Fluctuating patency of atherosclerotic cervical internal carotid artery treated by carotid endarterectomy successfully: a case report.

Spontaneous recanalization of an atherosclerotic internal carotid artery (ICA) occlusion has been previously reported as a rare phenomenon, but spontaneous re-occlusion shortly after recanalization under antiplatelet therapy has not been documented yet. A 63-year-old man presented with impaired consciousness and left-sided hemiparesis. Magnetic resonance imaging showed new infarction in the right middle cerebral artery territory because of right cervical internal carotid artery occlusion, which became spontaneously patent on computed tomography angiography on the sixth day of admission. So carotid endarterectomy was planned. However, the ICA was recurrently occluded on the preoperative magnetic resonance angiogram three weeks later on admission, which condition was also confirmed during the subsequent surgery. In patients with severe ICA stenosis, patency may dynamically change even under antiplatelet therapy.

Reconstruction of the temporal line for sinking skin flap syndrome using split rib grafts: a technical note.

Sinking skin flap syndrome (SSFS), also known as syndrome of the trephined, is one of the complications of decompressive craniectomy. The definitive treatment for the condition is cranioplasty, but there are cases where that is not an option. We report a seventy-seven-year-old male patient with disturbance of consciousness after removal of infected bone flap and debridement. The skin showed marked depression and SSFS was diagnosed. The scalp had contracted due to infection and debridement so as to need skin grafting. Cranioplasty with a full-size bone flap was not an option. Reconstruction of the temporal line with autologous rib graft was performed. The patient became alert after the operation.

How I do it: re-do surgery for recurrent trigeminal neuralgia.

BACKGROUND: When trigeminal neuralgia recurs after microvascular decompression surgery, re-operation may be indicated if trigeminal nerve compression remains. However, surgery for recurrent trigeminal neuralgia is more difficult because of adhesions between the prosthesis, such as the Teflon sling, and the surrounding structures, including the blood vessels, in addition to common post-open surgery adhesions. METHOD: A case of a patient with recurrent trigeminal neuralgia is presented. CONCLUSION: Preoperative evaluation of the compression of the trigeminal nerve is important. The pre-existing prosthesis does not necessarily need to be removed entirely.

[Original Ventriculoperitoneal Shunt for Pediatric Hydrocephalus].

Although the use of newly developed procedures such as endoscopic third ventriculostomy or coagulation of the choroid plexus has gradually expanded, ventriculoperitoneal(VP)shunts are still not obsolete. They are the most commonly performed surgery for treating pediatric hydrocephalus. Young neurosurgeons may frequently encounter this CSF diversion procedure in clinical practice. However, the VP shunt remains a failure-prone procedure, as exemplified by obstruction, infection, mechanical shunt failure, over drainage, and distal catheter site-specific failures. Therefore, surgery requires exquisite techniques, especially in the pediatric population, to meet the needs of the child's growth. This article sheds light on the refined methodology for pediatric VP shunting with meticulous details of the surgical technique. Neurosurgeons must always remember that appropriate ICP control has a major impact on patient development and that a stably functioning VP shunt can deliver the full potential of children with hydrocephalus.

The long-term outcome of CyberKnife-based stereotactic radiotherapy for central skull base meningiomas: a single-center experience.

Few reports exist demonstrating the effects of stereotactic radiotherapy (SRT) on the central skull base meningiomas (CSMs). A retrospective analysis of 113 patients was performed. The median age was 62 (IQR 50-72) years old, and 78 patients (69%) were female. Upfront SRT was performed in 41 (36%), where 17 (15%) patients were asymptomatic. The other SRT was for postoperative adjuvant therapy in 32 (28%), and for the recurrent or relapsed tumors in 40 (35%) patients. Previous operation was done in 74 patients (66%). Among the available pathology in 46 patients, 37 (80%) were WHO grade I, 8 (17%) were grade II, and 1 (2%) was grade III. The median prescribed dose covered 95% of the planning target volume was 25 (IQR 21-25) Gy, and the median target volume was 9.5 (IQR 3.9-16.9) cm3. The median progression-free survival (PFS) was 48 (IQR 23-73) months and 84% and 78% were free of tumor progression at 5 and 10 years respectively. The median follow-up was 49 (IQR 28-83) months. PFS was better in grade I than grade II (p = 0.02). No other baseline factors including the history of previous operation were associated with PD or PFS. Adverse events of radiation therapy were radiation-induced optic neuropathy (0.9%), and cerebral edema (4.4%). Asymptomatic cavernous carotid stenosis was found in three (2.7%), five (4.4%) underwent ventriculoperitoneal shunt placement for normal pressure hydrocephalus, and five (4.4%) died. SRT is useful for the management of CSMs with a low rate of adverse events.

