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Abstract Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Abstract DNA methylation is crucial for chromatin structure and gene expression and its aberrancies, including the global “hypomethylator phenotype”, are associated with cancer. Here we show that an underlying mechanism for this phenotype in the large proportion of the highly lethal brain tumor glioblastoma (GBM) carrying receptor tyrosine kinase gene mutations, involves the mechanistic target of rapamycin complex 2 (mTORC2), that is critical for growth factor signaling. In this scenario, mTORC2 suppresses the expression of the de novo DNA methyltransferase (DNMT3A) thereby inducing genome-wide DNA hypomethylation. Mechanistically, mTORC2 facilitates a redistribution of EZH2 histone methyltransferase into the promoter region of DNMT3A, and epigenetically represses the expression of DNA methyltransferase. Integrated analyses in both orthotopic mouse models and clinical GBM samples indicate that the DNA hypomethylator phenotype consistently reprograms a glutamate metabolism network, eventually driving GBM cell invasion and survival. These results nominate mTORC2 as a novel regulator of DNA hypomethylation in cancer and an exploitable target against cancer-promoting epigenetics.

Neurosurgery is complex surgery that requires a strategy that maximizes the removal of tumors and minimizes complications; thus, a safe environment during surgery should be guaranteed. In this study, we aimed to verify the safety of brain surgery using intraoperative magnetic resonance imaging (iMRI), based on surgical experience since 2000. Thus, we retrospectively examined 2,018 surgical procedures that utilized iMRI performed in the operating room at Tokyo Women's Medical University Hospital between March 2000 and October 2019. As per our data, glioma constituted the majority of the cases (1,711 cases, 84.8%), followed by cavernous hemangioma (61 cases, 3.0%), metastatic brain tumor (37 cases, 1.8%), and meningioma (31 cases, 1.5%). In total, 1,704 patients who underwent glioma removal were analyzed for mortality within 30 days of surgery and for reoperation rates and the underlying causes within 24 hours and 30 days of surgery. As per our analysis, only one death out of all the glioma cases (0.06%) was reported within the 30-day period. Meanwhile, reoperation within 30 days was performed in 37 patients (2.2%) due to postoperative bleeding in 17 patients (1.0%), infection in 12 patients (0.7%), hydrocephalus in 6 patients (0.4%), cerebrospinal fluid (CSF) leakage in 1 patient, and brain edema in 1 patient (0.06%). Of these, 14 cases (0.8%) of reoperation were performed within 24 hours, that is, 13 cases (0.8%) due to postoperative bleeding and 1 case (0.06%) due to acute hydrocephalus. Mortality rate within 30 days was less than 0.1%. Thus, information-guided surgery with iMRI can improve the safety of surgical resections, including those of gliomas.

Abstract Objective This study aimed to report the long‐term results of thalamotomy in 23 patients with task‐specific tremor. Methods Data of 23 patients with task‐specific tremor who underwent ventralis intermedius nucleus and posterior part of ventro‐oral nucleus thalamotomy at the Tokyo Women's Medical University Hospital between 2010 and 2022 were retrospectively analyzed. To evaluate neurological conditions, the severity of task‐specific tremor was divided into 0 (no tremor), 1 (slightly tremulous), 2 (moderately tremulous), 3 (accomplishing tasks with great difficulty), and 4 (unable to complete tasks). We also used the subscores “handwriting” (0–4) and “spiral drawing” (0–4) of the Clinical Rating Scales for Tremor. Evaluation scales were presented as medians and interquartile ranges. Results The severities of task‐specific tremor were 3.0 (3.0–4.0) preoperatively and 0.0 (0.0–0.0, p

Abstract A 62‐year‐old female experienced an extensive cerebral contusion in the left frontotemporal lobe due to an acute subdural hematoma at the age of 44 years. Six months after the injury, the patient developed epileptic seizures. The seizures were generalized with right cervical rotation and fencing posture. Despite prescriptions for four antiepileptic drugs, partial seizures occurred several times a month and focal to bilateral tonic‐clonic seizures once every 2 months. Video‐electroencephalography showed epileptic discharges in the left frontal lobe. The patient was subsequently referred to our department for palliative surgery. The patient underwent a left Forel‐H‐tomy. The prescription of antiepileptic drugs was not changed, and the patient was seizure free for 1 year. Forel‐H‐tomy, a surgical procedure for intractable epilepsy, was pioneered by Dennosuke Jinnai. Despite its previously reported remarkable efficacy, Forel‐H‐tomy has not been performed for several decades. Nevertheless, it remains a potential alternative treatment option for drug‐resistant epilepsy.

Various surgical treatments are available for occlusive subclavian and common carotid artery diseases. Nevertheless, to date, when cerebral endovascular treatment is utilized, revascularization via direct surgery may be required. This study reported five symptomatic cases of revascularization for CCA and SCA occlusive and stenotic lesions that were expected to be challenging to treat with endovascular treatment. We performed subclavian artery-common carotid artery or internal carotid artery bypass using artificial blood vessels or saphenous vein grafts in five patients with subclavian steal syndrome, symptomatic common carotid artery occlusion, and severe proximal common carotid artery stenosis. In this study, good bypass patency was achieved in all five cases. Although there were no intraoperative complications, one patient had a postoperative lymphatic leak. Moreover, there was no recurrence of stroke during postoperative follow-up for an average of 2 years. Conclusively, subclavian artery-common carotid artery bypass can be an effective surgical treatment for common carotid artery occlusion, proximal common carotid artery stenosis, and subclavian artery occlusion.

