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.

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.

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.

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.

AIMS: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. METHODS: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. RESULTS: In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. CONCLUSION: SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.

A Pediatric Case of Cauda Equina Dermoid Cyst Resected by Minimally Invasive Unilateral Hemilaminectomy.

A 3-year-old boy had difficulty sitting up and walking for several months. Magnetic resonance imaging (MRI) revealed an intradural tumor at the L3-4 level. The tumor was successfully resected by unilateral hemilaminectomy and diagnosed as dermoid cyst. The patient had an uneventful postoperative course without pain, and MRI found no recurrence after surgery. A small bone defect remained that might be favorably reconstructed with autologous and artificial bone. Hemilaminectomy allowed us to resect the cauda equina dermoid cyst with minimal invasiveness. Pediatric patients require follow-up as they are more likely to experience spinal deformity or instability after surgery.

Growth Curves for Intracranial Volume and Two-dimensional Parameters for Japanese Children without Cranial Abnormality: Toward Treatment of Craniosynostosis.

In the management of patients with craniosynostosis, it is important to understand growth curve of the normal cranium. Although three-dimensional (3D) computed tomography (CT) images taken in thin slices are easily available nowadays, data on the growth curves of intracranial volume (ICV), cranial length, cranial width, and cranial height in the normal cranium are mainly based on older studies using radiography, and there are insufficient reports using CT images especially taken in thin slices. The purpose of this study was to establish growth curves in the normal cranium of Japanese children using thin-slice images. Cranial images of 106 subjects (57 males, 49 females; aged 0-83 months) without significant cranial abnormalities were retrospectively analyzed. Using thin-slice CT images, the ICV and two-dimensional parameters such as cranial length, cranial width, and cranial height were measured by iPlan, followed by generating growth curves and calculating cephalic index (CI). ICV calculated from thin-slice CT images was compared with that obtained by substituting two-dimensional parameters into Mackinnon formula. The ICV growth curves for males and females were similar in shape. As with the ICV, the two-dimensional parameters increased most rapidly in the first year after birth. There was no significant difference in CI between the sexes or among any age groups. ICV calculated from thin-slice 3D CT images was 60% of that obtained from Mackinnon formula. These data will enable us to compare these specific measurements in craniosynostosis patients directly with those of normal children, which will hopefully help in managing these patients.

A case of transpetrosal penetrating head injury near the sigmoid sinus.

BACKGROUND: Penetrating brain injury is relatively rare, which occurs in 0.4% of all head trauma. In past reports, the orbit, nasal cavity, and oral cavity are the most common routes of entry of foreign substances into the skull. In this case report, we experienced a rare case of head trauma who injury through the petrosal bone. To the best of our knowledge, there is no similar literature. CASE DESCRIPTION: A 69-year-old man accidentally fell from a stepladder with a height of 3 m. There was a sprinkler on the ground, and it went through his posterior part of the right auricle at the collision. He was alert on admission. However, neurological examination showed right trigeminal, abducens, and facial nerve palsy. Computed tomography was performed, and it revealed that the objects penetrated the petrosal bone. Furthermore, it caused traumatic subarachnoid hemorrhage and acute subdural hemorrhage. Fortunately, it did not reach any cerebral artery and cerebral parenchyma. Immediately it was surgically removed with a good outcome. CONCLUSION: When suspected sigmoid sinus injury in head penetrating injury, craniotomy should be considered with bleeding from the sigmoid sinus during surgery.

Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats.

BACKGROUND: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. METHODS: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). RESULTS: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. CONCLUSIONS: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.

Spinal Cord Diffuse Midline Glioma, H3K27M- mutant Effectively Treated with Bevacizumab: A Report of Two Cases.

"Diffuse midline glioma (DMG), H3K27M-mutant" was newly classified in the revised World Health Organization (WHO) 2016 classification of central nervous system tumors. Spinal cord DMG, H3K27M-mutant is relatively rare, with poor prognosis, and there are no effective treatment protocols. In this study, we report two cases of spinal cord DMG, H3K27M-mutant treated with bevacizumab. The two patients were women in their 40s who initially presented with sensory impairment. MRI showed spinal intramedullary tumors, and each patient underwent laminectomy/laminoplasty and biopsy of the tumors. Histological examination initially suggested low-grade astrocytoma in case 1 and glioblastoma in case 2. Upon further immunohistochemical examination in case 1 and molecular examination in case 2, however, both cases were diagnosed as DMG, H3K27M-mutant. Case 1 was treated with radiation therapy and temozolomide (TMZ) chemotherapy, which induced a transient improvement of symptoms; 3 months after surgery, however, the patient's symptoms rapidly deteriorated. MRI showed tumor enlargement with edema to the medulla. Triweekly administration of bevacizumab improved her symptoms for the following 12 months. Case 2 was treated with bevacizumab from the beginning because of acute deterioration of breathing. After bevacizumab administration, both cases showed tumor regression on MRI and drastic improvement of symptoms within a few days. Although spinal cord DMG, H3K27M-mutant has an aggressive clinical course and poor prognosis, bevacizumab administration may offer the significant clinical benefit of alleviating edema, which improves patient's capacity for activities of daily life.

Long-Term Continuous Cervical Spinal Cord Stimulation Exerts Neuroprotective Effects in Experimental Parkinson's Disease.

BACKGROUND: Spinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson's disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients. OBJECTIVE: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. METHODS: We developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis. RESULTS: The 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group. CONCLUSIONS: This study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms.

Treatment Strategy for Progressive Cervical Internal Carotid Artery Stenosis Under Restriction of the Use of Antiplatelet Drugs.

