Integrative and comparative single-cell analysis reveals transcriptomic difference between human tumefactive demyelinating lesion and glioma.

Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which can be misdiagnosed as glioma. At present, there is no study comparing difference between the two disorders at the cellular level. Here, we perform integrative and comparative single-cell RNA sequencing (ScRNA-seq) transcriptomic analysis on TDL and glioma lesions. At single-cell resolution, TDL is comprised primarily of immune cells, which is completely different from glioma. The integrated analysis reveals a TDL-specific microglial subset involving in B cell activation and proliferation. Comparative analysis highlights remyelination function of glial cells and demyelination function of T cells in TDL. Subclustering and pseudotime trajectory analysis of T cells in TDL reveal their heterogeneity and diverse functions involving in TDL pathogenesis and recovery process. Our study identifies substantial differences between TDL and glioma at single-cell resolution. The observed heterogeneity and potentially diverse functions of cells in TDL may be critical in disease progression.

Glioblastoma in a female neurofibromatosis 1 patient without IDH1, BRAF V600E, and TERT promoter mutations: A case report.

RATIONALE: Glioblastoma is the most lethal and common malignant brain tumor but rare in patients with neurofibromatosis type 1. The clinical findings and pathological findings with gene signatures in female patients have not been well clarified. PATIENT CONCERNS: A 51-year-old female patient complained of headache and left limb weakness lasting for 20 days. The patient underwent a cesarean section 20 years ago and hysterectomy 1 year ago because of uterine leiomyomas. Multiple café-au-lait spots and neurofibromas were found over patient's chest, neck, back, and arms. The myodynamia of left distant and proximate epipodite were grade 0 and grade 1 respectively. The myodynamia of lower left limb was grade 3. DIAGNOSES: Magnetic resonance imaging revealed a malignant lesion which was most likely a glioblastoma in the right temporo-parietal lobe, approximately 5.6 × 5.9 × 6.9 cm in size with a rounded boundary. INTERVENTIONS: A right temporo-parietal craniotomy was performed to resect the space-occupying lesion for gross total removal. Then, the patient received concurrent chemoradiotherapy. Histological examination confirmed a glioblastoma without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. OUTCOMES: After surgery, the headache was relieved and the muscular strength of left limbs did improve. After receiving the standard treatment regimen, the patient was alive at 13 months follow-up. LESSONS: This is the first reported glioblastoma in female neurofibromatosis type 1 patient without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. Tumors in adult patients with these signatures were less aggressive with well-circumscribed border and had long-term survivals which strengthened the evidence that these patients may comprise a unique subset in glioblastoma.

Risk factors of acute coagulation dysfunction after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Although coagulopathy have been proved to be a contributor to a poor outcome of aneurysmal subarachnoid hemorrhage (aSAH), the risk factors for triggering coagulation abnormalities have not been studied after aneurysm clipping. METHODS: We investigated risk factors of coagulopathy and analyzed the relationship between acute coagulopathy and outcome after aneurysm clipping. The clinical data of 137 patients with ruptured CA admitted to our institution was collected and retrospectively reviewed. Patient demographic data (age, sex), smoking, alcohol use, hypertension, diabetes, Hunt-Hess grade, Fisher grade, operation time, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, intraoperative hemostatic drug treatment, calcium reduction (preoperative free calcium concentration-postoperative free calcium concentration) were recorded. Coagulation was assessed within 24 h. Postoperative hemorrhage and infarction, deep venous thrombosis (DVT), and mortality were analyzed. RESULTS: Coagulopathy was detected in a total of 51 cases (group I), while not in 86 cases (group II). Univariable analysis demonstrated that age, smoking, alcohol use, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, and calcium reduction (≥ 1.2 mg/dl) were related to coagulopathy. Non-conditional logistic regression analysis showed that age [OR, 1.037 (95% CI, 1.001-1.074); p = 0.045] and calcium reduction (≥ 1.2 mg/dl) [OR, 5.509 (95% CI, 1.900-15.971); p = 0.002] were considered as the risk factors for coagulopathy. Hunt-Hess grade [OR, 2.641 (95% CI, 1.079-6.331); p = 0.033] and operation time [OR, 0.107 (95% CI, 1.012-0.928); p = 0.043] were considered as the risk factors for hypocoagulopathy. There were 6 cases (11.7%) with cerebral infarction in group I, while 6 cases (6.98%) in group II (χ 2 = 0.918, p = 0.338). There were 4 cases (7.84%) with rebleeding in group I, while 5 cases (5.81%) in group II (χ 2 = 0.215, p = 0.643). The mortality was 9.80% (5/51) in group I, while 1.16% (1/86) in group II (χ 2 = 5.708, p = 0.017). DVT was not detected in all cases. CONCLUSIONS: In conclusion, age (≥ 65 years) and calcium reduction (≥ 1.2 mg/dl) were considered as the risk factors for coagulopathy and have been proved to be associated with higher mortality after aneurysm clipping.