Occipital artery-anterior cerebral artery bypass with posterior auricular artery-middle cerebral artery bypass for stenosis of the internal carotid artery bifurcation.

Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass, and STA-anterior cerebral artery (ACA) bypass, are options for direct revascularisation of anterior circulation. However, some patients don't have a suitable STA to use as a donor, so an alternative procedure must be performed. A 59-year-old, right-handed man presented with dysphasia and right-sided hemiparesis due to a transient ischaemic attack. Imaging studies revealed severe stenosis of the left internal carotid artery bifurcation. Iodoamphetamine single photon emission computed tomography demonstrated reduced cerebrovascular reserve capacity in the left hemisphere. The patient was started on antiplatelet therapy, but the ischaemic attacks persisted after one month. Thus, revascularisation of the ACA and MCA territories was considered. Digital subtraction angiography revealed prominence in the left occipital artery (OA) and posterior auricular artery (PAA), while the left STA was hypoplastic, terminating at the squamous suture level. Therefore, anastomoses were performed between both the OA and ACA and the PAA and MCA. Revascularisation was successful, and the ischaemic attacks disappeared. OA-ACA bypass, together with PAA-MCA bypass, may be effective for wide cerebral revascularisation when the STA is not available.

A Phenotypic Switch of Differentiated Glial Cells to Dedifferentiated Cells Is Regulated by Folate Receptor α.

In a previous study, we showed that folate receptor-α (FRα) translocates to the nucleus where it acts as a transcription factor and upregulates Hes1, Oct4, Sox2, and Klf4 genes responsible for pluripotency. Here, we show that acetylation and phosphorylation of FRα favor its nuclear translocation in the presence of folate and can cause a phenotypic switch from differentiated glial cells to dedifferentiated cells. shRNA-FRα mediated knockdown of FRα was used to confirm the role of FRα in dedifferentiation. Ocimum sanctum hydrophilic fraction-1 treatment not only blocks the folate mediated dedifferentiation of glial cells but also promotes redifferentiation of dedifferentiated glial cells, possibly by reducing the nuclear translocation of ~38 kDa FRα and subsequent interaction with chromatin assembly factor-1. Stem Cells 2019;37:1441-1454.

Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells.

Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRα regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FRα upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs. Quantitative RT-PCR and chromatin immunoprecipitation showed that FRα upregulates Oct4, Sox2, and Klf4 by binding to their cis-regulator elements-5' enhancer/promoters defined by H3K27Ac and p300 occupancy. FA via FRα downregulates miRNAs, miR-138 and miR-let-7, which target Oct4 and Trim71 (an Oct4 downstream effector), respectively. Co-immunoprecipitation data suggests that FRα interacts with the Drosha-DGCR8 complex to affect pre-miRNA processing. Transfecting anti-miR-138 or anti-miR-let-7 into non-proliferating neural crest cells (NCCs) derived from Splotch (Sp-/- ), restored their proliferation potential. In summary, these results suggest a novel pleiotropic role of FRα: (a) direct activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. Stem Cells 2016;34:2721-2732.

A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 -/- embryos.

