Persistent depression of the lambda site with progressive skull deformity may be a sign of suture closure: Case series and pathological consideration.

BACK GROUND: Flat head syndrome (FHS) sometimes occurs when a baby maintains the same head position during the first several months of life causing a skull deformity. FHS usually improves with time and natural growth, however, some shows aggravation against conservative treatment. We reviewed pathologically proved early closure of skull suture that may have seen secondary to FHS. METHODS: The clinical and radiological findings of the patients who showed progressive skull deformity resembling FHS were retrospectively reviewed. All the patients underwent surgical treatment and pathological specimens were obtained. RESULTS: The detected patients included two 5-month-old infants and one 1-year-old infant. The formers were conservatively treated without any obvious premature suture closure on computed tomography (CT), and later developed progressive tower-like skull deformities. The infants were diagnosed with possible premature fusion of Lambda site and underwent removal around lambda depression (LD). The latter showed evident sagittal suture closure on CT with digital markings, and was diagnosed with increased intracranial pressure and underwent cranioplasty of posterior expansion. Histopathological specimens obtained from the patients' resected sutures showed irregularly narrowed suture structure with ossification and fibrous tissue proliferation within them, supporting the diagnosis of premature closure of the sagittal sutures. Their postoperative courses were uneventful, and their skull deformities subsequently improved. CONCLUSIONS: Conservative therapy-resistant progressive occipital skull deformity with LD may be a sign of early suture closure, even if CT does not show obvious suture closure. The findings are helpful for early diagnosis and might lead to minimal invasive surgery if needed.

Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Combination of neuroendoscopic hematoma evacuation and endovascular coil embolization for a ruptured anterior choroidal artery aneurysm in patients with moyamoya disease: illustrative cases.

BACKGROUND: The treatment strategy for hemorrhagic moyamoya disease (MMD) due to a ruptured aneurysm at the distal portion of the anterior choroidal artery remains controversial. The authors successfully treated the ruptured aneurysm with neuroendoscopic hematoma evacuation, followed by endovascular coil embolization. OBSERVATIONS: The authors encountered two patients with massive hemorrhagic MMD whose MMD had already been diagnosed and who had a periventricular anastomosis due to a ruptured aneurysm of the distal portion of the anterior choroidal artery involving the periventricular anastomosis. In both cases, neuroendoscopic hematoma evacuation was performed for hemorrhagic MMD in the acute phase, followed by endovascular coil embolization of the ruptured aneurysm in the chronic phase. In both endovascular treatments, the patient's condition was stabilized by hematoma evacuation, allowing a detailed preoperative evaluation of the anatomical findings of the vessel and functional findings of intraoperative neurophysiological monitoring using continuous monitoring of motor evoked potentials to preserve motor function. LESSONS: Combination therapy can be useful for hemorrhagic MMD in patients with diagnosed MMD with a periventricular anastomosis. Additionally, a preoperative understanding of the vascular construction and intraoperative neurophysiological monitoring will aid in the successful coil embolization of aneurysms at the distal portion of the anterior choroidal artery with hemorrhagic MMD.

[Decision-Making Regarding Adjuvant Therapy for Hormone Receptor-Positive, HER2-Negative Early Breast Cancer].

In December 2021, abemaciclib was approved as an adjuvant treatment for hormone receptor-positive, HER2-negative, high-risk early breast cancer in Japan. The Oncotype DX Breast Cancer Recurrence Score program(Oncotype DX)is a test that can be used to limit overtreatment in hormone receptor-positive, HER2-negative, low-risk early breast cancer. Although the target groups of both these are different and usually without many overlapping indications, we encountered a case in which this therapy and test were used in a short time period. Our experience suggests that even if the result of Oncotype DX indicates that hormone therapy alone is sufficient, it does not imply that abemaciclib is unnecessary, although this has not been directly studied in the monarchE trial. While a wider choice of treatment options is desirable for patients, more clinical data and trials are needed to further validate the utility of abemaciclib without chemotherapy.

Coexistence of anterior cranial fossa dural arteriovenous fistula and arteriovenous malformation with the same drainage system: illustrative case.