Abstract A 30‐year‐old woman with tardive dystonia in the cervical region from long‐term antipsychotic meds was treated with radiofrequency ablation of the right pallidothalamic tract in the fields of Forel. The patient showed improvement in both cervical dystonia and obsessive–compulsive disorder after the procedure, with 77.4% improvement in cervical dystonia and 86.7% improvement in obsessive–compulsive disorder. Although the treatment site in this case was intended to treat cervical dystonia, the lesion was located in the optimal stimulation network for both obsessive–compulsive disorder and cervical dystonia, suggesting that neuromodulation of this region could potentially treat both simultaneously.

Abstract This study evaluated whether cell sheets containing a network of lymphatic endothelial cells (LECs) promoted lymphangiogenesis after transplantation in vivo. Cell sheets with a LEC network were constructed by co-culturing LECs and adipose-derived stem cells (ASCs) on temperature-responsive culture dishes. A cell ratio of 3:2 (vs. 1:4) generated networks with more branches and longer branch lengths. LEC-derived lymphatic vessels were observed 2 weeks after transplantation of a three-layered cell sheet construct onto rat gluteal muscle. Lymphatic vessel number, diameter and depth were greatest for a construct comprising two ASC sheets stacked on a LEC/ASC (3:2 ratio) sheet. Transplantation of this construct in a rat model of femoral lymphangiectomy led to the formation of functional lymphatic vessels containing both transplanted and host LECs. Further development of this technique may lead to a new method of promoting lymphangiogenesis.

Facial asymmetry is often seen in patients with skeletal mandibular prognathism and is associated with deformities in the maxillofacial and head regions. The maxillofacial deviation is three-dimensional and affects not only the lateral deviation of the mandible and midface, but also the cranium. This study conducted a three-dimensional morphological evaluation of the cranial base morphology of patients with skeletal mandibular prognathism (ANB < 0°, Wits < 0 mm) with the aim of examining the relationship between deformities of the head region and facial asymmetry. Data obtained from computed tomography conducted during the initial examination of patients with and without skeletal mandibular prognathism with facial asymmetry were used. Differences in the position of structures present in the cranial base were measured, and the association between cranial deformities and mandibular deviation was assessed. The middle cranial base area and the lateral deviation of the mandibular fossa were significantly larger in patients with facial asymmetry compared to those without facial asymmetry. In addition, a correlation between the amount of mandibular deviation and the area of the anterior cranial base was identified in patients with significant cranial deformity (p = 0.012). Given the identified association between the structure of the head region and facial asymmetry, further studies are needed to determine the factors implicated in the growth process.

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Abstract Background Neurosurgical ablation of Forel's field H1 for cervical dystonia, which is currently abandoned, was formerly used in the 1960s–1970s. Regardless of the lack of neuroimaging modalities and objective evaluation scales, the reported efficacy was significant. Although recent studies have reappraised the ablation of the pallidothalamic tract at Forel's field H1 for Parkinson's disease, the efficacy for cervical dystonia has not been investigated well. Methods Data of 35 patients with cervical dystonia who underwent unilateral pallidothalamic tractotomy at Forel's field H1 were retrospectively analyzed. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores, the neck score of the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), and adverse events were evaluated preoperatively and at the last available follow‐up period. Results The mean clinical follow‐up period was 13.9 ± 6.5 months. The mean TWSTRS total scores were 34.3 ± 14.0 preoperatively and 18.4 ± 16.5 at the last available follow‐up period (46.4% improvement, p

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129–214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1–42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.

Abstract Objective Ablation of the globus pallidus internus (pallidotomy) is an effective surgical intervention for dystonia. However, the current literature on the efficacy and safety of pallidotomy for dystonia is derived only from single‐case reports and small cohort studies. Methods We retrospectively analyzed patients with primary dystonia who underwent pallidotomy at our institution between 2014 and 2019. Neurological conditions were evaluated using the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS, range: 0–120). We evaluated the total BFMDRS score and each subitem score (nine body regions) in the patients who underwent unilateral and bilateral pallidotomy before surgery and at last available follow‐up. Moreover, postoperative complications were analyzed. Results We found that 69 and 20 patients underwent unilateral and bilateral pallidotomy respectively. The mean age at dystonia onset was 40.4 ± 15.2 years. The mean clinical follow‐up period was 17.2 ± 11.6 months. Unilateral pallidotomy significantly improved the total BFMDRS score from 11.2 ± 14.7 preoperatively to 5.4 ± 7.6 at last available follow‐up (51.8% improvement, p