PURPOSE: Maternal folate intake has reduced the incidence of human neural tube defects by 60-70 %. However, 30-40 % of cases remain nonresponsive to folate intake. The main purpose of this study was to understand the molecular mechanism of folate nonresponsiveness in a mouse model of neural tube defect. METHODS: We used a folate-nonresponsive Fkbp8 knockout mouse model to elucidate the molecular mechanism(s) of folate nonresponsiveness. Neurospheres were grown from neural stem cells isolated from the lumbar neural tube of E9.5 Fkbp8 (-/-) and wild-type embryos. Immunostaining was used to determine the protein levels of oligodendrocyte transcription factor 2 (Olig2), Nkx6.1, class III beta-tubulin (TuJ1), O4, glial fibrillary acidic protein (GFAP), histone H3 Lys27 trimethylation (H3K27me3), ubiquitously transcribed tetratricopeptide repeat (UTX), and Msx2, and quantitative real-time (RT)-PCR was used to determine the message levels of Olig2, Nkx6.1, Msx2, and noggin in neural stem cells differentiated in the presence and absence of folic acid. RESULTS: Fkbp8 (-/-)-derived neural stem cells showed (i) increased noggin expression; (ii) decreased Msx2 expression; (iii) premature differentiation--neurogenesis, oligodendrogenesis (Olig2 expression), and gliogenesis (GFAP expression); and (iv) increased UTX expression and decreased H3K27me3 polycomb modification. Exogenous folic acid did not reverse these markers. CONCLUSIONS: Folate nonresponsiveness could be attributed in part to increased noggin expression in Fkbp8 (-/-) embryos, resulting in decreased Msx2 expression. Folate treatment further increases Olig2 and noggin expression, thereby exacerbating ventralization.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study.

INTRODUCTION: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. METHODS: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. RESULTS: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26). CONCLUSION: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer. REGISTRATION: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Clinical Feature and General Management of Post-Hemorrhagic Hydrocephalus in Premature Infants.

Recently, the survival of the high-risk population of preterm infants has steadily improved, and the severity of prematurity is a growing threat of gestational-age-related fatal conditions. Posthemorrhagic hydrocephalus (PHH) is the most common but serious neurological complication in premature infants, which can have life-threatening consequences during the acute phase in the neonatal period and life-long psychomotor and cognitive sequelae in their later life. Although neonatologists, pediatric neurologists, and pediatric neurosurgeons have investigated a diversified strategy for several decades, a consensus on the best management of PHH in premature infants still must be reached. Several approaches have tried to reduce the incidence of intraventricular hemorrhage (IVH) and mitigate the effect of IVH-related hydrocephalus. This paper reviews and discusses the clinical feature of PHH in premature infants, general/nonsurgical management of prematurity for IVH prevention, and posthemorrhagic management, and how and when to intervene.

Modified extradural selective anterior clinoidectomy leaving the optic canal unopened for internal carotid aneurysms: A technical note.

Background: Anterior clinoidectomy is an established procedure used to decompress the optic nerve, mobilize the internal carotid artery (ICA), or enlarge the retrocarotid space. However, its use carries the risk of optic nerve injury. In certain surgeries, such as those for internal carotid aneurysms, propose modification to the anterior clinoidectomy for enlarging the retrocarotid space, especially in operations for ICA aneurysms. Methods: After the anterior clinoid process (ACP) is sufficiently exposed, the internal cancellous bone or pneumatization can be removed through a small window created at its lateral edge to reveal the compact bone of the optic canal. Since the compact bone of the inferior surface facing the ICA is absent or very thin, the ACP can be removed by drilling through the anchoring compact bone with the optic canal in direct sight. Results: In 10 consecutive internal carotid aneurysm cases, the ACP was successfully removed without opening of the optic canal to enlarge the retrocarotid space. Conclusions: Anterior clinoidectomy can be performed to enlarge the retrocarotid space without opening the optic canal from outside the dura.

CyberKnife Radiosurgery for Spinal Intramedullary Arteriovenous Malformations: A Single-Center Experience.