BACKGROUND: The authors report a rare case of coexistence of dural arteriovenous fistula (DAVF) and arteriovenous malformation (AVM), with a common trunk drainer from both DAVF and AVM in the left anterior cranial fossa (ACF) with simple DAVF in the right ACF. OBSERVATIONS: A 63-year-old female presented with seizure. Cerebral angiography showed bilateral DAVFs in the ACF and AVM in the left frontal lobe. A dilated frontal vein acted as a simple drainer of the right DAVF. In contrast, a dilated vein with large varix was the common drainer of both the left DAVF and the AVM. During surgery, indocyanine green videoangiography was performed with direct observation. In the left ACF, the drainer occlusion of the DAVF resulted in partial shrinkage of the varix and decreased distal blood flow. Additional main feeder occlusion of the AVM could decrease the blood flow further, but not completely because of the residual pial supplies for the AVM. Finally, the nidus of the AVM with varix was removed by en bloc resection. LESSONS: Neurosurgeons should be aware of the coexistence of DAVF and AVM with a common trunk drainer. Only simple occlusion of the drainer from DAVF is not sufficient, so removal of the AVM is essential.

Relationship between subarachnoid hemorrhage and nonocclusive mesenteric ischemia as a fatal complication: patient series.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) causes intestinal necrosis due to irreversible ischemia of the intestinal tract. The authors evaluated the incidence of NOMI in patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysms, and they present the clinical characteristics and describe the outcomes to emphasize the importance of recognizing NOMI. OBSERVATIONS: Overall, 7 of 276 consecutive patients with SAH developed NOMI. Their average age was 71 years, and 5 patients were men. Hunt and Kosnik grades were as follows: grade II, 2 patients; grade III, 3 patients; grade IV, 1 patient; and grade V, 1 patient. Fisher grades were as follows: grade 1, 1 patient; grade 2, 1 patient; and grade 3, 5 patients. Three patients were treated with endovascular coiling, 3 with microsurgical clipping, and 1 with conservative management. Five patients had abdominal symptoms prior to the confirmed diagnosis of NOMI. Four patients fell into shock. Two patients required emergent laparotomy followed by second-look surgery. Four patients could be managed conservatively. The overall mortality of patients with NOMI complication was 29% (2 of 7 cases). LESSONS: NOMI had a high mortality rate. Neurosurgeons should recognize that NOMI can occur as a fatal complication after SAH.

Anatomical and neurophysiological localization of the leg motor area at the medial central sulcus.

OBJECTIVE: The exact location of the leg motor area is still in debate due to the lack of landmarks such as 'precentral knob' in the medial cortex. This study tried to identify the leg motor area based on intraoperative neurophysiological data and neuroimaging techniques. METHODS: Intraoperative data of somatosensory evoked potential (SEP) elicited by tibial nerve stimulation and motor evoked potential (MEP) of the leg muscles induced by direct cortical stimulation were recorded using subdural electrodes placed in the medial cortex. We displayed the neurophysiological data on the individual MR images and the MNI52. RESULTS: Definite N40-P40 phase reversal was observed with the shallow grooves in the medial cortex in 5 cases. Leg MEP was successfully obtained in all 12 cases preserving the leg motor function. Superimposed SEP and leg MEP data on the MNI152 indicated the leg motor area was predominantly located in the posterior two-thirds between the vertical lines passing through the anterior commissure and the posterior commissure (VCP). CONCLUSIONS: Our study revealed the location of the leg motor area and the presence of the 'medial central sulcus' in the medial cortex. SIGNIFICANCE: The VCP can be useful landmark to identify the sensorimotor border in the medial cortex.

Ventricular opening and cerebrospinal fluid circulation accelerate the biodegradation process of carmustine wafers suggesting their immunomodulation potential in the human brain.