Abstract Forel‐H‐tomy for intractable epilepsy was introduced by Dennosuke Jinnai in the 1960s. Recently, Forel‐H‐tomy was renamed to “pallidothalamic tractotomy” and revived for the treatment of Parkinson's disease and dystonia. Two of our patients with movement disorders and comorbid epilepsy experienced significant seizure reduction after pallidothalamic tractotomy, demonstrating the efficacy of this method. The first was a 29‐year‐old woman who had temporal lobe epilepsy with focal impaired awareness seizure once every three months and an aura 10‐20 times daily, even with four antiseizure medicines. For the treatment of hand dyskinesia, she underwent left pallidothalamic tractotomy and her right‐hand dyskinesia significantly improved. Fourteen months later, she had experienced no focal impaired awareness seizure and the aura decreased to one to three times per month. The second case was that of a 15‐year‐old boy diagnosed with progressive myoclonic epilepsy, who developed generalized tonic‐clonic seizure, which manifested once every month, despite treatment with five antiseizure medicines. After surgery, myoclonic movements in his right hand slightly improved. A one‐year follow‐up revealed that he had not experienced a generalized tonic‐clonic seizure. The lesion locations in the two cases were close to the vicinity of Jinnai's Forel‐H‐tomy. Forel's field H deserves reconsideration as a treatment target for intractable epilepsy.

The maxillofacial region of patients with facial asymmetry is deformed not only in the mandible but also in the maxilla, suggesting that the head region may also be deformed. Therefore, in this study, skeletally originated mandibular prognathism with facial asymmetry was evaluated in relation to cranial morphology. The cranial morphology of patients who visited the Chiba Dental Center of Tokyo Dental College and were diagnosed with skeletal mandibular prognathism with facial asymmetry (asymmetry group: ANB 0° or less; Menton deviation 4 mm or more; 30 subjects) and without facial asymmetry (symmetry group: ANB less than 0°; Menton deviation less than 3 mm) was measured and evaluated. As a method, the length and area of the cranium were measured using axial cephalometric radiographs. In the asymmetry group, there was a significant difference in the left–right difference in the long diameter of the posterior part of the cranium compared to the symmetry group (p = 0.009). The asymmetry group also had significant differences in the central and occipital areas of the cranium on the left and right sides compared to the symmetry group (p < 0.001). In the asymmetry group, the direction of Menton deviation and the direction of head region deviation coincided in about 70% of the cases. There was also a positive correlation between head deviation and the amount of Menton deviation. The results of this study suggested that patients with facial asymmetry had greater head deformity than patients without facial asymmetry.

Moyamoya disease is an uncommon vascular disease, which causes obstruction and stenosis of arteries of the circle of Willis, and preferentially affects children and young adults. This disease is seen across the world, but is more common in East Asia. It may cause hemorrhagic or ischemic stroke, or transient ischemic attack. If symptoms or cerebral blood flow become worse, revascularization surgery is recommended. We present 2 cases of moyamoya disease who underwent bypass surgery. We also discuss the epidemiology, pathology, genomics, and symptomatology as well as diagnosis, and management of moyamoya disease.

Although there are several reports of the significant efficacy of zolpidem for treating dystonia, zolpidem is still considered an anecdotal treatment. Here, we evaluated the efficacy and safety of zolpidem for treating residual dystonia in patients who previously received various neurosurgical treatments majorly including deep brain stimulation and radiofrequency ablation. We retrospectively reviewed medical records from January 2021 to September 2021 to identify patients with dystonia who had been prescribed zolpidem after undergoing neurosurgery. Twenty patients were enrolled in this study, including those with blepharospasm (two), tongue dystonia (four), mouth dystonia (one), spasmodic dysphonia (two), cervical dystonia (six), focal hand dystonia (three), hemidystonia (two), blepharospasm with cervical dystonia (one), and mouth dystonia with cervical dystonia (one). Single doses of zolpidem ranged between 2.5 and 10 mg, while daily dosages ranged from 10 to 30 mg. The zolpidem dose prescribed was 5–10 mg, with single and daily doses of 7 ± 2.9 and 14.5 ± 6.0 mg, respectively. With zolpidem administration, the participants' Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale score significantly improved from 8.1 ± 6.7 to 3.7 ± 2.5 (50.6% improvement, p < 0.0001). Improvements in arm dystonia, blepharospasm, and spasmodic dysphonia were observed using the Arm Dystonia Disability Scale, Jankovic Rating Scale, and Voice Handicap Index, respectively. No improvements were observed in cervical dystonia on the Toronto Western Spasmodic Torticollis Rating Scale. Drowsiness, including three cases each of mild and moderate drowsiness, was the most frequent adverse effect (30%), which persisted for 2–3 h. Transient amnesia and rapid eye movement sleep behavior disorder occurred in two patients and one patient, respectively. Although our findings suggest that zolpidem can be a valuable treatment option for patients with residual dystonia after neurosurgical treatments, the beneficial effects for cervical dystonia were limited.