The classification of intracranial aneurysm neck: a single center research experience.

BACKGROUND: There is associating with incidence of unfavorable outcomes compared to microsurgical clippings. We are in order to investigate the outcomes of microsurgical clipping for intracranial aneurysms and determine the ideal clipping methods for different aneurysm subtypes. METHOD: Retrospectively analyzed the clinical characteristics and follow-up data (completely recorded) of 123 patients with 128 aneurysms were treated. 20 cases were treated as control group from October 2013 to December 2013. Since January 2014, aneurysms were classified base on the 20 cases of aneurysm imaging data. 103 patients were treated as experimental group, the classification of aneurysms previously proposed was used to estimate the way of surgery, and the guiding value of the genotype was verified according to the intraoperative findings. The proposed aneurysm classification is based on the virtual surface of the aneurysm and the parent artery, the aneurysm neck was classified as follows: subtype I, the curved surface of the neck is a single curved surface; subtype II, the neck is hyperboloid; subtype III, neck is a three-curved surface. Aneurysms were divided into further subtypes according to the ratio of the width of the aneurysm neck surface and the length of the artery circumference: subtype A, the ratio of the aneurysm neck surface to the parent artery was not more than 0.5; subtype B, more than 0.5. There are some clamping methods include simple, sliding, interlocking and hybrid. RESULTS: In the control group, patients did not undergo a suitable clipping scheme without classification of aneurysm neck (unclassed clipping). While causing the occurrence of occlusion adverse events, including neck residual, Tumor artery stenosis, electrophysiological changes, the lack of blood supply and so on. The experimental[page1image12073600]group was analyzed by using a predetermined clipping scheme (classed clipping), and the use of aneurysms clamps was approximately the same as expected. Compared the preoperative assessment with the actual situation, the consistency of the control group was 50% and the experimental group was 96%. Adverse events of classed clipping is 2%, another is 60%. There is a significant difference between the two groups (P < 0.05).Classed clipping of subject IA and IB are simple (mean 1.2 and 1.3 clips); classed clipping of subject IIA is simple and interlocking(mean 1.2 clips); classed clipping of subject IIB is sliding and hybrid(mean 2.05 clips); classed clipping of subject IIIA and IIIB are hybrid(mean 2.3 clips). CONCLUSION: There is a higher consistency in surgery through the above classification of preoperative assessment of clipping. There was no adverse event of intracranial aneurysm clipping in the clipping mode selected by the above classification, and satisfactory surgical clipping rate was achieved and no recurrence was found.

Coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms: A case report and literature review.