BACKGROUND: Acute ischemic stroke caused by cervical internal carotid artery stenosis (ICS) with altered consciousness and progressive paralysis leads to a poor neurologic prognosis. When such a patient is brought to the hospital in the hyperacute phase, intravenous tissue plasminogen activator is first administered. However, when an indwelling carotid artery stent is required after administration, physicians often hesitate to use antithrombotic drugs. In this report, we propose performing staged angioplasty (SAP) for such cases. METHODS: Four patients were retrospectively investigated. In all 4 patients, we immediately performed only percutaneous transluminal angioplasty (PTA) without antiplatelet drugs. If both cerebral perfusion on angiography and neurologic findings improved, no additional treatment was provided; otherwise, emergency carotid artery stenting (eCAS) was performed. In PTA-successful cases, eCAS or carotid endarterectomy (CEA) was performed with single or dual antiplatelet drugs at a later date. RESULTS: The success rate of PTA was 50% (2 of 4), and the overall treatment success rate was 100% (4 of 4). Three patients had favorable outcomes (modified Rankin Scale [mRS] score 0-2), but unfortunately, 1 patient had severe disability (mRS score >3) on discharge. The PTA-successful patients had no perioperative complications. On the other hand, 1 of the 2 patients who underwent eCAS experienced embolic complications, including distal embolization. CONCLUSIONS: In this investigation, both eCAS and SAP could be performed safety. However, performing SAP first without antiplatelet drugs to avoid hemorrhagic complications and cerebral hyperperfusion syndrome appears to have considerable validity.

A Case of Nonconsecutive Multiple-level Lumbar Spondylolysis Successfully Treated with Single-level Repair of the Pars Interarticularis.

Lumbar spondylolysis is commonly recognized at a single-level of the lumbar spine and frequently affects the L5 pars interarticularis unilaterally or bilaterally. Some reports have described multiple-level spondylolysis, most cases of which occur at consecutive lumbar segments. We herein present a rare case of lumbar spondylolysis involving nonconsecutive multiple-level segments; only eight such cases have been reported previously. A 38-year-old man presented with a 10-month history of chronic severe low back pain. Lumbar flexion-extension radiographs and computed tomography revealed spondylolysis at the level of L3 and L5, whereas no spondylolisthesis was present and the intervertebral disc spaces were maintained at all levels. Because 6 months of conservative management failed and repeated diagnostic blocks confirmed that the fracture of the L3 pars interarticularis was generating pain, repair of the bilateral L3 pars interarticularis with the smiley face rod method was performed. At the last follow-up 1 year after surgery, the patient had resumed normal life as a laborer and reported no back pain.

Repair of damaged cortical artery by direct micro-suture in surgical treatment of acute subdural hematoma: technical note.

BACKGROUND: In surgical treatment of acute subdural hematoma (ASDH), neurosurgeons frequently encounter bleeding from cortical arteries, which is usually controlled with bipolar coagulation. However, bipolar coagulation is associated with a risk of sacrificing the cortical artery, which may affect the prognosis of neurological symptoms when these cortical arteries supply critical areas. In this article, we describe microsurgical repair of damaged cortical arteries using a 10-0 nylon micro-suture in patients with arterial-origin ASDH. METHODS: After removal of the subdural hematoma, the exact bleeding point of the cortical artery was identified, and the 10-0 nylon suture stitches were placed on the arterial tear under a microscope. After completion of the micro-suture, vascular patency was confirmed by indocyanine green (ICG) videoangiography. RESULTS: From June 2015 through February 2017, microsurgical repair was performed for seven cortical arteries in six patients. All damaged arteries were located near the Sylvian fissure, and all tears were pinhole tears. The average blood flow occlusion time was 8 min (range, 0-15 min). The patency of all seven repaired arteries was successfully confirmed by ICG videoangiography. Postoperative cerebral infarction was not observed except in one patient with cerebral contusion and a history of severe head trauma. CONCLUSIONS: The present report demonstrates that repair of a cortical artery by the 10-0 nylon micro-suture is a simple and safe method with a low risk of sacrificing the artery. This technique may be a good option in the surgical treatment of arterial-origin ASDH, especially when the accompanying cerebral contusion is minimal.

A Case of Posterior Circulation Ischemic Stroke Caused by Heparin-Induced Thrombocytopenia after Detaining Hepatic Arterial Infusion Catheter.

In Japan, hepatic arterial infusion chemotherapy (HAIC) using reservoir system is recommended for patients with hepatocellular carcinoma (HCC) whose hepatic spare ability is favorable. Arterial infusion catheter is commonly detained in hepatic artery via femoral or brachial artery. In our hospital, catheter is often inserted by puncturing the left subclavian or brachial artery considering the patient's activities of daily living (ADL) during long-term detaining. However, it rarely causes posterior circulation ischemic stroke because of the left vertebral artery branches on the path of catheter. We herein report a case of posterior circulation ischemic stroke caused by heparin-induced thrombosis (HIT) after detaining hepatic arterial infusion catheter. A 63-year-old man who is under HAIC treatment for HCC was introduced to the department of neurological surgery because of vertigo and vomiting. Magnetic resonance imaging revealed sporadic fresh cerebral infarction in the bilateral cerebellar hemisphere. Carotid ultrasonography detected a floating thrombus around the part of the left vertebral subclavian artery bifurcation. Detained catheter was removed and continuous heparin administration was started immediately. However, thrombocytopenia occurred 5 days after the injection. Because 4T's score was 6 points, HIT was strongly suspected. We stopped heparin injection immediately and observed the patient's physical status strictly. After that, platelet value improved naturally. At the late date, antibodies specific for platelet factor 4/heparin complexes were positive and he was diagnosed with HIT.