Background: Glioblastoma is a highly aggressive primary malignant brain tumor. New treatments, especially ones that can eradicate subpopulations with stem-cell-like properties, are currently being explored. In vitro, epirubicin has demonstrated toxicity towards such populations. However, epirubicin fails to readily cross the blood-brain barrier. Furthermore, its efficacy against stem-like tumor cells growing within the neural tissue has not been fully addressed. Polymeric micelles are an advanced system developed to enhance drug delivery into tumors.Methods: We have investigated the effect of epirubicin micelles against murine glioma initiating cells (GICs) in vitro and ex vivo.Results: In vitro, epirubicin micelles inhibited the sphere growth of GICs in a dose-dependent manner. Furthermore, they also inhibited the growth of GIC-based tumors in ex vivo cultured brain slices from the tumor-bearing mice. This effect was inversely proportional to the tumor size at the beginning of the treatment.Conclusions: Our results suggest that epirubicin micelles are effective against murine glioma cells with stem cell properties and their use should be initiated at an early stage.

Abstract Mutations in the lysine methyltransferase 2B (KMT2B) gene have recently been reported to be associated with childhood‐onset generalized dystonia. There have been no studies investigating ablative treatments for the management of this disorder. Three patients underwent either a staged unilateral pallidotomy and contralateral pallidothalamic tractotomy (19‐year‐old man, 2‐year follow‐up), a unilateral pallidothalamic tractotomy (34‐year‐old man, 6‐month follow‐up) or a simultaneous unilateral pallidothalamic tractotomy and ventro‐oral thalamotomy (29‐year‐old man, 6‐month follow‐up). The average total patient score on the Burke‐Fahn‐Marsden Dystonia Rating Scale‐Movement Scale improved from 39.5 to 13.2 (66.6%) after the procedures. No significant complications were identified. Ablative treatments appear to be a promising alternative surgical option for generalized dystonia with KMT2B mutation.

Introduction: Moyamoya disease (MMD) is a rare cerebrovascular disease associated with cerebral infarction or hemorrhage. Hyperperfusion is the most significant complication of direct bypass surgery. Previous research has shown that an increase in cerebral blood flow (CBF) is strongly related to symptomatic hyperperfusion and highlighted the importance of postoperative assessment of CBF. Objective: The principal aims of this study were to quantitatively analyze the relationship between intraoperative graft flow and increase in CBF and to evaluate the effectiveness of intraoperative graft flow measurement during bypass surgery for patients with MMD. Methods: This study included 91 surgeries in 67 consecutive adult patients with MMD who underwent direct revascularization surgery at our institution between November 2013 and September 2018. Intraoperative graft flow of the branches and main trunk was measured in all patients, after anastomosis had been established. Postoperative CBF measurements were performed under sedation, immediately after surgery. Radiological hyperperfusion was defined as focal high uptake, as determined by CBF imaging immediately after surgery. Patients were divided into two groups (radiological hyperperfusion and nonradiological hyperperfusion groups), and the relationship between intraoperative graft flow and radiological hyperperfusion was analyzed. Results: Significant differences were observed between the radiological hyperperfusion and nonradiological hyperperfusion groups in terms of intraoperative graft flow of both the branch (median 72 vs. 42 mL/min, respectively; p < 0.01) and main trunk (median 113 vs. 68 mL/min, respectively; p < 0.01). A receiver-operating characteristic analysis was performed to test the utility of intraoperative flow as a quantitative measure. We set the cutoff values for the intraoperative branch and main trunk flow at 57 mL/min (sensitivity: 0.707, specificity: 0.702; area under the curve [AUC]: 0.773; 95% confidence interval [CI]: 0.675–0.871) and 84 mL/min (sensitivity: 0.667, specificity: 0.771; AUC: 0.78; 95% CI: 0.685–0.875), respectively. Conclusions: Measuring intraoperative graft flow during bypass surgery may be an effective means of predicting hyperperfusion and could serve to facilitate early therapeutic intervention such as strict blood pressure control.