PURPOSE: Opening the ventricular system during glioblastoma surgery is often necessary, but the consequent effect on the tumor microenvironment of glioblastoma remains unknown. Implantation of carmustine wafer enables direct drug delivery to the tumor site; however, the exact mechanism of the wafer's biodegradation process is unclear, and the available data is limited to in vivo non-human mammalian studies. We hypothesized that the ventricular opening affects the degradation process of the wafer and the glioblastoma tumor microenvironment. METHODS: This study included 30 glioblastoma patients. 21 patients underwent carmustine wafer implantation during initial surgery. All patients underwent repeated surgical resection upon recurrence, allowing for pathological comparison of changes associated with wafer implantation. Immunohistochemical analyses were performed using CD68, TMEM119, CD163, IBA1, BIN1, and CD31 antibodies to highlight microglia, macrophages, and tumor vascularity, and the quantitative scoring results were correlated with clinical, molecular, and surgical variables, including the effect of the ventricular opening. RESULTS: The carmustine wafer implanted group presented significantly less TMEM119-positive microglia within the tumor (P = 0.0002). Simple and multiple regression analyses revealed that the decrease in TMEM119-positive microglia was correlated with longer intervals between surgeries and opened ventricular systems. No correlation was observed between age, methylated O6-methylguanine DNA methyltransferase promoter expression, and the extent of surgical resection. CONCLUSIONS: Our study findings strongly suggest that biomaterials may possess immunomodulation capacity, which is significantly impacted by the ventricular opening procedure. Furthermore, our data highlights the pathophysiological effects of the ventricular opening within the surrounding human brain, especially after the wafer implantation.

Ribosomes and Ribosomal Proteins Promote Plasticity and Stemness Induction in Glioma Cells via Reprogramming.

Glioblastoma multiforme (GBM) is a lethal tumor that develops in the adult brain. Despite advances in therapeutic strategies related to surgical resection and chemo-radiotherapy, the overall survival of patients with GBM remains unsatisfactory. Genetic research on mutation, amplification, and deletion in GBM cells is important for understanding the biological aggressiveness, diagnosis, and prognosis of GBM. However, the efficacy of drugs targeting the genetic abnormalities in GBM cells is limited. Investigating special microenvironments that induce chemo-radioresistance in GBM cells is critical to improving the survival and quality of life of patients with GBM. GBM cells acquire and maintain stem-cell-like characteristics via their intrinsic potential and extrinsic factors from their special microenvironments. The acquisition of stem-cell-like phenotypes and aggressiveness may be referred to as a reprogramming of GBM cells. In addition to protein synthesis, deregulation of ribosome biogenesis is linked to several diseases including cancer. Ribosomal proteins possess both tumor-promotive and -suppressive functions as extra-ribosomal functions. Incorporation of ribosomes and overexpression of ribosomal protein S6 reprogram and induce stem-cell-like phenotypes in GBM cells. Herein, we review recent literature and our published data on the acquisition of aggressiveness by GBM and discuss therapeutic options through reprogramming.

Molecular analyses of rosette-forming glioneuronal tumor of the midbrain tegmentum: A report of two cases and a review of the FGFR1 status in unusual tumor locations.

Background: Rosette-forming glioneuronal tumor (RGNT) is a rare tumor that arises primarily in the posterior fossa, with molecular features of FGFR1 mutation. A previous study reported that brainstem RGNT accounts for only 2.7% cases; therefore, midbrain RGNT is infrequent. Case Description: The authors encountered two cases of RGNT located in the midbrain tegmentum (Case 1: 23-year-old woman and Case 2: 18-year-old boy), both exhibiting similar cystic components with gadolinium-enhanced cyst walls on preoperative magnetic resonance imaging, surgically resected through the occipital transtentorial approach. Histological findings in both cases comprised two characteristic architectures of neurocytic and glial components, typical of RGNT. Molecular assessment revealed no FGFR1 mutation in the initial specimen, but revealed FGFR1 K656E mutation in the recurrent specimen in Case 1 and showed no FGFR1 mutation but showed TERT C228T mutation in Case 2. Neither case revealed IDH1/2, BRAF, H3F3A K27, H3F3A G34, or HIST1H3B K27 mutations. DNA methylation-based classification (molecularneuropathology.org) categorized both cases as RGNT, whose calibrated scores were 0.99 and 0.47 in Cases 1 and 2, respectively. Conclusion: Midbrain tegmentum RGNTs exhibited typical histological features but varied FGFR1 statuses with TERT mutation. RGNT in rare locations may carry different molecular alterations than those in other common locations, such as the posterior fossa.

Ribosomal proteins induce stem cell-like characteristics in glioma cells as an "extra-ribosomal function".

