Intraventricular hemorrhage volume and younger age at surgery may be risk factors for postoperative hydrocephalus after hemispherotomy in children.

OBJECTIVE: Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition. METHODS: The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed. RESULTS: This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C. CONCLUSIONS: This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Safety, Feasibility, and Efficacy of Additional Extraventricular Anterior Commissurotomy With Corpus Callosotomy.

BACKGROUND: Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions. Anterior commissurotomy (AC) has been historically performed with CC. However, the efficacy and safety of adding AC to CC remain unknown. OBJECTIVE: To describe the surgical technique of extraventricular AC and retrospectively investigate its clinical efficacy and safety by assessing patients who underwent CC with and without AC. METHODS: AC has been added to CC at our institution since 2018. Fifty-five consecutive patients who received total callosotomy from 2016 to 2020 were included and categorized into 2 groups: 26 patients with additional AC and 29 patients without additional AC. Seizure outcome 1 year after surgery were compared between groups for assessing the efficacy of adding AC. The perioperative factors were compared for assessing the safety and feasibility. RESULTS: Seizure reduction rate (50% and 60%; P = .60) and disappearance of drop attacks (42% and 58%; P = .25) were not significantly different between CC and CC + AC groups. No statistical group differences were found in intraoperative estimated blood loss, number of days to first oral intake, duration of postoperative intravenous hydration, and length of hospital stay. CONCLUSION: Disconnection of the anterior commissure is a feasible and relatively safe procedure. This study failed to show the significant efficacy of adding AC to CC. However, further investigation is needed to prove its efficacy in ameliorating epilepsy.

Efficacy of a Novel Prophylactic Barbiturate Therapy for Severe Traumatic Brain Injuries: Step-down Infusion of a Barbiturate with Normothermia.

This study aimed to examine the beneficial effects of a novel prophylactic barbiturate therapy, step-down infusion of barbiturates, using thiamylal with normothermia (NOR+sdB), on the poor outcome in the patients with severe traumatic brain injuries (sTBI), in comparison with mild hypothermia (MD-HYPO). From January 2000 to March 2019, 4133 patients with TBI were admitted to our hospital. The inclusion criteria were: a Glasgow coma scale (GCS) score of ≤8 on admission, age between 20 and 80 years, intracranial hematoma requiring surgical evacuation of the hematoma with craniotomy and/or external decompression, and patients who underwent management of body temperature and assessed their outcome at 6-12 months. Finally, 43 patients were included in the MD-HYPO (n = 29) and NOR+sdB (n = 14) groups. sdB was initiated intraoperatively or immediately after the surgical treatment. There were no significant differences in patient characteristics, including age, sex, past medical history, GCS on admission, type of intracranial hematoma, and length of hospitalization between the two groups. Although NOR+sdB could not improve the patient's poor outcome either at discharge from the intensive care unit (ICU) or at 6-12 months after admission, the treatment inhibited composite death at discharge from the ICU. The mean value of the maximum intracranial pressure (ICP) in the NOR+sdB group was <20 mmHg throughout the first 120 h. NOR+sdB prevented composite death in the ICU in patients with sTBI, and we may obtain novel insights into the beneficial role of prophylactic barbiturate therapy from suppression of the elevated ICP during the first 120 h.

A novel step-down infusion method of barbiturate therapy: Its safety and effectiveness for intracranial pressure control.

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP.

Endoscopic third ventriculostomy for myelomeningocele-related hydrocephalus after shunt failure: Long-term outcome in a series of 8 patients.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) has now become an accepted mode of hydrocephalus treatment. However, the long-term effects of ETV for myelomeningocele-related hydrocephalus (MMC-rH) after shunt malfunction remains unclear. We aimed to assess the long-term outcome and the factors associated with the success of ETV for MMC-rH after shunt malfunction. METHODS: We performed a retrospective analysis of data collected between 2001 and 2018 from 8 patients with MMC-rH after shunt malfunction, who underwent ETV at the Kurume University Hospital and were followed up for at least 5 years. We extracted data regarding age, sex, clinical symptoms, radiological imaging, intraoperative findings, and outcomes. RESULTS: The overall success rate was 62.5% and their ETV success score is 67.5. The most frequent clinical symptom was intracranial hypertension symptoms (100 %), followed by Chiari type II symptoms (87.5 %). In preoperative MRI scans, we observed aqueduct stenosis in 6 cases, Chiari type II malformations in 7 cases, four patients had a narrow prepontine cistern, five patients had an absent septum pellucidum, and three presented with stenosis of the foramen of Monro. All cases in the failure group had the above 5 symptoms. Based on intraoperative findings, a thick third ventricle floor was found in 5 patients. Two patients had a thin hypothalamic adhesion in the third ventricle floor. They had no major complications. CONCLUSION: ETV for MMC-rH after shunt malfunction is an effective treatment option. However, we recommend that a neurosurgeon with extensive experience in neuroendoscopy perform ETV because MMC patients more often had intraventricular malformations than those with other hydrocephalus diseases.