PurposeWe developed a navigation system that superimposes the fractional anisotropy (FA) color map of pre-operative diffusion tensor imaging (DTI) and intraoperative magnetic resonance imaging (MRI). The current study aimed to investigate the usefulness of this system for neurophysiological monitoring and examination under awake craniotomy during tumor removal.MethodA total of 10 glioma patients (4 patients with right-side tumors; 5 men and 5 women; average age, 34 years) were evaluated. Among them, the tumor was localized to the frontal lobe, insular cortex, and parietal lobe in 8, 1, and 1 patient, respectively. There were 3 patients who underwent surgery on general anesthesia, while 7 patients underwent awake craniotomy. The index of DTI anisotropy taken pre-operatively (magnetic field: 3 tesla, 6 motion probing gradient directions) was analyzed as a color map (FA color map) and concurrently co-registered in the intraoperative MRI within the navigation. In addition to localization of the bipolar coagulator and the cortical stimulator for brain mapping on intraoperative MRI, the pre-operative FA color map was also concurrently integrated and displayed on the navigation monitor. This white matter nerve functional information was confirmed directly by using neurological examination and referring to the electrophysiological monitoring.ResultsIntraoperative MRI, integrated pre-operative FA color map, and microscopic surgical view were displayed on one screen in all 10 patients, and white matter fibers including the pyramidal tract were displayed as a reference in blue. Regarding motor function, motor-evoked potential was monitored as appropriate in all cases, and removal was possible while directly confirming motor symptoms under awake craniotomy. Furthermore, the white matter fibers including the superior longitudinal fasciculus were displayed in green. Importantly, it was useful not only to localize the resection site, but to identify language-related, eye movement-related, and motor fibers at the electrical stimulation site. All motor and/or language white matter tracts were identified and visualized with the co-registration and then with an acceptable post-operative neurological outcome.ConclusionCo-registering an intraoperative MR images and a pre-operative FA color map is a practical and useful method to predict the localization of critical white matter nerve functions intraoperatively in glioma surgery.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by transient dyskinetic movements, including dystonia, chorea, or both, triggered by sudden voluntary movements. Carbamazepine and other antiepileptic drugs (AEDs) are widely used in the treatment of PKD, and they provide complete remission in 80–90% of medically treated patients. However, the adverse effects of AEDs include drowsiness and dizziness, which interfere with patients' daily lives. For those with poor compatibility with AEDs, other treatment approaches are warranted.Case Report: A 19-year-old man presented to our institute with right hand and foot dyskinesia. He had a significant family history of PKD; his uncle, grandfather, and grandfather's brother had PKD. The patient first experienced paroxysmal involuntary left hand and toe flexion with left forearm pronation triggered by sudden voluntary movements at the age of 14. Carbamazepine (100 mg/day) was prescribed, which led to a significant reduction in the frequency of attacks. However, carbamazepine induced drowsiness, which significantly interfered with his daily life, especially school life. He underwent right-sided ventro-oral (Vo) thalamotomy at the age of 15, which resulted in complete resolution of PKD attacks immediately after the surgery. Four months after the thalamotomy, he developed right elbow, hand, and toe flexion. He underwent left-sided Vo thalamotomy at the age of 19. Immediately after the surgery, the PKD attacks resolved completely. However, mild dysarthria developed, which spontaneously resolved within three months. Left-sided PKD attacks never developed six years after the right Vo thalamotomy, and right-sided PKD attacks never developed two years after the left Vo thalamotomy without medication.Conclusion: The present case showed long-term suppression of bilateral PKDs after bilateral thalamotomy, which led to drug-free conditions.

The field of Forel (FF) is a subthalamic area through which the pallidothalamic tracts originating from the globus pallidus internus (GPi) traverse. The FF was used as a stereotactic surgical target (ablation and stimulation) to treat cervical dystonia in the 1960s and 1970s. Although recent studies have reappraised the ablation and stimulation of the pallidothalamic tract at FF for Parkinson’s disease, the efficacy of deep brain stimulation of FF (FF-DBS) for dystonia has not been well investigated. To confirm the efficacy and stimulation-induced adverse effects of FF-DBS, three consecutive patients with medically refractory dystonia who underwent FF-DBS were analyzed (tongue protrusion dystonia, cranio-cervico-axial dystonia, and hemidystonia). Compared to the Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale scores before surgery (23.3 ± 12.7), improvements were observed at 1 week (8.3 ± 5.9), 3 months (5.3 ± 5.9), and 6 months (4.7 ± 4.7, p = 0.0282) after surgery. Two patients had stimulation-induced complications, including bradykinesia and postural instability, all well controlled by stimulation adjustments.

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. However, it rarely invades and destroys bone. We report the first case of GBM of a very old patient, which eroded the dura and bone and finally resulted in a large facio-cranial subcutaneous lesion in the absence of prior surgery or radiation. Case description: A 93-year-old woman was presumed with a low-grade glioma (LGG), and the lesion was followed up with magnetic resonance imaging (MRI). Serial monitoring revealed no tumor growth until 2 years later, when the patient was admitted to our institution for anorexia and lack of spontaneity and flow of conversation. On admission, she oftentimes complained of severe right forehead skin pain. Computed tomography (CT) revealed enhancing mass lesions in the right frontal lobe and bone destruction. Upon inspection and palpation, a soft and swelling subcutaneous mass was evident at the forehead, the site of bone destruction. Contrast-enhanced MRI revealed ring-enhancing lesions with irregular borders, and the malignant transformation of LGG into GBM was suspected. The patient had severe skin pain at the region of the subcutaneous mass, so tumor resection of the subcutaneous mass was performed for removing the pain and a definitive diagnosis. The pathological diagnosis was isocitrate dehydrogenase (IDH)-mutated glioblastoma. Immunostaining revealed that the tumor was positive for IDH-1 and p53mutations but negative for ATRX. The patient died due to aspiration pneumonitis. Conclusions: We report a first case of GBM in a very old patient untreated with surgery or radiation that invaded and destroyed the calvaria during the natural progression of the disease. Calvarial destruction without prior surgery or radiation in very old patients association with extra- and intra-axial neoplasm should include GBM in the differential diagnosis, although this is very rare.