RATIONALE: There were a few case reports concerning epidermoid tumor coexisted with multiple cerebral aneurysms. Here, we present one case of coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms and performed a literature review. PATIENT CONCERNS: A 42 years old male patient was admitted to our institution with complaints of headache and dizziness. INTERVENTIONS: The radiological examinations showed a hypointense lesion in the right parasellar and petrous apex region and an ipsilateral saccular aneurysm originated from the M2-M3 junction of the right middle cerebral artery (MCA) and a saccular aneurysm of the clinoid segment of right internal carotid artery (ICA). INTERVENTIONS: The patients underwent a right frontotemporal approach for removal of the epidermoid tumor and clipping of the MCA aneurysm in one stage. The aneurysm located at the clinoid segment of ICA was invisible and untreated during operation. OUTCOMES: No postoperative complications were found in the patient. The patient's follow up after 5 years of surgical treatment was uneventful, and the untreated aneurysm remains stable. LESSONS: The coexistence of intracranial epidermoid tumor and cerebral aneurysm is a rare event. The secondly inflammation in cerebral arterial wall may be responsible for the aneurysm formation. Surgical treatment of the intracranial epidermoid tumor and cerebral aneurysm repair may be an optimal scheme in one stage.

Surgical Technique for Aneurysms at the A3 Segment of Anterior Cerebral Artery Via Anterior Interhemispheric Keyhole Approach.

AIM: Traditional craniotomies for treatment of the aneurysms at the A3 segment of anterior cerebral artery (A3As), such as frontal approach and interhemispheric approach, require pre-hairline incision and relatively long incision, extensive bone flap, inevitable supraorbital nerve injury, opening frontal sinus, and increased operative time. Here we reported anterior interhemispheric keyhole approach with minimally invasive advantages for treatment of A3As. MATERIAL AND METHODS: Thirteen A3As and one A1 aneurysm in thirteen patients were confirmed by computed tomographic angiography (CTA) and/or digital subtraction angiography (DSA). All patients underwent anterior interhemispheric keyhole approach with a hairline incision across the midline and a bone flap 3-4 cm in diameter, combined with external ventricular drainage, neuronavigation, intraoperative neurophysiological monitoring (IONM), and transcranial Doppler (TCD). Clinical characteristics and therapeutic results of the patients were analyzed, and the postoperative functional capacities of those patients were evaluated using Glasgow Outcome Scale (GOS) six months later. RESULTS: All aneurysms were successfully obliterated via the anterior interhemispheric keyhole approach combined with external ventricular drainage. Mean duration of surgery (from skin incision to wound closure) was 100 minutes with a range of 70 to 135 minutes. No severe interhemispheric keyhole approach related complications, postoperative infections, secondary intracranial haemorrhage, severe cerebral vasospasm, and aneurysmal neck remnants were detected. Median hospital stay after surgery was 9.0 days (range 8 to 11 days). And the postoperative functional capacities evaluated by GOS were normal six months later. CONCLUSION: The anterior interhemispheric keyhole approach combined with external ventricular drainage is a safe, effective, and minimally invasive craniotomy technique for the treatment of A3 aneurysms.

Retractorless Surgery for Anterior Circulation Aneurysms via a Pterional Keyhole Approach.

Brain retraction is required during many intracranial procedures to provide more working space. However, it is difficult to avoid brain retraction injury. Here, we report on retractorless surgery for anterior circulation aneurysms via a pterional keyhole approach. All patients undergoing a minimally invasive pterional keyhole approach within 3 days after hemorrhage by the same surgeon were included in the study. Patients were randomly assigned into group I (with the retractorless technique) and group II (with fixed retractors). Data on adequate clipping level, intraoperative ischemia induced by retraction, operation time, brain retraction injury, intraoperative blood loss, intraoperative aneurysm rupture, and modified Rankin Scale were collected for the 2 groups. A consecutive series of 47 patients (21 patients in group I, 26 patients in group II) successfully underwent a minimally invasive pterional keyhole approach. Statistical analysis revealed no significant between-group differences with regard to sex, age, Hunt-Hess grade, adequate clipping level, operation time, intraoperative blood loss, and aneurysm rupture (P > 0.05). However, no intraoperative ischemia was detected in group I, whereas 23.1% (6 of 26) of patients in group II had reversible ischemia. Furthermore, the proportion of brain retraction injuries in group I (5.3%) was lower than that in group II (34.6%). In addition, a better prognosis was obtained in patients who underwent retractorless surgery. With the careful and accurate use of a handheld suction device and operating instruments, the retractorless technique can replace fixed retraction, reduce brain retraction injury, and is applicable to surgeries on anterior circulation aneurysms via pterional keyhole approaches.

Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons of type II focal cortical dysplasia with refractory epilepsy.

Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis of these cells may be critical to the histological findings in type II FCD. Recent work has shown enhanced activation of the mTOR cascade in both balloon cells and dysmorphic neurons, suggesting a common pathogenesis for these two neuropathological hallmarks. A direct comparative analysis of balloon cells and dysmorphic neurons might identify a molecular link between balloon cells and dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation differentiates balloon cells from dysmorphic neurons. We used immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6 kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or moderate staining for components of the PDK1-AKT-mTOR signaling pathway was observed in both balloon cells and dysmorphic neurons. However, only a few pyramidal neurons displayed weak staining in control group (perilesional neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in dysmorphic neurons. Our data support the previously suggested pathogenic relationship between balloon cells and dysmorphic neurons concerning activation of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway between balloon cells and dysmorphic neurons may result from cell-specific gene expression.

[Surgical outcome and prognostic factors in focal cortical dysplasia with intractable epilepsy].

OBJECTIVE: To analyze surgical outcome and relevant surgical parameters including resection extent of epileptogenic zone,pathological subtype, brain MRS and MRI results in FCD with intractable epilepsy. METHODS: We retrospectively analyzed surgical outcomes of 35 patients with intractable epilepsy related to focal cortical dysplasia, accepted surgery in the first affiliated hospital of Fujian Medical University from January 2008 to January 2010, with 12-36 months of postoperative follow-up. The relevance between complete resection, pathological subtype, MRS and MRI result and surgical outcome were statistically evaluated. RESULTS: 22 patients (66.7%) were Engel class I, 5 patients (14.3%) were class II, 6 patients (17.2%) were class III, 2 patients (5.8%) were class IV. Complete resection of epileptogenic zone (P < 0.05), FCD type I (P < 0.05) correlated significantly with favorable surgical outcome. Other factors such as MRI results, abnormal NAA/CHO + Cr ratio on the contralateral side of epileptogenic zone, as well as MRS-accurate lateralization did not influence outcome. CONCLUSION: Overall, the surgical outcome of FCD is favorable. Complete resection, FCD type I correlates significantly with favorable surgical outcome.

Combined monitoring of evoked potentials during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms.

BACKGROUND: Neurophysiologic monitoring during surgery is to prevent permanent neurological injury resulting from surgical manipulation. To improve the accuracy and sensitivity of intraoperative neuromonitoring, combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEPs), somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) was attempted in microsurgery for lesions adjacent to the brainstem and intracranial aneurysms. METHODS: Monitoring of combined TES-MEPs with SSEPs was attempted in 68 consecutive patients with lesions adjacent to the brainstem as well as intracranial aneurysms. Among them, 31 patients (31 operations, 28 of posterior cranial fossa tumors, 3 of posterior circulation aneurysms) were also subjected to monitoring of BAEPs. The correlation of monitoring results and clinical outcome was studied prospectively. RESULTS: Combined monitoring of evoked potentials (EPs) was done in 64 (94.1%) of the 68 patients. MEPs monitoring was impossible for 4 patients (5.9%). No complication was observed during the combined monitoring in all the patients. In 45 (66.2%) of the 68 patients, EPs were stable, and they were neurologically intact. Motor dysfunction was detected by MEPs in 8 patients, SSEPs in 5, and BAEPs in 4, respectively. CONCLUSIONS: A close relationship exists between postoperative motor function and the results of TES-MEPs monitoring. TES-MEPs are superior to SSEPs and BAEPs in detecting motor dysfunction, but combined EPs serve as a safe, effective and invasive method for intraoperative monitoring of the function of the motor nervous system. Monitoring of combined EPs during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms may detect potentially hazardous maneuvers and improve the safety of subsequent procedures.