Cervical spinal cord stimulation exerts anti-epileptic effects in a rat model of epileptic seizure through the suppression of CCL2-mediated cascades.

Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure.

Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base.

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

Neurogenesis impairment with glial activation in the hippocampus-connected regions of intracerebroventricular streptozotocin-injected mice.

Adult neurogenesis in the hippocampus and subventricular zone (SVZ) is impaired by intracerebroventricular administration of streptozotocin (icv-STZ) to rodents. Although neural cells in the several brain regions which connect with the hippocampus or SVZ is thought to be involved in the adult neurogenesis, few studies have investigated morphological alterations of glial cells in these areas. The present study revealed that icv-STZ induces reduction of neural progenitor cells and a dramatic increase in reactive astrocytes and microglia especially in the hippocampus and various hippocampus-connected brain areas. In contrast, there was no significant neuronal damage excluding demyelination of the stria medullaris. The results indicate the hippocampal neurogenesis impairment of this model might be occurred by activated glial cells in the hippocampus, or hippocampus-connected regions.

[Initial Medical Care for Spinal Injury].

Neurosurgeons who treat head traumas often encounter cervical spinal injuries. They should be aware of the neurological symptoms, the severity of the symptoms, and the imaging features of cervical injuries. When surgery is required, fixation is often performed.

Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke.

The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation.

Inverted gull-wing hinge decompressive craniotomy for infantile acute subdural hematoma: A case report.

Infantile severe acute subdural hematomas (ASDHs) usually require a decompressive craniotomy. However, these infantile patients often suffer surgical site infection and aseptic bone-flap resorption after external decompression. In this report, we showed a case of a simplified hinge decompressive craniotomy in an infant with severe ASDH. A 2-month-old girl suffered from status epilepticus, impaired consciousness, multiple rib fractures, bilateral fundus hemorrhage, and a right ASDH. We performed a simplified hinge decompressive craniotomy, making a vascularized bone flap with a hinge using the partial temporal bone and temporal muscle and not fixing the bone flap like an inverted gull wing. Cranioplasty was performed 4 weeks after the decompression craniotomy with replaced resorbable substitute dura. Six months after the transfer, her development was generally in line with her age. The decompressive craniotomy with an inverted gull-wing hinge has shown a good outcome.

Trigeminal neuralgia caused by a persistent primitive trigeminal artery: preoperative three-dimensional multifusion imaging and computational fluid dynamics analysis. Illustrative case.

BACKGROUND: Trigeminal neuralgia (TN) is caused by trigeminal nerve compression by colliding vessels. Preoperative three-dimensional (3D) multifusion images are useful for surgical simulations. Moreover, computational fluid dynamics (CFD) analysis of colliding vessels may be useful for hemodynamic evaluation at the site of neurovascular contact (NVC). OBSERVATIONS: A 71-year-old woman had TN due to compression of the trigeminal nerve by the superior cerebellar artery (SCA) fused with the persistent primitive trigeminal artery (PTA). Preoperative 3D multifusion simulation images of silent magnetic resonance (MR) angiography and MR cisternography depicted the NVC, including the trigeminal nerve, SCA, and PTA. CFD analysis revealed the hemodynamic condition of the NVC, including the SCA and PTA. The wall shear stress magnitude (WSSm) at the NVC showed a local elevation due to flow confluence from the SCA and PTA. High WSSm was observed in the NVC. LESSONS: Preoperative simulation images of MR angiography and MR cisternography may depict the NVC. CFD analysis can provide the hemodynamic condition at the NVC.

IDH-mutant Astrocytoma Arising in the Brainstem with Symptom Improvement by Foramen Magnum Decompression: A Case Report.

Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway.

BACKGROUND: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. OBJECTIVE: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. METHODS: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. RESULTS: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. CONCLUSION: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction.

A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke.

BACKGROUND: Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. METHODS: Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 µl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. RESULTS: SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). CONCLUSIONS: This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.

Angioarchitecture of the Normal Lateral Spinal Artery and Craniocervical Junction Arteriovenous Fistula Using Contrast-enhanced Cone-beam CT.

BACKGROUND AND PURPOSE: The lateral spinal artery (LSA) perfuses the dorsolateral part of the spinal cord at the craniocervical junction (CCJ). We analyzed the angioarchitecture of the normal LSA and CCJ arteriovenous fistula (AVF). METHODS: The first study included 26 patients with a cerebral aneurysm of the posterior circulation. Using slab maximum intensity projection (MIP) images from three-dimensional rotational angiography (3D-RA) and contrast-enhanced cone-beam CT (CE-CBCT), we analyzed the origin of the LSA, its anastomosis with the posterior inferior cerebellar artery (PICA), the point where it reaches the spinal cord, and the visualized range. In the second study, we analyzed the angioarchitecture and treatment results of 7 CCJAVF lesions treated in our department between 2016 and 2021. RESULTS: We visualized the normal LSA for all patients. In 23 patients with an intradural origin PICA, all LSAs originated from the C1 or C2 radicular artery, and 8 patients had an anastomosis with the PICA. In three patients with a C1 level origin PICA, all LSAs originated from the PICA. All LSAs reached the dorsolateral part of the spinal cord. The mean visualized range of the LSA was 27.4 mm. The LSA was involved in five of seven CCJAVF lesions (71%). There was one lesion with a spinal infarction after LSA embolization. Other lesions were treated by direct interruption of the AVF, and the ASA and LSA were preserved. CONCLUSION: This is the first report that visualized the LSA's normal anatomy using slab MIP images from 3D-RA and CE-CBCT. Knowledge of LSA anatomy is critical to avoid complications during the treatment of CCJAVF.