It is difficult to treat atlantoaxial instability in patients with a high-riding vertebral artery or anomalies of the craniocervical junction. We report 2 successful cases in which the transspinal canal screwing technique was used because of difficulties performing conventional fixation methods. Case 1: A 78-year-old woman suffered from progressive myelopathy due to severe spinal cord compression with a congenital anomaly of the craniovertebral junction. Bilateral transspinal canal screws from the axis body with spondylolisthesis to the dens were inserted by retracting the dural sac medially after foramen magnum decompression and cervical laminoplasty. Case 2: A 20-year-old man with a spinal deformity due to Loeys-Dietz syndrome presented to our hospital for treatment of syringomyelia. He had no obvious neurological deficits, but spinal cord compression due to right atlantoaxial rotating dislocation was observed. A screw was inserted from the vertebral body of the axis to the right lateral mass of the atlas via the spinal canal after laminectomy of the atlas. The transspinal canal screwing technique is useful for treating atlantoaxial instability in cases where other fixation methods are difficult.

Background: The cerebellum plays an important role in the pathogenesis and pathophysiology of movement disorders, including tremor and dystonia. To date, there have been few reports on deep cerebellar stimulation.Case Report: The patient was a 35-year-old previously healthy man with no history of movement disorders. He developed a tremor and stiffness in his left hand at the age of 27 years, which was diagnosed as a dystonic tremor. We performed right thalamotomy, which resulted in a complete resolution of the tremor; however, the dystonia persisted. Subsequently, the patient developed left foot dystonia with inversion and a newly developed tremor in the right hand and foot. The patient underwent left ventralis intermedius (VIM) deep brain stimulation (VIM-DBS) and left pallidothalamic tract DBS (PTT-DBS). Left VIM-DBS completely resolved the right hand and foot tremor, and PTT-DBS significantly improved the left hand and foot dystonia. Three months postoperatively, the patient developed an infection and wound disruption at the surgical site. We performed palliative surgery for deep cerebellar stimulation via the posterior cranial region, which was not infected. The surgery was performed under general anesthesia with the patient lying in the prone position. Eight contact DBS electrodes were used. The placement of electrodes extended from the superior cerebellar peduncle to the dentate nucleus. Both the right hand and foot tremor improved with right cerebellar stimulation. Further, both the left hand and foot dystonia improved with left cerebellar stimulation. Right and left cerebellar stimulation led to no improvement in the left hand and foot dystonia and right hand and foot tremor, respectively. Stimulation-induced complications observed in the patient included dizziness, dysphagia, and dysarthria. After the surgery, the patient developed hypersalivation and hyperhidrosis in the left side of the body, both of which did not improve with adjustments of stimulation parameters. At the 6-month follow-up, the tremor and dystonia had almost completely resolved.Conclusion: Deep cerebellar stimulation deserves consideration as a potential treatment for tremor and dystonia.

The insular cortex (IC) participates in diverse complex brain functions, including social function, yet their cellular bases remain to be fully understood. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely moving and restrained social targets, we identified 2 subsets of AI neurons-a larger fraction of "Social-ON" cells and a smaller fraction of "Social-OFF" cells-that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during exploration under a particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.

Spinal cord infarction is reported to account for less than 1% of all strokes and is a relatively rare disease. In recent years, thoracic endovascular aortic repair (TEVAR) has become a common treatment for aortic aneurysms, and spinal cord ischemia is one of its complications. Most cases occur in the perioperative period; however, a few cases have been reported in the chronic stage. Here, we report a case of spinal cord infarction, 6 months after TEVAR. A 77-year-old man experienced sudden onset paraparesis following dumbbell exercises and defecation. He had a history of an infectious thoracoabdominal aortic aneurysm treated by TEVAR 6 months prior. Paralysis and disturbance of the thermal pain and tactile sensations of the lower limbs were observed, but proprioception and deep sensation were preserved. Computed tomography (CT) showed no evidence of intraspinal hemorrhage, new aortic dissection, or endoleak around the aortic stent placed from Th11 to L3. Magnetic resonance imaging (MRI) showed intramedullary hyperintensity from Th11 to the conus 2 days after onset. Anticoagulant therapy and rehabilitation were performed, and the lower-limb muscle strength gradually improved. After aortic stenting, particularly including the level of the Adamkiewicz artery, the risk of spinal cord ischemia must be monitored, because spinal circulation depends on collateral circulation.

Previous studies have shown that cognitive impairments in patients with brain tumors are not severe. However, to preserve the postsurgical QOL of patients with brain tumors, it is important to identify “primary” cognitive functions and associated brain regions that are more vulnerable to cognitive impairments following surgery. The objective of this study was to investigate primary cognitive factors affecting not only simple cognitive tasks but also several other cognitive tasks and associated brain regions. Patients with glioma in the left (n=33) and the right (n=21) hemisphere participated in the study. Seven neuropsychological tasks from five cognitive domains were conducted pre- and 6 months postoperation. Factor analyses were conducted to identify “primary” common cognitive functions affecting the task performance in left and right glioma groups. Next, lesion analyses were performed using voxel-based lesion-symptom mapping (VLSM) to identify critical brain regions related to impairments of the primary cognitive functions. Factor analysis revealed two primary cognitive components in each glioma group. The first cognitive component in the left glioma group affected the digit span forward and backward tasks and concept shifting and the letter-digit substitution tasks. VLSM analysis revealed significant regions from the posterior middle temporal gyri to the supramarginal gyrus. The second cognitive component affected verbal memory, and verbal fluency tasks and VLSM analysis indicated two different significant regions, the medial temporal regions and the middle temporal gyrus to the posterior parietal lobes. The first cognitive component in the right glioma group affected positive and negative factor loadings on the task, such that the positive cognitive component affected only the Stroop color-word task. VLSM related to deficits of the Stroop task revealed significant regions in the anterior medial frontal cortex. On the other hand, the negative component affected concept shifting, word fluency, and digit span forward tasks, and VLSM revealed significant regions in the right inferior frontal cortex. It is suggested that primary cognitive functions related to specific brain regions were possibly affected by glioma resection.

