Intraoperative rapid molecular diagnosis aids glioma subtyping and guides precise surgical resection.

OBJECTIVE: The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations. METHODS: A total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology-guided conventional surgical resection (non-AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology-guided glioma surgery. RESULTS: With NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology-guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p < 0.0001) and also improved median OS (26.77 vs. 13.47 months, p = 0.0289) and median PFS (15.90 vs. 10.57 months, p = 0.0181) in patients with glioblastoma. INTERPRETATION: Using AIGS intraoperatively to detect IDH/TERTp mutations to accurately diagnose glioma subtypes can help achieve maximum safe resection of gliomas, which in turn improves the survival prognosis of patients.

The first prospective application of AIGS real-time fluorescence PCR in precise diagnosis and treatment of meningioma: Case report.

Background: The emergence of the new WHO classification standard in 2021 incorporated molecular characteristics into the diagnosis system for meningiomas, making the diagnosis and treatment of meningiomas enter the molecular era. Recent findings: At present, there are still some problems in the clinical molecular detection of meningioma, such as low attention, excessive detection, and a long cycle. In order to solve these clinical problems, we realized the intraoperative molecular diagnosis of meningioma by combining real-time fluorescence PCR and AIGS, which is also the first known product applied to the intraoperative molecular diagnosis of meningioma. Implications for practice: We applied AIGS to detect and track a patient with TERTp mutant meningioma, summarized the process of intraoperative molecular diagnosis, and expounded the significance of intraoperative molecular diagnosis under the new classification standard, hoping to optimize the clinical decision-making of meningioma through the diagnosis and treatment plan of this case.

Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis.

BACKGROUND: With the advent of the molecular era, the diagnosis and treatment systems of glioma have also changed. A single histological type cannot be used for prognosis grade. Only by combining molecular diagnosis can precision medicine be realized. OBJECTIVE: To develop an automatic integrated gene detection system (AIGS) for intraoperative detection in glioma and to explore its positive role in intraoperative diagnosis and treatment. METHODS: We analyzed the isocitrate dehydrogenase 1 (IDH1) mutation status of 105 glioma samples and evaluated the product's potential value for diagnosis; 37 glioma samples were detected intraoperatively to evaluate the feasibility of using the product in an actual situation. A blinding method was used to evaluate the effect of the detection technology on the accuracy of intraoperative histopathological diagnosis by pathologists. We also reviewed the current research status in the field of intraoperative molecular diagnosis. RESULTS: Compared with next-generation sequencing, the accuracy of AIGS in detecting IDH1 was 100% for 105 samples and 37 intraoperative samples. The blind diagnostic results were compared between the 2 groups, and the molecular information provided by AIGS increased the intraoperative diagnostic accuracy of glioma by 16.2%. Using the technical advantages of multipoint synchronous detection, we determined the tumor molecular margins for 5 IDH-positive patients and achieved accurate resection at the molecular level. CONCLUSION: AIGS can quickly and accurately provide molecular information during surgery. This methodology not only improves the accuracy of intraoperative pathological diagnosis but also provides an important molecular basis for determining tumor margins to facilitate precision surgery.

The First Case Report of a Patient With Oligodendroglioma Harboring CHEK2 Germline Mutation.

Introduction: CHEK2 (Checkpoint kinase 2) germline mutations were associated with an elevated risk of breast cancer, colorectal cancer, and other familiar cancers. Loss-of-function variants in CHEK2 are known to be pathogenic. Germline CHEK2 mutations have also been observed in medulloblastoma and primary glioblastomas. Currently, there is no direct evidence supporting the relationship of CHEK2 with central nervous system tumors. Case presentation: A case of an oligodendroglioma patient harboring the germline CHEK2 p.R137* mutation was reported. CHEK2 p.R137* mutation occurred in the forkhead-associated domain. Given the absence of other known genetic predisposing risk factors, we considered that oligodendroglioma might be associated with the CHEK2 mutation. The patient in our case might have a high risk of breast cancer and other multiple primary tumors. Her siblings and offspring would have a 50% chance of having the same variant. Conclusion: We reported a case of an oligodendroglioma patient with a family history of gastrointestinal tumors harboring the germline CHEK2 pathogenic variation. This is the first report of the association between the CHEK2 pathogenic variation and brain tumors that warrants further validation in larger cohorts.

Intrasellar and Suprasellar Schwannoma Misdiagnosed as Pituitary Macroadenoma: A Case Report and Review of the Literature.