BACKGROUND: Intramedullary spinal arteriovenous malformation (ISAVM, glomus type) is a type of spinal cord arteriovenous malformation, which is a rare disease known often to have a complex vascular supply interfering with that of the spinal cord, and is in complex anatomical relations with cord structures and nerve roots. Though microsurgical and endovascular treatment has mainly been the standard options, in high-risk cases with these treatments, stereotactic radiotherapy (SRT) might be the option of choice. METHODS: We retrospectively reviewed 10 consecutive patients with ISAVM who received SRT using CyberKnife at the Japanese Red Cross Medical Center (Tokyo, Japan) from January 2011 to March 2022. RESULTS: No case in this series suffered from hemorrhage after applying SRT. One case experienced neurological impairment 10 years after SRT, which we attributed to venous congestion due to the remaining lesion. No case of radiation myelopathy was observed in this series. In one case, the nidus volume reduction and loss of flow voids were obvious, though improvement in the neurological outcome was not apparent. No radiological changes were observed in the other 9 patients. CONCLUSIONS: Even in lesions without radiological changes, no hemorrhagic events were observed for an average period of 4 years. SRT may be a feasible option in treating ISAVM, especially for lesions in which microsurgical resection and endovascular treatment are inapplicable. To ascertain the safety and efficacy of this approach, further studies with more patients and longer follow-up is required.

Hypofractionated Stereotactic Radiotherapy with CyberKnife for Large Arteriovenous Malformations and Arteriovenous Malformations Located in Eloquent Areas.

Literature has yet to establish an appropriate treatment strategy for large arteriovenous malformations (AVMs) and AVMs located in eloquent areas. In this study, the treatment outcomes of hypofractionated stereotactic radiotherapy (HSRT) with CyberKnife (CK) for large AVMs and AVMs in eloquent areas were evaluated. This study retrospectively evaluated 38 consecutive patients with AVMs treated with HSRT in the Japanese Red Cross Medical Center between August 2010 and July 2015. Obliteration rates and hemorrhage rates at 3- and 5-years of follow-up were calculated. Factors for hemorrhage and obliteration were analyzed with logistic regression analysis. Fourteen (36.8%) patients had a history of hemorrhage. Twenty (52.6%) AVMs were larger than 10 mL, and 34 (89.5%) AVMs were located in eloquent areas. The majority of the AVMs (84.2%) were classified into high grades (grades 3, 4, and 5) using the Spetzler-Martin grading scale. The median modified radiosurgery-based AVM score was 2.05, and the median Virginia Radiosurgery AVM Score was 3. The mean marginal dose was 24.5 ± 2.5 Gy. Twenty-three and 15 patients received three- and five-fraction stereotactic radiotherapy, respectively. At 3 and 5 years posttreatment, two (2.0%/year) and six (6.7%/year) patients had hemorrhage with obliteration rates of 15.2% and 16.7%, respectively. AVM localization in eloquent areas was a risk factor for obliteration failure. This study revealed that HSRT with CK for large AVMs and AVMs located in eloquent areas contributed to hemorrhage risk reduction and obliteration, at least in the early stages.

Totally Endoscopic Resection of Recurrent Convexity Meningioma Following Multiple Surgeries: Oblique Trajectory to Avoid Manipulation of a Vascularized Free Flap: A Technical Note.

BACKGROUND: Endoscopic surgery is widely used for intraventricular and skull base tumor resections; however, its utility is not limited to deep parts of the brain. METHODS: A 73-year-old female presented with left-side hemiparesis and seizures due to a relapsed atypical meningioma of convexity. The tumor was located just under a synthetic bone substitute and was covered by a delicate myocutaneous free flap, preventing the usual skin incision route to approach the lesion. RESULTS: The tumor was successfully removed using an endoscope without damaging the flap. CONCLUSIONS: With the aid of an endoscope, a superficial meningioma could be removed with the affected dura through a small craniotomy.

Two Cases of Rare Intratumoral Hemorrhage Following COVID-19 Vaccination.

The increase in the rate of mRNA vaccination against coronavirus disease 2019 (COVID-19) worldwide has been accompanied by reports of an increase in the side effects of the vaccine. In the field of neurosurgery, several cases of venous thrombosis have been reported as possible complications after COVID-19 vaccination. However, no such side effects have been reported in patients with brain tumors, and COVID-19 vaccination is considered safe for this patient population. In this report, we present the cases of two patients with brain tumors who experienced intratumoral hemorrhage as a possible side effect of the COVID-19 vaccine. In the first case, a 54-year-old man who had received CyberKnife treatment for a vestibular schwannoma eight years prior presented with tongue discomfort, right-side facial numbness, and dizziness since the day after his COVID-19 vaccination. MRI revealed intratumoral hemorrhage of the vestibular schwannoma. The second patient was a 60-year-old woman who presented with a sudden-onset headache and vomiting that had started three days after her COVID-19 vaccination. CT revealed a meningioma with intratumoral hemorrhage. Both patients had undergone surgery prior to this presentation, and their symptoms had improved. They had no risk factors for intratumoral hemorrhage, suggesting that it may be a side effect of the mRNA vaccine against COVID-19. Although the causal relationship is unclear, acute inflammation with predominantly lymphocytic infiltration and thrombogenicity after COVID-19 vaccination may damage the fragile microcirculation of the tumor.