Spinal subdural abscesses are rare lesions. We report the case of surgical site infection complicated with meningitis and rapidly progressive spinal subdural abscess caused by P. aeruginosa following transforaminal lumbar interbody fusion (TLIF). A 72-year-old woman was admitted to our hospital complaining of drop foot syndrome and sciatica caused by stenosis of the L5/6 intervertebral foramen accompanied by L5 lumbar vertebral fracture. Accordingly, TLIF of L5-L6 and balloon kyphoplasty of L5 were performed. On the 3rd postoperative day (POD), she was diagnosed with surgical site infection complicated with bacterial meningitis. Subcutaneous fluid, blood, and cerebrospinal fluid cultures indicated P. aeruginosa. On the 7th POD, a repeat MRI showed a large dorsal fluid collection consistent with a subdural infection and massive cauda equina compression. We performed debridement and instrument removal and found a dural laceration that was not observed during the first operation. An intraoperative insensible dural laceration may cause bacteria intrusion into the subdural space.

Tumoral calcinosis involving the spine is rare. The involvement of the thoracic spine is rarer than that of the cervical or lumbar spine. We report a case of thoracic tumoral calcinosis accompanied by vertebral fracture with increased concentrations of inflammatory markers and no abnormalities in serum calcinosis and phosphorus concentration. A 60-year-old woman presented with complete paraplegia. Her white blood cell count and C-reactive protein (CRP) concentration were elevated. The thoracic magnetic resonance imaging revealed vertebral fracture and an epidural mass that demonstrated low intensity on both T2- and T1-weighted images at the T9/10 dorsal side of the central canal. This lesion is larger in size than that observed in the previous 2 months. Her laboratory data showed signs of infection, and only decompression surgery without fixation for treatment and diagnosis was performed. Histopathological examination was consistent with tumoral calcinosis. Postoperatively, the patient’s white cell count and CRP concentration were normalized. We found that tumoral calcinosis can occur at the thoracic level on the basis of the spinal instability due to the vertebral compression fracture and the accompanying increase in inflammation indicated by increased white blood cell count and CRP concentration.

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

Abstract Background Continuous electroencephalogram (CEEG) monitoring is increasingly being used for brain monitoring in neurocritical care setting. This is because of the proven effectiveness of CEEG in diagnosing nonconvulsive status epilepticus (NCSE) as a cause of unexplained consciousness disorder. CEEG has been demonstrated to be effective in determining the response to, and outcome of, NCSE treatment. Main body In this review article, the authors described the indication and methods of CEEG and diagnosis based on EEG pattern. As a condition characterized by unexplained consciousness disorder, NCSE is frequently encountered in the neurocritical care setting and is only accompanied by an altered EEG change without any clinically apparent manifestation, such as convulsion. Thus, it is considered a form of status epilepticus manifesting mainly with consciousness disorder. This is a diagnostic challenge but should not be overlooked as NCSE is a curable condition. However, CEEG is required for the correct diagnosis of NCSE, which is difficult to perform in daily clinical practice. There also are several challenges regarding urgent EEG monitoring in the intensive care unit setting, including system-related problems, such as the preparation of mobile EEG devices and collodion-applied electrodes; human resource-related problems, such as staffing of EEG technicians and physicians who can respond flexibly to unscheduled needs; and EEG-specific difficulties in interpretation/diagnosis. These issues preclude the wide spread of CEEG in daily practice. Conclusion Recently, importance of CEEG was well accepted; however, no definitive diagnostic criteria exist for identifying EEG patterns suggestive of NCSE, especially the ambiguous significance of periodic discharges (PDs) further complicates the diagnosis of NCSE. Thus, analyzing the change in EEG patterns over time is important for the correct diagnosis of NCSE. Further studies are needed to collect sufficient CEEG data and assess the outcome of patients who have undergone therapeutic interventions.