Long-term outcomes of endoscopic third ventriculostomy for Blake's pouch cyst in adults.

OBJECTIVE: The optimal treatment method for persistent Blake's pouch cyst (BPC) remains unclear owing to its low prevalence. We aimed to characterize a patient population with adult BPC and to identify the risk factors associated with endoscopic third ventriculostomy (ETV) for BPC. This study reports the largest number of BPC cases in adults and is the first report to reveal the long-term outcomes of ETV in such patients. METHODS: We performed a retrospective analysis of data collected from seven adult patients with BPC between 2005 and 2019. They underwent ETV at the Kurume University Hospital and were followed up for five years or more. We extracted data regarding patient age, sex, clinical symptoms, radiological imaging, intraoperative findings and outcomes. RESULTS: The ages of the patients ranged between 30 and 60 years (45 ±â€¯12 years). The mean postoperative follow-up time was 92.1 ±â€¯13.5 months. The overall success rate was 71.4%. The most frequent symptom was headache (86%), followed by mild cognitive impairment (71%). The average cerebrospinal fluid pressure was slightly elevated (18.4 ±â€¯1.4 cmH2O). A decrease in ventricular size (Evans' index) detected early after ETV was associated with satisfactory clinical outcomes (p = 0.02). The incidence of prepontine scarring was observed in all cases of the ETV failure group. A significant risk factor for ETV was the to-and-fro movements of the third ventricle floor after ETV (p = 0.048). CONCLUSIONS: ETV could be a safe and effective treatment option for adult patients with BPC. It is important that prepontine scarring and the to-and-fro movements of the third ventricle after ETV should be confirmed carefully when performing ETV on adult patients with BPC.

Gamma knife surgery-induced aneurysm rupture associated with tissue plasminogen activator injection: A case report and literature review.

BACKGROUND: Cases involving delayed development of intracranial aneurysms related to gamma knife surgery (GKS) have been recently reported. Here, we present a rare case of GKS-induced aneurysm rupture after intravenous injection of tissue plasminogen activator (t-PA) for occlusion of the middle cerebral artery (MCA). To the best of our knowledge, this is the first case in which t-PA-induced rupture of a GKS-related unruptured aneurysm. CASE DESCRIPTION: A 56-year-old woman underwent GKS for left trigeminal neuralgia. Eighteen years later, she suddenly experienced MCA occlusion with consciousness disturbance and right hemiparesis. She received an intravenous injection of t-PA and then was transferred to our hospital. We confirmed residual thrombus, and she underwent mechanical thrombectomy successfully. A postthrombectomy brain computed tomography scan revealed subarachnoid hemorrhage with a hematoma in the left cerebellar hemisphere. Cerebral angiography revealed a small irregular-shaped aneurysm at the branching site of the left circumflex branch at the distal position of the anterior inferior cerebellar artery, which was not detected on initial imaging. Coil embolization was performed. One month after the ischemic attack, she was transferred to a rehabilitation hospital, with a modified Rankin Scale score of 5. CONCLUSIONS: The tendency to rupture is greater for GKS-induced aneurysms than for intrinsic unruptured aneurysms, according to previous reports. When performing acute treatment for cerebral infarction in patients with a history of GKS, the presence of aneurysms should be evaluated and we should keep in mind that GKS aneurysms are very small and tend to rupture.

Leptomeningeal Carcinomatosis After Neoplastic Cerebral Aneurysm Rupture.