A Rare Case of Idiopathic Spinal Cord Herniation Treated by DuraGen® Collagen Matrix Graft.

We report a rare case of idiopathic spinal cord herniation (ISCH) with a history of cerebrospinal fluid (CSF) leakage. ISCH is a protrusion of the spinal cord through a dural defect. Thin constructive interference in steady-state (CISS) images clearly demonstrated the herniated cord in the present case. The myelopathy worsened and the patient underwent surgery for reduction of herniated spinal cord; the dural defect was filled by placing collagen matrix graft (DuraGen®) between the inner and outer dural layers. The patient's symptoms have improved without relapse for 8 months since surgery. This method may be a good surgical option for cases of spinal cord herniation.

Two Cases of Monozygotic Twins with Early-onset Isolated (DYT1) Dystonia Effectively Treated with Bilateral Globus Pallidus Internus Stimulation.

Early-onset isolated (DYT1) dystonia is one of the most common forms of primary dystonia in childhood, and deep brain stimulation of the globus pallidus internus (GPi-DBS) is a highly effective treatment for it. However, the effectiveness of GPi-DBS in monozygotic twins with DYT1 dystonia has never been reported globally. Here, we report the cases of monozygotic twins with DYT1 dystonia who were treated using GPi-DBS, and we include a literature review. The younger brother showed an abnormal gait, with external rotation of the right lower leg at 6 years old. The symptoms gradually became so severe that he had difficulty walking on his own at 9 years of age. Treatment with levodopa-carbidopa partially resolved his symptoms, but most of the symptoms remained. Meanwhile, the older brother developed dystonia in both upper limbs at 8 years of age, with gradual symptom progression. At 13 years of age, they were diagnosed with DYT1 dystonia. Bilateral GPi-DBS was performed in both patients at 16 years of age. Their symptoms remarkably improved after surgery. The Burke-Fahn-Marsden dystonia rating scale (BFMDRS) movement score was reduced from 52 to 2 points for the younger brother and from 35 to 1 point for the older brother. Even if monozygotic twins have the same genes, the onset and severity of symptoms might vary in accordance with differences in epigenomic profiles. However, GPi-DBS treatment was very effective for the two cases; thus, we should consider the surgical interventions for each patient.

The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology.

PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

Predictive Factors of Return Home and Return to Work for Intensive Care Unit Survivors after Traumatic Brain Injury with a Follow-up Period of 2 Years.

Intensive care unit (ICU) survivors after traumatic brain injury (TBI) frequently have serious disabilities with subsequent difficulty in reintegration into society. We aimed to investigate outcomes for ICU survivors after moderate to severe TBI (msTBI) and to identify predictive factors of return home (RH) and return to work (RTW). This single-center retrospective cohort study was conducted on all trauma patients admitted to the emergency ICU of our hospital between 2013 and 2017. Of these patients, adult (age ≥ 18 years) msTBI patients with head Abbreviated Injury Scale ≥ 3 were extracted. We performed univariate/multivariate logistic regression analyses to explore the predictive factors of RH and RTW. Among a total of 146 ICU survivors after msTBI, 107 were included (median follow-up period: 26 months). The RH and RTW rates were 78% and 35%, respectively. Multivariate analyses revealed that the predictive factors of RH were age < 65 years (P < 0.001), HR < 76 bpm (P = 0.015), platelet count ≥ 19× 104/µL (P = 0.0037), D-dimer < 26 µg/mL (P = 0.034), and Glasgow Coma Scale (GCS) score > 8 (P = 0.0015). Similarly, the predictive factors of RTW were age < 65 years (P < 0.001) and GCS score > 8 (P = 0.0039). This study revealed that "age" and "GCS score on admission" affected RH and RTW for ICU survivors after msTBI.

[Infections in Functional Neurosurgery:Focusing on Device-based Surgery].

Functional neurosurgery for epilepsy, movement disorders, and spasticity includes some device-based surgeries such as deep brain stimulation, subdural electrode placement, vagus nerve stimulation, and baclofen pump implantation. These surgeries have a higher risk of surgical site infection(SSI)than other general neurological surgeries. Furthermore, because device removal after infection can significantly impair patients'activities of daily living and quality of life, SSI in functional neurosurgery is a worrisome surgical complication. In this study, we conducted a mini-review of the risk of infection in each device-based surgery and described associated surgical procedures and preparations performed at our institution, with a focus on infection prevention.