The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor microenvironment and acquire the potential to resist chemoradiotherapy. To investigate how GB cells acquire stem cell-like phenotypes, we focused on ribosomal proteins, because ribosome incorporation has been reported to induce stem cell-like phenotypes in somatic cells. Furthermore, dysregulation of ribosome biogenesis has been reported in several types of cancer. We focused on ribosomal protein S6, which promotes sphere-forming ability and stem cell marker expression in GB cells. We expect that investigation of dysregulation of ribosome biogenesis and extra-ribosomal function in GB will provide new insights about the plasticity, heterogeneity, and therapeutic resistance of GB cells, which can potentially lead to revolutionary therapeutic strategies.

[Hyponatremia Causing a Tonic-Clonic Seizure after Breast Cancer Surgery-The Medical Safety Perspective].

A 61-year-old woman was found to have calcifications in the CD region of the left breast. She had previously undergone total hysterectomy and bilateral oophorectomy for endometriosis at the age of 37 years. Since age 59 years, she had been attending an otorhinolaryngology clinic because of vertigo. Blood tests showed no abnormal findings. Left breast cancer (cT1N0M0, stage Ⅰ)was diagnosed, and left mastectomy and sentinel lymph node biopsy were performed. She developed postoperative nausea, and at 37 hours postoperatively, she was unable to communicate and exhibited suspected delirium. At 43 hours postoperatively a tonic-clonic seizure occurred. Hyponatremia, with serum sodium of 114 mEq/L, was present. Sodium supplementation was provided, and the patient became capable of communication 8 hours after seizure onset(Na 121 mEq/L). A hyponatremic tonic-clonic seizure is extremely rare after breast cancer surgery, and the abnormal behavior of the present patient 31 hours after surgery was also highly unusual. With such an unusual presentation, the possibility that something specific is happening must be considered. This case gave us the opportunity to review patient management after breast cancer surgery, emergency response and preparations, and nursing education from the medical safety perspective.

Long-term follow-up after BCNU wafer implantation in patients with newly diagnosed glioblastoma.

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, or Carmustine) wafers are intraoperatively implantable wafers used to achieve local tumor control. There is scarce data about the behavior of wafers in the long-term follow-up of implanted cases. We reviewed the data of 64 patients with newly diagnosed glioblastoma treated by surgery, BCNU wafers, radiation therapy, and temozolomide administration. This cohort included 55 patients who presented first recurrence, and 49 of them showed tumor progression to death. The MR imaging of each patient at the terminal stage and an autopsy case were used to elucidate the tumor progression pattern after the wafer implantation. We subdivided the first recurrence pattern into local, distant, and multifocal based on MR imaging or into infield, outfield, and marginal based on the radiation field. The first recurrence pattern was 33 patients (60%) with local, 13 (24%) with distant, and nine (16%) with multifocal recurrence, or 38 patients (69%) with infield, 13 (24%) with outfield, and four (7%) with marginal. The median and mean time intervals between MR imaging at the terminal stage and death were 2.0 and 2.3 months, respectively. Of note, 13 patients with first distant recurrence had no obvious radiological local tumor progression even at the terminal stage. Long-term follow-up after BCNU wafer implantation revealed that patients with first distant recurrence had long-lasting local tumor control until the terminal stage.

Leber's hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri: illustrative case.

BACKGROUIND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. OBSERVATIONS: The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2'-deoxyguanosine positivity, suggesting the presence of oxidative stress. LESSONS: LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.

A Case of Synchronous Occurrence of Intracranial Germinoma and Systemic Sarcoidosis.

Although the synchronous occurrence of testicular seminoma and systemic sarcoidosis has been reported, that of intracranial germinoma and systemic sarcoidosis is unknown. A 26-year-old man presented with symptoms of panhypopituitarism and consciousness disturbance. Imaging demonstrated a large nodule in the upper right lung field and swelling of multiple bilateral pulmonary and mediastinal lymph nodes in addition to the bifocal pineal and suprasellar tumors with obstructive hydrocephalus. The pathological diagnosis of the intracranial bifocal tumors was pure germinoma, whereas that of the mediastinal lymph nodes was epithelioid granuloma. Three courses of chemotherapy using carboplatin and etoposide were administered, followed by whole ventricle irradiation. The intracranial tumors completely disappeared, but the lung nodule and mediastinal lymph nodes progressed. Whole-body fluorine-18-fluorodeoxyglucose positron emission tomography demonstrated accumulation in the mediastinal lymphadenopathy, lung masses, and multiple lymph nodes of the whole body. Transbronchial lung biopsy revealed epithelioid granuloma with multinucleated giant cells. In conjunction with the high blood concentration of angiotensin-converting enzyme and soluble interleukin-2 receptor, these findings established a diagnosis of sarcoidosis. This is the first report of synchronous occurrence of intracranial germinoma and sarcoidosis. Such coexistence is extremely rare, but we should mind that sarcoidosis can occur with intracranial germinoma.

Aneurysms Arising from Persistent Arteries in the Vertebrobasilar Paramedian Longitudinal Axis: Two Case Reports.

A 50-year-old man and a 69-year-old woman with consciousness disturbance were diagnosed to have suffered from subarachnoid hemorrhage (SAH) involving the posterior fossa. In both cases, the initial 3D CT angiogram failed to reveal the SAH source in the vertebrobasilar system. Delayed 3D rotational angiography revealed aneurysms on unfamiliar aberrant arteries. One was a dissecting aneurysm located between the proximal part of the posterior inferior cerebellar artery and the distal part of the intracranial vertebral artery. It was trapped and resected; the patient subsequently presented with lateral medullary symptoms. The other aneurysm was between the distal posterior and the distal anterior inferior cerebellar artery. It was successfully embolized; there were no complications. We think that the aberrant aneurysm-harboring vessels encountered in these two patients were primitive arteries on or adjacent to the vertebrobasilar paramedian longitudinal axis and that they persisted past the embryologic stage. Such aneurysms arising from unfamiliar persistent arteries beside the brainstem are extremely rare but must be considered when the SAH source is not detected in the trunk of the vertebrobasilar system.

[Cerebral Amyloid Angiopathy-related Inflammation Demonstrating Early Venous Filling on Digital Subtraction Angiography:A Case Report].

Cerebral amyloid angiopathy-related inflammation(CAA-RI)is a rare condition thought to be caused by an inflammatory response to amyloid beta(Aß)protein in the walls of the small arteries and capillaries of the cerebral cortex. A 73-year-old female presented with left hemiparesis and dysarthria. Fluid-attenuated inversion recovery(FLAIR)imaging disclosed progressive enlargement of infiltrative white matter abnormalities in the right temporo-occipito-parietal lobes. Interestingly, digital subtraction angiography(DSA)demonstrated early venous filling. Pathological examination of the biopsy specimen demonstrated lymphocytes infiltration surrounding the blood vessels and in the thickened walls with amyloid-beta deposition. The diagnosis given was CAA-RI. The patient was successfully treated with high dose corticosteroids and clinical improvement was associated with shrinkage of the high intensity lesion on FLAIR imaging. Early venous filling resolved on the follow-up DSA. Most patients with CAA-RI can be treated with corticosteroids. However, the clinical condition will worsen without appropriate treatment. Early diagnosis is the key. If an expanding disease of the white matter appears in an elderly patient, we should exclude other cerebrovascular diseases by DSA, followed by biopsy without delay. The present case demonstrated that early venous filling on DSA may appear until inflammation is resolved by the treatment of CAA-RI.

[A Case of Familial Schwannomatosis Occurring as Intraorbital Schwannoma].

A 67-year-old male presenting with left exophthalmos and progressive visual disturbance was referred to our department. Tumors at the supraclavicular fossa and dorsal femoral region were resected at ages 27 and 45 years. His father and son had both been diagnosed with spinal tumors, and his son's tumor was pathologically diagnosed as a schwannoma. Brain MRI of his son demonstrated no intracranial tumor. Brain MRI of the patient revealed a multilobular tumor of 2 cm diameter compressing the optic nerve medially within the left muscle cone, and no other intracranial tumors. However, large masses lateral to the pharynx and intercostal nerve, as well as multiple spinal tumors were detected. Transcranial total resection of the intraorbital tumor was performed. The pathological diagnosis was consistent with a schwannoma. These clinical characteristics fulfilled the diagnostic criteria of familial schwannomatosis. The postoperative course was uneventful. His visual dysfunction and eye movement disorder resolved completely. The intraorbital tumor was believed to originate from the lacrimal nerve. Sequencing of all exons for SMARCB1 and LZTR1 using DNA extracted from the tumor did not reveal any mutations. This case is the third report on familial schwannomatosis in Japan.