BACKGROUND: Several possible mechanisms exist for the spread of a primary tumor to the leptomeninges in leptomeningeal carcinomatosis. This report describes a case caused by direct bleeding in the subarachnoid space from a neoplastic cerebral aneurysm rupture. CASE DESCRIPTION: A 48-year-old Japanese woman, who was diagnosed with breast carcinoma (pT3 pN2 M0) at the age of 45 years and underwent mastectomy and chemotherapy, was admitted in a coma following a sudden-onset severe headache. Computed tomography revealed diffuse hemorrhage in the subarachnoid space, and angiography revealed an aneurysm at the distal middle cerebral artery. Superficial temporal artery-middle cerebral artery bypass, aneurysmal trapping, and aneurysm resection were performed within 24 hours of admission. Staining for AE1/AE3 revealed accumulation of atypical cells with a high nuclear-cytoplasmic ratio in the aneurysmal wall. After showing initial improvement, she developed disturbed consciousness due to complicated ventricular enlargement on day 45. Although the cerebrospinal fluid in the acute phase had no atypical cells, subsequent testing revealed atypical cells, which supported a diagnosis of leptomeningeal carcinomatosis due to breast cancer dissemination. The patient died on day 78 after receiving standard endocrine therapy and radiation therapy. CONCLUSIONS: Tumor cells reach the leptomeninges via hematogenous spread or direct extension from preexisting lesions and can undergo neuraxis dissemination via the cerebrospinal fluid. Subarachnoid hemorrhage and leptomeningeal carcinomatosis are both devastating conditions with extremely poor prognoses. This patient experienced delayed disturbed consciousness leptomeningeal carcinomatosis with decreased performance status, which made it difficult to justify aggressive treatment on the basis of her poor prognosis.

Leakage sign for acute subdural hematoma in clinical treatment.

BACKGROUND: Acute subdural hematoma (ASDH) is a serious traumatic disease, and predictive methods for hematoma growth are necessary to decide whether emergent operation is necessary. This study aimed to evaluate the incidence of "leakage" using computed tomography angiography (CTA) in patients with ASDH and to identify its prognostic value. METHODS: Sixty-seven patients with ASDH were examined using CTA (mean age 64.1 ± 20.6 years; 24 men) by analyzing two serial scans (CTA phase and delayed phase). We defined a positive leakage sign as a > 10% increase in Hounsfield units (HU) in the region of interest. Hematoma expansion was determined using plain CT after 24 h in patients who did not undergo emergent surgery. RESULTS: Of the 67 patients, conservative therapy was administered to 35 patients; of these patients, 9 showed hematoma expansion, and 8 of these 9 patients (88.9%) showed positive leakage signs. The sensitivity and specificity of leakage signs to hematoma expansion in the no-surgery group were 88.8% and 76.1%, respectively. All positive leakage signs were found within 4.5 h of injury; patients showing negative leakage signs showed a decreased tendency towards hematoma 24 h after injury. Patients presenting with positive leakage signs had poor outcomes. CONCLUSIONS: The results indicated that the leakage sign is a sensitive predictor of hematoma expansion and poor outcomes in ASDH. If the hematoma is small but leakage sign-positive, strict observation is necessary and aggressive surgery may improve outcomes.

[Head Injuries due to Ladder-related Falls].

We examined the clinical characteristics and outcomes of patients who had fallen from ladders and statistically analyzed the prognostic factors, highlighting the impact of the coexistence of head injuries on their prognoses. The clinical records of patients who had experienced ladder-related falls who were admitted to the Advanced Emergency Medical Service Center at Kurume University Hospital between April 2013 and August 2015 were retrospectively reviewed. A total of 86 patients were enrolled. The mean patient age was 69.2 years, and 82 patients were male. The median fall height was 2.55 m. Sixty patients fell during non-professional use of the ladder. Forty-four patients experienced some type of head injury. Although the older patients had more frequent complications with head injuries, the height of the fall was not related statistically. The group of patients with head injuries exhibited trends of older age, lower Glasgow Coma Scale scores, higher Injury Severity Score, and poorer outcomes than those of the group of patients without head injuries. Multivariate analysis showed that head injury and non-professional use were independent risk factors for poor outcomes. Our results revealed that ladder-related falls with head injury can occur when older people are working at home, even if they have fallen from a low height. Especially when older men work with the ladder at home, local community-based education and guidance for the prevention of ladder-related fall injuries are needed.

Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.

BACKGROUND: Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN). METHODS: We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM. RESULTS: The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages. CONCLUSION: Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM.

Endoscopic biopsy for the diagnosis of neurosarcoidosis at the fourth ventricle outlet with hydrocephalus.

