mistake colors in the Stroop test. The subcortical fibers identified by AR coincided with the sites of symptom elicitation by SCS. We eventually removed a large part of the tumor. Postoperative MRI confirmed 96.2% resection. The patient was discharged without any new neurological deficits. AC with AR is useful for resection of gliomas in the dominant hemisphere. The patient consented to the procedure and to the publication of her image. The ethics committee of our hospital does not require approval for case reports.

Post-surgical Hearing Improvement in a Case of Jugular Foramen Schwannoma Despite the Lack of Response in a Preoperative Auditory Brainstem Response Test.

We report a rare case involving improved hearing after surgery for a jugular foramen schwannoma despite the lack of response during the preoperative auditory brainstem response (ABR) test. A left jugular foramen tumor was diagnosed in a 79-year-old man with hearing loss. No response was observed during the preoperative ABR test. However, his hearing improved after surgery using the lateral suboccipital approach. Following Gamma Knife radiation to the residual tumor post-surgery, the ABR test detected V waves. The hearing of patients with cerebellopontine angle tumors can improve even when there is no response during the preoperative ABR test.

Complete genome sequence of three Staphylococcus epidermidis strains isolated from patients with skin diseases in Japan.

Staphylococcus epidermidis is a member of the human skin microbiota as a commensal organism but could be an important opportunistic pathogen for immunocompromised individuals. Here, we report the complete genome sequence of three S. epidermidis strains isolated from patients with skin diseases.

Characterization of HIF-1α Knockout Primary Human Natural Killer Cells Including Populations in Allogeneic Glioblastoma.

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA-Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR-Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.

Characterization of a novel format scFv×VHH single-chain biparatopic antibody against metal binding protein MtsA.

Biparatopic antibodies (bpAbs) are engineered antibodies that bind to multiple different epitopes within the same antigens. bpAbs comprise diverse formats, including fragment-based formats, and choosing the appropriate molecular format for a desired function against a target molecule is a challenging task. Moreover, optimizing the design of constructs requires selecting appropriate antibody modalities and adjusting linker length for individual bpAbs. Therefore, it is crucial to understand the characteristics of bpAbs at the molecular level. In this study, we first obtained single-chain variable fragments and camelid heavy-chain variable domains targeting distinct epitopes of the metal binding protein MtsA and then developed a novel format single-chain bpAb connecting these fragment antibodies with various linkers. The physicochemical properties, binding activities, complex formation states with antigen, and functions of the bpAb were analyzed using multiple approaches. Notably, we found that the assembly state of the complexes was controlled by a linker and that longer linkers tended to form more compact complexes. These observations provide detailed molecular information that should be considered in the design of bpAbs.

Passive Approximator Vascular Closure Device Use in Patients with Shallow Femoral Artery Depth Increases Puncture-site Complications in Neuroendovascular Treatment.

OBJECTIVE: Puncture-site complications in interventional radiology sometimes cause severe conditions. Vascular closure devices play an important role in preventing puncture-site complications. Vascular closure devices are divided into 2 types, the directly suturing or clipping type (active approximators) and adherent sealant types (passive approximators). However, which types of vascular closure device are the safest and most effective for achieving hemostasis remains unclear. We analyzed the efficacy of each type of vascular closure device and risk factors for puncture-site complications. METHODS: This study investigated 327 consecutive cases of neuroendovascular surgery using a transfemoral procedure during a 2-year study period. Passive approximators (Angioseal [St Jude Medical, Saint Paul, MN] and Exoseal [Cordis Corporation, Miami, FL]) were mainly used in the first half and active approximators (Perclose [Abbot Vascular, Santa Clara, CA]) in the second. We compared groups and estimated risk factors for puncture-site complications. RESULTS: All procedures were successful. Comparing groups with and without puncture-site complications, use of passive approximators and ≥3 antithrombotic medications tended to be more frequent and distance from skin to femoral artery and body mass index tended to be lower in the group with complications without significance. The cutoff for femoral artery depth calculated from a receiver operating characteristic curve was 16.43 mm. Multivariate analysis revealed ≥3 antithrombotic medications (P = 0.002, OR 15.29, 95% CI 2.76-85.76) and passive approximator use in patients with femoral artery depth <16.43 mm (P < 0.001, OR 17.08, 95% CI 2.95-57.80) were significantly higher in the group with puncture-site complications. CONCLUSIONS: Passive approximator use in patients with shallow femoral artery depth increases puncture-site complications in neuroendovascular treatment.

Intraoperative monitoring of trigeminal neuralgia: a technical note.

