We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery.In this single-center ...retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (≥1 μg/mL) before surgery and on postoperative day (POD) 3 or 7.Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 μg/mL (sensitivity 0.636 and specificity 0.750). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 μg/mL.The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 μg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 μg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.
Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed ...as diagnostic and prognostic markers in PCNSL. In contrast, mutational analyses using cell‐free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell‐free DNA from PCNSL patients, we carried out droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in 14 consecutive PCNSL patients from whom paired tumor‐derived DNA and cell‐free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor‐derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell‐free DNAs evaluated by ddPCR (14/14) and TDS (13/14), the MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and in 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell‐free DNAs was traced in five patients; unexpectedly, the mutations disappeared after chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell‐free DNA and could be used as non‐invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.
Our findings might provide new perspectives on the utility of ddPCR‐based detection of L265P MyD88 mutations in cell‐free DNAs as a non‐invasive diagnostic marker of PCNSL.
Brain abscess is a pyogenic disease secondary to a bacterial, tuberculous, or fungal infection of the brain; thus, early detection and treatment are of crucial importance. Herein, we present a case ...of a brain abscess arising from dental sinusitis due to an incomplete infection defense mechanism linked to a post-fusion linear skull fracture. The patient initially presented with a persistent headache, which was diagnosed as frontal sinusitis. Consequently, antibiotic treatment was started. However, due to a refractory response to antibiotics, MRI was performed, which revealed a brain abscess in the frontal lobe adjacent to the right frontal sinus measuring 40 mm in diameter. This abscess was surgically drained and cultured. Initially, the patient was treated with three antibiotics, which were eventually de-escalated. The cultures revealed nasal commensal bacteria, suggesting a direct spillover from sinusitis leading to a brain abscess. A tooth with root inflammation, which had been left untreated and resulted in bone melting of the maxillary sinus wall, was extracted. After more than eight weeks of antimicrobial therapy, improvement in the clinical and imaging findings was noted, and the patient was discharged. Brain abscesses may develop from sinusitis even after linear fractures have healed due to a continued incomplete infection defense mechanism. Moreover, root and sinus infections should undergo evaluation, including the upper dental crown using coronal computed tomography, and treatment should be initiated promptly.
As a new concept of glioma therapy, immunotherapy combined with standard therapies is a promising modality to improve glioma patient survival. VEGF and its signaling pathway molecules not only ...inhibit angiogenesis but also may reinforce the immunosuppressive tumor microenvironment, including promotion of the accumulation of immunosuppressive tumor-associated macrophages (TAMs). In this review, we discuss VEGF-targeted therapy as a new treatment option of the TAM-targeted therapy for high-grade gliomas, as well as other TAM-targeted therapies. The authors also discuss the potential of these therapies combined with conventional immunotherapies.
This study analyzed risk factors for postoperative cerebrospinal fluid (CSF) leak after graded multilayer cranial base repair method with dural suturing. We performed surgery via the endoscopic ...endonasal approach (EEA) from 2012.6 to 2018.4, and those consecutive clinical data were prospectively accumulated and retrospectively analyzed. We tailored the repair method according to the intraoperative CSF leak grade. Among 388 surgeries via the EEA, there were 10 (2.6%) cases of postoperative CSF leak after graded repair with suturing. Postoperative CSF leak occurred in two of the 150 cases without intraoperative CSF leak (grade 0), one of the 104 cases with small (grade 1) intraoperative CSF leak, two of the 60 cases with moderate (grade 2) leak, and five of the 74 cases with large (grade 3) leak. Univariate analysis indicated that chordoma (P = 0.023), estimated tumor volume ≥ 7400 mm3 (P = 0.003), and maximum tumor diameter ≥ 32.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Additionally, among cases with intraoperative grade 3 CSF leak, chordoma (P = 0.021), estimated tumor volume ≥ 23000 mm3 (P = 0.003), and maximum tumor diameter ≥ 45.5 mm (P = 0.001) were significant risk factors for postoperative CSF leak. Maximum tumor diameter, estimated tumor volume, and chordoma tumor pathology are related to a higher risk of postoperative CSF leak.
Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) and photodynamic therapy (PDT) using talaporfin sodium for high grade glioma (PDD) have been widely used in Japan, contributing to ...extent of resection and improved median survival. Both techniques use photosensitizers and laser light of specific wavelengths. Photosensitivity is a well-known adverse event, but there are few reports of other adverse events in the department of neurosurgery. We experienced a case of marked hypotension after taking 5ALA, which delayed the start of surgery. We also experienced a case of depression during light shielding after PDT. We report our experience and discuss adverse events associated with 5ALA and talapofin sodium and their countermeasures.
Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective ...treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score ≥4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.
Abstract
Objective
We examined the functional connectivity (FC) in patients with migraine compared with healthy subjects before and after C2 peripheral nerve field stimulation with electroacupuncture ...(EA-C2-PNfS) to evaluate the effect of EA-C2-PNfS and elucidate the mechanism of migraine.
Methods
Twenty-six patients with migraine and 24 healthy controls were recruited. All patients underwent resting state functional magnetic resonance imaging before and after 3 months of EA-C2-PNfS. We evaluated a numerical rating scale, the Headache Impact Test, and the Self-Rating Depression Scale, which assesses depression. Healthy controls underwent magnetic resonance imaging twice at a 3-month interval without acupuncture. An analysis of FC in the region of interest in the pain matrix was performed.
Results
Twenty patients with migraine and 23 healthy controls (mean ± standard deviation: 44.9 ± 12.9 years of age) were included. Three patients had migraine with aura (55.0 ± 18.0 years of age), 11 patients had migraine without aura (MWoA) (45.6 ± 14.6 years of age), and six patients had chronic migraine (40.8 ± 13.9 years of age). The clinical assessments significantly improved after EA-C2-PNfS in the MWoA group only. In FC analysis, the MWoA group showed a significant decrease after EA-C2-PNfS in FC between the right hypothalamus and left insula. Right hypothalamus–related FC was lower before acupuncture in the chronic migraine group than in the MWoA group.
Conclusion
After EA-C2-PNfS for MWoA, significant changes in FC were observed at the hypothalamus and insula. Our results indicate that EA-C2-PNfS could improve migraine headache by modifying pain-related FC.
Human mesenchymal stem cells are a promising cell source for the treatment of stroke. Their primary mechanism of action occurs via neuroprotective effects by trophic factors, anti-inflammatory ...effects, and immunomodulation. However, the regeneration of damaged neuronal networks by cell transplantation remains challenging. We hypothesized that cells induced to neural lineages would fit the niche, replace the lesion, and be more effective in improving symptoms compared with stem cells themselves. We investigated the characteristics of induced neural cells from human dental pulp tissue and compared the transplantation effects between these induced neural cells and uninduced dental pulp stem cells. Induced neural cells or dental pulp stem cells were intracerebrally transplanted 5 days after cerebral infarction induced by permanent middle cerebral artery occlusion in immunodeficient mice. Effects on functional recovery were also assessed through behavior testing. We used immunohistochemistry and neuron tracing to analyze the differentiation, axonal extension, and connectivity of transplanted cells to the host's neural circuit. Transplantation of induced neural cells from human dental pulp ameliorated functional recovery after cerebral infarction compared with dental pulp stem cells. The induced neural cells comprised both neurons and glia and expressed functional voltage, and they were more related to neurogenesis in terms of transcriptomics. Induced neural cells had a higher viability than did dental pulp stem cells in hypoxic culture. We showed that induced neural cells from dental pulp tissue offer a novel therapeutic approach for recovery after cerebral infarction.
The programmed cell death‐1/programmed cell death‐ligand 1 (PD‐1/PD‐L1) pathway is involved in preventing immune system‐mediated destruction of malignant tumors including glioblastoma. However, the ...therapeutic influence of PD‐1/PD‐L1 inhibition alone in glioblastoma is limited. To develop effective combination therapy involving PD‐1/PD‐L1 inhibition, we used a non‐replicating virus‐derived vector, hemagglutinating virus of Japan‐envelope (HVJ‐E), to inhibit tumor cell PD‐L1 expression by delivering siRNA targeting PD‐L1. HVJ‐E is a promising vector for efficient delivery of enclosed substances to the target cells. Moreover, HVJ‐E provokes robust antitumoral immunity by activating natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), and by suppressing regulatory T lymphocytes (Treg). We hypothesized that we could efficiently deliver PD‐L1‐inhibiting siRNAs to tumor cells using HVJ‐E, and that synergistic activation of antitumoral immunity would occur due to the immunostimulating effects of HVJ‐E and PD‐1/PD‐L1 inhibition. We used artificially induced murine glioma stem‐like cells, TS, to create mouse (C57BL/6N) glioblastoma models. Intratumoral injection of HVJ‐E containing siRNA targeting PD‐L1 (siPDL1/HVJ‐E) suppressed the expression of tumor cell PD‐L1 and significantly suppressed tumor growth in subcutaneous models and prolonged overall survival in brain tumor models. Flow cytometric analyses of brain tumor models showed that the proportions of brain‐infiltrating CTL and NK cells were significantly increased after giving siPDL1/HVJ‐E; in contrast, the rate of Treg/CD4+ cells was significantly decreased in HVJ‐E‐treated tumors. CD8 depletion abrogated the therapeutic effect of siPDL1/HVJ‐E, indicating that CD8+ T lymphocytes mainly mediated this therapeutic effect. We believe that this non‐replicating immunovirotherapy may be a novel therapeutic alternative to treat patients with glioblastoma.
HVJ‐E containing PD‐L1 siRNA significantly prolonged overall survival in mouse brain glioblastoma models. The therapeutic performance was mediated by antitumor immune responses via increased proportions of brain‐infiltrating CTL and a decreased rate of Treg among CD4+ T cells. This non‐replicating immunovirotherapy appears to show great promise as an attractive novel alternative to treat patients with glioblastoma.
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