BACKGROUND: Fourth ventricle mass lesion in neurosarcoidosis is very rare and difficult to be diagnosed pathologically. We report a rare case of progressive hydrocephalus associated with neurosarcoidosis mass lesion located at the fourth ventricle outlet and suprasellar region. CASE DESCRIPTION: A 23-year-old man had a disturbance of consciousness and neck stiffness with fever. Magnetic resonance imaging revealed diffuse leptomeningeal enhancement, and the obstructive mass lesions at the outlet of the fourth ventricle. We performed an endoscopic biopsy of the enhanced lesion at the foramen Magendie, via foramen Monro and the aqueduct of the midbrain. Pathologically, the diagnosis of neurosarcoidosis was confirmed, and we started treatment with prednisolone. His neurological symptoms disappeared after ventriculo-peritoneal shunt and steroid therapy, and he was discharged without deficit 40 days after emergent admission. CONCLUSION: Endoscopic procedure is less invasive and more effective for biopsy of neurosarcoidosis with hydrocephalus, even if the lesion is located at the fourth ventricle outlet.

Anchoring structure of the calvarial periosteum revealed by focused ion beam/scanning electron microscope tomography.

An important consideration in regeneration therapy is the fact that the tissue surrounding an organ supports its function. Understanding the structure of the periosteum can contribute to more effective bone regeneration therapy. As a cellular source, the periosteum also assists bone growth and fracture healing; this further necessitates its direct contact with the bone. However, its anchoring strength appears to be inexplicably stronger than expected. In this study, we used focused ion beam/scanning electron microscope tomography to investigate ultrathin serial sections as well as the three dimensional ultrastructure of the periosteum to clarify the architecture of its anchoring strength, as such assessments are challenging using conventional methods. We discovered perforating fibres that arise from the bone surface at 30 degree angles. Additionally, the fibres across the osteoblast layer were frequently interconnected to form a net-like structure. Fibroblast processes were observed extending into the perforating fibres; their morphologies were distinct from those of typical fibroblasts. Thus, our study revealed novel ultrastructures of the periosteum that support anchorage and serve as a cellular source as well as a mechanical stress transmitter.

Subcutaneous transplantation promotes organ formation of the fetal rat urogenital sinus.

The aim of this study is to develop a novel experimental model of the subcutaneous transplantation of fetal urogenital sinus (UGS) into normal and castrated adult male rats for the pathophysiological investigation of the normal and developing prostate. Fetal UGS obtained from 20-day-old male rat embryos was subcutaneously transplanted into 7-week-old normal and castrated male rats. We observed the growth pattern, histopathological characteristics and immunohistochemical localization of cytokeratin 5 (CK 5), cytokeratin 8 (CK 8) and androgen receptor (AR) in the transplanted tissues. Almost all of the transplanted UGS organs gradually increased in weight over time in the non-castrated recipient animals, and the histopathological observations and immunohistochemical analysis of CK 5 and CK 8 revealed that the morphological changes in the tissues were in accordance with the features of normal prostate development. The histological characteristics included glandular epithelial dominant and stromal dominant area, with an increase in the glandular epithelial dominant areas over time and resemblance among a portion of the transplanted tissues within a certain period during the developmental course to the histopathology of human benign prostatic hyperplasia (BPH). The effects of androgens and resemblance in the immunohistochemical localization pattern changes in AR to that observed in the normal differentiating rat prostate were also noted. We conclude that the subcutaneous space provides an adequate microenvironment for UGS growth.

The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease.

Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimental studies conducted between 1984 and 2013. We propose that edaravone, which scavenges free radicals, may offer a novel option for treatment of cardiovascular diseases. However, additional clinical studies are necessary to verify the efficacy of edaravone.

Ruptured de novo aneurysm arising at a site remote from the anastomosis 14 years after superficial temporal artery-middle cerebral artery bypass: a case report.

BACKGROUND AND IMPORTANCE: The long-term outcome of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is unclear. We report a very rare case of a de novo aneurysm after bypass surgery. CLINICAL PRESENTATION: A 57-year-old woman who underwent STA-MCA bypass and internal carotid artery aneurysm treatment 14 years earlier developed a subarachnoid hemorrhage and a temporal lobe hematoma on the same side as the anastomosis. Angiography showed excellent patency of the STA bypass and a ruptured de novo saccular aneurysm at a site remote from the anastomosis. Neck clipping and hematoma evacuation were performed on the second day, and postoperative angiography showed complete aneurysmal clipping. The aneurysm was considered to be caused by hemodynamic stress because it was remote from the anastomosis and had developed after a prolonged interval of 14 years; furthermore, the aneurysm projected because of the hemodynamic force of the STA perfusion. CONCLUSION: This is the first reported case of a de novo MCA aneurysm that developed at a site remote from STA-MCA anastomosis because of hemodynamic force. Therefore, long-term control of blood pressure and repeated imaging examination should be performed to confirm patency and to identify aneurysm formation after STA-MCA bypass.