BACKGROUND: Intracranial schwannomas usually arise from sensory nerves with a predilection for the trigeminal nerve and the vestibular component of the eighth cranial nerve (VIII). Schwannoma arising in the sella and extending into the suprasellar region is exceedingly rare and easily misdiagnosed as pituitary macroadenoma. Only 26 cases of intrasellar schwannomas have been reported in the literature. CASE DESCRIPTION: A patient with an intrasellar schwannoma and suprasellar extension was presurgically diagnosed as having pituitary macroadenoma. Subtotal excision of the lesion was performed via an endoscopic endonasal transsphenoidal approach. Histopathology showed schwannoma. His symptoms improved after surgery. Magnetic resonance imaging 6 months after surgery showed a remnant schwannoma in the sella. CONCLUSIONS: Although schwannoma in the sellar region is rare, it remains an important differential diagnosis because of different surgical approaches.

Facial nerve function after large cystic vestibular schwannomas surgery via the retrosigmoid approach.

AIM: To evaluate long-term postoperative facial nerve function in patients undergoing large cystic vestibular schwannomas (VSs) surgery. MATERIAL AND METHODS: Surgical outcome of 36 patients with large cystic VS was retrospectively assessed, and compared with a group of 67 patients with large solid VS. RESULTS: The anatomical integrity of the facial nerve was preserved in 88.9% of cystic group patients and in 92.5% of solid group patients. At 1 year after surgery, 75.8% of the patients with cystic VSs had favorable facial nerve function and 24.2% had poor function. There was no significant difference in facial nerve outcomes between cystic and solid tumors. When the cyst wall was closely adherent to the facial nerve, near total or subtotal resection was associated with a better facial nerve outcome compared to total excision (P < 0.05). CONCLUSION: In most cystic VS patients, favorable facial nerve function can be attained by surgical treatment via retrosigmoid approach. Special care should be taken to remove entire cystic VSs as well as partial cystic VSs with anterior or medial located cysts. When a dissection plane cannot be developed between the cyst wall and the facial nerve, near total or subtotal resection is of benefit for facial nerve function.

Clinical and imaging features of central neurocytomas.

To describe the clinical and imaging characteristics of patients with central neurocytoma (CN), we reviewed data on 27 patients who had histologically confirmed CN and were treated in our institution between 1999 and 2010. Neuro-imaging findings on CT scan (n=18) and MRI (n=25) were retrospectively evaluated. There were 15 males and 12 females with a mean age of 29 years (range, 11-46 years). The most frequent presentations included headache (n=21) and vomiting (n=6). Tumor sites included bilateral lateral ventricles (n=10), right lateral ventricle (n=7), left lateral ventricle (n=7) and fourth ventricle (n=3). On MRI, the T1-weighted signal was hypointense in 12 patients and isointense in 13, and the T2-weighted signal was isointense in 8 patients and hyperintense in 15. CT scans/MRI revealed a cystic component in 18 patients. Tumors showed a mild to marked enhancement in 26 patients. Flow voids from tumor vessels on MRI were present in 14 patients, and calcification was noted in six of 18 patients with CT scans. All lateral ventricle tumors were resected through a transcortical or transcallosal approach. Gross total resection was achieved in 19 patients, near total in two and subtotal in six. One patient died of cerebral infarction in the perioperative period. At the last follow up, there were three known clinical recurrences in this series. However, no recurrence was noted in 17 patients who underwent gross total resection with no adjuvant therapy.

Clinical characteristics and surgical outcomes of patients with interdural epidermoid cyst of the cavernous sinus.

Interdural epidermoid cysts of the cavernous sinus originate within the lateral dural wall of the cavernous sinus. Few data are available on the diagnosis and treatment of these tumors. In this study, four patients with interdural epidermoid cyst of the cavernous sinus are reported and data from six patients reported in the English literature are summarized. Trigeminal nerve dysfunction, ophthalmoplegia, and headache were the common symptoms and signs. MRI was the primary diagnostic tool. Contrast enhanced MRI showed slight or strong rim enhancement in six of the 10 patients. All patients were treated by surgical resection using frontotemporal or pterional craniotomy via the intradural or interdural approach. Total removal was achieved in three of the four patients, and four of 10 patients in the whole series. Postoperative neurological function improved in all patients. During follow-up, there were three known clinical recurrences in the total group, but no recurrence in the four patients treated at Qilu Hospital of Shandong University. The findings suggest that aggressive surgical management is associated with good results and with low complication and recurrence rates, but radical resection at the risk of impairing the cranial nerves is not recommended.

Bioresonance hypothesis: a new mechanism on the pathogenesis of trigeminal neuralgia.

Trigeminal neuralgia (TN) is an uncommon disorder characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution. To date, the precise mechanism for TN remains unclear. Among a variety of causes of TN, the microvascular compression (MVC) hypothesis is the most popular one, but controversies still focus on the origin and pathogenesis of the disorder. A number of clinical phenomena still cannot be well explained. We propose a new hypothesis on the pathogenesis of TN - bioresonance. The bioresonance hypothesis states that when the vibration frequency of a structure surrounding the trigeminal nerve becomes close to its natural frequency, the resonance of the trigeminal nerve occurs. The bioresonance can damage trigeminal nerve fibers and lead to the abnormal transmission of the impulse, which may finally result in facial pain. Under the guidance of the bioresonance hypothesis, we hope to explore more non-invasive methods to treat or even cure TN.

Clinical presentation and treatment of distal posterior inferior cerebellar artery aneurysms: report on 5 cases.

BACKGROUND: Aneurysms of the PICA are uncommon. Most of them arise at the PICA origin from the VA, whereas distal PICA aneurysms are exceptional. A retrospective analysis of 457 patients with SAH treated in our hospital found 5 patients with 6 distal PICA aneurysms (approximately 1% of SAHs). CASE DESCRIPTION: All patients were female, with a mean age of 54 years. A 4-vessel cerebral angiogram performed immediately after admission showed an aneurysm located on the distal PICA. One patient was treated by an endovascular approach, and 3 patients were treated by surgical approach. The last patient had 2 distal high-flow aneurysms located on the distal PICA, which was the main arterial feeder of an AVM. The patient refused surgery or endovascular therapy. All 4 treated patients had good outcome at 3-month clinical follow-up. CONCLUSIONS: Distal PICA aneurysms are exceptionally rare and may be treated successfully with surgical or endovascular techniques. The therapeutic strategy, either surgical or endovascular, should be selected according to the condition of the patient, the arterial and aneurysmal morphology, and the preference of the medical team.

Functional and structural recovery of injured spinal cord following delayed X-irradiation in rats.

OBJECTIVE: To test the hypothesis that delayed X-irradiation can enhance the functional and structural recovery of the injured spinal cord in rats. METHODS: Seventy Sprague-Dawley rats were randomly divided into two groups, 35 rats in each. The control group sustained a one-minute clip compression (force of clip was 30 g) injury of the spinal cord at the T2 level, without X-irradiation. The experimental group received X-irradiation 14 days after injury. Neurological function was assessed by the modified Tarlov method, including hind limbs movement, inclined plane, and pain withdrawal. These tests were performed in a blinded fashion at 3, 7, 14, 21, 28, 35, and 42 days after injury. At 43 days after injury, histological examination of the injured spinal cord was performed following decapitation of the rats. RESULTS: Sixty-two rats met the experimental requirements (spinal cord injury was similar), 32 rats in experimental group and 30 rats in control group. Statistically significant difference was observed between the two groups in hind limbs movement and inclined plane (P < 0.01), but not in the pain withdrawal test. The edema and necrosis areas of injured spinal cords in experimental group were less than those in control group, and axons in experimental group were significantly more than those in control group (P < 0.01). CONCLUSION: Delayed X-irradiation following spinal cord injury may enhance functional recovery by improving and restoring structural integrity of the injured spinal cord in rats.

[Study of X-irradiation to enhance the functional and structural recovery of the injured spinal cord of rat].

OBJECTIVE: To explore whether X-irradiation can enhance the functional and structural recovery of the injured spinal cord of rats. METHODS: Seventy Sprague-Dawley rats received spinal cord injury by clip compression at the T2 level were randomly divided into two groups. The experimental group received X-irradiation at 14 days after injury, the control group did not receive X-irradiation. The functional tests were performed at day 3, 7, 14, 21, 28, 35, and 42 after irradiation including open field movement, inclined plane and pain withdrawal test. All injured rats were sacrificed at 43 days after injury and the injured spinal cords were taken out for histological tests. RESULTS: Sixty-two rats met the experimental requirements among 70 injured rats, 32 rats in experimental group and 30 rats in control group. Statistically significant difference was achieved between two groups in open field movement and inclined plane (P < 0.01), but not for the pain withdrawal test. The edema and necrosis area of injured spinal cords of experimental group were less than those in control group, and the number of axons of experimental group were more than those in control group. CONCLUSIONS: X-irradiation can enhance the functional recovery by improving and restoring structural integrity of the injured spinal cord.