Vomiting is a typical symptom of cerebellar hemorrhage. Usually only supportive care such as antiemetic drugs are available. A 76-year-old woman presented in a light coma. A head CT demonstrated right cerebellar hemorrhage and the hematoma was surgically evacuated. Her intractable vomiting started 3 weeks after surgery. Because her vomiting was unexplained, we checked her EEG, which demonstrated generalized periodic discharges. We diagnosed her with ictal vomiting. Anti-seizure medication was administered and vomiting was rapidly controlled. In conclusion, physicians must be aware that vomiting may rarely occur as a sign of seizures and status epilepticus. Keywords: Ictal vomiting, Nonconvulsive status epilepticus (NCSE), Cerebellar hemorrhage

Objective: One of the controversies in foramen magnum decompression (FMD) is the management of dura. Graft adhesion is the most common finding in revisions after FMD with duraplasty. Furthermore, certain number of patients after FMD without dural opening required revision surgery. The most common cause is excessive fibrosis over the preserved dura. On the other hand, FMD with dura left open could reduce the risk for symptomatic recurrence, although it was generally abandoned because of the higher risk of postoperative CSF leakage or meningitis. Purpose of this study was to re-evaluate FMD with dura left open after the application of tight fascial closures in order to reduce the risk of cerebrospinal fluid (CSF) leakage. We compared CSF-related complications of this surgery with other FMD techniques based on literature review. Patients and methods: Our retrospective study included 13 patients who underwent FMD with dura left open. We paid particular attention to prevent CSF leak by the tight suturing of fascial layers especially at both ends of each layer and keeping muscle attachments to inion intact. Results: CSF-related complications and symptomatic recurrence were not observed. The postoperative CSF collection contained within the tightly closed fasciae became of limited size over several months. Conclusion: FMD with dura left open did not show higher rate of CSF leakage as compared to other FMD techniques. The tight closure of fascial layers is essential to minimalize CSF leakage in this surgery. Moreover, it has the advantage of reducing symptomatic recurrence over other FMD techniques. Keywords: Cerebrospinal fluid leak, Chiari I malformation, Durotomy, Foramen magnum decompression

Abstract Background Esophageal submucosal hematoma is a rare complication after endovascular surgery. We report a case of an esophageal submucosal hematoma which may have been caused by rigorous cough during extubation. Case presentation A 75-year-old woman underwent endovascular treatment for unruptured cerebral aneurysm under general anesthesia. The patient received aspirin and clopidogrel before surgery and heparin during surgery. Activated clotting time was 316 s at the end of surgery. Protamine was not administered and continuous infusion of argatroban was started after surgery. She had a rigorous cough during removal of the tracheal tube and reported retrosternal discomfort postoperatively. She developed hemorrhagic shock after massive hematemesis. A diagnosis of esophageal submucosal hematoma was made by endoscopic examination and computed tomography. Hemostasis was achieved by compression with a Sengstaken-Blakemore tube and endoscopic cauterization. Blood pressure was recovered by blood transfusion. Endoscopic examination performed 7 days after surgery showed that esophageal submucosal hematoma had almost disappeared and slough had adhered to the mucosal laceration. The patient showed good recovery and was discharged 21 days after surgery. Conclusions Careful extubation and postoperative observation are required in patients receiving antiplatelet and anticoagulant therapy.

Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.

Considering the poor outcome of subarachnoid hemorrhage (SAH) due to the rupture of intracranial aneurysms (IA), mechanisms underlying the pathogenesis of IAs, especially the rupture of lesions, should be clarified. In the present study, a rat model of IAs in which induced lesions spontaneously ruptured resulting in SAH was used. In this model, the combination of the female sex and the bilateral ovariectomy increased the incidence of SAH, similar to epidemiological evidence in human cases. Importantly, unruptured IA lesions induced in female animals with bilateral ovariectomy were histopathologically similar to ruptured ones in the presence of vasa vasorum and the accumulation of abundant inflammatory cells, suggesting the exacerbation of the disease. The post-stenotic dilatation of the carotid artery was disturbed by the bilateral ovariectomy in female rats, which was restored by hormone replacement therapy. The in vivo study thus suggested the protective effect of estrogen from the ovary on endothelial cells loaded by wall shear stress. β-estradiol or dihydrotestosterone also suppressed the lipopolysaccharide-induced expression of pro-inflammatory genes in cultured macrophages and neutrophils. The results of the present study have thus provided new insights about the process regulating the progression of the disease.

ObjectiveThe goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin sodium (TS), which is used simultaneously for photodynamic therapy (PDT).MethodsPatients with suspected primary malignant glioma who were eligible for surgical removal of the tumor and PDT with TS were enrolled in this prospective study. Tissue samples were obtained from the contrast-enhanced (CE) region and from the surrounding non-contrast-enhanced (NCE) marginal tissue at the boundary between the tumor and normal tissue. The excised samples were set into a fluorescence measurement system, which consisted of a semiconductor laser with a 400-nm wavelength for excitation, and a compact spectrometer for detection, which were applied and received through a custom-made probe consisting of coaxial optical fibers. The fluorescence spectrum was obtained, and peak intensity was calculated. Tumor cellularity was histopathologically analyzed and semi-quantitatively classified into four (0–3) categories.Results86 samples from 17 surgical cases were available for fluorescence measurement and analysis. The fluorescence from TS had a single peak at 664 nm that was easily distinguished from the 400-nm excitation light. Samples from the CE regions showed higher fluorescence intensity than those from the NCE regions (P