The Treatment Outcome of CyberKnife-Based Stereotactic Radiotherapy for Intracranial and Extracranial Nonvestibular Schwannomas: A Single-Center Experience.

BACKGROUND: Data on the outcomes of CyberKnife-based hypofractionated stereotactic radiosurgery (hSRS) for intracranial and extracranial nonvestibular schwannomas (nVSs) are not sufficient. METHODS: Patients who underwent hSRS for nVSs between 2010 and 2019 were retrospectively reviewed. RESULTS: A total of 39 patients with 39 nVSs were identified. The mean age was 53 (±18) years, and 20 patients (51%) were women. Twenty-five patients (64%) had previous surgeries. Seventeen patients (44%) had nVSs extending outside the cranium. The mean prescribed dose covering 95% of the planning target volume was 22 Gy (±3.7 Gy), the mean fractionation was 4 (±2), and the mean target volume was 13 cm3 (±16 cm3). The radiological tumor control rate was 100% during the mean follow-up period of 67 months (±37 months). Thirty-seven patients (95%) were clinically stable during the mean follow-up period of 72 months (±35 months). Nine patients (23%) suffered from transient adverse radiation effects (AREs), including transient tumor expansion, and 2 (5%) suffered from permanent AREs. CONCLUSIONS: We summarized the treatment outcomes of hSRS for nVSs. Although all patients achieved radiological tumor control, the risk of either transient or permanent ARE was high. Therefore, it is necessary to monitor patients for clinical deterioration due to AREs.

Elongated styloid process as a possible cause of distal carotid artery dissection after carotid endarterectomy using indwelling shunt: A case report.

Background: A dissection beginning from a point distal to the endpoint of the carotid endarterectomy (CEA) is called distal carotid artery dissection (CAD), which is known as one of the significant surgical complications of CEA. Case Description: We present a case of distal CAD as a perioperative complication after CEA using indwelling shunt. We estimated this pathophysiology to be caused by the mechanical conflict of the inflated balloon with the elongated styloid process. Conclusion: Since a distal CAD can cause severe, irreversible neurological deficits, preoperative assessment of the styloid process should be routinely performed in CEA.

Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development.

The mechanism(s) behind folate rescue of neural tube closure are not well understood. In this study we show that maternal intake of folate prior to conception reverses the proliferation potential of neural crest stem cells in homozygous Splotch embryos (Sp(-/-)) via epigenetic mechanisms. It is also shown that the pattern of differentiation seen in these cells is similar to wild-type (WT). Cells from open caudal neural tubes of Sp(-/-) embryos exhibit increased H3K27 methylation and decreased expression of KDM6B possibly due to up-regulation of KDM6B targeting micro-RNAs such as miR-138, miR-148a, miR-185, and miR-339-5p. In our model, folate reversed these epigenetic marks in folate-rescued Sp(-/-) embryos. Using tissue from caudal neural tubes of murine embryos we also examined H3K27me2 and KDM6B association with Hes1 and Neurog2 promoters at embryonic day E10.5, the proliferative stage, and E12.5, when neural differentiation begins. In Sp(-/-) embryos compared with WT, levels of H3K27me2 associated with the Hes1 promoter were increased at E10.5, and levels associated with the Neurog2 promoter were increased at E12.5. KDM6B association with Hes1 and Neurog2 promoters was inversely related to H3K27me2 levels. These epigenetic changes were reversed in folate-rescued Sp(-/-) embryos. Thus, one of the mechanisms by which folate may rescue the Sp(-/-) phenotype is by increasing the expression of KDM6B, which in turn decreases H3K27 methylation marks on Hes1 and Neurog2 promoters thereby affecting gene transcription.