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.

ATG9B regulates bacterial internalization via actin rearrangement.

Invasive bacterial pathogens are internalized by host cells through endocytosis, which is regulated by a cascade of actin rearrangement signals triggered by host cell receptors or bacterial proteins delivered into host cells. However, the molecular mechanisms that mediate actin rearrangement to promote bacterial invasion are not fully understood. Here, we show that the autophagy-related (ATG) protein ATG9B regulates the internalization of various bacteria by controlling actin rearrangement. ATG knockout screening and knockdown experiments in HeLa cells identified ATG9B as a critical factor for bacterial internalization. In particular, cells with ATG9B knockdown exhibited an accumulation of actin filaments and phosphorylated LIM kinase and cofilin, suggesting that ATG9B is involved in actin depolymerization. Furthermore, the kinase activity of Unc-51-like autophagy-activating kinase 1 was found to regulate ATG9B localization and actin remodeling. These findings revealed a newly discovered function of ATG proteins in bacterial infection rather than autophagy-mediated immunity.

Management Approaches and Patient Outcomes for Giant Pituitary Neuroendocrine Tumors Classified as Knosp Grade 3 and 4.

Background Treatment of patients with a giant pituitary neuroendocrine tumor (GPitNET) is challenging. Here, we present the methods used for the clinical management of patients who underwent GPitNET resection mainly via endoscopic endonasal surgery along with multimodal support to avoid surgical complications, which can affect the outcomes. Methodology The medical records of 25 patients with a GPitNET who underwent endonasal endoscopic surgery were retrospectively reviewed. Complications were analyzed and factors affecting the extent of resection were evaluated. Results Gross total resection was achieved in six (24%), near-total resection (>90%) in nine (36%), and partial resection in 10 (40%) patients. Multivariate analyses revealed that tumors invading the middle fossa had negative effects on the extent of resection (odds ratio = 0.092, p = 0.047). Postoperative vision improved or normalized in 16 (64%), remained stable in eight (32%), and worsened in one (4%), while a new hormonal deficit was noted in seven (28%) patients. Complications included permanent oculomotor nerve palsy in one (4%) and transient oculomotor palsy in one (4%), apoplexy of the residual tumor resulting in ischemic stroke in one (4%), postoperative cerebrospinal fluid leakage in one (4%), and permanent diabetes insipidus in six (24%) patients. Conclusions For GPitNETs that extend into the middle fossa, our study underscored the difficulties in surgical extraction and the necessity for tailored treatment approaches. To ensure the safest and most complete removal possible, the surgical strategy must be specifically adapted to each case. Additionally, employing a comprehensive support approach is essential to reduce the chance of complications in patients impacted by this condition.

Pre-treatment systemic inflammation response index and systemic immune inflammation in patients with primary central nerve system lymphoma as a useful prognostic indicator.

PURPOSE: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL). METHODS: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded. RESULTS: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 109/L, n = 22) and high (≥ 1.43 × 109/L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS. CONCLUSION: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states.

Preoperative Blood Counts Predict Overall Survival in Patients Undergoing Surgical Removal of Brain Metastasis.

OBJECTIVE: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal. METHODS: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin. RESULTS: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio ≥ 3.17, platelet-lymphocyte ratio ≥112.7, systemic immune-inflammation index ≥594.4, systemic inflammation response index ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (P < 0.001). Furthermore, lower lymphocyte-monocyte ratio < 2.33 and prognostic nutritional index < 48.5 were unfavorable predictors. CONCLUSIONS: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and prognostic nutritional index, can predict the overall survival of patients treated with surgical removal for BM.

Antiseizure Medication-Induced Nystagmus During Eye Closure Identified by Electroencephalography.

Nystagmus is a well-known side effect of antiseizure medicines (ASMs), but it is often underestimated and overlooked. Here, we describe a case in which nystagmus during eye closure was identified early using routine electroencephalography (EEG). A 34-year-old man developed focal epilepsy after head trauma at the age of 25 years. The patient was treated with carbamazepine but liver dysfunction was observed; therefore, treatment was attempted with lacosamide (LCM) and lamotrigine. With an increase in the LCM dose, steep potential changes suggestive of horizontal nystagmus were observed in the electrooculogram, F7, and F8 on EEG, and the patient complained of eye shaking during eye closure. These symptoms and EEG findings improved with LCM dose reduction. If the presence of nystagmus is identified on EEG coincidentally and a patient's subjective symptoms with ASM are confirmed, it is advisable to taper and/or discontinue the causative agent.

Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice.

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury.