Bifocal germ cell tumor of pineal germinoma and neurohypophyseal embryonal carcinoma: illustrative case.

BACKGROUND: Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions. OBSERVATIONS: A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission. LESSONS: Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.

Brain-specific glycosylation enzyme GnT-IX maintains levels of protein tyrosine phosphatase receptor PTPRZ, thereby mediating glioma growth.

Gliomas are the most prevalent primary tumor of the central nervous system. Despite advances in imaging technologies, neurosurgical techniques, and radiotherapy, a cure for high-grade glioma remains elusive. Several groups have reported that protein tyrosine phosphatase receptor type Z (PTPRZ) is highly expressed in glioblastoma, and that targeting PTPRZ attenuates tumor growth in mice. PTPRZ is modified with diverse glycan, including the PTPRZ-unique human natural killer-1 capped O-mannosyl core M2 glycans. However, the regulation and function of these unique glycans are unclear. Using CRISPR genome-editing technology, we first demonstrated that disruption of the PTPRZ gene in human glioma LN-229 cells resulted in profoundly reduced tumor growth in xenografted mice, confirming the potential of PTPRZ as a therapeutic target for glioma. Furthermore, multiple glycan analyses revealed that PTPRZ derived from glioma patients and from xenografted glioma expressed abundant levels of human natural killer-1-capped O-Man glycans via extrinsic signals. Finally, since deficiency of O-Man core M2 branching enzyme N-acetylglucosaminyltransferase IX (GnT-IX) was reported to reduce PTPRZ protein levels, we disrupted the GnT-IX gene in LN-229 cells and found a significant reduction of glioma growth both in vitro and in the xenograft model. These results suggest that the PTPR glycosylation enzyme GnT-IX may represent a promising therapeutic target for glioma.

A Collision Tumor of Pit-1/SF-1-positive Double Pituitary Adenoma and a Craniopharyngioma Coexisting with Graves' Disease.

Double or multiple pituitary adenomas expressing different types of transcription factors and collision tumors of pituitary adenomas and craniopharyngiomas are rare. In this report, we present a case of pituitary adenoma of two different cell populations, Pit-1 and SF-1, and an adenoma and craniopharyngioma collision tumor with coexisting Graves' disease. The patient had a 16-mm pituitary tumor with pituitary stalk calcification and optic chiasm compression but no visual dysfunction. Based on hormonal profile results, the tumor in the sella was considered a nonfunctioning pituitary adenoma; nevertheless, the pituitary stalk was invaded by a different lesion, which was later confirmed to be a craniopharyngioma. Using an endoscopic endonasal approach, the pituitary adenoma was removed; however, a small remnant remained medial to the right cavernous sinus. Because the pituitary stalk lesion was isolated from the pituitary adenoma, it was preserved to maintain pituitary function. Three years after the initial surgery, the patient suffered from Graves' disease and was treated with antithyroid medications. However, the intrasellar residual and pituitary stalk lesions gradually increased in size. A second surgery was performed, and the residual intrasellar and stalk lesions were completely removed. As per the initial and second histopathologies, the pituitary adenoma comprised different cell groups positive for thyroid-(TSH) and follicle-stimulating hormones, and each cell group was positive for Pit-1 and SF-1. The pituitary stalk lesion was an adamantinomatous craniopharyngioma. We believe that TSH-producing adenoma was involved in the development of Graves' disease or that treatment for Graves' disease increased TSH-producing adenoma.

Current progress in genomics and targeted therapies for neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2), a multiple neoplasia syndrome, is a manifestation of an impaired expression of the merlin protein, exerting inhibitory effects on cell proliferation signals due to abnormalities of the NF2 gene located on chromosome 22. About half of patients inherit a germline mutation from a parent, and nearly 60% of de novo NF2 patients are estimated to have somatic mosaicism. The development of technical methods to detect NF2 gene mutation, including targeted deep sequencing from multiple tissues, improved the diagnostic rate of mosaic NF2. With improved understanding of genetics and pathogenesis, the diagnostic criteria for NF2 were updated to assist in identifying and diagnosing NF2 at an earlier stage. The understanding of cell signaling pathways interacting with merlin has led to the development of molecular-targeted therapies. Currently, several translational studies are searching for possible therapeutic agents targeting VEGF or VEGF receptors. Bevacizumab, an anti-VEGF monoclonal antibody, is widely used in many clinical trials aiming for hearing improvement or tumor volume control. Currently, a randomized, double-masked trial to assess bevacizumab is underway. In this randomized control trial, 12 other Japanese institutions joined the principal investigators in the clinical trial originating at Fukushima Medical University. In this review, we will be discussing the latest research developments regarding NF2 pathophysiology, including molecular biology, diagnosis, and novel therapeutics.

[Awake surgery for preservation of higher brain functions].

Awake surgery for gliomas has become a widely accepted neurosurgical method worldwide. However, it is applied mainly to restore speech and simple motor functions, and intraoperative applications to restore higher brain functions have not been established yet. Preserving these functions is crucial to restoring the normal social lives of patients postoperatively. In this review article, we focused on preserving spatial attention and higher motor functions, and discussed their neural basis, as well as, the application of awake surgery practices using effective tasks. For spatial attention, the line bisection task is the most popular and reliable; however, other tasks, such as exploratory tasks, can be used, depending on the location of the brain. For higher motor functions, we developed two tasks: 1) the PEG & COIN task, which evaluates grasping and approaching skills, and 2) the sponge-control task, which assesses somatosensory-dependent movement. Although scientific knowledge and evidence are still limited in this field of neurosurgery, we believe that expanding our knowledge about higher brain functions and developing specific and efficient intraoperative tasks to evaluate them will eventually preserve patients'quality of life.

[Current Topics on Precision Medicine for Neurofibromatosis Type 2].

Neurofibromatosis type 2(NF2)is a hereditary condition that causes bilateral vestibular schwannomas(VS), multiple schwannomas, and meningiomas. The prognosis is poor because the multiplicity of the tumors leads to a progressive decline in the quality of life, deafness, and death in an early age. NF2 is caused by a disorder in the tumor suppressor gene NF2, which encodes the merlin protein. Although it is an autosomal dominant disease, more than half of cases are presumed to be de novo caused by somatic mosaicism, the diagnosis rate of which has been improved by the recently introduced technology of targeted deep sequencing of DNA from multiple tissues. No chemotherapeutic drugs for treating NF2-related VS are available at present, and surgery and radiotherapy remain the only therapeutic options. Recently, a randomized, double-blind, multicenter clinical trial has started in Japan to verify the efficacy and safety of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, in treating NF2-related VS.

Intraoperative transcranial facial motor evoked potential monitoring in surgery of cerebellopontine angle tumors predicts early and late postoperative facial nerve function.

OBJECTIVE: We propose a novel method that predicts facial nerve function (FNF) calculated from the drop and recovery of facial motor evoked potential (FMEP) amplitude ratio during the surgery of cerebellopontine angle tumors. METHODS: We enrolled 73 patients with cerebellopontine angle tumor, and used a biphasic, constant current, and suprathreshold stimulation (BCS) protocol to record FMEP of the orbicularis oris. We measured the intraoperative minimum-to-baseline amplitude ratio (MBR), the final-to-baseline amplitude ratio (FBR), and the recovery value (RV). RV was measured by subtracting MBR from FBR. Using those values, we evaluated FNF both at early postoperative (EP) and late postoperative (LP) periods. RESULTS: We successfully obtained 62 FMEP readings. Facial palsies occurred in 22 patients during the EP period, and 14 patients recovered during the LP period. Both MBR and FBR showed a significant correlation with FNF in the EP period. RV showed a good predictive power of FNF recovery during the LP period for the first time. CONCLUSIONS: RV is a new and useful predictor of FNF recovery. MBR can be an intraoperative predictor of FNF in the EP period. SIGNIFICANCE: FNF outcome in the early and late postoperative periods can be predicted by FMEP.

Mechanical Thrombectomy for Acute Ischemic Stroke Caused by Prosthetic Aortic Valve Endocarditis Due to Exophiala dermatitidis Infection: A Case Report.

Prosthetic valve endocarditis (PVE) can cause large cerebral vessel occlusion. Many reports suggested that mechanical thrombectomy (MT) is effective and useful for early diagnosis from the histopathological findings of thrombus. We present the case of a 62-year-old man, with a history of prosthetic aortic valve replacement and pulmonary vein isolation for his atrial fibrillation, who developed a high fever and an acute neurological deficit, with left hemiplegia and speech disorder. He was diagnosed as having an acute right middle cerebral artery embolism and underwent an MT. The embolic source was found to be a PVE vegetation. However, histopathological analysis of the thrombus could not detect the actual diagnosis. Although he was treated for bacterial endocarditis, his blood culture revealed a rare fungal infection with Exophiala dermatitidis not until >3 weeks after admission. Subsequently, a ß-D-glucan assay also indicated elevated levels. Although he underwent an aortic valve replacement on day 36, MRI showed multiple minor embolic strokes till that day. Early diagnosis of fungal endocarditis and detection of the causative pathogen are still challenging, and the disease has a high risk of occurrence of early and repeated embolic stroke. In addition to clinical findings and pathological studies, ß-D-glucan assay might be a good tool for the diagnosis and evaluation of fungal endocarditis.

The superior frontal longitudinal tract: a connection between the dorsal premotor and the dorsolateral prefrontal cortices.

A few studies have identified the structural connection between the premotor area and the lateral prefrontal cortex (DLPFC) as the frontal longitudinal system (FLS). This study investigated the existence of a direct segment (none U-fibre) of the superior part of the FLS (sFLS), which connects the dorsal premotor cortex (PMd) and DLPFC and analysed its asymmetry and termination point patterns. A dataset of diffusion-weighted images from 48 subjects was used for generalised q-sampling imaging tractography. Additionally, a white-fibre dissection was conducted in two right hemispheres. An analysis of spatial location, termination points, laterality, and correlation with the subjects' gender or handedness was performed. The sFLS was found to have a deeper longitudinal bundle directly connecting the PMd and DLPFC. The bundle is referred to hereafter as the superior frontal longitudinal tract (SFLT). The SFLT was reconstructed in 100% of right and 88% of left hemispheres. It exhibited variable patterns in different subjects in their posterior terminations. In addition, it was found to possess a complicated spatial relationship with the adjacent bundles. The SFLT was revealed successfully in two cadaveric right hemispheres, where the posterior terminations were found to originate in the PMd independent of the superior longitudinal fasciculus.

[Corticospinal Tract Mapping by Calculating the Ratio of Subcortical to Cortical Stimulation Intensity:A Technical Note].

OBJECTIVE: Motor evoked potentials(MEPs)have been developed and utilized as safe surgical procedures. A correlation between the threshold intensity of direct stimulation MEPs and the distance of the corticospinal tract(CST)has been already established. However, MEPs are affected by anesthesia and patient-related conditions. Here, we describe a unique technique to avoid these effects. METHOD: When tumors developed in proximity to the CST, the transcortical MEP monitoring was done by placing grid electrodes on the primary motor cortex continuously while direct subcortical MEP mapping was conducted with a monopolar probe. The ratios of the subcortical to the transcortical stimulation intensity were calculated. The point at which the ratios reached 50% was defined as the surgical excision limit. DISCUSSION: MEPs are affected by anesthesia, paralysis, body temperature, and other factors. By measuring the ratio of the cortical stimulation intensity instead of the absolute value of the white matter stimulation intensity, various affecting factors can be avoided, and more accurate monitoring can become possible. CONCLUSION: By calculating the ratio of subcortical to cortical stimulation intensity, the corticospinal tract mapping is less likely to be influenced by the stimulation condition or facility setup, and this warrants further investigation.

Acute paradoxical brain herniation after decompressive craniectomy for severe traumatic brain injury: A case report.

BACKGROUND: Sinking skin flap syndrome or paradoxical brain herniation is an uncommon neurosurgical complication, which usually occurs in the chronic phase after decompressive craniectomy. We report a unique case presenting with these complications immediately after decompressive craniectomy for severe traumatic brain injury. CASE DESCRIPTION: A 65-year-old man had a right acute subdural hematoma (SDH), contusion of the right temporal lobe, and diffuse traumatic subarachnoid hemorrhage with midline shift to the left side. He underwent an emergency evacuation of the right SDH with a right decompressive frontotemporal craniectomy. Immediately after the operation, his neurological and computed tomography (CT) findings had improved. However, within 1 h after the surgery, his neurological signs deteriorated. An additional follow-up CT showed a marked midline shift to the left, i.e., paradoxical brain herniation, and his skin flap overlying the decompressive site was markedly sunken. We immediately performed an urgent cranioplasty with the right temporal lobectomy. He responded well to the procedure. We suspected that a cerebrospinal fluid leak had caused this phenomenon. CONCLUSION: Decompressive craniectomy for severe traumatic brain injury can lead to sinking skin flap syndrome and/or paradoxical brain herniation even in the acute phase. We believe that immediate cranioplasty allows the reversal of such neurosurgical complications.

Sequential Symptomatic Arterial Dissections in Multiple Vascular Beds in a Patient with Fibromuscular Dysplasia.

A 60-year-old man was admitted to our hospital because of abdominal pain and disturbed consciousness. Head magnetic resonance imaging showed right vertebral artery dissection and abdominal enhanced computed tomography showed dissection of the superior mesenteric artery. The patient was diagnosed as having fibromuscular dysplasia (FMD) based on conventional angiography. Although multiple vascular bed involvement is observed in approximately 40% of FMD patients, reports of sequential symptomatic dissections in various vascular beds are rare. Patients with FMD and dissection require close observation, and hemodynamic stabilization may prevent not only the further development of dissection, but also subsequent dissection of other arteries.